2198 - PET Tracer-Guided Radiotherapy Dose Escalation in Treatment-Naïve Glioblastoma: A Systematic Review of Prospective Clinical Trials

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 11

POSTER

Presenter(s)

Sai Kumar Samala, MD, MBBS - University of California Los Angeles, Los Angeles, CA

S. K. Samala¹, S. Raut², S. Sushant³, K. Raja⁴, A. Nair⁵, and M. Earle³; ¹The University of Texas Health Science Center at Houston, Houston, TX, ²Post Graduate Institute of Medical Sciences Satellite Center, Sangrur, India, ³All India Institute of Medical Sciences, New Delhi, India, ⁴All India Institute of Medical Sciences, Bilaspur, India, ⁵Oncolife Cancer Centre Pvt Ltd, Satara, India

Purpose/Objective(s):

Despite aggressive multimodal treatment, glioblastoma (GBM) outcomes remain poor with a median overall survival (OS) of 14.6-16.0 months. By providing superior visualization of the metabolic tumor extent compared to conventional MRI, PET imaging facilitates the safe escalation of targeted radiotherapy to biologically active disease. We systematically reviewed prospective clinical trials evaluating PET tracer-guided RT dose escalation exceeding 60 Gy EQD2 in treatment- naïve GBM.

Materials/Methods:

Following PRISMA guidelines we searched PubMed, Embase,Web of Science, Cochrane Library, Ovid MEDLINE, CINAHL, and ClinicalTrials.gov from January 2010 through 2025. for prospective trials or analyses of prospective trial datasets enrolling adults with newly diagnosed GBM where PET-informed target definition for RT dose escalation >60 Gy, with reported survival and/or toxicity outcomes. Two reviewers screened and abstracted data. Study quality was assessed qualitatively, given single-arm designs and heterogeneity in tracers/segmentation and dose prescriptions.

Results:

Four prospective trials enrolling 144 patients met the inclusion criteria. Three PET tracers were used: 18F-FET (n=2 studies, 39 patients), 18F-DOPA (n=1, 75 patients), and 68Ga-Pentixafor (n=1, 30 patients). All studies used simultaneous integrated boost (SIB) techniques in 30 fractions, with prescribed boost doses ranging from 67 to 78 Gy. Median OS ranged from 14.8 to 35.5 months across study cohorts, with all studies reporting median OS at or above the historical benchmark of 14.6 months. Grade 3+ radionecrosis rates ranged from 0% to 40%, with the 68Ga-Pentixafor-guided study reporting 0% radionecrosis at 67 Gy SIB and the 18F-FET pilot dose-escalation study (78 Gy) reporting 40% Grade 3-4 necrosis in evaluable patients. The largest trial (n=75, DOPA-PET, 76 Gy SIB) reported median OS of 16.0 months in the unmethylated primary cohort and 35.5 months in the methylated cohort, with 13.3% grade 3 CNS necrosis.

Conclusion:

PET tracer-guided RT dose escalation in treatment-naïve GBM is feasible with acceptable toxicity at doses of 67-78 Gy in 30 fractions. While single-arm studies suggest potential OS benefit, the lack of randomized data limits causal inference. Randomized trials incorporating PET-guided dose painting are needed to establish definitive evidence. Standardization of PET tracer selection, boost volume definition, and dose constraints is needed to advance this approach.