新辅助放化疗或单纯放疗治疗局限性软组织肉瘤患者的病理完全缓解和临床结局：NRG/RTOG 9514 和 0630 非随机临床试验。

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials.

机构信息

Rush University Medical Center, Chicago, Illinois.

NRG Oncology Statistics and Data Management Center, American College of Radiology.

出版信息

JAMA Oncol. 2023 May 1;9(5):646-655. doi: 10.1001/jamaoncol.2023.0042.

DOI:10.1001/jamaoncol.2023.0042

PMID:36995690

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10064284/

Abstract

IMPORTANCE

Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS).

OBJECTIVE

We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630.

DESIGN, SETTING, AND PARTICIPANTS: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes.

INTERVENTION

Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone.

MAIN OUTCOMES AND MEASURES

Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017.

RESULTS

Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45).

CONCLUSIONS AND RELEVANCE

This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies.

TRIAL REGISTRATION

ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).

摘要

重要性：病理完全缓解（pCR）可能与软组织肉瘤（STS）患者的预后相关。

目的：我们旨在确定新辅助放化疗（CT-RT）（放射治疗肿瘤学组 [RTOG] 9514）或术前图像引导放疗单独治疗（RT，RTOG 0630）的 STS 患者的 pCR 对生存结果的预后意义，并提供 RTOG 0630 的长期更新。

设计、设置和参与者：RTOG 已完成 2 项针对局部 STS 患者的多机构、非随机 2 期临床试验。RTOG 0630（n=79）和 RTOG 9514（n=64）的 143 名合格患者被纳入本研究的 pCR 辅助分析，其中 79 名患者来自 RTOG 0630，对其进行了长期结局评估。

干预措施：9514 号试验中的患者接受 CT 与 RT 交替治疗，而 0630 号试验中的患者接受术前 RT 单独治疗。

主要结果和测量：通过 Kaplan-Meier 法估计总生存期（OS）和无病生存期（DFS）率。尽可能通过多变量 Cox 模型分层估计危险比（HR）和 P 值；否则，通过分层对数秩检验计算 P 值。分析于 2016 年 12 月 14 日至 2017 年 4 月 13 日进行。

结果：总体而言，有 42 名（53.2%）男性；68 名（86.1%）为白人；平均（SD）年龄为 59.6（14.5）岁。对于 RTOG 0630，在中位随访 6.0 年时，初始报告后有 1 例新的局部区域复发和 1 例远处失败。来自两项研究，123 名患者可评估 pCR：9514 号试验中 14 名（27.5%），0630 号试验中 14 名（19.4%）为 pCR。pCR 患者的 5 年 OS 为 100%，而 pCR 患者的 5 年 OS 为 76.5%（95%CI，62.3%-90.8%）和 56.4%（95%CI，43.3%-69.5%），pCR 患者的 5 年 OS 为 56.4%（95%CI，43.3%-69.5%）。总体而言，与 pCR 患者相比，pCR 与 OS（P=0.01）和 DFS（HR，4.91；95%CI，1.51-15.93；P=0.008）的改善相关。pCR 患者的局部失败率为 0%，而 pCR 患者的局部失败率为 11.7%（95%CI，3.6%-25.1%）和 9.1%（95%CI，3.3%-18.5%），而 pCR 患者的局部失败率为 9.1%（95%CI，3.3%-18.5%）。非平滑肌肉瘤、脂肪肉瘤和黏液纤维肉瘤的组织学类型与较差的 OS 相关（HR，2.24；95%CI，1.12-4.45）。

结论和相关性：本研究对 2 项非随机临床试验进行了辅助分析，发现 pCR 与 STS 患者的生存改善相关，应作为未来研究中临床结局的预后因素。

试验注册：ClinicalTrials.gov 标识符：RTOG 0630（NCT00589121）；RTOG 9514（NCT00002791）。