Background: Although out-of-field radiation doses are lower than in-field doses, they may still contribute to late toxicities and second cancer risk in classical Hodgkin lymphoma (cHL) patients. Moreover, treatment planning systems (TPS) often underestimate these doses, especially in healthy tissues.

Methods: Dosimetric parameters were compared between pencil beam scanning proton therapy (PBS) and volumetric modulated arc therapy (VMAT) in a cohort of 20 patients from the PRO-Hodgkin study. Planning CT scans were reconstructed into virtual whole-body CTs using the IS²aR software. Out-of-field doses were estimated with analytical models and Monte Carlo simulations in whole-body phantoms, then integrated with TPS in-field doses to calculate total equivalent dose. Dose distributions, dose–volume histograms (DVHs), non-target tissue integral dose equivalent (NTIHs), mean organ doses, and lifetime attributable risks of Second cancer (LARs) were evaluated for critical healthy tissues.

Results: PBS consistently resulted in lower out-of-field doses than VMAT. In both modalities, contributions were relatively small, not exceeding 5% of the prescribed dose. For organs near the target such as thyroid, lungs, breasts, heart, and esophagus, mean dose differences between PBS and VMAT ranged from 1.3 to 4.5 Sv, while for distant organs differences remained below 0.3 Sv. Incorporating out-of-field doses into LAR estimates increased predicted risks, but PBS reduced these values by up to 40% compared to VMAT.

Conclusion: The radiation burden in high-precision radiotherapy, particularly from out-of-field radiation, should be accounted for in epidemiological studies and incorporated into treatment planning optimization to minimize second cancer risks in cHL patients.