Purpose: The aberrant of fibroblast growth factors and their receptors (FGF/FGFR) is an emerging target in the treatment of solid tumors. This study aimed to explore the landscape of FGF/FGFR alterations in a large cohort of cancer patients. Material and Methods: The formalin-fixed paraffin-embedded specimens of cancer patients who have underwent next-generation sequencing (NGS) from 2017 to 2019 in 3DMed Clinical Laboratory Inc. were included in this study. Findings: Of 12,372 Chinese cancer patients with more than 20 tumor types (60% male, median age, 58.0 [IQR, 49.0-66.0]), genomic alterations in FGF, FGFR, and both were observed in 895 (7.2%), 862 (7.0%), and 186 (1.5%) patients, respectively. The highest prevalence of FGF/FGFR mutations fell in esophagus cancer (61.6%, 98/159) and urinary tract cancer (52.7%, 145/275). The most common pathway-level mutations were FGFR single nucleotide variants (635, 5.1%) and FGF amplifications (628, 5.1%). The microsatellite instability status was negatively associated with amplifications (p=0.0017). Conclusion: FGF/FGFR alterations were widely occurred in cancer patients, and the mutational landscape may contribute to the further study design and development of FGF/FGFR inhibitors.
e17109 Background: Endometrial carcinoma is the most common gynecology malignancies in the worldwide. The clinical outcome of endometrial carcinoma is excellent, with disease specific survival rate over 90% in early stages. However, the prognosis of metastatic endometrial carcinoma is poor and the pattern of distant metastases has not been well characterized. In the present study, we sought to assess the incidence and prognosis of different distant metastatic sites in endometrial carcinoma. Methods: Patients who were diagnosed with endometrial carcinoma between 2010 and 2015 were identified according to the following criteria in the Surveillance, Epidemiology, and End Results (SEER) database: (1) confirmed age and older than 18 years old; (2) enrolled patients should have confirmed distant visceral metastatic status information. Kaplan-Meier analysis and log-rank tests were used to estimate the overall survival (OS) between difference groups. Data were analyzed with GraphPad Prism (version 7.01, GraphPad Software, USA), and R (version 4.3.1, R Development Core Team). Results: A total of 73328 patients with endometrial carcinoma were included. Median age of diagnosis was 62 years and 80.3% of patients were white. 92.8% of patents have received surgery. 4.2% of patients (3053/73328) suffered at least one site of distant metastases. The most common metastasis site was lung (1331/73328, 1.82%), followed by distant lymph nodes (1191/72703, 1.6%), liver (661/73328, 0.9%), bone (475/73328, 0.65%) and brain (133/73328, 0.18%). Median OS was 15 months, 4 months, 7 months, 9 months and 8 months for pure distant lymph node, brain, bone, lung and liver metastases, respectively. Furthermore, metastatic sites showed significant impact on OS in univariate analysis. Multivariate analysis with COX proportional regression model showed that distant metastatic sites were independent prognostic factors of OS. Conclusions: Lung is the most common distant metastatic site of endometrial carcinoma. Patients with pure distant lymph node metastasis exhibited the best overall survival, while patients with brain metastases had worst clinical prognosis compared with other metastatic sites.
Introduction: Platinum-resistant ovarian cancer is characterized by its poor prognosis and limited treatment options. Angiogenesis plays a fundamental role in the development of drug-resistance in ovarian cancer. Anlotinib, a novel oral multi-targeted tyrosine kinase inhibitor which targets a board spectrum of angiogenesis-associated growth factor receptors, has shown promising anti-tumor efficacy in clinical trials. Herein, we report a case of ovarian cancer treated with anlotinib plus etoposide after secondary cytoreductive surgery. Patient concerns: A 45-year-old female with primary platinum-resistant ovarian cancer who progressed rapidly after the first cytoreductive surgery, the second cytoreductive surgery, and several lines of treatment. The patient refused to receive intravenous chemotherapy any more. Diagnosis: Primary platinum-resistant ovarian cancer. Interventions: The oral combination treatment of anlotinib (12 mg, qd) and etoposide (100 mg, qd) were delivered. Outcomes: Finally, the patient was responsive to the orally treatment of anlotinib combined with etoposide. The patient has been alive with no evidence of disease progression for 18 weeks. Conclusion: Our case suggests that oral treatment of anlotinib combined with etoposide which is acceptable and convenient, may be an additional option for the management of platinum-resistant ovarian cancer.
Background: Gastric cancer (GC) is one of the leading causes of cancer death in China, while the nature of genetic factors related to GC has not been well-studied. Objectives: To assess the inherited genetic factors regarding pathogenic germline mutations in Chinese GC population. Methods: Genomic profiling of DNA was performed through next-generation sequencing with 381 cancer-related genes on tissue from patients with GC between January 1, 2017, and May 7, 2019. Results: 470 GC patients were included for analysis. A total of 28 (6.0%) patients were identified to harbor 25 different pathogenic or very likely pathogenic germline mutations in 15 genes. The variants fell most frequently in BRCA2 (n = 6, 1.28%), CHEK2 (n = 5, 1.06%), MUTYH (n = 3, 0.64%), CDH1 (n = 2, 0.43%), and ATM (n = 2, 0.43%). Of all the germline-mutated genes, 66.7% (n = 10) lay in the DNA damage repair pathways. Seven patients were identified to have a high TMB status, among whom two were also identified as MSI-H. Overall, 20 out of the 28 patients (71.4%) carried clinically actionable mutations. Conclusions: Our study has depicted the spectrum of pathogenic germline mutations in Chinese GC patients, which may provide valuable clues for the assessment of the genetic susceptibility and clinical management in GC.
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