Optimizing Preventive Adjuvant LINAC (OPAL) Radiation: A Phase II Trial of Daily Partial Breast Irradiation.

Abstract

PURPOSE/OBJECTIVE(S)\nTwice daily accelerated partial breast irradiation (APBI) may confer worse long-term cosmetic outcome than daily whole breast irradiation (WBI). We hypothesized that daily partial breast irradiation would yield improved cosmetic outcomes without compromising tumor control. To test this hypothesis, we conducted a phase II trial to evaluate a ten-fraction regimen of daily PBI (OPAL regimen).\n\n\nMATERIALS/METHODS\nFrom 2017-2018, 149 women aged ≥ 50 with DCIS or early invasive, ER+ breast cancer were enrolled into a multi-institutional phase II trial that treated the partial breast to 35 Gy in 10 daily fractions. Patients with close margins (< 2 mm) also received a boost of 9 Gy in 3 daily fractions. Toxicities were evaluated using CTCAE v4.0 and physician-reported cosmesis was assessed using the RTOG scale. The Breast Cancer Treatment Outcomes Scale (BCTOS) assessed patient-reported cosmesis, breast pain, and functional status. Outcomes were assessed at baseline, 6 months, 1 year, and annually thereafter. The primary outcome was incidence of grade ≥ 2 toxicity within 6 months of PBI initiation. To facilitate a comparison of the OPAL regimen to WBI, we identified 176 patients with similar clinical-pathologic features from our prior trial of WBI+boost in which toxicities were also prospectively collected. Differences in cross-sectional outcomes between the OPAL trial and historical WBI+boost cohort were tested using chi-square test. Mixed effect growth curve models evaluated outcomes over time adjusting for relevant covariates.\n\n\nRESULTS\nMedian age was 64 years and median follow-up was 2 years. All 149 patients received 35 Gy in 10 daily fractions and 26 received a boost. One patient developed an in-field DCIS recurrence. For the primary outcome, grade ≥ 2 toxicity within 6 months of PBI initiation was 14.1% with OPAL compared to 71% in the WBI+boost cohort (P < 0.001). At two years post-radiation, fatigue (8% vs 16%), hyperpigmentation (18% vs 30%), breast edema (0% vs 9%), superficial fibrosis (18% vs 31%), deep fibrosis (6% vs 13%), nipple areolar changes (6% vs 17%), and breast atrophy (19% vs 35%) were less prevalent in patients treated with OPAL (all P < 0.05). At two years, 93% of patients treated with OPAL had excellent/good cosmetic outcome compared to 77% of patients treated with WBI+boost (P < 0.001). In multivariable longitudinal analysis, treatment with OPAL was associated with improved patient-reported cosmetic outcome (P < 0.001), functional status (P\u202f=\u202f0.02), breast pain (P\u202f=\u202f0.003) and physician-reported cosmetic outcome (P < 0.001).\n\n\nCONCLUSION\nTreatment with this novel daily PBI regimen of 35 Gy in 10 daily fractions with selective boost yielded better cosmetic and functional outcomes and less breast pain and toxicity than WBI+boost with median follow up of 2 years. Daily external beam partial breast irradiation with 10 or fewer fractions merits further prospective evaluation.