Probabilistic Proton Treatment Planning: a novel approach for optimizing underdosage and overdosage probabilities of target and organ structures

Treatment planning uncertainties are typically managed using margin-based or robust optimization. Margin-based methods expand the clinical target volume (CTV) to a planning target volume, generally unsuited for proton therapy. Robust optimization considers worst-case scenarios, but its quality depends on the uncertainty scenario set: excluding extremes reduces robustness, while too many make plans overly conservative. Probabilistic optimization overcomes these limits by modeling a continuous scenario distribution. We propose a novel probabilistic optimization approach that steers plans toward individualized probability levels to control CTV and organs-at-risk (OARs) under- and overdosage. Voxel-wise dose percentiles ($d$) are estimated by expected value ($E$) and standard deviation (SD) as $E[d] \pm δ\cdot SD[d]$, where $δ$ is iteratively tuned to match the target percentile given Gaussian-distributed setup (3 mm) and range (3%) uncertainties. The method involves an inner optimization of $E[d] \pm δ\cdot SD[d]$ for fixed $δ$, and an outer loop updating $δ$. Polynomial Chaos Expansion (PCE) provides accurate and efficient dose estimates during optimization. We validated the method on a spherical CTV abutted by an OAR in different directions and a horseshoe-shaped CTV surrounding a cylindrical spine. For spherical cases with similar CTV coverage, $P(D_{2\%} > 30 Gy)$ dropped by 10-15%; for matched OAR dose, $P(D_{98\%} > 57 Gy)$ increased by 67.5-71%. In spinal plans, $P(D_{98\%} > 57 Gy)$ increased by 10-15% while $P(D_{2\%} > 30 Gy)$ dropped 24-28%. Probabilistic and robust optimization times were comparable for spherical (hours) but longer for spinal cases (7.5 - 11.5 h vs. 9 - 20 min). Compared to discrete scenario-based optimization, the probabilistic method offered better OAR sparing or target coverage depending on the set priorities.