Rothermundt, C.
Andreou, D.
Blay, J.-.
Brodowicz, T.
Desar, I.M.
Dileo, P.
Gelderblom, H.
Haas, R.
Jakob, J.
Jones, R.L.
Judson, I.
Kunz, W.G.
Liegl-Atzwanger, B.
Lindner, L.H.
Messiou, C.
Miah, A.B.
Reichardt, P.
Szkandera, J.
van der Graaf, W.T.
van Houdt, W.J.
Wardelmann, E.
Hofer, S.
Andreou, D.
Barth, T.
Bauer, S.
Blay, J.-.
Blum, V.
Bode, B.
Bonvalot, S.
Bovee, J.
Braam, P.
Brodowicz, T.
Broto, J.M.
Dei Tos, A.
Denschlag, D.
Desar, I.
Digklia, A.
Dileo, P.
Dirksen, U.
Douchy, T.
Duffaud, F.
Eriksson, M.
Fröhling, S.
Gelderblom, H.
Gronchi, A.
Haas, R.
Hardes, J.
Hartmann, W.
Hofer, S.
Hohenberger, P.
Hompes, D.
Huang, P.
Italiano, A.
Jakob, J.
Jones, R.
Judson, I.
Köhler, G.
Kollàr, A.
Krasniqi, F.
Krol, S.
Kunz, W.
Le Grange, F.
Le Pechoux, C.
LeCesne, A.
Leithner, A.
Liegl-Atzwanger, B.
Lindner, L.
Mechtersheimer, G.
Messiou, C.
Miah, A.
Pink, D.
Reichardt, P.
Romagosa, C.
Rothermundt, C.
Rutkowski, P.
Safwat, A.
Sangalli, C.
Szkandera, J.
Thway, K.
Tunn, P.-.
Van der Graaf, W.
Van Houdt, W.
Wardelmann, E.
Zachariah, R.
Botter, S.
Cerny, T.
(2023). Controversies in the management of patients with soft tissue sarcoma: Recommendations of the Conference on State of Science in Sarcoma 2022. European journal of cancer,
Vol.180,
pp. 158-179.
Casali, P.G.
Blay, J.Y.
Abecassis, N.
Bajpai, J.
Bauer, S.
Biagini, R.
Bielack, S.
Bonvalot, S.
Boukovinas, I.
Bovee, J.V.
Boye, K.
Brodowicz, T.
Buonadonna, A.
De Álava, E.
Dei Tos, A.P.
Del Muro, X.G.
Dufresne, A.
Eriksson, M.
Fedenko, A.
Ferraresi, V.
Ferrari, A.
Frezza, A.M.
Gasperoni, S.
Gelderblom, H.
Gouin, F.
Grignani, G.
Haas, R.
Hassan, A.B.
Hindi, N.
Hohenberger, P.
Joensuu, H.
Jones, R.L.
Jungels, C.
Jutte, P.
Kasper, B.
Kawai, A.
Kopeckova, K.
Krákorová, D.A.
Le Cesne, A.
Le Grange, F.
Legius, E.
Leithner, A.
Lopez-Pousa, A.
Martin-Broto, J.
Merimsky, O.
Messiou, C.
Miah, A.B.
Mir, O.
Montemurro, M.
Morosi, C.
Palmerini, E.
Pantaleo, M.A.
Piana, R.
Piperno-Neumann, S.
Reichardt, P.
Rutkowski, P.
Safwat, A.A.
Sangalli, C.
Sbaraglia, M.
Scheipl, S.
Schöffski, P.
Sleijfer, S.
Strauss, D.
Strauss, S.J.
Hall, K.S.
Trama, A.
Unk, M.
van de Sande, M.A.
van der Graaf, W.T.
van Houdt, W.J.
Frebourg, T.
Gronchi, A.
Stacchiotti, S.
(2022). Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology,
Vol.33
(1),
pp. 20-33.
Johnston, E.W.
Basso, J.
Winfield, J.
McCall, J.
Khan, N.
Messiou, C.
Koh, D.-.
Fotiadis, N.
(2022). Starting CT-guided robotic interventional oncology at a UK centre. ,
Vol.95
(1134),
p. 20220217.
show abstract
OBJECTIVE: A commercially available CT-guided robot offers enhanced abilities in planning, targeting, and confirming accurate needle placement. In this short communication, we describe our first UK experience of robotic interventional oncology procedures. METHODS: We describe the device, discuss installation, operation, and report upon needle insertion success, accuracy (path deviation; PD and tip deviation; TD), number of adjustments, complications, and procedural success. RESULTS: Nine patients (seven males), median age 66 years (range 43-79) were consented for biopsy or ablation between March and April 2021. Needle placement in biopsy was more accurate than ablation (median 1 vs 11 mm PD and 1 vs 20 mm TD) and required fewer adjustments (median 0 vs 5). No complications arose, and all procedures were successful (diagnostic material obtained or complete ablation at follow-up). CONCLUSION: Short procedure times and very high levels of accuracy were readily achieved with biopsy procedures, although tumour ablation was less accurate which likely reflects higher procedural complexity. ADVANCES IN KNOWLEDGE: Achieving highly accurate robotic biopsy with is feasible within a very short time span. Further work is required to maximise the potential of robotic guidance in tumour ablation procedures, which is likely due to higher complexity giving a longer learning curve..
Kantidakis, G.
Litière, S.
Gelderblom, H.
Fiocco, M.
Judson, I.
van der Graaf, W.T.
Italiano, A.
Marréaud, S.
Sleijfer, S.
Mechtersheimer, G.
Messiou, C.
Kasper, B.
(2022). Prognostic Significance of Bone Metastasis in Soft Tissue Sarcoma Patients Receiving Palliative Systemic Therapy: An Explorative, Retrospective Pooled Analysis of the EORTC-Soft Tissue and Bone Sarcoma Group (STBSG) Database. ,
Vol.2022,
p. 5815875.
show abstract
Background: Soft-tissue sarcomas (STS) constitute a rare group of heterogeneous mesenchymal tumours containing more than 100 histologic subtypes. Here, we investigate whether, and if so, to what extent, skeletal metastases affect the outcome of patients with advanced or metastatic disease. Materials and Methods: Selected patients participated in five clinical trials of EORTC-STBSG. Individuals were included if they started treatment with an active drug and had advanced/metastatic STS. The endpoints of interest were overall survival (OS) and progression-free survival (PFS). Univariate and multivariate pooled analyses (after correcting for 12 covariates) were employed with Kaplan-Meier and Cox regression to model the impact of bone metastasis at presentation per treatment line stratified by study. For the subset of patients with bone metastasis, the impact of another metastatic organ site was explored with multivariate Cox regression models. Results: 565 out of 1034 (54.6%) patients received first-line systemic treatment for locally advanced or metastatic disease. Bone metastases were present in 140 patients (77 first-line, 63 second-line or higher). The unadjusted difference in OS/PFS with or without bone metastasis was statistically significant only for first-line patients. For OS, the adjusted hazard ratios for bone metastasis presence were 1.33 (95%-CI: 0.99-1.78) and 1.11 (95%-CI: 0.81-1.52) for first-line/second-line or higher treated patients, respectively. Likewise, the adjusted hazard ratios for PFS were 1.31 (95%-CI: 1.00-1.73) and 1.07 (95%-CI: 0.80-1.43). Effects were not statistically significant, despite a trend in first-line patients for both endpoints. Subgroup analyses indicated bone and lymph node metastasis as the most detrimental combination for OS and bone and lung metastasis for PFS. Conclusions: Adult STS patients receiving palliative systemic therapy with bone metastasis carried an overall worse prognosis than STS patients without bone metastases. Skeletal metastasis was detrimental for both OS and PFS, independent of the treatment line. Findings may have implications for the management of these patients..
Castagnoli, F.
Doran, S.
Lunn, J.
Minchom, A.
O'Brien, M.
Popat, S.
Messiou, C.
Koh, D.-.
(2022). Splenic volume as a predictor of treatment response in patients with non-small cell lung cancer receiving immunotherapy. ,
Vol.17
(7),
p. e0270950.
show abstract
INTRODUCTION: The spleen is a lymphoid organ and we hypothesize that clinical benefit to immunotherapy may present with an increase in splenic volume during treatment. The purpose of this study was to investigate whether changes in splenic volume could be observed in those showing clinical benefit versus those not showing clinical benefit to pembrolizumab treatment in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: In this study, 70 patients with locally advanced or metastatic NSCLC treated with pembrolizumab; and who underwent baseline CT scan within 2 weeks before treatment and follow-up CT within 3 months after commencing immunotherapy were retrospectively evaluated. The splenic volume on each CT was segmented manually by outlining the splenic contour on every image and the total volume summated. We compared the splenic volume in those achieving a clinical benefit and those not achieving clinical benefit, using non-parametric Wilcoxon signed-rank test. Clinical benefit was defined as stable disease or partial response lasting for greater than 24 weeks. A p-value of <0.05 was considered statistically significant. RESULTS: There were 23 responders and 47 non-responders based on iRECIST criteria and 35 patients with clinical benefit and 35 without clinical benefit. There was no significant difference in the median pre-treatment volume (175 vs 187 cm3, p = 0.34), post-treatment volume (168 vs 167 cm3, p = 0.39) or change in splenic volume (-0.002 vs 0.0002 cm3, p = 0.97) between the two groups. No significant differences were also found between the splenic volume of patients with partial response, stable disease or progressive disease (p>0.017). Moreover, there was no statistically significant difference between progression-free survival and time to disease progression when the splenic volume was categorized as smaller or larger than the median pre-treatment or post-treatment volume (p>0.05). CONCLUSION: No significant differences were observed in the splenic volume of those showing clinical benefit versus those without clinical benefit to pembrolizumab treatment in NSCLC patients. CT splenic volume cannot be used as a potentially simple biomarker of response to immunotherapy..
Arthur, A.
Johnston, E.W.
Winfield, J.M.
Blackledge, M.D.
Jones, R.L.
Huang, P.H.
Messiou, C.
(2022). Virtual Biopsy in Soft Tissue Sarcoma How Close Are We?. ,
Vol.12,
p. 892620.
show abstract
A shift in radiology to a data-driven specialty has been unlocked by synergistic developments in imaging biomarkers (IB) and computational science. This is advancing the capability to deliver "virtual biopsies" within oncology. The ability to non-invasively probe tumour biology both spatially and temporally would fulfil the potential of imaging to inform management of complex tumours; improving diagnostic accuracy, providing new insights into inter- and intra-tumoral heterogeneity and individualised treatment planning and monitoring. Soft tissue sarcomas (STS) are rare tumours of mesenchymal origin with over 150 histological subtypes and notorious heterogeneity. The combination of inter- and intra-tumoural heterogeneity and the rarity of the disease remain major barriers to effective treatments. We provide an overview of the process of successful IB development, the key imaging and computational advancements in STS including quantitative magnetic resonance imaging, radiomics and artificial intelligence, and the studies to date that have explored the potential biological surrogates to imaging metrics. We discuss the promising future directions of IBs in STS and illustrate how the routine clinical implementation of a virtual biopsy has the potential to revolutionise the management of this group of complex cancers and improve clinical outcomes..
Zormpas-Petridis, K.
Tunariu, N.
Collins, D.J.
Messiou, C.
Koh, D.-.
Blackledge, M.D.
(2022). Deep-learned estimation of uncertainty in measurements of apparent diffusion coefficient from whole-body diffusion-weighted MRI. ,
Vol.149,
p. 106091.
show abstract
PURPOSE: To use deep learning to calculate the uncertainty in apparent diffusion coefficient (σADC) voxel-wise measurements to clinically impact the monitoring of treatment response and improve the quality of ADC maps. MATERIALS AND METHODS: We use a uniquely designed diffusion-weighted imaging (DWI) acquisition protocol that provides gold-standard measurements of σADC to train a deep learning model on two separate cohorts: 16 patients with prostate cancer and 28 patients with mesothelioma. Our network was trained with a novel cost function, which incorporates a perception metric and a b-value regularisation term, on ADC maps calculated by combinations of 2 or 3 b-values (e.g. 50/600/900, 50/900, 50/600, 600/900 s/mm2). We compare the accuracy of the deep-learning based approach for estimation of σADC with gold-standard measurements. RESULTS: The model accurately predicted the σADC for every b-value combination in both cohorts. Mean values of σADC within areas of active disease deviated from those measured by the gold-standard by 4.3% (range, 2.87-6.13%) for the prostate and 3.7% (range, 3.06-4.54%) for the mesothelioma cohort. We also showed that the model can easily be adapted for a different DWI protocol and field-of-view with only a few images (as little as a single patient) using transfer learning. CONCLUSION: Deep learning produces maps of σADC from standard clinical diffusion-weighted images (DWI) when 2 or more b-values are available..
Moulin, B.
Messiou, C.
Crombe, A.
Kind, M.
Hohenberger, P.
Rutkowski, P.
van Houdt, W.J.
Strauss, D.
Gronchi, A.
Bonvalot, S.
(2022). Diagnosis strategy of adipocytic soft-tissue tumors in adults: a consensus from European experts. European journal of surgical oncology,
Vol.48
(3),
pp. 518-525.
Mulligan, M.
Bonar, F.
Fanburg-Smith, J.
Melhem, L.
Messiou, C.
Kocoglu, M.
Streeten, E.
(2022). Revisiting the Case of Sarah Newbury’s Death from Mollities Ossium. Cancer investigation,
Vol.40
(6),
pp. 544-553.
Meyer, M.
Hohenberger, P.
Overhoff, D.
Bartsch, A.
Henzler, T.
Haubenreisser, H.
Ronald, J.
Schmidt, B.
Flohr, T.
Sedlmair, M.
Ota, H.
Messiou, C.
Schoenberg, S.O.
Riedel, R.F.
Nelson, R.C.
Marin, D.
(2022). Dual-Energy CT Vital Iodine Tumor Burden for Response Assessment in Patients With Metastatic GIST Undergoing TKI Therapy: Comparison With Standard CT and FDG PET/CT Criteria. American journal of roentgenology,
Vol.218
(4),
pp. 659-669.
Satchwell, L.
Wedlake, L.
Greenlay, E.
Li, X.
Messiou, C.
Glocker, B.
Barwick, T.
Barfoot, T.
Doran, S.
Leach, M.O.
Koh, D.M.
Kaiser, M.
Winzeck, S.
Qaiser, T.
Aboagye, E.
Rockall, A.
(2022). Development of machine learning support for reading whole body diffusion-weighted MRI (WB-MRI) in myeloma for the detection and quantification of the extent of disease before and after treatment (MALIMAR): protocol for a cross-sectional diagnostic test accuracy study. ,
Vol.12
(10),
p. e067140.
show abstract
INTRODUCTION: Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and can be challenging for radiologists who need to meet rapid turn-around requirements. Automated computational tools based on machine learning (ML) could assist the radiologist in terms of sensitivity and reading speed and would facilitate improved accuracy, productivity and cost-effectiveness. The MALIMAR study aims to develop and validate a ML algorithm to increase the diagnostic accuracy and reading speed of radiological interpretation of WB-MRI compared with standard methods. METHODS AND ANALYSIS: This phase II/III imaging trial will perform retrospective analysis of previously obtained clinical radiology MRI scans and scans from healthy volunteers obtained prospectively to implement training and validation of an ML algorithm. The study will comprise three project phases using approximately 633 scans to (1) train the ML algorithm to identify active disease, (2) clinically validate the ML algorithm and (3) determine change in disease status following treatment via a quantification of burden of disease in patients with myeloma. Phase 1 will primarily train the ML algorithm to detect active myeloma against an expert assessment ('reference standard'). Phase 2 will use the ML output in the setting of radiology reader study to assess the difference in sensitivity when using ML-assisted reading or human-alone reading. Phase 3 will assess the agreement between experienced readers (with and without ML) and the reference standard in scoring both overall burden of disease before and after treatment, and response. ETHICS AND DISSEMINATION: MALIMAR has ethical approval from South Central-Oxford C Research Ethics Committee (REC Reference: 17/SC/0630). IRAS Project ID: 233501. CPMS Portfolio adoption (CPMS ID: 36766). Participants gave informed consent to participate in the study before taking part. MALIMAR is funded by National Institute for Healthcare Research Efficacy and Mechanism Evaluation funding (NIHR EME Project ID: 16/68/34). Findings will be made available through peer-reviewed publications and conference dissemination. TRIAL REGISTRATION NUMBER: NCT03574454..
Bhaludin, B.N.
Tunariu, N.
Senthivel, N.
Babiker, A.
Soneji, N.D.
Hujairi, N.
Sharma, B.
McGrath, S.E.
Okines, A.F.
Ring, A.E.
Messiou, C.
Downey, K.
Koh, D.-.
(2022). Does the addition of whole-body MRI to routine imaging influence real-world treatment decisions in metastatic breast cancer?. ,
Vol.22
(1),
p. 26.
show abstract
BACKGROUND: The assessment of metastatic breast cancer (MBC) can be limited with routine imaging such as computed tomography (CT) especially in bone-only or bone-predominant disease. This analysis investigates the effects of the use of WBMRI in addition to the use of routine CT, bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) on influencing systemic anti-cancer treatment (SACT) decisions in patients with known MBC. METHODS: MBC patients undergoing SACT who had WBMRI undertaken within 8 weeks of either a routine CT, BS or FDG-PET/CT were reviewed retrospectively. The clinical indications for undertaking the WBMRI examinations were recorded. Data on the extent and distribution of the disease were collected and discordance/concordance of disease status across the imaging modalities were compared. SACT decisions at each time point were also evaluated. RESULTS: There were 105 MBC patients with 148 WBMRI studies paired with CT, BS or FDG-PET/CT. 50 pairs (33.8%) showed differences in the extent of disease, with 44 pairs due to additional sites (AS) reported on WBMRI alone. 81 patients (Group 1) had one WBMRI paired with routine imaging due to a variety of indications, with clinical symptoms (such as bone pain) being the most common (24.7%). 24 patients (Group 2) had more than one WBMRI study paired with routine imaging comprising 67 pairs. 13/67 pairs (19.4%) showed discordance in assessments. 10/13 pairs had progressive disease (PD) reported on WBMRI alone. SACT change due to AS reported on WBMRI alone occurred in 21/23 pairs (91.3%) in Group 1. SACT change due to PD reported on WBMRI alone in Group 2 occurred in 6/14 pairs (42.9%). SACT change due to AS/PD in both groups occurred in 11/102 pairs (10.8%) with known invasive ductal carcinoma (IDC) and 13/28 pairs (46.4%) with invasive lobular carcinoma (ILC). CONCLUSIONS: The use of WBMRI in MBC led to earlier recognition of PD and SACT change compared with the other imaging modalities. A higher proportion of discordant response assessments and SACT changes were observed in ILC compared with IDC in our patient group, although larger-scale studies are required to investigate this further..
Johnston, E.W.
Alves, A.
Messiou, C.
Napolitano, A.
Strauss, D.
Hayes, A.
Smith, M.J.
Benson, C.
Jones, R.L.
Gennatas, S.
Fotiadis, N.
(2022). Percutaneous cryoablation for desmoid fibromatosis: initial experience at a UK centre. Clinical radiology,
Vol.77
(10),
pp. 784-793.
Khan, M.
Wilkerson, H.
Vassos, N.
Hannay, J.A.
Thway, K.
Messiou, C.
Hayes, A.J.
Strauss, D.C.
Smith, M.J.
(2022). Oncologic outcomes of surgically managed primary pelvic soft tissue sarcoma; tumour biology or surgical constraints of the true pelvis?. European journal of surgical oncology,
.
Thrussell, I.
Winfield, J.M.
Orton, M.R.
Miah, A.B.
Zaidi, S.H.
Arthur, A.
Thway, K.
Strauss, D.C.
Collins, D.J.
Koh, D.-.
Oelfke, U.
Huang, P.H.
O'Connor, J.P.
Messiou, C.
Blackledge, M.D.
(2022). Radiomic Features From Diffusion-Weighted MRI of Retroperitoneal Soft-Tissue Sarcomas Are Repeatable and Exhibit Change After Radiotherapy. ,
Vol.12,
p. 899180.
show abstract
Background: Size-based assessments are inaccurate indicators of tumor response in soft-tissue sarcoma (STS), motivating the requirement for new response imaging biomarkers for this rare and heterogeneous disease. In this study, we assess the test-retest repeatability of radiomic features from MR diffusion-weighted imaging (DWI) and derived maps of apparent diffusion coefficient (ADC) in retroperitoneal STS and compare baseline repeatability with changes in radiomic features following radiotherapy (RT). Materials and Methods: Thirty patients with retroperitoneal STS received an MR examination prior to treatment, of whom 23/30 were investigated in our repeatability analysis having received repeat baseline examinations and 14/30 patients were investigated in our post-treatment analysis having received an MR examination after completing pre-operative RT. One hundred and seven radiomic features were extracted from the full manually delineated tumor region using PyRadiomics. Test-retest repeatability was assessed using an intraclass correlation coefficient (baseline ICC), and post-radiotherapy variance analysis (post-RT-IMS) was used to compare the change in radiomic feature value to baseline repeatability. Results: For the ADC maps and DWI images, 101 and 102 features demonstrated good baseline repeatability (baseline ICC > 0.85), respectively. Forty-three and 2 features demonstrated both good baseline repeatability and a high post-RT-IMS (>0.85), respectively. Pearson correlation between the baseline ICC and post-RT-IMS was weak (0.432 and 0.133, respectively). Conclusions: The ADC-based radiomic analysis shows better test-retest repeatability compared with features derived from DWI images in STS, and some of these features are sensitive to post-treatment change. However, good repeatability at baseline does not imply sensitivity to post-treatment change..
