Publications

Hall, E. Hussain, S.A. Porta, N. Lewis, R. Crundwell, M. Jenkins, P. Rawlings, C. Tremlett, J. Sreenivasan, T. Wallace, J. Syndikus, I. Sheehan, D. Lydon, A. Huddart, R. James, N. BC2001 Investigators, (2022). Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial. , , pp. S0302-2838(22)02265. show abstract

BACKGROUND: BC2001, the largest randomised trial of bladder-sparing treatment for muscle-invasive bladder cancer (MIBC), demonstrated improvement in locoregional control by adding fluorouracil and mitomycin C to radiotherapy (James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012;366:1477-88). There are limited data on long-term recurrence risk. OBJECTIVE: To determine whether benefit of adding chemotherapy to radiotherapy for MIBC is maintained in the long term. DESIGN, SETTING, AND PARTICIPANTS: A phase 3 randomised controlled 2 × 2 factorial trial was conducted. Between 2001 and 2008, 458 patients with T2-T4a N0M0 MIBC were enrolled; 360 were randomised to radiotherapy (178) or chemoradiotherapy (182), and 218 were randomised to standard whole-bladder radiotherapy (108) or reduced high-dose-volume radiotherapy (111). The median follow-up time was 9.9 yr. The trial is registered (ISRCTN68324339). INTERVENTION: Radiotherapy: 55 Gy in 20 fractions over 4 wk or 64 Gy in 32 fractions over 6.5 wk; concurrent chemotherapy: 5-fluorouracil and mitomycin C. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Locoregional control (primary endpoint), invasive locoregional control, toxicity, rate of salvage cystectomy, disease-free survival (DFS), metastasis-free survival (MFS), bladder cancer-specific survival (BCSS), and overall survival. Cox regression was used. The analysis of efficacy outcomes was by intention to treat. RESULTS AND LIMITATIONS: Chemoradiotherapy improved locoregional control (hazard ratio [HR] 0.61 [95% confidence interval {CI} 0.43-0.86], p = 0.004) and invasive locoregional control (HR 0.55 [95% CI 0.36-0.84], p = 0.006). This benefit translated, albeit nonsignificantly, for disease-related outcomes: DFS (HR 0.78 [95% CI 0.60-1.02], p = 0.069), MFS (HR 0.78, [95% CI 0.58-1.05], p = 0.089), overall survival (HR = 0.88 [95% CI 0.69-1.13], p = 0.3), and BCSS (HR 0.79 [95% CI 0.59-1.06], p = 0.11). The 5-yr cystectomy rate was 14% (95% CI 9-21%) with chemoradiotherapy versus 22% (95% CI 16-31%) with radiotherapy alone (HR 0.54, [95% CI 0.31-0.95], p = 0.034). No differences were seen between standard and reduced high-dose-volume radiotherapy. CONCLUSIONS: Long-term findings confirm the benefit of adding concomitant 5-fluorouracil and mitomycin C to radiotherapy for MIBC. PATIENT SUMMARY: We looked at long-term outcomes of a phase 3 clinical trial testing radiotherapy with or without chemotherapy for patients with invasive bladder cancer. We concluded that the benefit of adding chemotherapy to radiotherapy was maintained over 10 yr..

Bundred, N. Porta, N. Brunt, A.M. Cramer, A. Hanby, A. Shaaban, A.M. Rakha, E.A. Armstrong, A. Cutress, R.I. Dodwell, D. Emson, M.A. Evans, A. Hartup, S.M. Horgan, K. Miller, S.E. McIntosh, S.A. Morden, J.P. Naik, J. Narayanan, S. Ooi, J. Skene, A.I. Cameron, D.A. Bliss, J.M. (2022). Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results. Clinical cancer research : an official journal of the american association for cancer research, . show abstract

Rescigno, P. Gurel, B. Pereira, R. Crespo, M. Rekowski, J. Rediti, M. Barrero, M. Mateo, J. Bianchini, D. Messina, C. Fenor de la Maza, M.D. Chandran, K. Carmichael, J. Guo, C. Paschalis, A. Sharp, A. Seed, G. Figueiredo, I. Lambros, M. Miranda, S. Ferreira, A. Bertan, C. Riisnaes, R. Porta, N. Yuan, W. Carreira, S. de Bono, J.S. (2021). Characterizing CDK12-Mutated Prostate Cancers. Clinical cancer research : an official journal of the american association for cancer research, Vol.27 (2), pp. 566-574. show abstract

Purpose Cyclin-dependent kinase 12 (CDK12) aberrations have been reported as a biomarker of response to immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). Herein, we characterize CDK12-mutated mCRPC, presenting clinical, genomic, and tumor-infiltrating lymphocyte (TIL) data.Experimental design Patients with mCRPC consented to the molecular analyses of diagnostic and mCRPC biopsies. Genomic analyses involved targeted next-generation (MiSeq; Illumina) and exome sequencing (NovaSeq; Illumina). TILs were assessed by validated immunocytochemistry coupled with deep learning-based artificial intelligence analyses including multiplex immunofluorescence assays for CD4, CD8, and FOXP3 evaluating TIL subsets. The control group comprised a randomly selected mCRPC cohort with sequencing and clinical data available.Results Biopsies from 913 patients underwent targeted sequencing between February 2015 and October 2019. Forty-three patients (4.7%) had tumors with CDK12 alterations. CDK12-altered cancers had distinctive features, with some revealing high chromosomal break numbers in exome sequencing. Biallelic CDK12-aberrant mCRPCs had shorter overall survival from diagnosis than controls [5.1 years (95% confidence interval (CI), 4.0-7.9) vs. 6.4 years (95% CI, 5.7-7.8); hazard ratio (HR), 1.65 (95% CI, 1.07-2.53); P = 0.02]. Median intratumoral CD3 + cell density was higher in CDK12 cancers, although this was not statistically significant (203.7 vs. 86.7 cells/mm 2 ; P = 0.07). This infiltrate primarily comprised of CD4 + FOXP3 - cells (50.5 vs. 6.2 cells/mm 2 ; P < 0.0001), where high counts tended to be associated with worse survival from diagnosis (HR, 1.64; 95% CI, 0.95-2.84; P = 0.077) in the overall population.Conclusions CDK12-altered mCRPCs have worse prognosis, with these tumors surprisingly being primarily enriched for CD4 + FOXP3 - cells that seem to associate with worse outcome and may be immunosuppressive. See related commentary by Lotan and Antonarakis, p. 380 ..

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.

