Real-life nationwide characteristics and outcomes of small cell lung cancer over the last 20 years: Impact of immunotherapy on overall survival in a real-life setting.

BACKGROUND: The KBP studies are real-life nationwide, prospective, multicenter cohort studies of patients diagnosed with primary lung cancer that have been conducted in French non-academic public hospitals each decade since 2000. METHODS: Patients were analyzed in three prospective cohorts using the same methodology. In this study, we describe and compare the characteristics and outcomes of patients with small cell lung cancer (SCLC), with a focus on treatments in the 2020 cohort. FINDINGS: 8999 patients with lung cancer were included in the 2020 cohort, of whom 1137 had SCLC. From 2000 to 2010 and 2020, the proportion of patients with SCLC decreased from 16.4 % to 13.5 % and 12.6 % respectively. Between 2000 and 2020, the proportion of women increased from 15.5 % to 35.7 %. 15.4 % of patients with SCLC had limited-stage (LS) disease and 84.6 % of patients had extensive-stage (ES) disease. The 1-year overall survival (OS) rate for all patients with SCLC increased from 34.4 % in 2000 to 38.4 % in 2020. For ES-SCLC, multivariate analysis weighted with "entropy balancing" by including age, sex, performance status, number of metastatic sites, and brain metastases indicated an improvement in median OS from 8.1 months in patients receiving chemotherapy only to 11.1 months in patients receiving chemotherapy plus immunotherapy (HR 0.62, p < 0.001). INTERPRETATION: The proportion with SCLC has decreased over time, but the proportion of women has increased. The 1-year OS rates have improved over 20 years. The KBP-2020 cohort suggests a benefit of immunotherapy on OS in patients with ES-SCLC in the real-life setting.

Multidrug resistance-associated protein (MRP1) is overexpressed in DNA aneuploid carcinomatous cells in non-small cell lung cancer (NSCLC).

Resistance to chemotherapy is intrinsically present in most nonsmall-cell lung carcinomas (NSCLC). No parameter has yet been determined to predict the response to chemotherapy. However, MRP1 (multidrug resistance-associated protein) is suspected to play an important role in resistance to treatment. The genetic basis for this resistance is not clearly understood, but it could result from chromosome reassortments catalyzed by aneuploidy. The aim of this study was to investigate MRP1 expression concurrently to DNA ploidy analysis in order to evaluate the link between MRP1 expression and chromosome 16 (MRP1 gene location) aberrations in NSCLC before treatment. Eighty-four surgical tumor specimens, 18 selected samples containing more than 80% of carcinomatous cells and 11 samples from normal bronchial epithelium were studied. Samples were stained by MRP1 FITC indirect staining and propidium iodide and analyzed by Flow Cytometry. Fifty tumors contained at least 1 DNA-aneuploid clone and the percentage of MRP1-positive cells was higher in DNA-aneuploid cells (p = 0.0003). All tumors expressed MRP1, but the level of expression was 3-fold higher in DNA-aneuploid cells than in DNA-diploid cells (normal bronchial cells as well as carcinomatous cells) (p < 0.0001). FISH analysis of 24 tumor imprints using a chromosome 16 alpha-satellite centromere probe demonstrated significantly more frequent gain of chromosome 16 in DNA-aneuploid tumors. These results suggest that MRP1 overexpression in NSCLC could be a consequence of chromosome 16 reassortments catalyzed by aneuploidy and that DNA-aneuploid tumors could require different treatment modalities from those applied to DNA-diploid tumors.