Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial.

Published on May 23, 2020in The Lancet60.392
· DOI :10.1016/S0140-6736(20)30932-6
A.M. Brunt12
Estimated H-index: 12
(Keele University),
Joanne S Haviland27
Estimated H-index: 27
(ICR: Institute of Cancer Research)
+ 43 AuthorsJohn R Yarnold1
Estimated H-index: 1
(The Royal Marsden NHS Foundation Trust)
Sources
Abstract
Summary 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. Findings 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 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 local radiotherapy after primary surgery for early-stage breast cancer. Funding National Institute for Health Research Health Technology Assessment Programme.
Download
📖 Papers frequently viewed together
606 Citations
200860.39The Lancet
22 Authors (Søren M. Bentzen, ..., John Yarnold)
918 Citations
1,096 Citations
References28
Newest
#1F.A. Vicini (Mercy Medical Center (Baltimore, Maryland))H-Index: 6
#2Reena S. Cecchini (University of Pittsburgh)H-Index: 22
Last. Norman Wolmark (University of Pittsburgh)H-Index: 35
view all 27 authors...
Summary Background Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole...
115 CitationsSource
#1Timothy J. Whelan (Juravinski Cancer Centre)H-Index: 83
#2Jim A. Julian (Juravinski Cancer Centre)H-Index: 74
Last. Christopher FordH-Index: 1
view all 270 authors...
Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Can...
105 CitationsSource
#1S.L. Wang (Peking Union Medical College)H-Index: 4
#2Hui Fang (Peking Union Medical College)H-Index: 16
Last. Ye Xiong Li (Peking Union Medical College)H-Index: 8
view all 21 authors...
Summary Background To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. Methods This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in Chin...
90 CitationsSource
#1A.M. Brunt (ICR: Institute of Cancer Research)H-Index: 2
#1A.M. BruntH-Index: 12
Last. John Yarnold (ICR: Institute of Cancer Research)H-Index: 71
view all 15 authors...
27 CitationsSource
#1Benjamin D. Smith (University of Texas MD Anderson Cancer Center)H-Index: 62
#2Jennifer R. Bellon (Harvard University)H-Index: 36
Last. Reshma Jagsi (UM: University of Michigan)H-Index: 76
view all 16 authors...
Abstract Introduction The purpose of this guideline is to offer recommendations on fractionation for whole breast irradiation (WBI) with or without a tumor bed boost and guidance on treatment planning and delivery. Methods and materials The American Society for Radiation Oncology (ASTRO) convened a task force to address 5 key questions focused on dose-fractionation for WBI, indications and dose-fractionation for tumor bed boost, and treatment planning techniques for WBI and tumor bed boost. Guid...
220 CitationsSource
#1Dena R. Howard (University of Leeds)H-Index: 7
#2Julia Brown (University of Leeds)H-Index: 77
Last. Walter M. Gregory (University of Leeds)H-Index: 72
view all 4 authors...
Multi-arm clinical trials assessing multiple experimental treatments against a shared control group can offer efficiency advantages over independent trials through assessing an increased number of hypotheses. Published opinion is divided on the requirement for multiple testing adjustment to control the family-wise type-I error rate (FWER). The probability of a false positive error in multi-arm trials compared to equivalent independent trials is affected by the correlation between comparisons due...
25 CitationsSource
#1Charlotte E. Coles (University of Cambridge)H-Index: 39
#2Clare Griffin (ICR: Institute of Cancer Research)H-Index: 15
Last. Alastair M. ThompsonH-Index: 72
view all 53 authors...
Summary Background Local cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy. Methods IMPORT LOW is a multicentre, r...
210 CitationsSource
#1F.R. Bartlett (QA: Queen Alexandra Hospital)H-Index: 1
#2Ellen M. DonovanH-Index: 23
Last. Anna M. KirbyH-Index: 22
view all 11 authors...
Abstract Aims To evaluate the feasibility and heart-sparing ability of the voluntary breath-hold (VBH) technique in a multicentre setting. Materials and methods Patients were recruited from 10 UK centres. Following surgery for early left breast cancer, patients with any heart inside the 50% isodose from a standard free-breathing tangential field treatment plan underwent a second planning computed tomography (CT) scan using the VBH technique. A separate treatment plan was prepared on the VBH CT s...
27 CitationsSource
#1Csaba PolgárH-Index: 29
#2Oliver J. OttH-Index: 30
Last. Vratislav StrnadH-Index: 30
view all 27 authors...
Summary Background We previously confirmed the non-inferiority of accelerated partial breast irradiation (APBI) with interstitial brachytherapy in terms of local control and overall survival compared with whole-breast irradiation for patients with early-stage breast cancer who underwent breast-conserving surgery in a phase 3 randomised trial. Here, we present the 5-year late side-effects and cosmetic results of the trial. Methods We did this randomised, controlled, phase 3 trial at 16 centres in...
126 CitationsSource
#1A Murray Brunt (Keele University)H-Index: 6
#2Duncan Wheatley (Royal Cornwall Hospital)H-Index: 22
Last. Judith M Bliss (ICR: Institute of Cancer Research)H-Index: 78
view all 15 authors...
Abstract Background and purpose FAST-Forward is a phase 3 clinical trial testing a 1-week course of whole breast radiotherapy against the UK standard 3-week regimen after primary surgery for early breast cancer. Two acute skin toxicity substudies were undertaken to test the safety of the test schedules with respect to early skin reactions. Material and methods Patients were randomly allocated to 40Gy/15 fractions (F)/3-weeks, 27Gy/5F/1-week or 26Gy/5F/1-week. Acute breast skin reactions were gra...
