Explore the vast range of titles available.

High-quality randomised clinical trials testing moderately fractionated breast radiotherapy have clearly shown that local control and survival is at least as effective as with 2 Gy daily fractions with similar or reduced normal tissue toxicity. Fewer treatment visits are welcomed by patients and their families, and reduced fractions produce substantial savings for health-care systems. Implementation of hypofractionation, however, has moved at a slow pace. The oncology community have now reached an inflection point created by new evidence from the FAST-Forward five-fraction randomised trial and catalysed by the need for the global radiation oncology community to unite during the COVID-19 pandemic and rapidly rethink hypofractionation implementation. The aim of this paper is to support equity of access for all patients to receive evidence-based breast external beam radiotherapy and to facilitate the translation of new evidence into routine daily practice. The results from this European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus state that moderately hypofractionated radiotherapy can be offered to any patient for whole breast, chest wall (with or without reconstruction), and nodal volumes. Ultrafractionation (five fractions) can also be offered for non-nodal breast or chest wall (without reconstruction) radiotherapy either as standard of care or within a randomised trial or prospective cohort. The consensus is timely; not only is it a pragmatic framework for radiation oncologists, but it provides a measured proposal for the path forward to influence policy makers and empower patients to ensure equity of access to evidence-based radiotherapy.

Variation in sensitivity to radiation is an inherited genetic trait. This Perspective explores the possibility of genome-wide association studies to characterize genetic profiles that predict patient response to radiotherapy. A key challenge in radiotherapy is to maximize radiation doses to cancer cells while minimizing damage to surrounding healthy tissue. As severe toxicity in a minority of patients limits the doses that can be safely given to the majority, there is interest in developing a test to measure an individual's radiosensitivity before treatment. Variation in sensitivity to radiation is an inherited genetic trait and recent progress in genotyping raises the possibility of genome-wide studies to characterize genetic profiles that predict patient response to radiotherapy.

The IMPORT LOW trial evaluated partial-breast radiotherapy with intensity-modulated radiotherapy in women with early-stage breast cancer at below average risk of ipsilateral breast tumour recurrence (IBTR). 5-year results concluded non-inferiority of IBTR for reduced-dose and partial-breast radiotherapy, with similar or lower frequency of adverse effects compared with whole-breast radiotherapy. We report outcomes after 10 years. IMPORT LOW was a randomised, open-label, multicentre, non-inferiority, phase 3 trial. Women were eligible if they were aged 50 years or older and had had breast conservation surgery for unifocal invasive ductal adenocarcinoma, pT1–2 (tumour size of ≤3 cm), N0–1 (none to three positive axillary nodes), grades 1–3, with microscopic margins of non-cancerous tissue of 2 mm or more. Patients were ineligible if they had a previous malignancy of any kind (except non-melanomatous skin cancer), had undergone mastectomy, or had received neoadjuvant or concurrent adjuvant chemotherapy. Patients were randomly assigned (1:1:1) by randomly permuted blocks to radiotherapy regimens of 40 Gy in 15 fractions to the whole breast (whole-breast group), 36 Gy in 15 fractions to the whole breast plus 40 Gy in 15 fractions to the partial breast (reduced-dose group), or 40 Gy in 15 fractions to the partial breast (partial-breast group). Participants were stratified by treatment centre, without masking. The primary endpoint was IBTR. 10-year outcomes were analysed in the intention-to-treat population. Clinician-reported late adverse effects were evaluated in all participants with available data analysed according to allocated treatment. The study is registered in the ISRCTN registry (ISRCTN12852634) and is now complete. 2018 patients were recruited between May 3, 2007, and Oct 5, 2010, from 30 radiotherapy centres in the UK and randomly assigned to the whole-breast group (n=675), reduced-dose group (n=674), or partial-breast group (n=669). Two participants subsequently withdrew consent. Median age was 63 years (IQR 58–68). 854 (42%) of 2016 patients had grade 1 tumours, 959 (48%) had grade 2 tumours, and 200 (10%) had grade 3 tumours (three tumours were ungradable); 59 (3%) had node-positive disease. Median follow-up was 120 months (IQR 119–122) for the whole-breast group, 121 months (IQR 120–122) for the reduced-dose group, and 120 months (IQR 119–122) for the partial-breast group. By 10 years, IBTR events were reported for 45 of 2016 participants: 17 of 674 in the whole-breast group, 11 of 673 in the reduced-dose group, and 17 of 669 in the partial-breast group, with cumulative incidence of 2·8% (95% CI 1·8–4·5), 1·9% (1·1–3·5), and 3·0% (1·9–4·8), respectively. The estimated absolute difference in 10-year IBTR incidence was –1·02% (95% CI –1·98 to 0·99) for the reduced-dose group and 0·16% (–1·28 to 2·89) for the partial-breast group compared with the whole-breast group. Similar low levels of moderate or marked adverse effects were recorded for participants in all three groups in 10-year clinical assessments. Breast shrinkage had the highest incidence (30 [9%] of 321 in the whole-breast group, 28 [9%] of 322 in the reduced-dose group, and 22 [7%] of 333 in the partial-breast group). Long-term follow-up provides further evidence that partial-breast and reduced-dose radiotherapy are as safe and effective as whole-breast radiotherapy in patients with low-risk early breast cancer. These results reaffirm the use of partial-breast radiotherapy delivered with intensity-modulated radiotherapy in this population as standard of care. Cancer Research UK.

