Neuromuscular impairments in adult survivors of childhood acute lymphoblastic leukemia: associations with physical performance and chemotherapy doses.

BACKGROUND: Treatment regimens for childhood acute lymphoblastic leukemia (ALL) contain neurotoxic agents that may interfere with neuromuscular health. In this study, the authors examined associations between neuromuscular impairments and physical function and between neuromuscular impairments and doses of vincristine and intrathecal methotrexate used to treat leukemia among survivors of childhood ALL. METHODS: ALL survivors >10 years from diagnosis participated in neuromuscular performance testing. Treatment data were abstracted from medical records. Regression models were used to evaluate associations between treatment factors, neuromuscular impairments, and physical performance. RESULTS: Among 415 survivors (median age, 35 years; age range, 21-52 years), balance, mobility, and 6-minute walk (6MW) distances were 1.3 standard deviations below age-specific and sex-specific values in 15.4%, 3.6%, and 46.5% of participants, respectively. Impairments included absent Achilles tendon reflexes (39.5%), active dorsiflexion range of motion (ROM) <5 degrees (33.5%), and impaired knee extension strength (30.1%). In adjusted models (including cranial radiation), survivors who received cumulative intrathecal methotrexate doses ≥215 mg/m(2) were 3.4 times more likely (95% confidence interval, 1.2-9.8 times more likely) to have impaired ROM than survivors who received no intrathecal methotrexate, and survivors who received cumulative vincristine doses ≥39 mg/m(2) were 1.5 times more likely (95% CI, 1.0-2.5 times more likely) to have impaired ROM than survivors who received lower cumulative doses of vincristine. Higher intrathecal methotrexate doses were associated with reduced knee extension strength and 6MW distances. CONCLUSIONS: Neuromuscular impairments were prevalent in childhood ALL survivors and interfered with physical performance. Higher cumulative doses of vincristine and/or intrathecal methotrexate were associated with long-term neuromuscular impairments, which have implications on future function as these survivors age.

Symptoms of attention-deficit/hyperactivity disorder in long-term survivors of childhood leukemia.

BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (ALL) sometimes have clinical features that suggest attention-deficit/hyperactivity disorder (ADHD), though few studies have examined specific symptoms in survivors. PROCEDURE: Long-term survivors of childhood ALL (n = 161) received a neurological examination, while parents completed rating scales to establish formal criteria for ADHD. Symptom profiles were generated and compared across demographic and treatment characteristics, as well as medical tests associated with brain pathology. RESULTS: Prevalence rates of ADHD were similar in survivors (10.5%) compared to those reported in the general population (7-10%). However, 25.5% of survivors reported symptoms that impair functioning in multiple settings, with attention problems being most common. These symptoms were associated with cranial radiation therapy (CRT) (mean inattentive symptoms [SD] = 3.6 [3.19] for group treated with CRT vs. 1.6 [2.40] for non-CRT group, P = 0.0006), and survivors who demonstrated impaired anti-saccades during the neurologic exam (mean inattentive symptoms [SD] = 3.4 [3.29] for those with impaired anti-saccades vs. 1.4 [2.41] for those with normal anti-saccades; P = 0.0004). CONCLUSIONS: The presence of a neurologically-based phenotype of attention problems in survivors of leukemia that is not fully captured by the syndrome of ADHD suggests that treatments specific to childhood ALL should be explored.

Prospective medical assessment of adults surviving childhood cancer: study design, cohort characteristics, and feasibility of the St. Jude Lifetime Cohort study.

BACKGROUND: To facilitate prospective medical assessment of adults surviving pediatric malignancies and advance knowledge about long-term childhood cancer survivor health, St. Jude Children's Research Hospital (SJCRH) is establishing a lifetime cohort of survivors. METHODS: Eligibility criteria for inclusion in the St. Jude Lifetime Cohort (SJLIFE) study include: (1) diagnosis of childhood malignancy treated at SJCRH; (2) survival ≥ 10 years from diagnosis; and (3) current age ≥ 18 years. Three levels of participation are offered: (1) comprehensive evaluation on SJCRH campus; (2) limited home evaluation; or (3) completion of health surveys only. A systematic recruitment structure based upon blocks of 50 patients initially focused on leukemia and lymphoma survivors and patients eligible for pilot studies. RESULTS: As of January 1, 2010, 1,625 (42%) of 3,900 eligible ≥ 10-year survivors have been contacted. Among the first 1,000 potentially eligible survivors selected for recruitment, 971 were subsequently confirmed to fulfill eligibility criteria. To date, 898/971 (92.5%) have been successfully contacted of whom 825 (91.8%) have agreed to participate. Among participants, 88.6% agreed to comprehensive medical evaluation, 0.4% limited local evaluation, and 11.0% survey only. Anticipated minimum overall participation rate for medical evaluation is 75.3% (731/971). Comparison of those contacted who agreed versus declined to participate revealed a greater proportion of males who declined participation (P = 0.001). CONCLUSIONS: Early results of the SJLIFE study support its feasibility to recruit aging childhood cancer survivors to research investigations evaluating late health outcomes by medical assessments.

