Quantifying radiation therapy response using apparent diffusion coefficient (ADC) parametric mapping of pediatric diffuse intrinsic pontine glioma: a report from the pediatric brain tumor consortium
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Background and purpose
Baseline diffusion or apparent diffusion coefficient (ADC) characteristics have been shown to predict outcome related to DIPG, but the predictive value of post-radiation ADC is less well understood. ADC parametric mapping (FDM) was used to measure radiation-related changes in ADC and compared these metrics to baseline ADC in predicting progression-free survival and overall survival using a large multi-center cohort of DIPG patients (Pediatric Brain Tumor Consortium—PBTC).
Materials and methods
MR studies at baseline and post-RT in 95 DIPG patients were obtained and serial quantitative ADC parametric maps were generated from diffusion-weighted imaging based on T2/FLAIR and enhancement regions of interest (ROIs). Metrics assessed included total voxels with: increase in ADC (iADC); decrease in ADC (dADC), no change in ADC (nADC), fraction of voxels with increased ADC (fiADC), fraction of voxels with decreased ADC (fdADC), and the ratio of fiADC and fdADC (fDM Ratio).
A total of 72 patients were included in the final analysis. Tumors with higher fiADC between baseline and the first RT time point showed a trend toward shorter PFS with a hazard ratio of 6.44 (CI 0.79, 52.79, p = 0.083). In contrast, tumors with higher log mean ADC at baseline had longer PFS, with a hazard ratio of 0.27 (CI 0.09, 0.82, p = 0.022). There was no significant association between fDM derived metrics and overall survival.
Baseline ADC values are a stronger predictor of outcome compared to radiation related ADC changes in pediatric DIPG. We show the feasibility of employing parametric mapping techniques in multi-center studies to quantitate spatially heterogeneous treatment response in pediatric tumors, including DIPG.
KeywordsPediatric Brain tumor Brainstem glioma MR diffusion ADC parametric mapping
Functional diffusion map
Increase in ADC
Decrease in ADC
No change in ADC
Fraction of voxels with iADC
Fraction of voxels with dADC
Progression free survival
RC conceptualization, formal analysis, software, and writing—original draft, review and editing. MK statistical analysis, writing—review and editing. SV data curation, methodology, writing—review and editing. IFP project administration, writing—review and editing. AOT project administration, writing—review and editing. IJD writing—review and editing. TYP conceptualization, project administration, funding acquisition, writing—review and editing. AP conceptualization, project administration, funding acquisition, writing—review and editing.
This study was funded by: National Institute of Health (NIH) [Grant No. U01 CA81457]; National Library of Medicine (NLM) Grant No. 5T15LM007059-27; Memorial Sloan Kettering Cancer Center (MSKCC) [Grant No. P30 CA008748]; The Pediatric Brain Tumor Consortium Foundation; the Pediatric Brain Tumor Foundation of the United States; the American Lebanese Syrian Associated Charities and Ian’s Friends Foundation.
Compliance with ethical standards
Conflict of interest
Raf Ceschin and Dr. Ashok Panigrahy had full access to all of the data in the study and had final responsibility for the decision to submit for publication. The authors declare that there are no actual or potential conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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