Low-Stage Medulloblastoma: Final Analysis of Trial Comparing Standard-Dose With Reduced-Dose Neuraxis Irradiation

Authors: Thomas PRM, Deutsch M, Kepner JL, et al.
Source: Journal of Clinical Oncology, 18(16), 2000, pg 3004-3011

Background:

Medulloblastoma is a primitive cerebellar tumor of neuroectodermal origin. It is a childhood malignancy (median age 5-6) that has a high propensity for neuraxis spread. Hence, standard treatment involves craniospinal irradiation. This carries a rate of toxicity, including significant nausea, vomiting, pancytopenia, and late neuropsychological and growth defects. This obviously would like to be avoided, if possible, especially in young children. This study compares treatment with standard dose craniospinal irradiation (CSI) with reduced dose CSI, in the attempt to maintain efficacy but reduce toxicity of treatment.

Materials and Methods:

• 81 patients between the age of 3-21 yrs, with standard risk medulloblastoma formed the study group
• All had resection with postoperative evaluation including CT scan, myelography, and lumbar puncture
• The control group was treated with 36 Gy (20 fxs of 1.8 Gy) CSI with boost to the posterior fossa to 54 Gy
• The reduced dose group was treated with 23.4 Gy (13 fxs of 1.8 Gy) CSI with boost to the posterior fossa to 54 Gy

Results:

• The protocol was closed early because of a higher incidence of failure in the lower dose arm
• EFS was 62% (control) vs. 52% (reduced dose) at 5 and 8 years
• OS was 69% (control) vs. 59% (reduced dose) at 5 years
• The vast majority of patients relapsed in the neuraxis and isolated extraneural failures were fairly rare
• Patients that relapsed only in the neuraxis had a higher rate of relapse with lower doses

Author's Conclusions:

• Although the protocol was closed early, the conclusion that the reduced arm had more failures seemed to be maintained through time
• The results in the standard arm are consistent with historical results of 60-65% EFS and ~70% OS
• The entire point of the study was to reduce toxicity, which could not be evaluated, and could not be done without decreasing the efficacy of treatment

Clinical/Scientific Implications

The long-term toxicities of CSI can be devastating, with reports of decrease in IQ and growth well-documented. However, in medulloblastoma, CSI is needed as this disease has a high propensity to spread throughout the neuraxis (15-30% in even standard risk patients). This attempt to reduce CSI dose was unsuccessful, as it resulted in a higher rate of failure, which is obviously a very serious result of inadequate treatment. In children, though, toxicity may outweigh even treatment failure-especially when the toxicities of treatment are as serious as those documented with CSI. This report did lead to an additional study, which used chemotherapy and lower doses of CSI to treat standard risk medulloblastoma (Packer et al, JCO 17(7), 2127, 1999). These results were very positive, and chemotherapy with reduced dose (23.4 Gy) CSI has become the accepted standard of care in standard risk medulloblastoma.