Hussain, S.A. Porta, N. Hall, E. Salawu, A. Lewis, R. Sreenivasan, T. Wallace, J. Crundwell, M. Jenkins, P. Tremlett, J. Huddart, R. James, N.D. BC2001 Investigators, (2021). Outcomes in Patients with Muscle-invasive Bladder Cancer Treated with Neoadjuvant Chemotherapy Followed by (Chemo)radiotherapy in the BC2001 Trial. European urology, Vol.79 (2), pp. 307-315. show abstract

Background BC2001 demonstrated improved local control with the addition of chemotherapy to radiotherapy in 360 patients with muscle-invasive bladder cancer. Objective To establish whether such benefit remained in BC2001 patients who received prior neoadjuvant chemotherapy. Design, setting, and participants A total of 117 patients (33%) received neoadjuvant chemotherapy and were randomised to radiotherapy with (48%) or without (52%) concomitant chemotherapy. Patients were recruited between August 2001 and April 2008 from 28 UK centres. Intervention Platinum-based neoadjuvant chemotherapy, followed by radiotherapy with (cRT) or without (RT) synchronous 5-fluorouracil and mitomycin-C. Outcome measurements and statistical analysis Toxicity, locoregional control (LRC), overall survival (OS), and quality of life (QoL) were measured. Results and limitations Of the patients, 74% received gemcitabine plus cisplatin or carboplatin. Compliance rates with full-dose radiotherapy were cRT 93% and RT 92%. An excess of grade ≥3 toxicities while on (chemo)radiation occurred for cRT 33% versus RT 22%, although nonstatistically significant (p = 0.16). With 110 mo median follow-up for survival (interquartile range 96-123), cRT showed improved LRC though not statistically significant (adjusted hazard ratio [aHR] = 0.64, 95% confidence interval [CI] 0.33-1.23, p = 0.18). No differences in OS (aHR = 0.95, 95% CI 0.57-1.57, p = 0.8) were observed. No significant detriment in QoL was observed between cRT and RT in this subgroup of patients. Conclusions Neoadjuvant chemotherapy does not compromise the delivery of radical curative treatment. Although underpowered due to a small sample size, the benefit of chemoradiotherapy to improve local control in this group of patients receiving neoadjuvant chemotherapy is consistent with that observed in the main trial. Although a nonsignificant excess of toxicity was observed, there was no evidence of impaired QoL. Patient summary Chemotherapy before radical chemo(radiotherapy) is feasible and well tolerated..

Choudhury, A. Porta, N. Hall, E. Song, Y.P. Owen, R. MacKay, R. West, C.M. Lewis, R. Hussain, S.A. James, N.D. Huddart, R. Hoskin, P. BC2001 and BCON investigators, (2021). Hypofractionated radiotherapy in locally advanced bladder cancer: an individual patient data meta-analysis of the BC2001 and BCON trials. Lancet oncol, Vol.22 (2), pp. 246-255. show abstract

BACKGROUND: Two radiotherapy fractionation schedules are used to treat locally advanced bladder cancer: 64 Gy in 32 fractions over 6·5 weeks and a hypofractionated schedule of 55 Gy in 20 fractions over 4 weeks. Long-term outcomes of these schedules in several cohort studies and case series suggest that response, survival, and toxicity are similar, but no direct comparison has been published. The present study aimed to assess the non-inferiority of 55 Gy in 20 fractions to 64 Gy in 32 fractions in terms of invasive locoregional control and late toxicity in patients with locally advanced bladder cancer. METHODS: We did a meta-analysis of individual patient data from patients (age ≥18 years) with locally advanced bladder cancer (T1G3 [high-grade non-muscle invasive] or T2-T4, N0M0) enrolled in two multicentre, randomised, controlled, phase 3 trials done in the UK: BC2001 (NCT00024349; assessing addition of chemotherapy to radiotherapy) and BCON (NCT00033436; assessing hypoxia-modifying therapy combined with radiotherapy). In each trial, the fractionation schedule was chosen according to local standard practice. Co-primary endpoints were invasive locoregional control (non-inferiority margin hazard ratio [HR]=1·25); and late bladder or rectum toxicity, assessed with the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic tool (non-inferiority margin for absolute risk difference [RD]=10%). If non-inferiority was met for invasive locoregional control, superiority could be considered if the 95% CI for the treatment effect excluded the null effect (HR=1). One-stage individual patient data meta-analysis models for the time-to-event and binary outcomes were used, accounting for trial differences, within-centre correlation, randomised treatment received, baseline variable imbalances, and potential confounding from relevant prognostic factors. FINDINGS: 782 patients with known fractionation schedules (456 from the BC2001 trial and 326 from the BCON trial; 376 (48%) received 64 Gy in 32 fractions and 406 (52%) received 55 Gy in 20 fractions) were included in our meta-analysis. Median follow-up was 120 months (IQR 99-159). Patients who received 55 Gy in 20 fractions had a lower risk of invasive locoregional recurrence than those who received 64 Gy in 32 fractions (adjusted HR 0·71 [95% CI 0·52-0·96]). Both schedules had similar toxicity profiles (adjusted RD -3·37% [95% CI -11·85 to 5·10]). INTERPRETATION: A hypofractionated schedule of 55 Gy in 20 fractions is non-inferior to 64 Gy in 32 fractions with regard to both invasive locoregional control and toxicity, and is superior with regard to invasive locoregional control. 55 Gy in 20 fractions should be adopted as a standard of care for bladder preservation in patients with locally advanced bladder cancer. FUNDING: Cancer Research UK..

Winfield, J.M. Wakefield, J.C. Brenton, J.D. AbdulJabbar, K. Savio, A. Freeman, S. Pace, E. Lutchman-Singh, K. Vroobel, K.M. Yuan, Y. Banerjee, S. Porta, N. Ahmed Raza, S.E. deSouza, N.M. (2021). Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis. British journal of cancer, . show abstract

McHugh, D.J. Porta, N. Little, R.A. Cheung, S. Watson, Y. Parker, G.J. Jayson, G.C. O'Connor, J.P. (2021). Image Contrast, Image Pre-Processing, and T1 Mapping Affect MRI Radiomic Feature Repeatability in Patients with Colorectal Cancer Liver Metastases. Cancers, Vol.13 (2). show abstract

Mariam, N.B. Song, Y.P. Joseph, N. Hoskin, P. Reeves, K. Porta, N. James, N. Choudhury, A. (2021). Hypofractionation: less is more?. Oncotarget, Vol.12 (17), pp. 1729-1733. show abstract

Carreira, S. Porta, N. Arce-Gallego, S. Seed, G. Llop-Guevara, A. Bianchini, D. Rescigno, P. Paschalis, A. Bertan, C. Baker, C. Goodall, J. Miranda, S. Riisnaes, R. Figueiredo, I. Ferreira, A. Pereira, R. Crespo, M. Gurel, B. Nava Rodrigues, D. Pettitt, S.J. Yuan, W. Serra, V. Rekowski, J. Lord, C.J. Hall, E. Mateo, J. de Bono, J.S. (2021). Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial. Cancer discovery, . show abstract