Rata, M.
Blackledge, M.
Scurr, E.
Winfield, J.
Koh, D.-.
Dragan, A.
Candito, A.
King, A.
Rennie, W.
Gaba, S.
Suresh, P.
Malcolm, P.
Davis, A.
Nilak, A.
Shah, A.
Gandhi, S.
Albrizio, M.
Drury, A.
Roberts, S.
Jenner, M.
Brown, S.
Kaiser, M.
Messiou, C.
(2022). Implementation of Whole-Body MRI (MY-RADS) within the OPTIMUM/MUKnine multi-centre clinical trial for patients with myeloma. ,
Vol.13
(1),
p. 123.
show abstract
BACKGROUND: Whole-body (WB) MRI, which includes diffusion-weighted imaging (DWI) and T1-w Dixon, permits sensitive detection of marrow disease in addition to qualitative and quantitative measurements of disease and response to treatment of bone marrow. We report on the first study to embed standardised WB-MRI within a prospective, multi-centre myeloma clinical trial (IMAGIMM trial, sub-study of OPTIMUM/MUKnine) to explore the use of WB-MRI to detect minimal residual disease after treatment. METHODS: The standardised MY-RADS WB-MRI protocol was set up on a local 1.5 T scanner. An imaging manual describing the MR protocol, quality assurance/control procedures and data transfer was produced and provided to sites. For non-identical scanners (different vendor or magnet strength), site visits from our physics team were organised to support protocol optimisation. The site qualification process included review of phantom and volunteer data acquired at each site and a teleconference to brief the multidisciplinary team. Image quality of initial patients at each site was assessed. RESULTS: WB-MRI was successfully set up at 12 UK sites involving 3 vendor systems and two field strengths. Four main protocols (1.5 T Siemens, 3 T Siemens, 1.5 T Philips and 3 T GE scanners) were generated. Scanner limitations (hardware and software) and scanning time constraint required protocol modifications for 4 sites. Nevertheless, shared methodology and imaging protocols enabled other centres to obtain images suitable for qualitative and quantitative analysis. CONCLUSIONS: Standardised WB-MRI protocols can be implemented and supported in prospective multi-centre clinical trials. Trial registration NCT03188172 clinicaltrials.gov; registration date 15th June 2017 https://clinicaltrials.gov/ct2/show/study/NCT03188172..
Knill, A.K.
Blackledge, M.D.
Curcean, A.
Larkin, J.
Turajlic, S.
Riddell, A.
Koh, D.M.
Messiou, C.
Winfield, J.M.
(2022). Optimisation of b-values for the accurate estimation of the apparent diffusion coefficient (ADC) in whole-body diffusion-weighted MRI in patients with metastatic melanoma. ,
.
show abstract
OBJECTIVE: To establish optimised diffusion weightings ('b-values') for acquisition of whole-body diffusion-weighted MRI (WB-DWI) for estimation of the apparent diffusion coefficient (ADC) in patients with metastatic melanoma (MM). Existing recommendations for WB-DWI have not been optimised for the tumour properties in MM; therefore, evaluation of acquisition parameters is essential before embarking on larger studies. METHODS: Retrospective clinical data and phantom experiments were used. Clinical data comprised 125 lesions from 14 examinations in 11 patients with multifocal MM, imaged before and/or after treatment with immunotherapy at a single institution. ADC estimates from these data were applied to a model to estimate the optimum b-value. A large non-diffusing phantom was used to assess eddy current-induced geometric distortion. RESULTS: Considering all tumour sites from pre- and post-treatment examinations together, metastases exhibited a large range of mean ADC values, [0.67-1.49] × 10-3 mm2/s, and the optimum high b-value (bhigh) for ADC estimation was 1100 (10th-90th percentile: 740-1790) s/mm2. At higher b-values, geometric distortion increased, and longer echo times were required, leading to reduced signal. CONCLUSIONS: Theoretical optimisation gave an optimum bhigh of 1100 (10th-90th percentile: 740-1790) s/mm2 for ADC estimation in MM, with the large range of optimum b-values reflecting the wide range of ADC values in these tumours. Geometric distortion and minimum echo time increase at higher b-values and are not included in the theoretical optimisation; bhigh in the range 750-1100 s/mm2 should be adopted to maintain acceptable image quality but performance should be evaluated for a specific scanner. KEY POINTS: • Theoretical optimisation gave an optimum high b-value of 1100 (10th-90th percentile: 740-1790) s/mm2 for ADC estimation in metastatic melanoma. • Considering geometric distortion and minimum echo time (TE), a b-value in the range 750-1100 s/mm2 is recommended. • Sites should evaluate the performance of specific scanners to assess the effect of geometric distortion and minimum TE..
Latifoltojar, A.
Boyd, K.
Riddell, A.
Kaiser, M.
Messiou, C.
(2021). Characterising spatial heterogeneity of multiple myeloma in high resolution by whole body magnetic resonance imaging: Towards macro-phenotype driven patient management. Magnetic resonance imaging,
Vol.75,
pp. 60-64.
show abstract
Diagnosis of patients suspected of multiple myeloma requires a combination of serological and biochemical tests, bone marrow aspirate (BMA) and/or bone marrow trephine (BMT) biopsies as well as complementary information provided by whole-body cross-sectional imaging studies. However, given the heterogeneous nature of multiple myeloma, discrepancies can arise between disease burden on trephine and extent of disease within the marrow on whole-body magnetic resonance imaging (WB-MRI). Here, for the first time, we report on a series of symptomatic multiple myeloma patients for whom there was substantial discordance between disease burden on trephine and WB-MRI..
Messiou, C.
Porta, N.
Sharma, B.
Levine, D.
Koh, D.-.
Boyd, K.
Pawlyn, C.
Riddell, A.
Downey, K.
Croft, J.
Morgan, V.
Stern, S.
Cheung, B.
Kyriakou, C.
Kaczmarek, P.
Winfield, J.
Blackledge, M.
Oyen, W.J.
Kaiser, M.F.
(2021). Prospective Evaluation of Whole-Body MRI versus FDG PET/CT for Lesion Detection in Participants with Myeloma. Radiology: imaging cancer,
Vol.3
(5),
pp. e210048-e210048.
Kousi, E.
Messiou, C.
Miah, A.
Orton, M.
Haas, R.
Thway, K.
Hopkinson, G.
Zaidi, S.
Smith, M.
Barquin, E.
Moskovic, E.
Fotiadis, N.
Strauss, D.
Hayes, A.
Schmidt, M.A.
(2021). Descriptive analysis of MRI functional changes occurring during reduced dose radiotherapy for myxoid liposarcomas. ,
Vol.94
(1126),
p. 20210310.
show abstract
OBJECTIVES: Myxoid liposarcomas (MLS) show enhanced response to radiotherapy due to their distinctive vascular pattern and therefore could be effectively treated with lower radiation doses. This is a descriptive study to explore the use of functional MRI to identify response in a uniform cohort of MLS patients treated with reduced dose radiotherapy. METHODS: 10 patients with MLS were imaged pre-, during, and post-radiotherapy receiving reduced dose radiotherapy and the response to treatment was histopathologically assessed post-radiotherapy. Apparent diffusion coefficient (ADC), T2* relaxation time, volume transfer constant (Ktrans), initial area under the gadolinium curve over 60 s (IAUGC60) and (Gd) were estimated for a central tumour volume. RESULTS: All parameters showed large inter- and intrasubject variabilities. Pre-treatment (Gd), IAUGC60 and Ktrans were significantly different between responders and non-responders. Post-radiotherapy reductions from baseline were demonstrated for T2*, (Gd), IAUGC60 and Ktrans for responders. No statistically significant ADC differences were demonstrated between the two response groups. Significantly greater early tumour volume reductions were observed for responders. CONCLUSIONS: MLS are heterogenous lesions, characterised by a slow gradual contrast-agent uptake. Pre-treatment vascular parameters, early changes to tumour volume, vascular parameters and T2* have potential in identifying response to treatment. The delayed (Gd) is a suitable descriptive parameter, relying simply on T1 measurements. Volume changes precede changes in MLS functionality and could be used to identify early response. ADVANCES IN KNOWLEDGE: MLS are are characterised by slow gradual contrast-agent uptake. Measurement of the delayed contrast-agent uptake (Gd) is simple to implement and able to discriminate response..
Judson, I.
Messiou, C.
(2021). Vitamin D deficiency in the pathogenesis of leiomyoma and intravascular leiomyomatosis: A case report and review of the literature. Gynecologic oncology reports,
Vol.35,
pp. 100681-?.
show abstract
This is a case of recurrent intravascular leiomyomatosis in a pre-menopausal woman of African-Caribbean heritage. She presented in 2006 with multiple uterine leiomyomata, tumour invading the inferior vena cava (IVC) extending into the right atrium, and pulmonary metastases. Her initial presentation was treated surgically. On recurrence she was treated by oestrogen suppression using a combination of goserelin and letrozole, with a substantial response. She subsequently reported further regression of disease following exposure to strong sunlight enabling her to discontinue oestrogen suppression without relapse. The hypothesis is that the benefit was due to vitamin D. The role of hypovitaminosis D in the pathogenesis of uterine leiomyomata is discussed, including epidemiology data demonstrating a link between ethnicity and risk and the proven mechanisms by which vitamin D controls oestrogen and progesterone receptor expression and influences other signalling pathways involved in the pathogenesis of leiomyomas. Data indicating the intermediate malignancy nature of intravascular leiomyomatosis, are discussed. We are not aware of other reports indicating a link between intravascular leiomyomatosis and a lack of vitamin D..
Stacchiotti, S.
Miah, A.B.
Frezza, A.M.
Messiou, C.
Morosi, C.
Caraceni, A.
Antonescu, C.R.
Bajpai, J.
Baldini, E.
Bauer, S.
Biagini, R.
Bielack, S.
Blay, J.Y.
Bonvalot, S.
Boukovinas, I.
Bovee, J.V.
Boye, K.
Brodowicz, T.
Callegaro, D.
De Alava, E.
Deoras-Sutliff, M.
Dufresne, A.
Eriksson, M.
Errani, C.
Fedenko, A.
Ferraresi, V.
Ferrari, A.
Fletcher, C.D.
Garcia Del Muro, X.
Gelderblom, H.
Gladdy, R.A.
Gouin, F.
Grignani, G.
Gutkovich, J.
Haas, R.
Hindi, N.
Hohenberger, P.
Huang, P.
Joensuu, H.
Jones, R.L.
Jungels, C.
Kasper, B.
Kawai, A.
Le Cesne, A.
Le Grange, F.
Leithner, A.
Leonard, H.
Lopez Pousa, A.
Martin Broto, J.
Merimsky, O.
Merriam, P.
Miceli, R.
Mir, O.
Molinari, M.
Montemurro, M.
Oldani, G.
Palmerini, E.
Pantaleo, M.A.
Patel, S.
Piperno-Neumann, S.
Raut, C.P.
Ravi, V.
Razak, A.R.
Reichardt, P.
Rubin, B.P.
Rutkowski, P.
Safwat, A.A.
Sangalli, C.
Sapisochin, G.
Sbaraglia, M.
Scheipl, S.
Schöffski, P.
Strauss, D.
Strauss, S.J.
Sundby Hall, K.
Tap, W.D.
Trama, A.
Tweddle, A.
van der Graaf, W.T.
Van De Sande, M.A.
Van Houdt, W.
van Oortmerssen, G.
Wagner, A.J.
Wartenberg, M.
Wood, J.
Zaffaroni, N.
Zimmermann, C.
Casali, P.G.
Dei Tos, A.P.
Gronchi, A.
(2021). Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts. Esmo open,
Vol.6
(3),
pp. 100170-?.
show abstract
Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication..
Gennaro, N.
Reijers, S.
Bruining, A.
Messiou, C.
Haas, R.
Colombo, P.
Bodalal, Z.
Beets-Tan, R.
van Houdt, W.
van der Graaf, W.T.
(2021). Imaging response evaluation after neoadjuvant treatment in soft tissue sarcomas: Where do we stand?. Critical reviews in oncology/hematology,
Vol.160,
pp. 103309-103309.
Durie, E.
Nicholson, E.
Anthias, C.
Dunne, E.M.
Potter, M.
Ethell, M.
Messiou, C.
Brennan, J.
Eagle, S.
Talbot, J.
Smyth, G.
Ingram, W.
Saran, F.
Mandeville, H.C.
(2021). Determining the incidence of interstitial pneumonitis and chronic kidney disease following full intensity haemopoetic stem cell transplant conditioned using a forward-planned intensity modulated total body irradiation technique. Radiotherapy and oncology,
Vol.158,
pp. 97-103.
Petralia, G.
Koh, D.-.
Attariwala, R.
Busch, J.J.
Eeles, R.
Karow, D.
Lo, G.G.
Messiou, C.
Sala, E.
Vargas, H.A.
Zugni, F.
Padhani, A.R.
(2021). Oncologically Relevant Findings Reporting and Data System (ONCO-RADS): Guidelines for the Acquisition, Interpretation, and Reporting of Whole-Body MRI for Cancer Screening. Radiology,
Vol.299
(3),
pp. 494-507.
show abstract
Acknowledging the increasing number of studies describing the use of whole-body MRI for cancer screening, and the increasing number of examinations being performed in patients with known cancers, an international multidisciplinary expert panel of radiologists and a geneticist with subject-specific expertise formulated technical acquisition standards, interpretation criteria, and limitations of whole-body MRI for cancer screening in individuals at higher risk, including those with cancer predisposition syndromes. The Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) proposes a standard protocol for individuals at higher risk, including those with cancer predisposition syndromes. ONCO-RADS emphasizes structured reporting and five assessment categories for the classification of whole-body MRI findings. The ONCO-RADS guidelines are designed to promote standardization and limit variations in the acquisition, interpretation, and reporting of whole-body MRI scans for cancer screening. Published under a CC BY 4.0 license Online supplemental material is available for this article..
Wilkinson, M.J.
Snow, H.
Downey, K.
Thomas, K.
Riddell, A.
Francis, N.
Strauss, D.C.
Hayes, A.J.
Smith, M.J.
Messiou, C.
(2021). CT diagnosis of ilioinguinal lymph node metastases in melanoma using radiological characteristics beyond size and asymmetry. ,
Vol.5
(1),
p. zraa005.
show abstract
BACKGROUND: Diagnosis of lymph node (LN) metastasis in melanoma with non-invasive methods is challenging. The aim of this study was to evaluate the diagnostic accuracy of six LN characteristics on CT in detecting melanoma-positive ilioinguinal LN metastases, and to determine whether inguinal LN characteristics can predict pelvic LN involvement. METHODS: This was a single-centre retrospective study of patients with melanoma LN metastases at a tertiary cancer centre between 2008 and 2016. Patients who had preoperative contrast-enhanced CT assessment and ilioinguinal LN dissection were included. CT scans containing significant artefacts obscuring the pelvis were excluded. CT scans were reanalysed for six LN characteristics (extracapsular spread (ECS), minimum axis (MA), absence of fatty hilum (FH), asymmetrical cortical nodule (CAN), abnormal contrast enhancement (ACE) and rounded morphology (RM)) and compared with postoperative histopathological findings. RESULTS: A total of 90 patients were included. Median age was 58 (range 23-85) years. Eighty-eight patients (98 per cent) had pathology-positive inguinal disease and, of these, 45 (51 per cent) had concurrent pelvic disease. The most common CT characteristics found in pathology-positive inguinal LNs were MA greater than 10 mm (97 per cent), ACE (80 per cent), ECS (38 per cent) and absence of RM (38 per cent). In multivariable analysis, inguinal LN characteristics on CT indicative of pelvic disease were RM (odds ratio (OR) 3.3, 95 per cent c.i. 1.2 to 8.7) and ECS (OR 4.2, 1.6 to 11.3). Cloquet's node is known to be a poor predictor of pelvic spread. Pelvic LN disease was present in 50 per cent patients, but only 7 per cent had a pathology-positive Cloquet's node. CONCLUSION: Additional CT radiological characteristics, especially ECS and RM, may improve diagnostic accuracy and aid clinical decisions regarding the need for inguinal or ilioinguinal dissection..
Smrke, A.
Benson, C.
Strauss, D.C.
Hayes, A.J.
Thway, K.
Hallin, M.
Fisher, C.
Messiou, C.
Huang, P.H.
Jones, R.L.
Smith, M.J.
(2021). Gastrointestinal leiomyosarcoma demonstrate a predilection for distant recurrence and poor response to systemic treatments. European journal of surgical oncology,
Vol.47
(10),
pp. 2595-2601.
Wu, F.
Bernard, S.
Fayad, L.M.
Ilaslan, H.
Messiou, C.
Moulopoulos, L.A.
Mulligan, M.E.
(2021). Updates and Ongoing Challenges in Imaging of Multiple Myeloma: AJR Expert Panel Narrative Review. American journal of roentgenology,
Vol.217
(4),
pp. 775-785.
Shur, J.D.
Doran, S.J.
Kumar, S.
ap Dafydd, D.
Downey, K.
O’Connor, J.P.
Papanikolaou, N.
Messiou, C.
Koh, D.-.
Orton, M.R.
(2021). Radiomics in Oncology: A Practical Guide. Radiographics,
Vol.41
(6),
pp. 1717-1732.
Gronchi, A.
Miah, A.B.
Dei Tos, A.P.
Abecassis, N.
Bajpai, J.
Bauer, S.
Biagini, R.
Bielack, S.
Blay, J.Y.
Bolle, S.
Bonvalot, S.
Boukovinas, I.
Bovee, J.V.
Boye, K.
Brennan, B.
Brodowicz, T.
Buonadonna, A.
De Álava, E.
Del Muro, X.G.
Dufresne, A.
Eriksson, M.
Fagioli, F.
Fedenko, A.
Ferraresi, V.
Ferrari, A.
Frezza, A.M.
Gasperoni, S.
Gelderblom, H.
Gouin, F.
Grignani, G.
Haas, R.
Hassan, A.B.
Hecker-Nolting, S.
Hindi, N.
Hohenberger, P.
Joensuu, H.
Jones, R.L.
Jungels, C.
Jutte, P.
Kager, L.
Kasper, B.
Kawai, A.
Kopeckova, K.
Krákorová, D.A.
Le Cesne, A.
Le Grange, F.
Legius, E.
Leithner, A.
Lopez-Pousa, A.
Martin-Broto, J.
Merimsky, O.
Messiou, C.
Mir, O.
Montemurro, M.
Morland, B.
Morosi, C.
Palmerini, E.
Pantaleo, M.A.
Piana, R.
Piperno-Neumann, S.
Reichardt, P.
Rutkowski, P.
Safwat, A.A.
Sangalli, C.
Sbaraglia, M.
Scheipl, S.
Schöffski, P.
Sleijfer, S.
Strauss, D.
Strauss, S.
Sundby Hall, K.
Trama, A.
Unk, M.
van de Sande, M.A.
van der Graaf, W.T.
van Houdt, W.J.
Frebourg, T.
Casali, P.G.
Stacchiotti, S.
(2021). Soft tissue and visceral sarcomas: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up☆. Annals of oncology,
Vol.32
(11),
pp. 1348-1365.
Strauss, S.J.
Frezza, A.M.
Abecassis, N.
Bajpai, J.
Bauer, S.
Biagini, R.
Bielack, S.
Blay, J.Y.
Bolle, S.
Bonvalot, S.
Boukovinas, I.
Bovee, J.V.
Boye, K.
Brennan, B.
Brodowicz, T.
Buonadonna, A.
de Álava, E.
Dei Tos, A.P.
Garcia del Muro, X.
Dufresne, A.
Eriksson, M.
Fagioli, F.
Fedenko, A.
Ferraresi, V.
Ferrari, A.
Gaspar, N.
Gasperoni, S.
Gelderblom, H.
Gouin, F.
Grignani, G.
Gronchi, A.
Haas, R.
Hassan, A.B.
Hecker-Nolting, S.
Hindi, N.
Hohenberger, P.
Joensuu, H.
Jones, R.L.
Jungels, C.
Jutte, P.
Kager, L.
Kasper, B.
Kawai, A.
Kopeckova, K.
Krákorová, D.A.
Le Cesne, A.
Le Grange, F.
Legius, E.
Leithner, A.
López Pousa, A.
Martin-Broto, J.
Merimsky, O.
Messiou, C.
Miah, A.B.
Mir, O.
Montemurro, M.
Morland, B.
Morosi, C.
Palmerini, E.
Pantaleo, M.A.
Piana, R.
Piperno-Neumann, S.
Reichardt, P.
Rutkowski, P.
Safwat, A.A.
Sangalli, C.
Sbaraglia, M.
Scheipl, S.
