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一名肺腺癌患者在对酪氨酸激酶抑制剂产生不同反应后出现小肠转移,同时存在EML4-ALK V3和TP53突变:病例报告

Small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3 and TP53 mutations after distinct responses to tyrosine kinase inhibitors: A case report.

作者信息

Zhu Lingling, Zhao Yingchun, Zhang Yongqian, Liu Zhai, Ma Wenhua, Guo Ying, Wang Qian, Guo Yan, Lv Hengxu, Zhao Min

机构信息

Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.

出版信息

Heliyon. 2024 Oct 2;10(19):e38839. doi: 10.1016/j.heliyon.2024.e38839. eCollection 2024 Oct 15.

Abstract

BACKGROUND

Although anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have improved the survival rates of lung cancer patients with fusion mutations, their effectiveness varies significantly across different subtypes. We report a case of small intestine metastasis in a lung adenocarcinoma patient with co-occurring echinoderm microtubule-associated protein-like 4 ()- fusion variant 3 (V3) and tumor protein 53 () mutations after distinct responses to ALK-TKIs.

CASE PRESENTATION

A 45-year-old woman was diagnosed with stage IV lung adenocarcinoma with brain metastasis. Next-generation sequencing revealed - V3 and co-mutations. After the initial treatment with ensartinib, the patient experienced intracranial disease progression. Radiation therapy (RT) was then administered. Despite good response to RT for the intracranial disease, the primary tumor enlarged. Thus, the patient was treated with oral ensartinib concurrent with chemotherapy, with a partial response in both the primary tumor and intracranial metastases. However, after three cycles of treatment, the patient discontinued chemotherapy because of acute kidney injury. Subsequent thoracic RT resulted in a partial response of the primary tumor; however, new brain and bone metastases were detected, prompting a switch to lorlatinib. The patient developed symptoms of intestinal obstruction 14 months after the initial diagnosis. Surgical intervention revealed a poorly differentiated metastatic lung adenocarcinoma of the upper jejunum. Genetic testing confirmed - V3 and co-mutations and high expression of programmed cell death-ligand 1. Despite pembrolizumab treatment, the patient's condition deteriorated, and she passed away.

CONCLUSION

We reported a rare case of small intestinal metastasis in a lung adenocarcinoma patient with concurrent V3/ mutations after distinct responses to ALK-TKIs in different lesions. Our findings revealed heterogeneity in mutations and responses to ALK-TKIs, necessitating the close monitoring of genetic subtypes and associated mutations for tailored treatment strategies. Maintaining a heightened awareness of potential intestinal metastasis and vigilance in monitoring intestinal symptoms and abdominal metastases are pivotal for managing advanced lung adenocarcinoma.

摘要

背景

尽管间变性淋巴瘤激酶酪氨酸激酶抑制剂(ALK-TKIs)提高了伴有融合突变的肺癌患者的生存率,但其有效性在不同亚型之间差异显著。我们报告了1例肺腺癌患者发生小肠转移的病例,该患者同时存在棘皮动物微管相关蛋白样4()-融合变异体3(V3)和肿瘤蛋白53()突变,且对ALK-TKIs有不同反应。

病例介绍

一名45岁女性被诊断为伴有脑转移的IV期肺腺癌。二代测序显示-V3和共同突变。在接受恩沙替尼初始治疗后,患者出现颅内疾病进展。随后进行了放射治疗(RT)。尽管颅内疾病对RT反应良好,但原发肿瘤增大。因此,患者接受口服恩沙替尼联合化疗,原发肿瘤和颅内转移灶均有部分缓解。然而,在三个周期的治疗后,患者因急性肾损伤停止化疗。随后的胸部RT使原发肿瘤部分缓解;然而,检测到新的脑转移和骨转移,促使改用劳拉替尼。患者在初始诊断后14个月出现肠梗阻症状。手术干预显示空肠上段有低分化转移性肺腺癌。基因检测证实-V3和共同突变以及程序性细胞死亡配体1的高表达。尽管使用了帕博利珠单抗治疗,患者病情仍恶化并去世。

结论

我们报告了1例罕见的肺腺癌患者小肠转移病例,该患者同时存在V3/突变,且不同病灶对ALK-TKIs有不同反应。我们的研究结果揭示了突变和对ALK-TKIs反应的异质性,需要密切监测基因亚型和相关突变以制定个性化治疗策略。对晚期肺腺癌的管理而言,保持对潜在小肠转移的高度警惕以及监测肠道症状和腹部转移的警觉性至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1c/11489313/db4388851464/gr1.jpg

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