Journal Article
. 2019 Feb;20(3).
doi: 10.1016/S1470-2045(18)30813-1.

Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial

Shu-Lian Wang 1 Hui Fang 1 Yong-Wen Song 1 Wei-Hu Wang 1 Chen Hu 2 Yue-Ping Liu 1 Jing Jin 1 Xin-Fan Liu 1 Zi-Hao Yu 1 Hua Ren 1 Ning Li 1 Ning-Ning Lu 1 Yu Tang 1 Yuan Tang 1 Shu-Nan Qi 1 Guang-Yi Sun 1 Ran Peng 1 Shuai Li 1 Bo Chen 1 Yong Yang 1 Ye-Xiong Li 3 
Affiliations
  • PMID: 30711522
  •     29 citations

Abstract

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 China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962.

Findings: Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2-81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8-10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4-10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI -3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001).

Interpretation: Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients.

Funding: National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.

Conventional versus hypofractionated postmastectomy radiotherapy: a report on long-term outcomes and late toxicity.
Imjai Chitapanarux, Pitchayaponne Klunklin, +9 authors, Tanop Srisuwan.
Radiat Oncol, 2019 Oct 16; 14(1). PMID: 31610801    Free PMC article.
Variability in lymph node irradiation in patients with breast cancer-results from a multi-center survey in German-speaking countries.
K J Borm, K Kessel, +8 authors, S E Combs.
Strahlenther Onkol, 2019 Nov 14; 196(1). PMID: 31722060
Comparing hypofractionated to conventional fractionated radiotherapy in postmastectomy breast cancer: a meta-analysis and systematic review.
Lei Liu, Yongqiang Yang, +5 authors, Ye Tian.
Radiat Oncol, 2020 Jan 19; 15(1). PMID: 31952507    Free PMC article.
Systematic Review.
Hypofractionated Radiotherapy Dose Scheme and Application of New Techniques Are Associated to a Lower Incidence of Radiation Pneumonitis in Breast Cancer Patients.
Byung Min Lee, Jee Suk Chang, +3 authors, Yong Bae Kim.
Front Oncol, 2020 Mar 03; 10. PMID: 32117771    Free PMC article.
Recent advances in radiotherapy of breast cancer.
Jan Haussmann, Stefanie Corradini, +10 authors, Christiane Matuschek.
Radiat Oncol, 2020 Apr 02; 15(1). PMID: 32228654    Free PMC article.
Review.
First statement on preparation for the COVID-19 pandemic in large German Speaking University-based radiation oncology departments.
Stephanie E Combs, Claus Belka, +7 authors, Denise Bernhardt.
Radiat Oncol, 2020 Apr 09; 15(1). PMID: 32264908    Free PMC article.
Review.
COVID-19: Global radiation oncology's targeted response for pandemic preparedness.
Richard Simcock, Toms Vengaloor Thomas, +4 authors, Hina Saeed.
Clin Transl Radiat Oncol, 2020 Apr 11; 22. PMID: 32274425    Free PMC article.
Highly Cited.
Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. the COVID-19 pandemic breast cancer consortium.
Jill R Dietz, Meena S Moran, +16 authors, Katharine A Yao.
Breast Cancer Res Treat, 2020 Apr 26; 181(3). PMID: 32333293    Free PMC article.
Highly Cited.
Breast Radiation Therapy Under COVID-19 Pandemic Resource Constraints-Approaches to Defer or Shorten Treatment From a Comprehensive Cancer Center in the United States.
Lior Z Braunstein, Erin F Gillespie, +8 authors, Atif J Khan.
Adv Radiat Oncol, 2020 Apr 16; 5(4). PMID: 32292842    Free PMC article.
Review.
Challenges in Radiotherapy.
Stefanie Corradini, David Krug, +3 authors, Bruno Cutuli.
Breast Care (Basel), 2019 Jul 19; 14(3). PMID: 31316313    Free PMC article.
Appropriate arrangement of cancer treatment after COVID-19 epidemic peaks in China.
Hongnan Mo, Binliang Liu, Fei Ma.
J Cancer Res Clin Oncol, 2020 Jun 01; 146(10). PMID: 32474751    Free PMC article.
Can the Adoption of Hypofractionation Guidelines Expand Global Radiotherapy Access? An Analysis for Breast and Prostate Radiotherapy.
Omoruyi Credit Irabor, William Swanson, +7 authors, Wilfred Ngwa.
JCO Glob Oncol, 2020 Apr 29; 6. PMID: 32343628    Free PMC article.
Impact of Adjuvant Radiation Therapy in Patients With Male Breast Cancer: A Multicenter International Analysis.
Daniel Rolf, Khaled Elsayad, +16 authors, Oliver Micke.
