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

Xiaoqian Zhai; Ting Wang; Yiyun Lin; Jiabi Zhang; Yuqing Wang; Weiya Wang; Qinghua Zhou; Daxing Zhu

doi:10.3389/fonc.2023.1104910

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

Front Oncol. 2023 Mar 29:13:1104910. doi: 10.3389/fonc.2023.1104910. eCollection 2023.

Authors

Xiaoqian Zhai¹, Ting Wang¹, Yiyun Lin², Jiabi Zhang³, Yuqing Wang⁴, Weiya Wang⁵, Qinghua Zhou¹, Daxing Zhu¹

Affiliations

¹ Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
² Graduate School of Biomedical Sciences, MD Anderson Cancer Center UT Health, Houston, TX, United States.
³ Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, United States.
⁴ Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, TX, United States.
⁵ Pathology Department, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: INTS10-ALK and EML4-ALK; case report; complete pathologic response; crizotinib; lung cancer; neoadjuvant; stage IIIB-N3.

Publication types

Case Reports

Grants and funding

This work was supported by grants from the Regional Innovation Cooperation Project of the Sichuan Science and Technology Program [2021YFQ0029]. The 1•3•5 project for disciplines of excellence & Clinical Research Incubation Project, West China Hospital, Sichuan University, [2019HXFH002]; Wu Jieping Medical Foundation, [H1411140]; Natural Science Foundation of Sichuan Province, [2023NSFSC0722].