18F-DOPA-PET-Guided Re-Irradiation for Recurrent High-Grade Glioma: Initial Results of a Phase II Trial

W. Breen, R. S. Youland, S. Jacobson, D. H. Pafundi, P. D. Brown, C. H. Hunt, A. Mahajan, M. Ruff, S. Kizilbash, Joon Uhm, D. M. Routman, J. Jones, D. H. Brinkmann, N. N. Laack

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE/OBJECTIVE(S): In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation (re-RT). Delineating re-RT target volumes is especially challenging in the setting of the VEGF-inhibitor bevacizumab, which can produce an MRI pseudo response. The radiotracer 18F-DOPA crosses the blood brain barrier and demonstrates high uptake in tumor but low uptake in normal tissue. We hypothesized that utilizing 18F-DOPA-PET with MRI for target delineation of recurrent HGG would improve progression free survival at 3 months (PFS3) compared to historical controls treated with systemic therapy only. MATERIALS/METHODS: Adults with recurrent or progressive HGG previously treated with radiation were eligible for this single-arm, phase II prospective trial. A sample size of 20 was calculated to detect a 20% improvement from the historical control PFS3 of 20%, with a power of 85.9% (alpha 0.186). 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 (tumor/normal ratio > 1.5). Concurrent treatment with bevacizumab was encouraged but not required. Patients were followed at 1 and 3 months (primary endpoint), then every 2 months until 2 years or progression, defined by RANO criteria. RESULTS: Twenty patients completed treatment per protocol. Fifteen (75%) were male. Median age was 53 (range 38-69). Diagnosis was most commonly glioblastoma, IDH-wildtype (60%) or glioblastoma, IDH-mutant (20%). Prior to re-RT, 19 (95%) received previous salvage treatments including surgery (35%) and systemic therapy (90%). Bevacizumab was used prior to, during, and immediately following re-RT in 12 (60%), 14 (70%), and 16 (80%) patients, respectively. Median interval between RT courses was 21.5 months (range 5-167), with an interval > 12 months in 85%. Median MRI-defined, PET-defined, and combined tumor volumes were 17 cc (range 0-198), 14 cc (0.2-209), and 23.2 cc (4-258), respectively. 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%. At data lock in January 2021 with 9.7 months median follow-up, 17 (85%) had progressed and 13 (65%) had died. Median OS from re-RT was 8.5 months, with 1- and 2-year OS estimates of 31% and 15%, respectively. Median OS from initial diagnosis was 3.7 years. 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: The 18F-DOPA-PET guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.

Original languageEnglish (US)
Pages (from-to)S26-S27
JournalInternational journal of radiation oncology, biology, physics
Volume111
Issue number3
DOIs
StatePublished - Nov 1 2021

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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