Mateo, J. Porta, N. Bianchini, D. McGovern, U. Elliott, T. Jones, R. Syndikus, I. Ralph, C. Jain, S. Varughese, M. Parikh, O. Crabb, S. Robinson, A. McLaren, D. Birtle, A. Tanguay, J. Miranda, S. Figueiredo, I. Seed, G. Bertan, C. Flohr, P. Ebbs, B. Rescigno, P. Fowler, G. Ferreira, A. Riisnaes, R. Pereira, R. Curcean, A. Chandler, R. Clarke, M. Gurel, B. Crespo, M. Nava Rodrigues, D. Sandhu, S. Espinasse, A. Chatfield, P. Tunariu, N. Yuan, W. Hall, E. Carreira, S. de Bono, J.S. (2020). Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. The lancet. oncology, Vol.21 (1), pp. 162-174. show abstract

Background Metastatic castration-resistant prostate cancer is enriched in DNA damage response (DDR) gene aberrations. The TOPARP-B trial aims to prospectively validate the association between DDR gene aberrations and response to olaparib in metastatic castration-resistant prostate cancer.Methods In this open-label, investigator-initiated, randomised phase 2 trial following a selection (or pick-the-winner) design, we recruited participants from 17 UK hospitals. Men aged 18 years or older with progressing metastatic castration-resistant prostate cancer previously treated with one or two taxane chemotherapy regimens and with an Eastern Cooperative Oncology Group performance status of 2 or less had tumour biopsies tested with targeted sequencing. Patients with DDR gene aberrations were randomly assigned (1:1) by a computer-generated minimisation method, with balancing for circulating tumour cell count at screening, to receive 400 mg or 300 mg olaparib twice daily, given continuously in 4-week cycles until disease progression or unacceptable toxicity. Neither participants nor investigators were masked to dose allocation. The primary endpoint of confirmed response was defined as a composite of all patients presenting with any of the following outcomes: radiological objective response (as assessed by Response Evaluation Criteria in Solid Tumors 1.1), a decrease in prostate-specific antigen (PSA) of 50% or more (PSA50) from baseline, or conversion of circulating tumour cell count (from ≥5 cells per 7·5 mL blood at baseline to <5 cells per 7·5 mL blood). A confirmed response in a consecutive assessment after at least 4 weeks was required for each component. The primary analysis was done in the evaluable population. If at least 19 (43%) of 44 evaluable patients in a dose cohort responded, then the dose cohort would be considered successful. Safety was assessed in all patients who received at least one dose of olaparib. This trial is registered at ClinicalTrials.gov, NCT01682772. Recruitment for the trial has completed and follow-up is ongoing.Findings 711 patients consented for targeted screening between April 1, 2015, and Aug 30, 2018. 161 patients had DDR gene aberrations, 98 of whom were randomly assigned and treated (49 patients for each olaparib dose), with 92 evaluable for the primary endpoint (46 patients for each olaparib dose). Median follow-up was 24·8 months (IQR 16·7-35·9). Confirmed composite response was achieved in 25 (54·3%; 95% CI 39·0-69·1) of 46 evaluable patients in the 400 mg cohort, and 18 (39·1%; 25·1-54·6) of 46 evaluable patients in the 300 mg cohort. Radiological response was achieved in eight (24·2%; 11·1-42·3) of 33 evaluable patients in the 400 mg cohort and six (16·2%; 6·2-32·0) of 37 in the 300 mg cohort; PSA50 response was achieved in 17 (37·0%; 23·2-52·5) of 46 and 13 (30·2%; 17·2-46·1) of 43; and circulating tumour cell count conversion was achieved in 15 (53·6%; 33·9-72·5) of 28 and 13 (48·1%; 28·7-68·1) of 27. The most common grade 3-4 adverse event in both cohorts was anaemia (15 [31%] of 49 patients in the 300 mg cohort and 18 [37%] of 49 in the 400 mg cohort). 19 serious adverse reactions were reported in 13 patients. One death possibly related to treatment (myocardial infarction) occurred after 11 days of treatment in the 300 mg cohort.Interpretation Olaparib has antitumour activity against metastatic castration-resistant prostate cancer with DDR gene aberrations, supporting the implementation of genomic stratification of metastatic castration-resistant prostate cancer in clinical practice.Funding Cancer Research UK, AstraZeneca, Prostate Cancer UK, the Prostate Cancer Foundation, the Experimental Cancer Medicine Centres Network, and the National Institute for Health Research Biomedical Research Centres..

Huddart, R.A. Hall, E. Lewis, R. Porta, N. Crundwell, M. Jenkins, P.J. Rawlings, C. Tremlett, J. Campani, L. Hendron, C. Hussain, S.A. James, N.D. BC2001 Investigators, (2020). Patient-reported Quality of Life Outcomes in Patients Treated for Muscle-invasive Bladder Cancer with Radiotherapy ± Chemotherapy in the BC2001 Phase III Randomised Controlled Trial. European urology, Vol.77 (2), pp. 260-268. show abstract

Background BC2001, the largest randomised trial of bladder-sparing treatment for muscle-invasive bladder cancer, demonstrated improvement of local control and bladder cancer-specific survival from the addition of concomitant 5-fluorouracil and mitomycin C to radiotherapy.Objective To determine the impact of treatment on the health-related quality of life (HRQoL) of BC2001 participants.Design, setting, and participants 458 UK patients with T2-T4a N0 M0 transitional cell carcinoma of the bladder.Intervention Patients were randomised to the chemotherapy comparison (radiotherapy, 178, or chemoradiotherapy, 182); and/or to the radiotherapy comparison (standard, 108, or reduced high-dose volume radiotherapy, 111).Outcome measurements and statistical analysis Patients completed Functional Assessment of Cancer Therapy-Bladder (FACT-BL) questionnaires at baseline, end of treatment (EoT), and 6, 12, 24, 36, 48, and 60 months after radiotherapy. The primary endpoint was change from baseline in the bladder cancer subscale (BLCS) at 12 months.Results and limitations Data were available for 331 (92%) and 204 (93%) participants at baseline and for 192 (54%) and 114 (52%) at 12 months for the chemotherapy and radiotherapy comparisons, respectively. HRQoL declined at EoT (BLCS -5.06 [99% confidence interval: -6.12 to -4.00, p< 0.001]; overall FACT-B TOTAL score -8.22 [-10.76 to -5.68, p< 0.01]), recovering to baseline at 6 months and remaining similar to baseline subsequently. There was no significant difference between randomised groups at any time point.Conclusions Immediately following (chemo)radiotherapy, a significant proportion of patients report declines in HRQoL, which improve to baseline after 6 months. Two-thirds of patients report stable or improved HRQoL on long-term follow-up. There is no evidence of impairment in HRQoL resulting from the addition of chemotherapy.Patient summary Quality of life of bladder cancer patients treated with radiotherapy±chemotherapy deteriorates during treatment, but improves to at least pretreatment levels within 6 months. Addition of chemotherapy to radiotherapy does not affect patient-reported quality of life..

