In a phase II trial (RT2CR) reported in The Lancet Oncology, Thomas E. Merchant, DO, and colleagues found that limited surgery plus proton therapy was associated with a high rate of disease control and a low rate of severe complications in pediatric and adolescent patients with craniopharyngioma. Survival outcomes did not differ from those observed in a historical cohort of patients treated with limited surgery and photon therapy.
Study Details
In the trial, 94 patients enrolled between August 2011 and January 2016 at St. Jude Children’s Research Hospital and the University of Florida Health Proton Therapy Institute received limited surgery and proton therapy. The primary endpoints were progression-free survival and overall survival. Outcomes were compared to those from a cohort of 101 patients treated with limited surgery and photon therapy (photon cohort) between April 1998 and December 2013 at St. Jude Children’s Research Hospital.
Thomas E. Merchant, DO
Key Findings
In the study population, 3-year progression-free survival was 96.8% (95% confidence interval [CI] = 90.4%–99.0%) and 5-year progression-free survival was 93.6% (95% CI = 86.3%–97.1%). Overall survival was 100% at 3 and at 5 years.
In the historical photon cohort, 3-year progression-free survival was 96.0% (95% CI = 89.7%–98.5%) and 5-year progression-free survival was 90.0% (95% CI = 82.2%–94.5%). Overall survival was 100% at 3 years and 98.0% (95% CI = 92.3%–99.5%) at 5 years.
At 5 years in the study population, central nervous system (CNS) necrosis had occurred in 2% of patients, severe vasculopathy occurred in 4%, and permanent neurologic conditions unrelated to necrosis or vasculopathy occurred in 3%. Decline in vision from normal to abnormal occurred in 7% of 54 patients with normal vision at baseline. The most commonly reported grade 3 or 4 adverse events were headache (6%), vascular disorders (6%), and seizure (5%).
In the historical photon cohort, 2% of patients developed CNS necrosis, 7% developed severe vasculopathy, and 3% developed permanent neurologic conditions unrelated to necrosis or vasculopathy. Decline in vision from normal to abnormal occurred in 10% of 50 patients with normal vision at baseline.
Compared with the study group, longitudinal scores in the photon cohort showed decreases in intelligence quotient (IQ; –1.09 points per year, P = .0070) and adaptive functioning (self-care skills) measured by adaptive behavior scales (–1.48 points per year, P = .030). Estimated differences over 5 years favoring the study group were 4.58 points for IQ and 7.34 points for adaptive functioning.
The investigators concluded, “Proton therapy did not improve survival outcomes in pediatric and adolescent patients with craniopharyngioma compared with a historical cohort, and severe complication rates were similar. However, cognitive outcomes with proton therapy were improved over photon therapy. Children and adolescents treated for craniopharyngioma using limited surgery and postoperative proton therapy have a high rate of tumor control and [a] low rate of severe complications. The outcomes achieved with this treatment represent a new benchmark to which other regimens can be compared.”
Thomas E. Merchant, DO, of the Department of Radiation Oncology, St. Jude Children’s Research Hospital, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the American Lebanese Syrian Associated Charities, American Cancer Society, National Cancer Institute, and Research to Prevent Blindness. For full disclosures of the study authors, visit thelancet.com.
