Looi Wen Shen, Bradley Julie A, Liang Xiaoying, Shaw Christiana M, Leyngold Mark, Mailhot Vega Raymond B, Brooks Eric D, Rutenberg Michael S, Spiguel Lisa R, Giap Fantine, Mendenhall Nancy P
University of Florida Health Proton Therapy Institute, Jacksonville, FL, USA.
Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, FL, USA.
Int J Part Ther. 2022 Jan 18;8(4):55-67. doi: 10.14338/IJPT-21-00031.1. eCollection 2022 Spring.
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.
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.
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.
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.
放射性血管肉瘤（RAAS）是接受乳腺癌放射治疗患者中一种罕见的并发症。超分割加速再照射（HART）可提高手术后的局部控制率。质子治疗可能通过减轻潜在毒性进一步提高治疗比。
2015年至2021年期间，6例登记入前瞻性研究的局限性RAAS患者接受了质子治疗的HART。HART分别以1.5 Gy或1.0 Gy的分割剂量每日照射两次或三次。所有患者对大的选择性靶区给予45 Gy照射，随后追加照射，中位剂量为65（范围60 - 75）Gy。使用不良事件通用术语标准4.0前瞻性记录毒性反应。
中位随访时间为1.5（范围0.25 - 2.9）年。RAAS诊断时的中位年龄为73（范围60 - 83）岁，放疗结束至RAAS诊断的中位潜伏期为8.9（范围5 - 14）年。中位平均心脏剂量为2.2（范围0.1 - 4.96）Gy。HART在术后（n = 1）、术前（n = 3）、初次乳房切除术后局部复发的术前（n = 1）以及作为确定性治疗（n = 1）时进行。所有患者在整个随访期间疾病均得到局部控制。术前治疗的4例患者中有3例达到病理完全缓解。接受确定性治疗的患者在治疗后的PET/CT（正电子发射断层扫描 - 计算机断层扫描）扫描中出现完全代谢缓解。尽管疾病得到局部控制，但仍有2例患者发生远处转移性疾病并死于该病。3例患者出现3级急性毒性反应：2例接受术前HART的患者发生伤口裂开，1例术后发生3级伤口感染，但已缓解。
质子治疗的HART似乎对RAAS的局部控制有效，病理完全缓解率高且迄今为止无局部复发。然而，应警惕远处转移的监测。毒性反应与光子/电子系列相当。在这种大体积再照射情况下，质子治疗RAAS可能使正常组织受量降至最低。
