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.
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.
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.
The need for axillary radiotherapy in patients with invasive breast cancer (IBC) has been a topic of great debate in the last decade. Management of the axilla has evolved significantly over the past ...four decades with a trend towards de-escalation of surgical interventions and the aim of reducing morbidity and enhancing QOL without compromising long-term oncology outcomes. This review article will address the role of axillary irradiation with a focus on the omission of completion axillary lymph node dissection in selected patients with sentinel lymph node (SLN) positive early breast cancer (EBC) with reference to current guidelines based on evidence to date.
...boost volumes should be small and targeted. ...it is necessary that patients are empowered to exercise choices that reflect their individual preferences. RJ is funded by the Susan G Komen ...Foundation and has received grants paid to her institution for unrelated work from the National Institutes of Health, the Doris Duke Foundation, the Greenwall Foundation, the American Cancer Society, and Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium; was principal investigator on a contract to conduct an investigator-initiated study with Genentech on the financial toxicity experienced by patients with breast cancer, paid to her institution; received personal fees for an advisory or grant review service from the National Institutes of Health, the Doris Duke Foundation, and the Greenwall Foundation; served as an expert witness for Sherinian and Hasso, Dressman Benzinger LaVelle, and Kleinbard, unrelated to the topic of this Comment; and has stock options as compensation for her advisory board role in Equity Quotient, a company that evaluates culture in health-care companies unrelated to the topic of this Comment.
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.
There are few randomized controlled trial data to confirm that improved homogeneity with simple intensity-modulated radiotherapy (IMRT) decreases late breast tissue toxicity. The Cambridge Breast ...IMRT trial investigated this hypothesis, and the 5-year results are reported.
Standard tangential plans of 1,145 trial patients were analyzed; 815 patients had inhomogeneous plans (≥ 2 cm(3) receiving 107% of prescribed dose: 40 Gy in 15 fractions over 3 weeks) and were randomly assigned to standard radiotherapy (RT) or replanned with simple IMRT; 330 patients with satisfactory dose homogeneity were treated with standard RT and underwent the same follow-up as the randomly assigned patients. Breast tissue toxicities were assessed at 5 years using validated methods: photographic assessment (overall cosmesis and breast shrinkage compared with baseline pre-RT photographs) and clinical assessment (telangiectasia, induration, edema, and pigmentation). Comparisons between different groups were analyzed using polychotomous logistic regression.
On univariate analysis, compared with standard RT, fewer patients in the simple IMRT group developed suboptimal overall cosmesis (odds ratio OR, 0.68; 95% CI, 0.48 to 0.96; P = .027) and skin telangiectasia (OR, 0.58; 95% CI, 0.36 to 0.92; P = .021). No evidence of difference was seen for breast shrinkage, breast edema, tumor bed induration, or pigmentation. The benefit of IMRT was maintained on multivariate analysis for both overall cosmesis (P = .038) and skin telangiectasia (P = .031).
Improved dose homogeneity with simple IMRT translates into superior overall cosmesis and reduces the risk of skin telangiectasia. These results are practice changing and should encourage centers still using two-dimensional RT to implement simple breast IMRT.
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.
Tumour bed boost radiotherapy (RT) following breast conserving surgery reduces local recurrence in high-risk disease. There is recent debate over challenges to accurately localise tumour bed for RT ...boost delivery following volume replacement oncoplastic breast surgery (VR-OBS). This review evaluates the reporting of RT boost following VR-OBS in the literature published between January 2010 and December 2021. This review was in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Nine studies met the inclusion criteria (n = 670 patients), and RT boost was used in eight studies. Boost was administered in total to 384 patients (62.5% of irradiated patients). Only two studies reported boost planned target volumes and only one compared these against surgical specimen volumes. RT boost was not reported in most published studies on VR-OBS. Future prospective research are strongly needed to evaluate long-term outcomes of VR-OBS following RT boost, especially on breast cosmesis and patients’ satisfaction.
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•Tumour bed boost radiation therapy (RT) following breast conserving surgery reduces local recurrence in high-risk disease.•Concerns exist regarding localisation of tumour bed for RT boost following replacement type oncoplastic breast surgery (OBS).•This review evaluates the reporting of RT boost following volume replacement OBS.•RT boost was not reported in most published studies on volume replacement OBS.•Future research may evaluate the effect of boost RT on outcomes (breast cosmesis and patient satisfaction) following OBS.
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