Intratumor Heterogeneity Assessed by 18F-FDG PET/CT Predicts Treatment Response and Survival Outcomes in Patients with Hodgkin Lymphoma

Rationale and Objectives: Radiomic analysis of F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) images enables the extraction of quantitative information of intratumour heterogeneity. This study investigated whether the baseline F-18-FDG PET/CT radiomics can predict treatment response and survival outcomes in patients with Hodgkin lymphoma (HL). Materials and Methods: Thirty-five patients diagnosed with HL who underwent F-18-FDG PET/CT scans before and during chemotherapy were retrospectively enrolled in this investigation. For each patient, we extracted 709 radiomic features from pretreatment PET/CT images. Clinical variables (age, gender, B symptoms, bulky tumor, and disease stage) and radiomic signatures (intensity, texture, and wavelet) were analyzed according to response to therapy, progression-free survival (PFS), and overall survival (OS). Receiver operating characteristic curve, logistic regression, and Cox proportional hazards model were used to examine potential predictive and prognostic factors. Results: High-intensity run emphasis (HIR) of PET and run-length nonuniformity (RLNU) of CT extracted from gray-level run-length matrix (GLRM) in high-frequency wavelets were independent predictive factors for the treatment response (odds ratio [OR] = 36.4, p = 0.014; OR = 30.4, p = 0.020). Intensity nonuniformity (INU) of PET and wavelet short run emphasis (SRE) of CT from GLRM and Ann Arbor stage were independently related to PFS (hazard ratio [HR] = 9.29, p = 0.023; HR = 18.40, p = 0.012; HR = 7.46, p = 0.049). Zone-size nonuniformity (ZSNU) of PET from gray-level size zone matrix (GLSZM) was independently associated with OS (HR = 41.02, p = 0.001). Based on these factors, a prognostic stratification model was devised for the risk stratification of patients. The proposed model allowed the identification of four risk groups for PFS and OS (p < 0.001 and p < 0.001). Conclusion: HIR_GLRMPET and RLNU_GLRMCT in high-frequency wavelets serve as independent predictive factors for treatment response. ZSNU_GLSZMPET, INU_GLRMPET, and wavelet SRE_GLRMCT serve as independent prognostic factors for survival outcomes. The present study proposes a prognostic stratification model that may be clinically beneficial in guiding risk-adapted treatment strategies for patients with HL.