Factors Associated with Patient-Reported and Physician-Assessed Acute Toxicity after Hypofractionated Breast Radiotherapy, a Report from a Large Multi-Center Cohort Study

Purpose/Objective(s): In 2018 ASTRO published an update to the 2011 evidence-based guideline for the use of hypofractionated whole breast irradiation (HF-WBI), increasing the patient populations for whom expert consensus supports the use of HF-WBI. While individualized decision making is encouraged, this updated guideline has been expanded to support HF-WBI for patients \u3c50 years, receipt of chemotherapy, larger separation distance, and a diagnosis of DCIS. For some of these indications, however, only moderate data exist. Thus, we now assess patient and physician reported toxicity data in a large prospective registry for populations not well represented on the trials and in whom there is less experience with this approach. Materials/Methods: Prospective data were evaluated from 2,083 patients receiving HF-WBI plus boost, treated between 1/1/2016 – 8/31/2018 at 24 academic and community centers participating in a statewide consortium. A composite toxicity endpoint was defined as occurrence of self-reported (4-10 modified brief pain inventory) or physician-assessed moderate or severe breast pain (CTCAE v. 4.0 grade 2-3) when patient report absent, and/or physician-assessed presence of moist desquamation. Logistic regression models were constructed isolating the effect of specific criteria from the 2011 HF-WBI guidelines, specifically age \u3c50 years, separation distance \u3e25cm, chemotherapy use, and DCIS. This was further adjusted for patient BMI, breast volume, race, comorbidity, smoking status, and IMRT. Results: Mean age was 62 years, mean separation was 22cm. Twenty-two percent of patients were treated for DCIS with the remaining 78% treated for invasive cancer; 17% of patients received chemotherapy. Of the 2,083 patients, 376 patients had more than one 2011 guideline discordance (for ex. \u3c50 years with chemotherapy), therefore 1707 patients were included in this analysis. On multivariable analysis, patients age \u3c 50 years were estimated to be 82% more likely to experience toxicity than older patients (OR=1.82, 95% CI: 1.11-2.97, p=0.02). While unadjusted difference on univariate analysis showed increased toxicity with separation \u3e 25 cm, multivariable analysis revealed no significant difference in toxicity for separation \u3e 25 cm(p=0.25), DCIS (p=0.6753), or treatment following chemotherapy p=0.10). Conclusion: Young breast cancer patients may be at increased risk of acute toxicity compared with other patients when receiving HF-WBI. Additional work is needed to determine why patients \u3c50 years, who were notably underrepresented in the prospective trials establishing the safety and efficacy of HF-WBI, may experience increased breast pain and dermatitis. Work is underway in our group to determine if this same increased risk is appreciated for patients \u3c50 years receiving conventionally fractionated radiotherapy