The threat of the COVID-19 pandemic on reversing global life-saving gains in the survival of childhood cancer: a call for collaborative action from SIOP, IPSO, PROS, WCC, CCI, St Jude Global, UICC and WHPCA.

The COVID-19 pandemic poses an unprecedented health crisis in all socio-economic regions across the globe. While the pandemic has had a profound impact on access to and delivery of health care by all services, it has been particularly disruptive for the care of patients with life-threatening noncommunicable diseases (NCDs) such as the treatment of children and young people with cancer. The reduction in child mortality from preventable causes over the last 50 years has seen childhood cancer emerge as a major unmet health care need. Whilst survival rates of 85% have been achieved in high income countries, this has not yet been translated into similar outcomes for children with cancer in resource-limited settings where survival averages 30%. Launched in 2018, by the World Health Organization (WHO), the Global Initiative for Childhood Cancer (GICC) is a pivotal effort by the international community to achieve at least 60% survival for children with cancer by 2030. The WHO GICC is already making an impact in many countries but the disruption of cancer care during the COVID-19 pandemic threatens to set back this global effort to improve the outcome for children with cancer, wherever they may live. As representatives of the global community committed to fostering the goals of the GICC, we applaud the WHO response to the COVID-19 pandemic, in particular we support the WHO's call to ensure the needs of patients with life threatening NCDs including cancer are not compromised during the pandemic. Here, as collaborative partners in the GICC, we highlight specific areas of focus that need to be addressed to ensure the immediate care of children and adolescents with cancer is not disrupted during the pandemic; and measures to sustain the development of cancer care so the long-term goals of the GICC are not lost during this global health crisis.

Contemporary Treatment Patterns and Outcomes for Clinical Stage IS Testicular Cancer.

BACKGROUND: Controversy exists regarding the optimal management strategy for clinical stage IS seminomatous (SGCT) and nonseminomatous germ cell tumors (NSGCT) of the testis. OBJECTIVE: To assess contemporary treatment patterns and outcomes for clinical stage IS testicular cancer. DESIGN, SETTING, AND PARTICIPANTS: Using the National Cancer Data Base (2004-2012), we identified 1362 patients with clinical stage IS SGCT and NSGCT of the testis, treated with either adjuvant treatment (AT) or observation. OUTCOME MEASURES AND STATISTICAL ANALYSIS: We calculated the annual percent change (APC) to assess treatment trends. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare overall survival (OS) between AT and observation groups. Analyses were stratified by histologic type. RESULTS AND LIMITATIONS: Overall, there were 581 (43%) and 781 (57%) men with SGCT and NSGCT, respectively. Among men with SGCT, the use of AT decreased over the study period (APC=-2.7, 95% confidence interval [CI]: -4.4, -1.1, p=0.001). The 5-yr IPTW-adjusted rates of OS were 99% and 97% in the AT and observation groups, respectively (hazard ratio = 0.36, 95% CI: 0.12, 1.14, p=0.08). Among men with NSGCT, the use of AT remained stable over the study period (APC = +0.8, 95% CI: -0.7, +2.2, p=0.29). The 5-yr IPTW-adjusted rates of OS were 97% and 95% in the AT and observation groups, respectively (HR=0.66, 95% CI: 0.27, 1.61, p=0.36). Limitations include the lack of full treatment details and cancer-specific survival information. CONCLUSIONS: Trends in the use of AT significantly decreased over time for SGCT, while it remained stable for NSGCT. Nonetheless, we report 5-yr OS rates of ≥95% for both histologies without any significant benefit with the use of AT. Further studies are warranted to confirm these findings. PATIENT SUMMARY: We evaluated treatment trends and outcomes for stage IS testicular cancer. We found that treatment changed over time for seminoma and remained stable for nonseminoma; there was no significant survival benefit in the use of adjuvant treatment versus observation for both seminomatous and nonseminomatous germ cell tumors.

Vitamin D supplementation and growth in urban Mongol school children: Results from two randomized clinical trials.