Proximal dentatothalamocortical tract involvement in posterior fossa syndrome.

Posterior fossa syndrome is characterized by cerebellar dysfunction, oromotor/oculomotor apraxia, emotional lability and mutism in patients after infratentorial injury. The underlying neuroanatomical substrates of posterior fossa syndrome are unknown, but dentatothalamocortical tracts have been implicated. We used pre- and postoperative neuroimaging to investigate proximal dentatothalamocortical tract involvement in childhood embryonal brain tumour patients who developed posterior fossa syndrome following tumour resection. Diagnostic imaging from a cohort of 26 paediatric patients previously operated on for an embryonal brain tumour (13 patients prospectively diagnosed with posterior fossa syndrome, and 13 non-affected patients) were evaluated. Preoperative magnetic resonance imaging was used to define relevant tumour features, including two potentially predictive measures. Postoperative magnetic resonance and diffusion tensor imaging were used to characterize operative injury and tract-based differences in anisotropy of water diffusion. In patients who developed posterior fossa syndrome, initial tumour resided higher in the 4th ventricle (P = 0.035). Postoperative magnetic resonance signal abnormalities within the superior cerebellar peduncles and midbrain were observed more often in patients with posterior fossa syndrome (P = 0.030 and 0.003, respectively). The fractional anisotropy of water was lower in the bilateral superior cerebellar peduncles, in the bilateral fornices, white matter region proximate to the right angular gyrus (Tailerach coordinates 35, -71, 19) and white matter region proximate to the left superior frontal gyrus (Tailerach coordinates -24, 57, 20). Our findings suggest that multiple bilateral injuries to the proximal dentatothalamocortical pathways may predispose the development of posterior fossa syndrome, that functional disruption of the white matter bundles containing efferent axons within the superior cerebellar peduncles is a critical underlying pathophysiological component of posterior fossa syndrome, and that decreased fractional anisotropy in the fornices and cerebral cortex may be related to the abnormal neurobehavioural symptoms of posterior fossa syndrome.

Phase I and pharmacokinetic studies of erlotinib administered concurrently with radiotherapy for children, adolescents, and young adults with high-grade glioma.

PURPOSE: To estimate the maximum-tolerated dose (MTD) of erlotinib administered during and after radiotherapy, and to describe the pharmacokinetics of erlotinib and its metabolite OSI-420 in patients between 3 and 25 years with newly diagnosed high-grade glioma who did not require enzyme-inducing anticonvulsants. EXPERIMENTAL DESIGN: Five dosage levels (70, 90, 120, 160, and 200 mg/m(2) per day) were planned in this phase I study. Dose-limiting toxicities (DLT) were evaluated during first 8 weeks of therapy. Local radiotherapy (dose between 54 and 59.4 Gy) and erlotinib started preferentially on the same day. Erlotinib was administered once daily for a maximum of 3 years. Pharmacokinetic studies were obtained after first dose and on day 8 of therapy. Mutational analysis of EGFR kinase domain, PIK3CA, and PTEN was done in tumor tissue. RESULTS: Median age at diagnosis of 23 patients was 10.7 years (range, 3.7-22.5 years). MTD of erlotinib was 120 mg/m(2) per day. Skin rash and diarrhea were generally well controlled with supportive care. Dose-limiting toxicities were diarrhea (n = 1), increase in serum lipase (n = 1), and rash with pruritus (n = 1). The pharmacokinetic variables of erlotinib and OSI-420 in children were similar to those described in adults. However, there was no relationship between erlotinib dosage and drug exposure. No EGFR kinase domain mutations were observed. Two patients with glioblastoma harbored mutations in PIK3CA (n = 1) or PTEN (n = 1). CONCLUSIONS: Although the MTD of erlotinib in children with newly diagnosed high-grade glioma was 120 mg/m(2) per day, pharmacokinetic studies showed wide interpatient variability in drug exposure.

