Clinical Evidence on Particle Radiation, DNA Damage Response Inhibitors, and Immunotherapy for Mismatch...

Area of Science:

• Radiation Oncology
• Immunotherapy
• Colorectal Cancer Research

Background:

• Systematic review of particle therapy, DDRi, and immunotherapy for pMMR colorectal cancer.
• Focus on clinical and preclinical literature from 2014-2025.

Purpose of the Study:

• To evaluate the efficacy and safety of particle therapy, DDRi, and immunotherapy in pMMR colorectal cancer.
• To identify gaps in clinical research for these combined treatment modalities.

Main Methods:

• Systematic literature review across major databases.
• Inclusion of studies on particle radiotherapy (proton, alpha, carbon) alone or combined with DDRi/ICI.
• Inclusion of X-ray radiotherapy (XRT) combined with DDRi/ICI.

Main Results:

• 133 studies included, 62 clinical.
• Particle therapies demonstrate excellent local control and tissue sparing with manageable toxicity.
• Few trials combine radiation with DDRi; ICI combinations show promise with XRT.

Conclusions:

• Particle radiation and DDRi have preclinical immunostimulatory effects in pMMR rectal adenocarcinoma.
• Clinical trials combining all three modalities are scarce.
• Potential benefits exist, but prospective evaluation with toxicity monitoring is crucial.