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Proton therapy shows efficacy with low toxicity in pediatric high-risk neuroblastoma
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Children with high-risk neuroblastoma derived excellent outcomes from proton radiation therapy with minimal toxicity, according to results of the largest-ever cohort study of its kind published in International Journal of Radiation Oncology Biology Physics.
“These data are extremely encouraging and could be a game-changer for a number of reasons,” Christine E. Hill-Kayser, MD, chief of the pediatric radiation oncology service at Penn Medicine and an attending physician at Children’s Hospital of Philadelphia, said in a press release. “Not only did we observe excellent outcomes and minimal side effects that validate the use of [proton radiation therapy] in high-risk [patients with] neuroblastoma, we answered a lingering question about proton therapy — the concern that because it is so targeted, tumors may come back.”
Neuroblastoma accounts for more than 10% of all childhood cancer deaths and is the most prevalent cancer among infants. Because primary neuroblastoma tumors are often adrenal tumors, their proximity to the kidney, liver, pancreas and bowel makes them difficult to treat without damage to vital organs. Treatment typically includes radiation to the primary tumor site and persistent metastatic disease sites in combination with surgery and chemotherapy.
Kayser and colleagues assessed 45 patients (median age, 46 months; range, 10 months to 12 years; 51% male) with high-risk neuroblastoma who underwent proton radiation therapy at Children’s Hospital of Philadelphia/University of Pennsylvania Roberts Proton Therapy Center between September 2010 and September 2015. Forty patients (89%) had adrenal tumors.
Following systemic therapy, surgical removal of the tumor and high-dose chemotherapy with stem cell rescue, most patients received a radiation dose of 2,160 cGy (relative biological effectiveness) to the primary tumor bed and all metastatic sites. Eleven patients received a boost radiation dose due to gross residual disease, for a total dose of 3,600 cGy (relative biological effectiveness).
Radiation was administered to 10 sites of metastasis in eight patients.
The method of therapy changed during the study period from double-scattered proton beams (n = 19) to pencil beam scanning (n = 26), which became available in January 2013 and required less planning time and fewer resources. Two patients received double-scattered proton beans in combination with intensity modulated X-ray therapy.
At a median follow-up of 48.7 months (range, 11-90) from diagnosis, 37 patients (82%) remained alive and 32 (71%) showed no evidence of disease. Locoregional recurrence occurred in one patient, and 12 (27%) experienced relapse at nonradiated, distant sites.
Results showed freedom from primary site recurrence at 3, 4 and 5 years of 97% (95% CI, 0.8316-0.996).
Researchers observed OS rates of 89% (95% CI, 0.75-0.95) at 3 years and 80% (95% CI, 0.63-0.89) at 4 and 5 years. EFS rates were 77% (95% CI, 0.62-0.87) at 3 years and 70% (95% CI, 0.54-0.82) at 4 and 5 years.
Most acute toxicities during proton therapy were grade 1, including nausea (29%), fatigue (24%), vomiting (22%) and anorexia (18%). No patient has demonstrated WHO grade 3 or grade 4 long-term renal or liver toxicity.
“Tumors mostly did not come back, suggesting [proton radiation therapy] is effective, less toxic and a superior choice for our young patients who must endure intense treatment modalities in an effort to cure this high-risk cancer,” Hill-Kayser said in the press release. – by Jennifer Byrne
Disclosures: Hill-Kayser reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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