Linear energy transfer optimized proton therapy for rectal cancer

Area of Science:

• Radiation Oncology
• Medical Physics
• Preclinical Cancer Research

Background:

• Proton therapy offers potential advantages in dose distribution for cancer treatment.
• Linear Energy Transfer (LET) varies within proton beams and can influence biological effects.
• Optimizing LET in treatment planning may enhance therapeutic outcomes.

Purpose of the Study:

• To assess the feasibility and utility of an LET-optimized proton planning algorithm for locally advanced rectal cancer.
• To determine if LET optimization improves efficacy and reduces toxicity in preclinical models.

Main Methods:

• Five rectal cancer patients' plans were re-optimized using an LET-optimization algorithm.
• Dosimetric endpoints were evaluated, comparing LET-optimized plans to standard proton plans.
• Preclinical in vitro and in vivo models assessed tumor efficacy and normal tissue toxicity using comparable LET ranges.

Main Results:

• LET-optimized plans increased dose-averaged LET (LETd) and LET-weighted dose in the gross tumor volume (GTV).
• Target coverage (CTV V100%) was maintained or improved, with reduced dose to bladder and small bowel.
• Preclinical models showed increased tumor efficacy and decreased small bowel toxicity.

Conclusions:

• LET-optimized proton plans are feasible, improving LET in the GTV while maintaining target coverage and organ-at-risk sparing.
• Preclinical data suggest LET optimization can enhance tumor efficacy and reduce normal tissue toxicity in rectal cancer treatment.