Abstract PO2-22-05: A prospective phase I-II study of hypofractionated accelerated breast and nodal intensity modulated radiation therapy delivered in the prone position

Background In patients with breast cancer, prone radiotherapy (RT) has been shown to reduce heart and lung dose. Routinely used for whole breast (WB) RT, its use to treat regional lymph nodes (LNs) is not widespread. Methods In this phase I-II study (NCT02308488) patients treated with lumpectomy or mastectomy with 1-5 pathologically involved LNs underwent WBRT or post-mastectomy RT plus regional nodal RT using IMRT to the supraclavicular and level III axillary LNs. The prescription was 40.5Gy in 15 daily 2.7Gy fractions with a daily concomitant 0.5Gy tumor bed boost. Patients who underwent sentinel LN biopsy (SLNB) alone (no axillary dissection) had the level I-II axilla included in the RT field. The primary endpoints were incidence of >grade 2 acute toxicity per CTCAE v 3.0 and dosimetric feasibility. The secondary endpoint was late toxicity. Clinical outcomes were local recurrence (LR), disease free survival (DFS), distant recurrence free survival (DRFS) and overall survival (OS). Coverage constraints included planning target volume [PTV] V48Gy ≥ 98%, PTV breast V40.5Gy ≥ 95% and PTV nodes V38.5Gy ≥ 95%. Normal tissue constraints included heart V5Gy < 5%, ipsilateral lung V10Gy < 20%, contralateral lung V5Gy < 15%, ipsilateral brachial plexus (BP) maximal dose (Dmax) < 42Gy, spinal cord Dmax ≤ 3 7.5Gy, thyroid contralateral lobe Dmax ≤ 15Gy, esophagus V30Gy < 50% and Dmax ≤ 40.5Gy. Results From 2011-2016, 97 patients with stage IB-IIA breast cancer were enrolled. 66 underwent lumpectomy and 31 underwent mastectomy. 16 had SLNB alone. There were no grade 3 acute toxicities meeting the primary toxicity endpoint. Common acute low-grade toxicities included fatigue (grade 1: 65 [66.3%]; grade 2: 7 [7.1%]), esophagitis (grade 1: 7 [7.1%]; grade 2: 10 [10.2%]), dermatitis (grade 1: 82 [83.7%]; grade 2: 7 [7.1%]). At median and maximum follow up of 8.02 (IQR: 3.31) and 13.3 years, respectively, there were 2 LRs (2.1%). 8-year DRFS, DFS and OS were 88.1% (95% CI 81.3%, 95.4%), 85.7% (95% CI 78.4%, 94.6%) and 90.5% (95% CI 84%, 97.6%), respectively. Clinician-rated cosmesis (n=64) was excellent/good in 67.2% of cases and fair/poor in 6.3%. Patient- rated cosmesis (n=47) was excellent/good in 91.5% and fair/poor in 8.5%, with patients rating themselves more favorably than their physicians (p=0.0014). The incidence of maximum grade 1, 2 and 3 late toxicities were 49 (62.8%), 15 (19.2%), and 3 (3.8%), respectively. This included 2 grade 3 asymmetries,1 grade 3 pigmentation change, and 1 grade 2 pneumonitis. There was no brachial plexopathy. Among the 28 patients who underwent reconstruction, 17 were implant-based and 11 were autologous. Of the implant-based, 9 underwent RT to the tissue expander and 8 to the permanent implant. 11/28 patients had long-term plastic surgery follow up. There were 3 hospitalizations with reoperation post-RT (1 unplanned revision, 1 implant removal for threatened exposure, and 1 excision of fat necrosis). There was 1 incident of wound infection/cellulitis. With regard to dosimetric constraints, 54.3% of plans (95% CI 43.6%, 64.8%) met all constraints. 92% (95% CI 83%, 97%), 98% (95% CI 93%, 100%) and 89% (95% CI 80%, 94%) met the PTV tumor V48Gy, PTV breast V40.5Gy, and PTV nodes V38.5Gy coverage constraints, respectively. Heart, contralateral lung, spinal cord, and esophagus constraints were met by all patients. 95% (95% CI 88.6%, 98.4%) met the ipsilateral lung V10Gy and 99% (95% CI 94%, 100%) met the thyroid contralateral lobe constraint. The BP constraint was met in 73% (95% CI 63.0%, 81.0%) of plans with a mean increase of 1.61 Gy (SD 1.96 Gy) over target. Conclusion Toxicity was low and outcomes were excellent in this prospective trial of hypofractionated regional nodal RT in the prone position. Dosimetric constraints were only met in 54% of plans with the nodal coverage and the BP constraint as the most frequently unmet. These constraints may need to be modified and/or techniques refined to optimize hypofractionated prone nodal RT. Citation Format: Juhi Purswani, Olivier Maisonet, Julie Xiao, Jose R Teruel, Christine Hitchen, Xiaochun Li, Judith D. Goldberg, Carmen A. Perez, Silvia C. Formenti, Naamit K. Gerber. A prospective phase I-II study of hypofractionated accelerated breast and nodal intensity modulated radiation therapy delivered in the prone position [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-05.