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RT-22MRI AND FET PET FOR RADIOTHERAPY PLANNING IN RECURRENT HIGH-GRADE GLIOMA (HGG) IN A PROSPECTIVE PHASE I TRIAL

ABSTRACT: BACKGROUND AND PURPOSE: Re-irradiation of HGG at recurrence may be a viable treatment option for some patients. Positron emission tomography (PET) using the amino acid tracer, 18F-fluoro-ethyltyrosine (FET) may have higher specificity and sensitivity than MRI in this setting. Both FET PET and MRI were used for target delineation in a prospective trial. The purpose of this study was to evaluate the impact of FET PET on the radiotherapy target. MATERIAL AND METHODS: A phase I trial examined the safety of hypofractionated stereotactic re-irradiation at different dose levels. Patients in PS 0-2 with localized recurrence of HGG and no other treatment options were eligible. With MRI, tumor was manually contoured using T1 contrast enhanced sequences. For PET, a threshold of 1.6x mean in background was used in a semi-automatic segmentation procedure. The planning target volume for treatment was the combination of both tumor volumes (MRI and PET) plus a 2 mm margin. Matlab software was used for spatial analyses. (Trial identifier: NCT02025231). RESULTS: Twenty-eight patients were included (GBM: n = 22; grade 3 glioma: n = 6). All patients had received radiotherapy and temozolomide, and 61 % had previously received bevacizumab. Median tumor volume defined by MRI and PET was 34 cm3 (range: 0-230 cm3) and 24 cm3 (range:0-214 cm3), respectively. Using PET increased the total gross tumor volume by a median of 10 cm3 (range:0-77 cm3), compared to MRI alone. The median longest distance from the MRI-target to encompass the PET-target was 10 mm (range: 0.6 to 43 mm). CONCLUSION: Tumor volumes defined by MRI and PET were spatially separated by up to 43 mm indicating that large portions of PET positive tumor would be missed if the target was solely based on MRI (T1 + contrast). FET PET may be useful for tumor delineation in re-irradiation of HGG.

SUBMITTER: Moller S

PROVIDER: S-EPMC4218527 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Project description:ObjectivesDifferentiation between high-grade glioma (HGG) and post-treatment-related effects (PTRE) is challenging, but advanced imaging techniques were shown to provide benefit. We aim to investigate microstructure characteristics of metabolic compartments identified from amino acid PET and to evaluate the diagnostic potential of this multimodal and integrative O-(2-18F-fluoroethyl)-L-tyrosine-(FET)-PET and fast diffusion kurtosis imaging (DKI) approach for the detection of recurrence and IDH genotyping.MethodsFifty-nine participants with neuropathologically confirmed recurrent HGG (n = 39) or PTRE (n = 20) were investigated using static 18F-FET PET and a fast-DKI variant. PET and advanced diffusion metrics of metabolically defined (80-100% and 60-75% areas of 18F-FET uptake) compartments were assessed. Comparative analysis was performed using Mann-Whitney U tests with Holm-Šídák multiple-comparison test and Wilcoxon signed-rank test. Receiver operating characteristic (ROC) curves, regression, and Spearman's correlation analysis were used for statistical evaluations.ResultsCompared to PTRE, recurrent HGG presented increased 18F-FET uptake and diffusivity (MD60), but lower (relative) mean kurtosis tensor (rMKT60) and fractional anisotropy (FA60) (respectively p < .05). Diffusion metrics determined from the metabolic periphery showed improved diagnostic performance - most pronounced for FA60 (AUC = 0.86, p < .001), which presented similar benefit to 18F-FET PET (AUC = 0.86, p < .001) and was negatively correlated with amino acid uptake (rs = - 0.46, p < .001). When PET and DKI metrics were evaluated in a multimodal biparametric approach, TBRmax + FA60 showed highest diagnostic accuracy (AUC = 0.93, p < .001), which improved the detection of relapse compared to PET alone (difference in AUC = 0.069, p = .04). FA60 and MD60 distinguished the IDH genotype in the post-treatment setting.ConclusionDetection of glioma recurrence benefits from a multimodal and integrative PET/DKI approach, which presented significant diagnostic advantage to the assessment based on PET alone.Clinical relevance statementA multimodal and integrative 18F-FET PET/fast-DKI approach for the non-invasive microstructural characterization of metabolic compartments provided improved diagnostic capability for differentiation between recurrent glioma and post-treatment-related changes, suggesting a role for the diagnostic workup of patients in post-treatment settings.Key points• Multimodal PET/MRI with integrative analysis of 18F-FET PET and fast-DKI presents clinical benefit for the assessment of CNS cancer, particularly for the detection of recurrent high-grade glioma. • Microstructure markers of the metabolic periphery yielded biologically pertinent estimates characterising the tumour microenvironment, and, thereby, presented improved diagnostic accuracy with similar accuracy to amino acid PET. • Combined 18F-FET PET/fast-DKI achieved the best diagnostic performance for detection of high-grade glioma relapse with significant benefit to the assessment based on PET alone.

Project description:Abstract BACKGROUND There is a lack of treatment options for HGG and LGG patients. BRAFV600E mutations are uncommon in glioma, with a poor long-term prognosis. Combined BRAF/MEK inhibition extends progression-free survival (PFS) and overall survival (OS) in BRAF V600E–mutated melanoma, non small-cell lung cancer, and anaplastic thyroid cancer. METHODS This phase 2, open-label trial (NCT02034110) evaluated dabrafenib (BRAF inhibitor, 150mg BID) plus trametinib (MEK inhibitor, 2mg QD) in patients with BRAF V600E mutations in 9 rare tumor types, including HGG and LGG. Eligible patients had histologically-confirmed recurrent or progressive glioma (LGG:WHO grade 1 or 2; HGG:WHO grade 3 or 4), with HGG patients required to have received radiotherapy and first-line chemotherapy, or concurrent chemoradiation. Treatment continued until unacceptable toxicity, disease progression, or death. Primary endpoint was investigator-assessed objective response rate (ORR) using RANO criteria. Secondary endpoints included duration of response (DOR), PFS, OS, and safety. RESULTS Interim analysis (IA) #14 (data cutoff: April 2, 2018) reported additional 3 months follow-up, with 49 patients enrolled (HGG, n=39; LGG, n=10) and 3 patients not evaluable for response. In HGG patients, ORR was 27% (10/37; 95%CI: 13.8%-44.1%), including CR (n=1), PR (n=9), and SD (n=11), with 16 patients currently ongoing treatment. In LGG patients, ORR was 56% (5/9; 95%CI: 26.8%-79.3%), including PR (n=5) and SD (n=4), with 6 patients currently ongoing treatment. OS, PFS, and DOR will be presented (IA#15). In HGG patients, adverse events (AEs) included fatigue (33%), headache (31%), rash (28%), and pyrexia (23%); grade 3/4 AEs included neutropenia (8%) and fatigue (5%). In LGG patients, AEs included headache (70%), fatigue, pyrexia (60% each), nausea, and arthralgia (50% each); grade 3/4 AEs included fatigue (20%). CONCLUSIONS Dabrafenib plus trametinib demonstrated promising efficacy in patients with recurrent or refractory BRAF V600E‒mutated HGG or LGG, with manageable AEs and no new safety signals.

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RT-22MRI AND FET PET FOR RADIOTHERAPY PLANNING IN RECURRENT HIGH-GRADE GLIOMA (HGG) IN A PROSPECTIVE PHASE I TRIAL

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