Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial

This phase II trial compares the effect of adding proton spatially fractionatedradiotherapy (SFRT) or photon stereotactic body radiotherapy (SBRT) to standardimmunotherapy pembrolizumab before surgery (neoadjuvant) in treating patients with oralcavity squamous cell cancer that has spread to nearby tissue or lymph nodes (locallyadvanced) or that has come back where it first started (primary site) or near it(locoregionally recurrent) and have not had (naive) prior radiation. Radiation therapyuses high energy x‐rays, particles, or radioactive seeds to kill tumor cells and shrinktumors. Proton SFRT is a type of external beam radiation treatment that uses streams ofprotons (tiny particles with a positive charge) to deliver different doses of radiationto different parts of the tumor in a grid like pattern. This type of radiation killstumor cells but does not damage nearby tissues. SBRT is a type of external radiationtherapy that uses special equipment to position a patient and precisely deliver radiationto tumors in the body (except the brain). The total dose of radiation is divided intosmaller doses given over several days. This type of radiation therapy helps spare normaltissue. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help thebody's immune system attack the tumor, and may interfere with the ability of tumor cellsto grow and spread. Giving neoadjuvant proton SFRT or SBRT in combination withpembrolizumab may be safe and tolerable and may be an effective approach to shrink thetumor, reduce the extent of surgery and/or the need for further treatment in patientswith locally advanced or locoregionally recurrent oral cavity squamous cell cancer.