Multiparametric Characterization of Intracranial Gliomas Using Dynamic [18F]FET-PET and Magnetic Resonance Spectroscopy.

Both static and dynamic O-(2-[18F]fluoroethyl)-l-tyrosine-(FET)-PET and 1H magnetic resonance spectroscopy (MRS) are useful tools for grading and prognostication in gliomas. However, little is known about the potential of multimodal imaging comprising both procedures. We therefore acquired NAA/Cr and Cho/Cr ratios in multi-voxel MRS as well as FET-PET parameters in 67 glioma patients and determined multiparametric parameter combinations. Using receiver operating characteristics, differentiation between low-grade and high-grade glioma was possible by static FET-PET (area under the curve (AUC) 0.86, p = 0.001), time-to-peak (TTP; AUC 0.79, p = 0.049), and using the Cho/Cr ratio (AUC 0.72, p = 0.039), while the multimodal analysis led to improved discrimination with an AUC of 0.97 (p = 0.001). In order to distinguish glioblastoma from non-glioblastoma, MRS (NAA/Cr ratio, AUC 0.66, p = 0.031), and dynamic FET-PET (AUC 0.88, p = 0.001) were superior to static FET imaging. The multimodal analysis increased the accuracy with an AUC of 0.97 (p < 0.001). In the survival analysis, PET parameters, but not spectroscopy, were significantly correlated with overall survival (OS, static PET p = 0.014, TTP p = 0.012), still, the multiparametric analysis, including MRS, was also useful for the prediction of OS (p = 0.002). In conclusion, FET-PET and MRS provide complementary information to better characterize gliomas before therapy, which is particularly interesting with respect to the increasing use of hybrid PET/MRI for brain tumors

Surgical and functional outcome after resection of 64 petroclival meningiomas

Objective: The management of petroclival meningiomas (PCMs) remains notoriously difficult due to their close association with neurovascular structures and their complex anatomy, hence the surgical paradigm change from radical to functional resection in the past. With this study, we aimed to analyze surgical and functional outcomes of a modern consecutive series of patients with PCMs. Methods: We reviewed patient charts and imaging data of 64 consecutive patients from 2006 to 2018 with a PCM resected at our institution and compared surgical and functional outcomes between subgroups stratified by surgical approach. Results: Females comprised 67.2% of patients (n = 43), with a mean age of 55 years (median 56; range 21–84). Follow-up data were available for 68.8% and reached a mean of 42.3 months (range 1–129) with a median of 28.5 months. The mean tumor diameter was 37.3 mm (standard deviation (SD) 15.4; median 37.0). Infiltration of the cavernous sinus was observed in 34 cases (53.1%), and the lesions affected the brain stem in 28 cases (43.8%). Preoperative cranial nerve palsy was observed in 73.4% of cases; trigeminal neuropathy (42.2%), hearing loss (32.8%), and impairment of vision (18.8%) were the most common. A retrosigmoid approach was employed in 47 cases (78.1%), pterional in 10 (15.6%), combined petrosal in 2 (3.1%), and transnasal and subtemporal in 1 (1.6%). Fifteen cases (23.4%) were resected in a two-staged fashion. Gross total resection (GTR) was attempted in 30 (46.9%) cases without cavernous sinus infiltration and was achieved in 21 (70.0%) of these cases. Surgical complications occurred in 13 cases (20.3%), most commonly meningitis (n = 4; 6.3%). Postoperatively, 56 patients (87.5%) developed new cranial nerve palsy, of which 36 (63.6%) had improved or resolved on last follow up. Achieving GTR was not significantly associated with higher rates of surgical complications (chi-square; p = 0.288) or postoperative cranial nerve palsy (chi-square; p = 0.842). Of all cases, 20 (31.3%) underwent postoperative radiation. Tumor progression was observed in 10 patients (15.9%) after a mean 102 months (median 124). Conclusions: Surgical resection remains the mainstay of treatment for PCMs, with perioperative cranial neuropathies exhibiting favorable recovery rates. Most essentially, the preselection of patients with hallmarks of brain stem affection and cavernous sinus infiltration should dictate whether to strive for a functionally oriented strategy in favor of radical resection

Age-adjusted Charlson comorbidity index in recurrent glioblastoma: a new prognostic factor?

