Randomized phase III trial of metabolic imaging-guided dose escalation of radio-chemotherapy in patients with newly diagnosed glioblastoma (SPECTRO GLIO trial).

BACKGROUND: Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since magnetic resonance spectroscopic imaging (MRSI) has been shown to predict the site of relapse, we analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM. METHODS: In this multicentric prospective phase III trial, patients who had undergone biopsy or surgery for a GBM were randomly assigned to a standard dose (SD) of 60 Gy or a high dose (HD) of 60 Gy with an additional simultaneous integrated boost totaling 72 Gy to MRSI metabolic abnormalities, the tumor bed and residual contrast enhancements. Temozolomide was administered concomitantly and maintained for 6 months thereafter. RESULTS: One hundred and eighty patients were included in the study between March 2011 and March 2018. After a median follow-up of 43.9 months (95% CI [42.5; 45.5]), median OS was 22.6 months (95% CI [18.9; 25.4]) versus 22.2 months (95% CI [18.3; 27.8]) for HD, and median progression-free survival was 8.6 (95% CI [6.8; 10.8]) versus 7.8 months (95% CI [6.3; 8.6]), in SD versus HD, respectively. No increase in toxicity rate was observed in the study arm. The pseudoprogression rate was similar across the SD (14.4%) and HD (16.7%) groups. For O(6)-methylguanine-DNA methyltransferase (MGMT) methylated patients, the median OS was 38 months (95% CI [23.2; NR]) for HD patients versus 28.5 months (95% CI [21.1; 35.7]) for SD patients. CONCLUSION: The additional MRSI-guided irradiation dose totaling 72 Gy was well tolerated but did not improve OS in newly diagnosed GBM. TRIAL REGISTRATION: NCT01507506; registration date: December 20, 2011. https://clinicaltrials.gov/ct2/show/NCT01507506?cond=NCT01507506&rank=1.

Pseudoprogression in GBM versus true progression in patients with glioblastoma: A multiapproach analysis.

BACKGROUND AND PURPOSE: To investigate the feasibility of using a multiapproach analysis combining clinical data, diffusion- and perfusion-weighted imaging, and 3D magnetic resonance spectroscopic imaging to distinguish true tumor progression (TP) from pseudoprogression (PSP) in patients with glioblastoma. MATERIALS AND METHODS: Progression was suspected within 6 months of radiotherapy in 46 of the 180 patients included in the Phase-III SpectroGlio trial (NCT01507506). Choline/creatine (Cho/Cr), choline/N-acetyl aspartate (Cho/NAA) and lactate/N-acetyl aspartate (Lac/NAA) ratios were extracted. Apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps were calculated. ADC, relative CBV values and tumor volume (TV) were collected at relapse. Differences between TP and PSP were evaluated using Mann-Whitney tests, and p values were adjusted with Bonferroni correction. RESULTS: Patients with suspected progression underwent a new MRI scan 1 month after the first one. Of these, 28 were classified as PSP, and 18 as TP. After a median follow-up of 41 months, median overall survival was higher in PSP than in TP (25.2 vs 20.3 months; p = 0.0092). Lac/NAA and Cho/Cr ratios were higher in TP than in PSP (1.2 vs 0.5; p = 0.006; and 3 vs 2.2; p = 0.021). After multivariate regression analysis, TV was the most significant predictor of TP vs PSP, and the only one retained in the model (p = 0.028). CONCLUSION: Three spectroscopic ratios could be used to differentiate PSP from TP. TV at relapse was the most predictive factor in the multivariate analysis, and overall survival was higher in PSP than in TP.

Pseudoprogression in Glioblastoma: Role of Metabolic and Functional MRI-Systematic Review.

BACKGROUND: Glioblastoma is the most frequent malignant primitive brain tumor in adults. The treatment includes surgery, radiotherapy, and chemotherapy. During follow-up, combined chemoradiotherapy can induce treatment-related changes mimicking tumor progression on medical imaging, such as pseudoprogression (PsP). Differentiating PsP from true progression (TP) remains a challenge for radiologists and oncologists, who need to promptly start a second-line treatment in the case of TP. Advanced magnetic resonance imaging (MRI) techniques such as diffusion-weighted imaging, perfusion MRI, and proton magnetic resonance spectroscopic imaging are more efficient than conventional MRI in differentiating PsP from TP. None of these techniques are fully effective, but current advances in computer science and the advent of artificial intelligence are opening up new possibilities in the imaging field with radiomics (i.e., extraction of a large number of quantitative MRI features describing tumor density, texture, and geometry). These features are used to build predictive models for diagnosis, prognosis, and therapeutic response. METHOD: Out of 7350 records for MR spectroscopy, GBM, glioma, recurrence, diffusion, perfusion, pseudoprogression, radiomics, and advanced imaging, we screened 574 papers. A total of 228 were eligible, and we analyzed 72 of them, in order to establish the role of each imaging modality and the usefulness and limitations of radiomics analysis.