Abstract 175P
Background
EA5163 is a phase 3 randomized trial investigating first-line mono immunotherapy (IO) or IO with chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous work has retrospectively validated a CT based radiomic signature of tumor associated quantitative vessel tortuosity (QVT) for prognosticating outcomes in IO treated NSCLC (Alilou et al. Sci Adv 2022 ). In this study, we report initial results of evaluating QVT in assessing IO related treatment changes in EA5163, specifically associating changes in QVT (Δ-QVT) with changes in tumor volume (Δ-TV) between baseline (B) and 6 week post-treatment scans (TP1).
Methods
CT scans from 29 patients enrolled in EA5163 with measurable lung lesions at B and TP1 were included. Vasculature was automatically segmented in a 25mm region around manually annotated tumors in CT using MATLAB R2022b. 84 QVT features measuring tortuosity, curvature and angle statistics were extracted. No information on outcomes, survival, or treatment arm assignment was available due to the ongoing nature of the trial. Spearman correlation and false discovery rate corrected p-values were computed to associate Δ-QVT with Δ-TV in an unsupervised setting. A risk score (QRS) was generated as the output of a classifier previously trained on 5 Δ-QVT features prognostic of RECIST v1.1 response.
Results
14 Δ-QVT features were significantly (p<0.05) correlated with Δ-TV with an absolute range of 0.45 and 0.76. 4 features in the QRS signature were significantly correlated with Δ-TV (Table). QRS based stratification showed net decrease in TV in low risk patients, whereas a net increase in high-risk patients at TP 1 (p<0.001). The Δ-QVT features were not associated with baseline tumor volume. Table: 175P
Feature | Correlation | p-value |
Vessel volume | 0.71 | <0.001 |
1st bin of tortuosity histogram | 0.65 | 0.002 |
12th bin of angles histogram | 0.61 | 0.004 |
2nd bin of curvature histogram | 0.65 | 0.002 |
Vessel volume to tumor volume ratio | -0.48 | 0.053 |
Conclusions
This study demonstrated an association between CT derived radiomic biomarker Δ-QVT and Δ-TV in an ongoing prospective clinical trial. Validation of these results upon interim analyses or trial completion is warranted.
Clinical trial identification
NCT03793179.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study was coordinated by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under the following award numbers: U10CA180820, U10CA180794, UG1CA233234, UG1CA233270, and UG1CA233247. This study was also supported by an NCI grant NIH 1 R01CA257612-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Disclosure
V. Velcheti: Financial Interests, Personal, Advisory Board: ITeos Therapeutics, Bristol Myers Squibb, Merck, AstraZeneca/MedImmune, GSK, Amgen, Elevation Oncology, Merus, Taiho Oncology; Financial Interests, Institutional, Research Funding: Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantWorks, Genoptix, Altor BioScience, Merck, Bristol Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GSK. A. Gupta: Financial Interests, Personal, Other, Consultancy for future development of AI tools on chest radiographs: GE Healthcare; Financial Interests, Personal, Stocks/Shares, Own shares of the company presently valued at 56 dollars: Picture Health; Financial Interests, Institutional, Funding, Research support for ongoing AI projects around chest radiography: GE Healthcare. S.S. Ramalingam: Financial Interests, Personal, Other, Editor in Chief, Cancer journal: American Cancer Society; Financial Interests, Research Grant: Merck, AstraZeneca, Advaxis, BMS, Amgen, Takeda, Genmab, GSK. K. Kelly: Financial Interests, Personal, Royalties, Primary reviewer for the small cell lung cancer chapter: UPTODATE. H. Borghaei: Financial Interests, Personal, Advisory Board: BMS, Genentech, Eli Lilly, Merck, EMD-serono, AstraZeneca, Novartis, Genmab, Regeneron, Amgen, Takeda, PharmaMar, Jazz Pharma, Mirati, Daiichi, Guardant, Natera, Oncocyte, BeiGene, iTeo, Boehringer Ingelheim, Puma, BerGenbio, Janssen; Financial Interests, Personal, Other, Training discussion: Pfizer; Financial Interests, Personal, Other, DSMB: Novartis; Financial Interests, Institutional, Other, Clinical trial support: BMS, Amgen; Financial Interests, Personal, Stocks/Shares, Options for scientific advisory role: Sonnetbio; Financial Interests, Personal, Stocks/Shares, Options for scientific advisory board: Nucleai, Inspira (Rgenix); Financial Interests, Institutional, Trial Chair, Investigator initiated trial support: BMS; Financial Interests, Institutional, Coordinating PI, Investigator initiated trial support: Amgen, Lilly; Financial Interests, Personal and Institutional, Trial Chair, Chair steering committee: Miratti; Financial Interests, Personal and Institutional, Steering Committee Member: Amgen, AstraZeneca; Financial Interests, Personal, Steering Committee Member, Also trial support: BMS; Other, DSMB: Novartis, Takeda, Incyte, Springworks. A. Madabhushi: Financial Interests, Personal, Advisory Board, Serve on SAB and consult: SimbioSys; Financial Interests, Personal, Advisory Board: Aiforia, Picture Health; Financial Interests, Personal, Full or part-time Employment: Picture Health; Financial Interests, Personal, Ownership Interest: Picture Health, Elucid Bioimaging, Inspirata Inc; Financial Interests, Personal, Royalties: Picture Health, Elucid Bioimaging; Financial Interests, Institutional, Funding: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly. All other authors have declared no conflicts of interest.
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