Mateo, J. Seed, G. Bertan, C. Rescigno, P. Dolling, D. Figueiredo, I. Miranda, S. Nava Rodrigues, D. Gurel, B. Clarke, M. Atkin, M. Chandler, R. Messina, C. Sumanasuriya, S. Bianchini, D. Barrero, M. Petermolo, A. Zafeiriou, Z. Fontes, M. Perez-Lopez, R. Tunariu, N. Fulton, B. Jones, R. McGovern, U. Ralph, C. Varughese, M. Parikh, O. Jain, S. Elliott, T. Sandhu, S. Porta, N. Hall, E. Yuan, W. Carreira, S. de Bono, J.S. (2020). Genomics of lethal prostate cancer at diagnosis and castration resistance. The journal of clinical investigation, Vol.130 (4), pp. 1743-1751. show abstract

Kolinsky, M.P. Rescigno, P. Bianchini, D. Zafeiriou, Z. Mehra, N. Mateo, J. Michalarea, V. Riisnaes, R. Crespo, M. Figueiredo, I. Miranda, S. Nava Rodrigues, D. Flohr, P. Tunariu, N. Banerji, U. Ruddle, R. Sharp, A. Welti, J. Lambros, M. Carreira, S. Raynaud, F.I. Swales, K.E. Plymate, S. Luo, J. Tovey, H. Porta, N. Slade, R. Leonard, L. Hall, E. de Bono, J.S. (2020). A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer. Annals of oncology : official journal of the european society for medical oncology, Vol.31 (5), pp. 619-625. show abstract

Background Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence suggests that combined inhibition of the androgen receptor (AR) and AKT may be beneficial in mCRPC with PTEN loss.Patients and methods mCRPC patients who previously failed abiraterone and/or enzalutamide, received escalating doses of AZD5363 (capivasertib) starting at 320 mg twice daily (b.i.d.) given 4 days on and 3 days off, in combination with enzalutamide 160 mg daily. The co-primary endpoints were safety/tolerability and determining the maximum tolerated dose and recommended phase II dose; pharmacokinetics, antitumour activity, and exploratory biomarker analysis were also evaluated.Results Sixteen patients were enrolled, 15 received study treatment and 13 were assessable for dose-limiting toxicities (DLTs). Patients were treated at 320, 400, and 480 mg b.i.d. dose levels of capivasertib. The recommended phase II dose identified for capivasertib was 400 mg b.i.d. with 1/6 patients experiencing a DLT (maculopapular rash) at this level. The most common grade ≥3 adverse events were hyperglycemia (26.7%) and rash (20%). Concomitant administration of enzalutamide significantly decreased plasma exposure of capivasertib, though this did not appear to impact pharmacodynamics. Three patients met the criteria for response (defined as prostate-specific antigen decline ≥50%, circulating tumour cell conversion, and/or radiological response). Responses were seen in patients with PTEN loss or activating mutations in AKT, low or absent AR-V7 expression, as well as those with an increase in phosphorylated extracellular signal-regulated kinase (pERK) in post-exposure samples.Conclusions The combination of capivasertib and enzalutamide is tolerable and has antitumour activity, with all responding patients harbouring aberrations in the PI3K/AKT/mTOR pathway.Clinical trial number NCT02525068..

Mostafid, A.H. Porta, N. Cresswell, J. Griffiths, T.R. Kelly, J.D. Penegar, S.R. Davenport, K. McGrath, J.S. Campain, N. Cooke, P. Masood, S. Knowles, M.A. Feber, A. Knight, A. Catto, J.W. Lewis, R. Hall, E. (2020). CALIBER: a phase II randomized feasibility trial of chemoablation with mitomycin-C vs surgical management in low-risk non-muscle-invasive bladder cancer. Bju international, Vol.125 (6), pp. 817-826. show abstract

Objectives To evaluate the activity of intravesical mitomycin-C (MMC) to ablate recurrent low-risk non-muscle-invasive bladder cancer (NMIBC) and assess whether it may enable patients to avoid surgical intervention for treatment of recurrence.Patients and methods CALIBER is a phase II feasibility study. Participants were randomized (2:1) to treatment with four once-weekly MMC 40-mg intravesical instillations (chemoablation arm) or to surgical management. The surgical group was included to assess the feasibility of randomization. The primary endpoint was complete response to intravesical MMC in the chemoablation arm at 3 months, reported with exact 95% confidence intervals (CIs). Secondary endpoints included time to subsequent recurrence, summarized by Kaplan-Meier methods.Results Between February 2015 and August 2017, 82 patients with visual diagnosis of recurrent low-risk NMIBC were enrolled from 24 UK hospitals (chemoablation, n = 54; surgical management, n =28). The median follow-up was 24 months. Complete response at 3 months was 37.0% (20/54; 95% CI 24.3-51.3) with chemoablation and 80.8% (21/26; 95% CI 60.6-93.4) with surgical management. Amongst patients with complete response at 3 months, a similar proportion was recurrence-free by 12 months in both groups (84%). Amongst those with residual disease at 3 months, the 12-month recurrence-free proportion was lower in the surgical management group (40.0%) than in the chemoablation group (84%). Recruitment stopped early as chemoablation did not meet the prespecified threshold of 45% complete responses at 3 months.Conclusion Intravesical chemoablation in low-risk NMIBC is feasible and safe, but did not demonstrate sufficient response in the present trial. After chemoablation there may be a reduction in recurrence rate, even in non-responders, that is greater than with surgery alone. Further research is required to investigate the role and optimal schedule of neoadjuvant intravesical chemotherapy prior to surgery for NMIBC..

Cox, E. Saramago, P. Kelly, J. Porta, N. Hall, E. Tan, W.S. Sculpher, M. Soares, M. (2020). Effects of Bladder Cancer on UK Healthcare Costs and Patient Health-Related Quality of Life: Evidence From the BOXIT Trial. Clinical genitourinary cancer, Vol.18 (4), pp. e418-e442. show abstract

Syndikus, I. Cruickshank, C. Staffurth, J. Tree, A. Henry, A. Naismith, O. Mayles, H. Snelson, N. Hassan, S. Brown, S. Porta, N. Griffin, C. Hall, E. (2020). PIVOTALboost: A phase III randomised controlled trial of prostate and pelvis versus prostate alone radiotherapy with or without prostate boost (CRUK/16/018). Clinical and translational radiation oncology, Vol.25, pp. 22-28. show abstract

Kelly, J.D. Tan, W.S. Porta, N. Mostafid, H. Huddart, R. Protheroe, A. Bogle, R. Blazeby, J. Palmer, A. Cresswell, J. Johnson, M. Brough, R. Madaan, S. Andrews, S. Cruickshank, C. Burnett, S. Maynard, L. Hall, E. BOXIT Investigators, (2019). BOXIT-A Randomised Phase III Placebo-controlled Trial Evaluating the Addition of Celecoxib to Standard Treatment of Transitional Cell Carcinoma of the Bladder (CRUK/07/004). European urology, Vol.75 (4), pp. 593-601. show abstract

