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Simple Summary: Diffuse intrinsic pontine gliomas in children are rare, highly malignant infiltrating tumors in a location precluding surgical resection. The absence of non-invasive correlates of response and disease progression in these tumors invites the exploration of imaging biomarkers. Magnetic resonance spectroscopy is an advanced imaging technique for measuring cell metabolites. This study evaluated whether measurements of in vivo cell metabolites using magnetic resonance spectroscopy may serve as biomarkers of response to therapy, including progression. Single-voxel magnetic resonance spectra were serially acquired in two cohorts of patients with these tumors treated with radiation therapy with or without concurrent chemotherapy and prior to progression: 14 participants were enrolled in a clinical trial of adjuvant glioma-associated antigen peptide vaccines and 32 patients were enrolled who did not receive adjuvant vaccine therapy. In the vaccine cohort, an elevated myo-inositol/choline ratio after 2–3 doses was associated with longer survival. Scans performed up to 6 months before death showed a terminal decline in the myo-inositol/choline ratio. Higher myo-inositol/choline ratios following radiation therapy, consistent with less proliferate tumors and decreased cell turnover, were associated with longer survival, suggesting that this ratio can serve as a biomarker of prognosis following radiation therapy. Purpose: Diffuse intrinsic pontine gliomas (DIPG) are highly aggressive tumors with no currently available curative therapy. This study evaluated whether measurements of in vivo cell metabolites using magnetic resonance spectroscopy (MRS) may serve as biomarkers of response to therapy, including progression. Methods: Single-voxel MR spectra were serially acquired in two cohorts of patients with DIPG treated with radiation therapy (RT) with or without concurrent chemotherapy and prior to progression: 14 participants were enrolled in a clinical trial of adjuvant glioma-associated antigen peptide vaccines and 32 patients were enrolled who did not receive adjuvant vaccine therapy. Spearman correlations measured overall survival associations with absolute metabolite concentrations of myo-inositol (mI), creatine (Cr), and n-acetyl-aspartate (NAA) and their ratios relative to choline (Cho) during three specified time periods following completion of RT. Linear mixed-effects regression models evaluated the longitudinal associations between metabolite ratios and time from death (terminal decline). Results: Overall survival was not associated with metabolite ratios obtained shortly after RT (1.9–3.8 months post-diagnosis) in either cohort. In the vaccine cohort, an elevated mI/Cho ratio after 2–3 doses (3.9–5.2 months post-diagnosis) was associated with longer survival (rho = 0.92, 95% CI 0.67–0.98). Scans performed up to 6 months before death showed a terminal decline in the mI/Cho ratio, with an average of 0.37 ratio/month in vaccine patients (95% CI 0.11–0.63) and 0.26 (0.04–0.48) in the non-vaccine cohort. Conclusion: Higher mI/Cho ratios following RT, consistent with less proliferate tumors and decreased cell turnover, were associated with longer survival, suggesting that this ratio can serve as a biomarker of prognosis following RT. This finding was seen in both cohorts, although the association with OS was detected earlier in the vaccine cohort. Increased mI/Cho (possibly reflecting immune-effector cell influx into the tumor as a mechanism of tumor response) requires further study. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite significant survival improvements for adolescents and young adults (AYAs) with cancer overall, several subsets of AYAs lag behind. This is especially true for AYAs diagnosed with metastatic disease, where, for many types of cancer, fewer than 20% of patients are alive 5 years later. Which sociodemographic subgroups of AYAs are at highest risk for presenting with metastatic disease is not well understood. In this study using United States Surveillance, Epidemiology, and End Results Program data, we found significantly increased risk of metastatic disease across many cancer sites for non-Hispanic Blacks, males, and low socioeconomic status AYAs. In particular, metastatic melanoma was striking for demonstrating multiple sociodemographic disparities. Results of this study shed light on the relative roles of age, race/ethnicity, sex, and socioeconomic status in metastatic disease presentation. These will inform future, cancer-specific research to elucidate biological, social, and environmental mechanisms underlying these associations with metastatic disease. 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. [ABSTRACT FROM AUTHOR]