• 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

      Iveson, T; Kerr, R; Saunders, Mark P; Cassidy, J; Hollander, N; Tabernero, J; Haydon, A; Glimelius, B; Harkin, A; Allan, K; et al. (2018-04)
      6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.
    • 3-month versus 6-month adjuvant chemotherapy for patients with high-risk stage II and III colorectal cancer: 3-year follow-up of the SCOT non-inferiority RCT

      Iveson, T; Boyd, KA; Kerr, RS; Robles-Zurita, J; Saunders, Mark P; Briggs, AH; Cassidy, J; Hollander, NH; Tabernero, J; Haydon, A; et al. (2019)
      BACKGROUND: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. OBJECTIVES: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. DESIGN: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. SETTING: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. PARTICIPANTS: Adults aged ³?18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. INTERVENTIONS: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. MAIN OUTCOME MEASURES: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. RESULTS: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n?=?3035; 6-month analysis, n?=?3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority?=?0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand-foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ³?3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ³?5 years (p?<?0.001). Quality-of-life scores were better in the 3-month treatment group over months 4-6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient. CONCLUSIONS: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019-20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre - Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894). PLAIN-LANGUAGE-SUMMARY: Patients diagnosed with bowel cancer are likely to have surgery to remove the tumour. Patients diagnosed with a more advanced stage of the disease are then likely to be offered what is known as adjuvant chemotherapy Ð chemotherapy to kill any cancer cells that have already spread but cannot be seen. Adjuvant chemotherapy is usually given over 6 months using two medicines known as oxaliplatin and fluoropyrimidine. This chemotherapy has side effects of diarrhoea, nausea and vomiting, and it reduces the numbers of cells in the blood. It can also damage nerves, which causes discomfort, numbness and tingling; in some cases, this can go on for years. These side effects are more likely to develop with longer treatment. This study looked at whether or not shortening the time over which patients were given oxaliplatin and fluoropyrimidine chemotherapy reduced its effectiveness. In this large study of over 6000 patients, half of the patients were allocated by chance to be treated for 3 months and the other half to be treated for 6 months. Reducing the time that patients had chemotherapy from 6 months to 3 months did not make the treatment less effective. When patients treated with chemotherapy over 3 months were compared with those treated over 6 months, 77% of patients in both groups were well with no detectable disease 3 years after surgery. Patients were less likely to get side effects with 3-month chemotherapy. In particular, the chance of persistent long-term nerve damage was lower, resulting in patients with 3-month chemotherapy having better health-related quality of life. Overall, the study showed that 3-month adjuvant chemotherapy for patients with bowel cancer is as effective as 6-month adjuvant chemotherapy and causes fewer side effects.
    • Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial

      Birtle, A; Johnson, M; Chester, J; Jones, R; Dolling, D; Bryan, RT; Harris, C; Winterbottom, A; Blacker, A; Catto, JWF; et al. (2020)
      BACKGROUND: Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs. METHODS: We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m2) or carboplatin (area under the curve [AUC]4·5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m2) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants. FINDINGS: Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0·45, 95% CI 0·30-0·68; p=0·0001) at a median follow-up of 30·3 months (IQR 18·0-47·5). 3-year event-free estimates were 71% (95% CI 61-78) and 46% (36-56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported. INTERPRETATION: Gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population.
    • Complementary therapies in cancer: Patients’ views on their purposes and value pre and post receipt of complementary therapy—A multi-centre case study.

      Roberts, D; Wilson, C; Todd, C; Long, A; Mackereth, Peter A; Stringer, Jacqui; Carter, A; Parkin, S; Caress, A (2013)
    • Copy number signatures and mutational processes in ovarian carcinoma.

      Macintyre, G; Goranova, T; De Silva, D; Ennis, D; Piskorz, A; Eldridge, M; Sie, D; Lewsley, L; Hanif, A; Wilson, C; et al. (2018-09)
      The genomic complexity of profound copy number aberrations has prevented effective molecular stratification of ovarian cancers. Here, to decode this complexity, we derived copy number signatures from shallow whole-genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Measurement of signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes.
    • Correction: Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium

      Goranova, T; Ennis, D; Piskorz, A; Macintyre, G; Lewsley, L; Stobo, J; Wilson, C; Kay, D; Glasspool, R; Lockley, M; et al. (2019)
      This article was originally published under a CC BY NC SA License, but has now been made available under a CC BY 4.0 License. Erratum for: Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium. [Br J Cancer. 2017]
    • Current views on clinical oncology training from the 2015 oncology registrars' forum survey.

