Bridging the knowledge gaps in understanding the interactions of GD2 with signaling molecules within the glycosynapses, and the regulation of its cellular expression should improve therapeutic strategies targeting this ganglioside. In addition to anti-GD2 IgG mAbs, their drug conjugates, radiolabeled forms especially when genetically engineered to improve therapeutic index and novel bispecific forms or CARs to retarget T-cells are promising candidates for treating metastatic cancers.

Adult-onset neuroblastoma is rare and little is known about its biology and clinical course. There is no established therapy for adult-onset neuroblastoma. Anti-GD2 immunotherapy is now standard therapy in children with high-risk neuroblastoma; however, its use has not been reported in adults. Forty-four adults (18-71 years old) diagnosed with neuroblastoma between 1979 and 2015 were treated at Memorial Sloan Kettering Cancer Center. Five, 1, 5 and 33 patients had INSS stage 1, 2, 3 and 4 diseases, respectively. Genetic abnormalities included somatic ATRX (58%) and ALK mutations (42%) but not MYCN-amplification. In the 11 patients with locoregional disease, 10-year progression-free (PFS) and overall survival (OS) was 35.4 ± 16.1% and 61.4 ± 15.3%, respectively. Among 33 adults with stage 4 neuroblastoma, 7 (21%) achieved complete response (CR) after induction chemotherapy and/or surgery. Seven patients with primary refractory neuroblastoma (all with osteomedullary but no soft tissue disease) received anti-GD2 antibodies, mouse or humanized 3F8. Antibody-related adverse events were similar to those in children, response rate being 71.4%. In patients with stage 4 disease at diagnosis, 5-year PFS was 9.7± 5.3% and most patients who were alive with disease at 5 years died of neuroblastoma over the next 5 years, 10-year OS being only 19.0 ± 8.2%. Patients who achieved CR after induction had superior PFS and OS (p = 0.006, p = 0.031, respectively). Adult-onset neuroblastoma appeared to have different biology from pediatric or adolescent NB, and poorer outcome. Complete disease control appeared to improve long-term survival. Anti-GD2 immunotherapy was well tolerated and might be beneficial.

There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5–9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare.

Hematopoietic cell transplantation (HCT) survivors treated with total body irradiation (TBI) are known to be at increased risk for the development of cardiovascular risk factors (CVRF). We sought to characterize the incidence of CVRF in a TBI-exposed survivor cohort and describe prognostic indicators of their development. Retrospective analysis of CVRF in 1-year survivors of leukemia or lymphoma treated with TBI at Memorial Sloan Kettering from April 1987–May 2011. Eligible participants were≤ 21 years of age at TBI and were not on glucocorticoids at the time of entry to Long-Term Follow-Up. Survivors were assessed for obesity (body mass index [BMI]≥ 95th% for ages≤ 20; ≥30 kg/m2 for ages >20 years), elevated blood pressure, dyslipidemia (elevated triglycerides [TG], low high-density lipoprotein [HDL]), and glucose intolerance (fasting glucose ≥100 mg/dl); those with ≥3 risk factors were deemed to have a CVRF cluster, a surrogate for metabolic syndrome. Cox regression models were used to estimate hazard ratios (HRs) evaluating factors associated with each CVRF. In order to compare prevalence of CVRF in HCT survivors and the general population, survivors were compared to age-, sex-, and race-matched controls from the National Health and Nutrition Examination Survey (NHANES). 123 survivors were evaluated (62.6% male). Median age at TBI was 11.8 years (range 1.6–21.9); median followup was 8.0 years (1.01–24.6); median age at last followup 20.1 years (4.0–41.3). Five-year cumulative incidence of elevated blood pressure, elevated glucose, low HDL, hypertriglyceridemia, and obesity was 14.7%, 10.5%, 26.8%, 39.2%, and 16.0%, respectively, while 10-year cumulative incidence was 28.8%, 33.1%, 52.0%, 65.0%, and 18.6%, respectively. The cumulative incidence of CVRF cluster rose from 10.6% (5.6–17.5) at 5 years to 28.4% (18.8–38.7) at 10 years. In multivariate analysis, growth hormone (GH) deficiency (HR 8.6; 95% CI, 2.1–34.4, p=0.002), history of cranial radiation (HR 4.0; 95% CI, 1.7–9.6, p=0.002), and grade II-IV acute GVHD (HR 4.2; 95% CI, 1.5–12.2, p=0.008) were associated with risk of developing CVRF cluster. HCT survivors had an increased prevalence of hypertriglyceridemia and low HDL, but not glucose intolerance, elevated blood pressure, or CVRF cluster, when compared to a random sample of matched population controls. Given the young age of this HCT survivor cohort, these data highlight the importance of routine screening for CVRF starting in childhood among those exposed to TBI.