Abstract 5612: Shape features of extra-nodal lesions on positron emission tomography identifies responders to CAR-T-cell therapy

Abstract Background: Lymphoma is a common primary malignancy consisting of a heterogeneous collection of lymphoid neoplasms. Diffuse large B-cell lymphoma (DLBCL) is the most common, aggressive disease form that accounts for 30% of all lymphoma cases. The disease spreads systemically to involve organs other than lymph nodes 40% of the time, with 5-year survival of about 38% for intermediate grade disease. Recent development in chimeric antigen receptor (CAR) T-cell therapy has shown tremendous promise in providing a cure to patients with relapsed/refractory (R/R) DLBCL. We propose to develop an image-based biomarker to identify patients that would respond to engineer edcell-based treatments. Methods: We identified a cohort of 58 patients with R/R DLBCL, whose largest lesions on the baseline positron emission tomography/computed tomography (PET/CT) imaging were identified along with their anatomical sites related to non-lymphatics. The lesion’s co-registered PET imaging was used to converge on a regional boundary to obtain the most active part of the lesion, applying Standardized Uptake Value definition with 41% regional threshold. The lesion regions were characterized using imaging metrics (radiomics) broadly categorized into: Size (n=38), Shape (n=9), Texture (n=259),followed by principal component (PC) analysis to reduce the dimensionality in each of the feature categories. These Radiomics metrics along with whole body metabolic tumor volume (MTV) were used both collectively and independently to assess risk to disease progression measured by overall survival using Cox-regression model. We also compared the Radiomic metrics to MTV to identify linear dependency measured by Coefficient of Determination (R2). Results: PET scans shape features (extra nodal) that describes compactness to sphericity, represented as a principal component across the samples had a 21% increased risk to disease progression compared to 15% using MTV, with a CI of [1.0487, 1.417] and [1.04, 1.30] respectively. Patients have a median follow up of 1 year after CAR-T treatment. Shape-PC (Non-Lymph) lesions were not related to MTV with a correlation coefficient of 41.8% (R2 of 0.0725). Most non lymphatic lesions (top three sites) in our cohort were from lung, bone and liver. Patients with no non- lymphatic lesions were not part of this cohort. Conclusion: We identified Non-Size based features that are prognostic to patient response to treatment. These metrics provide complementary information to MTV and may serve as a surrogate to treatment response. Our features would require a secondary validation in a larger cohort prior to clinical use. Citation Format: Yoganand Balagurunathan, Zhouping Wei, Jin Qi, Erin Dean, Zachary Thompson, Jung Choi, Frederick Locke. Shape features of extra-nodal lesions on positron emission tomography identifies responders to CAR-T-cell therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5612.