The pH value is a potential physiological marker for clinical diagnosis as it is altered in pathologies such as tumors. While intracellular pH can be measured noninvasively via phosphorus spectroscopy (31P MRSI), Amide Proton Transfer‐Chemical Exchange Saturation Transfer (APT‐CEST) MRI has been suggested as an alternative method for pH quantification. To assess the suitability of APT‐CEST contrast for pH quantification, two approaches (magnetization transfer ratio asymmetry [MTRasym] and Lorentzian difference analysis [LDA]) for analyzing the Z‐spectrum have been correlated with pH values obtained by 31P MRSI. Fourteen patients with glioblastoma and 12 healthy controls were included. In contrast to MTRasym, the LDA is modeling the direct water saturation and the semi‐solid magnetization transfer, allowing a separate evaluation of the aliphatic nuclear Overhauser effect and the APT‐CEST. The results of our study show that the pH values obtained by 31P MRSI correspond well with both methods describing the APT‐CEST contrast. Two‐sample t‐test showed significant differences in MTRasym, LDA and pH obtained by 31P MRSI for regions of interest in glioblastoma, contralateral control areas and normal appearing white matter (P < 0.001). A slightly improved correlation between the amide signal and pH was found after performing LDA (r = 0.78) compared with MTRasym (r = 0.70). While both methods can be used to monitor pH changes, the LDA approach appears to be better suited.
In patients with glioblastoma, antiangiogenic therapy with bevacizumab (BEV) has been shown to improve progression-free survival (PFS), but not overall survival (OS). Especially in patients with an unusual infiltrative phenotype as seen in multifocal glioblastoma, the use of BEV therapy is still more controversial. Therefore, we prepared a retrospective case series with 16 patients suffering from a multifocal glioblastoma treated with BEV. We compared these patients to a matched control cohort of 16 patients suffering from glioblastoma with a single lesion treated with BEV. The objective of this study was to evaluate whether the course of disease differs in glioblastoma patients with a multifocal disease pattern compared to those with a single lesion only. Patients were treated with BEV monotherapy or BEV in combination with irinotecan or lomustine (CCNU). Response rates and PFS were similar in both groups. There was a trend for an unfavorable OS in the patient group with multifocal glioblastoma, which was expected due to the generally worse prognosis of multifocal glioblastoma. We investigated whether BEV therapy affects the invasive growth pattern as measured by the appearance of new lesions on magnetic resonance imaging (MRI). Under BEV therapy, there was a trend for a lower frequency of new lesions both in multifocal and solitary glioblastoma. Based on these results, BEV therapy at relapse appears to be justified to no lesser extent in multifocal glioblastoma than in solitary glioblastoma.
Background The randomized phase 3 CeTeG/NOA-09 trial assessed whether CCNU plus temozolomide was superior to temozolomide alone in newly diagnosed MGMT promoter methylated glioblastoma patients. Survival was significantly improved from 31.4 months (temozolomide) to 48.1 months (CCNU plus temozolomide). In view of this encouraging data, we assessed safety and efficacy of this regimen under real-life conditions. Methods We retrospectively collected clinical and radiographic data from adult newly diagnosed MGMT promoter methylated IDH wildtype glioblastoma patients from five neuro-oncology centers in Germany. For inclusion in our analysis, treatment with CCNU and temozolomide had to be performed for at least six weeks (one course). Results Seventy patients were included. Median progression-free survival was 14.4 months and median overall survival 33.8 months. Patients with TTFields treatment for at least eight weeks and CCNU plus temozolomide (n=22, 31%) had a prolonged progression-free survival compared to those with TTFields treatment for less than eight weeks (n=48, 69%) (21.5 versus 11.2 months; p=0.0105). In a multivariable Cox regression analysis, TTFields treatment for eight weeks or longer together with CCNU plus temozolomide and a Karnofsky performance score ≥ 90% were independent prognostic factors for progression-free and overall survival. Pseudoprogression occurred in n=16 (33%) of investigated n=49 (70%) patients. In n=31 (44%) patients high-grade hematotoxicity was observed. Conclusions The results from this multicentric trial indicate - under real-life conditions - toxicity and survival estimates comparable to the CeTeG/NOA-09 trial. TTFields therapy for at least eight weeks in combination with this regimen was independently associated with prolonged survival.
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