Several studies have reported associations between radiation toxicity and single nucleotide polymorphisms (SNPs) in candidate genes. Few associations have been tested in independent validation studies. This prospective study aimed to validate reported associations between genotype and radiation toxicity in a large independent dataset. 92 (of 98 attempted) SNPs in 46 genes were successfully genotyped in 1613 patients: 976 received adjuvant breast radiotherapy in the Cambridge breast IMRT trial (ISRCTN21474421, n=942) or in a prospective study of breast toxicity at the Christie Hospital, Manchester, UK (n=34). A further 637 received radical prostate radiotherapy in the MRC RT01 multicentre trial (ISRCTN47772397, n=224) or in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer (CHHiP) trial (ISRCTN97182923, n=413). Late toxicity was assessed 2 years after radiotherapy with a validated photographic technique (patients with breast cancer only), clinical assessment, and patient questionnaires. Association tests of genotype with overall radiation toxicity score and individual endpoints were undertaken in univariate and multivariable analyses. At a type I error rate adjusted for multiple testing, this study had 99% power to detect a SNP, with minor allele frequency of 0·35, associated with a per allele odds ratio of 2·2. None of the previously reported associations were confirmed by this study, after adjustment for multiple comparisons. The p value distribution of the SNPs tested against overall toxicity score was not different from that expected by chance. We did not replicate previously reported late toxicity associations, suggesting that we can essentially exclude the hypothesis that published SNPs individually exert a clinically relevant effect. Continued recruitment of patients into studies within the Radiogenomics Consortium is essential so that sufficiently powered studies can be done and methodological challenges addressed. Cancer Research UK, The Royal College of Radiologists, Addenbrooke's Charitable Trust, Breast Cancer Campaign, Cambridge National Institute of Health Research (NIHR) Biomedical Research Centre, Experimental Cancer Medicine Centre, East Midlands Innovation, the National Cancer Institute, Joseph Mitchell Trust, Royal Marsden NHS Foundation Trust, Institute of Cancer Research NIHR Biomedical Research Centre for Cancer.

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. 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. Between 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 five-fraction 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. 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 local radiotherapy after primary surgery for early-stage breast cancer. National Institute for Health Research Health Technology Assessment Programme.

In The Lancet Oncology, Vratislav Strnad and colleagues,1 report the long-term results of their multicentre, phase 3 trial investigating accelerated partial breast irradiation (APBI) using multicatheter brachytherapy for patients aged 40 years or older with early breast cancer, with a median follow-up of 10·36 years. 1328 women were randomly assigned to receive 50 Gy whole-breast irradiation delivered in 25 daily fractions over 5 weeks plus a 10 Gy tumour bed boost (n=673) or APBI (n=655) delivered as 30·1 Gy (seven fractions) and 32·0 Gy (eight fractions) of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days. Burger/Phanie/Science Photo Library This high-quality study adds to other longer-term ipsilateral breast tumour recurrence results from mainly external-beam APBI versus whole-breast irradiation trials, namely the Florence trial (n=520, median follow-up 10·7 years),2 NSABP B-39/RTOG 0413 (n=4216, median follow-up 10·2 years),3 and the RAPID trial (n=2135, median follow-up 8·6 years).4 These trials show similar, low local recurrence rates with no difference in overall survival using APBI or whole-breast irradiation, for patients at low-risk of breast cancer recurrence, and we await the 10-year results of IMPORT Low (ISRCTN12852634) and the ongoing Early Breast Cancer Triallist Group individual patient data meta-analysis of APBI in due course. Additionally, research has focused on de-escalation, but some patients report substantial toxicity with endocrine therapy. [...]we should also investigate de-escalation of systemic therapy using health-related quality of life endpoints where survival outcomes are equivalent.10 In conclusion, both brachytherapy and external-beam APBI radiotherapy are important and relevant treatments today for patients with low-risk breast cancer.

