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非小细胞肺癌免疫治疗和靶向治疗后挽救性手术的短期结果

Short-term results of salvage surgery after immune and target therapies in non-small cell lung cancer.

作者信息

Chiappetta Marco, Sassorossi Carolina, Lococo Filippo, Guerrera Francesco, Ruffini Enrico, Lyberis Paraskevas, Della Beffa Eleonora, Cafarotti Stefano, Patella Miriam, Freguia Stefania, Cancellieri Alessandra, Kuzmych Khrystina, Charles-Davies Diepriye, Bria Emilio, Margaritora Stefano

机构信息

Thoracic Surgery Unit, University "Magna Graecia", Catanzaro, Italy.

Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

出版信息

J Thorac Dis. 2025 Jul 31;17(7):4929-4939. doi: 10.21037/jtd-2025-387. Epub 2025 Jul 24.

Abstract

BACKGROUND

In the last years, the knowledge about the non-small cell lung cancer (NSCLC) biology led to development of target therapies and immunotherapy. However, most indication were to advanced stages, with large nodal involvement or presence of distant metastases. However, the clinical response may be unpredictable, and in some cases, it is possible to see a large clinical response with resolution of the parameter that contraindicated surgical treatment. In these cases, surgery could be re-considered, performing a salvage surgery approach, but evidences regarding the feasibility of this approach in these clinical scenarios are still missing. The objective of this study is to describe the clinical, surgical and pathological characteristics of patients who underwent salvage surgery after target therapy or immunotherapy, for initially non-resectable NSCLC.

METHODS

Data of patients undergone salvage surgery after target therapy or immunotherapy from three different centres from January 1, 2015 to December 31, 2022 were retrospectively collected and analyzed.

RESULTS

The final analysis was led on 30 patients meeting inclusion criteria. Preoperatively, 22 patients presented stage III disease, 8 presented stage IV. For 22 patients without distant metastases, initial contraindication to surgery was due to bulky/multi-stations N2 involvement, advanced tumor (T) stage with concomitant N1/N2 involvement, N3 involvement. Target therapy mutations were anaplastic lymphoma kinase (ALK) rearrangement (treated with alectinib) and epidermal growth factor receptor (EGFR; treated with gefitinib, osimertinib and afatinib) in 8 total cases. Other 22 patients underwent immunotherapy alone or in association with chemotherapy in 4 cases. Surgery consisted mostly of lobectomy/bilobectomy (27 patients), and was considered feasible in all cases but 2, with local involvement. No peri-operative mortality was reported. Complications occurred in 6 (20%) and the length of stay was averagely 5.9±2.8 days. Pathological examination showed downstaging in 26 patients, with 11 (36%) patients that presenting pathological complete response (pCR). pCR occurred in 37% adenocarcinoma and 33% squamous cell carcinomas. Complete pathological response was observed in 10 out of 22 patients treated with immunotherapy, 1 patient treated with alectinib. Median follow up was 12 months. Five patients had recurrence and 4 died due to cancer related causes.

CONCLUSIONS

Salvage surgery after target therapy or immunotherapy resulted to be a possible approach in selected patients.

摘要

背景

在过去几年中,对非小细胞肺癌(NSCLC)生物学的认识推动了靶向治疗和免疫治疗的发展。然而,大多数适应症是针对晚期阶段,伴有大量淋巴结受累或远处转移。然而,临床反应可能不可预测,在某些情况下,可能会出现显著的临床反应,使得之前禁忌手术治疗的参数得到缓解。在这些情况下,可以重新考虑手术,采用挽救性手术方法,但关于这种方法在这些临床场景中的可行性的证据仍然缺乏。本研究的目的是描述最初不可切除的NSCLC患者在接受靶向治疗或免疫治疗后接受挽救性手术的临床、手术和病理特征。

方法

回顾性收集并分析了2015年1月1日至2022年12月31日期间来自三个不同中心的接受靶向治疗或免疫治疗后进行挽救性手术的患者数据。

结果

对30名符合纳入标准的患者进行了最终分析。术前,22例患者为III期疾病,8例为IV期。对于22例无远处转移的患者,最初的手术禁忌是由于巨大/多站N2受累、伴有N1/N2受累的晚期肿瘤(T)期、N3受累。靶向治疗突变包括间变性淋巴瘤激酶(ALK)重排(用阿来替尼治疗)和表皮生长因子受体(EGFR;用吉非替尼、奥希替尼和阿法替尼治疗),共8例。另外22例患者单独接受免疫治疗,4例患者联合化疗。手术主要包括肺叶切除术/双肺叶切除术(27例患者),除2例有局部受累的情况外,所有病例均被认为可行。未报告围手术期死亡。6例(20%)出现并发症,平均住院时间为5.9±2.8天。病理检查显示26例患者分期降低,11例(36%)患者出现病理完全缓解(pCR)。腺癌患者中pCR发生率为37%,鳞状细胞癌患者中为33%。在接受免疫治疗的22例患者中有10例、接受阿来替尼治疗的1例患者观察到完全病理缓解。中位随访时间为12个月。5例患者复发且4例因癌症相关原因死亡。

结论

靶向治疗或免疫治疗后的挽救性手术对部分患者来说是一种可行的方法。

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