Background Non-muscle-invasive bladder cancer (NMIBC) has a significant risk of recurrence despite adjuvant intravesical therapy.Objective To determine whether celecoxib, a cyclo-oxygenase 2 inhibitor, reduces the risk of recurrence in NMIBC patients receiving standard treatment.Design, setting, and participants BOXIT (CRUK/07/004, ISRCTN84681538) is a double-blinded, phase III, randomised controlled trial. Patients aged ≥18 yr with intermediate- or high-risk NMIBC were accrued across 51 UK centres between 1 November 2007 and 23 July 2012.Intervention Patients were randomised (1:1) to celecoxib 200mg twice daily or placebo for 2 yr. Patients with intermediate-risk NMIBC were recommended to receive six weekly mitomycin C instillations; high-risk NMIBC cases received six weekly bacillus Calmette-Guérin and maintenance therapy.Outcome measurements and statistical analysis The primary endpoint was time to disease recurrence. Analysis was by intention to treat.Results and limitations A total of 472 patients were randomised (236:236). With median follow-up of 44 mo (interquartile range: 36-57), 3-yr recurrence-free rate (95% confidence interval) was as follows: celecoxib 68% (61-74%) versus placebo 64% (57-70%; hazard ratio [HR] 0.82 [0.60-1.12], p=0.2). There was no difference in high-risk (HR 0.77 [0.52-1.15], p=0.2) or intermediate-risk (HR 0.90 [0.55-1.48], p=0.7) NMIBC. Subgroup analysis suggested that time to recurrence was longer in pT1 NMIBC patients treated with celecoxib compared with those receiving placebo (HR 0.53 [0.30-0.94], interaction test p=0.04). The 3-yr progression rates in high-risk patients were low: 10% (6.5-17%) and 9.7% (6.0-15%) in celecoxib and placebo arms, respectively. Incidence of serious cardiovascular events was higher in celecoxib (5.2%) than in placebo (1.7%) group (difference +3.4% [-0.3% to 7.2%], p=0.07).Conclusions BOXIT did not show that celecoxib reduces the risk of recurrence in intermediate- or high-risk NMIBC, although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib.Patient summary Celecoxib was not shown to reduce the risk of recurrence in intermediate- or high-risk non-muscle-invasive bladder cancer (NMIBC), although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib..

Cullen, M. Huddart, R. Joffe, J. Gardiner, D. Maynard, L. Hutton, P. Mazhar, D. Shamash, J. Wheater, M. White, J. Goubar, A. Porta, N. Witts, S. Lewis, R. Hall, E. 111 Trial Management Group, (2019). The 111 Study: A Single-arm, Phase 3 Trial Evaluating One Cycle of Bleomycin, Etoposide, and Cisplatin as Adjuvant Chemotherapy in High-risk, Stage 1 Nonseminomatous or Combined Germ Cell Tumours of the Testis. European urology, . show abstract

BACKGROUND:Standard management in the UK for high-risk stage 1 nonseminoma germ cell tumours of the testis (NSGCTT) is two cycles of adjuvant bleomycin, etoposide (360 mg/m2), and cisplatin (BE360P) chemotherapy, or surveillance. OBJECTIVE:To test whether one cycle of BE500P achieves similar recurrence rates to two cycles of BE360P. DESIGN, SETTING, AND PARTICIPANTS:A total of 246 patients with vascular invasion-positive stage 1 NSGCTT or combined seminoma + NSGCTT were centrally registered in a single-arm prospective study. INTERVENTION:One cycle comprising bleomycin 30000 IU on days 1, 8, and 15, etoposide 165 mg/m2 on days 1-3, and cisplatin 50 mg/m2 on days 1-2, plus antibacterial and granulocyte colony stimulating factor prophylaxis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary endpoint was 2-yr malignant recurrence (MR); the aim was to exclude a rate of ≥5%. Participants had regular imaging and tumour marker (TM) assessment for 5 yr. RESULTS AND LIMITATIONS:The median follow-up was 49 mo (interquartile range 37-60). Ten patients with rising TMs at baseline were excluded. Four patients had MR at 6, 7, 13, and 27 mo; all received second-line chemotherapy and surgery and three remained recurrence-free at 5 yr. The 2-yr MR rate was 1.3% (95% confidence interval 0.3-3.7%). Three patients developed nonmalignant recurrences with localised teratoma differentiated, rendered disease-free after surgery. Grade 3-4 febrile neutropenia occurred in 6.8% of participants. CONCLUSIONS:BE500P is safe and the 2-yr MR rate is consistent with that seen following two BE360P cycles. The 111 study is the largest prospective trial investigating one cycle of adjuvant BE500P in high-risk stage 1 NSGCTT. Adoption of one cycle of BE500P as standard would reduce overall exposure to chemotherapy in this young population. PATIENT SUMMARY:Removing the testicle fails to cure many patients with high-risk primary testicular cancer since undetectable cancers are often present elsewhere. A standard additional treatment in Europe is two cycles of chemotherapy to eradicate these. This trial shows one cycle has few adverse effects and comparable outcomes to those seen with two cycles..

Haviland, J.S. Mannino, M. Griffin, C. Porta, N. Sydenham, M. Bliss, J.M. Yarnold, J.R. START Trialists' Group, (2018). Late normal tissue effects in the arm and shoulder following lymphatic radiotherapy: Results from the UK START (Standardisation of Breast Radiotherapy) trials. Radiotherapy and oncology : journal of the european society for therapeutic radiology and oncology, Vol.126 (1), pp. 155-162. show abstract

Cheang, M.C. Bliss, J.M. Viale, G. Speirs, V. Palmieri, C. Shaaban, A. Lønning, P.E. Morden, J. Porta, N. Jassem, J. van De Velde, C.J. Rasmussen, B.B. Verhoeven, D. Bartlett, J.M. Coombes, R.C. PathIES Sub-Committee, (2018). Evaluation of applying IHC4 as a prognostic model in the translational study of Intergroup Exemestane Study (IES): PathIES. Breast cancer research and treatment, Vol.168 (1), pp. 169-178. show abstract

Lorente, D. Ravi, P. Mehra, N. Pezaro, C. Omlin, A. Gilman, A. Miranda, M. Rescigno, P. Kolinsky, M. Porta, N. Bianchini, D. Tunariu, N. Perez, R. Mateo, J. Payne, H. Terstappen, L. IJzerman, M. Hall, E. de Bono, J. (2018). Interrogating Metastatic Prostate Cancer Treatment Switch Decisions: A Multi-institutional Survey. European urology focus, Vol.4 (2), pp. 235-244. show abstract