Schöffski, P.
Sleijfer, S.
Strauss, D.
Sundby Hall, K.
Trama, A.
Unk, M.
van de Sande, M.A.
van der Graaf, W.T.
van Houdt, W.J.
Frebourg, T.
Ladenstein, R.
Casali, P.G.
Stacchiotti, S.
(2021). Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of oncology,
Vol.32
(12),
pp. 1520-1536.
Renn, A.
Adejolu, M.
Messiou, C.
Bhaludin, B.
Strauss, D.C.
Thway, K.
Moskovic, E.
(2021). Overview of malignant soft-tissue sarcomas of the limbs. Clinical radiology,
Vol.76
(12),
pp. 940.e1-940.e16.
Bhaludin, B.N.
Thway, K.
Adejolu, M.
Renn, A.
Kelly-Morland, C.
Fisher, C.
Jones, R.L.
Messiou, C.
Moskovic, E.
(2021). Imaging features of primary sites and metastatic patterns of angiosarcoma. Insights into imaging,
Vol.12
(1),
pp. 189-?.
show abstract
Angiosarcomas are rare, aggressive soft tissue sarcomas originating from endothelial cells of lymphatic or vascular origin and associated with a poor prognosis. The clinical and imaging features of angiosarcomas are heterogeneous with a wide spectrum of findings involving any site of the body, but these most commonly present as cutaneous disease in the head and neck of elderly men. MRI and CT are complementary imaging techniques in assessing the extent of disease, focality and involvement of adjacent anatomical structures at the primary site of disease. CT plays an important role in the evaluation of metastatic disease. Given the wide range of imaging findings, correlation with clinical findings, specific risk factors and patterns of metastatic disease can help narrow the differential diagnosis. The final diagnosis should be confirmed with histopathology and immunohistochemistry in combination with clinical and imaging findings in a multidisciplinary setting with specialist sarcoma expertise. The purpose of this review is to describe the clinical and imaging features of primary sites and metastatic patterns of angiosarcomas utilising CT and MRI..
Doran, S.J.
Kumar, S.
Orton, M.
d'Arcy, J.
Kwaks, F.
O'Flynn, E.
Ahmed, Z.
Downey, K.
Dowsett, M.
Turner, N.
Messiou, C.
Koh, D.-.
(2021). "Real-world" radiomics from multi-vendor MRI: an original retrospective study on the prediction of nodal status and disease survival in breast cancer, as an exemplar to promote discussion of the wider issues. Cancer imaging : the official publication of the international cancer imaging society,
Vol.21
(1),
pp. 37-?.
show abstract
Background Most MRI radiomics studies to date, even multi-centre ones, have used "pure" datasets deliberately accrued from single-vendor, single-field-strength scanners. This does not reflect aspirations for the ultimate generalisability of AI models. We therefore investigated the development of a radiomics signature from heterogeneous data originating on six different imaging platforms, for a breast cancer exemplar, in order to provide input into future discussions of the viability of radiomics in "real-world" scenarios where image data are not controlled by specific trial protocols but reflective of routine clinical practice.Methods One hundred fifty-six patients with pathologically proven breast cancer underwent multi-contrast MRI prior to neoadjuvant chemotherapy and/or surgery. From these, 92 patients were identified for whom T2-weighted, diffusion-weighted and contrast-enhanced T1-weighted sequences were available, as well as key clinicopathological variables. Regions-of-interest were drawn on the above image types and, from these, semantic and calculated radiomics features were derived. Classification models using a variety of methods, both with and without recursive feature elimination, were developed to predict pathological nodal status. Separately, we applied the same methods to analyse the information carried by the radiomic features regarding the originating scanner type and field strength. Repeated, ten-fold cross-validation was employed to verify the results. In parallel work, survival modelling was performed using random survival forests.Results Prediction of nodal status yielded mean cross-validated AUC values of 0.735 ± 0.15 (SD) for clinical variables alone, 0.673 ± 0.16 (SD) for radiomic features only, and 0.764 ± 0.16 (SD) for radiomics and clinical features together. Prediction of scanner platform from the radiomics features yielded extremely high values of AUC between 0.91 and 1 for the different classes examined indicating the presence of confounding features for the nodal status classification task. Survival analysis, gave out-of-bag prediction errors of 19.3% (clinical features only), 36.9-51.8% (radiomic features from different combinations of image contrasts), and 26.7-35.6% (clinical plus radiomics features).Conclusions Radiomic classification models whose predictive ability was consistent with previous single-vendor, single-field strength studies have been obtained from multi-vendor, multi-field-strength data, despite clear confounding information being present. However, our sample size was too small to obtain useful survival modelling results..
Kalantar, R.
Lin, G.
Winfield, J.M.
Messiou, C.
Lalondrelle, S.
Blackledge, M.D.
Koh, D.-.
(2021). Automatic Segmentation of Pelvic Cancers Using Deep Learning: State-of-the-Art Approaches and Challenges. Diagnostics (basel, switzerland),
Vol.11
(11).
show abstract
The recent rise of deep learning (DL) and its promising capabilities in capturing non-explicit detail from large datasets have attracted substantial research attention in the field of medical image processing. DL provides grounds for technological development of computer-aided diagnosis and segmentation in radiology and radiation oncology. Amongst the anatomical locations where recent auto-segmentation algorithms have been employed, the pelvis remains one of the most challenging due to large intra- and inter-patient soft-tissue variabilities. This review provides a comprehensive, non-systematic and clinically-oriented overview of 74 DL-based segmentation studies, published between January 2016 and December 2020, for bladder, prostate, cervical and rectal cancers on computed tomography (CT) and magnetic resonance imaging (MRI), highlighting the key findings, challenges and limitations..
Brown, S.
Sherratt, D.
Hinsley, S.
Flanagan, L.
Roberts, S.
Walker, K.
Hall, A.
Pratt, G.
Messiou, C.
Jenner, M.
Kaiser, M.
Myeloma UK Early Phase Clinical Trial Network,
(2021). MUKnine OPTIMUM protocol: a screening study to identify high-risk patients with multiple myeloma suitable for novel treatment approaches combined with a phase II study evaluating optimised combination of biological therapy in newly diagnosed high-risk multiple myeloma and plasma cell leukaemia. Bmj open,
Vol.11
(3),
pp. e046225-?.
show abstract
Introduction Multiple myeloma (MM) is a plasma cell tumour with over 5800 new cases each year in the UK. The introduction of biological therapies has improved outcomes for the majority of patients with MM, but in approximately 20% of patients the tumour is characterised by genetic changes which confer a significantly poorer prognosis, generally termed high-risk (HR) MM. It is important to diagnose these genetic changes early and identify more effective first-line treatment options for these patients.Methods and analysis The Myeloma UK nine OPTIMUM trial (MUK nine ) evaluates novel treatment strategies for patients with HRMM. Patients with suspected or newly diagnosed MM, fit for intensive therapy, are offered participation in a tumour genetic screening protocol (MUK nine a ), with primary endpoint proportion of patients with molecular screening performed within 8 weeks. Patients identified as molecularly HR are invited into the phase II, single-arm, multicentre trial (MUK nine b ) investigating an intensive treatment schedule comprising bortezomib, lenalidomide, daratumumab, low-dose cyclophosphamide and dexamethasone, with single high-dose melphalan and autologous stem cell transplantation (ASCT) followed by combination consolidation and maintenance therapy. MUK nine b primary endpoints are minimal residual disease (MRD) at day 100 post-ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. The trial uses a Bayesian decision rule to determine if this treatment strategy is sufficiently active for further study. Patients identified as not having HR disease receive standard treatment and are followed up in a cohort study. Exploratory studies include longitudinal whole-body diffusion-weighted MRI for imaging MRD testing.Ethics and dissemination Ethics approval London South East Research Ethics Committee (Ref: 17/LO/0022, 17/LO/0023). Results of studies will be submitted for publication in a peer-reviewed journal.Trial registration number ISRCTN16847817, May 2017; Pre-results..
Fendler, A.
Shepherd, S.T.
Au, L.
Wilkinson, K.A.
Wu, M.
Byrne, F.
Cerrone, M.
Schmitt, A.M.
Joharatnam-Hogan, N.
Shum, B.
Tippu, Z.
Rzeniewicz, K.
Boos, L.A.
Harvey, R.
Carlyle, E.
Edmonds, K.
Del Rosario, L.
Sarker, S.
Lingard, K.
Mangwende, M.
Holt, L.
Ahmod, H.
Korteweg, J.
Foley, T.
Bazin, J.
Gordon, W.
Barber, T.
Emslie-Henry, A.
Xie, W.
Gerard, C.L.
Deng, D.
Wall, E.C.
Agua-Doce, A.
Namjou, S.
Caidan, S.
Gavrielides, M.
MacRae, J.
Kelly, G.
Peat, K.
Kelly, D.
Murra, A.
Kelly, K.
O'Flaherty, M.
Dowdie, L.
Ash, N.
Gronthoud, F.
Shea, R.L.
Gardner, G.
Murray, D.
Kinnaird, F.
Cui, W.
Pascual, J.
Rodney, S.
Mencel, J.
Curtis, O.
Stephenson, C.
Robinson, A.
Oza, B.
Farag, S.
Leslie, I.
Rogiers, A.
Iyengar, S.
Ethell, M.
Messiou, C.
Cunningham, D.
Chau, I.
Starling, N.
Turner, N.
Welsh, L.
van As, N.
Jones, R.L.
Droney, J.
Banerjee, S.
Tatham, K.C.
O'Brien, M.
Harrington, K.
Bhide, S.
Okines, A.
Reid, A.
Young, K.
Furness, A.J.
Pickering, L.
Swanton, C.
Gandhi, S.
Gamblin, S.
Bauer, D.L.
Kassiotis, G.
Kumar, S.
Yousaf, N.
Jhanji, S.
Nicholson, E.
Howell, M.
Walker, S.
Wilkinson, R.J.
Larkin, J.
Turajlic, S.
(2021). Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study. Nature cancer,
,
pp. ?-? (31).
Winfield, J.M.
Blackledge, M.D.
Tunariu, N.
Koh, D.-.
Messiou, C.
(2021). Whole-body MRI: a practical guide for imaging patients with malignant bone disease. Clinical radiology,
.
show abstract
Whole-body magnetic resonance imaging (MRI) is now a crucial tool for the assessment of the extent of systemic malignant bone disease and response to treatment, and forms part of national and international recommendations for imaging patients with myeloma or metastatic prostate cancer. Recent developments in scanners have enabled acquisition of good-quality whole-body MRI data within 45 minutes on modern MRI systems from all main manufacturers. This provides complimentary morphological and functional whole-body imaging; however, lack of prior experience and acquisition times required can act as a barrier to adoption in busy radiology departments. This article aims to tackle the former by reviewing the indications and providing guidance for technical delivery and clinical interpretation of whole-body MRI for patients with malignant bone disease..
Lai, A.Y.
Riddell, A.
Barwick, T.
Boyd, K.
Rockall, A.
Kaiser, M.
Koh, D.-.
Saffar, H.
Yusuf, S.
Messiou, C.
(2020). Interobserver agreement of whole-body magnetic resonance imaging is superior to whole-body computed tomography for assessing disease burden in patients with multiple myeloma. European radiology,
Vol.30
(1),
pp. 320-327.
show abstract
Objectives Whole-body MRI (WB-MRI) is recommended by the International Myeloma Working Group for all patients with asymptomatic myeloma and solitary plasmacytoma and by the UK NICE guidance for all patients with suspected myeloma. Some centres unable to offer WB-MRI offer low-dose whole-body CT (WB-CT). There are no studies comparing interobserver agreement and disease detection of contemporary WB-MRI (anatomical imaging and DWI) versus WB-CT. Our primary aim is to compare the interobserver agreement between WB-CT and WB-MRI in the diagnosis of myeloma.Methods Consecutive patients with newly diagnosed myeloma imaged with WB-MRI and WB-CT were prospectively reviewed. For each body region and modality, two experienced and two junior radiologists scored disease burden with final scores by consensus. Intraclass correlation coefficients (ICC), median scores, Wilcoxon signed-rank test and Spearman's correlation coefficients were calculated.Results There was no significant difference in overall observer scores between WB-MRI and WB-CT (p = 0.87). For experienced observers, interobserver agreement for WB-MRI was superior to WB-CT overall and for each region, without overlap in whole-skeleton confidence intervals (ICC 0.98 versus 0.77, 95%CI 0.96-0.99 versus 0.45-0.91). For inexperienced observers, although there is a trend for a better interobserver score for the whole skeleton on WB-MRI (ICC 0.95, 95%CI 0.72-0.98) than on WB-CT (ICC 0.72, 95%CI 0.34-0.88), the confidence intervals overlap.Conclusions WB-MRI offers excellent interobserver agreement which is superior to WB-CT for experienced observers. Although the overall burden was similar across both modalities, patients with lower disease burdens where MRI could be advantageous are not included in this series.Key points • Whole-body MRI is recommended by the International Myeloma Working Group for patients with multiple myeloma and solitary plasmacytoma and by the NICE guidance for those with suspected multiple myeloma. • Some centres unable to offer whole-body MRI (WB-MRI) offer low-dose whole-body CT (WB-CT). • This prospective study demonstrates that contemporary WB-MRI (with anatomical sequences and DWI) provides better interobserver agreement in assessing myeloma disease burden for the whole skeleton and across any individual body region in myeloma patients when compared with low-dose whole-body CT..
Drabbe, C.
Benson, C.
Younger, E.
Zaidi, S.
Jones, R.L.
Judson, I.
Chisholm, J.
Mandeville, H.
Fisher, C.
Thway, K.
Al Muderis, O.
Messiou, C.
Strauss, D.
Husson, O.
Miah, A.
Van der Graaf, W.T.
(2020). Embryonal and Alveolar Rhabdomyosarcoma in Adults: Real-Life Data From a Tertiary Sarcoma Centre. Clinical oncology,
Vol.32
(1),
pp. e27-e35.
Hameed, M.
Sandhu, A.
Soneji, N.
Amiras, D.
Rockall, A.
Messiou, C.
Wallitt, K.
Barwick, T.D.
(2020). Pictorial review of whole body MRI in myeloma: emphasis on diffusion-weighted imaging. The british journal of radiology,
Vol.93
(1115),
pp. 20200312-20200312.
show abstract
There have been major advances in myeloma imaging over the past few years with focal lesions on imaging now forming part of the disease defining criteria. Whole body diffusion-weighted MRI (WB-MRI) is considered the most sensitive technique for the detection of focal active lesions. This pictorial review will focus on imaging the spectrum of myelomatous disorders on WB-MRI including diffusion and Dixon sequences. The typical imaging patterns of disease are demonstrated including in the contexts of staging, presumed solitary plasmacytoma, smouldering myeloma and examples of paramedullary and extramedullary disease. The utility of diffusion-weighted imaging in response assessment is a major advantage and this will be exemplified here. .
Mcaddy, N.C.
Hallin, M.
Strauss, D.
Smith, M.
Hayes, A.
Yusuf, S.
Moskovic, E.
Fotiadis, N.
van Houdt, W.
Jones, R.L.
Gronchi, A.
Thway, K.
Messiou, C.
(2020). CT imaging improves histopathological grading of retroperitoneal leiomyosarcomas. European journal of surgical oncology,
Vol.46
(2),
pp. 288-292.
Gennatas, S.
Chamberlain, F.
Smrke, A.
Stewart, J.
Hayes, A.
Roden, L.
Messiou, C.
Kowa, J.-.
Estival, A.
Chauhan, D.
Thway, K.
Fisher, C.
van der Graaf, W.T.
Jones, R.L.
Benson, C.
(2020). A Timely Oral Option: Single-Agent Vinorelbine in Desmoid Tumors. ,
Vol.25
(12),
pp. e2013-e2016.
show abstract
INTRODUCTION: Desmoid tumors (DT) are rare collagen-forming tumors that can exhibit locally aggressive patterns of behavior. The aim of this study was to evaluate the efficacy and safety of treatment of DT with single-agent oral vinorelbine. MATERIALS AND METHODS: A retrospective review of patients treated with vinorelbine 90 mg orally on days 1, 8, and 15 of a 28-day cycle from January 2004 to July 2019 was performed. Response was assessed using RECIST version 1.1. Descriptive statistics were employed. RESULTS: A total of 29 patients were included. Response rate was 20.7% (6/29), and clinical benefit rate (response by RECIST 1.1 and/or clinical symptom improvement) was 65.5% (19/29). No patient experienced grade 3 or above toxicity. Common toxicities were grade 1-2 nausea (14/26, 48.3%), fatigue (9/26, 31.0%), and diarrhea (4/26, 13.8%). CONCLUSION: Single-agent oral vinorelbine is an effective, safe, and well-tolerated treatment for DT. It represents a new oral alternative for management of DT..
Desmoid Tumor Working Group,
(2020). The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients. European journal of cancer (oxford, england : 1990),
Vol.127,
pp. 96-107.
show abstract
Desmoid tumor (DT; other synonymously used terms: Desmoid-type fibromatosis, aggressive fibromatosis) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. Previously surgery was the standard primary treatment modality; however, in recent years a paradigm shift towards a more conservative management has been introduced and an effort to harmonise the strategy amongst clinicians has been made. We present herein an evidence-based, joint global consensus guideline approach to the management of this disease focussing on: molecular genetics, indications for an active treatment, and available systemic therapeutic options. This paper follows a one-day consensus meeting held in Milan, Italy, in June 2018 under the auspices of the European Reference Network for rare solid adult cancers, EURACAN, the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) as well as Sarcoma Patients EuroNet (SPAEN) and The Desmoid tumour Research Foundation (DTRF). The meeting brought together over 50 adult and pediatric sarcoma experts from different disciplines, patients and patient advocates from Europe, North America and Japan..
Mayerhoefer, M.E.
Archibald, S.J.
Messiou, C.
Staudenherz, A.
Berzaczy, D.
Schöder, H.
(2020). MRI and PET/MRI in hematologic malignancies. Journal of magnetic resonance imaging,
Vol.51
(5),
pp. 1325-1335.
Arthurs, O.J.
Goh, V.
Hoggard, N.
Booth, T.
Messiou, C.
The, J.
Plumb, A.
Bidaut, L.
Turmezei, T.
Jethwa, K.
Robinson, P.
Hall-Craggs, M.
(2020). Professional development and research are being neglected: a commentary on the 2019 RCR radiologists' supporting professional activities (SPA) survey. Clinical radiology,
Vol.75
(5),
pp. 348-350.
Kaiser, M.F.
Boyd, K.
Koh, D.
Rata, M.
Blackledge, M.
Messiou, C.
(2020). Improving real‐world myeloma patient access to whole body MRI through “open‐access” knowledge sharing: The UK experience. Ejhaem,
Vol.1
(1),
pp. 361-363.
Winder, A.
Strauss, D.C.
Jones, R.L.
Benson, C.
Messiou, C.
Chaudry, M.A.
Smith, M.J.
(2020). Robotic surgery for gastric gastrointestinal stromal tumors: A single center case series. Journal of surgical oncology,
Vol.122
(4),
pp. 691-698.
Snow, H.
Hazell, S.
Francis, N.
Mohammed, K.
O'Neill, S.
Davies, E.
Mansfield, D.
Messiou, C.
Hujairi, N.
Nicol, D.
Harrington, K.
Smith, M.
(2020). Prostate-specific membrane antigen expression in melanoma metastases. Journal of cutaneous pathology,
Vol.47
(12),
pp. 1115-1122.
show abstract
Background Prostate-specific membrane antigen (PSMA) is a prostatic epithelial protein that is used as a radiotracer (68Ga-PSMA-11) for prostate cancer staging. PSMA-PET/CT (positron emission tomography/computed tomography) performed for prostate cancer has been observed to detect melanoma metastases. The aim of this study was to investigate the performance of PSMA immunohistochemistry on resected melanoma metastases to explore its use as a diagnostic imaging biomarker for melanoma.Methods A total of 41 specimens with stage III/IV melanoma were stained with PSMA immunohistochemistry. All specimens required both disease and control regions. Two pathologists scored the specimens and a receiver operating characteristic (ROC) curve was plotted. Western blot and multiplex immunofluorescence were also performed.Results The area under the ROC curve was 0.82, suggesting that PSMA has excellent discriminatory power in melanoma metastases. Sensitivity is 82.9% and specificity 73.2%. Immunohistochemistry and Western blot reveal that PSMA staining in melanoma consistently and most intensely occurs in tumor neovasculature. Multiplex immunofluorescence shows that melanocytes may also weakly express PSMA.Conclusion The performance of PSMA immunohistochemistry in melanoma metastases contrasts with that reported in prostate cancer studies. This study indicates that PSMA shows promise for use as a novel biomarker in melanoma and justifies further research in the clinical setting with potential as a PET/CT radiotracer and intraoperative fluorescence marker for melanoma..
Mcaddy, N.C.
Saffar, H.
Litière, S.
Jespers, P.
Schöffski, P.
Messiou, C.
