Peter de Blank

Alex's Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007-2011

The CBTRUS Statistical Report: Alexs Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007–2011 comprehensively describes the current population-based incidence of primary malignant and non-malignant brain and CNS tumors in children ages 0–14 years, collected and reported by central cancer registries covering approximately 99.8% of the United States population (for 2011 only, data were available for 50 out of 51 registries). Overall, brain and CNS tumors are the most common solid tumor, the most common cancer, and the most common cause of cancer death in infants and children 0–14 years. This report aims to serve as a useful resource for researchers, clinicians, patients, and families.

American Brain Tumor Association Adolescent and Young Adult Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012.

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH USA Central Brain Tumor Registry of the United States, Hinsdale, IL USA Department of Pediatric Hematology-Oncology, Rainbow Babies and Children s Hospital, Cleveland, OH USA Division of Hematology, Oncology and BMT, Nationwide Children’s Hospital and The Ohio State University, Columbus, OH USA School of Public Health, University of Memphis, Memphis, TN USA Keck School of Medicine, University of Southern California, Los Angeles, CA USA Department of Pediatric Hematology and Oncology, Cleveland Clinic Children’s Hospital, Cleveland, OH USA Solon High School, Solon, OH USA

Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010.

Time trends in cancer incidence rates (IR) are important to measure the changing burden of cancer on a population over time. The overall IR of cancer in the United States is declining. Although central nervous system tumors (CNST) are rare, they contribute disproportionately to mortality and morbidity. In this analysis, the authors examined trends in the incidence of the most common cancers and CNST between 2000 and 2010.

The descriptive epidemiology of atypical teratoid/rhabdoid tumors in the United States, 2001–2010

BACKGROUND Atypical teratoid/rhabdoid tumor is a rare malignant CNS tumor that most often affects children ≤ 3 years old. The Central Brain Tumor Registry of the United States contains the largest aggregation of population-based incidence data for primary CNS tumors in the US. Its data were used to describe the incidence, associated trends, and relative survival after diagnosis of atypical teratoid/rhabdoid tumor. METHODS Using data from 50 cancer registries between 2001 and 2010, age-adjusted incidence rates per 100 000 and 95% CIs were calculated by sex, race, Hispanic ethnicity, age at diagnosis, and location of tumor in the CNS for children aged 0 to 19 years. Relative survival rates and 95% CIs were also calculated. RESULTS The average annual age-adjusted incidence rate was 0.07 (95% CI: 0.07, 0.08). Incidence rates did not significantly vary by sex, race, or ethnicity. Age had a strong effect on incidence rate, with highest incidence among children <1 year, and decreasing incidence with increasing age. The 6-month, 1-year, and 5-year relative survival rates for all ages were 65.0%, 46.8%, and 28.3%, respectively. Atypical teratoid/rhabdoid tumor can occur anywhere in the CNS, but supratentorial tumors were more common with increasing age. CONCLUSION We confirm differences in survival by age at diagnosis, treatment pattern, and location of tumor in the brain. This contributes to our understanding of these tumors and may stimulate research leading to improved treatment of this devastating childhood disease.

Fractional anisotropy of the optic radiations is associated with visual acuity loss in optic pathway gliomas of neurofibromatosis type 1

BACKGROUND No more than half of patients with neurofibromatosis type 1 (NF1)-associated optic pathway gliomas (OPGs) develop vision loss. Prospectively identifying those who will require therapy remains challenging, because no reliable factors have yet been identified that predict future vision loss. To determine whether brain tissue microstructure is associated with visual acuity loss, we examined diffusion tensor imaging (DTI) and ophthalmologic evaluations in children with NF1-associated OPG. METHODS We retrospectively reviewed ophthalmology records and concurrent DTI measurements of the optic nerves, tracts, and radiations from 50 children with NF1-associated OPGs. Multivariate linear regression measured the association between fiber trajectory quantity and white matter integrity on visual acuity measured by the logarithm of the minimal angle of resolution (logMAR). RESULTS In multivariate analysis, fractional anisotropy (FA) of the optic radiations was associated with visual acuity loss (adjusted coefficient = -6.081 logMAR/FA; P = .006) after adjusting for age, extent of tumor, DTI acquisition type, prior chemotherapy, and fundus examination findings. The association remained after eliminating tumors involving the optic radiations. In an evaluation of 15 subjects with paired ophthalmologic examination and DTI a year apart, initial FA of the optic radiation was associated with a trend toward change in visual acuity a year later (coefficient = -2.652 logMAR/FA; P = .069). CONCLUSIONS A decrease in FA of the optic radiations is associated with abnormal visual acuity in NF1-associated OPGs and may be predictive of visual acuity loss during the following year.