BACKGROUND: For recurrent glioblastoma (GB) patients, several therapy options have been established over the last years such as more aggressive surgery, re-irradiation or chemotherapy. Age and the Karnofsky Performance Status Scale (KPSS) are used to make decisions for these patients as these are established as prognostic factors in the initial diagnosis of GB. This study’s aim was to evaluate preoperative patient comorbidities by using the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for recurrent GB patients. METHODS: In this retrospective analysis we could include 123 patients with surgery for primary recurrence of GB from January 2007 until December 2016 (43 females, 80 males, mean age 57 years (range 21–80 years)). Preoperative age, sex, ACCI, KPSS and adjuvant treatment regimes were recorded for each patient. Extent of resection (EOR) was recorded as a complete/incomplete resection of the contrast-enhancing tumor part. RESULTS: Median overall survival (OS) was 9.0 months (95% CI 7.1–10.9 months) after first re-resection. Preoperative KPSS > 80% (P < 0.001) and EOR (P = 0.013) were associated with significantly improved survival in univariate analysis. Including these factors in multivariate analysis, preoperative KPSS < 80 (HR 2.002 [95% CI: 1.246–3.216], P = 0.004) and EOR are the only significant prognostic factor (HR 1.611 [95% CI: 1.036–2.505], P = 0.034). ACCI was not shown as a prognostic factor in univariate and multivariate analyses. CONCLUSION: For patients with surgery for recurrent glioblastoma, the ACCI does not add further information about patient’s prognosis besides the well-established KPSS and extent of resection

Brain metastases in the elderly – Impact of residual tumor volume on overall survival

BackgroundDue to demographic changes and an increased incidence of cancer with age, the number of patients with brain metastases (BMs) constantly increases, especially among the elderly. Novel systemic therapies, such as immunotherapy, have led to improved survival in recent years, but intracranial tumor progression may occur independently of a systemically effective therapy. Despite the growing number of geriatric patients, they are often overlooked in clinical trials, and there is no consensus on the impact of BM resection on survival.ObjectivesThe aim of this study was to analyze the impact of resection and residual tumor volume on clinical outcome and overall survival (OS) in elderly patients suffering from BM.MethodsPatients ≥ 75 years who had surgery for BM between April 2007 and January 2020 were retrospectively included. Residual tumor burden (RTB) was determined by segmentation of early postoperative brain MRI (72 h). Contrast-enhancing tumor subvolumes were segmented manually. “Postoperative tumor volume” refers to the targeted BMs. Impact of preoperative Karnofsky performance status scale (KPSS), age, sex and RTB on OS was analyzed. Survival analyses were performed using Kaplan-Meier estimates for the univariate analysis and the Cox regression proportional hazards model for the multivariate analysis.ResultsOne hundred and one patients were included. Median age at surgery was 78 years (IQR 76-81). Sixty-two patients (61%) had a single BM; 16 patients (16%) had two BMs; 13 patients (13%) had three BMs; and 10 patients (10%) had more than three BMs. Median preoperative tumor burden was 10.3 cm3 (IQR 5–25 cm3), and postoperative tumor burden was 0 cm3 (IQR 0–1.1 cm3). Complete cytoreduction (RTB = 0) was achieved in 52 patients (52%). Complete resection of the targeted metastases was achieved in 78 patients (78%). Median OS was 7 months (IQR 2–11). In univariate analysis, high preoperative KPSS (HR 0.986, 95% CI 0.973–0.998, p = 0.026) and small postoperative tumor burden (HR 1.025, 95% CI 1.002–1.047, p = 0.029) were significantly associated with prolonged OS. Patients with RTB = 0 survived significantly longer than those with residual tumor did (12 [IQR 5–19] vs. 5 [IQR 3–7] months, p = 0.007). Furthermore, prolongation of survival was significantly associated with surgery in patients with favorable KPSS, with an adjusted HR of 0.986 (p = 0.026). However, there were no significances regarding age.ConclusionsRTB is a strong predictor for prolonged OS, regardless of age or cancer type. Postoperative MRI should confirm the extent of resection, as intraoperative estimates do not warrant a complete resection. It is crucial to aim for maximal cytoreduction to achieve the best long-term outcomes for these patients, despite the fact the patients are advanced in age