(2020). iCREATE: imaging features of primary and metastatic alveolar soft part sarcoma from the EORTC CREATE study. Cancer imaging,
Vol.20
(1).
show abstract
Abstract
Background
Alveolar Soft Part Sarcoma (ASPS) is a rare, slow-growing, but highly vascular soft tissue sarcoma, characterised by a high rate of metastases at presentation. Although imaging features of the primary are well described, less detail is available on the imaging pattern of metastatic ASPS. The EORTC 90101 (CREATE) study assessed the efficacy of Crizotinib in patients with metastatic ASPS and presents a unique opportunity to describe the imaging phenotype of primary and metastatic ASPS, based on prospectively collected imaging.
Methods
A retrospective review of the staging CT scans of 32 patients with ASPS from the CREATE study was undertaken and the imaging features of primary and metastatic disease were assessed.
Results
Imaging of the primary tumour was available in 7/32 cases (28%). All primary tumours demonstrated marked vascularity with prominent feeding vessels (7/7, 100%). The most frequent sites of metastases included lung (30/32, 94%), nodal (7/32, 22%), bone (5/32, 16%) and muscle/subcutaneous (5/32, 16%). Features of hypervascularity were identified at all sites, more appreciable in the lungs, with feeding vessels frequently demonstrated in pulmonary metastases (21/32, 66%).
Conclusion
Analysis of imaging from the CREATE cohort of patients with metastatic ASPS demonstrates that metastases from ASPS are predominantly hypervascular and demonstrate feeding vessels comparable to primary ASPS, suggesting potential sensitivity of this rare sarcoma for antivascular/antiangiogenic treatment approaches.
.
Cojocaru, E.
Thway, K.
Fisher, C.
Messiou, C.
Zaidi, S.
Miah, A.B.
Benson, C.
Gennatas, S.
Huang, P.
Jones, R.L.
(2020). Efficacy of Gemcitabine-based Chemotherapy in Clear Cell Sarcoma of Soft Tissue. Anticancer research,
Vol.40
(12),
pp. 7003-7007.
show abstract
Background/aim Clear cell sarcoma (CCS) is an aggressive sarcoma subtype, resistant to conventional anthracycline-based chemotherapy and radiation. The diagnosis is often challenging due to similarities with malignant melanoma.Patients and methods We aimed to analyse the activity of gemcitabine-based chemotherapy in a cohort of patients with CCS treated at the Royal Marsden Hospital.Results Five patients with metastatic CCS received gemcitabine as first- or second-line systemic therapy. The median time-to-progression was 10 weeks. The median number of cycles of gemcitabine-based therapy was 3 (range=2-7 cycles). Median overall survival in our cohort was 66 months from the initial diagnosis but in the metastatic setting, the overall survival was reduced to 28 months.Conclusion Gemcitabine-based therapy has modest activity in CCS. There remains a significant unmet medical need for novel, effective therapies for this disease..
Isaac, A.
Lecouvet, F.
Dalili, D.
Fayad, L.
Pasoglou, V.
Papakonstantinou, O.
Ahlawat, S.
Messiou, C.
Weber, M.-.
Padhani, A.R.
(2020). Detection and Characterization of Musculoskeletal Cancer Using Whole-Body Magnetic Resonance Imaging. Seminars in musculoskeletal radiology,
Vol.24
(06),
pp. 726-750.
show abstract
AbstractWhole-body magnetic resonance imaging (WB-MRI) is gradually being integrated into clinical pathways for the detection, characterization, and staging of malignant tumors including those arising in the musculoskeletal (MSK) system. Although further developments and research are needed, it is now recognized that WB-MRI enables reliable, sensitive, and specific detection and quantification of disease burden, with clinical applications for a variety of disease types and a particular application for skeletal involvement. Advances in imaging techniques now allow the reliable incorporation of WB-MRI into clinical pathways, and guidelines recommending its use are emerging. This review assesses the benefits, clinical applications, limitations, and future capabilities of WB-MRI in the context of other next-generation imaging modalities, as a qualitative and quantitative tool for the detection and characterization of skeletal and soft tissue MSK malignancies..
Croft, J.
Riddell, A.
Koh, D.-.
Downey, K.
Blackledge, M.
Usher, M.
Boyd, K.
Kaiser, M.
Messiou, C.
(2020). Inter-observer agreement of baseline whole body MRI in multiple myeloma. Cancer imaging : the official publication of the international cancer imaging society,
Vol.20
(1),
pp. 48-?.
show abstract
Background Whole body magnetic resonance imaging (MRI) is now incorporated into international guidance for imaging patients with multiple myeloma. The aim of this study was to investigate inter-observer agreement of triple reported baseline whole-body MRI in myeloma and highlight potential pitfalls.Methods Fifty-seven patients with symptomatic myeloma at first presentation or relapse and planned for autologous stem cell transplant were included. All patients completed baseline whole body MRI within 2 weeks prior to starting treatment. Each scan was reported independently by 3 radiologists using a defined scoring system. Differences in observer scores were compared using analysis of variance (ANOVA) and inter-observer agreement assessed using intra class correlation coefficient (ICC).Results There was no significant difference in mean observer scores for whole skeleton and ICC demonstrated excellent inter-observer agreement at 0.91. ICC varied between skeletal regions with spine, pelvis and ribs showing good inter-observer agreement, whereas skull and long bones were moderate. Scans with variation in observer scores were re-examined and cause of discrepancies identified. This information was used to describe potential anatomical pitfalls in reporting .Conclusion Whole-body MRI has excellent inter-observer agreement in reporting symptomatic myeloma at baseline. Inter-observer agreement varied between skeletal regions highlighting specific areas of difficulty..
CHAMBERLAIN, F.
ENGELMANN, B.
AL-MUDERIS, O.
MESSIOU, C.
THWAY, K.
MIAH, A.
ZAIDI, S.
CONSTANTINIDOU, A.
BENSON, C.
GENNATAS, S.
JONES, R.L.
(2020). Low-grade Fibromyxoid Sarcoma: Treatment Outcomes and Efficacy of Chemotherapy. In vivo,
Vol.34
(1),
pp. 239-245.
SEBIO, A.N.
CONSTANTINIDOU, A.
BENSON, C.
ANTONIOU, G.
MESSIOU, C.
MIAH, A.
ZAIDI, S.
PETRUCKEVITCH, A.N.
AL-MUDERIS, O.
THWAY, K.
VAN DER GRAAF, W.T.
JONES, R.L.
(2019). Gemcitabine Re-challenge in Metastatic Soft Tissue Sarcomas: A Therapeutic Option for Selected Patients. Anticancer research,
Vol.39
(1),
pp. 347-351.
Winfield, J.M.
Miah, A.B.
Strauss, D.
Thway, K.
Collins, D.J.
deSouza, N.M.
Leach, M.O.
Morgan, V.A.
Giles, S.L.
Moskovic, E.
Hayes, A.
Smith, M.
Zaidi, S.H.
Henderson, D.
Messiou, C.
(2019). Utility of Multi-Parametric Quantitative Magnetic Resonance Imaging for Characterization and Radiotherapy Response Assessment in Soft-Tissue Sarcomas and Correlation With Histopathology. Frontiers in oncology,
Vol.9,
pp. 280-?.
show abstract
Purpose: To evaluate repeatability of quantitative multi-parametric MRI in retroperitoneal sarcomas, assess parameter changes with radiotherapy, and correlate pre-operative values with histopathological findings in the surgical specimens. Materials and Methods: Thirty patients with retroperitoneal sarcoma were imaged at baseline, of whom 27 also underwent a second baseline examination for repeatability assessment. 14/30 patients were treated with pre-operative radiotherapy and were imaged again after completing radiotherapy (50.4 Gy in 28 daily fractions, over 5.5 weeks). The following parameter estimates were assessed in the whole tumor volume at baseline and following radiotherapy: apparent diffusion coefficient (ADC), parameters of the intra-voxel incoherent motion model of diffusion-weighted MRI (D, f , D * ), transverse relaxation rate, fat fraction, and enhancing fraction after gadolinium-based contrast injection. Correlation was evaluated between pre-operative quantitative parameters and histopathological assessments of cellularity and fat fraction in post-surgical specimens (ClinicalTrials.gov, registration number NCT01902667). Results: Upper and lower 95% limits of agreement were 7.1 and -6.6%, respectively for median ADC at baseline. Median ADC increased significantly post-radiotherapy. Pre-operative ADC and D were negatively correlated with cellularity ( r = -0.42, p = 0.01, 95% confidence interval (CI) -0.22 to -0.59 for ADC; r = -0.45, p = 0.005, 95% CI -0.25 to -0.62 for D), and fat fraction from Dixon MRI showed strong correlation with histopathological assessment of fat fraction ( r = 0.79, p = 10 -7 , 95% CI 0.69-0.86). Conclusion: Fat fraction on MRI corresponded to fat content on histology and therefore contributes to lesion characterization. Measurement repeatability was excellent for ADC; this parameter increased significantly post-radiotherapy even in disease categorized as stable by size criteria, and corresponded to cellularity on histology. ADC can be utilized for characterizing and assessing response in heterogeneous retroperitoneal sarcomas..
Blackledge, M.D.
Winfield, J.M.
Miah, A.
Strauss, D.
Thway, K.
Morgan, V.A.
Collins, D.J.
Koh, D.-.
Leach, M.O.
Messiou, C.
(2019). Supervised Machine-Learning Enables Segmentation and Evaluation of Heterogeneous Post-treatment Changes in Multi-Parametric MRI of Soft-Tissue Sarcoma. Frontiers in oncology,
Vol.9,
pp. 941-?.
show abstract
Background: Multi-parametric MRI provides non-invasive methods for response assessment of soft-tissue sarcoma (STS) from non-surgical treatments. However, evaluation of MRI parameters over the whole tumor volume may not reveal the full extent of post-treatment changes as STS tumors are often highly heterogeneous, including cellular tumor, fat, necrosis, and cystic tissue compartments. In this pilot study, we investigate the use of machine-learning approaches to automatically delineate tissue compartments in STS, and use this approach to monitor post-radiotherapy changes. Methods: Eighteen patients with retroperitoneal sarcoma were imaged using multi-parametric MRI; 8/18 received a follow-up imaging study 2-4 weeks after pre-operative radiotherapy. Eight commonly-used supervised machine-learning techniques were optimized for classifying pixels into one of five tissue sub-types using an exhaustive cross-validation approach and expert-defined regions of interest as a gold standard. Final pixel classification was smoothed using a Markov Random Field (MRF) prior distribution on the final machine-learning models. Findings: 5/8 machine-learning techniques demonstrated high median cross-validation accuracies (82.2%, range 80.5-82.5%) with no significant difference between these five methods. One technique was selected (Naïve-Bayes) due to its relatively short training and class-prediction times (median 0.73 and 0.69 ms, respectively on a 3.5 GHz personal machine). When combined with the MRF-prior, this approach was successfully applied in all eight post-radiotherapy imaging studies and provided visualization and quantification of changes to independent STS sub-regions following radiotherapy for heterogeneous response assessment. Interpretation: Supervised machine-learning approaches to tissue classification in multi-parametric MRI of soft-tissue sarcomas provide quantitative evaluation of heterogeneous tissue changes following radiotherapy..
Barwick, T.
Bretsztajn, L.
Wallitt, K.
Amiras, D.
Rockall, A.
Messiou, C.
(2019). Imaging in myeloma with focus on advanced imaging techniques. The british journal of radiology,
Vol.92
(1096),
pp. 20180768-20180768.
Messiou, C.
Hillengass, J.
Delorme, S.
Lecouvet, F.E.
Moulopoulos, L.A.
Collins, D.J.
Blackledge, M.D.
Abildgaard, N.
Østergaard, B.
Schlemmer, H.-.
Landgren, O.
Asmussen, J.T.
Kaiser, M.F.
Padhani, A.
(2019). Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma: Myeloma Response Assessment and Diagnosis System (MY-RADS). Radiology,
Vol.291
(1),
pp. 5-13.
show abstract
Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. Published under a CC BY 4.0 license. Online supplemental material is available for this article..
Ahmed, N.
Sriskandarajah, P.
Burd, C.
Riddell, A.
Boyd, K.
Kaiser, M.
Messiou, C.
(2019). Detection of avascular necrosis on routine diffusion-weighted whole body MRI in patients with multiple myeloma. The british journal of radiology,
Vol.92
(1097),
pp. 20180822-?.
show abstract
OBJECTIVE:Current therapies for multiple myeloma, which include corticosteroids, increase risk of avascular necrosis. The aim of this study was to assess incidental detection of femoral head avascular necrosis on routine whole body MRI including diffusion weighted MRI. METHODS:All whole body MRI studies, performed on patients with known multiple myeloma between 1 January 2010 to 1 May 2017 were assessed for features of avascular necrosis. RESULTS:650 whole body MR scans were analysed. 15 patients (6.6%) had typical MR features of avascular necrosis: 2/15 (13.3%) had femoral head collapse, 4/15 (26.7%) had bilateral avascular necrosis and 9/15 (60%) were asymptomatic. CONCLUSION:This is the first report of avascular necrosis detected on routine whole body MRI in patients with multiple myeloma. Targeted review of femoral heads in multiple myeloma patients undergoing whole body MR is recommended, including in patients without symptoms. ADVANCES IN KNOWLEDGE:Whole body MR which includes diffusion-weighted MRI is extremely sensitive for evaluation of bone marrow. Although whole body MRI is primarily used for evaluation of multiple myeloma disease burden, it also presents an unique opportunity to evaluate the femoral heads for signs of avascular necrosis which can predate symptoms..
TONG, D.
CONSTANTINIDOU, A.
ENGELMANN, B.
CHAMBERLAIN, F.
THWAY, K.
FISHER, C.
HAYES, A.
FOTIADIS, N.
MESSIOU, C.
MIAH, A.B.
ZAIDI, S.H.
BENSON, C.
VAN DER GRAAF, W.
JONES, R.L.
(2019). The Role of Local Therapy in Multi-focal Epithelioid Haemangioendothelioma. Anticancer research,
Vol.39
(9),
pp. 4891-4896.
JALY, A.A.
THWAY, K.
TOUSKA, P.
WALE, A.
MIAH, A.
KERAWALA, C.
RIVA, F.
MOSKOVIC, E.
JONES, R.L.
STRAUSS, D.
DAFYDD, D.A.
MESSIOU, C.
(2019). Imaging Soft-tissue Sarcomas of the Head and Neck: A Tertiary Soft-tissue Sarcoma Unit Experience. Anticancer research,
Vol.39
(11),
pp. 6223-6230.
van Houdt, W.J.
Husson, O.
Patel, A.
Jones, R.L.
Smith, M.J.
Miah, A.B.
Messiou, C.
Moskovic, E.
Al-Muderis, O.
Benson, C.
Zaidi, S.
Dunlop, A.
Strauss, D.C.
Hayes, A.J.
van der Graaf, W.T.
(2019). Outcome of Primary Desmoid Tumors at All Anatomic Locations Initially Managed with Active Surveillance. Annals of surgical oncology,
Vol.26
(13),
pp. 4699-4706.
Cairncross, L.
Snow, H.A.
Strauss, D.C.
Smith, M.J.
Sjokvist, O.
Messiou, C.
Thway, K.
Hayes, A.J.
(2019). Diagnostic performance of MRI and histology in assessment of deep lipomatous tumours. British journal of surgery,
Vol.106
(13),
pp. 1794-1799.
show abstract
Abstract
Background
Deep lipomatous tumours can be benign lipomas or intermediate/locally recurring atypical lipomatous tumours (ALTs). Differentiating between these two entities clinically and radiologically is difficult. The aims of this study were to report a series of deep lipomatous tumours, comparing the clinical, radiological and pathological features of ALTs and lipomas; and to predict the likelihood of a lipomatous tumour being ALT based on anatomical site and MRI characteristics.
Methods
This was a retrospective review of patients with deep lipomatous tumours presenting over 6 years to a tertiary sarcoma centre, with preoperative MRI, and preoperative or postoperative histology including MDM2 gene analysis. Sensitivity, specificity, predictive values and accuracy in diagnosing ALT were calculated for MRI and histopathological features.
Results
Some 248 patients were included; 81 (32·7 per cent) had a final diagnosis of ALT. ALTs were larger than lipomas (median 19 versus 10 cm; P < 0·001); there was no ALT smaller than 5 cm. A tumour presenting in the lower limb was more likely to be an ALT than a lesion at any other site (48·4 versus 13·5 per cent; P < 0·001). In patients with lipomatous tumours at sites other than the lower limbs, MRI had a negative predictive value of 95 per cent for excluding ALT.
Conclusion
Despite concern, most deep lipomatous tumours (nearly 70 per cent) are benign lipomas. Certain features imply that tumours are almost never ALT: smaller than 5 cm or located outside the lower limb with no suspicious characteristics on MRI. Tumours with these features might safely and confidently be managed outside tertiary sarcoma centres.
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Chamberlain, F.
Cojocaru, E.
Scaranti, M.
Noujaim, J.
Constantinou, A.
Thway, K.
Fisher, C.
Messiou, C.
Strauss, D.C.
Miah, A.
Zaidi, S.
Benson, C.
Gennatas, S.
Jones, R.L.
(2019). Adult soft tissue myoepithelial carcinoma: treatment outcomes and efficacy of chemotherapy. Medical oncology (northwood, london, england),
Vol.37
(2),
pp. 13-?.
show abstract
Soft tissue myoepithelial carcinomas are a rare, malignant subgroup of myoepithelial tumours mostly arising in the extremities with equal predilection for women and men. The mainstay of management of localised disease is complete surgical resection. Despite optimal treatment, 40-45% of tumours recur. Data regarding the efficacy of systemic therapy for advanced and metastatic disease are lacking. The primary aim of this study was to evaluate the outcome of all patients with soft tissue myoepithelial carcinoma treated at a single referral centre. The secondary aim was to establish the efficacy of systemic therapies in patients with advanced disease. A retrospective review of the prospectively maintained Royal Marsden Sarcoma Unit database was performed to identify soft tissue myoepithelial carcinoma patients treated between 1996 and 2019. Patient baseline characteristics and treatment history were recorded. Response to systemic therapy was evaluated using RECIST 1.1. We identified 24 patients treated at our institution between 1996 and 2019,12 males and 12 females. Median age at presentation was 49.6 years [interquartile range (IQR) 40.5-63.3 years]. Twenty-two out of 24 patients (91.7%) underwent primary surgical resection. Nine patients (37.5%) received systemic treatment. A partial response was documented in one patient treated with doxorubicin. The median progression-free survival for first-line chemotherapy was 9.3 months. Myoepithelial carcinoma frequently recurs after complete surgical resection. Conventional chemotherapy demonstrated some activity in myoepithelial carcinoma, however, more effective systemic therapies are required and enrolment in clinical trial should be encouraged..
Messiou, C.
Morosi, C.
(2018). Imaging in retroperitoneal soft tissue sarcoma. Journal of surgical oncology,
Vol.117
(1),
pp. 25-32.
show abstract
Patients with retroperitoneal sarcoma can present to a variety of clinicians with non-specific symptoms and retroperitoneal sarcomas can be incidental findings. Failure to recognize retroperitoneal sarcomas on imaging can lead to inappropriate management in non-specialist centers. Therefore it is critical that the possibility of retroperitoneal sarcoma should be considered with prompt referral to a soft tissue sarcoma unit. This review guides clinicians through a diagnostic pathway, introduces concepts in response assessment and new imaging developments..
(2018). Clear Cell Sarcoma-like Tumor of the Gastrointestinal Tract: Clinical Outcome and Pathologic Features of a Molecularly Characterized Tertiary Center Case Series. Anticancer research,
Vol.38
(3).
Libertini, M.
Mitra, I.
van der Graaf, W.T.
Miah, A.B.
Judson, I.
Jones, R.L.
Thomas, K.
Moskovic, E.
Szucs, Z.
Benson, C.
Messiou, C.
(2018). Aggressive fibromatosis response to tamoxifen: lack of correlation between MRI and symptomatic response. Clinical sarcoma research,
Vol.8,
pp. 13-?.
show abstract
Background One of the commonly used systemic agents for the treatment of aggressive fibromatosis is the anti-oestrogen drug tamoxifen. However, data on efficacy and optimum methods of response assessment are limited, consisting mainly of small case series and reports.Methods A retrospective database was used to identify consecutive patients diagnosed with aggressive fibromatosis (AF) and treated with tamoxifen plus/minus non-steroidal anti-inflammatory drugs at our tertiary referral centre between 2007 and 2014. MRI and symptom changes were recorded.Results Thirty-two patients (13 male 19 female, median age 41 years) were included. Median duration of treatment with tamoxifen was 316 days. Of 9 patients with progressive disease by RECIST 1.1 (28%): 4 patients experienced worsening symptoms; 3 patients had improved symptoms and 2 had no change in symptoms. Of 22 patients with stable disease (69%): 11 had no change in symptoms; 6 had improved symptoms and 5 patients had worsening symptoms. One patient achieved a partial response with improved symptoms.Conclusions No relationship was identified between symptomatic benefit and response by RECIST 1.1 on MRI. Prospective studies in AF should incorporate endpoints focusing on patient symptoms..
Noujaim, J.
Constantinidou, A.
Messiou, C.
Thway, K.
Miah, A.
Benson, C.
Judson, I.
Jones, R.L.
