Glioblastoma (GBM) is the most common high-grade primary brain tumor in adults. Standard multi-modality treatment of glioblastoma with surgery, temozolomide chemotherapy, and radiation results in transient tumor control but inevitably gives way to disease progression. The need for additional therapeutic avenues for patients with GBM led to interest in anti-angiogenic therapies, and in particular, bevacizumab. We sought to determine the efficacy of bevacizumab as a treatment for newly diagnosed GBM. We conducted a literature search using the PubMed database and Google Scholar to identify randomized controlled trials (RCTs) since 2014 investigating the safety and efficacy of bevacizumab in the treatment of adult patients (18 years and older) with newly diagnosed GBM. Only Level Ι data that reported progression-free survival (PFS) and overall survival (OS) were included for analysis. Random effects meta-analyses on studies with newly diagnosed glioblastoma were conducted in R to estimate the pooled hazard ratio (HR) for PFS and OS. Six RCTs met requirements for meta-analysis, revealing a pooled estimate of PFS HR suggesting a 33% decreased risk of disease progression (HR 0.67, 95% CI, 0.58–0.78; p < 0.001) with bevacizumab therapy, but no effect on OS (HR = 1, 95% CI, 0.85–1.18; p = 0.97). A pooled estimate of the mean difference in OS months of −0.13 predicts little difference in time of survival between treatment groups (95% CI, −1.87–1.61). The pooled estimate for the mean difference in PFS months was 2.70 (95% CI, 1.89–3.50; p < 0.001). Meta-analysis shows that bevacizumab therapy is associated with a longer PFS in adult patients with newly diagnosed glioblastoma, but had an inconsistent effect on OS in this patient population.
BackgroundThe CELESTIAL, RESORCE, and REACH‐2 trials showed survival benefit of cabozantinib, regorafenib, and ramucirumab, respectively, in hepatocellular carcinoma (HCC) patients treated with sorafenib who had good performance status (ECOG 0‐1) and liver function (Child‐Pugh‐A). This study characterizes subsequent treatments received by HCC patients after sorafenib, and determines the proportion of patients eligible for novel therapies if strict eligibility criteria (SEC) were utilized compared to more liberal modified eligibility criteria (MEC, including ECOG 2, Child‐Pugh‐B7).MethodsHCC patients who received sorafenib between 2008 and 2017 were included from the Canadian HCC CHORD Database. Patients were classified as eligible or ineligible based on available CELESTIAL, RESORCE, and REACH‐2 trial SEC or MEC. Median overall survival (mOS) was assessed using the Kaplan‐Meier method.ResultsA total of 730 patients were identified; and 172 (23.6%) received subsequent treatment. Patients who received subsequent treatment had longer mOS than those who did not (12.1 vs 3.3 months; P < .001). Using SEC, only 13.1% of patients would be eligible for cabozantinib, regorafenib, or ramucirumab. Expanding eligibility to include patients who meet MEC increased the proportion of eligible patients to 31.7%. Higher ineligibility for regorafenib and ramucirumab was driven by trial‐specific criteria, including sorafenib intolerance (28%) for RESORCE and AFP <400 (58.9%) for REACH‐2.ConclusionsA small proportion of real‐world HCC patients would be eligible for cabozantinib, regorafenib, or ramucirumab if SEC in clinical trials were followed, while more than double would be eligible if MEC were applied. Patients who received subsequent treatment had improved mOS, regardless of whether they met SEC or MEC.
Primary spinal cord tumors represent a hetereogeneous group of central nervous system malignancies whose management is complex given the relatively uncommon nature of the disease and variety of tumor subtypes, functional neurologic deficits from the tumor, and potential morbidities associated with definitive treatment. Advances in neuroimaging; integration of diagnostic, prognostic, and predictive molecular testing into tumor classification; and developments in neurosurgical techniques have refined the current role of radiotherapy in the multimodal management of patients with primary spinal cord tumors, and corroborated the need for prospective, multidisciplinary discussion and treatment decision making. Radiotherapeutic technological advances have dramatically improved the entire continuum from treatment planning to treatment delivery, and the development of stereotactic radiosurgery and proton radiotherapy provides new radiotherapy options for patients treated in the definitive, adjuvant, or salvage setting. The objective of this comprehensive review is to provide a contemporary overview of the management of primary intradural spinal cord tumors, with a focus on radiotherapy.
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