Hyperfractionated-Accelerated Reirradiation with Proton Therapy for Radiation-Associated Breast Angiosarcoma

Int J Part Ther. 2022 Jan 18;8(4):55-67. doi: 10.14338/IJPT-21-00031.1. eCollection 2022 Spring.


Purpose: Radiation-associated angiosarcoma (RAAS) is a rare complication among patients treated with radiation therapy for breast cancer. Hyperfractionated-accelerated reirradiation (HART) improves local control after surgery. Proton therapy may further improve the therapeutic ratio by mitigating potential toxicity.

Materials and methods: Six patients enrolled in a prospective registry with localized RAAS received HART with proton therapy between 2015 and 2021. HART was delivered twice or thrice daily in fraction sizes of 1.5 or 1.0 Gy, respectively. All patients received 45 Gy to a large elective volume followed by boosts to a median dose of 65 (range, 60-75) Gy. Toxicity was recorded prospectively by using the Common Terminology Criteria for Adverse Events, version 4.0.

Results: The median follow-up duration was 1.5 (range, 0.25-2.9) years. The median age at RAAS diagnosis was 73 (range, 60-83) years with a median latency of 8.9 (range, 5-14) years between radiation therapy completion and RAAS diagnosis. The median mean heart dose was 2.2 (range, 0.1-4.96) Gy. HART was delivered postoperatively (n = 1), preoperatively (n = 3), preoperatively for local recurrence after initial management with mastectomy (n = 1), and as definitive treatment (n = 1). All patients had local control of disease throughout follow-up. Three of 4 patients treated preoperatively had a pathologic complete response. The patient treated definitively had a complete metabolic response on her posttreatment PET/CT (positron emission tomography-computed tomography) scan. Two patients developed distant metastatic disease despite local control and died of their disease. Acute grade 3 toxicity occurred in 3 patients: 2 patients undergoing preoperative HART experienced wound dehiscence and 1 postoperatively developed grade 3 wound infection, which resolved.

Conclusion: HART with proton therapy appears effective for local control of RAAS with a high rate of pathologic complete response and no local recurrences to date. However, vigilant surveillance for distant metastasis should occur. Toxicity is comparable to that in photon/electron series. Proton therapy for RAAS may maximize normal tissue sparing in this large-volume reirradiation setting.

Keywords: angiosarcoma; breast cancer; cancer outcomes; hyperfractionated radiation; second malignancies.