UPDATED RESULTS OF A PILOT-STUDY OF LOW-DOSE CRANIOSPINAL IRRADIATIONPLUS CHEMOTHERAPY FOR CHILDREN UNDER 5 WITH CEREBELLAR PRIMITIVE NEUROECTODERMAL TUMORS (MEDULLOBLASTOMA)

Purpose: Children under 5 years old with medulloblastoma (MB) have a p oor prognosis. They are more susceptible to the deleterious effects of craniospinal irradiation (CSART) and have a higher relapse Fate when treated with low-dose CSART alone. We, thus, embarked on a prospective trial testing the usefulness of very low dose CSART and adjuvant chem otherapy. This is an update of a previous report on these patients. Me thods and Materials: Between January 1988 and March 1990, 10 patients with medulloblastoma were treated using 18 Gy radiation therapy (RT) t o the craniospinal axis, a posterior fossa (PF) boost to 50.4-55.8 Gy and chemotherapy consisting of vincristine (VCR) weekly during RT. Thi s was followed by VCR, cis-diamminedichloroplatinum (CDDP), and lomust ine (CCNU) for eight, 6-week cycles. Patients between 18 and 60 months of age without evidence of tumor dissemination were eligible for stud y. Follow-up was available until September 1994 with a median follow-u p for living patients of 6.3 years from diagnosis. Results: Actuarial survival at over 6 years is 70 +/- 20%. Three of the 10 patients relap sed and died. in one patient, the relapse developed in the spine and b rain outside the posterior fossa, in the second, concurrently in the p osterior fossa, brain and spine, and the third, only in the spine. One surviving child developed a brain stem infarct 4.8 years after diagno sis and has since almost fully recovered. A mean intelligence quotient (IQ) score of 103 in six patients surviving at least 1 year is unchan ged from the baseline group score of 107. Five children tested at base line and 2 years following treatment had IQ scores of 101 and 102, res pectively. Six children tested at baseline and at 3 years had IQ score s of 106 and 96, respectively. Excluding the child tested shortly afte r his brain stem infarct, baseline and 3 year IQ scores were 103 and 9 7, respectively. Five of the seven long-term survivors grew at rates s ignificantly below their expected velocities during the follow-up peri od, while the others grew normally. Three patients have received growt h hormone, and none have required thyroid replacement. Conclusions: Th ese data suggest that medulloblastoma patients can be cured with chemo therapy and reduced doses of craniospinal irradiation. The low doses o f CSART given by us in conjunction with cis-platin-based chemotherapy produce minimal neurocognitive damage. Growth velocities in very young children so treated are, however, dramatically reduced. Better means of improving the therapeutic ratio are still needed.