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Background We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial.Methods FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1-3, pN0-1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1•6% excess for five-fraction schedules (critical hazard ratio [HR] of 1•81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132. FindingsBetween Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71•5 months (IQR 71•3 to 71•7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0•86 (95% CI 0•51 to 1•44) for 27 Gy in five fractions and 0•67 (0•38 to 1•16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2•1% (1•4 to 3•1); estimated absolute differences versus 40 Gy in 15 fractions were -0•3% (-1•0 to 0•9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior fivefraction schedule: p=0•0022 vs 40 Gy in 15 fractions) and -0•7% (-1•3 to 0•3) for 26 Gy in five fractions (p=0•00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9•9%) 40 Gy patients, 155 (15•4%) of 1005 27 Gy patients, and 121 of 1020 (11•9%) 26 Gy patients. Across all clinician assessments from 1-5 years, odds ratios versus 40 Gy in 15 fractions were 1•55 (95% CI 1•32 to 1•83, p<0•0001) for 27 Gy in five fractions and 1•12 (0•94 to 1•34, p=0•20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy.Interpretation 26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant l...

PurposeCancer-related fatigue (CRF) is a frequent and distressing symptom experienced after cancer treatment. RESTORE is the first web-based resource designed to enhance self-efficacy to manage CRF following curative-intent treatment. The aim of this study is to test the proof of concept and inform the design of an effectiveness trial.MethodsA multi-centre parallel-group two-armed (1:1) exploratory randomised controlled trial (RCT) with qualitative process evaluation was employed in the study. Participants (≥18 years; ≤5 years post treatment with moderate to severe fatigue) were recruited and randomly assigned to RESTORE or a leaflet. Feasibility and acceptability were measured by recruitment, attrition, intervention adherence, completion of outcome measures and process evaluation. Change in self-efficacy to manage CRF was also explored. Outcome measures were completed at baseline (T0), 6 weeks (T1) and 12 weeks (T2). Data were analysed using mixed-effects linear regression and directed content analysis.ResultsOne hundred and sixty-three people participated in the trial and 19 in the process evaluation. The intervention was feasible (39 % of eligible patients consented) and acceptable (attrition rate 36 %). There was evidence of higher fatigue self-efficacy at T1 in the intervention group vs comparator (mean difference 0.51 [−0.08 to 1.11]), though the difference in groups decreased by 12 weeks. Time since diagnosis influenced perceived usefulness of the intervention. Modifications were suggested.ConclusionProof of concept was achieved. The RESTORE intervention should be subject to a definitive trial with some adjustments. Provision of an effective supportive resource would empower cancer survivors to manage CRF after treatment completion.Trial registrationISRCTN67521059

PURPOSE Electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) is an online eHealth system for patients to self-report symptoms during cancer treatment. It provides automated severity-dependent patient advice guiding self-management or medical contact and displays the reports in electronic patient records. This trial evaluated the impact of eRAPID on symptom control, healthcare use, patient self-efficacy, and quality of life (QOL) in a patient population treated predominantly with curative intent. METHODS Patients with colorectal, breast, or gynecological cancers commencing chemotherapy were randomly assigned to usual care (UC) or the addition of eRAPID (weekly online symptom reporting for 18 weeks). Primary outcome was symptom control (Functional Assessment of Cancer Therapy-General, Physical Well-Being subscale [FACT-PWB]) assessed at 6, 12, and 18 weeks. Secondary outcomes were processes of care (admissions or chemotherapy delivery), patient self-efficacy, and global quality of life (Functional Assessment of Cancer Therapy–General, EQ5D-VAS, and EORTC QLQ-C30 summary score). Multivariable mixed-effects repeated-measures models were used for analyses. Trial registration: ISRCTN88520246. RESULTS Participants were 508 consenting patients (73.6% of 690 eligible) and 55 health professionals. eRAPID compared to UC showed improved physical well-being at 6 ( P = .028) and 12 ( P = .039) weeks and no difference at 18 weeks (primary end point) ( P = .69). Fewer eRAPID patients (47%) had clinically meaningful physical well-being deterioration than UC (56%) at 12 weeks. Subgroup analysis found benefit in the nonmetastatic group at 6 weeks ( P = .0426), but not in metastatic disease. There were no differences for admissions or chemotherapy delivery. At 18 weeks, patients using eRAPID reported better self-efficacy ( P = .007) and better health on EQ5D-VAS ( P = .009). Average patient compliance with weekly symptom reporting was 64.7%. Patient adherence was associated with clinician's data use and improved FACT-PWB at 12 weeks. CONCLUSION Real-time monitoring with electronic patient-reported outcomes improved physical well-being (6 and 12 weeks) and self-efficacy (18 weeks) in a patient population predominantly treated with curative intent, without increasing hospital workload.

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