Phase III Randomized Trial of Proton vs. Photon Therapy for Patients with Non-metastatic Breast Cancer Receiving Comprehensive Nodal Radiation: A Radiotherapy Comparative Effectiveness (Radcomp) Consortium Trial: Health-Related Quality of Life Outcomes

Abstract

Purpose/Objective(s)

To compare patient-reported body image and function, fatigue, and other measures of health-related quality of life (HRQOL) in a multi-institutional phase III randomized controlled trial of patients with non-metastatic breast cancer undergoing comprehensive nodal irradiation with either proton radiotherapy (PrRT) vs. photon radiotherapy (PhRT).

Materials/Methods

The primary HRQOL endpoints were PROMIS Fatigue, Satisfaction with Breast Cosmetic Outcomes, BREAST-Q adverse effects of radiotherapy, and FACT-B. Other domains, including FACIT-TS-G and PRO-CTCAE (severity, interference, frequency of chest pain and shortness of breath), were evaluated as secondary endpoints of HRQOL. HRQOL questionnaires were collected at baseline, at the end of RT, and at 1- and 6-month post-RT follow-ups. Repeated measures linear and generalized linear mixed models were used to compare the impact of treatment on continuous and ordinal/binary HRQOL scores, respectively. The study was powered for the primary endpoint of major cardiovascular events, which provided sufficient power to detect clinically meaningful differences in HRQOL, defined by an effect size of greater than 0.33, in mixed-effects models assuming a correlation of 0.40 or higher.

Results

1,239 patients were randomized to PrRT (n = 624) or PhRT (n = 615). The median age was 50 years (range, 21-92). Most patients had a mastectomy (69.7%), 0-2 cardiovascular risk factors (80.6%), and left or bilateral cancer (61.8%). FACT-B completion rate at 6 months was 86.5%. There were no clinically meaningful differences by treatment arm in the PROMIS Fatigue total score, Satisfaction with Breast Cosmetic Outcomes score, BREAST-Q total score, and FACT-B trial outcome index score. PRO-CTCAE severity of shortness of breath, when categorized as 0 vs. 1-4, favored protons (OR=0.74, 95% CI:0.59-0.93, p<0.01); but, when categorized as 0-2 vs 3-4, there was no difference between arms. Other PRO-CTCAEs assessed were similar between arms. FACIT items statistically significant in favor of protons included willingness to recommend treatment (OR=0.13, 95% CI:0.08-0.22, p<0.001) and choose treatment again (OR=0.11, 95% CI:0.07-0.18, p<0.001).

Conclusion

In the first randomized study comparing proton to photon radiation for breast cancer, HRQOL through 6 months was excellent and similar between treatment arms. Differences were noted in shortness of breath, willingness to recommend treatment, and to choose treatment again, which should be interpreted with caution in this unblinded study. Loco-regional control and major cardiac events, the primary endpoints of the RadComp trial, will be reported according to the study’s statistical plan in the future.