在 ALK 阳性 NSCLC 中，从非小细胞肺癌 (NSCLC) 向具有间变性淋巴瘤激酶 (ALK) 阳性的小细胞肺癌 (SCLC) 的组织学转变极为罕见。迄今为止，有关SCLC转化病例的报道有限，此类患者的最佳治疗策略和预后仍不清楚。该病例首次描述了劳拉替尼治疗对艾乐替尼治疗产生耐药性后携带 ALK 融合 V1180L 突变的 NSCLC 转化为 SCLC 的有效性。我们介绍了艾乐替尼诱导的 ALK 阳性 NSCLC 转化为 SCLC 的病例获得艾来替尼耐药后出现 ALK V1180L 突变。该患者在化疗无效后通过劳拉替尼治疗实现了疾病缓解。 2022年4月，一名53岁男性被诊断出患有左肺下叶ALK阳性晚期低分化腺癌，伴神经内分泌分化。诊断伴有多发骨转移和脑转移，分期为cT3N2M1。艾乐替尼治疗 8 个月后，胸部计算机断层扫描 (CT) 和头颅磁共振成像 (MRI) 显示疾病进展。病理和遗传学分析表明转化为肺小细胞癌并伴有ALK融合V1180L突变。两个周期的EP化疗效果不佳后，开始口服劳拉替尼治疗。随后一个月的治疗结果显示，根据胸部 CT 的结果，左肺病变显着减少，根据头颅 MRI 的结果，颅内病变也显着减少。服用lorlatinib 5个月后，病灶持续缩小，患者的生活质量明显改善。目前，患者仍处于持续改善的状态。本研究证实了lorlatinib对携带V1180L突变的ALK阳性SCLC转化患者的疗效。此外，它强调了对 ALK-TKI 耐药后转变为 SCLC 的患者进行基因检测的必要性，因为如果确定了基因驱动因素，靶向治疗可能仍然有效。版权所有 © 2023 作者。由 Elsevier B.V. 出版。保留所有权利。

Histological transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) with anaplastic lymphoma kinase (ALK) positivity is extremely uncommon in ALK-positive NSCLC. To date, there have been limited reports regarding cases of SCLC transformation, and the optimal therapeutic strategies and prognosis for such patients remain unclear. This case is the first to describe the effectiveness of lorlatinib in treating a patient with SCLC that transformed from NSCLC harboring the ALK fusion V1180L mutation following acquired resistance to alectinib therapy.We present a case of alectinib-induced transformation from ALK-positive NSCLC to SCLC with an ALK V1180L mutation after acquiring alectinib resistance. The patient achieved disease remission with lorlatinib treatment following ineffective chemotherapy. In April 2022, a 53-year-old male was diagnosed with ALK-positive advanced poorly differentiated adenocarcinoma with neuroendocrine differentiation in the left lower lobe of the lung. The diagnosis was accompanied by multiple bone metastases and brain metastases, categorizing the stage as cT3N2M1. Following 8 months of alectinib treatment, chest computed tomography (CT) and cranial magnetic resonance imaging (MRI) revealed disease progression. Pathological and genetic analyses indicated the transformation to pulmonary small cell carcinoma accompanied by ALK fusion V1180L mutation. After the administration of two cycles of EP chemotherapy with unsatisfactory response, oral lorlatinib therapy was initiated. A subsequent month of treatment resulted in notable reduction of the left lung lesion according to chest CT, as well as a significant decrease in intracranial lesions based on cranial MRI. After taking lorlatinib for 5 months, the lesions continue to shrink, and there is a noticeable improvement in the patient's quality of life. Currently, the patient remains in a state of sustained improvement.This study affirms the efficacy of lorlatinib in patients with ALK-positive SCLC transformation harboring the V1180L mutation. Furthermore, it underscores the imperative of conducting genetic testing in patients who transition to SCLC following ALK-TKI resistance, as targeted therapies may remain efficacious if a genetic driver is identified.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.