Prospective phase II study of radiotherapy dose escalation in grade 4 glioma using 68Ga-Pentixafor PET scan

Abstract

Background and purposeLocal failure remains the major concern in grade 4 glioma or glioblastoma (GBM). Pilot studies have shown radiotherapy (RT) dose response relationship in GBM. Here we present our preliminary data of RT dose escalation using 68Ga-Pentixafor PET scan. High 68Ga-pentixafor uptake in glioma cells helps in sharp demarcation between tumor and normal brain. Materials and methodsThis phase II prospective study was conducted from 2018 to 2020. Thirty, biopsy proven cases of grade 4 glioma were included. All patients underwent post-operative MRI of the brain and 68Ga-Pentixafor PET scan. RT was planned in 2-phases. Phase-1 GTV (GTV1) comprised of T2/flair abnormality, PET-avid disease and post-op cavity. A margin of 2cm was given to GTV-1 to create phase-1 CTV (CTV1), which was further expanded to 0.5cm to generate phase-1 PTV (PTV1). A radiation dose of 46Gy/23fr was prescribed to PTV-1. Phase-2 GTV (GTV2) consisted of CT/MRI contrast enhancing lesion, PET avid disease and post op cavity. A margin of 0.5 cm was given to GTV2 to create phase-2 CTV (CTV2) which was expanded 0.5 cm to create phase-2 PTV (PTV2). RT dose of 14 Gy/7 fr was prescribed to PTV2. PET avid disease was delineated as GTV PET and a margin of 3mm was given to generate PTV-PET which received escalated RT dose 21 Gy/7fr by simultaneous integrated boost (SIB) in phase 2 (Total dose to PTV PET=67 Gy/30 fr). All patients received concurrent and adjuvant temozolomide. The data was prospectively maintained in Microsoft Excel sheet. SPSS v 23 was used for statistical analysis. The primary endpoints were estimation of the Overall survival (OS) and Progression free survival (PFS), and secondary endpoint was to measure the incidence of radiation necrosis. Categorical variables were reported as frequency and percentage and quantitative variables were reported as median and range. ResultsData from thirty patients were analysed. A median overall survival (OS) of 23 months was observed with estimated 1, 2 and 3 years OS of 90%, 40% and 17.8% respectively. A significant association of OS was seen with extent of surgery (p=0.04) and kernofsky performance status (p=0.007). No patient developed significant radiation necrosis. ConclusionThe index study did not show any survival benefit from dose escalation RT. However; all of the patients tolerated the treatment well and none of them developed radiation necrosis. Considering the small sample size as a limitation of the index study, role of 68Ga-pentixafor PET scan for radiation dose escalation should be further explored. Clinical trial numberCTRI/2019/05/019146