Metabolic imaging in recurrent gliomas: comparative performance of 18F-FDOPA, 18F-fluorocholine and 18F-FDG PET/CT.

PURPOSE: The aim of this study was to directly evaluate glucose, amino-acid and membrane metabolism in tumor cells for diagnosis and prognostication of recurrent gliomas. METHODS: Fifty-five patients (median age = 36 years; 33 men) with histologically proven gliomas and suspected recurrence were prospectively recruited and underwent 18F-FDG (Fluorodeoxyglucose), 18F-FDOPA (fluorodopa) and 18F-Fluorocholine-PET/CT. Images were evaluated by two physicians visually and quantitatively [lesion-SUVmax, tumor (T) to gray-matter (G) and metabolically-active tumor volumes (MTV)]. After median follow-up of 51.5 months, recurrence was diagnosed in 49 patients. Thirty-one patients died with a median survival of 14 months. RESULTS: Diagnostic-accuracies for 18F-FDOPA, 18F-Fluorocholine,18F-FDG and contrast-enhanced-MRI were 92.7% (95% CI 82.7-97.1), 81.8% (69.7-89.8), 45.5% (33.0-58.5) and 44.7% (30.2-60.3), respectively. Among the 20 lesions, missed by MRI; 18F-FDOPA, 18F-Fluorocholine and 18F-FDG were able to detect 19, 14 and 4 lesions. Corresponding area-under-the-curves (T/G ratios) were 0.817 (0.615-1.000), 0.850 (0.736-0.963) and 0.814 (0.658-0.969), when differentiating recurrence from treatment-induced changes. In univariate-survival-analysis, 18F-FDOPA-T/G, visually detectable recurrence in 18F-FDG, 18F-FDOPA-MTV, cell-lineage and treatment-type were significant parameters. In Multivariate-Cox-regression analysis, 18F-FDOPA-MTV [HR = 1.009 (1.001-1.017); P  = 0.024 (~0.9% increase in hazard for every mL increase of MTV)] and cell-lineage [3.578 (1.447-8.846); P  = 0.006] remained significant. 18F-FDOPA-MTV cutoff <29.59 mL predicted survival higher than 2 years. At cutoff ≥29.59 mL, HR at 2 years was 2.759 (1.310-5.810). CONCLUSION: 18F-FDOPA-PET/CT can diagnose recurrence with high accuracy and MTV predicts survival. 18F-Fluorocholine is a good alternative. Higher 18F-FDG uptake is an adverse prognostic indicator.

Hypo-fractionated accelerated radiotherapy with concurrent and maintenance temozolomide in newly diagnosed glioblastoma: updated results from phase II HART-GBM trial.

BACKGROUND: Glioblastoma (GBM) patients have poor survival outcomes despite treatment advances and most recurrences occur within the radiation field. Survival outcomes after dose escalation through hypofractionated accelerated RT(HART) were evaluated in this study. We previously reported the study's initial results showing similar survival outcomes with acceptable toxicities. Updated results after 5 years are being analysed to determine long-term survival trends. PATIENTS AND METHODS: 89 patients of newly diagnosed GBM after surgery were randomized to conventional radiotherapy (CRT) or HART. CRT arm received adjuvant RT 60 Gy in 30 fractions over 6 weeks and the HART arm received 60 Gy in 20 fractions over 4 weeks, both with concurrent and adjuvant temozolomide. RESULTS: 83 patients were eligible for analysis. After a median follow-up of 18.9 months, the median OS was 26.5 months and 22.4 months in the HART and CRT arms respectively. 5 year OS was 18.4% in the HART arm versus 3.8% in the CRT arm. This numerical difference in overall survival between the two arms was not statistically significant. The median PFS was not significantly different. CONCLUSION: The long-term results of the trial support HART as a promising treatment option with comparable survival outcomes to the current standard of care. Phase III trials are required for further validation of this regimen which has the potential to become the new standard of care in GBM.

Hypofractionated accelerated radiotherapy (HART) with concurrent and adjuvant temozolomide in newly diagnosed glioblastoma: a phase II randomized trial (HART-GBM trial).

INTRODUCTION: Maximal safe surgical resection followed by adjuvant chemoradiation has been standard for newly diagnosed glioblastoma multiforme (GBM). Hypofractionated accelerated radiotherapy (HART) has the potential to improve outcome as it reduces the overall treatment time and increases the biological effective dose. METHODS: Between October 2011 and July 2017, a total of 89 newly diagnosed GBM patients were randomized to conventional fractionated radiotherapy (CRT) or HART. Radiotherapy was delivered in all patients with a three-dimensional conformal radiotherapy technique in CRT arm (60 Gy in 30 fractions over 6 weeks @ 2 Gy/per fraction) or simultaneous integrated boost intensity modulated radiotherapy in HART arm (60 Gy in 20 fractions over 4 weeks @ 3 Gy/per fraction to high-risk planning target volume (PTV) and 50 Gy in 20 fractions over 4 weeks @ 2.5 Gy/per fraction to low-risk PTV). The primary endpoint of the trial was overall survival (OS). RESULTS: After a median follow-up of 11.4 months (Range: 2.9-42.5 months), 26 patients died and 39 patients had progression of the disease. Median OS for the entire cohort was 23.4 months. Median OS in the CRT and HART arms were 18.07 months (95% CI 14.52-NR) and 25.18 months (95% CI 12.89-NR) respectively, p = 0.3. Median progression free survival (PFS) for the entire cohort was 13.5 months (Range: 11.7-15.7 months). In multivariate analysis patients younger than 40 years of age, patients with a gross total resection of tumor and a mutated IDH-1 had significantly better OS. PFS was significantly better for patients with a gross total resection of tumor and a mutated IDH-1. All patients included in the trial completed the planned course of radiation. Only two patients required hospital admission for features of raised intracranial tension. One patient in the HART arm required treatment interruption. CONCLUSION: HART is comparable to CRT in terms of survival outcome. HART arm had no excess treatment interruption and minimal toxicity. Dose escalation, reduction in overall treatment time, is the advantages with use of HART.