1150 - Dosimetric Predictors of Pneumonitis In Patients with Localized HER2-Positive Breast Cancer Receiving Radiotherapy and Trastuzumab-Emtansine
Presenter(s)
H. Bacon1, X. Y. Ye2, Z. A. Liu3, G. Lee1,4, E. Hahn1,4, E. Amir5, P. Lindsay4,6, T. Tadic1,4, A. J. Hope1,4, and C. A. Koch1,4; 1Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 2Department of Biostatistics, University Health Network, Toronto, ON, Canada, 3Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 4Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 5Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 6Department of Radiation Oncology, University of Toronto, ON, Canada
Purpose/Objective(s): For patients with localized HER2+ breast cancer with residual disease after neoadjuvant chemotherapy with HER2-targeted therapy, adjuvant radiotherapy (RT) and trastuzumab-emtansine (T-DM1) are established standard of care treatments. We previously reported that patients who receive RT and T-DM1 are at increased risk for pneumonitis, with a rate of Grade =2 pneumonitis (G2P) of 11.1% in a large institutional cohort. The goal for this study was to investigate dosimetric associations of pneumonitis in patients who receive adjuvant T-DM1 and RT.
Materials/Methods: This is a retrospective single institution study including all patients who received adjuvant RT and T-DM1 from 2019-2024 with available plans for analysis. Clinical and toxicity data were collected via chart review. All plans were input into Raystation 2023B (research build). If boosts were planned on a separate image dataset, a deformable registration was performed. EQD2 corrections were performed on each plan using an
?/ß=3 Gy, followed by plan summation. Cumulative dose volume histograms were then extracted for bilateral lungs and heart. An initial screen for significant dosimetric parameters was performed by assessing all univariate Spearman correlation coefficients (R) for lung and heart V1-V60Gy (EQD2). The association of G2P with the significant dosimetric parameters (p<0.05) identified in initial screen were then determined using the univariate (UVA) and multivariable (MVA) Fine-Gray competing risk regression models accounting for the competing risk of death.Results: Of 90 eligible patients, 89 had plans available for analysis. 10 patients had G2P. In the initial screen, Lung V36-V38Gy were significantly associated with G2P, with a peak correlation at V36Gy (R=0.19, p=0.04). Heart V18-42Gy were significantly associated with G2P, with a peak at V34Gy (R=0.27, p<0.01). On UVA, heart V34Gy, lung V36Gy, mean heart dose (MHD), and fractionation (conventional vs. hypofractionation vs. ultrahypofractionation) were significantly associated with G2P. On MVA, lung V36 Gy (HR=1.03, 95% CI 1.02-1.05, p<0.01), heart V34 Gy (HR=1.09, 95% CI=1.05-1.12, p<0.01), and MHD (HR = 1.55, 95% CI=1.19-2.00, p<0.01) were significantly associated with G2P. Notably, MLD was not associated with G2P.
Conclusion: Concurrent treatment with T-DM1 and RT is associated with an increased risk of G2P. Careful planning with attention to unique dosimetric parameters, including lung V36Gy, heart V34Gy, and MHD, may mitigate pneumonitis risk in these patients.