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18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study

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Abstract

Purpose

Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions.

Methods

Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation.

Results

Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2).

Conclusions

In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.

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Data availability

Research data are stored in an institutional repository and will be shared upon request to the corresponding author.

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Acknowledgements

The authors would like to thank Robin Davis for data support for this study and philanthropic support by the Kerscher family.

Funding

Cleveland Clinic Department of Radiation Oncology, Cleveland Clinic Lerner Research Institute (Research Programs Committee Grant #326), Cleveland Clinic Imaging Institute, and Blue Earth Diagnostics.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

    Martin C. Tom, John H. Suh, Timothy D. Smile, Erin S. Murphy, Jennifer S. Yu & Samuel T. Chao

  2. Department of Nuclear Medicine, Cleveland Clinic, Cleveland, OH, USA

    Frank P. DiFilippo, Steve S. Huang & Guiyun Wu

  3. Department of Radiology, Cleveland Clinic, Cleveland, OH, USA

    Stephen E. Jones & Scott Johnson

  4. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA

    John H. Suh, Erin S. Murphy, Jennifer S. Yu, Gene H. Barnett, Lilyana Angelov, Alireza M. Mohammadi, David M. Peereboom, Glen H. J. Stevens, Manmeet S. Ahluwalia & Samuel T. Chao

  5. Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Nancy A. Obuchowski

  6. Department of Neurological Surgery, Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

    Gene H. Barnett, Lilyana Angelov & Alireza M. Mohammadi

  7. Taussig Cancer Institute, Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

    David M. Peereboom & Manmeet S. Ahluwalia

  8. Department of Neurology, Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

    Glen H. J. Stevens

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  1. Martin C. Tom
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Contributions

MCT, FDP, SEJ, and STC wrote the main manuscript text. NAO: responsible for statistical analysis. All authors reviewed the manusript.

Corresponding author

Correspondence to Martin C. Tom.

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Conflict of interest

MCT: Honoraria from ViewRay. Institutional research funding from Blue Earth Diagnostics Ltd. Personal fees from Elsevier. FPD: None. SEJ: None. JHS: Scientific advisory board for and consulting fees from Philips, Novocure. Leadership role with American Board of Radiology, International Radiosurgery Research Foundation, International Stereotactic Radiosurgery Society. NAO: Grants or contracts from Quantitative Imaging Biomarker Alliance. Honoraria from NCI Clinical Imaging Steering committee and ECOG-ACRIN DBMB. TDS: None. ESM: None. JSY: None. GHB: Monteris Medical, Inc. Plymouth, Minnesota. LA: None. AMM: None. SSH: None. GW: None. SJ: None. DMP: None. GHJS: None. MSA: Receipt of grants/research supports: Astrazeneca, BMS, Bayer, Incyte, Pharmacyclics, Novocure, Mimivax, Merck. Receipt of honoraria or consultation fees: Bayer, Novocure, Kiyatec, Insightec, GSK, Xoft, Nuvation, Cellularity, SDP Oncology, Apollomics, Prelude, Janssen, Tocagen, Voyager Therapeutics, Viewray, AnHeart Therapeutics, Caris Lifesciences, Theraguix, Pyramid biosciences. Scientific advisory board: Modifi bio, Pyramid Biosciences, Cairn Therapeutics, Bugworks. Stock shareholder: Doctible, Mimivax, Cytodyn, MedInnovate Advisors LLC. STC: Honoraria from Varian Medical Systems and Blue Earth Diagnostics. Travel support from Blue Earth Diagnostics.

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11060_2023_4377_MOESM1_ESM.pdf

Supplemental Fig. 1. Representative Cases. The upper panels depict imaging for Patient A showing new enhancement after SRS and associated 18F-fluciclovine PET/CT demonstrating low uptake. Biopsy returned radiation necrosis. The lower panels depict imaging for Patient B showing new enhancement after SRS and associated 18F-fluciclovine PET/CT demonstrating high uptake. Biopsy returned viable tumor as indicated by the arrow. (PDF 1221 KB)

Supplementary file2 (DOCX 33 KB)

Supplementary file3 (DOCX 21 KB)

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Tom, M.C., DiFilippo, F.P., Jones, S.E. et al. 18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study. J Neurooncol 163, 647–655 (2023). https://doi.org/10.1007/s11060-023-04377-5

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