Adv Radiat Oncol, 2020 Jun 13; 5(3). PMID: 32529127    Free PMC article.
Older Cancer Patients during the COVID-19 Epidemic: Practice Proposal of the International Geriatric Radiotherapy Group.
Nam P Nguyen, Vincent Vinh-Hung, +12 authors, Juliette Thariat.
Cancers (Basel), 2020 May 23; 12(5). PMID: 32438703    Free PMC article.
1-week hypofractionated adjuvant whole-breast radiotherapy: towards a new standard?
Antonin Levy, Sofia Rivera.
Lancet, 2020 Jun 26; 395(10237). PMID: 32580882    Free PMC article.
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.
Adrian Murray Brunt, Joanne S Haviland, +21 authors, FAST-Forward Trial Management Group.
Lancet, 2020 Jun 26; 395(10237). PMID: 32580883    Free PMC article.
Comparison of Treatment Outcome between Hypofractionated Radiotherapy and Conventional Radiotherapy in Postmastectomy Breast Cancer.
Chokaew Tovanabutra, Kanyarat Katanyoo, +2 authors, Sitthi Sukauichai.
Asian Pac J Cancer Prev, 2020 Jan 28; 21(1). PMID: 31983173    Free PMC article.
5-Year Update of a Multi-Institution, Prospective Phase 2 Hypofractionated Postmastectomy Radiation Therapy Trial.
Matthew M Poppe, Zeinab A Yehia, +7 authors, Atif J Khan.
Int J Radiat Oncol Biol Phys, 2020 Apr 15; 107(4). PMID: 32289474    Free PMC article.
Implementation of breast cancer continuum of care in low- and middle-income countries during the COVID-19 pandemic.
Hagar Elghazawy, Joaira Bakkach, +9 authors, Sana Al-Sukhun.
Future Oncol, 2020 Jul 28; 16(31). PMID: 32715776    Free PMC article.
Variation in the use of radiotherapy fractionation for breast cancer: Survival outcome and cost implications.
Vikneswary Batumalai, Geoff P Delaney, +4 authors, Michael Barton.
Radiother Oncol, 2020 Jul 30; 152. PMID: 32721419    Free PMC article.
Radiation oncology in times of COVID-2019: A review article for those in the eye of the storm - An Indian perspective.
Ritika Harjani Hinduja, Karishma George, Mansi Barthwal, Vibhay Pareek.
Semin Oncol, 2020 Aug 21; 47(5). PMID: 32819712    Free PMC article.
Review.
Influence of Radiation Dose to Reconstructed Breast Following Mastectomy on Complication in Breast Cancer Patients Undergoing Two-Stage Prosthetic Breast Reconstruction.
Jee Suk Chang, Seung Yong Song, +6 authors, Yong Bae Kim.
Front Oncol, 2019 Apr 27; 9. PMID: 31024845    Free PMC article.
Highlights of the 16th St Gallen International Breast Cancer Conference, Vienna, Austria, 20-23 March 2019: personalised treatments for patients with early breast cancer.
Consuelo Morigi.
Ecancermedicalscience, 2019 Jul 10; 13. PMID: 31281421    Free PMC article.
The Effect of Post-mastectomy Radiotherapy in Patients With Metaplastic Breast Cancer: An Analysis of SEER Database.
Jun Wang, Wen-Wen Zhang, +3 authors, San-Gang Wu.
Front Oncol, 2019 Sep 03; 9. PMID: 31475106    Free PMC article.
Strategies to maximize available resources with minimum cost escalation for improving radiotherapy accessibility in the post COVID-19 era : An analysis for Asia.
Niloy R Datta, Sneha Datta, Massoud Samiei.
Adv Radiat Oncol, 2020 Oct 01;. PMID: 32995668    Free PMC article.
Timing of Chemotherapy and Radiotherapy Following Breast-Conserving Surgery for Early-Stage Breast Cancer: A Retrospective Analysis.
Si-Ye Chen, Yu Tang, +17 authors, Ye-Xiong Li.
Front Oncol, 2020 Oct 20; 10. PMID: 33072604    Free PMC article.
The use of moderately hypofractionated post-operative radiation therapy for breast cancer in clinical practice: A critical review.
Gustavo Nader Marta, Charlotte Coles, +10 authors, Philip Poortmans.
Crit Rev Oncol Hematol, 2020 Oct 23; 156. PMID: 33091800    Free PMC article.
Review.
Late-term effects of hypofractionated chest wall and regional nodal radiotherapy with two-dimensional technique in patients with breast cancer.
Budhi Singh Yadav, Anshuma Bansal, +3 authors, Divya Dahiya.
Radiat Oncol J, 2020 Oct 06; 38(2). PMID: 33012154    Free PMC article.
Risk stratification for prediction of locoregional recurrence in patients with pathologic T1-2N0 breast cancer after mastectomy.
Jianyang Wang, Yu Tang, +16 authors, Yexiong Li.
BMC Cancer, 2020 Nov 25; 20(1). PMID: 33228588    Free PMC article.