Cosmetic Results and Side Effects of Accelerated Partial-Breast Irradiation Versus Whole-Breast Irradiation for Low-Risk Invasive Carcinoma of the Breast: The Randomized Phase III IRMA Trial

Abstract

PURPOSE The results in terms of side effects vary among the published accelerated partial-breast irradiation (APBI) studies. Here, we report the 5-year results for cosmetic outcomes and toxicity of the IRMA trial. METHODS We ran this randomized phase III trial in 35 centers. Women with stage I-IIA breast cancer treated with breast-conserving surgery, age ≥ 49 years, were randomly assigned 1:1 to receive either whole-breast irradiation (WBI) or external beam radiation therapy APBI (38.5 Gy/10 fraction twice daily). Patients and investigators were not masked to treatment allocation. The primary end point was ipsilateral breast tumor recurrence. We hereby present the analysis of the secondary outcomes, cosmesis, and normal tissue toxicity. All side effects were graded with the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Radiation Morbidity Scoring Schema. Analysis was performed with both intention-to-treat and as-treated approaches. RESULTS Between March 2007 and March 2019, 3,309 patients were randomly assigned to 1,657 WBI and 1,652 APBI; 3,225 patients comprised the intention-to-treat population (1,623 WBI and 1,602 APBI). At a median follow-up of 5.6 (interquartile range, 4.0-8.4) years, adverse cosmesis in the APBI patients was higher than that in the WBI patients at 3 years (12.7% v 9.2%; P = .009) and at 5 years (14% v 9.8%; P = .012). Late soft tissue toxicity (grade ≥ 3: 2.8% APBI v 1% WBI, P < .0001) and late bone toxicity (grade ≥ 3: 1.1% APBI v 0% WBI, P < .0001) were significantly higher in the APBI arm. There were no significant differences in late skin and lung toxicities. CONCLUSION External beam radiation therapy-APBI with a twice-daily IRMA schedule was associated with increased rates of late moderate soft tissue and bone toxicities, with a slight decrease in patient-reported cosmetic outcomes at 5 years when compared with WBI, although overall toxicity was in an acceptable range.

Prospective study of once-daily accelerated partial breast irradiation using 3-dimensional conformal external beam radiotherapy for Japanese women: 12-year outcomes, toxicity, and cosmesis

“…Following the RAPID results, the recently published ASTRO guidelines do not recommend twice-daily APBI with EBRT with respect to toxicity and cosmesis [20]. Consistent with the RAPID study, the IRMA trial, which randomly assigned over 3300 patients to receive twice-daily APBI of 38.5 Gy in 10 fractions or WBI, showed that twice-daily APBI had higher rates of late soft tissue toxicity (2.8% vs. 1%), bone toxicity (1.1% vs. 0%), and adverse cosmesis [21]. The randomized trial by Boutrus et al [22] compared once-daily APBI vs. twice-daily APBI schemes with EBRT (38.5 Gy in 10 fractions) on 113 patients.…”

Revisiting Combined Modality Therapy in Older Patients With Luminal Breast Cancer Through the Patient Lens

“…47 Notably, these studies have 5-year primary end points and rely on ET adherence for a minimum of 5 years, which may not be realistic in many settings. 11,12,48 In the Lumina trial of women 55 years and older treated with ET alone, using careful patient selection including negative SLN biopsy in all patients, Ki67 proliferation index <13.25%, and 83% ET adherence, the 5-year LR rate was 2.3% (95% CI, 1.2 to 4.1). Recurrence data on patients followed in the past 5 years were not provided.…”