      Kosmin, M; Brown, S; Hague, Christina; Said, J; Wells, L; Wilson, C; Mount Vernon Cancer Centre, Northwood, Middlesex, UK (2016-05-12)
      The major role of the Oncology Registrars' Forum (ORF) of the Royal College of Radiologists is to voice the opinions of the clinical oncology trainee body and work towards improving all aspects of clinical oncology training in the UK. In order to provide data to support these efforts, the ORF undertakes a biennial survey of all trainees. As with the previous surveys, this year's ORF survey produced data that highlight areas of good training as well as new and ongoing areas of concern. This summary highlights the key survey results and provides recommendations for improving the delivery of clinical oncology training in the UK.
    • Erratum to 'Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome'

      Lee, Rebecca J; Wysocki, O; Bhogal, T.; Shotton, Rohan; Tivey, Ann; Angelakas, Angelos; Aung, T.; Banfill, Kathryn; Baxter, M.; Boyce, H.; et al. (2021-04-01)
    • Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial.

      James, R; Glynne-Jones, R; Meadows, H; Cunningham, D; Myint, A; Saunders, Mark P; Maughan, T; McDonald, A; Essapen, S; Leslie, M; et al. (2013-05)
      Chemoradiation became the standard of care for anal cancer after the ACT I trial. However, only two-thirds of patients achieved local control, with 5-year survival of 50%; therefore, better treatments are needed. We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response, and whether maintenance chemotherapy after chemoradiation improves survival.
    • A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial.

      Smith, I; Ahern, Roger; Coombes, G; Howell, Anthony; Ebbs, S; Hickish, T; O'Brien, M; Mansi, J; Wilson, C; Robinson, A; et al. (2004-05)
      BACKGROUND: To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer. PATIENTS AND METHODS: Four hundred and twenty-six women with histologically proven 3 cm invasive early breast cancer were randomised to receive pre-operative infusional 5-FU 200 mg/m(2) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2) intravenous (i.v.) bolus on day 1 and cisplatin 60 mg/m(2) i.v. bolus on day 1, both repeating 3-weekly (infusional ECisF), or conventional bolus doxorubicin 60 mg/m(2) i.v. on day 1 and cyclophosphamide 600 mg/m(2) i.v. on day 1, both repeating 3-weekly (AC), both schedules for six courses. Patients subsequently had local therapy (surgery or radiotherapy or both) and tamoxifen 20 mg orally daily as appropriate. RESULTS: The 5 year results for AC and infusional ECisF, respectively, were as follows: overall response, 75% and 77%; complete clinical remission, 31% and 34%; pathological complete remission (pathCR), 16% for both; and pathCR with residual ductal carcinoma in situ (DCIS), 25% and 24%. Mastectomy rates were 37% and 34%, respectively. Five-year overall survival was 74% for AC and 82% for infusional ECisF (hazard ratio 0.76, 95% confidence interval 0.51-1.13; P = 0.18). Both treatments were well tolerated. Grade III/IV lethargy, vomiting, alopecia and plantar-palmar erythema were significantly greater for infusional ECisF; grade III/IV leucopenia was significantly greater for AC. CONCLUSIONS: Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer; with a median 5 year follow-up, the infusion-based schedule shows a non-significant trend towards improved survival.
    • A randomised study evaluating the use of pyridoxine to avoid capecitabine dose modifications.

      Corrie, P; Bulusu, R; Wilson, C; Armstrong, G; Bond, S; Hardy, R; Lao-Sirieix, S; Parashar, D; Ahmad, A; Daniel, F; et al. (2012-08-07)
      Pyridoxine is frequently used to treat capecitabine-induced hand-foot syndrome (HFS), although the evidence of benefit is lacking. We performed a randomised placebo-controlled trial to determine whether pyridoxine could avoid the need for capecitabine dose modifications and improve outcomes.
    • Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.

      Goranova, T; Ennis, D; Piskorz, A; Macintyre, G; Lewsley, L; Stobo, J; Wilson, C; Kay, D; Glasspool, R; Lockley, M; et al. (2017-03-30)
      Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC).
    • SCOT: a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant oxaliplatin combination chemotherapy for colorectal cancer.

      Robles-Zurita, J; Boyd, KA; Briggs, AH; Iveson, T; Kerr, RS; Saunders, Mark P; Cassidy, J; Hollander NH; Tabernero, J; Segelov, E; et al. (2018)
      BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3?M) versus the usually given 6 months (6?M) of adjuvant chemotherapy in colorectal cancer. METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULTS: The 3?M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3?M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3?M had lower QALYs than 6?M (not statistically significant). CONCLUSIONS: Overall, 3?M dominates 6?M with no significant detrimental impact on QALYs. The results provide the economic case that a 3?M treatment strategy should be considered a new standard of care