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Assessment of treatment response to dendritic cell vaccine in patients with glioblastoma using a multiparametric MRI-based prediction model

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Abstract

Purpose

Autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) is a promising treatment modality for glioblastomas. The purpose of this study was to investigate the potential utility of multiparametric MRI-based prediction model in evaluating treatment response in glioblastoma patients treated with DCVax-L.

Methods

Seventeen glioblastoma patients treated with standard-of-care therapy + DCVax-L were included. When tumor progression (TP) was suspected and repeat surgery was being contemplated, we sought to ascertain the number of cases correctly classified as TP + mixed response or pseudoprogression (PsP) from multiparametric MRI-based prediction model using histopathology/mRANO criteria as ground truth. Multiparametric MRI model consisted of predictive probabilities (PP) of tumor progression computed from diffusion and perfusion MRI-derived parameters. A comparison of overall survival (OS) was performed between patients treated with standard-of-care therapy + DCVax-L and standard-of-care therapy alone (external controls). Additionally, Kaplan–Meier analyses were performed to compare OS between two groups of patients using PsP, Ki-67, and MGMT promoter methylation status as stratification variables.

Results

Multiparametric MRI model correctly predicted TP + mixed response in 72.7% of cases (8/11) and PsP in 83.3% (5/6) with an overall concordance rate of 76.5% with final diagnosis as determined by histopathology/mRANO criteria. There was a significant concordant correlation coefficient between PP values and histopathology/mRANO criteria (r = 0.54; p = 0.026). DCVax-L-treated patients had significantly prolonged OS than those treated with standard-of-care therapy (22.38 ± 12.8 vs. 13.8 ± 9.5 months, p = 0.040). Additionally, glioblastomas with PsP, MGMT promoter methylation status, and Ki-67 values below median had longer OS than their counterparts.

Conclusion

Multiparametric MRI-based prediction model can assess treatment response to DCVax-L in patients with glioblastoma.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CL:

Coefficient of linear anisotropy

CP:

Coefficient of planar anisotropy

CS:

Coefficient of spherical anisotropy

CAR-T:

Chimeric antigen receptor T-cell

CCRT:

Concurrent chemoradiation therapy

DCVax-L:

Autologous tumor lysate-pulsed dendritic cell vaccine

DTI:

Diffusion tensor imaging

DSC:

Dynamic susceptibility contrast

FA:

Fractional anisotropy

GBM:

Glioblastoma

IDH :

Isocitrate dehydrogenase

MD:

Mean diffusivity

MGMT:

O6-methylguanine-DNA-methyltransferase

MRI:

Magnetic resonance imaging

OS:

Overall survival

PP:

Predictive probability of tumor progression

PsP:

Pseudoprogression

rCBV:

Relative cerebral blood volume

SOC:

Standard-of-care

TMZ:

Temozolomide

TP:

True progression

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Acknowledgements

The support of Penn Neuroradiology Clinical Research Core (Ms. Lauren Karpf, Ms. Lisa Desiderio, and Dr. Shadi Asadollah) and Penn Neurosurgery Clinical Research Division (Ms. Eileen Maloney) and clinical research coordinators is gratefully acknowledged. The dendritic cell vaccine trial at the University of Pennsylvania was sponsored by Northwest Biotherapeutics, the protocol, “A Phase-3 Clinical Trial Evaluating DC Vax®L, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma Multiforme”, approved by the Abramson Cancer Center – CTSRMC (Clinical Trials Scientific Review Committee (UPCC # 34313) and the Institutional Review Board (#81817). The data analyses and the drafting of the manuscript were performed by the authors, independent of the sponsor.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Authors and Affiliations

  1. Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Laiz Laura de Godoy, Sanjeev Chawla, Sumei Wang, Laurie A. Loevner & Suyash Mohan

  2. Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Steven Brem & Donald M. O’Rourke

  3. Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Steven Brem, Donald M. O’Rourke & Arati Desai

  4. Glioblastoma Translational Center of Excellence, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Steven Brem, Donald M. O’Rourke, MacLean P. Nasrallah & Arati Desai

  5. Clinical Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    MacLean P. Nasrallah

  6. Department of Neurosurgery, University of California Los Angeles David Geffen School of Medicine & Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA

    Linda M. Liau

Authors
  1. Laiz Laura de Godoy
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Contributions

Laiz Laura de Godoy: Conceptualization; Data curation; Investigation; Project administration; Writing—original draft; Writing—review & editing. Sanjeev Chawla: Conceptualization; Data curation; Investigation; Methodology; Supervision; Writing—original draft; Writing—review & editing. Steven Brem: Conceptualization; Investigation; Supervision; Writing—review & editing. Sumei Wang: Formal analysis; Methodology; Software; Writing—review & editing. Donald M. O’Rourke: Investigation; Writing—review & editing. MacLean P. Nasrallah: Data curation; Investigation; Writing—review & editing. Arati Desai: Investigation; Writing—review & editing. Laurie A. Loevner: Investigation; Writing—review & editing. Linda M. Liau: Conceptualization; Investigation; Writing—review & editing. Suyash Mohan: Conceptualization; Investigation; Methodology; Supervision; Writing—review & editing.

Corresponding author

Correspondence to Sanjeev Chawla.

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Conflict of interest

Dr. S. Brem received partial support of travel expenses in 2022 from Northwest Biotherapeutics. The remaining authors do not have any potential conflicts of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. The DCVax-L trial at the University of Pennsylvania, “A Phase-3 Clinical Trial Evaluating DC Vax®L, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma Multiforme” was sponsored by Northwest Biotherapeutics, using the protocol, NCT00045968. It was approved by the Abramson Cancer Center—CTSRMC (Clinical Trials Scientific Review Committee (UPCC # 34313) and the Institutional Review Board (#81817).

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

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de Godoy, L.L., Chawla, S., Brem, S. et al. Assessment of treatment response to dendritic cell vaccine in patients with glioblastoma using a multiparametric MRI-based prediction model. J Neurooncol 163, 173–183 (2023). https://doi.org/10.1007/s11060-023-04324-4

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  • DOI: https://doi.org/10.1007/s11060-023-04324-4

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