BACKGROUND: Symptomatic vitamin D deficiency is associated with slowed growth in children. It is unknown whether vitamin D repletion in children with asymptomatic serum vitamin D deficiency can restore normal growth. OBJECTIVE: We tested the impact of vitamin D-supplementation on serum concentrations of 25-hydroxyvitamin D [25(OH)D] and short-term growth in Mongol children, with very low serum vitamin D levels in winter. DESIGN: We conducted two randomized, double-blind, placebo-controlled trials in urban school age children without clinical signs of rickets. The Supplementation Study was a 6-month intervention with an 800 IU vitamin D3 supplement daily, compared with placebo, in 113 children aged 12-15 years. A second study, the Fortification Study, was a 7-week intervention with 710 ml of whole milk fortified with 300 IU vitamin D3 daily, compared with unfortified milk, in 235 children aged 9-11 years. RESULTS: At winter baseline, children had low vitamin D levels, with a mean (±SD) serum 25-hydroxyvitamin D [25(OH)D] concentration of 7.3 (±3.9) ng/ml in the Supplementation Study and 7.5 (±3.8) ng/ml in the Fortification Study. The serum levels increased in both vitamin D groups-by 19.8 (±5.1) ng/ml in the Supplementation Study, and 19.7 (±6.1) ng/ml in the Fortification Study. Multivariable analysis showed a 0.9 (±0.3 SE) cm greater increase in height in the vitamin-D treated children, compared to placebo treated children, in the 6-month Supplementation Study (p = 0.003). Although the children in the 7-week Fortification Study intervention arm grew 0.2 (±0.1) cm more, on average, than placebo children this difference was not statistically significant (p = 0.2). There were no significant effects of vitamin D supplements on differences in changes in weight or body mass index in either trial. For the Fortification Study, girls gained more weight than boys while taking vitamin D 3 (p-value for interaction = 0.03), but sex was not an effect modifier of the relationship between vitamin D3 and change in either height or BMI in either trial. CONCLUSIONS: Correcting vitamin D deficiency in children with very low serum vitamin D levels using 800 IU of vitamin D3 daily for six months increased growth, at least in the short-term, whereas, in a shorter trial of 300 IU of D fortified milk daily for 7 weeks did not.

Insurance status and disparities in disease presentation, treatment, and outcomes for men with germ cell tumors.

BACKGROUND: People aged 26 to 34 years represent the greatest proportion of the uninsured, and they have the highest incidence of testicular cancers. The aim of this study was to investigate the association between insurance status and cancer outcomes in men diagnosed with germ cell tumors. METHODS: The Surveillance, Epidemiology, and End Results database was used to identify 10,211 men diagnosed with germ cell gonadal neoplasms from 2007 to 2011. Associations between insurance status and characteristics at diagnosis and receipt of treatment were examined with log-binomial regression. The association between insurance status and mortality was assessed with Cox proportional hazards regression. RESULTS: Uninsured patients had an increased risk of metastatic disease at diagnosis (relative risk [RR], 1.26; 95% confidence interval [CI], 1.15-1.38) in comparison with insured patients, as did Medicaid patients (RR, 1.62; 95% CI, 1.51-1.74). Among men with metastatic disease, uninsured and Medicaid patients were more likely to be diagnosed with intermediate/poor-risk disease (RR for uninsured patients, 1.22; 95% CI, 1.04-1.44; RR for Medicaid patients, 1.39; 95% CI, 1.23-1.57) and were less likely to undergo lymph node dissection (RR for uninsured patients, 0.74; 95% CI, 0.57-0.94; RR for Medicaid patients, 0.76; 95% CI, 0.63-0.92) in comparison with insured patients. Men without insurance were more likely to die of their disease (hazard ratio [HR], 1.88; 95% CI, 1.29-2.75) in comparison with insured men, as were those with Medicaid (HR, 1.51; 95% CI, 1.08-2.10). CONCLUSIONS: Patients without insurance and patients with Medicaid have an increased risk of presenting with advanced disease and dying of the disease in comparison with those who have insurance. Future studies should examine whether implementation of the Patient Protection and Affordable Care Act reduces these disparities. Cancer 2016;122:3127-35. © 2016 American Cancer Society.

Beyond the bench and the bedside: economic and health systems dimensions of global childhood cancer outcomes.

Globally, the number of new cases of childhood cancer continues to rise, with a widening gulf in outcomes across countries, despite the availability of effective cure options for many pediatric cancers. Economic forces and health system realities are deeply embedded in the foundation of disparities in global childhood cancer outcomes. A truly global effort to close the childhood cancer divide therefore requires systemic solutions. Analysis of the economic and health system dimensions of childhood cancer outcomes is essential to progress in childhood cancer survival around the globe. The conceptual power of this approach is significant. It provides insight into how and where pediatric oncology entwines with broader political and economic conditions, and highlights the mutual benefit derived from systems-oriented solutions.

Vitamin D deficiency in reproductive age Mongolian women: a cross sectional study.

