Optimizing Preventive Adjuvant Linac-Based (OPAL) Radiation: A Phase 2 Trial of Daily Partial Breast Irradiation

Abstract

Purpose: Evidence supports use of partial-breast irradiation (PBI) in the management of early breast cancer, but the optimal dose-fractionation remains unsettled.

Methods and materials: We conducted a phase 2 clinical trial (OPAL trial) to evaluate a novel PBI dosing schedule of 35 Gy in 10 daily fractions. Patients with close (<2 mm) margins also received a boost of 9 Gy in 3 fractions. Eligible patients underwent margin-negative lumpectomy for ductal carcinoma in situ or estrogen receptor-positive invasive breast cancer, up to 3 cm, pTis-T2 N0. The primary outcome was any grade ≥2 toxic effect occurring from the start of radiation through 6 months of follow-up. Secondary outcomes included patient-reported cosmesis, breast pain, and functional status, measured using the Breast Cancer Treatment Outcomes Scale, and physician-reported cosmesis, measured using the Radiation Therapy and Oncology Group scale. The Cochran-Armitage trend test and multivariable mixed-effects longitudinal growth curve models compared outcomes for the OPAL study population with those for a control group of similar patients treated with whole-breast irradiation (WBI) plus boost.

Results: All 149 patients enrolled on the OPAL trial received the prescribed dose, and 17.4% received boost. The median age was 64 years; 83.2% were White, and 73.8% were overweight or obese. With median follow-up of 2.0 years, 1 patient (0.7%) experienced in-breast recurrence. Prevalence of the primary toxicity outcome was 17.4% (26 of 149 patients) in the OPAL trial compared with 72.7% (128 of 176 patients) in the control WBI-plus-boost cohort (P < .001). In longitudinal multivariable analysis, treatment on the OPAL trial was associated with improved patient-reported cosmesis (P < .001), functional status (P = .004), breast pain (P = .004), and physician-reported cosmesis (P < .001).

Conclusions: Treatment with daily PBI was associated with substantial reduction in early toxicity and improved patient- and physician-reported outcomes compared with WBI plus boost. Daily external-beam partial-breast irradiation with 13 or fewer fractions merits further prospective evaluation.

Trial registration: ClinicalTrials.gov NCT03077841.

Fig. 1.

Longitudinal patient-reported outcomes and physician-reported cosmesis comparing patients treated on the OPAL trial to similar patients treated with whole-breast irradiation plus boost on a prior clinical trial. (A-C) Patient-reported cosmetic outcome, functional status, and breast pain, respectively, assessed using the Breast Cancer Treatment Outcomes Scale, with a score of 1 indicating no difference between the treated breast and the contralateral breast that served as an internal control, a score of 2 indicating a small difference, 3 indicating a moderate difference, and 4 indicating a large difference. (D) Cosmetic outcome rated by the treating physician, with a score of 1 indicating excellent outcome, 2 indicating good outcome, 3 indicating fair outcome, and 4 indicating poor outcome, using the Radiation Therapy and Oncology Group scale. *P < .05 for comparison of outcomes in OPAL patients compared with the whole-breast irradiation plus boost control cohort for each time point indicated, using the Student t test. Error bars indicate 95% confidence intervals. Abbreviation: OPAL = Optimizing Preventive Adjuvant Linac-Based Radiation.