ARST0332 研究中高分级非横纹肌肉瘤软组织肉瘤行放疗的局部控制：儿童肿瘤协作组研究报告。
Local Control For High-Grade Nonrhabdomyosarcoma Soft Tissue Sarcoma Assigned to Radiation Therapy on ARST0332: A Report From the Childrens Oncology Group.
机构信息
Department of Radiation Oncology (LM, SSD) and Department of Pediatrics (SS), Stanford University, Stanford, California.
Department of Surgery, University of North Carolina, Chapel Hill, North Carolina.
出版信息
Int J Radiat Oncol Biol Phys. 2021 Jul 1;110(3):821-830. doi: 10.1016/j.ijrobp.2021.01.051. Epub 2021 Feb 3.
PURPOSE
The ARST0332 trial for pediatric and young adults with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) used risk-based treatment including primary resection with lower-than-standard radiation doses to optimize local control (LC) while minimizing long-term toxicity in those requiring radiation therapy (RT). RT for high-grade NRSTS was based on extent of resection (R0: negative margins, R1: microscopic margins, R2/U: gross disease/unresectable); those with >5 cm tumors received chemotherapy (CT; ifosfamide/doxorubicin). This analysis evaluates LC for patients assigned to RT and prognostic factors associated with local recurrence (LR).
METHODS AND MATERIALS
Patients aged <30 years with high-grade NRSTS received RT (55.8 Gy) for R1 ≤5 cm tumor (arm B); RT (55.8 Gy)/CT for R0/R1 >5 cm tumor (arm C); or neoadjuvant RT (45 Gy)/CT plus delayed surgery, CT, and postoperative boost to 10.8 Gy R0 <5 mm margins/R1 or 19.8 Gy for R2/unresected tumors (arm D).
RESULTS
One hundred ninety-three eligible patients had 24 LRs (arm B 1/15 [6.7%], arm C 7/65 [10.8%], arm D 16/113 [14.2%]) at median time to LR of 1.1 years (range, 0.11-5.27). Of 95 eligible for delayed surgery after neoadjuvant therapy, 89 (93.7%) achieved R0/R1 margins. Overall LC after RT were as follows: R0, 106 of 109 (97%); R1, 51 of 60 (85%); and R2/unresectable, 2 of 6 (33%). LR predictors include extent of delayed resection (P <.001), imaging response before delayed surgery (P < .001), histologic subtype (P <.001), and no RT (P = .046). The 5-year event-free survival was significantly lower (P = .0003) for patients unable to undergo R0/R1 resection.
CONCLUSIONS
Risk-based treatment for young patients with high-grade NRSTS treated on ARST0332 produced very high LC, particularly after R0 resection (97%), despite lower-than-standard RT doses. Neoadjuvant CT/RT enabled delayed R0/R1 resection in most patients and is preferred over adjuvant therapy due to the lower RT dose delivered.
目的
ARST0332 试验针对的是患有非横纹肌肉瘤软组织肉瘤（NRSTS）的儿科和年轻成人患者，采用基于风险的治疗方法，包括原发肿瘤切除术和低于标准剂量的放射治疗，以优化局部控制（LC），同时最大限度地降低需要放射治疗（RT）的患者的长期毒性。对于高级别 NRSTS，RT 基于切除范围（R0：阴性边缘，R1：显微镜下边缘，R2/U：大体疾病/不可切除）；对于肿瘤直径＞5cm 的患者，给予化疗（CT；异环磷酰胺/多柔比星）。本分析评估了接受 RT 治疗的患者的 LC 情况，以及与局部复发（LR）相关的预后因素。
方法和材料
年龄＜30 岁的高级别 NRSTS 患者接受 RT（55.8Gy）治疗，适用于 R1 肿瘤直径≤5cm（B 臂）；R0/R1 肿瘤直径＞5cm 时接受 RT（55.8Gy）/CT（C 臂）治疗；或新辅助 RT（45Gy）/CT 加延迟手术、CT 和术后 10.8Gy 补充放疗，用于 R0 肿瘤边缘＜5mm 或 R1 肿瘤或 R2/不可切除肿瘤边缘 19.8Gy（D 臂）。
结果
193 例患者中有 24 例发生 LR（B 臂 1/15[6.7%]，C 臂 7/65[10.8%]，D 臂 16/113[14.2%]），LR 中位时间为 1.1 年（范围 0.11-5.27）。95 例有资格接受新辅助治疗后延迟手术的患者中，89 例（93.7%）达到了 R0/R1 边缘。RT 后总的 LC 如下：R0，109 例中的 106 例（97%）；R1，60 例中的 51 例（85%）；R2/不可切除，6 例中的 2 例（33%）。LR 的预测因素包括延迟手术切除范围（P＜0.001）、延迟手术前影像学反应（P＜0.001）、组织学亚型（P＜0.001）和未接受 RT（P=0.046）。无法进行 R0/R1 切除的患者 5 年无事件生存率显著降低（P=0.0003）。
结论
ARST0332 试验中，对患有高级别 NRSTS 的年轻患者采用基于风险的治疗方法，尽管放射治疗剂量低于标准剂量，但仍能获得非常高的 LC，尤其是在达到 R0 切除时（97%）。新辅助 CT/RT 使大多数患者能够进行延迟的 R0/R1 切除，并且由于提供的放射治疗剂量较低，优于辅助治疗。
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