Diagnostics and treatment of diffuse intrinsic pontine glioma: where do we stand?

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. METHODS: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. RESULTS: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. CONCLUSION: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.

Maternal Serum Cobalamin at 18 Weeks of Pregnancy Predicts Infant Cobalamin Status at 6 Months-A Prospective, Observational Study.

Background: An adequate maternal cobalamin status is crucial for fetal and infant neurodevelopment. Pregnancy-induced physiologic changes make evaluation of maternal cobalamin status in pregnancy difficult. Objective: We have investigated maternal cobalamin status during pregnancy in order to establish a maternal cobalamin concentration which secures an optimal infant cobalamin status during the first 6 mo of life. Methods: In an observational, prospective study, markers of cobalamin status including serum cobalamin, plasma total homocysteine (tHcy), and plasma methylmalonic acid (MMA) were assessed in healthy pregnant women (n = 114) from week 18 of pregnancy through 6 mo postpartum and related to infant cobalamin status at 6 mo. Healthy, never-pregnant women aged 18-40 y (n = 123) were included as controls. Results: Compared to controls, all markers of cobalamin status were lower in pregnant women. Median serum cobalamin concentration progressively decreased from week 18 to week 36 of pregnancy (356 to 302 pmol/L, P < 0.001) and increased by >40% by 6 wk postpartum (518 pmol/L). The metabolic markers increased from week 18 of pregnancy to 6 wk postpartum: median plasma tHcy 3.9 to 7.7 µmol/L (P < 0.001), and MMA 0.13 to 0.17 µmol/L (P < 0.001). The serum cobalamin concentration of infants at age 6 mo correlated with maternal serum cobalamin concentration during pregnancy and postpartum (rho = 0.36-0.55, P < 0.001). A maternal serum cobalamin concentration <394 pmol/L during week 18 of pregnancy was associated with an increased risk (OR: 4.2; 95% CI: 1.5, 11.5) of infant biochemical cobalamin deficiency at 6 mo (defined as tHcy ≥6.5 µmol/L). Conclusions: The maternal serum cobalamin concentration in early pregnancy is a strong predictor for later maternal and infant cobalamin status. To secure an optimal infant cobalamin status during the first 6 mo of life, we recommend a maternal serum cobalamin concentration >394 pmol/L at week 18 of pregnancy. This should be confirmed in an intervention study. This trial was registered at clinicaltrials.gov as NCT03272022.

Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease.

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.

Physical activity behaviors and screen time in young childhood cancer survivors: the Physical Activity in Childhood Cancer Survivors Study.

PURPOSE: In childhood cancer survivors (CCS), high physical activity (PA) and low sedentary time may reduce risks of late-effects. PA behaviors and screen time, and how they relate to moderate-to-vigorous PA (MVPA) in CCS, are largely unknown. We examined PA behaviors and screen time, and their cross-sectional associations with MVPA. METHODS: CCS from any cancer diagnosis (≥ l year post-treatment), aged 9-16 years at study, were eligible in the international Physical Activity in Childhood Cancer Survivors (PACCS) study. PA behaviors (school transport, intensity-effort in physical education ("PE intensity"), leisure-time PA) and screen time were assessed by self-report, and MVPA by accelerometers (ActiGraph GT3X-BT). Multivariable linear regressions were used to assess associations between PA behaviors and screen time with MVPA. RESULTS: We included 481 CCS (48% girls, mean age 12.2 years). Passive school transport (prevalence 42%) was associated with 10% lower MVPA/day (ß = 6.6 min, 95% CI 3.3-10.0), low PE intensity (prevalence 21%) with 16% lower MVPA/day (ß = 10.2 min, 95% CI 6.0-14.3), and low leisure-time PA (prevalence 34%) with 15% lower MVPA/day (ß = 9.4 min, 95% CI 1.0-17.7), compared to active school transport, high PE intensity and high leisure-time PA, respectively. High screen time was not associated with MVPA. CONCLUSION: Interventions aiming to increase PA behaviors rather than reducing screen time may be more efficient in promoting a healthy lifestyle in CCS through increased MVPA. Encouraging active transport, high PE intensity, and high leisure-time PA seems important in survivorship care. IMPLICATIONS FOR CANCER SURVIVORS: Young CCS may benefit from engaging in active transport, high PE intensity, and high leisure-time PA.

Physical Activity Among Adolescent Cancer Survivors: The PACCS Study.

OBJECTIVES: Physical activity (PA) may modify risks of late effects after cancer. We aimed to examine levels of PA and sedentary time (ST) in a large, international sample of adolescent childhood cancer survivors in relation to sociodemographic and cancer-related factors and compare levels of PA and ST to reference cohorts. METHODS: Survivors from any cancer diagnosis who had completed cancer treatment ≥1 year ago, aged 9 to 16 years, were eligible for the multicenter Physical Activity in Childhood Cancer Survivors study. PA and ST were measured by ActiGraph GT3X+ accelerometers. We performed linear regression analyses to assess factors associated with moderate-to-vigorous PA (MVPA) and ST, and compared marginal means of total PA, MVPA, and ST in 432 survivors to sex- and age-stratified references (2-year intervals) using immediate t-tests for aggregated data. RESULTS: Among survivors, 34% fulfilled the World Health Organization's PA recommendation of ≥60 min of daily MVPA on average and their ST was 8.7 hours per day. Being female, older, overweight, a survivor of central nervous system tumor, or having experienced relapse were associated with lower MVPA and/or higher ST. Generally, male survivors spent less time in MVPA compared with references, whereas female survivors had similar levels. Both male and female survivors had higher ST than references in nearly all age groups. CONCLUSIONS: The low PA and high ST in this large sample of adolescent childhood cancer survivors is worrisome. Combined, our results call for targeted interventions addressing both PA and ST in follow-up care after childhood cancer.