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Initial results of a phase II trial of 18F-DOPA PET-guided re-irradiation for recurrent high-grade glioma

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Abstract

Purpose

In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation. The radiotracer 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (18F-DOPA) crosses the blood brain barrier and demonstrates high uptake in tumor, but low uptake in normal tissue. This study investigated whether 18F-DOPA positron emission tomography (PET) and MRI guided re-irradiation for recurrent HGG may improve progression free survival (PFS).

Methods

Adults with recurrent or progressive HGG previously treated with radiation were eligible. The primary endpoint was a 20% improvement from the historical control PFS at 3 months (PFS3) of 20% with systemic therapy alone. Re-RT dose was 35 Gy in 10 fractions. The target volume was MRI T1 contrast-enhancement defined tumor plus 18F-DOPA PET defined tumor.

Results

Twenty patients completed treatment per protocol. Diagnosis was most commonly glioblastoma, IDH-wildtype (60%). MRI-defined volumes were expanded by a median 43% (0–436%) by utilizing 18F-DOPA PET. PFS3 was 85% (95% CI 63.2–95.8%), meeting the primary endpoint of PFS3 ≥ 40%. With 9.7 months median follow-up, 17 (85%) had progressed and 15 (75%) had died. Median OS from re-RT was 8.8 months. Failure following re-RT was within both the MRI and PET tumor volumes in 75%, MRI only in 13%, PET only in 0%, and neither in 13%. Four (20%) patients experienced grade 3 toxicity, including CNS necrosis (n = 2, both asymptomatic with bevacizumab initiation for radiographic findings), seizures (n = 1), fatigue (n = 1), and nausea (n = 1). No grade 4–5 toxicities were observed.

Conclusion

18F-DOPA PET-guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.

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Data availability

Data used for this analysis is available upon request from the corresponding author.

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Author notes

  1. William G. Breen and Ryan S. Youland are co-first authors.

Authors and Affiliations

  1. Department of Radiation Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    William G. Breen, Paul D. Brown, Anita Mahajan, David M. Routman, Jamecca E. Jones, Debra H. Brinkmann & Nadia N. Laack

  2. Minnesota Oncology, St. Paul, MN, USA

    Ryan S. Youland

  3. Department of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Sharmila Giri & Sawyer B. Jacobson

  4. Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA

    Deanna H. Pafundi

  5. Department of Radiology, Mayo Clinic, Rochester, MN, USA

    Christopher H. Hunt

  6. Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA

    Michael W. Ruff, Sani H. Kizilbash & Joon H. Uhm

Authors
  1. William G. Breen
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  2. Ryan S. Youland
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  3. Sharmila Giri
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  4. Sawyer B. Jacobson
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  5. Deanna H. Pafundi
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  6. Paul D. Brown
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  9. Michael W. Ruff
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  12. David M. Routman
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  13. Jamecca E. Jones
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  15. Nadia N. Laack
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by WGB, SG, SBJ, and DB. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Nadia N. Laack.

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Conflict of interest

Dr. Ruff receives royalties and planned/pending patents unrelated to this work. Dr. Kizilbash receives grant funding to the institution and investigational product for preclinical studies, unrelated to this work.

Informed consent

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

Research involved in human and animal rights

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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This study was presented as an oral presentation at the ASTRO 2021 Annual Meeting.

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Breen, W.G., Youland, R.S., Giri, S. et al. Initial results of a phase II trial of 18F-DOPA PET-guided re-irradiation for recurrent high-grade glioma. J Neurooncol 158, 323–330 (2022). https://doi.org/10.1007/s11060-022-04011-w

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  • DOI: https://doi.org/10.1007/s11060-022-04011-w

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