⭐️ABSTRACT 8052: NIBIT-EPI-MESO study ❓Can methylation profiling identify which pts with malignant pleural mesothelioma (MPM) may respond favorably to immunotherapy? 1⃣Unsupervised methylation profiling of 83 samples identified four MPM subsets: (1) Demethylated (DEM), (2) Low, (3) Intermediate (INT), and (4) CpG island methylator phenotype (CIMP). 2⃣LOW/DEM methylation subtypes were enriched among responder (R) pts and INT/CIMP were enriched among non-responders (p =0.002) 3⃣Most fascinating (to me) was no association with histologic subtype (p=0.33). Based on Checkmate-743 [image below] would have expected sarcomatoid subtype to be heavily susceptible to a response. 4⃣Few key limitations: - Retrospective - Small functional TME subset (n=35) - Mixed ICI regimens (anti–CTLA-4 ± PD-1/PD-L1) complicate attribution of response 📋KEY POINT: I LOVE the idea of using immune-based classifiers (in this case methylation based) to develop strategies to determine who will benefit with ICI among patients with MPM (9/13) 🔗Checkmate-743: pubmed.ncbi.nlm.nih.gov/3348… @lcsmchat @OncoAlert @OncLive @Lung_Cancers @Onco_Nexus @LungCancerRx @LungCancerEu @MedwatchKate

⭐️ABSTRACT 8010: Air Pollution and Risk of Lung Cancer 📔The seminal 2023 @Nature paper showed a significant association in environmental particulate matter measuring ≤2.5 μm (PM2.5) and risk for #EGFR #NSCLC. 1⃣This large NCDB analysis (>1 million pts) suggests chronic PM₂.₅ exposure is associated with more advanced lung cancer findings 2⃣Key findings: - Each standard deviation increase in PM₂.₅ → ~5% higher odds of stage III/IV disease -In multipollutant models, PM₂.₅ remained significant (OR = 1.062, 95% CI: 1.047–1.076; p , 0.001), with combined pollution burden linked to a 3.1% increase in odds (95% CI: 1.5–4.7%; p , 0.001). 3⃣Caveats: -The study cannot distinguish if air pollution accelerates tumor progression (plausible) OR if air pollution here is linked with other determinants of care (smoking prevalence, occupational exposure, health care access) -No smoking pack year data? I understand the problems and recall biases associated with getting smoking level data, but seems like it would be important. -Ecologic exposure fallacy (county-level pollution ≠ individual exposure or risk) 📋KEY POINT: Emerging and ongoing population level data suggests link between air pollution and lung cancer risk. 😡RANT: We need more investment into these type of studies, to truly parse out these signals. This can only happen with funding. Sadly we are lacking vision, competence, and expertise from our elected officials and from our health care administration. (12/13) @lcsmchat @OncoAlert @OncLive @Lung_Cancers @Onco_Nexus @LungCancerRx @LungCancerEu @MedwatchKate @YoungLungCancer @DrCatharineY