Health status in long-term survivors of pediatric craniopharyngiomas.

Craniopharyngiomas are the third most common pediatric brain tumor and most common pediatric suprasellar tumor. Contemporary treatment of craniopharyngiomas uses limited surgery and radiation in an effort to minimize morbidity, but the long-term health status of patients treated in this fashion has not been well described. The purpose of this study was to analyze the health status of long-term survivors of pediatric craniopharyngioma treated primarily with radiation and conservative surgical resection. Medical records of all long-term survivors of craniopharyngioma treated at St. Jude Children's Research Hospital and then transferred to the long-term follow-up clinic were reviewed. The initial cohort comprised 55 patients. Of these, 51 (93%) were alive at the time of this analysis. The median age at diagnosis was 7.1 years (range, 1.2-17.6 years), and 29 (57%) were male. At the time of analysis, the median survival was 7.6 years (range, 5.0-21.3 years). Diagnosis and treatment included surgical biopsy, resection (n = 50), and radiation therapy (n=48). Only 1 patient received chemotherapy. Polyendocrinopathy was the most common morbidity, with hypothyroidism (96%), adrenocorticotropic hormone deficiency (84%), and diabetes insipidus (53%) occurring most frequently. Half of the patients were hypogonadal, and 33 (65%) were overweight or obese. The most common neurologic problems included shunt dependence (37%), seizures (28%), and headaches (39%). Psychological and educational deficits were also identified in a significant number of these individuals. Despite efforts to reduce morbidity in these patients, many survivors remain burdened with significant medical complications. In a small percentage of patients, complications may result in death even during extended remission of craniopharyngioma. Because of the broad spectrum or morbidities experienced, survivors of craniopharyngioma continue to benefit from multidisciplinary care.

Evolution of neurological impairment in pediatric infratentorial ependymoma patients.

BACKGROUND: Infratentorial ependymoma is a common central nervous system tumor of childhood and in patients >1 year of age is treated with maximally feasible surgical resection and radiotherapy. Because of this tumor typically arises within the 4th ventricle and can invade the brainstem, patients are at risk for significant neurological impairment. PURPOSE: To characterize the incidence, evolution, and persistence of neurologic impairment in children with infratentorial ependymoma following maximal safe surgery and conformal or intensity-modulated radiation therapy (CRT/IMRT). PATIENTS AND METHODS: After surgical resection, 96 children with non-metastatic infratentorial ependymoma were enrolled on a phase II study of image-guided radiation therapy and were prospectively followed with interval comprehensive neurological examinations. Late adverse neurological severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. RESULTS: The most common deficits detected at baseline examination were limb dysmetria, cranial nerve VI/VII palsy, limb paresis, dysphagia, and truncal ataxia/hypotonia. When present, gait dysfunction and dysphagia were often severe. Oculomotor dysfunction, facial paresis, dysphagia, and gait impairment improved over time. With the exception of hearing loss, in the survivor cohort, very few severe late effects (CTCAE Grade 3/4/5) were present at 60 months survival. CONCLUSION: In general, neurological deficits were maximal in the post-operative period and either remained stable or improved during radiation and the post-treatment evaluation period. With the exception of hearing, the majority of chronic residual neurological deficits in this at-risk population are mild and only minimally intrude upon daily life.

Alexander disease: An important mimicker of focal brainstem glioma.

We report the case of a 6-year-old male who was referred to a tertiary oncology center with a focal brainstem lesion which was presumed to be neoplastic. Due to the symmetric nature of the lesion on magnetic resonance imaging, the evaluation was expanded to investigate other possible causes and eventual diagnosis of Alexander's disease (AD) was made. AD is a neurodegenerative disease which must be included in the differential for tumor-like lesions within the posterior fossa.

Recurrent intrathecal methotrexate induced neurotoxicity in an adolescent with acute lymphoblastic leukemia: Serial clinical and radiologic findings.