(2018). Successful Ifosfamide Rechallenge in Soft-Tissue Sarcoma. American journal of clinical oncology,
Vol.41
(2),
pp. 147-151.
Winfield, J.M.
Poillucci, G.
Blackledge, M.D.
Collins, D.J.
Shah, V.
Tunariu, N.
Kaiser, M.F.
Messiou, C.
(2018). Apparent diffusion coefficient of vertebral haemangiomas allows differentiation from malignant focal deposits in whole-body diffusion-weighted MRI. European radiology,
Vol.28
(4),
pp. 1687-1691.
show abstract
OBJECTIVES:The aim of this study was to identify apparent diffusion coefficient (ADC) values for typical haemangiomas in the spine and to compare them with active malignant focal deposits. METHODS:This was a retrospective single-institution study. Whole-body magnetic resonance imaging (MRI) scans of 106 successive patients with active multiple myeloma, metastatic prostate or breast cancer were analysed. ADC values of typical vertebral haemangiomas and malignant focal deposits were recorded. RESULTS:The ADC of haemangiomas (72 ROIs, median ADC 1,085×10-6mm2s-1, interquartile range 927-1,295×10-6mm2s-1) was significantly higher than the ADC of malignant focal deposits (97 ROIs, median ADC 682×10-6mm2s-1, interquartile range 583-781×10-6mm2s-1) with a p-value < 10-6. Receiver operating characteristic (ROC) analysis produced an area under the curve of 0.93. An ADC threshold of 872×10-6mm2s-1 separated haemangiomas from malignant focal deposits with a sensitivity of 84.7 % and specificity of 91.8 %. CONCLUSIONS:ADC values of classical vertebral haemangiomas are significantly higher than malignant focal deposits. The high ADC of vertebral haemangiomas allows them to be distinguished visually and quantitatively from active sites of disease, which show restricted diffusion. KEY POINTS:• Whole-body diffusion-weighted MRI is becoming widely used in myeloma and bone metastases. • ADC values of vertebral haemangiomas are significantly higher than malignant focal deposits. • High ADCs of haemangiomas allows them to be distinguished from active disease..
Chew, W.
Benson, C.
Thway, K.
Hayes, A.
Miah, A.
Zaidi, S.
Lee, A.T.
Messiou, C.
Fisher, C.
van der Graaf, W.T.
Jones, R.L.
(2018). Clinical Characteristics and efficacy of chemotherapy in sclerosing epithelioid fibrosarcoma. Medical oncology (northwood, london, england),
Vol.35
(11),
pp. 138-?.
show abstract
Background
Sclerosing epithelioid fibrosarcoma (SEF) is a very rare soft tissue sarcoma subtype. Clinically it is an aggressive tumour; however, to our knowledge there are no published reports regarding the efficacy of chemotherapy in SEF. Therefore, the aim of this study was to document the outcome of a series of patients with SEF treated at a single referral centre with reference to systemic therapy.
Methods
A retrospective search of a prospectively maintained database was performed to identify all patients diagnosed with SEF between 1990 and 2017. The diagnosis was confirmed in each case by a dedicated soft tissue sarcoma pathologist. We analysed those with recurrent disease and the effect of systemic chemotherapy in the metastatic setting.
Results
Thirteen patients were identified, median overall survival from diagnosis and metastasis were 47.3 (95% CI 25.0-131.9) and 16.3 (95% CI 5.3-20.6) months, respectively. In total, 12 (92.3%) patients developed metastatic disease of which 10 died of disease, 1 was lost to follow-up and 1 had recently commenced palliative treatment. Among the 10 patients with metastatic disease, 7 received palliative chemotherapy. Palliative chemotherapy resulted in partial response in 1 patient, stable disease in 3 patients and progressive disease in 3 patients. Median time to disease progression was 2.7 (95% CI 1.2-4.4) months. Two of 13 patients were treated with adjuvant chemotherapy, receiving 6 cycles of liposomal doxorubicin and 1 cycle of doxorubicin, respectively, with a metastasis-free survival of 28.2 and 7.1 months, respectively.
Conclusion
SEF is an aggressive sarcoma subtype with a poor outcome and with limited responsiveness to conventional chemotherapy. Patients with this subtype should be considered for participation in clinical trials with novel agents. Further investigation into the biology of this rare disease is required to improve outcomes..
Schrage, Y.
Hartgrink, H.
Smith, M.
Fiore, M.
Rutkowski, P.
Tzanis, D.
Messiou, C.
Servois, V.
Bonvalot, S.
van der Hage, J.
(2018). Surgical management of metastatic gastrointestinal stromal tumour. European journal of surgical oncology,
Vol.44
(9),
pp. 1295-1300.
Owen, C.
Constantinidou, A.
Miah, A.B.
Thway, K.
Fisher, C.
Benson, C.
Zaidi, S.
Messiou, C.
VAN DER Graaf, W.T.
Jones, R.L.
(2018). Synovial Sarcoma of the Thyroid Gland, Diagnostic Pitfalls and Clinical Management. Anticancer research,
Vol.38
(9),
pp. 5275-5282.
show abstract
Background/aim Synovial sarcoma is a soft tissue sarcoma that tends to affect young adults. There are few reports on primary synovial sarcoma of the thyroid and the aim of this study was to document the clinical and pathological features of synovial sarcoma occurring at this site.Case presentation A retrospective review of a prospectively maintained database was performed to identify patients with synovial sarcoma of the thyroid treated at the Royal Marsden Hospital between 2000 and 2017. Five patients were identified that underwent initial surgical management of localized disease. The mean age at presentation was 38 years, and male to female ratio was 4:1. In 3 out of 5 cases, the diagnosis of synovial sarcoma was made on the post-operative excision specimen. Two of these patients were treated at our institution on the development of metastatic disease. We conducted a literature review and identified 12 previously reported cases of synovial sarcoma of the thyroid.Conclusion Synovial sarcoma of the thyroid is rare and can be challenging to diagnose. The clinical presentation is typically indistinguishable from that of thyroid cancer and most cases are diagnosed post-operatively on an excision specimen. The clinical and pathological features are similar to synovial sarcoma arising at other sites. In our experience, the rarity of the diagnosis can lead to difficulty in establishing the correct diagnosis and determining the appropriate treatment pathway. It is important that physicians are aware of this diagnosis to facilitate prompt referral to a specialist centre, for specialist follow-up and treatment which is different to the thyroid cancer pathway..
Haas, R.L.
Gronchi, A.
van de Sande, M.A.
Baldini, E.H.
Gelderblom, H.
Messiou, C.
Wardelmann, E.
Le Cesne, A.
(2018). Perioperative Management of Extremity Soft Tissue Sarcomas. Journal of clinical oncology,
Vol.36
(2),
pp. 118-124.
show abstract
Surgery is potentially curative for primary nonmetastatic extremity soft tissue sarcomas. After surgery alone, patients may remain at risk for local recurrences and/or metastatic disease. To reduce the likelihood of a local relapse, the addition of radiotherapy (RT) to limb-sparing surgery may result in higher local control rates of at least 85%. Generally, it can be stated that local control after both preoperative and postoperative RT is comparable, but that preoperative RT comes with a more favorable toxicity profile after prolonged follow-up, albeit at the cost of a higher wound complication rate. Furthermore, recent data suggest that preoperative RT is more cost effective. To reduce the risk of subsequent metastatic disease, systemic chemotherapy can be introduced early during the primary management of these patients. These systemic chemotherapy regimens can also be applied both preoperatively and postoperatively. Finally, with the aim of increasing the antitumor response of perioperative RT, these agents may even be combined with RT, concurrently and sequentially. While designing new preoperative combination regimens, responses should be carefully monitored by both sophisticated radiologic and pathologic evaluations. This article reviews all these aspects, in addition to limb-sparing surgery. .
Donners, R.
Blackledge, M.
Tunariu, N.
Messiou, C.
Merkle, E.M.
Koh, D.-.
(2018). Quantitative Whole-Body Diffusion-Weighted MR Imaging. Magnetic resonance imaging clinics of north america,
Vol.26
(4),
pp. 479-494.
Messiou, C.
Kaiser, M.
(2018). Whole-Body Imaging in Multiple Myeloma. Magnetic resonance imaging clinics of north america,
Vol.26
(4),
pp. 509-525.
Lindner, L.H.
Litière, S.
Sleijfer, S.
Benson, C.
Italiano, A.
Kasper, B.
Messiou, C.
Gelderblom, H.
Wardelmann, E.
Le Cesne, A.
Blay, J.-.
Marreaud, S.
Hindi, N.
Desar, I.M.
Gronchi, A.
van der Graaf, W.T.
(2018). Prognostic factors for soft tissue sarcoma patients with lung metastases only who are receiving first-line chemotherapy: An exploratory, retrospective analysis of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma. International journal of cancer,
Vol.142
(12),
pp. 2610-2620.
Pender, A.
Davis, E.J.
Chauhan, D.
Messiou, C.
Al-Muderis, O.
Thway, K.
Fisher, C.
Zaidi, S.
Miah, A.
Judson, I.
van der Graaf, W.
Keedy, V.L.
Benson, C.
Jones, R.L.
(2018). Poor treatment outcomes with palliative gemcitabine and docetaxel chemotherapy in advanced and metastatic synovial sarcoma. Medical oncology (northwood, london, england),
Vol.35
(10),
pp. 131-?.
show abstract
The outcome for patients with unresectable or metastatic soft tissue sarcoma remains poor with few treatment options. Synovial sarcoma is a rare type of sarcoma, predominantly affecting adolescents and young adults. Following failure of first-line anthracycline-based chemotherapy, several salvage options are available. We reviewed the safety and efficacy of gemcitabine/docetaxel chemotherapy in two tertiary oncology centres. We identified patients treated with gemcitabine/docetaxel between 2004 and 2016 in a UK and a US oncology centre using retrospective pharmacy and medical records. Treatment response, toxicity and outcome data were collected. Twenty one patients were treated with gemcitabine/docetaxel, the majority as a second- or third-line treatment for metastatic disease. The response rate was 5% with a median progression-free survival of 2 months (95% CI 1.3-3.7). Toxicities reported were as expected for this chemotherapy combination. Treatment was not discontinued due to toxicity. Gemcitabine/docetaxel chemotherapy shows little efficacy in synovial sarcoma and should not be offered to this patient group outside a clinical trial context..
Spain, L.
Walls, G.
Messiou, C.
Turajlic, S.
Gore, M.
Larkin, J.
(2017). Efficacy and toxicity of rechallenge with combination immune checkpoint blockade in metastatic melanoma: a case series. Cancer immunology, immunotherapy : cii,
Vol.66
(1),
pp. 113-117.
show abstract
Background The efficacy and potential toxicity of rechallenge with combination ipilimumab and nivolumab has not been described. Retreatment of patients with immune checkpoint inhibitors in the setting of prior significant toxicity lacks evidence-based guidance.Methods We present the first three, consecutive patients who received re-treatment with combination ipilimumab and nivolumab for metastatic melanoma managed at our institution.Results Rechallenge with combination ipilimumab and nivolumab in the setting of prior grade 3 toxicity with initial combination therapy is feasible, and responses are seen. We highlight the fact that grade 3 toxicity is likely to recur, but if so, can be manageable.Conclusions Retreatment with ipi + nivo may be considered an option in carefully selected, well-informed patients. More research is required to delineate the benefits and risks with this approach..
Ap Dafydd, D.
Messiou, C.
Thway, K.
Strauss, D.C.
Nicol, D.L.
Moskovic, E.
(2017). Paratesticular Sarcoma: Typical Presentation, Imaging Features, and Clinical Challenges. Urology,
Vol.100,
pp. 163-168.
show abstract
Objective To describe the major imaging features, together with clinical data, of paratesticular sarcomas.Materials and methods A retrospective analysis was performed of available imaging and clinical data of 77 consecutive cases of paratesticular sarcoma referred to the soft tissue sarcoma center at the Royal Marsden hospital between January 2006 and January 2015.Results Of the total cases, 87% had been referred postoperatively, 43% of which had been imaged preoperatively and 24% of which required re-resection due to incomplete initial excision. On imaging, abnormal fat was present in 73% of paratesticular liposarcomas, with solid or enhancing components indicating high-grade tumors. Leiomyosarcomas and rhabdomyosarcomas were all purely solid masses.Conclusion Paratesticular sarcomas are rare, and lack of awareness may compromise treatment and outcome. They may be mistaken for common clinical problems such as inguinal hernias and epididymal cysts. Surgery for these presumed diagnoses may result in inadequate clearance and an increased risk of recurrence. A low threshold for imaging atypical paratesticular masses is needed, as this may better inform management..
Szucs, Z.
Messiou, C.
Wong, H.H.
Hatcher, H.
Miah, A.
Zaidi, S.
van der Graaf, W.T.
Judson, I.
Jones, R.L.
Benson, C.
(2017). Pazopanib, a promising option for the treatment of aggressive fibromatosis. Anti-cancer drugs,
Vol.28
(4),
pp. 421-426.
show abstract
Desmoid tumour/aggressive fibromatosis (DT/AF) is a rare soft-tissue neoplasm that is locally aggressive but does not metastasize. There is no standard systemic treatment for symptomatic patients, although a number of agents are used. Tyrosine kinase inhibitors have recently been reported to show useful activity. We reviewed our bi-institutional (Royal Marsden Hospital, Cambridge University Hospitals) experience with the tyrosine kinase inhibitor pazopanib in the treatment of progressing DT/AF. Eight patients with DT/AF were treated with pazopanib at Royal Marsden Hospital and Cambridge University Hospitals between June 2012 and June 2016. The median age of the patients was 37.5 (range: 27-60) years. The median duration of pazopanib treatment was 12 (range: 5-22) months and for three patients the treatment is ongoing. Three patients discontinued treatment early (patient preference, intolerable toxicity and logistical reasons, respectively). None of the patients showed radiological progression while on treatment, best responses according to Response Evaluation Criteria In Solid Tumors 1.1 were partial response in 3/8 and stable disease in 5/8 cases. Six patients derived clinical benefit from treatment in terms of improved function and/or pain reduction. Median progression-free survival was 13.5 (5-36) months. Only one patient experienced intolerable toxicity (grade 3 hypertension) leading to early treatment discontinuation. In our series of patients with DT/AF, pazopanib demonstrated important activity both in terms of symptom control (75%) and absence of radiological progression (100%). Results of ongoing confirmatory trials are eagerly awaited..
Winfield, J.M.
Tunariu, N.
Rata, M.
Miyazaki, K.
Jerome, N.P.
Germuska, M.
Blackledge, M.D.
Collins, D.J.
de Bono, J.S.
Yap, T.A.
deSouza, N.M.
Doran, S.J.
Koh, D.-.
Leach, M.O.
Messiou, C.
Orton, M.R.
(2017). Extracranial Soft-Tissue Tumors: Repeatability of Apparent Diffusion Coefficient Estimates from Diffusion-weighted MR Imaging. Radiology,
Vol.284
(1),
pp. 88-99.
show abstract
Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%-6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = -0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies-a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations. Online supplemental material is available for this article..
Messiou, C.
Moskovic, E.
Vanel, D.
Morosi, C.
Benchimol, R.
Strauss, D.
Miah, A.
Douis, H.
van Houdt, W.
Bonvalot, S.
(2017). Primary retroperitoneal soft tissue sarcoma: Imaging appearances, pitfalls and diagnostic algorithm. European journal of surgical oncology : the journal of the european society of surgical oncology and the british association of surgical oncology,
Vol.43
(7),
pp. 1191-1198.
show abstract
Although retroperitoneal sarcomas are rare tumours, they can be encountered by a wide variety of clinicians as they can be incidental findings on imaging or present with non specific symptoms and signs. Surgical resection can offer hope of cure and patient outcomes are improved when patients are managed in high-volume specialist centers. Failure to recognize retroperitoneal sarcomas on imaging can lead to inappropriate management in inexperienced centers. Therefore it is critical that a diagnosis of retroperitoneal sarcoma should be considered in the differential diagnosis of a retroperitoneal mass with prompt referral to a soft tissue sarcoma unit. In particular, the most common retroperitoneal sarcoma subtypes, liposarcoma and leiomyosarcoma, have characteristic imaging appearances which are discussed. This review therefore aims to set the context and guide clinicians through a diagnostic pathway for retroperitoneal masses in adults which arise extrinsic to the solid abdominal viscera..
Young, R.J.
Litière, S.
Lia, M.
Hogendoorn, P.C.
Fisher, C.
Mechtersheimer, G.
Daugaard, S.
Sciot, R.
Collin, F.
Messiou, C.
Grünwald, V.
Gronchi, A.
van der Graaf, W.
Wardelmann, E.
Judson, I.
(2017). Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy: a subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study. Acta oncologica (stockholm, sweden),
Vol.56
(7),
pp. 1013-1020.
show abstract
Background The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin-ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy improved tumor response and progression-free survival, but differences in overall survival (OS) were not statistically significant. We analyzed factors prognostic for tumor response and OS, and assessed histological subgroup and tumor grade as predictive factors to identify patients more likely to benefit from combination chemotherapy.Methods Central pathology review was performed by six reference pathologists. Gender, age, performance status, time from first presentation with sarcoma to starting palliative chemotherapy, tumor grade, histological subgroup, primary tumor site involvement, and sites of metastases were assessed as prognostic factors.Results Three hundred and ten patients were included in this study. Discordance between local and central pathology opinion of tumor histology and tumor grade was observed in 98 (32%) and 122 (39%) cases, respectively. In multivariate analysis, liposarcoma patients had improved tumor response compared to other histological subgroups, whilst patients with metastases other than lung, liver or bone had a poorer response [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.23-0.78; p = 0.006]. Patients with bone metastases had reduced OS [hazard ratio (HR) 1.56, 95% CI 1.16-2.09; p = 0.003]. By central pathology review, patients with undifferentiated pleomorphic sarcoma (UPS) had improved tumor response and OS with doxorubicin-ifosfamide compared to single-agent doxorubicin (OR 9.90, 95% CI 1.93-50.7 and HR 0.44, 95% CI 0.26-0.79, respectively). Grade III tumors had improved response with combination chemotherapy but there was no interaction between chemotherapy and grade on OS.Conclusions Prospective central pathology review of tumor histology should be integrated into future STS clinical trials. Doxorubicin-ifosfamide may be most appropriate for young, fit patients with poorly differentiated Grade III tumors including UPS..
van Houdt, W.J.
Zaidi, S.
Messiou, C.
Thway, K.
Strauss, D.C.
Jones, R.L.
(2017). Treatment of retroperitoneal sarcoma: current standards and new developments. Current opinion in oncology,
Vol.29
(4),
pp. 260-267.
show abstract
Purpose of review Retroperitoneal sarcomas are rare tumors and with complex treatment. In this manuscript we give an overview of current standards in treatment of this disease and discuss new developments.Recent findings Surgery with complete resection of the primary tumor is still the only curative modality. The role of preoperative radiotherapy is not clear and is currently being investigated in a clinical trial. Neo-adjuvant chemotherapy is not the standard of care but can be considered occasionally when complete resection is uncertain. Local and distant recurrent disease carries a dismal prognosis, although long-term survival can be achieved. Liposarcomas tend to recur locally, whereas distant recurrences are more often seen in leiomyosarcoma and other subtypes. Outcome improves when patients are treated in high volume sarcoma centers. In the metastatic setting, newer systemic agents have recently been approved.Summary Treatment of retroperitoneal sarcomas is complex and all patients should be treated in multidisciplinary sarcoma centers. Increasing international collaboration of expert centers in sharing expertise and performing clinical trials might lead to better treatment and improved survival..
Smith, H.G.
Tzanis, D.
Messiou, C.
Benson, C.
van der Hage, J.A.
Fiore, M.
Bonvalot, S.
Hayes, A.J.
(2017). The management of soft tissue tumours of the abdominal wall. European journal of surgical oncology : the journal of the european society of surgical oncology and the british association of surgical oncology,
Vol.43
(9),
pp. 1647-1655.
show abstract
Soft tissue tumours of the abdominal wall account for approximately 10% of all soft tissue tumours. Tumours at this site comprise a heterogeneous group of pathologies with distinct clinical behaviours and responses to treatment. The management of these tumours has largely been extrapolated from studies of soft tissue tumours at other sites. This review aims to summarise the existing data relating to abdominal wall tumours and suggest principles for managing soft tissue tumours at this site.Relevant articles were retrieved from a comprehensive literature search using the PubMed database. Key words included abdominal wall, soft tissue tumours, surgery, radiotherapy and chemotherapy. No restrictions on publication date were used.The most common pathologies presenting in the abdominal wall are desmoid tumours, soft-tissue sarcoma and dermatofibrosarcoma protuberans (DFSP). Desmoid tumours should be managed with an initial period of observation, with surgery reserved for progressive lesions. Surgery should be the primary treatment for soft-tissue sarcomas and DFSP, with radiotherapy reserved for large-high grade tumours and preferentially given pre-operatively.Abdominal wall tumours are rare and should be managed in centres with experience in the management of soft tissue tumours. Management should be tailored to the biological behaviour of specific pathologies..
van Houdt, W.J.
Patel, A.K.
Jones, R.L.
Smith, M.J.
Miah, A.
