5MO - Novel radiologic phenotypes of chaotic tumor angiogenesis associated with poor ICI outcomes in NSCLC

Background

VEGF and immune checkpoint inhibitor (ICI) combination treatments have recently shown efficacy in non-small cell lung cancer (NSCLC), highlighting the role of tumor vasculature in outcomes. Conventional biomarkers focus on genetic or immune factors, but overlook the vascular complexity of tumors. We discovered two Imaging Tumor Angiogenesis Phenotypes (ITAP) in patients with advanced NSCLC associated with overall survival (OS) and progression-free survival (PFS).

Methods

We have developed a suite of proven, interpretable Quantitative Vessel Tortuosity (QVT) metrics quantifying tumor vascular complexity (twistedness, volume, curvature and branching) via radiology. We extracted 577 QVT features from CT scans prior to ICI monotherapy of a cohort of 406 patients with advanced NSCLC. Phenotypes were discovered using unsupervised dimensionality reduction (t-SNE) and clustering (k-means). Phenotypes were tested for outcome associations and independence from clinical variables in a subset of 186 patients.

Results

We identified two discrete outcome-associated phenotypes of tumor vascularity: ITAP-High was characterized by chaotic vascular shape: increased tumor vessel torsion, curvature, volume and radius. ITAP-Low had fewer variations in vessel shape and size across the tumor vasculature. ITAP-High was significantly associated with adverse outcomes: OS (HR=1.6 (1.1-2.3), p=0.02) and PFS (HR=1.8 (1.3-2.5), p<0.005), independent of patient age, gender, histology, and PD-L1 expression (negative, low, high) in a multivariable evaluation.

Conclusions

Our findings suggest that tumor vascularity plays a critical role in NSCLC outcomes. We introduce a unique and non-invasive biomarker approach that could assist in identifying patients eligible for ICI/VEGF dual agents, and improve monitoring. Further studies are needed to explore associations between these phenotypes and response to combined therapies.

Legal entity responsible for the study

Picture Health, Inc.

Funding

Picture Health Inc.

Disclosure

V. Velcheti: Financial Interests, Personal, Advisory Board: Picture Health. R. Chitalia: Financial Interests, Personal, Full or part-time Employment: Picture Health; Financial Interests, Personal, Stocks or ownership: Picture Health. C. Leibowitz: Financial Interests, Personal, Financially compensated role: Picture Health. K. Zhang: Financial Interests, Personal, Full or part-time Employment: Picture Health; Financial Interests, Personal, Stocks or ownership: Picture Health; Financial Interests, Personal, Stocks/Shares: Sirona Medical. A. Madabhushi: Financial Interests, Personal, Stocks/Shares: Picture Health; Financial Interests, Personal, Stocks or ownership: Picture Health. N. Braman: Financial Interests, Personal, Financially compensated role: Picture Health; Financial Interests, Personal, Stocks or ownership: Picture Health; Financial Interests, Personal, Stocks/Shares: Tempus AI.