74 CitationsSource
Cited By153
Newest
#1Fadoua Rais (McGill University)
#2James M. G. Tsui (McGill University)H-Index: 7
Last. Tarek Hijal (McGill University)H-Index: 13
view all 10 authors...
BACKGROUND AND PURPOSE Breast cancer locoregional (LR) radiation in the elderly requires careful consideration between the benefits of aggressive treatment and its potential toll on these patients. Extreme weekly LR hypofractionated radiation (HFRT), delivering >5 Gy per fraction, may be better suited in such a population. It represents a good compromise between RT omission and exhaustive daily radiation. This study aims to report the local and LR control rate as well as the acute and long-term ...
Source
#1Vivian Jolley BeaH-Index: 1
#1Vivian Jolley Bea (Houston Methodist Hospital)
Last. Lisa A. NewmanH-Index: 75
view all 4 authors...
Source
De-escalating therapy in breast cancer means doing less to achieve the same outcomes. Surgery to the breast de-escalated from the Halsted radical mastectomy to the modified radical mastectomy, and then to breast-conserving surgery (BCS), which is the current standard of care for early breast cancer. BCS includes a course of radiotherapy, which was de-escalated from a 6-week course to a 3-week course, with a boost to the tumour bed. As the majority of local recurrences occur in the quadrant where...
Source
#1S. Bockel (University of Paris-Sud)H-Index: 1
#1Sophie Bockel (University of Paris-Sud)H-Index: 4
Last. Sofia Rivera (University of Paris-Sud)H-Index: 13
view all 9 authors...
Resume null null L’augmentation des nouveaux cas de cancer du sein dans un monde aux ressources sanitaires limitees fait de l’hypofractionnement en radiotherapie mammaire un enjeu majeur de sante publique. De recents resultats d’essais randomises evaluant l’hypofractionnement extreme pour la radiotherapie adjuvante du sein en totalite ou l’irradiation partielle du sein sont susceptibles de modifier nos pratiques. Nous rapportons ici une revue des effets secondaires et des resultats oncologiques ...
Source
Abstract null Introduction null The Research and Clinical Trials Therapeutic Radiographers network is a College of Radiographers Specialist Interest Group. It was established to develop and facilitate a support network for therapeutic radiographers working in roles which involve the delivery of radiotherapy clinical trials. Its establishment highlighted the challenges faced by therapeutic radiographers employed in these roles. Consequently, the authors sought to formally capture the working land...
Source
#1Fallon E. Chipidza (Harvard University)H-Index: 4
Last. Shekinah N. Elmore (Harvard University)H-Index: 6
view all 10 authors...
PURPOSE Few sub-Saharan African studies have ascertained utilization for postmastectomy radiation (PMRT) for breast cancer, the second most common cancer among African women. We estimated PMRT utilization and identified predictors of PMRT receipt in Zimbabwe. METHODS Retrospective patient cohort included non-metastatic breast cancer patients treated from 2014 to 2019. PMRT eligibility was assigned per NCCN guidelines. Patients receiving chemotherapy for non-metastatic disease were also included....
Source
#1Jean-Philippe Pignol (EUR: Erasmus University Rotterdam)H-Index: 27
#2Nienke Hoekstra (EUR: Erasmus University Rotterdam)H-Index: 3
Last. Frank A. ViciniH-Index: 95
view all 6 authors...
Purpose – Secondary lung cancer (SLC) can offset the benefit of adjuvant breast radiotherapy (RT) and risks compound sharply after 25 to 30 years. We hypothesized that SLC risk is mainly an issue for early-stage breast cancer, and that lives could be saved using different RT techniques. Patients and Methods – The SEER database was used to extract breast patient age, stage survival, radiotherapy utilisation over time and per stage, and to assess the factors associated with increased SLC risk with...
Source
#1Vesna Benković (University of Zagreb)H-Index: 15
#2Nikola BorojevicH-Index: 2
Last. Mirta MilićH-Index: 20
view all 5 authors...
Purpose null Patient immobilization by general volatile anesthesia (VA) may be necessary during medical radiology treatment, and its use has increased in recent years. Although ionizing radiation (IR) is a well-known genotoxic and cytotoxic agent, and VA exposure has caused a range of side effects among patients and occupationally exposed personnel, there are no studies to date comparing DNA damage effects from combined VA and single fractional IR dose exposure. null Material and methods null We...
Source
#1Orit Kaidar-Person (Sheba Medical Center)H-Index: 6
#2Birgitte Vrou Offersen (Aarhus University Hospital)H-Index: 26
Last. V. Strand (FAU: University of Erlangen-Nuremberg)
view all 13 authors...
Abstract null null Delineation of target and ‘organ at risk (OAR)’ volumes is a critical part of modern radiation therapy planning, the next essential step after deciding the indication, patient discussion and image acquisition. Adoption of volume-based treatment planning for non-metastatic breast cancer has increased greatly along with the use of improved planning techniques, essential for modern therapy. However, identifying the volumes on a planning CT is no easy task. The current paper is wr...
Source
#1Brijesh Kumar Singh (AIIMS: All India Institute of Medical Sciences)
#2Manjunath Maruti Pol (AIIMS: All India Institute of Medical Sciences)H-Index: 3
Last. Adarsh Barwad (AIIMS: All India Institute of Medical Sciences)H-Index: 5
view all 4 authors...
A 52-year-old man presented with a recurrent right side breast lump. He had undergone excision of a lump on the right breast followed by adjuvant chemoradiotherapy 1 year ago for a diagnosis of pleomorphic liposarcoma. Imaging revealed a 47×36 mm lesion on the right side of the chest wall involving the pectoralis muscle. The patient underwent right radical mastectomy. Histology of the specimen showed an undifferentiated pleomorphic sarcoma infiltrating into the underlying skeletal muscle. Theref...
Source