PURPOSE: The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation. MATERIALS AND METHODS: Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration. RESULTS: In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics. CONCLUSION: The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.

Having metastatic disease at diagnosis poses the great risk of death among AYAs with cancer from all sociodemographic subgroups. This “landscape” study utilized United States Surveillance, Epidemiology, and End Results Program data from 2000–2016 to identify subgroups of AYAs at highest risk for presenting with metastases across twelve cancer sites having a poor-prognosis (5-year survival <50% with metastases). Adjusted odds ratios for risk of metastatic disease presentation were compared for AYAs in aggregate and by sociodemographic subgroup (race/ethnicity, sex, socioeconomic status [SES]). In general, AYAs who were male, racial/ethnic minorities, or low SES were at consistently greatest risk of metastases. Strikingly, having metastatic melanoma was independently associated with multiple AYA sociodemographic subgroups, including males (aOR 3.11 [95% CI 2.64–3.66]), non-Hispanic Blacks (4.04 [2.32–7.04]), Asian Pacific Islanders (2.99 [1.75–5.12]), Hispanics (2.37 [1.85–3.04]), and low SES (2.30 [1.89–2.80]). Non-Hispanic Blacks were more likely to present with metastatic cancer in all sites, except for bone, rhabdomyosarcoma, and stomach. Low SES AYAs are more likely to present with metastatic melanoma, bone tumors, soft tissue sarcomas, breast, cervical, lung, and stomach carcinomas. Building on these results, future cancer-specific studies should investigate the connection between sociodemographic risk factors and biological drivers of metastases. This line of research has potential to inform targeted public health and screening efforts to facilitate risk reduction and earlier detection of these deadly diseases.

Background: Although survival has improved dramatically for most adolescents and young adults (AYA; 15–39 years old) with cancer, it remains poor for those presenting with metastatic disease. To better characterize this subset, we conducted a landscape survival comparison with older adults (40–79 years). Methods: Using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, we examined incident cases of poor-prognosis metastatic cancers (5-year survival < 50%) among AYAs (n = 11,518) and older adults (n = 345,681) and compared cause-specific survival by sociodemographic characteristics (race/ethnicity, sex, and socioeconomic status). Adjusted HRs (aHR) for death from metastatic disease [95% confidence intervals (95% CI)] were compared between AYAs and older adults (Pint). Results: AYAs had significantly better survival than older adults for every cancer site except kidney, where it was equivalent (range of aHRs = 0.91; 95% CI, 0.82–1.02 for kidney cancer to aHR = 0.33; 95% CI, 0.26–0.42 for rhabdomyosarcoma). Compared with their older adult counterparts, greater survival disparities existed for AYAs who were non-Hispanic Black with uterine cancer (aHR = 2.20; 95% CI, 1.25–3.86 versus aHR = 1.40; 95% CI, 1.28–1.54; Pint = 0.049) and kidney cancer (aHR = 1.51; 95% CI, 1.15–1.98 versus aHR = 1.10; 95% CI, 1.03–1.17; Pint = 0.04); non-Hispanic Asian/Pacific Islanders with ovarian cancer (aHR = 1.47; 95% CI, 1.12–1.93 versus aHR = 0.89; 95% CI, 0.84–0.95; Pint<0.001); and males with colorectal cancer (aHR = 1.21; 95% CI, 1.10–1.32 versus aHR = 1.08; 95% CI, 1.06–1.10; Pint = 0.045). Conclusions: AYAs diagnosed with these metastatic cancers have better survival than older adults, but outcomes remain dismal. Impact: Overcoming the impact of metastasis in these cancers is necessary for continuing progress in AYA oncology. Sociodemographic disparities affecting AYAs within kidney, uterine, ovarian, and colorectal cancer could indicate plausible effects of biology, environment, and/or access and should be explored.

Supplementary Table from Survival of Adolescents and Young Adults with Prevalent Poor-Prognosis Metastatic Cancers: A Population-Based Study of Contemporary Patterns and Their Implications

Background:Although survival has improved dramatically for most adolescents and young adults (AYA; 15–39 years old) with cancer, it remains poor for those presenting with metastatic disease. To better characterize this subset, we conducted a landscape survival comparison with older adults (40–79 years).Methods:Using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, we examined incident cases of poor-prognosis metastatic cancers (5-year survival < 50%) among AYAs (n = 11,518) and older adults (n = 345,681) and compared cause-specific survival by sociodemographic characteristics (race/ethnicity, sex, and socioeconomic status). Adjusted HRs (aHR) for death from metastatic disease [95% confidence intervals (95% CI)] were compared between AYAs and older adults (Pint).Results:AYAs had significantly better survival than older adults for every cancer site except kidney, where it was equivalent (range of aHRs = 0.91; 95% CI, 0.82–1.02 for kidney cancer to aHR = 0.33; 95% CI, 0.26–0.42 for rhabdomyosarcoma). Compared with their older adult counterparts, greater survival disparities existed for AYAs who were non-Hispanic Black with uterine cancer (aHR = 2.20; 95% CI, 1.25–3.86 versus aHR = 1.40; 95% CI, 1.28–1.54; Pint = 0.049) and kidney cancer (aHR = 1.51; 95% CI, 1.15–1.98 versus aHR = 1.10; 95% CI, 1.03–1.17; Pint = 0.04); non-Hispanic Asian/Pacific Islanders with ovarian cancer (aHR = 1.47; 95% CI, 1.12–1.93 versus aHR = 0.89; 95% CI, 0.84–0.95; Pint<0.001); and males with colorectal cancer (aHR = 1.21; 95% CI, 1.10–1.32 versus aHR = 1.08; 95% CI, 1.06–1.10; Pint = 0.045).Conclusions:AYAs diagnosed with these metastatic cancers have better survival than older adults, but outcomes remain dismal.Impact:Overcoming the impact of metastasis in these cancers is necessary for continuing progress in AYA oncology. Sociodemographic disparities affecting AYAs within kidney, uterine, ovarian, and colorectal cancer could indicate plausible effects of biology, environment, and/or access and should be explored.