Luisa Bellu

Effectiveness of antiangiogenic drugs in glioblastoma patients: A systematic review and meta-analysis of randomized clinical trials

BACKGROUND glioblastomas are highly vascularized tumors and various antiangiogenic drugs have been investigated in clinical trials showing unclear results. We performed a systematic review and a meta-analysis to clarify and evaluate their effectiveness in glioblastoma patients. PATIENTS AND METHODS we searched relevant published and unpublished randomized clinical trials analyzing antiangiogenic drugs versus chemotherapy in glioblastoma patients from January 2006 to January 2016 in MEDLINE, WEB of SCIENCE, ASCO, ESMO and SNO databases. RESULTS fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056). Bevacizumab did not improve overall survival. Twelve trials (4113 patients) were analyzed for progression-free survival. Among antiangiogenic drugs, only bevacizumab demonstrated an improvement of progression-free survival (HR=0.63, p<0.001), both alone (HR=0.60, p=0.003) or in combination to chemotherapy (HR=0.63; p<0.001), both as first-line treatment (HR=0.70, p<0.001) or in recurrent disease (HR=0.52, p<0.001). CONCLUSIONS antiangiogenic drugs did not improve overall survival in glioblastoma patients, either as first or second-line treatment, and either as single agent or in combination with chemotherapy. Among antiangiogenic drugs, only bevacizumab improved progression-free survival regardless of treatment line, both as single agent or in combination with chemotherapy.

Diagnostic Value of Plasma and Urinary 2-Hydroxyglutarate to Identify Patients With Isocitrate Dehydrogenase-Mutated Glioma

BACKGROUND Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert α-ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine could predict the presence of IDH1/2 mutations in patients with glioma. MATERIALS AND METHODS All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry. RESULTS A total of 84 patients were enrolled: 38 with R132H-IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1, 21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma, urine, and plasma/urine ratio (Ratio_2HG). We found a significant difference in the Ratio_2HG between patients with and without an IDH1 mutation (22.2 ± 8.7 vs. 15.6 ± 6.8; p < .0001). The optimal cutoff value for Ratio_2HG to identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high-grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma, we found a correlation between the Ratio_2HG value and the response to treatment. CONCLUSION Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients.

Cisplatin and temozolomide combination in the treatment of supratentorial anaplastic ependymoma.

Anaplastic ependymomas are rare tumors in adult patients. Maximal safe resection and use of radiation therapy are standard treatment approaches in patients with anaplastic ependymoma. Recurrent anaplastic ependymomas are treated by reoperation when the tumors are surgically accessible, by radiotherapy if not previously administered and by salvage chemotherapy. However, the role of chemotherapy is still unclear. A few retrospective studies showed interesting results with platinum-based regimens, while the administration of temozolomide alone demonstrated conflicting results. We present, for the first time, the case of a patient with anaplastic ependymoma refractory to platinum-based chemotherapy and temozolomide only, but showing a prolonged reduction of the lesion after receiving combination chemotherapy with cisplatin and temozolomide. A brief review of the literature on the treatment of anaplastic ependymoma follows.

An Overview of Fotemustine in High-Grade Gliomas: From Single Agent to Association with Bevacizumab

Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.

Cognitive Rehabilitation in Patients with Gliomas and Other Brain Tumors: State of the Art

Disease prognosis is very poor in patients with brain tumors. Cognitive deficits due to disease or due to its treatment have an important weight on the quality of life of patients and caregivers. Studies often take into account quality of life as a fundamental element in the management of disease and interventions have been developed for cognitive rehabilitation of neuropsychological deficits with the aim of improving the quality of life and daily-life autonomy of patients. In this literature review, we will consider the published studies of cognitive rehabilitation over the past 20 years.

425PTHE ROLE OF TEMOZOLOMIDE AND RADIATION THERAPY IN ELDERLY PATIENTS WITH GLIOBLASTOMA: A MONOINSTITUTIONAL RETROSPECTIVE STUDY

ABSTRACT Aim: The efficacy of temozolomide(TMZ) plus radiation therapy(RT) in elderly patients(EP) with glioblastoma(GBM) is unclear. We describe our experience of combining RT with concurrent TMZ in EP. Methods: Medical records of patients ≥65 years old with newly GBM, histologically confirmed and treated at Venetian Institute of Oncology – Padua, were reviewed. Concomitant TMZ was 75mg/m2/die. The adjuvant treatment consisted of TMZ 150-200mg/m2/die for six cycles. Results: We analyzed 67 consecutive patients(PTS), 35 males and 32 females; the average age was 71 (range 65-86); ECOG PS was 0-1 in 37 PTS and 2-3 in 30 PTS; complete surgery was performed in 41 PTS, partial surgery in 24 PTS. MGMT was analyzed in 46 PTS: methylated(met) MGMT in 21 PTS (46%). 36 PTS were treated with RT 40Gy in 15 fractions, 23 PTS with RT 60Gy in 30 fractions, 8 PTS with only TMZ. For all PTS, PFS and OS was 7 and 12.4 ms, respectively. PFS was 7.2 vs 6.7 ms (p = 0.5), OS was 11.9 vs 13.8 ms (p = 0.3), for PTS treated with RT 40Gy and 60Gy, respectively. PFS was 7.2 vs 4.5 ms (p = 0.04), OS was 13 vs 7.3 ms (p Conclusions: RT plus TMZ is effective and safe in EP with GBM. RT + TMZ treatment seems more effective than only TMZ. PFS and OS were not statistically different between RT 40Gy or 60Gy. RT + TMZ treatment and met MGMT were independent predictors of longer survival. In contrast, severe haematological toxicity was higher in PTS with RT + TMZ compared to TMZ alone. Disclosure: All authors have declared no conflicts of interest.