The influence of cardiac substructure dose on survival in a large lung cancer stereotactic radiotherapy cohort using a robust personalized contour analysis.

Background/purpose: Radiation-induced cardiac toxicity in lung cancer patients has received increased attention since RTOG 0617. However, large cohort studies with accurate cardiac substructure (CS) contours are lacking, limiting our understanding of the potential influence of individual CSs. Here, we analyse the correlation between CS dose and overall survival (OS) while accounting for deep learning (DL) contouring uncertainty, $\alpha \text{/}\beta$ uncertainty and different modelling approaches.

Materials/methods: This single institution, retrospective cohort study includes 730 patients (early-stage tumours (I or II). All treated: 2009-2019), who received stereotactic body radiotherapy (≥ 5 Gy per fraction). A DL model was trained on 70 manually contoured patients to create 12 cardio-vascular structures. Structures with median dice score above 0.8 and mean surface distance (MSD) <2 mm during testing, were further analysed. Patientspecific CS dose was used to find the correlation between CS dose and OS with elastic net and random survival forest models (with and without confounding clinical factors). The influence of delineation-induced dose uncertainty on OS was investigated by expanding/contracting the DL-created contours using the MSD ± 2 standard deviations.

Results: Eight CS contours met the required performance level. The left atrium (LA) mean dose was significant for OS and an LA mean dose of 3.3 Gy (in EQD2) was found as a significant dose stratum.

Conclusion: Explicitly accounting for input parameter uncertainty in lung cancer survival modelling was crucial in robustly identifying critical CS dose parameters. Using this robust methodology, LA mean dose was revealed as the most influential CS dose parameter.