Automatic Quantification of Serial PET/CT Images for Pediatric Hodgkin Lymphoma Patients Using a Longitudinally-Aware Segmentation Network

$\textbf{Purpose}$: Automatic quantification of longitudinal changes in PET scans for lymphoma patients has proven challenging, as residual disease in interim-therapy scans is often subtle and difficult to detect. Our goal was to develop a longitudinally-aware segmentation network (LAS-Net) that can quantify serial PET/CT images for pediatric Hodgkin lymphoma patients. $\textbf{Materials and Methods}$: This retrospective study included baseline (PET1) and interim (PET2) PET/CT images from 297 patients enrolled in two Children's Oncology Group clinical trials (AHOD1331 and AHOD0831). LAS-Net incorporates longitudinal cross-attention, allowing relevant features from PET1 to inform the analysis of PET2. Model performance was evaluated using Dice coefficients for PET1 and detection F1 scores for PET2. Additionally, we extracted and compared quantitative PET metrics, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in PET1, as well as qPET and $\Delta$SUVmax in PET2, against physician measurements. We quantified their agreement using Spearman's $\rho$ correlations and employed bootstrap resampling for statistical analysis. $\textbf{Results}$: LAS-Net detected residual lymphoma in PET2 with an F1 score of 0.606 (precision/recall: 0.615/0.600), outperforming all comparator methods (P<0.01). For baseline segmentation, LAS-Net achieved a mean Dice score of 0.772. In PET quantification, LAS-Net's measurements of qPET, $\Delta$SUVmax, MTV and TLG were strongly correlated with physician measurements, with Spearman's $\rho$ of 0.78, 0.80, 0.93 and 0.96, respectively. The performance remained high, with a slight decrease, in an external testing cohort. $\textbf{Conclusion}$: LAS-Net achieved high performance in quantifying PET metrics across serial scans, highlighting the value of longitudinal awareness in evaluating multi-time-point imaging datasets.