Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.
Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.
Purpose: The current National Comprehensive Cancer Network (NCCN) guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X-mutant patients, it is unclear which regimen is the preferred treatment option. Experimental Design: A large cohort of 4,228 treatment-naïve patients with lung cancer who underwent targeted next-generation sequencing (NGS) testing was screened for EGFR p.G719X mutation. A multicenter cohort involving 68 EGFR p.G719X-mutant patients with advanced NSCLC and NGS profiling was retrospectively enrolled to evaluate clinical responses to afatinib (n = 37) and the third-generation EGFR-TKIs (n = 31). Ba/F3 cells stably expressing the EGFR p.G719A mutation were created to investigate the response to EGFR-TKIs in vitro. Results: Concurrent EGFR p.E709X mutations, being the most frequent co-occurring EGFR mutation in EGFR p.G719X-mutant NSCLC (∼30%), exerted a detrimental effect on outcomes in patients treated with third-generation EGFR-TKI [G719X/E709X vs. G719X; objective response rate (ORR): 0.00% vs. 47.62%, P < 0.001; mPFS: 7.18 vs. 14.2 months, P = 0.04, respectively]. Conversely, no significant difference was found in the treatment efficacy of afatinib between EGFR p.G719X/E709X and EGFR p.G719X patients (G719X/E709X vs. G719X; ORR: 71.43% vs. 56.67%, P = 0.99; mPFS: 14.7 vs. 15.8 months, P = 0.69, respectively). In vitro experiments elucidated a resistant drug sensitivity and poor inhibition of EGFR phosphorylation in Ba/F3 cells expressing EGFR p.G719A/E709K mutation upon the third-generation EGFR-TKI treatment. Conclusions: Co-occurring EGFR p.E709X mutation mediated primary resistance to the third-generation EGFR-TKIs in EGFR p.G719X-mutant patients but remained sensitive to afatinib. A personalized treatment strategy should be undertaken based on the coexisting EGFR p.E709X mutation status.
Background: Immunotherapy has exhibited efficacy in thymic carcinoma patients; however, there are insufficient data to confirm this efficacy in thymoma. The toxicity of immunotherapy also remains to be determined.Methods: The efficacy and safety of immunotherapy were analyzed in 11 thymoma patients who received PD‐1 inhibitors according to a range of relevant indexes including the objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and immunotherapy‐related adverse events.Results: The PFS and OS rates for all patients were 12.8 and 56.5 months, respectively. No difference in efficacy was detected between monotherapy and combination therapy (PFS: 12.8 vs 2.2 months, P = 0.787; OS: 73.8 vs 56.5 months, P = 0.367). The ORRs and DCRs for all patients were 27.3% and 90.9%, respectively. The incidence of adverse events was 45.5% among the 11 thymoma patients, including immune‐related myocarditis (36.4%), immune‐related liver damage (18.2%), and myasthenia gravis (18.2%). In the whole cohort of patients, the rate of adverse events of grade 3 or higher was 36.4%. The rates of adverse events of grade 3 or 4 in B3‐type and non‐B3‐type thymoma patients were 0% and 62.5%, respectively.Conclusions: Immunotherapy elicited a response in thymoma patients; however, more attention should be paid to the immune‐related adverse events.
The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.