IMPORTANCE Neoadjuvant checkpoint inhibition in patients with high-risk stage III melanoma shows high pathologic response rates associated with a durable relapse-free survival. Whether a therapeutic lymph node dissection (TLND) can be safely omitted when a major pathologic response in the largest lymph node metastasis at baseline (index lymph node; ILN) is obtained is currently being investigated. A previous small pilot study (n = 12) showed that the response in the ILN may be representative of the pathologic response in the entire TLND specimen. OBJECTIVE To assess the concordance of response between the ILN and the total lymph node bed in a larger clinical trial population. DESIGN, SETTING, AND PARTICIPANTS Retrospective pathologic response analysis of a multicenter clinical trial population of patients from the randomized Study to Identify the Optimal Adjuvant Combination Scheme of Ipilimumab and Nivolumab in Melanoma Patients (OpACIN) and Optimal Neo-Adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo) trials. Included patients were treated with 6 weeks neoadjuvant ipilimumab plus nivolumab. Patient inclusion into the trials was conducted from August 12, 2015, to October 24, 2016 (OpACIN), and November 24, 2016, and June 28, 2018 (OpACIN-neo). Data were analyzed from April 1, 2020, to August 31, 2021. MAIN OUTCOMES AND MEASURES Concordance of the pathologic response between the ILN and the TLND tumor bed. The pathologic response of the ILN was retrospectively assessed according to the International Neoadjuvant Melanoma Consortium criteria and compared with the pathologic response of the entire TLND specimen. RESULTS A total of 82 patients treated with neoadjuvant ipilimumab and nivolumab followed by TLND (48 [59%] were male; median age, 58.5 [range, 18-80] years) were included. The pathologic response in the ILN was concordant with the entire TLND specimen response in 81 of 82 patients (99%) and in 79 of 82 patients (96%) concordant when comparing the ILN response with the response in every individual lymph node. In the single patient with a discordant response, the ILN response (20% viable tumor, partial pathologic response) underestimated the entire TLND specimen response (5% viable, near-complete pathologic response). Two other patients each had 1 small nonindex node that contained 80% viable tumor (pathologic nonresponse) whereas all other lymph nodes (including the ILN) showed a partial pathologic response. In these 2 patients, the risk of regional relapse might potentially have been increased if TLND had been omitted. CONCLUSIONS AND RELEVANCE The results of this study suggest that the pathologic response of the ILN may be considered a reliable indicator of the entire TLND specimen response and may support the ILN response-directed omission of TLND in a prospective trial.

中文翻译：

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III 期黑色素瘤患者新辅助检查点抑制剂治疗后病理反应评估中总淋巴结盆地指数淋巴结的代表性。


重要性 高危 III 期黑色素瘤患者的新辅助检查点抑制显示出与持久无复发生存相关的高病理缓解率。目前正在研究当基线时最大淋巴结转移（索引淋巴结；ILN）出现主要病理反应时是否可以安全地省略治疗性淋巴结清扫术（TLND）。之前的一项小型试点研究（n = 12）表明，ILN 中的反应可能代表整个 TLND 标本的病理反应。目的 评估较大临床试验人群中 ILN 与总淋巴结床反应的一致性。设计、设置和参与者 对来自随机研究的多中心临床试验患者群体进行回顾性病理反应分析，以确定伊匹单抗和纳武单抗在黑色素瘤患者中的最佳辅助组合方案 (OpACIN) 以及伊匹单抗和纳武单抗的最佳新辅助组合方案（OpACIN-neo）试验。纳入的患者接受 6 周新辅助伊匹单抗加纳武单抗治疗。患者纳入试验的时间为2015年8月12日至2016年10月24日（OpACIN），以及2016年11月24日至2018年6月28日（OpACIN-neo）。对2020年4月1日至2021年8月31日的数据进行分析。 主要结果和措施 ILN和TLND瘤床之间病理反应的一致性。根据国际新辅助黑色素瘤联盟标准回顾性评估ILN的病理反应，并与整个TLND标本的病理反应进行比较。结果 共有 82 名患者接受新辅助伊匹单抗和纳武单抗治疗，随后接受 TLND（48 名 [59%] 为男性；中位年龄 58 岁）。包括 5 [范围，18-80] 岁）。当比较 ILN 反应与每个淋巴结的反应时，82 名患者中有 81 名 (99%) 的 ILN 病理反应与整个 TLND 标本反应一致，82 名患者中有 79 名 (96%) 一致。在反应不一致的单个患者中，ILN 反应（20% 存活肿瘤，部分病理反应）低估了整个 TLND 标本反应（5% 存活，接近完全病理反应）。另外两名患者各有 1 个小非指标淋巴结，其中包含 80% 的存活肿瘤（病理无反应），而所有其他淋巴结（包括 ILN）均显示部分病理反应。在这 2 名患者中，如果省略 TLND，区域复发的风险可能会增加。结论和相关性 本研究的结果表明，ILN 的病理反应可被视为整个 TLND 标本反应的可靠指标，并可能支持前瞻性试验中以 ILN 反应为导向的 TLND 省略。