靶向治疗联合局部巩固手术治疗CCDC6-RET融合的低转移IVA期肺腺癌：病例报告

摘要(中文译文)

非小细胞肺癌（NSCLC）的精准治疗已扩展至罕见驱动基因。RET融合是肺癌中的罕见靶点，关于靶向治疗联合局部巩固性手术用于晚期寡转移患者的数据有限。本文报告一例经selpercatinib初始全身治疗后成功行手术切除的病例。患者为68岁从不吸烟男性，诊断为右肺上叶腺癌（cT3N3M1，IVA期），伴同侧肺转移及颈部、腋窝淋巴结转移，符合寡转移特征。通过下一代测序鉴定出CCDC6-RET融合。患者接受selpercatinib治疗三个月作为初始全身治疗。治疗后影像学评估提示部分缓解。患者随后成功接受胸腔镜右肺上叶前段切除术及淋巴结清扫。术后病理证实残留存活肿瘤细胞15%，未达到主要病理缓解（MPR）。由于靶向治疗后原增大淋巴结明显缩小并呈瘢痕样改变，术中行局限性淋巴结清扫，所有送检淋巴结均为阴性。术后病理分期为ypT1aN0M0。术后继续辅助selpercatinib治疗，7个月随访期间无复发迹象。本病例表明，对于携带CCDC6-RET融合且为寡转移性疾病的晚期肺腺癌精选患者，selpercatinib初始全身治疗后行局部巩固性手术是一种可行的多模式策略。这并非IVA期肺癌的常规推荐，而需在特定寡转移病例中经多学科讨论后个体化决策。

Abstract

Precision therapy for non-small cell lung cancer (NSCLC) has expanded to include rare driver genes. RET fusion is a rare target in lung cancer, and data on targeted therapy combined with local consolidation surgery in advanced patients with oligometastatic status are limited. This article reports a case of successful surgical resection following initial systemic treatment with selpercatinib. A 68-year-old never-smoking male was diagnosed with adenocarcinoma of the right upper lobe (cT3N3M1, stage IVA) with ipsilateral pulmonary metastasis and cervical and axillary lymph node metastases, consistent with oligometastatic features. A CCDC6-RET fusion was identified via next-generation sequencing. The patient received selpercatinib for three months as initial systemic therapy. Post-treatment imaging assessment indicated a partial response. The patient subsequently underwent successful thoracoscopic anterior segmentectomy of the right upper lobe with lymph node dissection. Postoperative pathology confirmed 15% residual viable tumor cells, which did not achieve major pathological response (MPR). Due to marked shrinkage and scar-like changes in the originally enlarged lymph nodes after targeted therapy, limited lymph node dissection was performed intraoperatively, and all submitted lymph nodes were negative. The postoperative pathological stage was ypT1aN0M0. Adjuvant selpercatinib was continued postoperatively, with no signs of recurrence during 7 months of follow-up. This case demonstrates that for selected patients with advanced lung adenocarcinoma harboring a CCDC6-RET fusion and oligometastatic disease, initial systemic therapy with selpercatinib followed by local consolidative surgery is a feasible multimodal strategy. This is not a routine recommendation for stage IV lung cancer but requires individualized decision-making after multidisciplinary discussion in specific oligometastatic cases.

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