Background For patients with early breast cancer considered at very-low risk of local relapse, risks of radiotherapy may outweigh the benefits. Decisions regarding treatment omission can lead to patient uncertainty (decisional conflict), which may be lessened with patient decision aids (PDA). PRIMETIME (ISRCTN 41579286) is a UK-led biomarker-directed study evaluating omission of adjuvant radiotherapy in breast cancer; an embedded Study Within A Trial (SWAT) investigated whether PDA reduces decisional conflict using a cluster stepped-wedge trial design. Methods PDA diagrams and a video explaining risks and benefits of radiotherapy were developed in close collaboration between patient advocates and PRIMETIME trialists. The SWAT used a cluster stepped-wedge trial design, where each cluster represented the radiotherapy centre and referring peripheral centres. All clusters began in the standard information group (patient information and diagrams) and were randomised to cross-over to the enhanced information group (standard information plus video) at 2, 4 or 6 months. Primary endpoint was the decisional conflict scale (0–100, higher scores indicating greater conflict) which was assessed on an individual participant level. Multilevel mixed effects models used a random effect for cluster and a fixed effect for each step to adjust for calendar time and clustering. Robust standard errors were also adjusted for the clustering effect. Results Five hundred twenty-one evaluable questionnaires were returned from 809 eligible patients (64%) in 24 clusters between April 2018 and October 2019. Mean decisional conflict scores in the standard group (N = 184) were 10.88 (SD 11.82) and 8.99 (SD 11.82) in the enhanced group (N = 337), with no statistically significant difference [mean difference − 1.78, 95%CI − 3.82–0.25, p = 0.09]. Compliance with patient information and diagrams was high in both groups although in the enhanced group only 121/337 (36%) reported watching the video. Conclusion The low levels of decisional conflict in PRIMETIME are reassuring and may reflect the high-quality information provision, such that not everyone required the video. This reinforces the importance of working with patients as partners in clinical trials especially in the development of patient-centred information and decision aids.

The current COVID-19 pandemic challenges oncologists to profoundly re-organize oncological care in order to dramatically reduce hospital visits and admissions and therapy-induced immune-related complications without compromising cancer outcomes. Since COVID-19 is a novel disease, guidance by scientific evidence is often unavailable, and impactful decisions are inevitably made on the basis of expert opinions. Here we report how the seven comprehensive cancer centers of Cancer Core Europe have organized their healthcare systems at an unprecedented scale and pace to make their operations ‘pandemic proof’. We identify and discuss many commonalities, but also important local differences, and pinpoint critical research priorities to enable evidence-based remodeling of cancer care during the COVID-19 pandemic. Also, we discuss how the current situation offers a unique window of opportunity for assessing the effects of de-escalating anticancer regimens, which may fast-forward the development of more-refined and less-toxic treatments. By sharing our joint experiences, we offer a roadmap for proceeding and aim to mobilize the global research community to generate the data that are critically needed to offer the best possible care to patients. The Cancer Core Europe centers share their experience on caring for patients with cancer during the COVID-19 pandemic ― a time of challenges and opportunities for cancer health professionals, researchers and patients alike.

Background The impact of cancer transcends physical health, affecting mental wellbeing, financial stability, and ability to perform daily tasks, influencing not only patients but also the broader community. Methods Online anonymous surveys (24/01/2023–03/03/2023) were disseminated via charities to individuals treated for breast cancer in the UK and their carers. Multivariable ordered logistic regression models were used to investigate demographic, cancer-related and employment factors associated with physical, wellbeing and financial Quality-of-Life (QoL). Results 470 and 136 participants reported primary (PBC) and metastatic (MBC) breast cancer, respectively. 27% PBC and 35% MBC participants reported experience of financial problems. 17% PBC and 47% MBC participants reported trouble fulfilling caring responsibilities at the time of survey completion. For PBC participants, reports of financial problems were associated with difficulties seeking help for physical or wellbeing issues, which were associated with worse physical and wellbeing QoL. Financial problems, and other challenges were more commonly reported among MBC participants. These factors may impact QoL similarly, so there was no evidence of specific explanatory factors for MBC participants. Conclusions Better understanding of wider impact of breast cancer could lead to better policy and support. Future clinical trials should incorporate more comprehensive assessment of breast cancer’s wider effects.

As we mark 150 years since the birth of Marie Curie, we reflect on the global advances made in radiation oncology and the current status of radiation therapy (RT) research. Large-scale international RT clinical trials have been fundamental in driving evidence-based change and have served to improve cancer management and to reduce side effects. Radiation therapy trials have also improved practice by increasing quality assurance and consistency in treatment protocols across multiple centres. This review summarises some of the key RT practice-changing clinical trials over the last two decades, in four common cancer sites for which RT is a crucial component of curative treatment: breast, lung, urological and lower gastro-intestinal cancer. We highlight the global inequality in access to RT, and the work of international organisations, such as the International Atomic Energy Agency (IAEA), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the United Kingdom National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad), that aim to improve access to RT and facilitate radiation research. We discuss some emerging RT technologies including proton beam therapy and magnetic resonance linear accelerators and predict likely future directions in clinical RT research.