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Rate of change in maximum 18F-FDOPA PET uptake and non-enhancing tumor volume predict malignant transformation and overall survival in low-grade gliomas

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Abstract

Purpose

To examine whether the rate of change in maximum 18F-FDOPA PET uptake and the rate of change in non-enhancing tumor volume could predict malignant transformation and residual overall survival (OS) in low grade glioma (LGG) patients who received serial 18F-FDOPA PET and MRI scans.

Methods

27 LGG patients with ≥ 2 18F-FDOPA PET and MRI scans between 2003 and 2016 were included. The rate of change in FLAIR volume (uL/day) and maximum normalized 18F-FDOPA specific uptake value (nSUVmax/month), were compared between histological and molecular subtypes. General linear models (GLMs) were used to integrate clinical information with MR-PET measurements to predict malignant transformation. Cox univariate and multivariable regression analyses were performed to identify imaging and clinical risk factors related to OS.

Results

A GLM using patient age, treatment, the rate of change in FLAIR and 18F-FDOPA nSUVmax could predict malignant transformation with > 67% sensitivity and specificity (AUC = 0.7556, P = 0.0248). A significant association was observed between OS and continuous rates of change in PET uptake (HR = 1.0212, P = 0.0034). Cox multivariable analysis confirmed that continuous measures of the rate of change in PET uptake was an independent predictor of OS (HR = 1.0242, P = 0.0033); however, stratification of patients based on increasing or decreasing rate of change in FLAIR (HR = 2.220, P = 0.025), PET uptake (HR = 2.148, P = 0.0311), or both FLAIR and PET (HR = 2.354, P = 0.0135) predicted OS.

Conclusions

The change in maximum normalized 18F-FDOPA PET uptake, with or without clinical information and rate of change in tumor volume, may be useful for predicting the risk of malignant transformation and estimating residual survival in patients with LGG.

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Funding

This study was funded by grants from the American Cancer Society (ACS) Research Scholar Grant (RSG-15-003-01-CCE) (Ellingson); American Brain Tumor Association (ABTA) Research Collaborators Grant (ARC1700002) (Ellingson); National Brain Tumor Society (NBTS) Research Grant (Ellingson, Cloughesy); NIH/NCI UCLA Brain Tumor SPORE (1P50CA211015-01A1) (Ellingson, Lai, Cloughesy, Nghiemphu); NIH/NCI 1R21CA223757-01 (Ellingson).

Author information

Author notes

  1. Talia C. Oughourlian and Jingwen Yao have contributed equally to this work.

Authors and Affiliations

  1. UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Talia C. Oughourlian, Jingwen Yao, Jacob Schlossman, Catalina Raymond, Hiroyuki Tatekawa & Benjamin M. Ellingson

  2. Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Talia C. Oughourlian, Jacob Schlossman, Catalina Raymond, Hiroyuki Tatekawa, Noriko Salamon, Whitney B. Pope & Benjamin M. Ellingson

  3. Neuroscience Interdepartmental Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Talia C. Oughourlian, Jacob Schlossman & Benjamin M. Ellingson

  4. Department of Bioengineering, Henry Samueli School of Engineering, University of California Los Angeles, Los Angeles, CA, USA

    Jingwen Yao & Benjamin M. Ellingson

  5. UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Matthew Ji, Phioanh L. Nghiemphu, Albert Lai & Timothy F. Cloughesy

  6. Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Matthew Ji, Phioanh L. Nghiemphu, Albert Lai & Timothy F. Cloughesy

  7. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Johannes Czernin

  8. UCLA Brain Tumor Imaging Laboratory, Departments of Radiological Sciences and Psychiatry, David Geffen School of Medicine, University of California Los Angeles, 924 Westwood Blvd., Suite 615, Los Angeles, CA, 90024, USA

    Benjamin M. Ellingson

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  1. Talia C. Oughourlian
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  2. Jingwen Yao
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  11. Albert Lai
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Contributions

TFC reports advisory roles with Roche, Trizel, Medscape, Bayer, Amgen, Odonate Therapeutics, Pascal Biosciences, Bayer, Del Mar Pharmaceuticals, Tocagen, Karyopharm, GW Pharma, Kiyatec, Abbvie, Boehinger Ingelheim, VBI, Deciphera, VBL, Agios, Merck, Roche, Genocea, Celgene, Puma, Lilly, BMS, Cortice, Wellcome Trust, Novocure, Novogen, Boston Biomedical, Sunovion, Human Longevity, Insys, ProNai, Pfizer, Notable labs, Medqia. Stock options with Notable Labs. Member of the board for the 501c3 Global Coalition for Adaptive Research. U.S. Provisional Application No.: 62/819322. Title: Compositions and methods for treating cancer. BME reports advisory and consulting roles with MedQIA, Roche, Agios, Siemens, Medicenna, Imaging Endpoints, Novogen, Northwest Biopharmaceuticals, Image Analysis Groupm Concoceutics, BeiGene, VBL, and Tocagen. Dr. Ellingson also has research grants with Siemens, Roche, and Janssen.

Corresponding author

Correspondence to Benjamin M. Ellingson.

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

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Oughourlian, T.C., Yao, J., Schlossman, J. et al. Rate of change in maximum 18F-FDOPA PET uptake and non-enhancing tumor volume predict malignant transformation and overall survival in low-grade gliomas. J Neurooncol 147, 135–145 (2020). https://doi.org/10.1007/s11060-020-03407-w

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