Generalized approach for radiotherapy treatment planning by optimizing projected health outcome: preliminary results for prostate radiotherapy patients.

Research in cancer care increasingly focuses on survivorship issues, e.g. managing disease- and treatment-related morbidity and mortality occurring during and after treatment. This necessitates innovative approaches that consider treatment side effects in addition to tumor cure. Current treatment-planning methods rely on constrained iterative optimization of dose distributions as a surrogate for health outcomes. The goal of this study was to develop a generally applicable method to directly optimize projected health outcomes. We developed an outcome-based objective function to guide selection of the number, angle, and relative fluence weight of photon and proton radiotherapy beams in a sample of ten prostate-cancer patients by optimizing the projected health outcome. We tested whether outcome-optimized radiotherapy (OORT) improved the projected longitudinal outcome compared to dose-optimized radiotherapy (DORT) first for a statistically significant majority of patients, then for each individual patient. We assessed whether the results were influenced by the selection of treatment modality, late-risk model, or host factors. The results of this study revealed that OORT was superior to DORT. Namely, OORT maintained or improved the projected health outcome of photon- and proton-therapy treatment plans for all ten patients compared to DORT. Furthermore, the results were qualitatively similar across three treatment modalities, six late-risk models, and 10 patients. The major finding of this work was that it is feasible to directly optimize the longitudinal (i.e. long- and short-term) health outcomes associated with the total (i.e. therapeutic and stray) absorbed dose in all of the tissues (i.e. healthy and diseased) in individual patients. This approach enables consideration of arbitrary treatment factors, host factors, health endpoints, and times of relevance to cancer survivorship. It also provides a simpler, more direct approach to realizing the full beneficial potential of cancer radiotherapy.