The deferral of postoperative radiotherapy (RT) to the craniospinal axis has occurred at an increasing rate among children with medulloblastoma, and this deferral of treatment was associated with worse survival, according to the results of a study published in JAMA Oncology.
“Further study is needed to determine reasons for postoperative RT deferral and to identify subgroups of patients who may be safely managed with postoperative RT deferral, perhaps with the aid of molecular subtyping,” wrote researchers led by Benjamin H. Kann, MD, of Yale University School of Medicine in New Haven, Connecticut.
Medulloblastoma is a common pediatric malignancy, and postoperative RT to the craniospinal axis is a standard of care. However, this RT is associated with adverse effects in long-term survivors of the disease. Several studies in recent years have evaluated postoperative RT deferral and treatment with adjuvant chemotherapy in children aged younger than 3 years. Although results have been conflicting, these studies have led to an acceptance of RT deferral in some patients, according to the researchers.
With this analysis, Kann and colleagues wanted to evaluate recent trends in postoperative RT deferral in children with medulloblastoma aged 3 to 8 years. They used data from the National Cancer Data Base for children diagnosed between 2004 and 2012 without distant metastases. Patients were classified as having postoperative RT deferral if they did not receive RT within 90 days of surgery.
They identified 816 patients, of whom 15.1% had deferred RT. Looking at the data by age, significantly more 3-year-olds had deferred RT compared with 8-year-olds (36.8% vs 4.1%; P < .001). Several factors were identified that were associated with increased likelihood of deferral, including age (odds ratio [OR], 0.57 [95% CI, 0.49–0.67 per year]) and year of diagnosis (OR, 1.18 [95% CI, 1.08–1.29 per year]).
“Our analysis suggests that, in young children with medulloblastoma, it is predominantly patient age, not clinicopathologic risk, that drives postoperative RT deferral. There were substantial increases in use with each increasing year of age from 3 to 8 years, especially from ages 3 to 5 years,” the researchers wrote. “This trend could be explained by the concern about age-dependent, long-term toxic effects from craniospinal irradiation and cerebellar RT, particularly in very young children.”
The survival analysis included 474 patients, of whom 17.5% had deferred RT. With a median follow-up of about 5 years, those children who received RT had significantly better 5-year overall survival compared with those who had deferred (82.0% vs 63.4%; P < .001).
Postoperative RT deferral was associated with poorer overall survival (hazard ratio, 1.95 [95% CI, 1.15–3.31]).
“While there was a clear survival detriment for postoperative RT deferral, postoperative RT dose de-escalation from 36.0 Gy craniospinal irradiation to 23.4 Gy or 18.0 Gy was not an independent predictor of inferior overall survival,” the researchers noted.