Abstract
BACKGROUND AND PURPOSE: Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma.
MATERIALS AND METHODS: A clinical trial using the poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor veliparib concurrently with radiation therapy, followed by maintenance therapy with veliparib + temozolomide, in children with diffuse intrinsic pontine glioma was conducted by the Pediatric Brain Tumor Consortium. Standard MR imaging, DWI, dynamic contrast-enhanced perfusion, and DSC perfusion were performed at baseline and approximately every 2 months throughout treatment. ADC histogram metrics of T2-weighted FLAIR and enhancing tumor volume, dynamic contrast-enhanced permeability metrics for enhancing tumors, and tumor relative CBV from DSC perfusion MR imaging were calculated. Baseline values, post-radiation therapy changes, and longitudinal trends for all metrics were evaluated for associations with survival and pseudoprogression.
RESULTS: Fifty children were evaluable for survival analyses. Higher baseline relative CBV was associated with shorter progression-free survival (P = .02, Q = 0.089) and overall survival (P = .006, Q = 0.055). Associations of higher baseline mean transfer constant from the blood plasma into the extravascular extracellular space with shorter progression-free survival (P = .03, Q = 0.105) and overall survival (P = .03, Q = 0.102) trended toward significance. An increase in relative CBV with time was associated with shorter progression-free survival (P < .001, Q < 0.001) and overall survival (P = .004, Q = 0.043). Associations of longitudinal mean extravascular extracellular volume fraction with progression-free survival (P = .03, Q = 0.104) and overall survival (P = .03, Q = 0.105) and maximum transfer constant from the blood plasma into the extravascular extracellular space with progression-free survival (P = .03, Q = 0.102) trended toward significance. Greater increases with time were associated with worse outcomes. True radiologic progression showed greater post-radiation therapy decreases in mode_ADC_FLAIR compared with pseudoprogression (means, −268.15 versus −26.11, P = .01.)
CONCLUSIONS: ADC histogram, perfusion, and permeability MR imaging metrics in diffuse intrinsic pontine glioma are useful in predicting survival and pseudoprogression.
ABBREVIATIONS:
- DCE
- dynamic contrast-enhanced
- DIPG
- diffuse intrinsic pontine glioma
- Kep
- rate constant from extravascular extracellular space back into blood plasma
- Ktrans
- transfer constant from blood plasma into extravascular extracellular space
- OS
- overall survival
- PBTC
- Pediatric Brain Tumor Consortium
- PFS
- progression-free survival
- rCBV
- relative CBV
- RT
- radiation therapy
- TMZ
- temozolomide
- ve
- extravascular extracellular volume fraction
- vp
- blood-plasma volume fraction
Footnotes
This work was supported by the National Institutes of Health (UM1 CA081457 and P30 CA008748), the Pediatric Brain Tumor Consortium Foundation, the Pediatric Brain Tumor Foundation of the United States, and the American Lebanese Syrian Associated Charities.
Paper previously presented at: Annual Meeting of the American Society of Neuroradiology, May 18–23, 2019; Boston, Massachusetts.
Disclosures: Sridhar Vajapeyam—RELATED: Grant: National Institutes of Health.* Ira J. Dunkel—UNRELATED: Consultancy: Apexigen, Bristol-Myers Squibb, Celgene, Pfizer, Roche, Comments: all unpaid or de minimis compensation; Grants/Grants Pending: Bristol-Myers Squibb, Genentech, Novartis, Comments: Funds were provided to my institution to cover the cost of clinical trials for which I was institutional Principal Investigator.* Tina Young Poussaint—RELATED: Grant: Pediatric Brain Tumor Consortium Neuroimaging Center Grant, Comments: National Institutes of Health subcontract from the Pediatric Brain Tumor Consortium*; UNRELATED: Royalties: Springer, Comments: Atlas of Pediatric Brain Tumors. Patricia Baxter—RELATED: Grant: National Cancer Institute, Comments: Pediatric Brain Tumor Consortium (UO1) (2UM1CA081457)*; Support for Travel to Meetings for the Study or Other Purposes: Pediatric Brain Tumor Consortium (UO1) (2UM1CA081457).* Arzu Onar-Thomas—RELATED: Grant: National Cancer Institute Cancer Therapy Evaluation Program Pediatric Brain Tumor Consortium grant (2UM1CA081457)*; UNRELATED: Consultancy: Roche, Eli Lilly, Comments: participation on Pediatric Advisory Committee for 1 specific project for each company; Grants/Grants Pending: Pfizer, Celgene, Apexigen, Novartis, Merck, Comments: grants for clinical trial costs conducted by the Pediatric Brain Tumor Consortium.* *Money paid to the institution.
- © 2020 by American Journal of Neuroradiology
Indicates open access to non-subscribers at www.ajnr.org