Vitamin D production is critical not only for rickets prevention but for its role in several chronic diseases of adulthood. Maternal vitamin D status also has consequences for the developing fetus. This study assessed the prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D]<20ng/ml) and insufficiency [25(OH)D=20-29ng/ml] in spring, among reproductive age Mongolian women. Blood was drawn in March and April, 2009 from 420 Mongolian women, 18-44 years of age. Serum 25(OH)D concentrations were measured, anthropometric measurements were performed and information was collected by interview on lifestyle, dietary and reproductive factors. Logarithm-transformed 25(OH)D levels were compared across risk factor categories by analysis of variance. Linear regression analysis was used to assess the independent associations of factors with vitamin D status. Cutaneous vitamin D3 synthesis was assessed between December and July using a standard 7-dehydrocholesterol ampoule model. The vast majority of women 415 (98.8%) had serum 25(OH)D<20ng/ml (50nmol/l) with an additional 4 women (<1%) in the insufficient range (20-29ng/ml); only one women (0.2%) had sufficient levels (>30ng/ml or 75nmol/l). 25(OH)D concentrations were positively and independently associated with educational status and use of vitamin D supplements, but not with other demographic, lifestyle, reproductive, or anthropometric factors. 25(OH)D levels were not associated with dietary factors in this population, as there is little access to foods containing vitamin D in Mongolia. No production of previtamin D3 was observed until March and was maximally effective in April and was sustained through July. These data suggest that the prevalence of vitamin D deficiency in spring among reproductive age women in Mongolia is high. Given the lack of naturally vitamin D-rich food in the diet and limited use of vitamin D supplements, food fortification and/or supplementation with vitamin D should be considered among these women.

A comparison of migrants to, and women born in, urban Mongolia: demographic, reproductive, anthropometric and lifestyle characteristics.

BACKGROUND: Mongolia has experienced vast migration from rural to urban areas since the 1950s. We hypothesized that women migrating to Ulaanbaatar, the capital, would differ in factors related to future chronic disease risk compared with women who were born in Ulaanbaatar. METHODS: Premenopausal mothers (aged <44 years) of children attending two schools (one in the city centre and one in the outskirts) in Ulaanbaatar were recruited for the study. During April and May 2009, 420 women were interviewed about migration, reproductive history and lifestyle factors and anthropometric measurements were taken. RESULTS: Women born in (n=178) and outside (n=242) Ulaanbaatar were similar in education and marital status, but the latter appeared to have a more traditional lifestyle including being more likely to have lived as a nomadic herder (22.3% vs 5.6%; p<0.001) and to currently live in a traditional yurt or ger (40.1% vs 29.2%). Ever-use of hormonal contraception was more common in women born outside Ulaanbaatar (52.1% vs 38.2%; p=0.005) and their age at first live birth was older (26.0% vs 20.8% for ≥ 25 vs <25 years). Although the number of pregnancies was similar, the number of live births was greater for those born outside Ulaanbaatar (p=0.002). Women born in Ulaanbaatar were more likely to have smoked cigarettes (24.7% vs 11.2%; p<0.001). Women born outside Ulaanbaatar were more likely to consume the traditional meat and dairy diet. CONCLUSION: Rural migrants to Mongolia's capital have retained a traditional lifestyle in some, but not all, respects. Internal migrant populations may provide the opportunity to assess the effect of changes in isolated risk factors for subsequent chronic disease.

Red meat consumption during adolescence among premenopausal women and risk of breast cancer.

BACKGROUND: Adolescence may be a period of increased susceptibility to breast cancer due to regular division of undifferentiated cells that occurs between puberty and first birth. Red meat consumption during early adult life has been associated with breast cancer, but intake during adolescence has not been examined prospectively. We aimed to assess the relationship between red meat intake during adolescence and premenopausal breast cancer. METHODS: We examined the incidence of invasive premenopausal breast cancer prospectively within the Nurses' Health Study II. A total of 39,268 premenopausal women who completed a validated 124-item food frequency questionnaire on their diet during high school, were followed for 7 years, from 1998 to 2005. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). RESULTS: 455 cases of invasive premenopausal breast cancer were diagnosed between 1998 and 2005. Compared with women in the lowest quintile of red meat intake during high school, the multivariate-adjusted RR for the highest quintile of intake was 1.34 (95% CI, 0.94-1.89; P(trend) = 0.05). A significant linear association was observed with every additional 100 g of red meat consumed per day (RR, 1.20; 95% CI, 1.00-1.43; P = 0.05). This association was more pronounced in hormone receptor-positive tumors (RR, 1.36; 95% CI, 1.08-1.70; P = 0.008) and was not significant in hormone receptor-negative tumors (RR, 0.99; 95% CI, 0.61-1.61, P = 0.97). CONCLUSION: Higher red meat intake in adolescence may increase the risk of premenopausal breast cancer.