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Add-on conformal irradiation improves outcome of pediatric medulloblastoma

NEW YORK (Reuters Health) – Event-free survival is better in young children with nonmetastatic medulloblastoma when conformal radiation therapy is added to postoperative chemotherapy, according to a study conducted in Australia and North America.

Given that cognitive and motor function didn’t seem to decline, “these data are provocative and may prompt a reassessment of the role of irradiation in high-risk infants with these tumors,” the researchers conclude.

Dr. David M. Ashley, at the Andrew Love Cancer Center, Barwon Health, in Geelong, Victoria, Australia, and colleagues explain in the Journal of Clinical Oncology online July 30 that craniospinal irradiation is standard for older children with embryonal neoplasms, but toxicity is unacceptably high in very young kids. For them, treatment has relied on postoperative combination chemotherapy.

To see if conformal radiation therapy (CRT) could benefit this age group, the authors studied 74 children between eight months and three years of age with nonmetastatic medulloblastoma.

As described in the report, “After initial surgery, children received four cycles of induction chemotherapy, followed by age- and response-adjusted CRT to the posterior fossa (18 or 23.4 Gy) and tumor bed (cumulative 50.4 or 54 Gy) and maintenance chemotherapy.”

Event-free survival at four years was 50%, and four-year overall survival was 69%, the team reports. They note that these figures compare favorably to outcomes documented in a previous trial of postoperative multiagent chemotherapy alone, in which the corresponding survival rates were 25% and 46%.

Analyzing neurodevelopmental outcomes, the investigators saw a general delay in development before tumor diagnosis, and a decline from baseline to pre-irradiation. However, they write, “Over a four-year post-treatment time frame, we did not observe a clinically significant decline in either cognitive or motor function after the delivery of chemotherapy and CRT.”

Dr. Ashley and colleagues found that the desmoplastic/nodular subtype of medulloblastoma was associated with better outcomes, with an event-free survival rate of 58% in this subgroup. Therefore, they comment, “Future studies will use histopathologic typing (desmoplastic/nodular versus nondesmoplastic/nodular) to stratify patients for therapy by risk of relapse.”

“This is an important study” commented Dr. Girish Dhall, “showing an increase in survival when compared to the results from the predecessor study from the same cooperative group.”

Dr. Dhall who was not involved in the current study, is with the pediatric hematology-oncology division at Childrens Hospital Los Angeles and the University of Southern California.

“However,” he continued in an email to Reuters Health, “other cooperative groups (German Pediatric Brain Tumor Study Group, “Head Start”) have reported higher survival rates with preservation of neurocognitive function using high-dose chemotherapy approach and either no or delayed XRT (focal irradiation).”

Dr. Dhall concluded on a cautionary note. “Although authors in this paper report no decline in cognitive function after chemotherapy and focal XRT, the follow-up is short and it remains to be seen if this holds up as the patients get older as many cognitive functions, such as executive functioning, are not apparent in younger patients.”


J Clin Oncol 2012.