Systemic and intrathecal methotrexate (MTX) are integral components of acute lymphoblastic leukemia (ALL) therapy, but can be associated with neurotoxicity. We describe here the case of an adolescent male with T-cell ALL who developed recurrent episodes of subacute neurotoxicity characterized by slurred speech, emotional lability, and hemiparesis after intrathecal MTX administration. Serial magnetic resonance imaging with diffusion-weighted imaging showed recurrent areas of restricted diffusion within cerebral hemispheric white matter, which correlated chronologically with the administration of intrathecal therapy and severity of clinical symptoms. Resolution of diffusion abnormalities did not preclude further toxicity and a large lesion could cause persisting symptoms.

Growth effects of methylphenidate among childhood cancer survivors: a 12-month case-matched open-label study.

BACKGROUND: To investigate the effect of stimulant medication [methylphenidate (MPH)] on growth patterns among survivors of childhood cancer (acute lymphoblastic leukemia or brain tumor). PROCEDURE: Using a case-matched comparison design, childhood cancer survivors participating in a 12-month open-label MPH trial (n = 51) were compared with childhood cancer survivors not taking MPH (n = 51). Measures of body mass index (BMI), height, and weight were obtained at hospital visits and corrected for gender and age using Centers for Disease Control normative data. RESULTS: Significant deceleration of BMI and weight, but not height, was observed during the 12-month MPH trial for those children taking MPH. CONCLUSIONS: Childhood cancer survivors taking MPH experience significant, though modest, deceleration of BMI and weight across the first year of MPH intervention. The absence of height deceleration, and the presence of only modest BMI and weight deceleration, suggests that MPH is reasonably well tolerated by childhood cancer survivors with respect to growth. Such findings are encouraging in light of increasing evidence that MPH mitigates some of the cognitive late-effects of cancer treatments. Nevertheless, on a case-by-case basis, clinicians should balance the intended benefits of MPH with potential growth effects in this vulnerable population.

Sperm cryopreservation practices among adolescent cancer patients at risk for infertility.

To assess sperm cryopreservation among males newly diagnosed with cancer aged 13 years and older, attending oncologists assigned infertility risk (yes/no) to patients and reported whether their patients engaged in sperm cryopreservation. Only 28.1% of informed at-risk patients banked sperm. Utilization of sperm banking was significantly associated with a diagnosis of central nervous system (CNS) malignancy or non-CNS solid tumor diagnosis, higher socioeconomic status, and not being a member of an Evangelical religious group. These results suggest that sperm banking is underutilized among adolescent males newly diagnosed with cancer, and that strategies to increase the engagement in this fertility preservation method are needed.

Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies.

Long-term outcomes of seizures that develop during treatment of childhood hematological malignancies have not been described. We analyzed seizure outcome in 62 children with leukemia or lymphoma treated at our institution. There was a median follow-up of 6.5 years since first seizure. Seizure etiology included intrathecal or systemic methotrexate in 24, leucoencephalopathy in 11, brain hemorrhage or thrombosis in 11, meningitis in 4, and no identifiable cause in 12. Seizures remained uncontrolled in 18, and risk factors for poor control included female sex (P = .02), no seizure control with first antiseizure drug (P = .08), and longer interval between cancer diagnosis and seizure onset (P = .09). Poor seizure control after initial antiseizure drug also predicted recurrent seizure after drug withdrawal (P = .04). In conclusion, seizures are controlled with medications in a majority of patients with hematological cancer. After a period without seizures, antiseizure drug withdrawal in appropriately selected patient has a high success rate.

Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study.

