Are We Missing Acute Toxicities Associated with Hypofractionated Breast Irradiation? A Report from a Large Multi-Center Cohort Study
Beydoun H, Jagsi R, Griffith K, Burmeister JW, Moran JM, Vicini FA, Dilworth JT, Hayman JA, Paximadis P, Boike TP, Gustafson GS, Radawski JD, Walker EM, Pierce LJ, and Dominello MM. Are We Missing Acute Toxicities Associated with Hypofractionated Breast Irradiation? A Report from a Large Multi-Center Cohort Study. Int J Radiat Oncol Biol Phys 2019; 105(1):E51.
Int J Radiat Oncol Biol Phys
Purpose/Objective(s): The efficacy and long-term safety of hypofractionated whole breast irradiation (HF-WBI) has been established through multiple randomized trials. However, data on acute toxicities associated with HF-WBI remain more limited. Since 2013, our group has prospectively collected data on acute toxicities associated with HF-WBI based on weekly evaluation during treatment and assessment at 1 month after completion of radiotherapy. In October 2015, we intentionally shifted the post-treatment assessment time-point from 1 month to 2 weeks post-completion of treatment. This change was intended to evaluate whether a closer follow-up (f/u) might result in the detection of otherwise unobserved acute toxicities for patients receiving HF-WBI. In this study we report whether 2-week f/u has resulted in increased sensitivity for detecting acute toxicity as compared with 4-wk f/u. Materials/Methods: We prospectively compared acute toxicity for patients treated with HF-WBI at 25 participating institutions. We compared patients treated between 1/1/2013 and 8/31/2015 (before 2-week f/u up was adopted – “4 wk f/u cohort”) to patients treated between 1/1/2016 – 8/31/2018 (after adoption of a 2-week f/u – “2 wk f/u cohort”). Acute toxicity was considered the maximum reported composite toxicity from 7 days prior to the completion of radiotherapy until 42 days (6 weeks) following completion. Composite toxicity was defined as self-reported or physician-assessed moderate or severe breast pain, and/or physician-assessed presence of moist desquamation. Multivariable logistic regression models were used to assess difference in toxicity by cohort using ASTRO HF-WBI 2018 Guideline v. 2011 Guideline, and further adjusted for BMI, breast volume, race, presence of comorbidity, smoking status, and use of IMRT. Results: 2243 patients who received post-lumpectomy radiation and boost were analyzed, 1369 patients in the 2-wk f/u cohort and 874 in the 4-wk f/u cohort. Occurrence of composite acute toxicity was similar between the 2 cohorts, 28.4% for 2-wk f/u cohort vs 26.9% for the 4-wk f/u cohort, adjusted p=0.66. When analyzing only patients who met all ASTRO HF-WBI Guideline v. 2011 criteria, no difference in acute toxicity was noted; 26.5% with 2-wk f/u vs 25.0% with 4-wk f/u, adjusted p=0.83. Finally, with 2 wk f/u compared with 4 wk f/u, additional acute toxicities were not detected for patients who were younger <50 years (p=0.72), received chemotherapy (p=0.93), had ductal carcinoma in-situ (p=0.13), or had separation >25 cm, (p=0.43), yet otherwise guideline compliant. Conclusion: A closer post-treatment follow-up for patients receiving HF-WBI did not reveal a significant increased incidence of acute toxicities at 2 weeks compared to 4 weeks. This study provides physicians and patients with additional data on the safety and tolerability of HF-WBI and the appropriateness of the interval of follow-up.