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      Case Report: Adjuvant Crizotinib Therapy Exerted Favorable Survival Benefit in a Resectable Stage IIIA NSCLC Patient With Novel LDLR–ROS1 Fusion

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          Abstract

          Novel adjuvant strategies are needed to optimize outcomes after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC). The adjuvant treatment of ROS Proto-Oncogene 1 ( ROS1) fusion-positive resected NSCLC is challenging because there is no curative confirmed randomized controlled trial. Next-generation sequencing (NGS) and immunohistochemistry (IHC) staining were performed on the biopsy sample. In this case, we identified a novel LDLR–ROS1 fusion in a resectable stage IIIA NSCLC patient. The patient received crizotinib as adjuvant treatment and achieved recurrence-free survival (RFS) for 29 months, without significant symptoms of toxicity. In this case, we report a novel LDLR–ROS1 fusion responding to crizotinib in a patient with lung adenocarcinoma, supporting the use of adjuvant treatment with the ROS1 inhibitor exerting clinical survival benefit in ROS1 fusion-positive resected NSCLC.

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          Most cited references6

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          Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer

          Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown.
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            Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial

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              ROS1-ADGRG6 : a case report of a novel ROS1 oncogenic fusion variant in lung adenocarcinoma and the response to crizotinib

              Background ROS1 rearrangements are validated drivers in lung cancer, which have been identified in a small subset (1–2%) of patients with non-small cell lung cancer (NSCLC). To date, 18 fusion genes of ROS1 have been identified in NSCLC. The ALK inhibitor (crizotinib) exhibits therapeutic effect against ROS1-rearranged NSCLC. Next-generation sequencing (NGS) technology represents a novel tool for ROS1 detection that covers many fusion genes. Case presentation A 55-year-old female with EGFR mutation (L858R) was diagnosed with lung adenocarcinoma, who was responsive to first-generation EGFR-tyrosine kinase inhibitor (TKI). Afterwards, she developed acquired resistance accompanied with a ROS1 rearrangement. A NGS assay showed that the tumor had a novel ROS1-ADGRG6 rearrangement generated by the fusion of exons of 1–33 of ROS1 on chr6: q22.1 to exons of 2–26 of ADGRG6 on chr6: q24.2. The patient was obviously responsive to crizotinib. Conclusion We firstly identified ROS1-ADGRG6 fusion variant in NSCLC by NGS, which should be considered in further ROS1 detecting assays.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                01 March 2022
                2022
                : 12
                : 837219
                Affiliations
                [1] 1Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, China
                [2] 2The Medical Department, Jiangsu Simcere Diagnostics Co. , Ltd., Nanjing, China
                [3] 3Nanjing Simcere Medical Laboratory Science Co. , Ltd., Nanjing, China
                [4] 4The State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co. , Ltd., Nanjing, China
                Author notes

                Edited by: Dharmendra Kumar Yafav, Gachon University, South Korea

                Reviewed by: Geeta G. Sharma, City of Hope National Medical Center, United States; Luca Porcu, Mario Negri Pharmacological Research Institute (IRCCS), Italy

                *Correspondence: An-guo Chen, chenag119@ 123456126.com

                This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.837219
                8921990
                35299735
                40137afe-232a-42a5-b3df-88043e0e5158
                Copyright © 2022 Chen, Chen, Li, Zhao and Xiao

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 December 2021
                : 25 January 2022
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 6, Pages: 4, Words: 1047
                Categories
                Oncology
                Case Report

                Oncology & Radiotherapy
                ros1 fusion,crizotinib,adjuvant treatment,nsclc,case report
                Oncology & Radiotherapy
                ros1 fusion, crizotinib, adjuvant treatment, nsclc, case report

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