Volumetric endpoints in diffuse intrinsic pontine glioma: comparison to cross-sectional measures and outcome correlations in the International DIPG/DMG Registry

Author:

Lazow Margot A123ORCID,Nievelstein Martijn T45,Lane Adam16ORCID,Bandopadhayhay Pratiti7,DeWire-Schottmiller Mariko1,Fouladi Maryam23ORCID,Glod John W8,Greiner Robert J9,Hoffman Lindsey M10,Hummel Trent R16,Kilburn Lindsay11,Leary Sarah12,Minturn Jane E13,Packer Roger11,Ziegler David S1415ORCID,Chaney Brooklyn1,Black Katie1ORCID,de Blank Peter16,Leach James L516

Affiliation:

1. Brain Tumor Center, Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio , USA

2. Pediatric Neuro-Oncology Program, Nationwide Children’s Hospital , Columbus, Ohio , USA

3. Department of Pediatrics, The Ohio State University College of Medicine , Columbus, Ohio , USA

4. Radboud University Medical Center , Nijmegen , Netherlands

5. Department of Radiology and Medical Imaging, Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio , USA

6. Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, Ohio , USA

7. Dana Farber Cancer Institute, Harvard Cancer Center , Boston, Massachusetts , USA

8. Cancer for Cancer Research, National Cancer Institute , Bethesda, Maryland , USA

9. Division of Oncology, Penn State Health Children’s Hospital , Hershey, Pennsylvania , USA

10. Division of Oncology, Phoenix Children’s Hospital , Phoenix, Arizona , USA

11. Division of Oncology, Children’s National Medical Center , Washington, DC , USA

12. Cancer and Blood Disorders Center, Seattle Children’s Hospital , Seattle, Washington , USA

13. Division of Oncology, Children’s Hospital of Philadelphia , Philadelphia, Pennsylvania , USA

14. Kids Cancer Centre, Sydney Children’s Hospital, Sydney , NSW , Australia

15. School of Women’s and Children’s Health, University of New South Wales , Sydney, NSW , Australia

16. Department of Radiology, University of Cincinnati College of Medicine , Cincinnati, Ohio , USA

Abstract

Abstract Background Cross-sectional tumor measures are traditional clinical trial endpoints; however volumetric measures may better assess tumor growth. We determined the correlation and compared the prognostic impact of cross-sectional and volumetric measures of progressive disease (PD) among patients with DIPG. Methods Imaging and clinical data were abstracted from the International DIPG Registry. Tumor volume and cross-sectional product (CP) were measured with mint Lesion™ software using manual contouring. Correlation between CP and volume (segmented and mathematical [ellipsoid] model) thresholds of PD were assessed by linear regression. Landmark analyses determined differences in survival (via log-rank) between patients classified as PD versus non-PD by CP and volumetric measurements at 1, 3, 5, 7, and 9 months postradiotherapy (RT). Hazard ratios (HR) for survival after these time points were calculated by Cox regression. Results A total of 312 MRIs (46 patients) were analyzed. Comparing change from the previous smallest measure, CP increase of 25% (PD) correlated with a segmented volume increase of 30% (R2 = 0.710), rather than 40% (spherical model extrapolation). CP-determined PD predicted survival at 1 month post-RT (HR = 2.77), but not other time points. Segmented volumetric-determined PD (40% threshold) predicted survival at all imaging timepoints (HRs = 2.57, 2.62, 3.35, 2.71, 16.29), and 30% volumetric PD threshold predicted survival at 1, 3, 5, and 9 month timepoints (HRs = 2.57, 2.62, 4.65, 5.54). Compared to ellipsoid volume, segmented volume demonstrated superior survival associations. Conclusions Segmented volumetric assessments of PD correlated better with survival than CP or ellipsoid volume at most time points. Semiautomated tumor volume likely represents a more accurate, prognostically-relevant measure of disease burden in DIPG.

Funder

Curing Kids Cancer

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Neurology (clinical),Oncology

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