Talal El Zarif

Background: There is limited data on immune checkpoint inhibitor (ICI) use in patients with non-small cell lung cancer (NSCLC) and known pericardial effusions. Methods: This international multi-center observational retrospective study included patients with advanced NSCLC with or without pericardial effusions receiving ICIs. Immune-related adverse events (irAEs) were graded per CTCAE v5.0. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Cox proportional hazards multivariable models assessed the association between survival outcomes and clinicopathologic variables, and an inverse probability of treatment weighting (IPTW) model compared outcomes between the two groups. Results: A total of 1248 patients with advanced NSCLC treated with ICIs across 13 institutions were included. Of these, 85 patients (6.8%) had pre-existing pericardial effusions. Compared to controls, patients with pericardial effusions were younger (median age 63 vs 67 years, P = .007), diagnosed more frequently with PD-L1 positive tumors (96% vs 76%, P < .001), and had a higher median number of baseline metastatic sites (3 vs 1, P < .001). IrAEs were similar between both groups (42% vs 38%), and no cardiac irAEs occurred in patients with pericardial effusions. PFS (median 5.6 vs 4.6 months, P = .3) and OS (median 10.2 vs 14.7 months, P = .50) were not statistically different between patients with pericardial effusions and the controls, respectively. In both multivariable and IPTW models, pericardial effusions were not associated with PFS or OS. Conclusions: Among patients with NSCLC and pre-existing pericardial effusions, ICIs demonstrate meaningful clinical benefit similar to those without effusions, with no new cardiac or severe toxicities.

Supplementary Table S5. Top TFs by clique enrichment score (CES) in basal-squamous and luminal BLCA samples.

Supplementary Figure S2. Heatmap of BLCA sample clustering based on H3K27ac data.

Supplementary Figure S5. Sample-level allele fraction at top 100 most imbalanced SNPs. C0: luminal, C1: basal-squamous.

Supplementary Table S11. CWAS hits and contribution to bladder cancer risk.

Supplementary Table S6. MARGE regulatory potential scores for basal-squamous and luminal BLCA samples.

Supplementary Table S1. Clinical and tumor characteristics for 28 patients with bladder or upper tract carcinoma included in the analysis.

Supplementary Figure S4. CRISPR dependency scores of nominated luminal and basal-squamous master TFs based on the DepMap dataset.

Supplementary Table S4. Top TFs by CaCTS score in basal-squamous and luminal BLCA samples.

Supplementary Figure S9. Overall survival in the bladder cancer TCGA cohort by UGT1A10 and SPINK1 expression (top vs. bottom quartiles shown).