140 - Accelerated Partial Breast Irradiation (APBI) Delivered in Three Fractions is Safe and Efficacious: Preliminary Results from a Phase 2 Study
Presenter(s)
A. J. Khan1, V. G. Familia2, Q. LaPlant3, M. B. Bernstein1, D. M. Guttmann1, E. F. Gillespie4, J. E. Panoff5, A. J. Xu3, N. Toumbacaris6, Z. Zhang6, M. Reyngold3, J. J. Cuaron3, L. Z. Braunstein1, A. Ionescu1, L. Hong7, and S. N. Powell3; 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Hospital of Special Surgery, New York, NY, 3Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 4University of Washington, Department of Radiation Oncology, Seattle, WA, 5Miami Cancer Institute Baptist Health South Florida, Miami, FL, 6Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 7Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): We explored a novel APBI schedule that is completed in 3 treatment days, with planning and delivery potentially completed in a single work week. We also tested the efficacy of APBI in a cohort of “intermediate risk” women generally understudied in the randomized data, using a nested non-inferiority design. We hypothesized that this APBI schedule is tolerable and efficacious.
Materials/Methods: This phase 2 study had co-primary endpoints of toxicity and local failure. Patients were age = 40, with unicentric invasive or in situ breast cancer = 3 cm, node-negative, with negative margins. For the toxicity endpoint, we defined grade 3 or higher AEs occurring over a 2-year observation period as the binary outcome of interest. 130 evaluable patients were needed to demonstrate that the 2-year toxicity rate was 4% or lower, with a type 2 error rate of about 0.15, if no more than 7 patients experienced toxicity within 2 years.
For the co-primary endpoint of local failure we defined “intermediate risk” patients as either 1) age 40-49 2) genomic score high on Oncotype RS or PAM50 3) presence of LVI 4) Invasive lobular carcinoma (ILC) 5) surgical margins <1 mm for invasive or in situ disease 6) cT1-T2N0 patients who achieve ypT1 N0 disease after neoadjuvant chemotherapy (NAC). We planned to enroll at least 65 such evaluable intermediate-risk patients in the overall cohort of 130 patients, and if at most 4 of them experienced local failure within 3 years then the treatment would be considered effective under the alternative hypothesis that the 3-yr local failure rate is at most 2%.
Results: 145 patients were enrolled from 12/2019- 2/2023 and followed for a median of 41.2 months (95% CI 37.1-43.9). Median age was 66 and the median tumor size was 1.1 cm. Among 65 intermediate risk patients (ILC = 29, high genomic risk = 15, LVI=10, 40-49 = 7, post-NAC = 2, multiple risk factors = 2), 37 have been followed for at least 3 years and there have been no local or regional recurrences, and one distant recurrence. A single grade 3 event that was possibly related to RT (breast pain, crude rate 1%) and 18 grade 2 events that were at least possibly related to RT (crude rate 13%) primarily chest wall pain and fibrosis/induration.
Conclusion: This shortened schedule of APBI appears to be safe and tolerable with a low likelihood of toxicity. In the intermediate-risk cohort, local control appears to be excellent and comparable to usual low-risk breast cancers. Based on these findings, we have amended the study to add a registry cohort for additional data collection on cosmesis, and to expand the intermediate risk cohort to 90 total patients.