Background Evaluation of responses to treatment for metastatic castration-resistant prostate cancer (mCRPC) remains challenging. Consensus criteria based on prostate-specific antigen (PSA) and clinical and radiologic biomarkers are inconsistently utilized. Circulating tumor cell (CTC) counts can inform prognosis and response, but are not routinely used.Objective To evaluate the use of biomarkers and trends in clinical decision-making in current mCRPC treatment.Design, setting, and participants A 23-part online questionnaire was completed by physicians treating mCRPC.Outcome measures and statistical analysis Results are presented as the proportion (%) of physicians responding to each of the options. We used χ 2 and Fisher's tests to compare differences.Results and limitations A total of 118 physicians (22.1%) responded. Of these, 69.4% treated ≥50 mCRPC patients/year. More physicians administered four or fewer courses of cabazitaxel (27.9%) than for docetaxel (10.4%), with no significant difference in the number of courses between bone-only disease and Response Evaluation Criteria in Solid Tumours (RECIST)-evaluable disease. Some 74.5% of respondents considered current biomarkers useful for monitoring disease, but only 39.6% used the Prostate Cancer Working Group (PCWG2) criteria in clinical practice. PSA was considered an important biomarker by 55.7%, but only 41.4% discarded changes in PSA before 12 wk, and only 39.4% were able to identify bone-scan progression according to PCWG2. The vast majority of physicians (90.5%) considered clinical progression to be important for switching treatment. The proportion considering biomarkers important was 71.6% for RECIST, 47.4% for bone scans, 23.2% for CTCs, and 21.1% for PSA. Although 53.1% acknowledged that baseline CTC counts are prognostic, only 33.7% would use CTC changes alone to switch treatment in patients with bone-only disease. The main challenges in using CTC counts were access to CTC technology (84.7%), cost (74.5%), and uncertainty over utility as a response indicator (58.2%).Conclusions A significant proportion of physicians discontinue treatment for mCRPC before 12 wk, raising concerns about inadequate response assessment. Many physicians find current biomarkers useful, but most rely on symptoms to drive treatment switch decisions, suggesting there is a need for more precise biomarkers.Patient summary In this report we analyse the results of a questionnaire evaluating tools for clinical decision-making completed by 118 prostate cancer specialists. We found that most physicians favour clinical progression over prostate-specific antigen or imaging, and that criteria established by the Prostate Cancer Working Group are not widely used..

Franco, P. Porta, N. Holliday, J.D. Willett, P. (2017). Molecular similarity considerations in the licensing of orphan drugs. Drug discovery today, Vol.22 (2), pp. 377-381. show abstract

Choudhury, A. West, C.M. Porta, N. Hall, E. Denley, H. Hendron, C. Lewis, R. Hussain, S.A. Huddart, R. James, N. (2017). The predictive and prognostic value of tumour necrosis in muscle invasive bladder cancer patients receiving radiotherapy with or without chemotherapy in the BC2001 trial (CRUK/01/004). British journal of cancer, Vol.116 (5), pp. 649-657. show abstract

Perez-Lopez, R. Mateo, J. Mossop, H. Blackledge, M.D. Collins, D.J. Rata, M. Morgan, V.A. Macdonald, A. Sandhu, S. Lorente, D. Rescigno, P. Zafeiriou, Z. Bianchini, D. Porta, N. Hall, E. Leach, M.O. de Bono, J.S. Koh, D.-. Tunariu, N. (2017). Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone Metastases in Prostate Cancer: A Pilot Study. Radiology, Vol.283 (1), pp. 168-177. show abstract

Purpose To determine the usefulness of whole-body diffusion-weighted imaging (DWI) to assess the response of bone metastases to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods A phase II prospective clinical trial of the poly-(adenosine diphosphate-ribose) polymerase inhibitor olaparib in mCRPC included a prospective magnetic resonance (MR) imaging substudy; the study was approved by the institutional research board, and written informed consent was obtained. Whole-body DWI was performed at baseline and after 12 weeks of olaparib administration by using 1.5-T MR imaging. Areas of abnormal signal intensity on DWI images in keeping with bone metastases were delineated to derive total diffusion volume (tDV); five target lesions were also evaluated. Associations of changes in volume of bone metastases and median apparent diffusion coefficient (ADC) with response to treatment were assessed by using the Mann-Whitney test and logistic regression; correlation with prostate-specific antigen level and circulating tumor cell count were assessed by using Spearman correlation (r). Results Twenty-one patients were included. All six responders to olaparib showed a decrease in tDV, while no decrease was observed in all nonresponders; this difference between responders and nonresponders was significant (P = .001). Increases in median ADC were associated with increased odds of response (odds ratio, 1.08; 95% confidence interval [CI]: 1.00, 1.15; P = .04). A positive association was detected between changes in tDV and best percentage change in prostate-specific antigen level and circulating tumor cell count (r = 0.63 [95% CI: 0.27, 0.83] and r = 0.77 [95% CI: 0.51, 0.90], respectively). When assessing five target lesions, decreases in volume were associated with response (odds ratio for volume increase, 0.89; 95% CI: 0.80, 0.99; P = .037). Conclusion This pilot study showed that decreases in volume and increases in median ADC of bone metastases assessed with whole-body DWI can potentially be used as indicators of response to olaparib in mCRPC. Online supplemental material is available for this article..

Goodall, J. Mateo, J. Yuan, W. Mossop, H. Porta, N. Miranda, S. Perez-Lopez, R. Dolling, D. Robinson, D.R. Sandhu, S. Fowler, G. Ebbs, B. Flohr, P. Seed, G. Rodrigues, D.N. Boysen, G. Bertan, C. Atkin, M. Clarke, M. Crespo, M. Figueiredo, I. Riisnaes, R. Sumanasuriya, S. Rescigno, P. Zafeiriou, Z. Sharp, A. Tunariu, N. Bianchini, D. Gillman, A. Lord, C.J. Hall, E. Chinnaiyan, A.M. Carreira, S. de Bono, J.S. TOPARP-A investigators, (2017). Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition. Cancer discovery, Vol.7 (9), pp. 1006-1017. show abstract

Martínez-Momblán, M.A. Gómez, C. Santos, A. Porta, N. Esteve, J. Úbeda, I. Halperin, I. Campillo, B. Guillaumet, M. Webb, S.M. Resmini, E. (2016). A specific nursing educational program in patients with Cushing’s syndrome. Endocrine, Vol.53 (1), pp. 199-209.

Wilkins, A. Furness, A. Corbett, R.W. Bloomfield, A. Porta, N. Morris, S. Ali, Z. Larkin, J. Harrington, K. (2015). The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma. British journal of cancer, Vol.113 (9), pp. 1275-1281. show abstract

Lincker, H. Ziogas, C. Carr, M. Porta, N. Eichler, H.-. (2014). Where do new medicines originate from in the EU?. Nature reviews drug discovery, Vol.13 (2), pp. 92-93.