Benson, C.
Zaidi, S.
Messiou, C.
Moskovic, E.
Strauss, D.C.
Hayes, A.J.
Husson, O.
van der Graaf, W.T.
(2017). Prognosis of desmoid tumours initially managed with surveillance only at all anatomical locations. Annals of oncology,
Vol.28.
Nanni, C.
Cottereau, A.S.
Lopci, E.
Bodet-Milin, C.
Coronado, M.
Pro, B.
Kim, W.S.
Trotman, J.
Barrington, S.
Duhrsen, U.
Vander Borght, T.
Zamagni, E.
Kraeber-Bodéré, F.
Messiou, C.
Rahmouni, A.
Buvat, I.
Andre, M.
Hertzberg, M.
Oyen, W.
Casasnovas, O.
Luminari, S.
Garderet, L.
Montravers, F.
Kobe, C.
Kluge, R.
Versari, A.
Zucca, E.
Moreau, P.
Cheson, B.
Haioun, C.
Gallamini, A.
Meignan, M.
(2017). Report of the 6th International Workshop on PET in lymphoma. Leukemia & lymphoma,
Vol.58
(10),
pp. 2298-2303.
show abstract
Two hundred and ten nuclear medicine physicians, radiologists, and hematologists from 26 countries attended the 6th International Workshop on Positron Emission Tomography (PET) in Lymphoma and Myeloma held in Menton, France, in September 2016. The meeting was under the auspices of the European Lymphoma Institute (ELI), the European Association of Nuclear Medicine (EANM) the Lymphoma Study Association (LYSA), the Italian Foundation on Lymphoma (FIL) and the Carnot Institute for Lymphoma (CALYM). Forty scientific posters were presented. For the first time, specialists in the field of multiple myeloma (MM) were involved in the expert session. The aim was to establish from the experience of Italian and French studies new guidelines of FDG-PET/CT reporting for myeloma staging and restaging. The meeting dedicated an entire session to MM imaging followed by a session on the role of PET in Peripheral T cell Lymphoma. An entire session addressed the issues of Deauville scale particularly for end treatment assessment and the challenging consequences of immunomodulatory treatments on PET reporting. A specific session presented the potential role of baseline metabolic tumor measurement to predict outcome and identify different risk categories and the main results obtained in different lymphoma entities were described. Whether it could replace clinical staging has been extensively discussed. The more recent results obtained in the H10 trial have been presented and compared to the published data in early stage Hodgkin lymphoma. Finally, the ongoing studies using PET for guiding therapeutic strategies have been reported by the various lymphoma cooperative groups that participated to the meeting..
Kasper, B.
Baumgarten, C.
Garcia, J.
Bonvalot, S.
Haas, R.
Haller, F.
Hohenberger, P.
Penel, N.
Messiou, C.
van der Graaf, W.T.
Gronchi, A.
Desmoid Working Group,
(2017). An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG). Annals of oncology : official journal of the european society for medical oncology,
Vol.28
(10),
pp. 2399-2408.
show abstract
Desmoid-type fibromatosis is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Currently, there is no established or evidence-based treatment approach available for this disease. Therefore, in 2015 the European Desmoid Working Group published a position paper giving recommendations on the treatment of this intriguing disease. Here, we present an update of this consensus approach based on professionals' AND patients' expertise following a round table meeting bringing together sarcoma experts from the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group with patients and patient advocates from Sarcoma PAtients EuroNet. In this paper, we focus on new findings regarding the prognostic value of mutational analysis in desmoid-type fibromatosis patients and new systemic treatment options..
Morone, M.
Bali, M.A.
Tunariu, N.
Messiou, C.
Blackledge, M.
Grazioli, L.
Koh, D.-.
(2017). Whole-Body MRI: Current Applications in Oncology. Ajr. american journal of roentgenology,
Vol.209
(6),
pp. W336-W349.
show abstract
Objective The purpose of this article is to review current image acquisition and interpretation for whole-body MRI, clinical applications, and the emerging roles in oncologic imaging, especially in the assessment of bone marrow diseases.Conclusion Whole-body MRI is an emerging technique used for early diagnosis, staging, and assessment of therapeutic response in oncology. The improved accessibility and advances in technology, including widely available sequences (Dixon and DWI), have accelerated its deployment and acceptance in clinical practice..
Seifert, H.
Hirata, E.
Gore, M.
Khabra, K.
Messiou, C.
Larkin, J.
Sahai, E.
(2016). Extrinsic factors can mediate resistance to
BRAF
inhibition in central nervous system melanoma metastases. Pigment cell & melanoma research,
Vol.29
(1),
pp. 92-100.
Wardelmann, E.
Haas, R.L.
Bovée, J.V.
Terrier, P.
Lazar, A.
Messiou, C.
LePechoux, C.
Hartmann, W.
Collin, F.
Fisher, C.
Mechtersheimer, G.
DeiTos, A.P.
Stacchiotti, S.
Jones, R.L.
Gronchi, A.
Bonvalot, S.
(2016). Evaluation of response after neoadjuvant treatment in soft tissue sarcomas; the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC–STBSG) recommendations for pathological examination and reporting. European journal of cancer,
Vol.53,
pp. 84-95.
Smith, H.G.
Hannay, J.A.
Thway, K.
Messiou, C.
Smith, M.J.
Strauss, D.C.
Hayes, A.J.
(2016). Elastofibroma dorsi: The clunking tumour that need not cause alarm. The annals of the royal college of surgeons of england,
Vol.98
(03),
pp. 208-211.
show abstract
Introduction Elastofibromas are rare, pseudo-tumours arising at the inferior pole of the scapula that have a characteristic presentation. Due to their tissue of origin and size, they may often be mistaken for soft tissue sarcomas. We present the management of patients diagnosed with elastofibroma at a single institution. Methods Patients diagnosed with elastofibroma between January 1995 and January 2015 were identified from a prospectively maintained histopathology database. Electronic patient records, imaging and pathology reports were retrieved and reviewed. Results Thirty seven patients were identified, with a median age of 66 years and a male-to-female ratio of 1:1.6. All tumours occurred in the characteristic subscapular location. The median maximum tumour diameter was 8.2cm. A synchronous contralateral lesion (15.8%) was found in six patients. Cross-sectional imaging was performed in 29 patients, with magnetic resonance imaging the most common modality (59.5%). Diagnosis was confirmed with percutaneous biopsy in all but one patient, who proceeded directly to surgery. Eighteen patients were managed non-operatively; 19 opted for surgical excision due to significant symptoms. Excision was performed in a marginal fashion and, at a median follow-up of 5 months, no functional impairment or local recurrences were observed. Conclusions Soft tissue masses greater than 5cm in diameter should prompt the clinician to exclude soft tissue sarcoma. The diagnosis of elastofibroma may be alluded to by its typical presentation and can be confirmed by percutaneous biopsy. After excluding malignancy, these lesions can be safely managed non-operatively, with surgery reserved for symptomatic patients. .
Messiou, C.
Bonvalot, S.
Gronchi, A.
Vanel, D.
Meyer, M.
Robinson, P.
Morosi, C.
Bloem, J.L.
Terrier, P.H.
Lazar, A.
Le Péchoux, C.
Wardelman, E.
Winfield, J.M.
Boulet, B.
Bovée, J.
Haas, R.L.
(2016). Evaluation of response after pre-operative radiotherapy in soft tissue sarcomas; the European Organisation for Research and Treatment of Cancer – Soft Tissue and Bone Sarcoma Group (EORTC – STBSG) and Imaging Group recommendations for radiological examination and reporting with an emphasis on magnetic resonance imaging. European journal of cancer,
Vol.56,
pp. 37-44.
Wale, A.
Pawlyn, C.
Kaiser, M.
Messiou, C.
(2016). Frequency, distribution and clinical management of incidental findings and extramedullary plasmacytomas in whole body diffusion weighted magnetic resonance imaging in patients with multiple myeloma. Haematologica,
Vol.101
(4),
pp. e142-e144.
Orton, M.R.
Messiou, C.
Collins, D.
Morgan, V.A.
Tessier, J.
Young, H.
deSouza, N.
Leach, M.O.
(2016). Diffusion-weighted MR imaging of metastatic abdominal and pelvic tumours is sensitive to early changes induced by a VEGF inhibitor using alternative diffusion attenuation models. European radiology,
Vol.26
(5),
pp. 1412-1419.
Vlenterie, M.
Litière, S.
Rizzo, E.
Marréaud, S.
Judson, I.
Gelderblom, H.
Le Cesne, A.
Wardelmann, E.
Messiou, C.
Gronchi, A.
van der Graaf, W.T.
(2016). Outcome of chemotherapy in advanced synovial sarcoma patients: Review of 15 clinical trials from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group; setting a new landmark for studies in this entity. European journal of cancer,
Vol.58,
pp. 62-72.
Pawlyn, C.
Fowkes, L.
Otero, S.
Jones, J.R.
Boyd, K.D.
Davies, F.E.
Morgan, G.J.
Collins, D.J.
Sharma, B.
Riddell, A.
Kaiser, M.F.
Messiou, C.
(2016). Whole-body diffusion-weighted MRI: a new gold standard for assessing disease burden in patients with multiple myeloma?. Leukemia,
Vol.30
(6),
pp. 1446-1448.
Rata, M.
Collins, D.J.
Darcy, J.
Messiou, C.
Tunariu, N.
Desouza, N.
Young, H.
Leach, M.O.
Orton, M.R.
(2016). Assessment of repeatability and treatment response in early phase clinical trials using DCE-MRI: comparison of parametric analysis using MR- and CT-derived arterial input functions. European radiology,
Vol.26
(7),
pp. 1991-1998.
Grünwald, V.
Litière, S.
Young, R.
Messiou, C.
Lia, M.
Wardelmann, E.
van der Graaf, W.
Gronchi, A.
Judson, I.
EORTC STBSG,
(2016). Absence of progression, not extent of tumour shrinkage, defines prognosis in soft-tissue sarcoma - An analysis of the EORTC 62012 study of the EORTC STBSG. European journal of cancer (oxford, england : 1990),
Vol.64,
pp. 44-51.
show abstract
Background Anthracycline-based chemotherapy remains the mainstay of first-line treatment in metastatic or advanced soft-tissue sarcoma (STS). Age, performance status, tumour histology and tumour grade are recognised prognostic factors; however, the prognostic value of tumour response and tumour shrinkage is ill-defined.Methods Patients recruited to the European Organisation for Research and Treatment of Cancer 62012 trial with advanced intermediate or high-grade STS, who received at least one cycle of chemotherapy and one tumour assessment of response, were eligible for this study. Kaplan-Meier estimates of overall survival (OS) by tumour response were computed using a landmark approach after two, four, and six cycles of chemotherapy. The prognostic role of the kinetics of tumour response was analysed by Cox proportional hazards.Results Three hundred eighty-nine patients were included in this study. Compared to stable or responding patients, patients with progressive disease (PD) after two, four and six cycles of chemotherapy achieved a worse OS: hazard ratio [HR] 2.62 (95% confidence interval [CI] 1.72-4.00), p < 0.001; HR 2.23 (95% CI 1.4-3.56), p = 0.0001; and HR 3.16 (95% CI 1.96-5.08), p = 0.0001, respectively. However, patients with stable or responding disease achieved similar OS outcomes. Correspondingly, patients with an increase in tumour size by 10% or more correlated with a worse OS in Cox proportional hazard analysis.Conclusions No association between prognosis and amount of tumour shrinkage was detected. Interestingly, an increase in tumour size by at least 10% correlated with a worse OS, but re-defining PD as a ≥10% increase in tumour size did not translate into a better discrimination of survival outcomes for responders versus stable disease. Disease control rather than tumour response is a valuable end-point in advanced or metastatic STS receiving palliative anthracycline-based chemotherapy, supporting the use of time-to-event end-points in future STS trials..
Wang, J.
Strauss, D.C.
Messiou, C.
Thway, K.
(2016). Endometriosis of Extra-Abdominal Soft Tissues. International journal of surgical pathology,
Vol.24
(6),
pp. 497-503.
show abstract
While endometriosis, defined as the presence of endometrial tissue in extrauterine sites, is most frequently encountered within the peritoneal cavity, a small but significant proportion of cases occur at extra-abdominal soft tissue sites, particularly in relation to previous abdominal surgery. We reviewed the cases of endometriosis of soft tissue sites seen at a tertiary soft tissue center. All cases of extra-abdominal soft tissue endometriosis diagnosed at this institution over a 13-year period were reviewed, and clinical and pathologic findings were recorded. Forty-five patients had diagnoses of soft tissue endometriosis and there were 34 diagnostic biopsies and 26 surgical excision specimens. All but 1 case were abdominal wall lesions, with 1 located in the upper arm. A total of 33 patients presented with lesions in scars of previous operations (31 in Pfannenstiel incisions for Caesarean sections, presenting with a median interval of 6 years (range 1-16 years) following surgery). The lesions ranged in size from 1 to 8 cm (median 3.5 cm). One case showed decidualized stroma with trophoblast cells, while 2 had secondary adenocarcinoma arising from endometriosis. Eighteen cases were tested for β-catenin expression immunohistochemically, of which 5 showed at least focal nuclear positivity in the surrounding fibrous tissue (although not within glands or stroma). Soft tissue endometriosis is seen most commonly in surgical scars, particularly following Caesarean sections. Spontaneous endometriosis also most commonly occurs in the abdominal wall, although can occur exceptionally at unusual sites, such as extremities. Secondary changes, including carcinomas, can arise from endometriosis. The differential diagnosis of these lesions includes fibromatosis, which may be erroneously diagnosed on small, nonrepresentative core biopsy specimens. .
Payne, G.S.
Harris, L.M.
Cairns, G.S.
Messiou, C.
deSouza, N.M.
Macdonald, A.
Saran, F.
Leach, M.O.
(2016). Validating a robust double-quantum-filtered (1) H MRS lactate measurement method in high-grade brain tumours. Nmr in biomedicine,
Vol.29
(10),
pp. 1420-1426.
show abstract
(1) H MRS measurements of lactate are often confounded by overlapping lipid signals. Double-quantum (DQ) filtering eliminates lipid signals and permits single-shot measurements, which avoid subtraction artefacts in moving tissues. This study evaluated a single-voxel-localized DQ filtering method qualitatively and quantitatively for measuring lactate concentrations in the presence of lipid, using high-grade brain tumours in which the results could be compared with standard acquisition as a reference. Paired standard acquisition and DQ-filtered (1) H MR spectra were acquired at 3T from patients receiving treatment for glioblastoma, using fLASER (localization by adiabatic selective refocusing using frequency offset corrected inversion pulses) single-voxel localization. Data were acquired from 2 × 2 × 2 cm(3) voxels, with a repetition time of 1 s and 128 averages (standard acquisition) or 256 averages (DQ-filtered acquisition), requiring 2.15 and 4.3 min respectively. Of 37 evaluated data pairs, 20 cases (54%) had measureable lactate (fitted Cramér-Rao lower bounds ≤ 20%) in either the DQ-filtered or the standard acquisition spectra. The measured DQ-filtered lactate signal was consistently downfield of lipid (1.33 ± 0.03 ppm vs 1.22 ± 0.08 ppm; p = 0.002), showing that it was not caused by lipid breakthrough, and that it matched the lactate signal seen in standard measurements (1.36 ± 0.02 ppm). In the absence of lipid, similar lactate concentrations were measured by the two methods (mean ratio DQ filtered/standard acquisition = 1.10 ± 0.21). In 7/20 cases with measurable lactate, signal was not measureable in the standard acquisition owing to lipid overlap but was quantified in the DQ-filtered acquisition. Conversely, lactate was undetected in seven DQ-filtered acquisitions but visible using the standard acquisition. In conclusion, the DQ filtering method has proven robust in eliminating lipid and permits uncontaminated measurement of lactate. This is important validation prior to use in tissues outside the brain, which contain large amounts of lipid and which are often susceptible to motion..
(2016). Management of Recurrent Retroperitoneal Sarcoma (RPS) in the Adult: A Consensus Approach from the Trans-Atlantic RPS Working Group. Annals of surgical oncology,
Vol.23
(11),
pp. 3531-3540.
Thway, K.
Noujaim, J.
Zaidi, S.
Miah, A.B.
Benson, C.
Messiou, C.
Jones, R.L.
Fisher, C.
(2016). Desmoplastic Small Round Cell Tumor. International journal of surgical pathology,
Vol.24
(8),
pp. 672-684.
show abstract
Desmoplastic small round cell tumor (DSRCT) is an aggressive small round cell neoplasm which predominantly occurs intra-abdominally in adolescents and young adults with a male predominance, and which is characterized by a recurrent t(11;22)(p13;q12) translocation leading to formation of the EWSR1-WT1 fusion gene, which generates a chimeric protein with transcriptional regulatory activity. Histologically, DSRCT has a characteristic morphology, of islands of monotonous small cells within prominent sparsely cellular fibroblastic stroma, and immunohistochemically it shows polyphenotypic multidirectional differentiation, with expression of epithelial, muscle, and neural markers. However, DSRCT can arise more rarely in other sites and exhibit a spectrum of both histologic features and immunoprofile, which may confuse diagnosis with other small round cell neoplasms. Correct diagnosis is important to ensure correct treatment and prognostication; DSRCT are almost universally fatal neoplasms with patients usually succumbing to disease within the first 2 years of diagnosis. While combination treatment strategies can confer a survival benefit, the overall prognosis remains poor. Further insight into the tumorigenic molecular changes generated by the fusion oncogene may lead to the generation of specific targeted therapies. We review DSRCT, discussing morphology and immunohistochemistry, molecular genetic findings, potential targeted treatments, and the differential diagnosis. .
Smith, H.G.
Thway, K.
Messiou, C.
Barton, D.P.
Thomas, J.M.
Hayes, A.J.
Strauss, D.C.
Smith, M.J.
(2016). Selective marginal resections in the management of aggressive angiomyxomas. Journal of surgical oncology,
Vol.114
(7),
pp. 828-832.
Harris, L.M.
Tunariu, N.
Messiou, C.
Hughes, J.
Wallace, T.
DeSouza, N.M.
Leach, M.O.
Payne, G.S.
(2015). Evaluation of lactate detection using selective multiple quantum coherence in phantoms and brain tumours. Nmr in biomedicine,
Vol.28
(3),
pp. 338-343.
Payne, G.S.
deSouza, N.M.
Messiou, C.
Leach, M.O.
(2015). Single‐shot single‐voxel lactate measurements using FOCI‐LASER and a multiple‐quantum filter. Nmr in biomedicine,
Vol.28
(4),
pp. 496-504.
Giles, S.L.
deSouza, N.M.
Collins, D.J.
Morgan, V.A.
West, S.
Davies, F.E.
Morgan, G.J.
Messiou, C.
(2015). Assessing myeloma bone disease with whole-body diffusion-weighted imaging: comparison with x-ray skeletal survey by region and relationship with laboratory estimates of disease burden. Clinical radiology,
Vol.70
(6),
pp. 614-621.
Otero, S.
Moskovic, E.C.
Strauss, D.C.
Benson, C.
Miah, A.B.
Thway, K.
Messiou, C.
(2015). Desmoid-type fibromatosis. Clinical radiology,
Vol.70
(9),
pp. 1038-1045.
Ng, W.
Messiou, C.
Smith, M.
Thway, K.
(2015). p16 Expression in Fat Necrosis. International journal of surgical pathology,
Vol.23
(7),
pp. 544-548.
show abstract
Distinguishing well-differentiated liposarcoma (WDL) from lipoma is of clinical and prognostic importance, but can be difficult on imaging and histology alone. WDL characteristically harbor amplifications of the MDM2 and CDK4 cell cycle oncogenes and overexpress the cell cycle regulator p16. Fluorescence in situ hybridization (FISH) to assess for MDM2 and CDK4 gene amplification is the diagnostic gold standard, and immunohistochemistry for the overexpressed MDM2 and CDK4 proteins is also useful but may not be routinely offered by pathology laboratories. p16 immunohistochemistry is a sensitive marker for WDL and is in the repertoire of most laboratories, and it has been suggested as a useful method of distinguishing WDL from lipomas when other ancillary modalities are not readily available. We describe a case of a large retroperitoneal adipocytic mass occurring in a 27-year-old male, which was clinically and radiologically in keeping with WDL. Histologically this was a differentiated adipocytic neoplasm with prominent fibrous septa and fat necrosis, more suggestive of retroperitoneal lipoma. Immunohistochemistry showed diffuse, strong nuclear expression of p16 in the areas of fat necrosis. However, CDK4 was negative and the lesion lacked evidence of MDM2 amplification with FISH. Diffuse expression of p16 in areas of fat necrosis in large or deep lipomas highlights the potential for diagnostic misinterpretation as well differentiated liposarcoma, and we therefore emphasize that p16 immunohistochemistry should always be interpreted as part of a panel with CDK4 +/− MDM2 in the differential diagnosis of WDL and lipoma. .
Messiou, C.
Kaiser, M.
(2015). Whole body diffusion weighted
MRI
– a new view of myeloma. British journal of haematology,
Vol.171
(1),
pp. 29-37.
Wilkinson, M.J.
Fitzgerald, J.E.
