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Background : We aimed to evaluate the prognostic value of imaging biomarkers on 18F-FDG PET/CT in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing first-line chemo-immunotherapy. Methods: In this multicenter and retrospective study, we considered two cohorts, depending on the type of first-line therapy: chemo-immunotherapy (CIT) versus chemotherapy alone (CT). All patients underwent baseline 18-FDG PET/CT before therapy between June 2016 and September 2021. We evaluated clinical, biological, and PET parameters, and used cutoffs from previously published studies or predictiveness curves to assess the association with progression-free survival (PFS) or overall survival (OS) with Cox prediction models. Results: Sixty-eight patients were included (CIT: CT) (36: 32 patients). The median PFS was 5.9:6.5 months, while the median OS was 12.1:9.8 months. dNLR (the derived neutrophils/(leucocytes-neutrophils) ratio) was an independent predictor of short PFS and OS in the two cohorts ( p < 0.05). High total metabolic tumor volume (TMTV high if > 241 cm 3 ) correlated with outcomes, but only in the CIT cohort (PFS for TMTV high in multivariable analysis: HR 2.5; 95%CI 1.1-5.9). Conclusion: Baseline 18F-FDG PET/CT using TMTV could help to predict worse outcomes for ES-SCLC patients undergoing first-line CIT. This suggests that baseline TMTV may be used to identify patients that are unlikely to benefit from CIT.

Background : The National Lung Screening Trial (NLST) and NELSON study opened the debate on the relevance of lung cancer (LC) screening in subjects exposed to occupational respiratory carcinogens. This analysis reported the incremental cost-effectiveness ratios (ICER) of an organized LC screening program for an asbestos-exposed population. Methods: Using Markov modelization, individuals with asbestos exposure were either monitored without intervention or annual low-dose thoracic computed-tomography (LDTCT) scan LC screening. LC incidence came from a prospective observational cohort of subjects with occupational asbestos exposure. The intervention parameters were those of the NLST study. Utilities and LC-management costs came from published reports. A sensitivity analysis evaluated different screening strategies. Results: The respective quality-adjusted life year (QALY) gain, supplementary costs and ICER [95% confidence interval] were: 0.040 [0.010-0.065] QALY, 6900 [3700-11,800] € and 170,000 [75,000-645,000] €/QALY for all asbestos-exposed subjects; and 0.144 [0.071-0.216] QALY, 13,000 [5700-26,800] € and 90,000 [35,000-276,000] €/QALY for smokers with high exposure. When screening was based on biennial LDTCT scans, the ICER was 45,000 [95% CI: 15,000-116,000] €/QALY. Conclusions: Compared to the usual ICER thresholds, biennial LDTCT scan LC screening for smokers with high occupational exposure to asbestos is acceptable and preferable to annual scans.

Brigatinib is a next-generation ALK inhibitor (ALKi) that shows efficacy in ALK inhibitor naïve and post-crizotinib ALK+ advanced NSCLCs (aNSCLCs). The efficacy of brigatinib was retrospectively assessed in patients with aNSCLCs included in the brigatinib French Early-Access Program (1 August 2016−21 January 2019). The primary endpoint was investigator-assessed progression-free survival (invPFS) and the primary analysis was updated in 2021 with a longer follow-up, focused on post-brigatinib lorlatinib efficacy. Sixty-six centers included 183 patients: median age 60 ± 12.7 years; 78.3% never/former smokers; median of 3 ± 1 previous lines and 2 ± 0.5 ALKis; 37.1% ECOG PS 2 and 55.6% >3 metastatic sites. The median follow-up from brigatinib initiation was 40.4 months (95% CI 38.4−42.4). InvPFS was 7.4 months (95% CI 5.9−9.6), median duration of treatment (mDOT) was 7.3 months (95% CI 5.8−9.4) and median overall survival (mOS) was 20.3 months (95% CI 15.6−27.6). The median DOT and OS from brigatinib initiation tend to decrease with the number of ALK inhibitors used in previous lines of therapy. Based on the data collected, 92 (50.3%) patients received ≥1 agent(s) post-brigatinib and 68 (73.9%) of them received lorlatinib, with 51 (75%) immediately receiving it post-brigatinib, 12 (17.6%) receiving it after one and 5 (7.4%) after ≥2 subsequent treatments. The median follow-up was 29.9 (95% CI 25.7−33.1) months. Lorlatinib mDOT was 5.3 (95% CI 3.6−7.6) months with a median OS from lorlatinib initiation of 14.1 (95% CI 10.3−19.2) months. The results of the brigALK2 study confirm the efficacy of brigatinib in a population of heavily pretreated ALK+ aNSCLC patients and provide new data on the activity of lorlatinib after brigatinib.

Backgrounds: Malignant pleural mesothelioma (MPM) is a cancer with poor prognosis. Second-line and onward therapy has many options, including immune-checkpoint inhibitors with demonstrated efficacy: 10−25% objective response rate (ORR) and 40−70% disease-control rate (DCR) in clinical trials on selected patients. This study evaluated real-life 2L+ nivolumab efficacy in MPM patients and looked for factors predictive of response. Methods: This retrospective study included (September 2017−July 2021) all MPM patients managed in 11 French centers. Results: The 109 enrolled patients’ characteristics were: median age: 69 years; 67.9% men; 82.6% epithelioid subtype. Strictly, second-line nivolumab was given to 51.4%. Median PFS and OS were 3.8 (3.2−5.9) and 12.8 (9.2−16.4) months. ORR was 17/109 (15.6%); 34/109 patients had a stabilized disease (DCR 46.8%). Univariable analysis identified several parameters as significantly (p < 0.05) prognostic of OS [HR (95% CI)]: biphasic subtype: 3.3 (1.52−7.0), intermediate Lung Immune Prognostic Index score: 0.46 (0.22−0.99), progression on the line preceding nivolumab: 2.1 (1.11−3.9) and age > 70 years: 2.5 (1.5−4.0). Multivariable analyses retained only biphasic subtype: 3.57 (1.08−11.8) and albumin < 25 g/L: 10.28 (1.5−70.7) as significant and independent predictors. Conclusions: Second-line and onward nivolumab is effective against MPM in real life but with less effectiveness in >70 years. Ancillary studies are needed to identify the predictive factors.

Although organized, low-dose, computed-tomography (CT) scan lung-cancer screening has been shown to lower all-cause and lung-cancer-specific mortality, the primary cause of death for subjects eligible for such screening remains cardiovascular (CV) mortality. This meta-analysis study was undertaken to evaluate the impact of screening-scan-detected coronary artery calcifications (CACs) on CV and all-cause mortality. We conducted a systematic review and meta-analysis of studies reporting CV mortality according to the Agatson CAC score for participants in a lung-cancer screening program of randomized clinical or cohort studies. PubMed, Embase, and Cochrane databases were screened in June 2020. Two authors independently selected articles and extracted data. Six studies, including 20,175 subjects, were retained. CV and all-cause mortality rates were higher for subjects with CAC scores >0, with respective relative risks of 2.02 [95% CI 1.23-3.32] and 2.29 [95% CI 1.00-5.21]. Both mortality rates were even higher for those with high CAC scores (>400 or >1000). CACs are more common in men than in women, with an odds ratio of 1.49 [95% CI 1.40-1.59]. The presence of CAC is associated with CV mortality with an RR of 2.05 [95% CI 1.20-3.57] in men and 2.37 [CI 95% 1.29-5.09] in women, respectively. Analysis of lung-cancer-screening scans for CACs is a tool able to predict CV mortality. Prospective studies within those programs are needed to assess the benefit of primary CV prevention based on CAC detection.