78 Exploratory radiomics analysis in unresectable hepatocellular carcinoma treated with durvalumab alone or combined with tremelimumab or bevacizumab

Background The Phase 2 Study 22 [ NCT02519348] demonstrated the efficacy of durvalumab alone (D) or combined with tremelimumab (D+T) or bevacizumab (D+B) in unresectable hepatocellular carcinoma (HCC).1 2 We analyzed baseline and end-of-treatment (EOT) abdominal CT scans to explore associations between image features and clinical outcomes, including overall survival (OS), progression-free survival (PFS), and lesion-specific responses.Methods Arterial phase CTs from 124 patients, free of artifacts, were reviewed; measurable HCC lesions (>10 mm) and entire liver were delineated by radiologists. Radiomic features from tumor, peri-tumoral regions, and liver were extracted.OS and PFS were modeled using Cox regression with baseline radiomic features of liver or lesions. Performances were reported as concordance index (c-index).For patients with measurable tumors at both baseline and EOT, individual lesion response was defined by volumetric change (growing/shrinking) and exponential decay/growth rates were estimated. Multivariate mixed-effect models were assessed to create a classification model (60-40 train-test split) to distinguish growing/shrinking lesions using baseline radiomic features of lesions, with performance reported as AUC.Results Among 124 patients, 93 (SR-1) had measurable tumors with 490 lesions at baseline; 31 (SR-2) were determined not measurable or ‘diffuse’. Median tumor burdens were 112 cm 3 (D, n=39), 66 cm3 (D+T, n=32), and 39 cm3 (D+B, n=22).OS was shorter for SR-2 than SR-1 for D and D+T (424 and 217 days respectively), with a similar trend observed for B+D. Univariate analysis identified eight liver-based radiomic features associated with SR-2.A survival model using liver radiomic features had a c-index of 0.61 (124 patients, 3-fold cross-validation), surpassing lesion-based OS models. For PFS, the best performance was achieved using radiomic features of the largest lesion (c-index=0.62, SR-1).In 57 patients from SR-1 with suitable EOT scan, 298 lesions were tracked. Combination therapy yielded a higher tumor decay rate than D-monotherapy, with similar growth-rates for non-responding lesions across treatments. In responding lesions, median tumor half-life decreased from ~670 days to ~215 days (combination arms). A baseline mixed-effects model achieved AUC of 0.86 in lesion response classification.Conclusions Deep lesion level analyses revealed the impact of combination therapy in shrinking lesions, complementing RECIST assessment. High-throughput radiomic detection of the negative prognostic feature ‘diffuse’ appears feasible. For immunotherapy response/resistance, baseline radiomic features may predict OS, PFS, lesion-level outcome and could be utilized to identify candidate features. Limitations include sample size and potential overfitting, requiring validation in a larger cohort.Acknowledgements Image quality control, radiology reads, segmentations, and statistical analysis was performed by Radiomics.bioTrial Registration ClinicalTrials.gov identifier: NCT02519348References Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, et al. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I/II study. J Clin Oncol 2021;39:2991-3001.Lim HY, Heo J, Kim T-Y, Tai WMD, Kang Y-K, Lau G, et al. Safety and efficacy of durvalumab plus bevacizumab in unresectable hepatocellular carcinoma: results from the phase 2 study 22 (NCT02519348). J Clin Oncol 2022; 40: abs 436.Ethics Approval This open-label, phase I/II study was conducted at 19 sites in nine countries (ClinicalTrials.gov identifier: NCT02519348) according to the Declaration of Helsinki. All patients provided written informed consent. Protocol approval was obtained from institutional review boards or ethics committees at each site.

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