Strauss, D.C.
Hayes, A.J.
Thomas, J.M.
Messiou, C.
Fisher, C.
Benson, C.
Tekkis, P.P.
Judson, I.
(2015). Surgical treatment of gastrointestinal stromal tumour of the rectum in the era of imatinib. British journal of surgery,
Vol.102
(8),
pp. 965-971.
show abstract
Abstract
Background
Gastrointestinal stromal tumours (GISTs) of the rectum often require radical surgery to achieve complete resection. This study investigated the management and outcome of surgery for rectal GISTs and the role of imatinib.
Methods
A cohort study was undertaken of patients identified from a database at one tertiary sarcoma referral centre over a continuous period, from January 2001 to January 2013.
Results
Over 12 years, 19 patients presented with a primary rectal GIST. Median age was 57 (range 30–77) years. Neoadjuvant imatinib was used in 15 patients, significantly reducing mean tumour size from 7·6 (95 per cent c.i. 6·1 to 9·0) to 4·1 (2·8 to 5·3) cm (P < 0·001). Nine of these patients underwent surgical resection. Imatinib therapy enabled sphincter-preserving surgery to be undertaken in seven patients who would otherwise have required abdominoperineal resection or pelvic exenteration for tumour clearance. Neoadjuvant imatinib treatment also led to a significant reduction in mean(s.d.) tumour mitotic count from 16(16) to 4(9) per 50 high-power fields (P = 0·015). Imatinib was used only as adjuvant treatment in two patients. There were three deaths, all from unrelated causes. Eleven of the 13 patients who underwent resection were alive without evidence of recurrence at latest follow-up, with a median disease-free survival of 38 (range 20–129) months and overall survival of 62 (39–162) months.
Conclusion
The use of neoadjuvant imatinib for rectal GISTs significantly decreased both tumour size and mitotic activity, which permitted less radical sphincter-preserving surgery.
.
Maruzzo, M.
Martin-Liberal, J.
Messiou, C.
Miah, A.
Thway, K.
Alvarado, R.
Judson, I.
Benson, C.
(2015). Pazopanib as first line treatment for solitary fibrous tumours: the Royal Marsden Hospital experience. Clinical sarcoma research,
Vol.5
(1).
Messiou, C.
Collins, D.J.
Morgan, V.A.
Bianchini, D.
de Bono, J.S.
de Souza, N.M.
(2014). Use of apparent diffusion coefficient as a response biomarker in bone: effect of developing sclerosis on quantified values. Skeletal radiology,
Vol.43
(2),
pp. 205-208.
Miah, A.B.
Hannay, J.
Benson, C.
Thway, K.
Messiou, C.
Hayes, A.J.
Strauss, D.C.
(2014). Optimal management of primary retroperitoneal sarcoma: an update. Expert review of anticancer therapy,
Vol.14
(5),
pp. 565-579.
Giles, S.L.
Messiou, C.
Collins, D.J.
Morgan, V.A.
Simpkin, C.J.
West, S.
Davies, F.E.
Morgan, G.J.
deSouza, N.M.
(2014). Whole-body diffusion-weighted MR imaging for assessment of treatment response in myeloma. Radiology,
Vol.271
(3),
pp. 785-794.
show abstract
Purpose To determine the feasibility of whole-body diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of treatment response in myeloma.Materials and methods This prospective single-institution study was HIPAA-compliant with local research ethics committee approval. Written informed consent was obtained from each subject. Eight healthy volunteers (cohort 1a) and seven myeloma patients (cohort 1b) were imaged twice to assess repeatability of quantitative apparent diffusion coefficient (ADC) estimates. Thirty-four additional myeloma patients (cohort 2) underwent whole-body DW imaging before treatment; 26 completed a posttreatment imaging. Whole-body DW data were compared before and after treatment by using qualitative (ie, observer scores) and quantitative (ie, whole-body segmentation of marrow ADC) methods. Serum paraproteins and/or light chains or bone marrow biopsy defined response.Results Whole-body DW imaging scores were significantly different between observers (P < .001), but change in scores between observers after treatment was not (P = .49). Sensitivity and specificity for detecting response according to observer scores were 86% (18 of 21 patients) and 80% (4 of 5 patients) for both observers. ADC measurement was repeatable: mean coefficient of variation was 3.8% in healthy volunteers and 2.8% in myeloma patients. Pretreatment ADC in cohort 2 was significantly different from that in cohort 1a (P = .03), but not from that in cohort 1b (P = .2). Mean ADC increased in 95% (19 of 20) of responding patients and decreased in all (five of five) nonresponders (P = .002). A 3.3% increase in ADC helped identify response with 90% sensitivity and 100% specificity; an 8% increase (greater than repeatability of cohort 1b) resulted in 70% sensitivity and 100% specificity. There was a significant negative correlation between change in ADC and change in laboratory markers of response (r = -0.614; P = .001).Conclusion Preliminary work demonstrates whole-body DW imaging is a repeatable, quantifiable technique for assessment of treatment response in myeloma..
Bashir, U.
Moskovic, E.
Strauss, D.
Hayes, A.
Thway, K.
Pope, R.
Messiou, C.
(2014). Soft-tissue masses in the abdominal wall. Clinical radiology,
Vol.69
(10),
pp. e422-e431.
Lecouvet, F.E.
Talbot, J.N.
Messiou, C.
Bourguet, P.
Liu, Y.
de Souza, N.M.
(2014). Monitoring the response of bone metastases to treatment with Magnetic Resonance Imaging and nuclear medicine techniques: A review and position statement by the European Organisation for Research and Treatment of Cancer imaging group. European journal of cancer,
Vol.50
(15),
pp. 2519-2531.
Kollàr, A.
Maruzzo, M.
Messiou, C.
Cartwright, E.
Miah, A.
Martin-Liberal, J.
Thway, K.
McGrath, E.
Dunlop, A.
Khabra, K.
Seddon, B.
Dileo, P.
Linch, M.
Judson, I.
Benson, C.
(2014). Regorafenib treatment for advanced, refractory gastrointestinal stromal tumor: a report of the UK managed access program. Clinical sarcoma research,
Vol.4
(1).
Martin-Liberal, J.
Benson, C.
Messiou, C.
Fisher, C.
Judson, I.
(2014). Reversion of Hormone Treatment Resistance with the Addition of an mTOR Inhibitor in Endometrial Stromal Sarcoma. Case reports in medicine,
Vol.2014,
pp. 1-5.
show abstract
Background. Endometrial stromal sarcomas (ESS) are a subtype of gynaecological sarcomas characterized by the overexpression of hormone receptors. Hormone treatment is widely used in ESS but primary or acquired resistance is common. The mammalian target of rapamycin (mTOR) pathway has been suggested to play a key role in the mechanisms of hormone resistance. Recent studies in breast and prostate cancer demonstrate that this resistance can be reversed with the addition of an mTOR inhibitor. This phenomenon has never been reported in ESS.Methods. We report the outcome of one patient with pretreated, progressing low grade metastatic ESS treated with medroxyprogesterone acetate in combination with the mTOR inhibitor sirolimus.Results. Partial response was achieved following the addition of sirolimus to the hormone treatment. Response has been maintained for more than 2 years with minimal toxicity and treatment is ongoing.Conclusion. This case suggests that the resistance to the hormone manipulation in ESS can be reversed by the addition of an mTOR pathway inhibitor. This observation is highly encouraging and deserves further investigation..
Sandhu, S.K.
Papadopoulos, K.
Fong, P.C.
Patnaik, A.
Messiou, C.
Olmos, D.
Wang, G.
Tromp, B.J.
Puchalski, T.A.
Balkwill, F.
Berns, B.
Seetharam, S.
de Bono, J.S.
Tolcher, A.W.
(2013). A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer chemotherapy and pharmacology,
Vol.71
(4),
pp. 1041-1050.
Martin-Liberal, J.
Benson, C.
McCarty, H.
Thway, K.
Messiou, C.
Judson, I.
(2013). Pazopanib is an active treatment in desmoid tumour/aggressive fibromatosis. Clinical sarcoma research,
Vol.3
(1).
Martin-Liberal, J.
Alam, S.
Constantinidou, A.
Fisher, C.
Khabra, K.
Messiou, C.
Olmos, D.
Mitchell, S.
Al-Muderis, O.
Miah, A.
Linch, M.
Jones, R.L.
Scurr, M.
Judson, I.
Benson, C.
(2013). Clinical Activity and Tolerability of a 14-Day Infusional Ifosfamide Schedule in Soft-Tissue Sarcoma. Sarcoma,
Vol.2013,
pp. 1-6.
Messiou, C.
Orton, M.
Ang, J.E.
Collins, D.J.
Morgan, V.A.
Mears, D.
Castellano, I.
Papadatos-Pastos, D.
Brunetto, A.
Tunariu, N.
Mann, H.
Tessier, J.
Young, H.
Ghiorghiu, D.
Marley, S.
Kaye, S.B.
deBono, J.S.
Leach, M.O.
deSouza, N.M.
(2012). Advanced Solid Tumors Treated with Cediranib: Comparison of Dynamic Contrast-enhanced MR Imaging and CT as Markers of Vascular Activity. Radiology,
Vol.265
(2),
pp. 426-436.
Messiou, C.
Giles, S.
Collins, D.J.
West, S.
Davies, F.E.
Morgan, G.J.
Desouza, N.M.
(2012). Assessing response of myeloma bone disease with diffusion-weighted MRI. The british journal of radiology,
Vol.85
(1020),
pp. e1198-e1203.
Messiou, C.
Cook, G.
Reid, A.H.
Attard, G.
Dearnaley, D.
de Bono, J.S.
de Souza, N.M.
(2011). The CT flare response of metastatic bone disease in prostate cancer. Acta radiol,
Vol.52
(5),
pp. 557-561.
show abstract
Background New or worsening bone lesions in patients responding to treatment, known as the flare phenomenon is well described on (99m)Tc-MDP bone scintigraphy, but to our knowledge has not previously been described on CT. The appearance of new or worsening bone sclerosis on CT in patients with prostate cancer may therefore be erroneously classified as disease progression. Purpose To assess the incidence of osteoblastic healing flare response at 3-month CT assessment in patients with castrate-resistant prostate cancer and to identify associated features that enable differentiation from progressive metastatic bone disease at 3 months. Material and Methods CT scans of 67 patients with castrate-resistant prostate cancer undergoing treatment were reviewed by a radiologist blinded to clinical outcome. Changes in number, size, and density of metastatic bone lesions were documented and Response Evaluation Criteria in Solid Tumours (RECIST) in soft tissue lesions, alkaline phosphatase, prostate specific antigen, and (99m)Tc-MDP bone scans were used for correlation. Results Of the 39 patients who had 3- and 6-month follow-up, eight patients (21%) demonstrated an increase in number, size, or density of sclerotic lesions on the 3-month CT scan despite improvement in PSA and soft tissue lesions. Three out of eight patients (8%) maintained partial response/remained stable at follow-up and were defined as showing a flare response: in this group bone metastases evident on CT showed a qualitative and quantitative increase in density and no lesions faded at 3 months. In contrast, in all patients who progressed at 3 months by PSA/RECIST criteria (n = 8) bone lesions showed a mixed pattern with some lesions increasing and others decreasing in density. Conclusion The incidence of flare response of metastatic bone disease evident at 3-month post-treatment CT in patients with prostate cancer undergoing systemic treatment is 8%. In patients with falling PSA and stable/responding soft tissue disease at 3 months an increase in bone sclerosis in the absence of fading bone metastases can be interpreted as flare and is likely to represent a response..
Messiou, C.
Collins, D.J.
Morgan, V.A.
Desouza, N.M.
(2011). Optimising diffusion weighted MRI for imaging metastatic and myeloma bone disease and assessing reproducibility. Eur radiol,
.
show abstract
OBJECTIVES: To establish normal bone marrow values of apparent diffusion coefficient (ADC) over an age range, compare them with metastatic and myelomatous involvement, to establish reproducibility and to optimise b values. METHODS: The ADCs of bone marrow in 7 volunteers (mean age 29.7 years), 34 volunteers (mean age 63.3 years) and 43 patients with metastatic and myelomatous involvement (mean age 65.5 years) were measured. In 9 volunteers diffusion weighted MRI was repeated within 7 days. b values were derived to optimise contrast between normal and pathological marrow. RESULTS: The mean ADC of bone marrow in younger volunteers was significantly higher than that of older volunteers. The coefficient of reproducibility was 14.8%. The ADC mean of metastatic and myeloma bone disease was [Formula: see text]. An ADC threshold of 655 × 10(-6) mm(2)s(-1) separated normal and abnormal marrow with a sensitivity and specificity of 90% and 93% respectively. Contrast between normal and abnormal marrow was optimal at b = 1389 smm(-2). CONCLUSION: The reproducibility of ADC measurements in bone is equivalent to published data for soft tissue with a high sensitivity and specificity for separating abnormal from age matched normal bone marrow. A b value of around 1,400 smm(-2) is optimal for imaging bone marrow..
Kyriazi, S.
Collins, D.J.
Messiou, C.
Pennert, K.
Davidson, R.L.
Giles, S.L.
Kaye, S.B.
deSouza, N.M.
(2011). Metastatic Ovarian and Primary Peritoneal Cancer: Assessing Chemotherapy Response with Diffusion-weighted MR Imaging—Value of Histogram Analysis of Apparent Diffusion Coefficients. Radiology,
Vol.261
(1),
pp. 182-192.
Messiou, C.
Collins, D.J.
Giles, S.
de Bono, J.S.
Bianchini, D.
de Souza, N.M.
(2011). Assessing response in bone metastases in prostate cancer with diffusion weighted MRI. European radiology,
Vol.21
(10),
pp. 2169-2177.
Messiou, C.
deSouza, N.M.
(2011). Metastasis imaging: Current concepts and future challenges. Cancer biomarkers,
Vol.7
(4-5),
pp. 171-172.
Messiou, C.
Collins, D.J.
Morgan, V.A.
Robson, M.D.
deBono, J.S.
Bydder, G.M.
deSouza, N.M.
(2010). Quantifying sclerotic bone metastases with 2D ultra short TE MRI: a feasibility study. Cancer biomarkers : section a of disease markers,
Vol.7
(4),
pp. 211-218.
show abstract
Introduction Ultra Short TE MRI allows signal to be detected from tissues with a very short T2.The aims of this study were to optimize a 2D UTE MRI sequence for imaging and quantification of sclerotic bone metastases, establish T2* values of sclerotic components and investigate the feasibility of using the method to assess changes in T2* of sclerotic metastases and their relation to attenuation values in patients on treatment.Methods Twenty-two subjects were recruited in 3 cohorts. Cohort 1 was used to optimize the 2-D UTE sequence, cohort 2 was used to establish T2* measurements using a range of TEs and cohort 3 was used to assess T2* changes with treatment response and relate them to changes on electron density as measured by CT Hounsfield Units.Results Sagittal 2D UTE MRI of the lumbar spine is feasible demonstrating short T2 components in normal volunteers. In patients with bone metastases secondary to prostate carcinoma T2* can be measured and mean T2* of sclerotic metastases measured with TEs of 0.07, 0.27, 0.47 and 0.67 ms was 8.5 ms.T2* shortened by 20.0% in responders and increased by 24.4% in progressors.Discussion The significant linear relationship between percentage change in T2* as derived from UTE MRI and percentage change in HU from corresponding CT studies is indirect evidence that they are measuring effects of the same process.If the relationship between T2* and electron density holds true in further studies it offers potential for MR guided radiotherapy planning as well as attenuation correction for PET/MRI..
Messiou, C.
deSouza, N.M.
(2010). Diffusion Weighted Magnetic Resonance Imaging of metastatic bone disease: A biomarker for treatment response monitoring. Cancer biomarkers,
Vol.6
(1),
pp. 21-32.
Fong, P.C.
Yap, T.A.
Boss, D.S.
Carden, C.P.
Mergui-Roelvink, M.
Gourley, C.
De Greve, J.
Lubinski, J.
Shanley, S.
Messiou, C.
A'Hern, R.
Tutt, A.
Ashworth, A.
Stone, J.
Carmichael, J.
Schellens, J.H.
de Bono, J.S.
Kaye, S.B.
(2010). Poly(ADP)-Ribose Polymerase Inhibition: Frequent Durable Responses in BRCA Carrier Ovarian Cancer Correlating With Platinum-Free Interval. Journal of clinical oncology,
Vol.28
(15),
pp. 2512-2519.
show abstract
Purpose Selective tumor cell cytotoxicity can be achieved through a synthetic lethal strategy using poly(ADP)-ribose polymerase (PARP) inhibitor therapy in BRCA1/2 mutation carriers in whom tumor cells have defective homologous recombination (HR) DNA repair. Platinum-based chemotherapy responses correlate with HR DNA repair capacity. Olaparib is a potent, oral PARP inhibitor that is well tolerated, with antitumor activity in BRCA1/2 mutation carriers. Patients and Methods Patients with BRCA1/2-mutated ovarian cancer were treated with olaparib within a dose-escalation and single-stage expansion of a phase I trial. Antitumor activity was subsequently correlated with platinum sensitivity. Results Fifty patients were treated: 48 had germline BRCA1/2 mutations; one had a BRCA2 germline sequence change of unknown significance, and another had a strong family history of BRCA1/2-associated cancers who declined mutation testing. Of the 50 patients, 13 had platinum-sensitive disease, 24 had platinum-resistant disease, and 13 had platinum-refractory disease (according to platinum-free interval). Twenty (40%; 95% CI, 26% to 55%) achieved Response Evaluation Criteria in Solid Tumors (RECIST) complete or partial responses and/or tumor marker (CA125) responses, and three (6.0%) maintained RECIST disease stabilization for more than 4 months, giving an overall clinical benefit rate of 46% (95% CI, 32% to 61%). Median response duration was 28 weeks. There was a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory subgroups (69%, 45%, and 23%, respectively). Post hoc analyses indicated associations between platinum sensitivity and extent of olaparib response (radiologic change, P = .001; CA125 change, P = .002). Conclusion Olaparib has antitumor activity in BRCA1/2 mutation ovarian cancer, which is associated with platinum sensitivity. .
Reid, A.H.
Attard, G.
Danila, D.C.
Oommen, N.B.
Olmos, D.
Fong, P.C.
Molife, L.R.
Hunt, J.
Messiou, C.
Parker, C.
Dearnaley, D.
Swennenhuis, J.F.
Terstappen, L.W.
Lee, G.
Kheoh, T.
Molina, A.
Ryan, C.J.
Small, E.
Scher, H.I.
de Bono, J.S.
(2010). Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J clin oncol,
Vol.28
(9),
pp. 1489-1495.
show abstract
The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer (CRPC)..
Forster, M.D.
Patnaik, A.
Sandhu, S.K.
Papadopoulos, K.
Tromp, B.J.
Messiou, C.
Balkwill, F.
Berns, B.
De Bono, J.S.
Tolcher, A.W.
(2010). Pre-final analysis of first-in-human, first-in-class, phase I clinical trial of CNTO 888, a human monoclonal antibody to the CC-chemokine ligand 2 (CCL2) in patients (pts) with advanced solid tumors. Journal of clinical oncology,
Vol.28
(15_suppl),
pp. 2548-2548.
Messiou, C.
deSouza, N.M.
(2009). State-of-the-art imaging for detecting cancer in the clinic. Future oncol,
Vol.5
(2),
pp. 135-139.
Messiou, C.
Morgan, V.A.
De Silva, S.S.
Ind, T.E.
deSouza, N.M.
(2009). Diffusion weighted imaging of the uterus: regional ADC variation with oral contraceptive usage and comparison with cervical cancer. Acta radiol,
Vol.50
(6),
pp. 696-701.
show abstract
There is growing interest in diffusion weighted magnetic resonance imaging (MRI) of cervical carcinoma but normal uterine appearances and effects of the oral contraceptive pill (OCP) have not been described..
Doyle, S.
Messiou, C.
Rutherford, J.M.
Dineen, R.A.
(2009). Cancer presenting during pregnancy: radiological perspectives. Clinical radiology,
Vol.64
(9),
pp. 857-871.
Attard, G.
Reid, A.H.
A'Hern, R.
Parker, C.
Oommen, N.B.
Folkerd, E.
Messiou, C.
Molife, L.R.
Maier, G.
Thompson, E.
Olmos, D.
Sinha, R.
Lee, G.
Dowsett, M.
Kaye, S.B.
Dearnaley, D.
Kheoh, T.
Molina, A.
de Bono, J.S.
(2009). Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J clin oncol,
Vol.27
(23),
pp. 3742-3748.
show abstract
It has been postulated that castration-resistant prostate cancer (CRPC) commonly remains hormone dependent. Abiraterone acetate is a potent, selective, and orally available inhibitor of CYP17, the key enzyme in androgen and estrogen biosynthesis..
Sandhu, S.K.
Fong, P.C.
Patnaik, A.
Papadopoulos, K.
Messiou, C.
Hoare, S.
Olmos, D.
Tromp, B.J.
Puchalski, T.A.
Balkwill, F.
Berns, B.
Debono, J.S.
Tolcher, A.W.