PURPOSE: Childhood acute lymphoblastic leukemia (ALL) is treated with potentially neurotoxic drugs and neurologic complications in long-term survivors are inadequately studied. This study investigated neurologic morbidity and its effect on quality of life in long-term survivors of childhood ALL. METHODS: Prospective, single institution, cross-sectional, institutional review board-approved study of long-term ALL survivors. Participants were recruited from institutional clinics. Participants answered an investigator-administered questionnaire followed by evaluation by a neurologist. Quality of life (QOL) was also assessed. RESULTS: Of the 162 participants recruited over a 3-year period, 83.3% reported at least one neurologic symptom of interest, 16.7% had single symptom, 11.1% had two symptoms, and 55.6% had three or more symptoms. Symptoms were mild and disability was low in the majority of participants with neurologic symptoms. Median age at ALL diagnosis was 3.9 years (0.4-18.6), median age at study enrollment was 15.7 years (6.9-28.9), and median time from completion of ALL therapy was 7.4 years (1.9-20.3). On multivariable analyses, female sex correlated with presence of dizziness, urinary incontinence, constipation, and neuropathy; use of ≥10 doses of triple intrathecal chemotherapy correlated with urinary incontinence, back pain, and neuropathy; cranial radiation with ataxia; history of ALL relapse with fatigue; and CNS leukemia at diagnosis with seizures. Decline in mental QOL was associated with migraine and tension type headaches, while physical QOL was impaired by presence of dizziness and falls. Overall, good QOL and physical function was maintained by a majority of participants. CONCLUSIONS: Neurologic symptoms were present in 83% long-term ALL survivors. Symptoms related morbidity and QOL impairment is low in majority of survivors. Female sex, ≥10 doses of intrathecal chemotherapy, and history of ALL relapse predispose to impaired QOL. IMPLICATIONS FOR CANCER SURVIVORS: This study will educate survivors and their care providers regarding cancer or treatment-related neurologic symptoms and morbidity. This study will help them understand factors contributing to impaired QOL when present.

Headache types, related morbidity, and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross sectional study.

BACKGROUND: Increased headache prevalence was recently reported in survivors of childhood ALL. Headache sub types, related morbidity, and effect on quality of life has not been reported thus far. OBJECTIVE: To study headache prevalence and type, related disability, and quality of life in a cohort of childhood acute lymphoblastic leukemia (ALL) survivors. METHODS: Childhood ALL survivors in at least 1-year of remission and 5 years from diagnosis completed questionnaires and were evaluated by a neurologist. Disability was evaluated with Pediatric Migraine Disability Assessment scale and the Short Form-36 Health Survey assessed quality of life. RESULTS: Thirty nine of 72 (54%) females and 37 of 90 (41%) males reported headaches. Median time from ALL diagnosis to first headache was 5.2 years and median age at headache onset was 10.1 years in 76 participants with headache. Migraine headaches were diagnosed in 51 (31%) and episodic tension-type headaches in 49 (30%); migraine and tension-type headaches co-existed in 24 (15%) and 18 (11%) participants had chronic daily headaches. Fatigue was associated with migraine headache while hypertension and female gender associated with tension type headache. Headache-related disability was mild in 22 (29%), moderate in 7 (9%), and severe in 5 (7%) survivors, and was absent in the remaining 42 (55%) survivors with headache. Both migraine and tension type headaches associated with reduced mental component scores, while headache related disability associated with a reduced physical component scores. CONCLUSIONS: Headaches are common in ALL survivors but only a minority has significant disability or impairment of quality of life.

Survival and long-term health and cognitive outcomes after low-grade glioma.

Long-term morbidity for children with low-grade glioma (LGG) requires exposure-specific characterization. Overall survival (OS) and progression-free survival (PFS) were estimated for 361 children diagnosed with LGG between 1985 and 2007 at a single institution. Five-year survivors (n = 240) received risk-based clinical assessment. Cumulative incidence of late effects 15 years from diagnosis were estimated. Risk factors for adverse health were identified using Fine and Gray's approach to Cox's proportional hazards model, accounting for death as a competing risk. OS at 15 years was 86% (95% confidence interval [CI] 82%-90%), and PFS was 55% (95% CI 51%-58%). Among the 240 5-year survivors, the 5-, 10-, and 15-year cumulative incidence of adverse outcomes included blindness: 10%, 13%, and 18%, respectively; hearing loss: 8%, 14%, and 22%; obesity/overweight: 18%, 35%, and 53%; hyperinsulinism: 1%, 5%, and 24%; growth hormone deficiency: 13%, 27%, and 29%;thyroid hormone deficiency: 16%, 28%, and 33%; and adrenocorticotropic hormone (ACTH) deficiency: 12%, 22%, and 26%. Multivariable models demonstrated radiation therapy to be a significant independent predictor of hearing loss, growth hormone deficiency, abnormal thyroid function, and ACTH deficiency. Diencephalic location was a statistically significant independent risk factor for blindness, growth hormone deficiency, abnormal thyroid function, and ACTH deficiency. Among the 182 5-year survivors assessed for intellectual function, 34% had an intelligence quotient (IQ) below average (<85), associated with younger age at diagnosis, epilepsy, and shunt placement. Survivors of childhood LGG experience substantial long-term adverse effects that continue to increase well beyond the 5-year survival time point.

