Search

Background: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical., Methods: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety., Findings: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1 + PD-1 + CD8 + stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3)., Conclusions: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation., Funding: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL)., Competing Interests: Declaration of interests Y. Lu has an invited speaker/project lead/principal investigator role with Roche, AstraZeneca, and BeiGene and an invited speaker role with Pfizer, Merck Sharp & Dohme, and Bristol-Myers Squibb. L.Z., Y. Zhang, M.H., Y.G., Y. Liu, J.Z., and B.Z. have an invited investigator role with Roche. J.S., C.X., H.W.,(9) L. Wu, Z. Yuan, N.B., M.F., and Yaping Xu have an invited principal investigator role with Roche., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Metachronous second primary lung cancer (MSPLC) is not that rare but is seldom studied., Objective: We aim to compare real-world survival outcomes between different surgery strategies and radiotherapy for MSPLC., Methods: This retrospective study analyzed data collected from patients with MSPLC between 1988 and 2012 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) analyses and machine learning were performed to compare variables between patients with MSPLC. Survival curves were plotted using the Kaplan-Meier method and were compared using log-rank tests., Results: A total of 2451 MSPLC patients were categorized into the following treatment groups: 864 (35.3%) received radiotherapy, 759 (31%) underwent surgery, 89 (3.6%) had surgery plus radiotherapy, and 739 (30.2%) had neither treatment. After PSM, 470 pairs each for radiotherapy and surgery were generated. The surgery group had significantly better survival than the radiotherapy group (P<.001) and the untreated group (563 pairs; P<.001). Further analysis revealed that both wedge resection (85 pairs; P=.004) and lobectomy (71 pairs; P=.002) outperformed radiotherapy in overall survival for MSPLC patients. Machine learning models (extreme gradient boosting, random forest classifier, adaptive boosting) demonstrated high predictive performance based on area under the curve (AUC) values. Least absolute shrinkage and selection operator (LASSO) regression analysis identified 9 significant variables impacting cancer-specific survival, emphasizing surgery's consistent influence across 1 year to 10 years. These variables encompassed age at diagnosis, sex, year of diagnosis, radiotherapy of initial primary lung cancer (IPLC), primary site, histology, surgery, chemotherapy, and radiotherapy of MPSLC. Competing risk analysis highlighted lower mortality for female MPSLC patients (hazard ratio [HR]=0.79, 95% CI 0.71-0.87) and recent IPLC diagnoses (HR=0.79, 95% CI 0.73-0.85), while radiotherapy for IPLC increased mortality (HR=1.31, 95% CI 1.16-1.50). Surgery alone had the lowest cancer-specific mortality (HR=0.83, 95% CI 0.81-0.85), with sublevel resection having the lowest mortality rate among the surgical approaches (HR=0.26, 95% CI 0.21-0.31). The findings provide valuable insights into the factors that influence cumulative cancer-specific mortality., Conclusions: Surgical resections such as wedge resection and lobectomy confer better survival than radiation therapy for MSPLC, but radiation can be a valid alternative for the treatment of MSPLC., (©Yue Zheng, Ailin Zhao, Yuqi Yang, Laduona Wang, Yifei Hu, Ren Luo, Yijun Wu. Originally published in JMIR Cancer (https://cancer.jmir.org), 12.06.2024.)