Variation in Risk of Hospital-Onset Clostridium difficile Infection Across β-Lactam Antibiotics in Children With New-Onset Acute Lymphoblastic Leukemia

BACKGROUND Antibiotic exposure is common among children with leukemia. However, limited data exist regarding the risk of Clostridium difficile infection (CDI) across anti-pseudomonal β-lactam antibiotics commonly used for fever and neutropenia. METHODS A multicenter cohort of children with newly diagnosed acute lymphoblastic leukemia (ALL) was established from 43 freestanding childrens hospitals from 1999 to 2009. Patients were followed until their index CDI event, defined by the CDI ICD-9 code plus a C difficile test charge, or until 180 days from ALL diagnosis. Cox proportional hazards models were performed to identify the hazards of CDI after exposure to anti-pseudomonal β-lactams, adjusting for demographics, other antibiotic exposures, severity of illness, antacids, gastrointestinal manipulation, and confounding by hospital. RESULTS A cohort of 8268 ALL patients was assembled; median age was 5.5 years (interquartile range, 3.26-10.58). Two-hundred sixty-eight (3.2%) patients developed CDI within 180 days of ALL diagnosis. Each 1-day increase in exposure to an anti-pseudomonal β-lactam within the prior 30 days was associated with a significantly increased risk for CDI (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01, 1.09). Ceftazidime (HR, 1.05; 95% CI, 1.02, 1.08) and cefepime (HR, 1.07; 95% CI, 1.02, 1.12) were each independently associated with CDI. CONCLUSIONS Efforts to reduce total exposure to anti-pseudomonal β-lactam agents may help to reduce the risk of CDI in children with newly diagnosed ALL. Cefepime and ceftazidime were independently associated with CDI, whereas anti-pseudomonal penicillins and carbapenems were not. These findings, if confirmed, have potential implications for antibiotic choice during periods of fever and neutropenia.

Years of life lived with disease and years of potential life lost in children who die of cancer in the United States, 2009.

Incidence and survival rates are commonly reported statistics, but these may fail to capture the full impact of childhood cancers. We describe the years of potential life lost (YPLL) and years of life lived with disease (YLLD) in children and adolescents who died of cancer in the United States to estimate the impact of childhood cancer in the United States in 2009. We examined mortality data in 2009 among children and adolescents <20 years old in both the National Vital Statistics System (NVSS) and the Surveillance, Epidemiology, and End Results (SEER) datasets. YPLL and YLLD were calculated for all deaths due to cancer. Histology‐specific YPLL and YLLD of central nervous system (CNS) tumors, leukemia, and lymphoma were estimated using SEER. There were 2233 deaths and 153,390.4 YPLL due to neoplasm in 2009. CNS tumors were the largest cause of YPLL (31%) among deaths due to cancer and were the cause of 1.4% of YPLL due to all causes. For specific histologies, the greatest mean YPLL per death was due to atypical teratoid/rhabdoid tumor (78.0 years lost). The histology with the highest mean YLLD per death in children and adolescents who died of cancer was primitive neuroectodermal tumor (4.6 years lived). CNS tumors are the most common solid malignancy in individuals <20 years old and have the highest YPLL cost of all cancers. This offers the first histology‐specific description of YPLL in children and adolescents and proposes a new measure of cancer impact, YLLD, in individuals who die of their disease. YPLL and YLLD complement traditional indicators of mortality and help place CNS tumors in the context of other childhood malignancies.

A rare case of ectopic recurrence of a craniopharyngioma diagnosed 17 years after initial presentation

Ectopic recurrence of craniopharyngioma 17 years after initial diagnosis is exceedingly rare in pediatric neuro-oncology. Only 23 cases of ectopic recurrence in children with craniopharyngioma are described in the literature with a median time to recurrence of 3 years. We describe a patient diagnosed at 5 years of age, presenting with neck pain and ataxia 17 years after diagnosis. Her original follow-up care was fragmented and included surveillance imaging for 10 years after surgery and endocrine management of panhypopituitarism. Rare, extremely late relapse of this tumor highlights the importance of extended multidisciplinary follow-up care that includes neuro-oncologists in a late-effects/survivorship program.

Systemic Chemotherapy and White Matter Integrity in Tracts Associated with Cognition Among Children With Neurofibromatosis Type 1.

Children with neurofibromatosis type 1 (NF1) are predisposed to both brain tumors and cognitive deficits. While changes in white matter integrity after multimodal therapy are associated with cognitive dysfunction, the effect of isolated chemotherapy in NF1 is unknown. To determine whether chemotherapy is associated with white matter microstructural changes, we examined diffusion tensor imaging (DTI) in NF1 subjects.

Impact of vision loss among survivors of childhood central nervous system astroglial tumors.

The impact of impaired vision on cognitive and psychosocial outcomes among long‐term survivors of childhood low‐grade gliomas has not been investigated previously but could inform therapeutic decision making.