Memory deficits in long-term survivors of childhood brain tumors may primarily reflect general cognitive dysfunctions

BACKGROUND: To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction. PROCEDURE: We studied 126 patients with brain tumors diagnosed before the age of 15 years and treated January 1970 through February 1997 in Eastern Denmark. Sixty-nine of the 126 patients had received RT. In addition to working memory and long-term memory (LTM), general intelligence (IQ) was assessed. RESULTS: The mean test scores in nearly all memory tests were lower than expected from available norms. In multiple linear regression, treatment with RT, hemisphere tumor location, and hydrocephalus treated with a shunt at the time of diagnosis were found to be significant risk factors for memory deficits. When IQ was included as a covariate, RT did not significantly predict memory performance, while shunt and tumor location remained significant for several but not all tests. CONCLUSION: These results suggest that in patients treated with RT, memory deficits primarily reflect a general cognitive dysfunction, and it is likely that these intelligence deficits may compromise the chances of success of special memory training. In contrast, memory deficits in non-irradiated patients may to some degree reflect specific cognitive dysfunctions being most pronounced for patients treated with a shunt and for patients with hemispheric tumors.     

Survey of long‐term follow‐up programs in the United States for survivors of childhood brain tumors

Introduction

Despite recognition that childhood brain tumor survivors often suffer multiple late effects following therapy, little is known regarding the long‐term follow‐up (LTFU) programs for these patients.

Methods

A 16‐question survey was mailed to member institutions of the Children's Oncology Group in the United States. Institutions were asked about the size of their brain tumor program, activities of the LTFU programs and perceived barriers to follow‐up.

Results

One hundred forty‐five (74%) of 197 institutions returned surveys. Care for patients <21 years old at diagnosis who are >2 years following completion of therapy was provided at a designated neuro‐oncology LTFU clinic (31.2%), a general LTFU program for childhood cancer survivors (30.4%), or a general pediatric oncology program (29.7%). Institutions with a neuro‐oncology LTFU clinic were more likely to use neuro‐psychological testing following radiation therapy (P = 0.001), have longer duration of continued surveillance imaging (P = 0.02), use growth hormone replacement for medulloblastoma survivors (P < 0.001) and continue the use of growth hormone into adulthood (P = 0.05) than those with a general pediatric oncology program. Perceived barriers to care of brain tumor survivors included limited access and lack of insurance (32.1%), lack of funding or dedicated time for providers (22.9%), patients' uncertainty about need to follow‐up (20.6%), and patients' desire to not be followed in a pediatric cancer program (12.2%).

Conclusions

Considerable variation exists across institutions in the United States in the delivery of follow‐up care for survivors of childhood brain tumors. We encourage additional investigation to better define and implement optimal follow‐up care for childhood brain tumor survivors. Pediatr Blood Cancer 2009; 53:1295–1301. © 2009 Wiley‐Liss, Inc.     

Cognitive deficits in long-term survivors of childhood brain tumors: Identification of predictive factors

BACKGROUND: To describe cognitive function and to evaluate the association between potentially predictive factors and cognitive outcome in an unselected population of survivors of childhood brain tumors. PROCEDURE: We studied a consecutive sample of 133 patients (76 had received radiotherapy (RT)) who had a brain tumor diagnosed before the age of 15 years and were treated during the period January 1970 through February 1997 in the Eastern part of Denmark. Biologic effective dose of irradiation (BED) was assessed in 71 patients. One hundred twenty-seven patients were able to cooperate to WISC-R and WAIS-R. Multiple regression models were constructed to evaluate relationships between possible risk factors and cognitive outcome. RESULTS AND CONCLUSIONS: The mean intelligence (IQ) scores were substantially lower than the expected means of the general population. Younger age at diagnosis, tumor site in cerebral hemisphere, hydrocephalus treated with shunt, and treatment with RT were found to be significant predictors of lower cognitive functions. RT was the most important risk factor for impaired intellectual outcome. The mean observed full scale IQ was 97.1 (SD = 14.3) for the non-irradiated patients and 78.8 (SD = 14.3) for the irradiated patients (adjusted P < 0.001). Verbal IQ, but not performance and full scale IQ, had a significant negative correlation to BED to the tumor site (P < 0.05). These results can be used to identify subgroups of children who are at increased risk for cognitive deficits allowing early and goal-directed intervention.     

Computed tomography brain scans in long term survivors of childhood acute lymphoblastic leukemia

There have been varying frequencies cited for the occurrence of abnormal brain CT scans in Jeukemic patients and confiding evidence about the significance of these abnormalities and their relationship to sanctuary therapy. Our study of CT brain scans in 26 long survivors of acute lymphoblastic leukemia showed an overall prevalence of 35% abnormal scans. There was no statistically significant difference between the number of abnormal scans seen in patients given radiotherapy as part of their CNS prophylaxis and those receiving only intrathecal methotrexate. Because the children in each treatment group were evenly matched with respect to other treatment variables possibly relevant to the causation of abnormal brain scans, a strong case is made for more rigorous design of such studies, preferably in a prospective fashion, looking simultaneously at other parameters of brain structure and function.     

An analysis of SEER data of increasing risk of secondary malignant neoplasms among long-term survivors of childhood brain tumors

BACKGROUND: Advances made in treatment of a childhood brain cancer have extended the lives of many children and adolescents. Treatment success, however, brings the opportunity to assess late effects; most worrying among these are secondary malignant neoplasms (SMN). Even though the cumulative incidence is quite small, long-term follow-up is required because treatment-induced cancers can occur years after initial treatment. PROCEDURE: The purpose of this project was to determine what treatments and what host characteristics of children treated for a primary brain cancer are associated with an increase in the risk of a SMN in long-term survivors. Data were analyzed from 2,056 5-year survivors, of primary brain cancer in the surveillance, epidemiology, and end results (SEER) database between 1973 and 1998. Thirty-nine patients developed a SMN. Cox regression models were used to evaluate the independent contribution of a number of risk factors. RESULTS: The most important risk factor for developing a SMN in 5-year survivors was the era in which the primary cancer was treated. Compared to treatment prior to 1979, patients treated between 1979 and 1984 had a 4.7-fold increase in risk (P = 0.001), while those treated after 1985 had a 6.7-fold increase in risk. (P = 0.002). Patients treated most recently carry the greatest risk of SMN development even after controlling for radiotherapy. This could be due to the increase in intensive treatment compared to earlier years. CONCLUSION: Although the absolute excess risk of SMN remains quite low, continued surveillance is needed to evaluate long-term effects of new therapies for primary brain tumors.