Dysembryoplastic neuroepithelial tumors and cognitive outcome: cure at a price?

BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNETs) are benign glioneuronal tumors that occur in children. These tumors are characterized by seizures, lack of neurologic deficits, and a seemingly benign course after resection. METHODS: A retrospective review was conducted of data relating to 11 children diagnosed with DNETs between January 1988 and December 2007 at St. Jude Children's Research Hospital. This report documented the clinical features, neurocognitive function, and treatment outcomes in this institutional series. RESULTS: The patient cohort included 8 boys and 3 girls (median age at diagnosis, 10 years); all patients presented with seizures: 4 complex partial, 3 generalized tonic-clonic, 2 absence, 1 partial simple, and 1 not classified. Of the 11 patients, 1 died of cardiac fibrosis, and tumors recurred or progressed in 4 (36%) patients. Seizure control was achieved in all patients but 1. Of the 9 patients who completed neuropsychologic testing, only 3 (33%) functioned at or above the expected level of same-age peers. CONCLUSIONS: The high recurrence and progression rates of DNETs and the high rate of abnormal neurocognitive test results noted in the current study highlight the need for regular follow-up and appropriate academic counseling of children with these tumors.

Prospective collection of tissue samples at autopsy in children with diffuse intrinsic pontine glioma.

BACKGROUND: Brain tissue obtained at autopsy has been used in research for non-oncologic disorders. However, to the best of the authors' knowledge, this tool has never been systematically used in large investigational studies for cancer. A prospective, multicenter study was conducted to assess the feasibility of tissue collection at autopsy and its suitability for molecular analyses in children with diffuse intrinsic pontine glioma. METHODS: Tumor tissue was collected at the time of diagnosis, if clinically indicated, or at autopsy. Normal brain tissue was also collected at autopsy. The integrity of DNA and RNA was evaluated in all samples. Logistic data regarding autopsies were recorded. The feasibility of tissue collection at autopsy was assessed for patients treated at a single institution over a 43-month period. RESULTS: Tumor samples were collected at the time of diagnosis (n = 3) or at autopsy (n = 38) at 29 centers across the United States; samples were obtained at diagnosis and autopsy in 2 cases. The median interval from death to autopsy was 7.7 hours. DNA and RNA with minimal or partial degradation, which were suitable for genome-wide analysis, were obtained from 100% and 63% of tumor samples, respectively. At the coordinating institution, approximately 40% of parents consented to autopsy and 40% declined. During the study period, 12 autopsies were performed on patients who did not receive therapy at the coordinating center. CONCLUSIONS: Multicenter, biological studies based on tissue obtained at autopsy appear to be feasible in children with brain cancer. The current experience established a new paradigm for brain tissue collection, which may increase the potential for research studies in patients with cancer.

Neurocognitive outcome 12 months following cerebellar mutism syndrome in pediatric patients with medulloblastoma.

The aim is to prospectively assess early neurocognitive outcome of children who developed cerebellar mutism syndrome (CMS) following surgical resection of a posterior fossa embryonal tumor, compared with carefully matched control patients. Children who were enrolled on an ongoing IRB-approved protocol for treatment of embryonal tumors, were diagnosed with postoperative CMS, and had completed prospectively planned neuropsychological evaluation at 12 months postdiagnosis were considered eligible. The cognitive outcomes of these patients were examined in comparison to patients without CMS from the same treatment protocol and matched with regard to primary diagnosis, age at diagnosis, and risk/corresponding treatment (n = 22 pairs). Seventeen were also matched according to gender, and 14 were also matched according to race. High-risk patients received 36-39.6 Gy CSI and 3D conformal boost to the primary site to 55.8-59.4 Gy. Average-risk patients received 23.4 Gy CSI and 3D conformal boost to the primary site to 55.8 Gy. Significant group differences were found on multiple cognitive outcomes. While the matched control patients exhibited performance in the average range, patients who developed CMS postsurgery were found to have significantly lower performance in processing speed, attention, working memory, executive processes, cognitive efficiency, reading, spelling, and math. Patients treated for medulloblastoma who experience postoperative CMS show an increased risk for neurocognitive impairment, evident as early as 12 months following diagnosis. This study highlights the need for careful follow-up with neuropsychological evaluation and for obtaining critical support for patients and their families.