Stroke impact on mortality and psychologic morbidity within the Childhood Cancer Survivor Study.

BackgroundPoor socioeconomic and health-related quality of life (HRQOL) outcomes in survivors of childhood cancer can lead to distress and overall negatively impact the lives of these individuals. The current report has highlighted the impact of stroke and stroke recurrence on mortality, psychological HRQOL, and socioeconomic outcomes within the Childhood Cancer Survivor Study (CCSS).MethodsThe CCSS is a retrospective cohort study with longitudinal follow-up concerning survivors of pediatric cancer who were diagnosed between 1970 and 1986. Mortality rates per 100 person-years were calculated across 3 periods: 1) prior to stroke; 2) after first stroke and before recurrent stroke; and 3) after recurrent stroke. Socioeconomic outcomes, the standardized Brief Symptoms Inventory-18, the Medical Outcomes Study 36-Item Short Form Health Survey, and the CCSS-Neurocognitive Questionnaire also were assessed.ResultsAmong 14,358 participants (median age, 39.7 years), 224 had a stroke after their cancer diagnosis (single stroke in 161 patients and recurrent stroke in 63 patients). Based on 2636 deaths, all-cause late mortality rates were 0.70 (95% CI, 0.68-0.73) prior to stroke, 1.03 (95% CI, 0.73-1.46) after the first stroke, and 2.42 (95% CI, 1.48-3.94) after the recurrent stroke. Among 7304 survivors, those with stroke were more likely to live with a caregiver (single stroke odds ratio [OR], 2.3 [95% CI, 1.4-3.8]; and recurrent stroke OR, 5.3 [95% CI, 1.7-16.8]) compared with stroke-free survivors. Stroke negatively impacted task efficiency (single stroke OR, 2.4 [95% CI, 1.4-4.1] and recurrent stroke OR, 3.3 [95% CI, 1.1-10.3]) and memory (single stroke OR, 2.1 [95% CI, 1.2-3.7]; and recurrent stroke OR, 3.5 [95% CI, 1.1-10.5]).ConclusionsStroke and stroke recurrence are associated with increased mortality and negatively impact HRQOL measures in survivors of pediatric cancer

Early detection of recurrent medulloblastoma: the critical role of diffusion-weighted imaging.

BackgroundImaging diagnosis of medulloblastoma recurrence relies heavily on identifying new contrast-enhancing lesions on surveillance imaging, with diffusion-weighted imaging (DWI) being used primarily for detection of complications. We propose that DWI is more sensitive in detecting distal and leptomeningeal recurrent medulloblastoma than T1-weighted postgadolinium imaging.MethodsWe identified 53 pediatric patients with medulloblastoma, 21 of whom developed definitive disease recurrence within the brain. MRI at diagnosis of recurrence and 6 months prior was evaluated for new lesions with reduced diffusion on DWI, contrast enhancement, size, and recurrence location.ResultsAll recurrent medulloblastoma lesions demonstrated reduced diffusion. Apparent diffusion coefficient (ADC) measurements were statistically significantly lower (P = .00001) in recurrent lesions (mean=0.658, SD=0.072) as compared to contralateral normal region of interest (mean=0.923, SD=0.146). Sixteen patients (76.2%) with disease recurrence demonstrated contrast enhancement within the recurrent lesions. All 5 patients with nonenhancing recurrence demonstrated reduced diffusion, with a mean ADC of 0.695 ± 0.101 (normal=0.893 ± 0.100, P = .0027). While group 3 and group 4 molecular subtypes demonstrated distal recurrence more frequently, nonenhancing metastatic disease was found in all molecular subtypes.ConclusionRecurrent medulloblastoma lesions do not uniformly demonstrate contrast enhancement on MRI, but all demonstrate reduced diffusion. Our findings support that DWI is more sensitive than contrast enhancement for detection of medulloblastoma recurrence, particularly in cases of leptomeningeal nonenhancing disease and distal nonenhancing focal disease. As such, recurrent medulloblastoma can present as a reduced diffusion lesion in a patient with normal postgadolinium contrast MRI

Case-based review: pediatric medulloblastoma.

Medulloblastoma is the most common malignant brain tumor affecting children. These tumors are high grade with propensity to metastasize within the central nervous system and, less frequently, outside the neuraxis. Recent advancements in molecular subgrouping of medulloblastoma refine diagnosis and improve counseling in regards to overall prognosis. Both are predicated on the molecular drivers of each subgroup-WNT-activated, SHH-activated, group 3, and group 4. The traditional therapeutic mainstay for medulloblastoma includes a multimodal approach with surgery, radiation, and multiagent chemotherapy. As we discover more about the molecular basis of medulloblastoma, efforts to adjust treatment approaches based on molecular risk stratification are under active investigation. Certainly, the known neurological, developmental, endocrine, and psychosocial injury related to medulloblastoma and its associated therapies motivate ongoing research towards improving treatment for this life-threatening tumor while at the same time minimizing long-term side effects

Circulating tumor DNA sequencing provides comprehensive mutation profiling for pediatric central nervous system tumors

Molecular profiling of childhood CNS tumors is critical for diagnosis and clinical management, yet tissue access is restricted due to the sensitive tumor location. We developed a targeted deep sequencing platform to detect tumor driver mutations, copy number variations, and heterogeneity in the liquid biome. Here, we present the sensitivity, specificity, and clinical relevance of our minimally invasive platform for tumor mutation profiling in children diagnosed with CNS cancer