RESUMO
Radiation therapy (RT) is a critical part of definitive therapy for pediatric high-grade glioma (pHGG). RT is designed to treat residual tumor defined on conventional MRI (cMRI), though pHGG lesions may be ill-characterized on standard imaging. Spectroscopic MRI (sMRI) measures endogenous metabolite concentrations in the brain, and Choline (Cho)/N-acetylaspartate (NAA) ratio is a highly sensitive biomarker for metabolically active tumor. We provide a preliminary report of our study introducing a novel treatment approach of whole brain sMRI-guided proton therapy for pHGG. An observational cohort (c1 = 10 patients) receives standard of care RT; a therapeutic cohort (c2 = 15 patients) receives sMRI-guided proton RT. All patients undergo cMRI and sMRI, a high-resolution 3D whole-brain echo-planar spectroscopic imaging (EPSI) sequence (interpolated resolution of 12 µL) prior to RT and at several follow-up timepoints integrated into diagnostic scans. Treatment volumes are defined by cMRI for c1 and by cMRI and Cho/NAA ≥ 2x for c2. A longitudinal imaging database is used to quantify changes in lesion and metabolite volumes. Four subjects have been enrolled (c1 = 1/c2 = 3) with sMRI imaging follow-up of 4-18 months. Preliminary data suggest sMRI improves identification of pHGG infiltration based on abnormal metabolic activity, and using proton therapy to target sMRI-defined high-risk regions is safe and feasible.
Assuntos
Neoplasias Encefálicas , Glioma , Terapia com Prótons , Humanos , Criança , Espectroscopia de Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Glioma/diagnóstico por imagem , Glioma/radioterapia , Imageamento por Ressonância Magnética/métodosRESUMO
Accurate radiation therapy (RT) targeting is crucial for glioblastoma treatment but may be challenging using clinical imaging alone due to the infiltrative nature of glioblastomas. Precise targeting by whole-brain spectroscopic MRI, which maps tumor metabolites including choline (Cho) and N-acetylaspartate (NAA), can quantify early treatment-induced molecular changes that other traditional modalities cannot measure. We developed a pipeline to determine how spectroscopic MRI changes during early RT are associated with patient outcomes to provide insight into the utility of adaptive RT planning. Data were obtained from a study (NCT03137888) where glioblastoma patients received high-dose RT guided by the pre-RT Cho/NAA twice normal (Cho/NAA ≥ 2x) volume, and received spectroscopic MRI scans pre- and mid-RT. Overlap statistics between pre- and mid-RT scans were used to quantify metabolic activity changes after two weeks of RT. Log-rank tests were used to quantify the relationship between imaging metrics and patient overall and progression-free survival (OS/PFS). Patients with lower Jaccard/Dice coefficients had longer PFS (p = 0.045 for both), and patients with lower Jaccard/Dice coefficients had higher OS trending towards significance (p = 0.060 for both). Cho/NAA ≥ 2x volumes changed significantly during early RT, putting healthy tissue at risk of irradiation, and warranting further study into using adaptive RT planning.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/diagnóstico por imagem , Glioblastoma/radioterapia , Glioblastoma/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Planejamento da Radioterapia Assistida por ComputadorRESUMO
Glioblastoma (GBM) is a fatal disease, with poor prognosis exacerbated by difficulty in assessing tumor extent with imaging. Spectroscopic MRI (sMRI) is a non-contrast imaging technique measuring endogenous metabolite levels of the brain that can serve as biomarkers for tumor extension. We completed a three-site study to assess survival benefits of GBM patients when treated with escalated radiation dose guided by metabolic abnormalities in sMRI. Escalated radiation led to complex post-treatment imaging, requiring unique approaches to discern tumor progression from radiation-related treatment effect through our quantitative imaging platform. The purpose of this study is to determine true tumor recurrence timepoints for patients in our dose-escalation multisite study using novel methodology and to report on median progression-free survival (PFS). Follow-up imaging for all 30 trial patients were collected, lesion volumes segmented and graphed, and imaging uploaded to our platform for visual interpretation. Eighteen months post-enrollment, the median PFS was 16.6 months with a median time to follow-up of 20.3 months. With this new treatment paradigm, incidence rate of tumor recurrence one year from treatment is 30% compared to 60-70% failure under standard care. Based on the delayed tumor progression and improved survival, a randomized phase II trial is under development (EAF211).