Central Nervous System
Prevention and Therapy
Prevention
Treatment of both leukemia and brain tumors has been modified when possible to reduce or omit radiation therapy (RT).
Brain tumors:
The Pediatric Oncology Group/Children’s Cancer Group organized a study in
1986 for children with low stage medulloblastoma in which the RT dose to the neuraxis was randomized to either 23.4 Gy or 36 Gy. The study was closed prematurely because of an increased risk of neuraxis dissemination in the lower radiation dose arm. IQ testing in younger children treated on the low dose RT arm of this study (surviving a median of 8 years) had a 10–15 point advantage. This did not apply to older children.
The International Society of Pediatric Oncology and the German Society of Pediatric Oncology gave up-front chemotherapy followed by either 35 Gy or 25 Gy CSRT to children
with medulloblastoma. Chemotherapy included procarbazine, vincristine and MTX. Despite the addition of chemotherapy, the reduced radiation dose arm was associated with
poor survivals.
Although reduced dose neuraxis radiation in these studies was associated with worse survivals than standard radiation, the Children’s Cancer Group mounted a study to determine whether adding lomustine, vincristine and cisplatin to reduced neuraxis radiation (23.4 Gy) might improve survivals while still reducing neurotoxicity. There was no standard radiation arm in this study for comparison. Survivals were excellent with a 79% progression free survival at 5 years. Neurotoxicity however was significant. The rate of decline in IQ after 4 years was 17.4 points overall and 20.8 points in children <7 years of age at treatment. In addition many of the children became hearing impaired from the Cis-platinum.
Building on the survival success of the prior study, Packer and colleagues from the Children’s Oncology Group mounted a 2 armed study of reduced neuraxis radiation coupled with 2 different chemotherapy arms for children with average risk
medulloblastoma. The event free and overall survival at 5 years for the group was 81% and 86%, respectively. Although late effects studies are ongoing, it is likely that based on the prior study, cognitive problems will remain. In addition grade 3 or 4 hearing loss was identified in 25% of the patients treated with cisplatin, 7 children developed second malignancies and 24% developed cerebellar mutism syndrome.
Leukemias:
Cranial radiotherapy (RT) is far less frequently given in the treatment of leukemia and now only reserved for patients with very high risk disease.
The dose of cranial RT for cranial prophylaxis has been reduced to 12 Gy in 8 fractions only.
Previous studies where the RT dose was reduced from 24 Gy to 18 Gy did not show a significant difference in neurocognitive function, however, when the dose of RT was reduced, IT and IV MTX was also intensified which may have resulted in a further reduction in neurocognitive function.
Therapy:
Brain injury rehabilitation may have a positive effect on attention dysfunction in the short term. However, the long-term clinical significance of these interventions remains to be determined.
Symptoms in survivors of childhood ALL and brain tumors show correspondence with children with ADHD, and it has been suggested that these survivors might benefit from stimulant medication.
In a randomized, double blind, placebo-controlled trial in a mixed group of childhood ALL and brain tumor survivors, Mulhern et al. found significant improvement with methylphenidate to be reported by teachers and parents on the Conners’ Rating Scales and by teachers on the Social Skills Rating System.
However, more research will need to be performed in this area to demonstrate possible benefits of pharmacological intervention in survivors of childhood ALL.
Examples of Canadian rehabilitation programs:
Disability Vocational Rehabilitation Program
GF Strong Rehabilitation Center
