Sep 30

SS 46 - Right-Sizing Radiation in Early Breast Cancer: Omission, Shortening, and Targeted Approaches

LBA 16 - Prospective Randomized study of Accelerated Radiation Therapy (PRART)

09:25am - 09:35am ET

Room 258

Presenter(s)

Fereshteh Talebi, MD - Harbor-UCLA Medical Center, Los Angeles, CA

F. Talebi¹, F. Gregucci¹, M. Patel¹, T. Cigler², E. Andreopoulou², L. Newman³, M. Cristofanilli², V. Chen¹, M. B. Fenton-Kerimian¹, J. Ng¹, and S. C. Formenti¹; ¹Department of Radiation Oncology, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, ²Weill Cornell Medical College, New York, NY, ³Weill Cornell Medical College, Dept of Surgery, New York, NY

Purpose/Objective(s): Whole-breast radiotherapy is traditionally delivered over three weeks, but a shorter two-week course could reduce the burden of treatment if it proves equally safe and effective. NCT04175210 is a prospective randomized trial that tested whether a 2-week regimen with a concomitant tumor bed boost in prone position is non-inferior to a standard 3-week regimen for grade =2 acute toxicity in women with Stage 0 (Tis) or T1–2N0 breast cancer treated after breast-conserving surgery. Fibrosis, breast cosmesis, and local recurrence-free survival at 3 years were evaluated as secondary endpoints.

Materials/Methods: The study was designed to randomize 400 patients to standard whole-breast radiotherapy with a concomitant boost to 48 Gy in 15 fractions (Arm 1) or an accelerated regimen of 32 Gy with a concomitant boost to 42 Gy in 10 fractions (Arm 2). The 3-week regimen was expected to cause grade =2 acute toxicity in about 10% patients; an absolute increase of more than 5% (a 15% ceiling) was set as the threshold for unacceptable toxicity. With a one-sided alpha of 0.025, a sample size of 400 patients gives the study 79% power to rule out this margin. Late toxicity and cosmesis were compared between arms with Fisher’s exact and Wilcoxon rank-sum tests.

Results: Between November 2019 and April 2025, 430 patients were screened and 427 were randomized (Arm 1, n=213; Arm 2, n=214; IRB No. 19-07020533); 31 withdrew before starting treatment, leaving 396 evaluable patients. At a median follow-up of 3 years (95% CI, 2.89–3.18; data cutoff July 1, 2026), grade =2 acute toxicity occurred in 15.3% of Arm 1 patients versus 8.6% of Arm 2 patients, a difference of -6.7%; the upper bound of the one-sided 97.5% confidence interval was -0.3%, which fell within the prespecified 5% non-inferiority margin (p<0.001). Late toxicity was infrequent and comparable between arms: grade =2 fibrosis occurred in 1.1% versus 2.7% (p=0.6), telangiectasia in 1.1% versus 0.5% (p=0.7), and poor cosmesis in 1.0% versus 3.6% (p=0.2) in arm 1 versus arm 2, respectively. Among the 346/396 patients evaluable for the secondary endpoints, 7 patients experienced fibrosis or telangiectasia (3 in Arm 1, 4 in Arm 2), with no difference in cumulative incidence between arms (log-rank p=0.75; HR 1.27, 95% CI 0.28–5.69). Among the 203 patients (51.3%) with at least three years of follow-up, there were 7 cases of local recurrence (Arm 1: n=4; Arm 2: n=3), 2 cases of distant metastasis (Arm 1: n=2; Arm 2: n=0), and 1 death due to gastric cancer (Arm 1: n=1; Arm 2: n=0). There were no significant differences between arms in local recurrence (HR 0.73, 95% CI 0.16–3.28; p=0.68)or distant metastasis–free survival (log-rank p=0.15).

Conclusion:

A 2-week whole-breast radiotherapy regimen with a concomitant boost delivered in the prone position is non-inferior to the standard 3-week regimen for acute toxicity, with comparable late toxicity and 3-year efficacy outcomes.