Retrospective analysis and IMRT replanning of a 3D-CRT murine dose painting study for preclinical oxygen-guided radiotherapy

A recent parallel-opposed 3D-conformal radiotherapy (3D-CRT) study in mice compared dose escalation (boost) in hypoxic (pO2 ≤ 10 torr) and non-hypoxic tumor subvolumes. They found a hypoxic boost led to significantly greater (p < 1e-4) tumor control probability than an equivalent non-hypoxic boost. We imported imaging and treatment data from this study for 31 SCC7 squamous carcinoma murine leg tumor cases-16 hypoxic boost and 15 non-hypoxic boost plans into a commercial treatment planning system for preclinical radiotherapy. Treatments were retrospectively recalculated with a fast Monte Carlo dose engine. We replanned cases with 3-field IMRT using an analogous uncertainty budget as 3D-CRT. Comparing both treatment groups, the hypoxic boost treatments had a significantly higher hypoxic fraction receive the boost prescription as planned in 3D-CRT (p < 1e-4) and IMRT (p < 1e-4). Surprisingly, retrospective 3D-CRT non-hypoxic boost treatments had a significantly lower non-hypoxic fraction receive the boost prescription (p < 1e-4). 3D-CRT non-hypoxic boost also substantially underdosed the entire tumor between 48-68 Gy compared to the "equivalent" hypoxic boost. In IMRT, the non-hypoxic volume receiving boost prescription was significantly higher in the non-hypoxic boost (p = 0.0215) and dosing in the entire tumor was identical between boost groups. This study displays IMRT's potential to advance the quality of preclinical dose painting studies.