Progression-Free Survival after Proton Therapy for Childhood Craniopharyngioma: Early Results From a Prospective Trial

Abstract

Clinical trials that include proton therapy for children should be designed to compare disease control rates to those observed when using photon therapy. We designed a prospective phase II clinical trial to estimate progression-free for children with craniopharyngioma treated with proton therapy using a 5-mm clinical target volume (CTV) margin (NCT01419067) while monitoring for evidence that the 3-year PFS was unacceptably low compared to that observed for a historical cohort of patients treated with photon therapy (NCT00187226). The study accrued 94 children and young adults with craniopharyngioma who started proton therapy between 9/19/2011 and 02/22/2016 using the passive-scattering method at the University of Florida Health Proton Therapy Institute. The median age and range at the time of proton therapy was 9.4 years (range (2-20.2 years). Proton therapy was planned using an anatomically constrained CTV 5-mm margin surrounding the gross tumor volume (GTV) defined as residual tumor and post-operative tumor (when applicable) and 3-mm planning target volume margin. Patients were monitored once weekly using MR imaging. Cyst expansion required re-planning (n = 8), drainage (n = 4), or both (n = 2) to maintain coverage. The total prescribed dose was 54CGE in 30 fractions and the median elapsed days was 43 (range 40-50). Dated from the start of proton therapy, patients were followed at St. Jude Children’s Research Hospital in Memphis, Tennessee with clinical evaluation and MR imaging at baseline and every 3 months for the first year and then every 6 months through 5 years. Compliance with on-site follow-up was 98% and 869 on-site MRI evaluations contributed to this report. With a median follow-up 2.65 years (range 0.50-5.23 years), the progression-free survival estimated at 36 months was 97.8% ± 2.5%. More than 46 patients completed 3 years of follow-up at the time of this report. The results were compared to a cohort of 101 children with craniopharyngioma treated at St. Jude Children’s Research Hospital with photon-based conformal or intensity-modulated radiation therapy (54 Gy in 30 fractions) between 4/6/1998 and 1/22/2014. The progression-free survival estimate at 36 months was 96.0% ± 1.9% for the photon cohort. Using the targeting guidelines and proton therapy delivery methods described in this clinical trial, the progression-free survival estimates were comparable to those observed when using photon therapy. Prior reports from this series revealed similar risks of severe treatment-related complications. Final analysis will be performed 3 years after the last patient has been treated with proton therapy, with one additional year to calculate 95% exact confidence interval estimates of the binomial probability of completing three years free of failure and Kaplan-Meier estimates of PFS and overall survival.