ASO Author Reflections: CTNNB1 and Fusion Genes as Predictors for Recurrence in Resected Early-Stage Lung Adenocarcinoma
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ASO AUTHOR REFLECTIONS
ASO Author Reflections: CTNNB1 and Fusion Genes as Predictors for Recurrence in Resected Early-Stage Lung Adenocarcinoma In Ae Kim, MD, PhD1,2, Wan Seop Kim, MD, PhD1,3, and Kye Young Lee, MD, PhD1,2 1
Precision Medicine Lung Cancer Center, Konkuk University Medical Center, Seoul, Republic of Korea; 2Department of Pulmonary Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 3Department of Pathology, Konkuk University School of Medicine, Seoul, Republic of Korea
PAST Despite complete surgical resection with mediastinal lymph node dissection, early lung adenocarcinoma has a recurrence rate of 20% to 50%, and the patients eventually die of recurrent lung cancer.1 To prevent relapse, adjuvant chemotherapy is recommended for patients with resected early-stage lung cancer. However, its benefit for stage 1B patients is controversial. Therefore, physicians recommend adjuvant chemotherapy, depending on pathologic risk factors, without considering genetic mutations that may cause high recurrent risk.2 PRESENT In this study,3 the authors hypothesized that specific genetic alterations might affect recurrence and compared the molecular profiles of patient groups with and without recurrence by performing a targeted next-generation sequencing (NGS) analysis for 207 cancer-related genes in 230 early-stage lung adenocarcinomas. A multivariate analysis showed that the CTNNB1 mutation and fusion genes (ALK, ROS1, and RET) were independent predictive markers of recurrence. Epidermal growth factor receptor (EGFR) mutations constituted a favorable prognostic factor, but the EGFR/CTNNB1 co-mutation was a negative
Ó Society of Surgical Oncology 2020 First Received: 20 October 2020 Accepted: 21 October 2020 K. Y. Lee, MD, PhD e-mail: [email protected]
predictive factor (hazard ratio [HR] 19.2; p \ 0.001). To date, clinical studies have been conducted based on the presence of major specific driver mutations, and the interaction of co-occurring mutations has not been considered. As a result, the recurrence of early tumors or adenocarcinoma harboring EGFR mutations with complete resection has not been explained. This study found that these tumors might have CTNNB1 mutation or fusion genes. The authors analyzed the effect of adjuvant chemotherapy on patients with CTNNB1 mutations. Unfortunately, the patients with CTNNB1 mutations experienced recurrence irrespective of adjuvant chemotherapy. Reports show a resistance of CTNNB1s to chemotherapy.4 Thus, patients with CTNNB1 mutation need intensive surveillance for early detection of recurrence, or therapy targeting b-catenin pathway in clinical trials should be treated for them.5 This study also observed that fusion genes (ALK, ROS1, and RET) were related to a shorter recurrence-free survival.6 Therefore, it is important to administer adjuvant-targeted therapy for resected earlystage lung cancer with ALK or fusion mutation. FUTURE The results of this study underscore the importance of incorporating tailored risk assessments according to genomic a
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