(2009). Abstract A102: First-in-man, first-in-class, pharmacokinetic and pharmacodynamic phase I clinical trial of a human monoclonal antibody CNTO888 to CC-chemokine ligand 2 (CCL2) / monocyte chemoattractant protein (MCP-1) in patients with advanced solid tumors. Molecular cancer therapeutics,
Vol.8
(12_Supplement),
pp. A102-A102.
show abstract
Abstract
Background: The chemokine CCL2 / MCP-1 is highly expressed in multiple tumor types. Overexpression of CCL2 is associated with more advanced disease and a worse prognosis in some cancers. CCL2 plays a pivotal role in recruitment of tumor-associated macrophages and osteoclastic differentiation resulting in enhanced tumorigenesis and promotion of skeletal metastasis. CCL2 fosters angiogenesis, tumor proliferation, migration and metastasis through PI3K and NFkB signalling. CNTO888 is a human IgG1k monoclonal antibody with high CCL2 binding affinity and promising preclinical antitumor activity.
Methods: CNTO888 was administered as a 90-minute infusion on days 1, 29 of cycle 1 and subsequently on a two-weekly schedule to patients with advanced solid tumors. Pharmacodynamic assessments included free and bound CCL2 levels, circulating tumor and endothelial cell enumeration, C-telopeptide levels and other markers of bone turnover. Paired tumor biopsies were mandatory in the 2nd expansion cohort to define pharmacodynamic effects in tumor. Pre- and post-treatment diffusion contrast-enhanced computed tomography studies were carried out to explore the potential antiangiogenic effects of CNTO888.
Results: A total of 43 patients were treated with CNTO888: 21 patients during the dose escalation (0.3mg/kg, 1mg/kg, 3mg/kg, 10mg/kg, 15 mg/kg doses) and 22 patients in 2 dose expansion cohorts (10mg/kg and 15mg/kg doses). CNTO888 was well tolerated with mild toxicities namely fatigue, nausea, vomiting, headaches and one case of vasculitic rash. No dose limiting toxicities (DLTs) were observed. Preliminary pharmacokinetic data for CNTO888 doses ≥ 10mg/kg demonstrated dose proportional kinetics with a bi-exponential decline and t1/2 of 4.4–6.9 days. The 10mg/kg dose level achieved more than the steady-state concentrations required to inhibit chemotaxis and calcium mobilization as defined by preclinical studies. Dosedependent increases in bound CCL2 levels of > 1000-fold were demonstrated, confirming target modulation. An advanced ovarian cancer patient treated at 0.3mg/kg CNTO888 achieved a CA125 response by Gynaecologic Cancer Intergroup criteria with meaningful RECIST disease stabilisation for 10 months. A further two patients demonstrated RECIST stable disease > 6 months at 15mg/kg CNTO888 (ocular melanoma and neuroendocrine tumor).
Conclusions: CNTO888 is well tolerated with no DLT. Pharmacokinetics are dose proportional, with evidence of pharmacodynamic target inhibition. The recommended phase II dose for single agent CNTO888 is 15mg/kg, every two weeks. Preliminary evidence of antitumor activity has been observed.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A102..
Messiou, C.
Cook, G.
deSouza, N.M.
(2009). Imaging metastatic bone disease from carcinoma of the prostate. Br j cancer,
Vol.101
(8),
pp. 1225-1232.
show abstract
Imaging bone metastases from prostate cancer presents several challenges. The lesions are usually sclerotic and appear late on the conventional X-ray. Bone scintigraphy is the mainstay of lesion detection, but is often not suitable for assessment of treatment response, particularly because of a 'flare' phenomenon after therapy. Magnetic resonance imaging is increasingly used in assessment, and newer techniques allow quantitation. In addition to (18)F-fluorodeoxyglucose ((18)FDG), newer PET isotopes are also showing promise in lesion detection and response assessment. This article reviews the available imaging modalities for evaluating prostatic bony metastases, and links them to the underlying pathological changes within bone lesions..
MESSIOU, C.
CHALMERS, A.G.
BOYLE, K.
WILSON, D.
SAGAR, P.
(2008). Pre-operative MR assessment of recurrent rectal cancer. The british journal of radiology,
Vol.81
(966),
pp. 468-473.
Charles-Edwards, E.M.
Messiou, C.
Morgan, V.A.
De Silva, S.S.
McWhinney, N.A.
Katesmark, M.
Attygalle, A.D.
deSouza, N.M.
(2008). Diffusion-weighted Imaging in Cervical Cancer with an Endovaginal Technique: Potential Value for Improving Tumor Detection in Stage Ia and Ib1 Disease. Radiology,
Vol.249
(2),
pp. 541-550.
Spencer, J.A.
(2008). MR staging of endometrial cancer: needed or wanted?. Cancer imaging,
Vol.8
(1),
pp. 1-5.
Messiou, C.
Robinson, P.
O’Connor, P.J.
Grainger, A.
(2006). Subacute posteromedial impingement of the ankle in athletes: MR imaging evaluation and ultrasound guided therapy. Skeletal radiology,
Vol.35
(2),
pp. 88-94.
Messiou, C.
Chalmers, A.
Boyle, K.
Sagar, P.
(2006). Surgery for recurrent rectal carcinoma: The role of preoperative magnetic resonance imaging. Clinical radiology,
Vol.61
(3),
pp. 250-258.
Messiou, C.
Spencer, J.A.
Swift, S.E.
(2006). MR staging of endometrial carcinoma. Clinical radiology,
Vol.61
(10),
pp. 822-832.
Messiou, C.
Chalmers, A.G.
Dexter, S.
(2005). An unusual case of ureteric obstruction. The british journal of radiology,
Vol.78
(933),
pp. 848-850.
Hutcheon, G.
(2001). Water absorption and surface properties of novel poly(ethylmethacrylate) polymer systems for use in bone and cartilage repair. Biomaterials,
Vol.22
(7),
pp. 667-676.
Stoneham, A.
Thway, K.
Messiou, C.
Smith, M.
Cyclist's nodule: no smooth ride. Bmj case reports,
,
pp. bcr2015213087-bcr2015213087.
Tunariu, N.
Blackledge, M.
Messiou, C.
Petralia, G.
Padhani, A.
Curcean, S.
Curcean, A.
Koh, D.-.
What's New for Clinical Whole-body MRI (WB-MRI) in the 21st Century. The british journal of radiology,
Vol.93
(1115),
pp. 20200562-?.
show abstract
Whole-body MRI (WB-MRI) has evolved since its first introduction in the 1970s as an imaging technique to detect and survey disease across multiple sites and organ systems in the body. The development of diffusion-weighted MRI (DWI) has added a new dimension to the implementation of WB-MRI on modern scanners, offering excellent lesion-to-background contrast, while achieving acceptable spatial resolution to detect focal lesions 5 to 10 mm in size. MRI hardware and software advances have reduced acquisition times, with studies taking 40-50 min to complete.The rising awareness of medical radiation exposure coupled with the advantages of MRI has resulted in increased utilization of WB-MRI in oncology, paediatrics, rheumatological and musculoskeletal conditions and more recently in population screening. There is recognition that WB-MRI can be used to track disease evolution and monitor response heterogeneity in patients with cancer. There are also opportunities to combine WB-MRI with molecular imaging on PET-MRI systems to harness the strengths of hybrid imaging. The advent of artificial intelligence and machine learning will shorten image acquisition times and image analyses, making the technique more competitive against other imaging technologies..
Cojocaru, E.
Palahepitiva Gamage, G.
Butler, J.
Barton, D.P.
Thway, K.
Fisher, C.
Messiou, C.
Miah, A.B.
Zaidi, S.
Gennatas, S.
Benson, C.
Huang, P.
Jones, R.L.
Clinical management and outcomes of primary ovarian leiomyosarcoma - Experience from a sarcoma specialist unit. Gynecologic oncology reports,
Vol.36,
pp. 100737-?.
show abstract
Ovarian sarcomas account for 1% of all ovarian malignancies and amongst these, primary ovarian leiomyosarcoma is the rarest subtype. Primary ovarian leiomyosarcoma has a very poor prognosis, with less than 20% of patients being alive at 5 years. Only a few cases have been published in the literature and there is very limited knowledge on the clinical behaviour and optimal management of these tumours. We have performed a retrospective analysis of a prospectively maintained database to identify all primary ovarian leiomyosarcoma diagnosed and treated at the Royal Marsden NHS Foundation Trust between 1998 and 2020. Sixteen patients were identified from our database and fifteen were eligible for the analysis. Twelve patients presented with localized disease and underwent initial surgery and three patients had metastatic disease at presentation. Recurrence-free survival post-surgery was 16 months. Eight patients received first-line chemotherapy and four patients received second-line chemotherapy. Two patients had indolent metastatic disease and benefited from local therapies only. The median overall survival in the metastatic setting in our cohort was 51 months, which is consistent with previously published cases. Primary ovarian leiomyosarcoma is an extremely rare malignancy with a poor prognosis. This study is the largest case series of primary ovarian leiomyosarcoma published to date, providing clinically important information regarding survival and metastatic rate as well as treatment outcomes in the metastatic setting..
Barwick, T.
Orton, M.
Koh, D.M.
Kaiser, M.
Rockall, A.
Tunariu, N.
Blackledge, M.
Messiou, C.
Repeatability and reproducibility of apparent diffusion coefficient and fat fraction measurement of focal myeloma lesions on whole body magnetic resonance imaging. The british journal of radiology,
Vol.94
(1120),
pp. 20200682-?.
show abstract
Objective To assess intra- and inter-reader variability of apparent diffusion coefficient (ADC) and fat fraction (FF) measurement in focal myeloma bone lesions and the influence of lesion size.Methods 22 myeloma patients with focal active disease on whole body MRI were included. Two readers outlined a small (5-10 mm) and large lesion (>10 mm) in each subject on derived ADC and FF maps; one reader performed this twice. Intra- and inter-reader agreement for small and large lesion groups were calculated for derived statistics from each map using within-subject standard deviation, coefficient of variation, interclass correlation coefficient measures, and visualized with Bland-Altman plots.Results For mean ADC, intra- and inter-reader repeatability demonstrated equivalently low coefficient of variation (3.0-3.6%) and excellent interclass correlation coefficient (0.975-0.982) for both small and large lesions. For mean FF, intra- and inter-reader repeatability was significantly poorer for small lesions compared to large lesions (intra-reader within-subject standard variation estimate is 2.7 times higher for small lesions than large lesions ( p = 0.0071), and for inter-reader variations is 3.8 times higher ( p = 0.0070)).Conclusion There is excellent intra- and inter-reader agreement for mean ADC estimates, even for lesions as small as 5 mm. For FF measurements, there is a significant increase in coefficient of variation for smaller lesions, suggesting lesions >10 mm should be selected for lesion FF measurement.Advances in knowledge ADC measurements of focal myeloma have excellent intra- and inter-reader agreement. FF measurements are more susceptible to lesion size as intra- and inter-reader agreement is significantly impaired in lesions less than 10 mm..
Custers, J.A.
Davis, L.
Messiou, C.
Prins, J.B.
van der Graaf, W.T.
The patient perspective in the era of personalized medicine: What about scanxiety?. Cancer medicine,
Vol.10
(9),
pp. 2943-2945.
show abstract
Frequency of scanning has accelerated in the era of personalized medicine and is related, but not restricted, to the exploding number of clinical trials for new cancer treatments. Particularly in drug trials, but also in clinical practice, patients are followed up by scans frequently, which may vary from every 6 to 12 weeks until progression. The authors aimed to raise awareness for this underreported but widely present "Sword of Damocles" scan-related issue also referred to as 'scanxiety.'.
Zormpas-Petridis, K.
Tunariu, N.
Curcean, A.
Messiou, C.
Curcean, S.
Collins, D.J.
Hughes, J.C.
Jamin, Y.
Koh, D.-.
Blackledge, M.D.
Accelerating Whole-Body Diffusion-weighted MRI with Deep Learning-based Denoising Image Filters. Radiology. artificial intelligence,
Vol.3
(5),
pp. e200279-?.
show abstract
Purpose To use deep learning to improve the image quality of subsampled images (number of acquisitions = 1 [NOA 1 ]) to reduce whole-body diffusion-weighted MRI (WBDWI) acquisition times. Materials and methods Both retrospective and prospective patient groups were used to develop a deep learning-based denoising image filter (DNIF) model. For initial model training and validation, 17 patients with metastatic prostate cancer with acquired WBDWI NOA 1 and NOA 9 images (acquisition period, 2015-2017) were retrospectively included. An additional 22 prospective patients with advanced prostate cancer, myeloma, and advanced breast cancer were used for model testing (2019), and the radiologic quality of DNIF-processed NOA 1 (NOA 1-DNIF ) images were compared with NOA 1 images and clinical NOA 16 images by using a three-point Likert scale (good, average, or poor; statistical significance was calculated by using a Wilcoxon signed ranked test). The model was also retrained and tested in 28 patients with malignant pleural mesothelioma (MPM) who underwent lung MRI (2015-2017) to demonstrate feasibility in other body regions. Results The model visually improved the quality of NOA 1 images in all test patients, with the majority of NOA 1-DNIF and NOA 16 images being graded as either "average" or "good" across all image-quality criteria. From validation data, the mean apparent diffusion coefficient (ADC) values within NOA 1-DNIF images of bone disease deviated from those within NOA 9 images by an average of 1.9% (range, 1.1%-2.6%). The model was also successfully applied in the context of MPM; the mean ADCs from NOA 1-DNIF images of MPM deviated from those measured by using clinical-standard images (NOA 12 ) by 3.7% (range, 0.2%-10.6%). Conclusion Clinical-standard images were generated from subsampled images by using a DNIF. Keywords: Image Postprocessing, MR-Diffusion-weighted Imaging, Neural Networks, Oncology, Whole-Body Imaging, Supervised Learning, MR-Functional Imaging, Metastases, Prostate, Lung Supplemental material is available for this article. Published under a CC BY 4.0 license..
Kalantar, R.
Messiou, C.
Winfield, J.M.
Renn, A.
Latifoltojar, A.
Downey, K.
Sohaib, A.
Lalondrelle, S.
Koh, D.-.
Blackledge, M.D.
CT-Based Pelvic T1-Weighted MR Image Synthesis Using UNet, UNet++ and Cycle-Consistent Generative Adversarial Network (Cycle-GAN). Frontiers in oncology,
Vol.11,
pp. 665807-?.
show abstract
Background Computed tomography (CT) and magnetic resonance imaging (MRI) are the mainstay imaging modalities in radiotherapy planning. In MR-Linac treatment, manual annotation of organs-at-risk (OARs) and clinical volumes requires a significant clinician interaction and is a major challenge. Currently, there is a lack of available pre-annotated MRI data for training supervised segmentation algorithms. This study aimed to develop a deep learning (DL)-based framework to synthesize pelvic T 1 -weighted MRI from a pre-existing repository of clinical planning CTs.Methods MRI synthesis was performed using UNet++ and cycle-consistent generative adversarial network (Cycle-GAN), and the predictions were compared qualitatively and quantitatively against a baseline UNet model using pixel-wise and perceptual loss functions. Additionally, the Cycle-GAN predictions were evaluated through qualitative expert testing (4 radiologists), and a pelvic bone segmentation routine based on a UNet architecture was trained on synthetic MRI using CT-propagated contours and subsequently tested on real pelvic T 1 weighted MRI scans.Results In our experiments, Cycle-GAN generated sharp images for all pelvic slices whilst UNet and UNet++ predictions suffered from poorer spatial resolution within deformable soft-tissues (e.g. bladder, bowel). Qualitative radiologist assessment showed inter-expert variabilities in the test scores; each of the four radiologists correctly identified images as acquired/synthetic with 67%, 100%, 86% and 94% accuracy. Unsupervised segmentation of pelvic bone on T1-weighted images was successful in a number of test cases.Conclusion Pelvic MRI synthesis is a challenging task due to the absence of soft-tissue contrast on CT. Our study showed the potential of deep learning models for synthesizing realistic MR images from CT, and transferring cross-domain knowledge which may help to expand training datasets for 21 development of MR-only segmentation models..
Fu, X.
Zhao, Y.
Lopez, J.I.
Rowan, A.
Au, L.
Fendler, A.
Hazell, S.
Xu, H.
Horswell, S.
Shepherd, S.T.
Spencer, C.E.
Spain, L.
Byrne, F.
Stamp, G.
O'Brien, T.
Nicol, D.
Augustine, M.
Chandra, A.
Rudman, S.
Toncheva, A.
Furness, A.J.
Pickering, L.
Kumar, S.
Koh, D.-.
Messiou, C.
Dafydd, D.A.
Orton, M.R.
Doran, S.J.
Larkin, J.
Swanton, C.
Sahai, E.
Litchfield, K.
Turajlic, S.
TRACERx Renal Consortium,
Bates, P.A.
Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study. Nature ecology & evolution,
Vol.6
(1),
pp. 88-102.
show abstract
Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution..
Fendler, A.
Au, L.
Shepherd, S.T.
Byrne, F.
Cerrone, M.
Boos, L.A.
Rzeniewicz, K.
Gordon, W.
Shum, B.
Gerard, C.L.
Ward, B.
Xie, W.
Schmitt, A.M.
Joharatnam-Hogan, N.
Cornish, G.H.
Pule, M.
Mekkaoui, L.
Ng, K.W.
Carlyle, E.
Edmonds, K.
Rosario, L.D.
Sarker, S.
Lingard, K.
Mangwende, M.
Holt, L.
Ahmod, H.
Stone, R.
Gomes, C.
Flynn, H.R.
Agua-Doce, A.
Hobson, P.
Caidan, S.
Howell, M.
Wu, M.
Goldstone, R.
Crawford, M.
Cubitt, L.
Patel, H.
Gavrielides, M.
Nye, E.
Snijders, A.P.
MacRae, J.I.
Nicod, J.
Gronthoud, F.
Shea, R.L.
Messiou, C.
Cunningham, D.
Chau, I.
Starling, N.
Turner, N.
Welsh, L.
van As, N.
Jones, R.L.
Droney, J.
Banerjee, S.
Tatham, K.C.
Jhanji, S.
O’Brien, M.
Curtis, O.
Harrington, K.
Bhide, S.
Bazin, J.
Robinson, A.
Stephenson, C.
Slattery, T.
Khan, Y.
Tippu, Z.
Leslie, I.
Gennatas, S.
Okines, A.
Reid, A.
Young, K.
Furness, A.J.
Pickering, L.
Gandhi, S.
Gamblin, S.
Swanton, C.
Nicholson, E.
Kumar, S.
Yousaf, N.
Wilkinson, K.A.
Swerdlow, A.
Harvey, R.
Kassiotis, G.
Larkin, J.
Wilkinson, R.J.
Turajlic, S.
Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study. Nature cancer,
Vol.2
(12),
pp. 1321-1337.
show abstract
AbstractPatients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer..
Bhaludin, B.N.
Tunariu, N.
Koh, D.-.
Messiou, C.
Okines, A.F.
McGrath, S.E.
Ring, A.E.
Parton, M.M.
Sharma, B.
Gagliardi, T.
Allen, S.D.
Pope, R.
Johnston, S.R.
Downey, K.
A review on the added value of whole-body MRI in metastatic lobular breast cancer. European radiology,
Vol.32
(9),
pp. 6514-6525.
Johnston, E.W.
Fotiadis, N.
Cummings, C.
Basso, J.
Tyne, T.
Lameijer, J.
Messiou, C.
Koh, D.-.
Winfield, J.M.
Developing and testing a robotic MRI/CT fusion biopsy technique using a purpose-built interventional phantom. European radiology experimental,
Vol.6
(1).
show abstract
Abstract
Background
Magnetic resonance imaging (MRI) can be used to target tumour components in biopsy procedures, while the ability to precisely correlate histology and MRI signal is crucial for imaging biomarker validation. Robotic MRI/computed tomography (CT) fusion biopsy offers the potential for this without in-gantry biopsy, although requires development.
Methods
Test–retest T1 and T2 relaxation times, attenuation (Hounsfield units, HU), and biopsy core quality were prospectively assessed (January–December 2021) in a range of gelatin, agar, and mixed gelatin/agar solutions of differing concentrations on days 1 and 8 after manufacture. Suitable materials were chosen, and four biopsy phantoms were constructed with twelve spherical 1–3-cm diameter targets visible on MRI, but not on CT. A technical pipeline was developed, and intraoperator and interoperator reliability was tested in four operators performing a total of 96 biopsies. Statistical analysis included T1, T2, and HU repeatability using Bland–Altman analysis, Dice similarity coefficient (DSC), and intraoperator and interoperator reliability.
Results
T1, T2, and HU repeatability had 95% limits-of-agreement of 8.3%, 3.4%, and 17.9%, respectively. The phantom was highly reproducible, with DSC of 0.93 versus 0.92 for scanning the same or two different phantoms, respectively. Hit rate was 100% (96/96 targets), and all operators performed robotic biopsies using a single volumetric acquisition. The fastest procedure time was 32 min for all 12 targets.
Conclusions
A reproducible biopsy phantom was developed, validated, and used to test robotic MRI/CT-fusion biopsy. The technique was highly accurate, reliable, and achievable in clinically acceptable timescales meaning it is suitable for clinical application.
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