Department of Radiation Oncology, Technical University Munich (TUM), Ismaninger Straße 22, 81675, Munich, Germany.
DKTK Partner Site Munich, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Munich, Germany.
Strahlenther Onkol. 2020 Dec;196(12):1103-1115. doi: 10.1007/s00066-020-01670-4. Epub 2020 Aug 3.
Radiotherapy (RT) is persistently gaining significance in the treatment of pediatric tumors. However, individual features of a growing body and multifocal stages complicate this approach. Tomotherapy offers advantages in the treatment of anatomically complex tumors with low risks of side effects. Here we report on toxicity incidence and outcome of tomotherapy with a focus on multitarget RT (mtRT).
From 2008 to 2017, 38 children diagnosed with sarcoma were treated with tomotherapy. The median age was 15 years (6-19 years). Toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03 and classified into symptoms during RT, acutely (0-6 months) and late (>6 months) after RT, and long-term sideeffects (>24 months).
The main histologies were Ewing sarcoma (n = 23 [61%]) and alveolar rhabdomyosarcoma (n = 5 [13%]). RT was performed with a median total dose of 54 Gy (40.5-66.0 Gy) and a single dose of 2 Gy (1.80-2.27 Gy). Twenty patients (53%) received mtRT. Median follow-up was 29.7 months (95% confidence interval 15.3-48.2 months) with a 5-year survival of 55.2% (±9.5%). The 5‑year survival rate of patients with mtRT (n = 20) was 37.1 ± 13.2%, while patients who received single-target RT (n = 18) had a 5-year survival rate of 75 ± 10.8%. Severe toxicities (grade 3 and 4) emerged in 14 patients (70%) with mtRT and 7 patients (39%) with single-target RT. Two non-hematological grade 4 toxicities occurred during RT: one mucositis and one radiodermatitis. After mtRT 5 patients had grade 3 toxicities acute and after single-target RT 4 patients. One patient had acute non-hematological grade 4 toxicities (gastritis, pericarditis, and pericardial effusion) after mtRT. Severe late effects of RT occurred in 2 patients after mtRT and in none of the single-target RT patients. No severe long-term side effects appeared.
Our results showed acceptable levels of acute and late toxicities, considering the highly advanced diseases and multimodal treatment. Hence, tomotherapy is a feasible treatment method for young patients with anatomically complex tumors or multiple targets. Especially mtRT is a promising and innovative treatment approach for pediatric sarcomas, delivering unexpectedly high survival rates for patients with multifocal Ewing sarcomas in this study, whereby the limited number of patients should invariably be considered in the interpretation.
放射治疗（RT）在小儿肿瘤的治疗中一直具有重要意义。然而，不断生长的身体的个体特征和多灶性阶段使这种方法变得复杂。调强适形放疗（Tomotherapy）在治疗具有低副作用风险的解剖结构复杂肿瘤方面具有优势。在此，我们报告了 Tomotherapy 的毒性发生率和结果，重点介绍了多靶区放疗（mtRT）。
2008 年至 2017 年，我们对 38 名诊断为肉瘤的儿童采用 Tomotherapy 进行治疗。中位年龄为 15 岁（6-19 岁）。毒性根据常见不良事件术语标准第 4.03 版进行分级，并分为放疗期间的症状、放疗后 0-6 个月（急性）和放疗后>6 个月（晚期）以及>24 个月（长期）的副作用。
主要组织学类型为尤文肉瘤（n=23 [61%]）和肺泡横纹肌肉瘤（n=5 [13%]）。放疗总剂量中位数为 54 Gy（40.5-66.0 Gy），单次剂量为 2 Gy（1.80-2.27 Gy）。20 名患者（53%）接受了 mtRT。中位随访时间为 29.7 个月（95%置信区间 15.3-48.2 个月），5 年生存率为 55.2%（±9.5%）。接受 mtRT（n=20）的患者 5 年生存率为 37.1±13.2%，而接受单靶区 RT（n=18）的患者 5 年生存率为 75±10.8%。14 名接受 mtRT 的患者（70%）和 7 名接受单靶区 RT 的患者（39%）出现严重毒性（3 级和 4 级）。在放疗期间出现 2 例非血液学 4 级毒性：1 例黏膜炎和 1 例放射性皮炎。mtRT 后有 5 例患者出现 3 级急性毒性，单靶区 RT 后有 4 例。1 例患者在 mtRT 后出现非血液学 4 级急性毒性（胃炎、心包炎和心包积液）。2 例患者在 mtRT 后出现严重的晚期放疗毒性，而单靶区 RT 患者均未出现。没有出现严重的长期副作用。
考虑到高度进展性疾病和多模式治疗，我们的结果显示出可接受的急性和晚期毒性水平。因此，Tomotherapy 是治疗具有复杂解剖结构或多个靶区的年轻患者的可行方法。特别是 mtRT 是一种有前途和创新的治疗方法，为多灶性尤文肉瘤患者提供了出乎意料的高生存率，在解释结果时应始终考虑到患者数量有限的情况。
