ABSTRACT
This cohort study examines the incidence, risks, and characteristics of deep vein thrombosis, pulmonary embolism, arterial thrombosis, and stroke among patients with nonsmall cell lung cancer (NSCLC) and RET fusions.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Thromboembolism , Humans , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Prevalence , Thromboembolism/epidemiology , Proto-Oncogene Proteins c-ret/geneticsABSTRACT
We report the case of a patient with metastatic breast cancer who presented with an orthostatic headache. After a comprehensive diagnostic workup including MRI and lumbar puncture, we maintained the diagnosis of intracranial hypotension (IH). The patient was therefore treated with two consecutive non targeted epidural blood patches, resulting in the remission of IH symptoms for 6 months. IH in cancer patients is a rarer cause of headache than carcinomatous meningitis. As the diagnosis can be made by standard examination and the treatment is relatively simple and effective, IH deserves to be better known by oncologists.
Subject(s)
Breast Neoplasms , Intracranial Hypotension , Meningeal Carcinomatosis , Humans , Female , Breast Neoplasms/complications , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/therapy , Intracranial Hypotension/complications , Intracranial Hypotension/diagnostic imagingABSTRACT
PURPOSE: Angiogenesis plays a key role in glioblastoma, but most anti-angiogenic therapy trials have failed to change the poor outcome of this disease. Despite this, and because bevacizumab is known to alleviate symptoms, it is used in daily practice. We aimed to assess the real-life benefit in terms of overall survival, time to treatment failure, objective response, and clinical benefit in patients with recurrent glioblastoma treated with bevacizumab. METHODS: This was a monocentric, retrospective study including patients treated between 2006 and 2016 in our institution. RESULTS: 202 patients were included. The median duration of bevacizumab treatment was 6 months. Median time to treatment failure was 6.8 months (95%CI 5.3-8.2) and median overall survival was 23.7 months (95%CI 20.6-26.8). Fifty percent of patients had a radiological response at first MRI evaluation, and 56% experienced symptom amelioration. Grade 1/2 hypertension (n = 34, 17%) and grade one proteinuria (n = 20, 10%) were the most common side effects. CONCLUSIONS: This study reports a clinical benefit and an acceptable toxicity profile in patients with recurrent glioblastoma treated with bevacizumab. As the panel of therapies is still very limited for these tumors, this work supports the use of bevacizumab as a therapeutic option.
Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Bevacizumab/therapeutic use , Glioblastoma/diagnostic imaging , Glioblastoma/drug therapy , Retrospective Studies , Medical Futility , Angiogenesis Inhibitors/therapeutic use , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/chemically induced , Neoplasm Recurrence, Local/pathologyABSTRACT
Diffuse gliomas, the most frequent and aggressive primary central nervous system neoplasms, currently lack effective curative treatments, particularly for cases lacking the favorable prognostic marker IDH mutation. Nonetheless, advances in molecular biology allowed to identify several druggable alterations in a subset of IDH wild-type gliomas, such as NTRK and FGFR-TACC fusions, and BRAF hotspot mutations. Multi-tyrosine kinase inhibitors, such as regorafenib, also showed efficacy in the setting of recurrent glioblastoma. IDH inhibitors are currently in the advanced phase of clinical evaluation for patients with IDH-mutant gliomas. Several immunotherapeutic approaches, such as tumor vaccines or checkpoint inhibitors, failed to improve patients' outcomes. Even so, they may be still beneficial in a subset of them. New methods, such as using pulsed ultrasound to disrupt the blood-brain barrier, gene therapy, and oncolytic virotherapy, are well tolerated and may be included in the therapeutic armamentarium soon.
ABSTRACT
OBJECTIVE: To assess whether RAF and MEK inhibitors (RAFi/MEKi) can provide long-term clinical benefit in adult patients with BRAF V600-mutant glial and glioneuronal tumors (GGNTs), we analyzed tumor response and long-term outcome in a retrospective cohort. METHODS: We performed a retrospective search in the institutional databases of 6 neuro-oncology departments for adult patients with recurrent or disseminated BRAF V600-mutant GGNTs treated with RAFi/MEKi. RESULTS: Twenty-eight adults with recurrent or disseminated BRAF V600-mutant gangliogliomas (n = 9), pleomorphic xanthoastrocytomas (n = 9), and diffuse gliomas (n = 10) were included in the study. At the time that treatment with RAFi/MEKi was started, all tumors displayed radiologic features of high-grade neoplasms. Thirteen patients received RAFi as single agents (vemurafenib [n = 11], dabrafenib [n = 2]), and 15 received combinations of RAFi/MEKi (vemurafenib + cobimetinib [n = 5], dabrafenib + trametinib [n = 10]). Eleven patients achieved a partial or complete response (11 of 28, 39%), with a median reduction of -78% in their tumor burden. Responders experienced a median increase of 10 points in their Karnofsky Performance Status (KPS) score and a median progression-free survival of 18 months, which was longer than achieved with first-line treatment (i.e., 7 months, p = 0.047). Responders had better KPS score (p = 0.018) and tended to be younger (p = 0.061) and to be treated earlier (p = 0.099) compared to nonresponders. Five patients were rechallenged with RAFi/MEKi at progression, with novel tumor responses in 2. On univariate and multivariate analyses, response to RAFi/MEKi was an independent predictor of overall survival. CONCLUSIONS: Our study highlights the long-term clinical benefits of RAFi/MEKi in adult patients with BRAF V600-mutant GGNTs and encourages rechallenge in responders. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, for adult patients with BRAF V600-mutant GGNT, RAFi/MEKi can reduce tumor burden and provide clinical benefit.
Subject(s)
Brain Neoplasms/drug therapy , Glioma/drug therapy , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Outcome Assessment, Health Care , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins B-raf/genetics , Adult , Astrocytoma/drug therapy , Astrocytoma/genetics , Azetidines/pharmacology , Brain Neoplasms/genetics , Databases, Factual , Female , Ganglioglioma/drug therapy , Ganglioglioma/genetics , Glioma/genetics , Humans , Imidazoles/pharmacology , Karnofsky Performance Status , MAP Kinase Kinase Kinases/antagonists & inhibitors , Male , Middle Aged , Oximes/pharmacology , Piperidines/pharmacology , Progression-Free Survival , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Pyridones/pharmacology , Pyrimidinones/pharmacology , Retrospective Studies , Vemurafenib/pharmacology , raf Kinases/antagonists & inhibitorsABSTRACT
Zika virus (ZIKV) infection has been associated with neurologic disorders including Guillain-Barré syndrome (GBS). In New Caledonia during the ZIKV outbreak (2014-2015), case-control and retrospective studies have been performed to assess the link between ZIKV and GBS. Among the 15 cases included, 33% had evidence of a recent ZIKV infection compared to only 3.3% in the 30 controls involved. All patients were Melanesian, had facial diplegia and similar neurophysiological pattern consistent with acute inflammatory demyelinating polyneuropathy, and recovered well. Furthermore, during the peak of ZIKV transmission, we observed a number of GBS cases higher than the calculated upper limit, emphasizing the fact that ZIKV is now a major trigger of GBS.
