Primary CNS Lymphoma Grommes, Christian; DeAngelis, Lisa M
Journal of clinical oncology,
07/2017, Letnik:
35, Številka:
21
Journal Article
Recenzirano
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Primary CNS lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The ...prognosis of patients with PCNSL has improved during the last decades with the introduction of high-dose methotrexate. However, despite recent progress, results after treatment are durable in half of patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting. To our knowledge, no randomized trial has been conducted for recurrent/refractory disease, leaving many questions unanswered about optimal first-line and salvage treatments. This review will give an overview of the presentation, evaluation, and treatment of immunocompetent patients with PCNSL.
Treatment of Brain Metastases Lin, Xuling; DeAngelis, Lisa M
Journal of clinical oncology,
10/2015, Letnik:
33, Številka:
30
Journal Article
Recenzirano
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Brain metastases (BMs) occur in 10% to 20% of adult patients with cancer, and with increased surveillance and improved systemic control, the incidence is likely to grow. Despite multimodal treatment, ...prognosis remains poor. Current evidence supports use of whole-brain radiation therapy when patients present with multiple BMs. However, its associated cognitive impairment is a major deterrent in patients likely to live longer than 6 months. In patients with oligometastases (one to three metastases) and even some with multiple lesions less than 3 to 4 cm, especially if the primary tumor is considered radiotherapy resistant, stereotactic radiosurgery is recommended; if the BMs are greater than 4 cm, surgical resection with or without postoperative whole-brain radiation therapy should be considered. There is increasing evidence that systemic therapy, including targeted therapy and immunotherapy, is effective against BM and may be an early choice, especially in patients with sensitive primary tumors. In patients with progressive systemic disease, limited treatment options, and poor performance status, best supportive care may be appropriate. Regardless of treatment goals, use of corticosteroids or antiepileptic medications is helpful in symptomatic patients. In this review, we provide a summary of current therapy, as well as developments in the treatment of BM from solid tumors.
IMPORTANCE Glioblastomas and malignant gliomas are the most common primary malignant brain tumors, with an annual incidence of 5.26 per 100 000 population or 17 000 new diagnoses per year. These ...tumors are typically associated with a dismal prognosis and poor quality of life. OBJECTIVE To review the clinical management of malignant gliomas, including genetic and environmental risk factors such as cell phones, diagnostic pitfalls, symptom management, specific antitumor therapy, and common complications. EVIDENCE REVIEW Search of PubMed references from January 2000 to May 2013 using the terms glioblastoma, glioma, malignant glioma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and brain neoplasm. Articles were also identified through searches of the authors’ own files. Evidence was graded using the American Heart Association classification system. FINDINGS Only radiation exposure and certain genetic syndromes are well-defined risk factors for malignant glioma. The treatment of newly diagnosed glioblastoma is based on radiotherapy combined with temozolomide. This approach doubles the 2-year survival rate to 27%, but overall prognosis remains poor. Bevacizumab is an emerging treatment alternative that deserves further study. Grade III tumors have been less well studied, and clinical trials to establish standards of care are ongoing. Patients with malignant gliomas experience frequent clinical complications, including thromboembolic events, seizures, fluctuations in neurologic symptoms, and adverse effects from corticosteroids and chemotherapies that require proper management and prophylaxis. CONCLUSIONS AND RELEVANCE Glioblastoma remains a difficult cancer to treat, although therapeutic options have been improving. Optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment.
Neurotoxicity caused by traditional chemotherapy and radiotherapy is widely recognized in patients with cancer. The adverse effects of newer therapeutics, such as biological and immunotherapeutic ...agents, are less well established, and are associated with considerable neurotoxicity in the central and peripheral nervous systems. This Review addresses the main neurotoxicities of cancer treatment with a focus on the newer therapeutics. Recognition of these patterns of toxicity is important because drug discontinuation or dose adjustment might prevent further neurological injury. Knowledge of these toxicities also helps to differentiate treatment-related symptoms from progression of cancer or its involvement of the nervous system. Familiarity with the neurological syndromes associated with cancer treatments enables clinicians to use the appropriate treatment for the underlying malignancy while minimizing the risk of neurological damage, which might preserve patients' quality of life.
Cancer patients face an increased risk of arterial thromboembolism; however, it is uncertain when this excess risk begins. This study evaluated the risk of arterial thromboembolism before cancer ...diagnosis. Using the population-based Surveillance Epidemiology and End Results-Medicare linked dataset, we identified 374 331 patients ≥67 years of age with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, uterine, pancreatic, gastric cancer, or non-Hodgkin lymphoma from 2005 through 2013. Cancer patients were individually matched by demographics and comorbidities to Medicare beneficiaries without cancer, who served as controls. Validated diagnosis codes were used to identify arterial thromboembolic events, defined as a composite of myocardial infarction or ischemic stroke. The Mantel-Haenszel estimator was used to compare risks of arterial thromboembolic events between cancer and noncancer groups during 30-day periods in the 360 days before date of cancer diagnosis. From 360 to 151 days before cancer diagnosis, the 30-day interval risks of arterial thromboembolic events were similar between cancer patients and matched controls. From 150 to 1 day before cancer diagnosis, the interval 30-day risks of arterial thromboembolic events were higher in cancer patients vs matched controls, progressively increasing as the cancer diagnosis date approached and peaking during the 30 days immediately before cancer diagnosis, when 2313 (0.62%) cancer patients were diagnosed with an arterial thromboembolic event vs 413 (0.11%) controls (odds ratio, 5.63; 95% confidence interval, 5.07-6.25). In conclusion, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis in older persons and peaks in the 30 days before.
