Abstract
Some studies have revealed that specific genetic mutations could be associated with chemotherapy response or even survival in small-cell lung cancer (SCLC). Our retrospective study aimed to identify the correlation between genetic mutations and progression-free survival (PFS) in extensive-stage SCLC after first-line chemotherapy. A total of 75 patients with extensive-stage SCLC confirmed by histopathology from February 2018 to February 2019 were retrospectively analyzed. The biopsy specimens of all patients were analyzed by Next-Generation Sequencing (NGS). All patients received first-line chemotherapy and follow-up at Shanghai Chest Hospital. Eleven genes were mutated in, at least, 10% of the 75 patients, including TP53 (96%), RB1 (77%), SMAD4 (32%), NOTCH1 (21%), PTEN (16%), FGFR1 (16%), KDR (15%), PIK3CA (15%), ROS1 (15%), BRCA2 (13%), and ERBB4 (10%). The median number of mutated genes among all patients was 5. Patients with more than 5 mutated genes (PFS = 6.7 months, P=0.004), mutant TP53 (PFS = 5.0 months, P=0.011), and mutant BRCA2 (PFS = 6.7 months, P=0.046) had better PFS after first-line chemotherapy than other patients. Multivariate Cox regression analysis showed that patients who achieved a PR (HR 3.729, 95% CI 2.038–6.822), had more than 5 mutated genes (HR 1.929, 95% CI 1.096–3.396), had BRCA2 mutations (HR 4.581, 95% CI 1.721–12.195), and had no liver metastasis (HR 0.415, 95% CI 0.181–0.951) showed improvements in PFS after first-line chemotherapy. In conclusion, the number of mutated genes and BRCA2 mutation status in extensive-stage SCLC were significantly related to PFS after first-line chemotherapy.
Highlights
Small-cell lung cancer (SCLC) is a malignant neuroendocrine tumor with an epithelial source and accounts for approximately 15% to 17% of all diagnosed lung cancers [1].e unique biological characteristics of SCLC include a close association with smoking, rapid proliferation, and early hematogenous metastasis [2]. us, 80% of patients are at an extensive stage when first diagnosed. e liver, bone, kidney, and brain are several common distant metastasis sites
Another study focused on cisplatinresistant target genes and genes associated with poor prognosis in SCLC, and the results indicated that DNAH10 mutations were significantly associated with cisplatin resistance, poor overall survival (OS), and worse progression-free survival (PFS) in SCLC [12]. erefore, DNAH10 mutations may have potential value in predicting cisplatin resistance and poor survival in SCLC
Since gene-related research on SCLC is limited, the relationship between genetic mutations and survival in SCLC is worth further study. is study may be helpful for identifying SCLC patients who could benefit from chemotherapy, which is of great practical significance. us, the main purpose of our retrospective study is as follows: first, to investigate the mutation status of extensive-stage SCLC patients, including nonsmoking and female patients, and second, to identify the correlation between genetic mutations and PFS in extensive-stage SCLC patients after first-line chemotherapy
Summary
Small-cell lung cancer (SCLC) is a malignant neuroendocrine tumor with an epithelial source and accounts for approximately 15% to 17% of all diagnosed lung cancers [1]. E liver, bone, kidney, and brain are several common distant metastasis sites For these extensive-stage patients, the current first-line standard chemotherapy is etoposide plus carboplatin or cisplatin [3]. With the application of NGS technology, many studies have revealed that genetic mutation rates are extremely high in SCLC [7,8,9]. Most patients with extensive-stage SCLC have relatively good responses to first-line chemotherapy, but they will eventually experience chemotherapy resistance and relapse. E abovementioned studies suggest that specific genetic mutations may be associated with chemotherapy response or survival in SCLC. Us, the main purpose of our retrospective study is as follows: first, to investigate the mutation status of extensive-stage SCLC patients, including nonsmoking and female patients, and second, to identify the correlation between genetic mutations and PFS in extensive-stage SCLC patients after first-line chemotherapy Since gene-related research on SCLC is limited, the relationship between genetic mutations and survival in SCLC is worth further study. is study may be helpful for identifying SCLC patients who could benefit from chemotherapy, which is of great practical significance. us, the main purpose of our retrospective study is as follows: first, to investigate the mutation status of extensive-stage SCLC patients, including nonsmoking and female patients, and second, to identify the correlation between genetic mutations and PFS in extensive-stage SCLC patients after first-line chemotherapy
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