Parametric Response Mapping of Apparent Diffusion Coefficient as an Imaging Biomarker to Distinguish Pseudoprogression from True Tumor Progression in Peptide-Based Vaccine Therapy for Pediatric Diffuse Intrinsic Pontine Glioma.
OBJECTIVE
Immune response to cancer therapy may result in pseudoprogression, which can only be identified retrospectively and may disrupt an effective therapy. This study assesses whether serial parametric response mapping (a voxel-by-voxel method of image analysis also known as functional diffusion mapping) analysis of ADC measurements following peptide-based vaccination may help prospectively distinguish progression from pseudoprogression in pediatric patients with diffuse intrinsic pontine gliomas.


METHODS
From 2009 to 2012, 21 children, 4-18 years of age, with diffuse intrinsic pontine gliomas were enrolled in a serial peptide-based vaccination protocol following radiation therapy. DWI was acquired before immunotherapy and at 6-week intervals during vaccine treatment. Pseudoprogression was identified retrospectively on the basis of clinical and radiographic findings, excluding DWI. Parametric response mapping was used to analyze 96 scans, comparing ADC measures at multiple time points (from the first vaccine to up to 12 weeks after the vaccine was halted) with prevaccine baseline values. Log-transformed fractional increased ADC, fractional decreased ADC, and parametric response mapping ratio (fractional increased ADC/fractional decreased ADC) were compared between patients with and without pseudoprogression, by using generalized estimating equations with inverse weighting by cluster size.


RESULTS
Median survival was 13.1 months from diagnosis (range, 6.4-24.9 months). Four of 21 children (19%) were assessed as experiencing pseudoprogression. Patients with pseudoprogression had higher fitted average log-transformed parametric response mapping ratios (P = .01) and fractional decreased ADCs (P = .0004), compared with patients without pseudoprogression.


CONCLUSIONS
Serial parametric response mapping of ADC, performed at multiple time points of therapy, may distinguish pseudoprogression from true progression in patients with diffuse intrinsic pontine gliomas treated with peptide-based vaccination.
From the Departments of Radiology (R.C., A.P.) Biomedical Informatics (R.C., A.P.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Departments of Radiology (R.C., A.P.).
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Ceschin
Children's Hospital of Pittsburgh, University of Pittsburgh Cancer Institute (B.F.K., S.R.A., H.O., R.I.J., I.F.P., A.P.) Department of Biostatistics, Graduate School of Public Health (B.F.K.), University of Pittsburgh, Pittsburgh, Pennsylvania.
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Kurland
Children's Hospital of Pittsburgh, University of Pittsburgh Cancer Institute (B.F.K., S.R.A., H.O., R.I.J., I.F.P., A.P.).
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Abberbock
Department of Radiological Sciences (B.M.E.), University of California, Los Angeles, Los Angeles, California.
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Ellingson
Surgery (H.O.) Neurosurgery (H.O., I.F.P.) Immunology (H.O.) Children's Hospital of Pittsburgh, University of Pittsburgh Cancer Institute (B.F.K., S.R.A., H.O., R.I.J., I.F.P., A.P.).
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Okada
Pediatrics (R.I.J.) Pediatrics (R.I.J.) Children's Hospital of Pittsburgh, University of Pittsburgh Cancer Institute (B.F.K., S.R.A., H.O., R.I.J., I.F.P., A.P.).
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RI
Jakacki
Neurosurgery (H.O., I.F.P.) Neurosurgery (I.F.P.) Children's Hospital of Pittsburgh, University of Pittsburgh Cancer Institute (B.F.K., S.R.A., H.O., R.I.J., I.F.P., A.P.).
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Pollack
From the Departments of Radiology (R.C., A.P.) Biomedical Informatics (R.C., A.P.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Departments of Radiology (R.C., A.P.) Children's Hospital of Pittsburgh, University of Pittsburgh Cancer Institute (B.F.K., S.R.A., H.O., R.I.J., I.F.P., A.P.) panigrahya@upmc.edu.
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Panigrahy
D000293:Adolescent; D020295:Brain Stem Neoplasms / Q000473:pathology* / Q000628:therapy; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007114:Immunization / Q000379:methods; D008297:Male; D012189:Retrospective Studies
D019496:Cancer Vaccines