Case report: Complete pathological admission in N3 unresectable locally advanced lung adenocarcinoma with a novel INTS10-ALK and EML4-ALK fusion after neoadjuvant crizotinib

• Published in: Frontiers in oncology Vol. 13; p. 1104910
• Main Authors: Zhai, Xiaoqian, Wang, Ting, Lin, Yiyun, Zhang, Jiabi, Wang, Yuqing, Wang, Weiya, Zhou, Qinghua, Zhu, Daxing
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 29.03.2023
• Subjects: complete pathologic response; crizotinib; INTS10-ALK and EML4-ALK; lung cancer; neoadjuvant; Oncology; stage IIIB-N3; lung cancer; crizotinib; neoadjuvant; stage IIIB-N3; complete pathologic response; case report; INTS10-ALK and EML4-ALK
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2023.1104910

Although anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have impressive response in advanced lung adenocarcinoma with anaplastic lymphoma kinase (ALK) fusion, no guidelines point to the potential benefits of neoadjuvant ALK-TKIs for N3 unresectable locally advanced lung cancer. Current ongoing clinical trials mainly focus on the efficacy of neoadjuvant ALK-TKIs in resectable locally advanced lung cancer and ignore the role of neoadjuvant ALK-TKIs in N3 unresectable locally advanced lung cancer. We report a lung cancer case with a novel INTS10-ALK and EML4-ALK rearrangement that achieved complete pathologic response to neoadjuvant crizotinib. We conducted molecular pathologic analysis by using next-generation sequencing (NGS). Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples and profiled using a capture-based targeted sequencing panel consisting of 56 lung cancer-related genes. Our study reported a patient with stage IIIB-N3 lung adenocarcinoma with an unreported dual ALK rearrangement (INTS10-ALK and EML4-ALK) who received 5 months of crizotinib, followed by R0 right upper lobectomy, achieving complete pathological response (ypT0 ypN0). No recurrence of the tumor was found for 3 years postoperatively. The case supports the strategy of neoadjuvant ALK inhibitors for N3 unresectable locally advanced lung cancer, expanding the spectrum of treatment of stage IIIB-N3 lung cancer.