PSMA PET-CT for radiation planning and response assessment in High Grade Gliomas

Summary: Intracranial high-grade gliomas (HGG), especially glioblastoma have a poor prognosis despite standard of care multi-modal treatment. There is a strong clinical need for predictive and prognostic imaging biomarkers assessing treatment response. Prostate specific membrane antigen (PSMA) has demonstrated excellent clinical utility for prostate cancers, allowing both extent of disease evaluation using F18- and Ga68-PSMA positron emission tomography (PET) as well as radionuclide therapy using Lu177-PSMA. PSMA expression has been demonstrated in HGG as well. Our purpose was to assess the utility of PSMA-PET in HGG radiation therapy (RT) planning and response assessment. Patients with HGG (grade 3 or 4) who underwent PSMA PET-CT after surgical resection or biopsy and prior to RT were included in this study. PSMA avidity was quantitatively analyzed using standardized uptake value (SUV) measurements including maximum SUV of the lesion (SUVmax); SUV ratio referencing right parotid (SUVRp), and superior sagittal sinus (SUVRsss). Mann-Whitney test and Wilcoxon sign rank test were used for intergroup comparison between independent and paired samples respectively. Kaplan-Meier method was used for survival analysis. A total of 27 patients with HGG underwent PSMA PET-CT, of which 20 underwent PET prior to RT and were included in this study. Of these, 15 were males (75%), 18 were WHO grade 4 (90%), and 7 were MGMT methylated (35%). Nine patients had gross-total resection (45%), 8 had subtotal resection (40%) and 3 underwent biopsy only (15%). All patients underwent adjuvant RT with concurrent Temozolomide, with a median dose of 60 Gy (60 Gy/30 fractions = 14, 52.5 Gy/15 fractions = 6, PET guided dose escalation to 75 Gy in 2 patients). Post-operative MRI suggested residual tumor in 13 patients and equivocal result for 1 patient. Additional PSMA avidity without MRI changes was identified in 4 patients. The mean tumor SUVmax, SUVRp and SUVRsss for patients with PSMA avid disease (n=18) vs those without (n=2) was 7.23 vs 1.53 (p=0.002, Mann Whitney test); 0.57 vs 0.15 (p=0.008); and 6.47 vs 1.78 (p=0.008). Additionally, 13 of 20 patients had follow-up PSMA PET post-treatment, at a median of 4 months after RT. Post-RT SUVmax decreased by 32.4% (7.1 to 4.8, p=0.05) (n=11). Of the 2 patients with no PSMA avidity at baseline, 1 continued to be disease free (SUVmax 1.28 vs 0.6), while the other patient had a local recurrence at 9 months reflected as increase in PSMA PET SUVmax from 1.83 to 5.71. Median OS from diagnosis was 20.2 months (range 0-43.1 months) and 1y-OS was 65.1%. PSMA PET SUVmax was significantly higher in HGG patients with residual disease identified on follow-up imaging and demonstrated significant decrease post-RT. Our results suggest upfront PSMA PET can improve tumor delineation and potentially improve treatment outcomes. Rituraj Upadhyay, MD (Presenting Author) - The Ohio State University; Pavnesh Kumar, MD (Co-Author) - The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Wexner Medical Ctr.; Bingfeng Tang, MD (Co-Author) - The Ohio State University; Erika Bello-Pardo, BS (Co-Author) - James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Ctr.; Divya Yadav, MD (Co-Author) - Weill-Cornell Medical Center; Sasha Beyer (she/her/hers), MD, PhD (Co-Author) - The Ohio State University; Raj Singh, MD (Co-Author) - Department of Radiation Oncology, The James Cancer Hospital and Solove Research Institute at The Ohio State University Wexner Medical Center; Raju Raval (he/him/his), MD, DPhil (Co-Author) - The Ohio State University; Evan Thomas (he/him/his), MD, PhD (Co-Author) - The Ohio State University; Jana Ivanidze, MD, PhD (Co-Author) - Weill-Cornell Medical Center; Joshua D.. Palmer, MD (Co-Author) - Department of Radiation Oncology, The James Cancer Hospital and Solove Research Institute at The Ohio State University Wexner Medical Center