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Prophylactic cranial irradiation dose effects on late cognitive function in children treated for acute lymphoblastic
F E Halberg1, J H Kramer, I M Moore
1Department of Radiation Oncology, University of California, San Francisco 94143.
Insights
Reducing cranial radiation dose for acute lymphoblastic leukemia (ALL) from 2400 cGy to 1800 cGy significantly improved cognitive function and academic performance in children. Lower doses minimized long-term neurotoxicity, demonstrating acceptable outcomes.
Area of Science:
- Pediatric Oncology
- Neuropsychology
- Radiation Oncology
Background:
- Prophylactic central nervous system (CNS) treatment improves survival in childhood acute lymphoblastic leukemia (ALL).
- High-dose cranial irradiation (2400 cGy) is linked to long-term neurocognitive deficits.
- Previous studies on reduced doses (1800 cGy) yielded inconsistent results.
Purpose of the Study:
- To assess the impact of different whole brain radiotherapy (WBRT) doses (1800 cGy vs. 2400 cGy) on cognitive function in children with ALL.
- To compare neurocognitive outcomes between children receiving 1800 cGy WBRT and those receiving 2400 cGy WBRT, with a control group receiving no CNS therapy.
Main Methods:
- Retrospective study comparing three groups: 19 children treated with 2400 cGy WBRT, 16 with 1800 cGy WBRT, and 12 controls (Wilms' tumor, no CNS therapy).
- All patients received intrathecal methotrexate; WBRT groups received 2400 cGy or 1800 cGy.
- Cognitive function (IQ) and academic abilities (reading, spelling, arithmetic) assessed using standardized tests (WISC-R, WRAT) after a minimum of 70 months off therapy.
Main Results:
- Children treated with 1800 cGy demonstrated significantly better Full-Scale, Verbal, and Performance IQ scores compared to the 2400 cGy group.
- The 1800 cGy group performed comparably to the control group, while the 2400 cGy group showed deficiencies in IQ and academic performance.
- Children receiving 2400 cGy had an average IQ deficit of approximately 12 points compared to the 1800 cGy group; deficits were more pronounced in those irradiated before age 5.
Conclusions:
- Reducing cranial radiotherapy dose from 2400 cGy to 1800 cGy significantly mitigates neurocognitive deficits in children treated for ALL.
- The 1800 cGy dose level appears to reduce neurotoxicity to acceptable levels, maintaining cognitive function comparable to controls.
- Long-term follow-up data support the reduction of cranial RT dose as a strategy to minimize late effects of CNS prophylaxis in pediatric leukemia survivors.
Abstract:
Prophylactic central nervous system treatment has dramatically improved the disease-free survival of children with acute lymphoblastic leukemia (ALL). Long-term neuropsychological sequelae are documented in children who received 2400 cGy prophylactic cranial irradiation. The dose was reduced to 1800 cGy. Available reports on developmental consequences, with short follow-up, have yielded inconsistent results. This study assesses radiation dose effects on cognitive function in children with leukemia who received central nervous system prophylaxis with 2400 cGy versus 1800 cGy whole brain radiotherapy. All leukemic children also received intrathecal methotrexate. A control group of children (treated for Wilms' tumor) received no central nervous system therapy. Nineteen children were treated with 2400 cGy, 16 children with 1800 cGy. The 12 control children received no irradiation. All patients were off therapy for at least 70 months. The 1800 cGy and 2400 cGy patient groups were off therapy for equivalent periods of time (range 70-123 mo) at follow-up testing. Mean age at diagnosis was 49 months, at testing: 142 months. The male to female ratio was 1/1. Standardized psychological tests were administered. Full-Scale, Verbal, and Performance IQ were measured with the Wechsler Intelligence Scale for Children-Revised. Wide Range Achievement Testing evaluated reading, spelling, and arithmetic abilities. Children treated with 1800 cGy performed significantly better than those who received 2400 cGy, and at the same level as controls. There were statistically significant differences between the 1800 cGy and 2400 cGy subjects in all measures. 2400 cGy patients had deficiencies in IQ and academic performance. 1800 cGy patients scored approximately 12 points higher than 2400 cGy children. Eleven children, two in the control group, two in the 1800 cGy, and seven in the 2400 cGy group had IQ scores of less than 90. Eight of the nine irradiated children with deficits had radiotherapy before age 5. These results indicate a mild, but diffuse information processing deficit in children who received 2400 cGy, but not in children who received 1800 cGy. These findings with a minimum of 6 years of follow-up provide new information on late effects of CNS prophylaxis in ALL. Reducing the cranial RT dose from 2400 cGy to 1800 cGy reduced neurotoxicity to acceptable levels.