Pedrós, C. Quintana, B. Rebolledo, M. Porta, N. Vallano, A. Arnau, J.M. (2014). Prevalence, risk factors and main features of adverse drug reactions leading to hospital admission. European journal of clinical pharmacology, Vol.70 (3), pp. 361-367.

Coelho, S. Ortíz, F. Gelpi, R. Koskinen, P. Porta, N. Bestard, O. Melilli, E. Taco, O. Torras, J. Honkanen, E. Grinyó, J.M. Cruzado, J.M. (2014). Sterile Leukocyturia Is Associated With Interstitial Fibrosis and Tubular Atrophy in Kidney Allograft Protocol Biopsies. American journal of transplantation, Vol.14 (4), pp. 908-915.

Franco, P. Porta, N. Holliday, J.D. Willett, P. (2014). The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation. Journal of cheminformatics, Vol.6 (1). show abstract

Yildirim, T. Yilmaz, R. Altindal, M. Turkmen, E. Arici, M. Altun, B. Erdem, Y. Guliyev, O. Erkmen Uyar, M. Tutal, E. Bal, Z. Sezer, S. Erkmen Uyar, M. Bal, U. Bal, Z. Tutal, E. Say n, B. Guliyev, O. Erdemir, B. Sezer, S. O'Rourke-Potowki, A. Gauge, N. Penny, H. Cronin, A. Frame, S. Goldsmith, D.J. Yagan, J.A. Chandraker, A. Velickovic Radovanovic, R.M. Catic Djordjevic, A. Mitic, B. Stefanovic, N. Cvetkovic, T. Serpieri, N. Grosjean, F. Sileno, G. Torreggiani, M. Esposito, V. Mangione, F. Abelli, M. Castoldi, F. Catucci, D. Esposito, C. Dal Canton, A. Vatazin, A.V. Zulkarnaev, A.B. Borst, C. Liu, Y. Thoning, J. Tepel, M. Libetta, C. Margiotta, E. Borettaz, I. Canevari, M. Martinelli, C. Lainu, E. Abelli, M. Meloni, F. Sepe, V. Dal Canton, A. Miguel Costa, R. Vasquez Martul, E. Reboredo, J. Rivera, C. Simonato, F. Tognarelli, G. Daidola, G. Gallo, E. Burdese, M. Cantaluppi, V. Biancone, L. Segoloni, G.P. Burdese, M. Priora, M. Messina, M. Tamagnone, M. Daidola, G. Linsalata, A. Lavacca, A. Biancone, L. Segoloni, G. Zuidema, W. Erdman, R. van de Wetering, J. Dor, F. Roodnat, J. Massey, E. Timmerman, L. IJzermans, J. Weimar, W. Goldsmith, D.J. Sibley-Allen, C. Hilton, R. Moghul, M. Burnapp, L. Blake, G. Koo, T.Y. Park, J.-. Park, H.C. Kim, G.-. Lee, C.H. Oh, I.H. Kang, C.M. Hwang, J.K. Park, S.C. Choi, B.S. Chun, H.J. Kim, J.I. Yang, C.W. Moon, I.S. Van Laecke, S. Van Biesen, W. Nagler, E.V. Taes, Y. Peeters, P. Vanholder, R. Pruthi, R. Ravanan, R. Casula, A. Harber, M. Roderick, P. Fogarty, D. Cho, A. Shin, J.-. Jang, H.R. Lee, J.E. Huh, W. Kim, D.J. Oh, H.Y. Kim, Y.-. Sancho Calabuig, A. Gavela Martinez, E. Kanter Berga, J. Beltran Catalan, S. Avila Bernabeu, A.I. Pallardo Mateu, L.M. Gonzalez, E. Polanco, N. Molina, M. Gutierrez, E. Garcia Puente, L. Sevillano, A. Morales, E. Praga, M. Andres, A. Banasik, M. Boratynska, M. Koscielska-Kasprzak, K. Bartoszek, D. Myszka, M. Zmonarski, S. Nowakowska, B. Wawrzyniak, E. Halon, A. Chudoba, P. Klinger, M. Rojas-Rivera, J. Gonzalez, E. Polanco, N. Morales, E. Andres, A. Morales, J.M. Egido, J. Praga, M. Kopecky, C.M. Haidinger, M. Kaltenecker, C. Antlanger, M. Marsche, G. Holzer, M. Kovarik, J. Werzowa, J. Hecking, M. Saemann, M.D. Hwang, J.K. Kim, J.M. Koh, E.S. Chung, B.H. Park, S.C. Choi, B.S. Kim, J.I. Yang, C.W. Kim, Y.S. Moon, I.S. Banasik, M. Boratynska, M. Koscielska-Kasprzak, K. Krajewska, M. Mazanowska, O. Kaminska, D. Bartoszek, D. Zabinska, M. Halon, A. Malkiewicz, B. Patrzalek, D. Klinger, M. Sulowicz, J. Szostek, S. Wojas-Pelc, A. Ignacak, E. Sulowicz, W. Bellizzi, V. Calella, P. Cupisti, A. Capitanini, A. D'Alessandro, C. Giannese, D. Camocardi, A. Conte, G. Barsotti, M. Bilancio, G. Luciani, R. Locsey, L. Seres, I. Kovacs, D. Asztalos, L. Paragh, G. Wohlfahrtova, M. Balaz, P. Rokosny, S. Wohlfahrt, P. Bartonova, A. Viklicky, O. Kers, J. Geskus, R.B. Meijer, L.J. Bemelman, F. ten Berge, I.J. Florquin, S. Hwang, J.-. Jiang, M.-. Lu, Y.-. Weng, S.-. Testa, A. Porto, G. Sanguedolce, M. Spoto, B. Parlongo, R. Pisano, A. Enia, G. Tripepi, G. Zoccali, C. Zuidema, W. Mamode, N. Lennerling, A. Citterio, F. Massey, E. Van Assche, K. Sterckx, S. Frunza, M. Jung, H. Pascalev, A. Johnson, R. Loven, C. Weimar, W. Dor, F. Soleymanian, T. Keyvani, H. Jazayeri, S.M. Fazeli, Z. Ghamari, S. Mahabadi, M. Chegeni, V. Najafi, I. Ganji, M.R. Meys, K.M. Groothoff, J.W. Jager, K. Schaefer, F. Tonshoff, B. Mota, C. Cransberg, K. van Stralen, K. Gurluler, E. Gures, N. Alim, A. Gurkan, A. Cakir, U. Berber, I. Van Laecke, S. Caluwe, R. Nagler, E. Van Biesen, W. Peeters, P. Van Vlem, B. Vanholder, R. Sulowicz, J. Wojas-Pelc, A. Ignacak, E. Betkowska-Prokop, A. Kuzniewski, M. Krzanowski, M. Sulowicz, W. Masson, I. Flamant, M. Maillard, N. Cavalier, E. Moranne, O. Alamartine, E. Mariat, C. Delanaye, P. Canas Sole, L.L. Iglesias Alvarez, E. Pastor, M.C. Moreno Flores, F.F. Abujder, V.V. Graterol, F.F. Bonet Sol, J.J. Lauzurica Valdemoros, R.R. Yoshikawa, M. Kitamura, K. Nakai, K. Goto, S. Fujii, H. Ishimura, T. Takeda, M. Fujisawa, M. Nishi, S. Prasad, N. Gurjer, D. Bhadauria, D. Gupta, A. Sharma, R. Kaul, A. Cybulla, M. West, M. Nicholls, K. Torras, J. Sunder-Plassmann, G. Feriozzi, S. Lo, S. Wong, P.Y. Ip, D. Wong, C.K. Chow, V.C. Mo, S.K. Molnar, M. Ujszaszi, A. Czira, M.E. Novak, M. Mucsi, I. Cruzado, J.M. Coelho, S. Porta, N. Bestard, O. Melilli, E. Taco, O. Rivas, I. Grinyo, J. Pouteau, L.-. N'Guyen, J.-. Hami, A. Hourmant, M. Ghahramani, N. Karparvar, Z. Shadrou, S. Ghahramani, M. Fauvel, J.P. Hadj-Aissa, A. Buron, F. Morelon, E. Ducher, M. Heine, C. Glander, P. Neumayer, H.-. Budde, K. Liefeldt, L. Montero, N. Webster, A.C. Royuela, A. Zamora, J. Crespo, M. Pascual, J. Adema, A.Y. van Dorp, W.T. Mallat, M.J. de Fijter, H.W. Kim, Y.S. Hong, Y.A. Chung, B.H. Park, C.W. Yang, C.W. Kim, Y.-. Choi, B.S. Suleymanlar, G. Uzundurukan, Z. Kapuagas, A. Sencan, I. Akdag, R. Pascual, J. Torio, A. Mas, V. Perez-Saez, M.J. Mir, M. Faura, A. Montes-Ares, O. Checa, M.D. Crespo, M. Sawinski, D. Trofe-Clark, J. Sparkes, T. Patel, P. Goral, S. Bloom, R. Kim, H.J. Park, S.J. Kim, T.H. Kim, Y.W. Kim, Y.H. Kang, S.W. Abdel Halim, M. Gheith, O. Al-Otaibi, T. Mosaad, A. Awadeen, W. Said, T. Nair, P. Nampoory, M.R. (2013). Transplantation: clinical studies - A. Nephrology dialysis transplantation, Vol.28 (suppl 1), pp. i275-i292.

