Magnetic Resonance Spectroscopy Metabolites as Biomarkers of Disease Status in Pediatric Diffuse Intrinsic Pontine Gliomas (DIPG) Treated with Glioma-Associated Antigen Peptide Vaccines
| العنوان: | Magnetic Resonance Spectroscopy Metabolites as Biomarkers of Disease Status in Pediatric Diffuse Intrinsic Pontine Gliomas (DIPG) Treated with Glioma-Associated Antigen Peptide Vaccines |
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| المؤلفون: | Ashok Panigrahy, Regina I. Jakacki, Ian F. Pollack, Rafael Ceschin, Hideho Okada, Marvin D. Nelson, Gary Kohanbash, Girish Dhall, Stefan Bluml |
| المصدر: | Cancers, vol 14, iss 23 Cancers; Volume 14; Issue 23; Pages: 5995 |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, myo-inositol, Prevention, MR spectroscopy, brainstem glioma, pediatric brain tumor, Oncology and Carcinogenesis, Neurosciences, Brain Disorders, Brain Cancer, Vaccine Related, creatine, Orphan Drug, Rare Diseases, Good Health and Well Being, Oncology, choline, Clinical Research, immunotherapy, vaccine therapy, Biomedical Imaging, Immunization, Cancer, Biotechnology |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6694 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d596941f56fa7427bfd88dec24f36ffTest https://doi.org/10.3390/cancers14235995Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7d596941f56fa7427bfd88dec24f36ff |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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