Hypofractionation of Post Mastectomy Radiation
Novick K, Chadha M, Harris E, Daroui P, Freedman G, Gao W, Hunt K, Park C, Rewari A, Suh W, Walker E, and Wong J. Hypofractionation of Post Mastectomy Radiation. International Journal of Radiation Oncology Biology Physics 2020; 108(2):E25.
International Journal of Radiation Oncology Biology Physics
Background: The dose delivered to the chest wall is usually 50-50.4 Gy in 1.8-2 Gy daily fractions. The original studies for hypofractionation in breast cancer included a limited number of patients treated with mastectomy, but most did not have treatment of regional nodal volumes. As familiarity with hypofractionation of radiation to the intact breast has increased, there is a growing interest in use of hypofractionation of post mastectomy radiation.
Objectives: The American Radium Society (R) Appropriate Use Criteria (TM) Breast Cancer Committee examined the evidence for the use of hypofractionation in post mastectomy radiation.
Methods: A PRISMA search was conducted to find available evidence for hypofractionation of post mastectomy radiation. The Committee then reached a Delphi consensus for the use of hypofractionation for post mastectomy radiation in 2 clinical variants.
Results: Randomized studies of hypofractionated PMRT show lower levels of acute toxicity and similar outcomes, albeit with more limited follow up (Wang 2019, Zhao 2016, Versmessen 2012, Shahid 2009, Van Parijis 2012). A phase III study from China randomizing 820 high-risk patients to conventional (50 Gy in 25 fractions) versus hypofractionated radiation (43.5 Gy in 15 fractions) has reported non-inferiority at 5 years of follow up in respect of LRF and improvements in acute grade 3 skin toxicity (Wang 2019). All patients had treatment of the chest wall, level III axilla and supraclavicular fossa. Most patients received treatment to the chest wall using 6 MeV electrons using 2-dimensional treatment planning. Acute grade 3 skin toxicity was 3% in the hypofractionated group and 8% in the conventional fractionated group (p<0.0001). A randomized trial by Van Parijis (2012) showed similar heart function and pulmonary function between conventional radiation and hypofractionated radiation. Grade 1 skin toxicity was improved with hypofractionation (60% versus 30%). Quality of life was likewise improved for patients with hypofractionated treatment in a randomized trial by Versmessen et al (2012). Shahid et al (2009) randomized 300 patients to 27 Gy in 5 fractions, 35 Gy in 10 fractions and 40 Gy in 15 fractions. Local control and toxicity were similar in all three schedules. The Alliance for Clinical Trials in Oncology is currently investigating with a phase III study of 880 participants the effect of a hypofractionated regimen of PMRT on patients who have breast reconstruction. A prospective phase II study of hypofractionated radiation to the postmastectomy chest wall and regional lymph nodes followed by a scar boost for a total of 49.95 Gy in 15 fractions found no grade 3 toxicities, but 29% reconstructive complications (Khan 2017). The Delphi consensus reported a median rating of 4 with high level of agreement, indicating that use of hypofractionation in post mastectomy radiation may be appropriate, particularly in the setting of a clinical trial.
Conclusions: Although interest in hypofractionated treatment for PMRT is growing, additional follow up is necessary to determine the long-term safety and efficacy before generalized use. However, it may be appropriate outside the context of a clinical trial for patients without reconstruction if conventional fractionation is not available or is clinically challenging.