Increased vulnerability of the spinal cord to radiation or intrathecal chemotherapy during adolescence: A report from the Children's Oncology Group

Purpose. To assess the rate of spinal cord toxicity in adolescents resulting from chemoradiotherapy of parameningeal sarcoma. Methods and Materials. Of 152 patients with parameningeal sarcoma treated per the Intergroup Rhabdomyosarcoma Study Group protocol from 1977 through 1989, eight developed paralyzing ascending myelitis after intrathecal chemotherapy with cytosine arabinoside, methotrexate, and hydrocortisone administered during and after radiation therapy to volumes that included part of the spinal cord. The eight cases include three not previously published. Results. Of eight patients who developed CNS toxicity after intrathecal chemotherapy and radiotherapy for parameningeal rhabdomyosarcoma, all but one were between 13 and 18 years of age when treated. This severe toxicity occurred in one quarter of 28 adolescents treated with the regimen in comparison with one of 123 children 12 years of age or less (P<0.0001), a rate that was as much as 30 times higher in the adolescents. Lengthening of the spinal cord during the pubertal growth spurt may account for the apparent increased vulnerability. Conclusions. Chemoradiotoxicity-associated spinal cord injury appears to be more likely to occur in adolescents than in younger or older ages. This observation appears to reverse a conventional wisdom in which the central nervous system is thought to become more resistant to the neurotoxic effects of chemoradiotherapy as it matures.