•Among 748 662 Medicare beneficiaries, the risk of arterial thromboembolic events was increased 69% in the year before cancer diagnosis.•The increased risk of arterial thromboembolic events began 5 months before cancer was officially diagnosed and peaked in the month prior.
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One-quarter to one-third of ischemic strokes have no established mechanism after standard diagnostic evaluation and are classified as embolic stroke of undetermined source (ESUS). Failure of ...randomized trials to demonstrate a benefit of direct oral anticoagulants over aspirin for the treatment of ESUS as a single homogeneous entity has led to renewed interest by stroke experts to divide ESUS into subgroups. Emerging data suggest that active cancer, which is present in 5% to 10% of patients with ESUS, is a distinct and important subgroup of ESUS with unique clinical characteristics, underlying pathophysiologies, and treatment and prognostic considerations. Furthermore, the prevalence of cancer-related ESUS is expected to increase as patients with cancer, even those with distant metastases, survive longer due to improvements in cancer treatments. In this topical review, we examine the epidemiological link between ESUS and cancer, the clinical features and potential mechanistic underpinnings of ESUS with cancer (with a focus on novel biomarkers and their relationship to recurrent stroke and other thromboembolic events), and the potential treatment strategies for cancer-related ESUS. We include a critical appraisal of existing data and ongoing or planned clinical trials of different antithrombotic approaches. As cancer-related ESUS is a dynamic disease with variable course, we recommend close collaboration between neurologists and oncologists to develop individualized management plans.
•Immune checkpoint inhibitors (ICIs) may induce immune-mediated polyneuropathy in rare cases.•ICI-related neuropathy presents as acute demyelinating polyneuropathy or axonal painful ...neuropathy.•Electrophysiological tests are useful in evaluation of ICI-related neuropathy.
To report the electrodiagnostic features of immune checkpoint inhibitor (ICI)-related neuropathy.
We retrospectively reviewed clinical presentations and electrodiagnostic features of 23 patients studied after receiving immune checkpoint inhibitors (ICIs). The presentations for electrodiagnostic evaluation included an acute neuropathy or neuromuscular junction disorder. We applied established electrodiagnostic criteria for polyneuropathy and acute demyelinating neuropathy.
We identified acute demyelinating neuropathy (13 cases), axonal sensory motor neuropathy (5), pure sensory neuropathy (4) and mononeuropathy (1). 13 patients had acute demyelinating neuropathy confirmed by demonstrating demyelination in 2 or more nerves; 3 additional patients had demyelination in only one nerve. Analysis of motor nerve conduction parameters revealed demyelination involving median and ulnar nerve distal motor latencies as well as median, ulnar and peroneal nerve conduction velocities. Conduction block was found in median, ulnar and peroneal nerves. The remaining one-third patients without demyelination had acute painful axonal neuropathy. Coexisting myopathic changes (6) and neuromuscular junction dysfunction (4) were also identified.
Our findings suggest that, while immune-mediated motor nerve demyelination is the primary underlying mechanism of ICI-related neuropathy, axonal painful neuropathy can also be an important presentation. Early recognition and effective intervention may reduce morbidity and permanent disability.
Electrophysiological studies might be useful in the evaluation of ICI-related neuropathy.
Abstract
Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that affects the brain parenchyma, spinal cord, eyes, and cerebrospinal fluid without evidence of ...systemic, non-CNS involvement. PCNSL is uncommon and only a few randomized trials have been completed in the first-line setting. Over the past decades, the prognosis of PCNSL has improved, mainly due to the introduction and widespread use of high-dose methotrexate, which is now the backbone of all first-line treatment polychemotherapy regimens. Despite this progress, durable remission is recorded in only 50% of patients, and therapy can be associated with significant late neurotoxicity. Here, we overview the epidemiology, clinical presentation, staging evaluation, prognosis, and current up-to-date treatment of immunocompetent PCNSL patients.
No environmental exposure, other than previous ionising radiation, or behavioural or lifestyle choices are known to increase the risk of developing these tumours.2 Atopic conditions might protect ...against the development of a malignant brain tumour, but the biological basis for this association in unknown.3 In The Lancet Neurology, the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 20164 reports a 4·63 per 100 000 person-years global incidence of malignant CNS tumours, which represents a 17·3% increase from 1990 to 2016. Incidence is also dependent upon ascertainment, and accurate diagnosis of a CNS tumour requires access to modern neuroimaging and neurosurgery. ...it is unsurprising that incidence is lowest in resource-limited environments, such as sub-Saharan Africa and Central America, and the highest incidence is observed in the highest quintile of the Socio-demographic Index (SDI). ...the GBD Study gives us the most up-to-date assessment of the minimum burden of malignant CNS tumours over time.
Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of ...limited access to tumor tissue.
We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer.
We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations.
The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS.
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