Muñoz, L. Moure, R. Porta, N. Gonzalez, L. Guerra, R. Alcaide, F. Santin, M. (2013). GeneXpert® for smear-negative pulmonary tuberculosis: does it play a role in low-burden countries?. Diagnostic microbiology and infectious disease, Vol.75 (3), pp. 325-326.

Fernández-Lorente, L. Riera, L. Bestard, O. Carrera, M. Gomà, M. Porta, N. Torras, J. Melilli, E. Gil-Vernet, S. Grinyó, J.M. Cruzado, J.M. (2012). Long-Term Results of Biopsy-Guided Selection and Allocation of Kidneys From Older Donors in Older Recipients. American journal of transplantation, Vol.12 (10), pp. 2781-2788.

Porta, N. Calle, M.L. Malats, N. Gómez, G. (2012). A dynamic model for the risk of bladder cancer progression. Statistics in medicine, Vol.31 (3), pp. 287-300.

Porta, N. Bonet, C. Cobo, E. (2007). Discordance between reported intention-to-treat and per protocol analyses. Journal of clinical epidemiology, Vol.60 (7), pp. 663-669.

Mateo, J. Carreira, S. Sandhu, S. Miranda, S. Mossop, H. Perez-Lopez, R. Nava Rodrigues, D. Robinson, D. Omlin, A. Tunariu, N. Boysen, G. Porta, N. Flohr, P. Gillman, A. Figueiredo, I. Paulding, C. Seed, G. Jain, S. Ralph, C. Protheroe, A. Hussain, S. Jones, R. Elliott, T. McGovern, U. Bianchini, D. Goodall, J. Zafeiriou, Z. Williamson, C.T. Ferraldeschi, R. Riisnaes, R. Ebbs, B. Fowler, G. Roda, D. Yuan, W. Wu, Y.M. Cao, X. Brough, R. Pemberton, H. A'Hern, R. Swain, A. Kunju, L.P. Eeles, R. Attard, G. Lord, C.J. Ashworth, A. Rubin, M.A. Knudsen, K.E. Feng, F.Y. Chinnaiyan, A.M. Hall, E. de Bono, J.S. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. The new england journal of medicine, Vol.373 (18), pp. 1697-1708. show abstract

Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the prostate-specific antigen level or a confirmed reduction in the circulating tumor-cell count from 5 or more cells per 7.5 ml of blood to less than 5 cells per 7.5 ml. Targeted next-generation sequencing, exome and transcriptome analysis, and digital polymerase-chain-reaction testing were performed on samples from mandated tumor biopsies.Overall, 50 patients were enrolled; all had received prior treatment with docetaxel, 49 (98%) had received abiraterone or enzalutamide, and 29 (58%) had received cabazitaxel. Sixteen of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes--including BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2--in 16 of 49 patients who could be evaluated (33%). Of these 16 patients, 14 (88%) had a response to olaparib, including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations. The specificity of the biomarker suite was 94%. Anemia (in 10 of the 50 patients [20%]) and fatigue (in 6 [12%]) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib.Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. (Funded by Cancer Research UK and others; ClinicalTrials.gov number, NCT01682772; Cancer Research UK number, CRUK/11/029.)..

Bliss, J. Porta, N. Toms, C. Banerjee, S. Stewart, J. Natrajan, R. Lord, C. ATARI trial: ATR inhibitor in combination with olaparib in gynaecological cancers with ARID1A loss or no loss (ENGOT/GYN1/NCRI). International journal of gynecological cancer, .

Bliss, J. Porta, N. Emson, M. Miller, S. Morden, J. Combined Peri-operative Lapatinib and Trastuzumab in Early HER2 Positive Breast Cancer can Identify Early Responders: Results from the UK EPHOS-B Trial (CRUK/08/002. Clinical cancer research, .

Hall, E. Parr, H. Porta, N. Joint Models for Dynamic Prediction in Localised Prostate Cancer: A Literature Review. , .

Philipps, L. Hall, E. Porta, N. Hafeez, S. Huddart, R. James, N. Correlation of clinician and patient reported outcomes in the BC2001 trial. , .

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