Direct minimization of normal-tissue toxicity via an NTCP-based IMPT planning method

Intensity-modulated proton therapy (IMPT) planning often relies on physical dose constraints to balance tumor control and sparing of organs at risk (OARs). However, focusing solely on these dose objectives does not always minimize the normal-tissue toxicity, which is quantified as normal tissue complication probability (NTCP). NTCP is also a quantitative criterion for patient selection between proton and photon treatments.

This study introduces an NTCP-based IMPT planning (NTCP-IMPT) method designed to directly minimize normal-tissue toxicity while maintaining tumor coverage.

NTCP-IMPT simultaneously optimizes NTCP and dose-volume histogram (DVH)-based physical dose objectives while adhering to the minimum-monitor-unit (MMU) constraint for plan deliverability. The optimization problem is solved by the interior-point method. To assess its efficacy in reducing normal-tissue toxicity, NTCP-IMPT is compared with standard IMPT (without NTCP optimization) for four head-and-neck (HN) cancer patients in terms of physical dose quality and NTCP of xerostomia and dysphagia.

Across all four patients, NTCP-IMPT plans met target dose criteria (D_95% ≥ 100% and D_2% ≤ 110%) while maintaining maximum doses to the spinal cord and brainstem comparable to standard IMPT. NTCP-IMPT also reduced mean doses to parotid glands, submandibular glands, oral cavity, and pharyngeal constrictor muscles (PCMs). Compared to the standard IMPT, NTCP-IMPT achieved average reductions in NTCP for xerostomia (grade ≥ 2: 3.67%; grade ≥3: 1.07%) and dysphagia (grade ≥ 2: 7.54%; grade ≥ 3: 3.72%).

NTCP-IMPT effectively minimizes normal-tissue toxicity and improves the sparing of OARs associated with side effects while maintaining comparable tumor coverage compared to standard IMPT.