Phase 2 Prospective Trial of Personalized Radiation Therapy Fractionation in Human Papillomavirus Positive...

We previously developed a model of pretreatment growth and on-treatment response dynamics, the proliferation saturation index (PSI) model, which derives the proliferating and radiosensitive proportion of a tumor based on clinically observed net growth before therapy. We hypothesized that personalization of fractionation using PSI would increase the percentage of patients achieving a rapid reduction in tumor size during radiation therapy (RT) for early-stage human papillomavirus related squamous cancers of the oropharynx.

In this single-center nonrandomized phase 2 single-arm trial, 113 patients underwent screening, and 57 patients were consented and enrolled. Pretreatment PSI was calculated, and patients were assigned to 60 to 70 Gy in 30 to 35 fractions given once daily (PSI ≤ 0.75) or 60 to 69.6 Gy in 50 to 58 fractions given twice daily (PSI > 0.75). The primary endpoint of the study was the rate of patients with ≥32% reduction in tumor volume at 4 weeks of RT, with a planned sample size of 60 patients, with an interim analysis after 49 patients. Secondary end points included locoregional failure (LRF), progression-free survival (PFS), and overall survival (OS).

A total of 55 patients evaluable for the primary endpoint were consented and enrolled, and 32 (58%; 95% CI, 44%-71%) met the primary endpoint of ≥32% reduction at 4 weeks of RT, meeting criteria for efficacy, leading to early study closure. For the 54 patients evaluable for secondary endpoints, the cumulative incidence of LRF at 2 years was 2% (95% CI, 0-5.8), with a 2-year PFS of 92% (95% CI, 85-100), and a 2-year OS of 96% (95% CI, 91-100).

Personalized RT fractionation based on PSI suggests a promising rate of midtreatment response with favorable LF, PFS, and OS.