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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

  • Clinical Study
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Abstract

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).

Results

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.

Conclusions

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.

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Abbreviations

fDM:

Functional diffusion map

iADC:

Increase in ADC

dADC:

Decrease in ADC

nADC:

No change in ADC

fiADC:

Fraction of voxels with iADC

fdADC:

Fraction of voxels with dADC

RT:

Radiation treatment

OS:

Overall survival

PFS:

Progression free survival

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Funding

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.

Author information

Author notes

  1. Tina Young Poussaint and Ashok Panigrahy have contributed equally as senior authors.

Authors and Affiliations

  1. Department of Radiology, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, 4401 Penn Avenue, Suite 2464, Pittsburgh, PA, 15201, USA

    Rafael Ceschin & Ashok Panigrahy

  2. Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Rafael Ceschin & Ashok Panigrahy

  3. Department of Preventive Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA

    Sridhar Vajapeyam & Tina Young Poussaint

  4. Department of Radiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA

    Sridhar Vajapeyam & Tina Young Poussaint

  5. Department of Biostatistics, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA

    Mehmet Kocak & Arzu Onar-Thomas

  6. Department of Neurosurgery, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Ian F. Pollack

  7. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Ira J. Dunkel

  8. Pediatric Imaging Research Center, Department of Pediatric Radiology, UPMC Children’s Hospital of Pittsburgh, 45th Street and Penn Avenue, Pittsburgh, PA, 15224, USA

    Rafael Ceschin

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  1. Rafael Ceschin
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  2. Mehmet Kocak
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Contributions

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.

Corresponding author

Correspondence to Rafael Ceschin.

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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.

Ethical approval

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.

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Informed consent was obtained from all individual participants included in the study.

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Ceschin, R., Kocak, M., Vajapeyam, S. et al. 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. J Neurooncol 143, 79–86 (2019). https://doi.org/10.1007/s11060-019-03133-y

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  • DOI: https://doi.org/10.1007/s11060-019-03133-y

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