Department of Radiation Oncology, University of California Los Angeles (UCLA), Los Angeles, California.
Division of Surgical-Oncology, Department of Surgery, University of California Los Angeles, Los Angeles, California.
Clin Cancer Res. 2020 Apr 15;26(8):1829-1836. doi: 10.1158/1078-0432.CCR-19-3524. Epub 2020 Feb 13.
In a single-institution phase II study, we evaluated the safety of a 5-day dose-equivalent neoadjuvant radiotherapy (RT) regimen for high-risk primary soft tissue sarcoma.
Patients received neoadjuvant RT alone (30 Gy in five fractions) to the primary tumor with standard margins. The primary endpoint was grade ≥2 late-radiation toxicity. Major wound complications, local recurrences, and distant metastases were also examined. In exploratory analysis, we evaluated germline biomarkers for wound toxicity and the effects of the study on treatment utilization.
Over 2 years, 52 patients were enrolled with median follow-up of 29 months. Seven of 44 evaluable patients (16%) developed grade ≥2 late toxicity. Major wound complications occurred in 16 of 50 patients (32%); a signature defined by 19 germline SNPs in miRNA-binding sites of immune and DNA damage response genes, in addition to lower extremity tumor location, demonstrated strong predictive performance for major wound complications. Compared with the preceding 2-year period, the number of patients treated with neoadjuvant RT alone at our institution increased 3-fold, with a concomitant increase in the catchment area.
A shorter 5-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after 2-year follow-up. Five-day RT significantly increased utilization of neoadjuvant RT at our high-volume sarcoma center. With further validation, a putative germline biomarker for wound complications may guide safer RT utilization.
在一项单机构的 II 期研究中，我们评估了 5 天剂量等效新辅助放疗（RT）方案治疗高危原发性软组织肉瘤的安全性。
患者单独接受新辅助 RT（原发肿瘤标准边缘 30 Gy，5 次分割）。主要终点是≥2 级晚期放射性毒性。还检查了主要伤口并发症、局部复发和远处转移。在探索性分析中，我们评估了与伤口毒性相关的种系生物标志物以及该研究对治疗利用的影响。
在 2 年期间，共招募了 52 名患者，中位随访时间为 29 个月。44 名可评估患者中有 7 名（16%）发生了≥2 级晚期毒性。50 名患者中有 16 名（32%）发生了主要伤口并发症；除下肢肿瘤位置外，还定义了一个由 miRNA 结合位点的免疫和 DNA 损伤反应基因中的 19 个种系 SNP 组成的特征，对主要伤口并发症具有很强的预测性能。与前 2 年相比，我院接受单纯新辅助 RT 治疗的患者数量增加了 3 倍，同时收治区域也扩大了。
在 2 年随访后，较短的 5 天新辅助 RT 方案导致伤口并发症和≥2 级毒性的发生率良好。5 天 RT 显著增加了我院大容量肉瘤中心新辅助 RT 的利用。随着进一步验证，一种潜在的伤口并发症种系生物标志物可能有助于更安全地使用 RT。
