Long-term Impact of Medulloblastoma Treatment in Childhood

Abstract & Commentary

By Adília Hormigo, MD, PhD, Attending Neurologist, Memorial Sloan-Kettering Cancer Center, and Assistant Professor of Neurology, Weill Cornell Medical College. Dr. Hormigo reports no financial relationships relevant to this field of study.

Synopsis: Many survivors of medulloblastoma, who were treated with craniospinal radiation, develop physical and cognitive impairments as adults.

Source: Edelstein K, et al. Early aging in adult survivors of childhood medulloblastoma: Long-term neurocognitive, functional, and physical outcomes. Neuro-Oncology 2011;13:536-545.

Medulloblastoma is the most frequent childhood brain tumor and the treatment usually consists of surgical resection and adjuvant craniospinal radiation with chemotherapy. The 5-year survival rate is approximate 80% for the average risk patient. In this paper, the authors analyzed a cohort of 20 adult survivors of childhood medulloblastoma, who were followed for 4 years and underwent physical and neuropsychological evaluation at a median interval of 15.5 years after diagnosis. The patients were treated with craniospinal radiation and 9 patients also received chemotherapy. The investigators noted physical, functional, and neurocognitive deficits. Hypothyroidism was found in 60%, hearing loss in 55%, and secondary neoplasms in 25% of patients. Meningioma was the most frequent of the secondary tumors. Eighty-five percent of the survivors were supported and lived with parents, 90% had frequented programs at school for learning disabilities, and 45% were not competitively employed and attended school full-time. Neurocognitive evaluation showed that working memory, executive function, academic achievement, and motor dexterity were significantly impaired. Furthermore, working memory continued to decline over time. Younger age at diagnosis also was associated with a lower intelligence quotient and less academic achievement.

Commentary

This work attempts to assess the consequences of treatment in adult survivors of childhood medulloblastoma. The long-term morbidity of the survivors included chronic physical conditions and cognitive dysfunction. This study has limitations inherent to a retrospective cohort and as such, there is no understanding of when the physical and cognitive impairments started, which started first, how they interrelate, and progress. It is conceivable that auditory impairment could contribute to the development of learning disability and neurocognitive impairments. In addition, it is unclear how much the chemotherapy added to the toxicity of craniospinal radiotherapy and the late effects of treatment. In fact, some researchers are focused on developing therapeutics in which the primary treatment is chemotherapy with bone marrow transplant, with or without craniospinal radiation. Another limitation in this selected cohort is the exclusion of some survivors that might have been followed by a general physician out of the academic medical center where the study took place. Only a prospective study linked to standard treatment or a clinical trial with follow-up to adulthood will be able to answer these questions and assess the severity of deficits. These are important issues for planning future treatments to rescue, prevent, and reduce the disabilities of patients who are survivors of childhood medulloblastoma, and who are expected to live longer, as treatment continues to improve.

References

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2. Frange P, et. al. From childhood to adulthood: Long-term outcome of medulloblastoma patients. The Institut Curie experience (1980-2000). J Neuro-Oncol 2009;95:271-279.

3. Sands SA, et al. Neuropsychological functioning of children treated with intensive chemotherapy followed by myeloablative consolidation chemotherapy and autologous hematopoietic cell rescue for newly diagnosed CNS tumors: An analysis of the Head Start II survivors. Pediatr Blood Cancer 2010;54:429-436.