Safe Brain Tumor Resection Does not Depend on Surgery Alone - Role of Hemodynamics

Aim of this study was to determine if perioperative hemodynamics have an impact on perioperative infarct volume and patients' prognosis. 201 cases with surgery for a newly diagnosed or recurrent glioblastoma were retrospectively analyzed. Clinical data and perioperative hemodynamic parameters, blood tests and time of surgery were recorded. Postoperative infarct volume was quantitatively assessed by semiautomatic segmentation. Mean diastolic blood pressure (dBP) during surgery (rho -0.239, 95% CI -0.11 - -0.367, p = 0.017), liquid balance (rho 0.236, 95% CI 0.1-0.373, p = 0.017) and mean arterial pressure (MAP) during surgery (rho -0.206, 95% CI -0.07 - -0.34, p = 0.041) showed significant correlation to infarct volume. A rank regression model including also age and recurrent surgery as possible confounders revealed mean intraoperative dBP, liquid balance and length of surgery as independent factors for infarct volume. Univariate survival analysis showed mean intraoperative dBP and MAP as significant prognostic factors, length of surgery also remained as significant prognostic factor in a multivariate model. Perioperative close anesthesiologic monitoring of blood pressure and liquid balance is of high significance during brain tumor surgery and should be performed to prevent or minimize perioperative infarctions and to prolong survival

Targeted therapies in patients with newly diagnosed glioblastoma - a systematic meta-analysis of randomized clinical trials

Glioblastoma (GB) is the most common malignant primary brain tumor in adults. The standard of care for newly diagnosed GB involves surgical resection followed by radiochemotherapy with temozolomide, with or without tumor-treating fields. In recent years, various efforts have been made to identify suitable molecularly targeted treatment options for malignant brain tumors. This meta-analysis provides an overview of recently published randomized controlled trials (RCTs) with and without molecular stratification, analyzing targeted agents in patients with newly diagnosed GB. The Cochrane Library, MEDLINE (Ovid), ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform, and Google Scholar were searched for RCTs on targeted therapies in patients with newly diagnosed glioblastoma. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted and pooled in a random-effects meta-analysis. Twelve RCTs (n=3,941 patients) involving protein kinase inhibitors, proteasome and histone deacetylase inhibitors, anti-angiogenic approaches, and poly (ADP-ribose) polymerase (PARP) inhibitors were included in the meta-analysis. None of the targeted agents achieved a significant benefit with regard to OS (HR=0.98 [95% Confidence Interval (CI) 0.86-1.11, p=0.7731]. By comparison, targeted therapy showed a benefit for PFS (HR=0.83 [95% CI 0.74-0.94, p=0.0037], especially for patients with an unmethylated O6-Methylguanin-DNA-methyltransferase (MGMT) promoter (0.75 [95% CI 0.56-0.99, p=0.0440]). Prolongation of PFS was largely driven by VEGF inhibition with bevacizumab (HR=0.70 [95% CI 0.61-0.80, p=0.0000]). VEGF inhibition with bevacizumab prolonged PFS in patients with newly diagnosed glioblastoma compared with standard care. However, no improvement in OS was observed with any of the targeted agents