Clinical trials in melanoma patients with brain metastases.
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ABSTRACT:
SUBMITTER: Yushak ML
PROVIDER: S-EPMC4834841 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Publications
Clinical trials in melanoma patients with brain metastases.
Yushak Melinda L ML Chiang Veronica L VL Kluger Harriet M HM
Pigment cell & melanoma research 20150820 6
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Project description:Background: Brain metastases are observed in more than 40% of all patients with stage 4 melanoma. In recent years, more extensive use of stereotactic radiation (STRT) and the advent of immune checkpoint inhibitors have positively impacted outcomes in patients with metastatic melanoma.brain metastases. Here, we examined real world clinical outcomes of patients presenting with melanoma brain metastases (MBMs). Methods: This retrospective review evaluated MBMs patients treated at The Ottawa Hospital from April 2000 to July 2017. Clinical, radiologic, pathologic and treatment information were gathered from the electronic medical records. The primary outcome was overall survival. The proportional Cox regression model was employed for survival data, while the Fisher's exact and Mann-Whitney U tests analyzed the relationship between categorical and continuous data, respectively. Results: This retrospective study included 276 patients. Brain metastases were detected symptomatically in 191 patients (69.2%); the rates of detection by routine screening were 4.6% in the pre-2012 era and 11.7% in the contemporary era (p = 0.029). Median survival was three months. Predictors of overall survival were age, higher lactate dehydrogenase (LDH) values, multiple brain lesions, more extensive extracranial disease, neurological symptoms, infratentorial lesions and treatment type. Multivariable analysis demonstrated that stereotactic radiotherapy (STRT) was associated with a hazard ratio of 0.401 (p < 0.001) for survival; likewise, immune checkpoint inhibitor therapy was associated with a hazard ratio of 0.375 (p < 0.001). Conclusion: The findings from this study as "real world" data are consistent with results of pivotal clinical trials in MBMs patients and support contemporary locoregional and immunotherapy practices.
| S-EPMC7903273 | biostudies-literature
Project description:BackgroundBreast cancer brain metastases (BCBM) are the final frontier in neuro-oncology for which more efficacious therapies are required. In this work, we explore clinical trials in BCBM, and determine the shortcomings in the development of new BCBM therapies to shed light on potential areas for enhancement.MethodsOn July 9, 2018, we searched ClinicalTrials.gov for all interventional and therapeutic clinical trials involving BCBM, without limiting for date or location. Information on trial characteristics, including phase, status, start and end dates, study design, primary endpoints, selection criteria, sample size, experimental interventions, results, and publications were collected and analyzed.ResultsFifty-three trials fulfilled the selection criteria. Median trial duration across phases ranged between 3 and 6 years. More than half of the trials were conducted in the United States. Although 94% of the trials were in early phases (I-II), 20% of patients were in phase III trials. Two phase III trials were anteceded by phase II trials that were non-randomized; one reported positive results. Approximately one-third of the trials were completed, whereas 23% of trials were terminated early; mostly due to inadequate enrollment. Only 13% of all trials and 22% of completed trials had published results directly linked to their primary outcomes.ConclusionsThe low number of trials and accrual numbers, the lack of diversity, and the scarcity of published results represent the main troubles in clinical BCBM research. Optimization of BCBM trials is necessary to achieve effective therapies.
| S-EPMC6753353 | biostudies-literature
Project description:Relapses in the brain remain a major obstacle to cure in many patients with advanced melanoma. At present, the management of melanoma brain metastases continues to rely heavily on surgical and radiotherapeutic interventions, which have become safer and more effective with modern imaging, surgery and radiation technologies. Additionally, novel targeted and immunotherapeutic agents, shown to generate meaningful intracranial response and survival benefit in patients with melanoma brain metastases when compared with historical controls, expand systemic treatment options for this subset of patients. These systemic therapies become particularly important when intracranial disease burden precludes neuro- or radio-surgery. Considerable multidisciplinary research effort is ongoing to improve outcomes for melanoma patients with brain metastases, a key challenge in the management of advanced melanoma.
| S-EPMC6094653 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
| S-ECPF-GEOD-50496 | biostudies-other
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-05-08 | E-GEOD-50496 | biostudies-arrayexpress
Project description:Simple Summary Melanoma has the highest mortality rate of all skin cancers and its prognosis is worsened by metastasis to the brain. Before discovering new treatments for metastases, the prognosis of patients was poor. Currently, research is being conducted on new drugs using immunotherapy (immune checkpoint inhibitors: anti-PD-1, anti-CTLA-4) and targeted therapy (BRAF and MEK inhibitors) to improve the prognosis of patients. In this article, we summarize the current state of knowledge about the effects of treating brain metastases with new systemic therapies. Abstract Melanoma is a type of skin cancer in which there is a strong correlation between its occurrence and exposure to ultraviolet radiation. Although it is not the most common skin cancer, it has the highest mortality rate of all skin cancers. The prognosis of patients is significantly worsened by melanoma metastasis to the brain, which often occurs in patients with advanced disease. The formation and development of melanoma metastases to the brain involve a very complex process, and their mechanisms are not fully understood. One of the ways for metastatic melanoma cells to survive and develop cancer in the brain environment is the presence of oncogenic BRAF mutation, which occurs in up to 50% of metastatic melanoma cases. Before discovering new methods of treating metastases, the overall survival of patients with this disease was 6 months. Currently, research is being conducted on new drugs using immunotherapy (immune checkpoint inhibitors: anti-PD-1, anti-CTLA-4) and targeted therapy (BRAF and MEK inhibitors) to improve the prognosis of patients. In this article, we summarize the current state of knowledge about the results of treating brain metastases with new systemic therapies.
| S-EPMC10452790 | biostudies-literature
Project description:Brain metastases are about ten times more frequent than a brain primary tumor, being present in 20-40% of adults with systemic cancer. Together with lung cancer and breast cancer, skin cancers such as melanoma are top primary tumors which metastasizes to the brain. Advanced melanoma is well known for its propensity to metastasize to the brain, with 80% of patients presenting brain metastasis at the autopsy. However, current therapies are not very efficient and brain metastases are in most of the cases lethal. Treatment of melanoma brain metastases with surgery and/or radiation therapy results in a median overall survival of only about four months after diagnosis. New immunotherapies such as targeted or immunomodulatory drugs, many in clinical trials, have shown promise, with some immunomodulatory drugs being able to at least double the overall survival rates for patients with melanoma brain metastases. This review focuses on the recent advances and future potential of using immunotherapy, such as the newly developed immunomodulatory drugs, for melanoma brain metastases therapy. Immunomodulatory drugs bring a great promise as new tools for melanoma treatment in particular and for the treatment of other types of malignancies in general.
| S-EPMC7086063 | biostudies-literature
Project description:Opinion statementBrain metastases are a major clinical challenge occurring in up to 60% of patients suffering from metastatic melanoma. They cause significant clinical symptoms and impair the overall survival prognosis. The introduction of targeted therapies including BRAF and MEK inhibitors as well as CTLA-4 and PD-1 axis targeting immune checkpoint inhibitors have dramatically improved the treatment and prognosis of patients with extracranial metastatic melanoma. Although, similar response rates for extra- and intracranial metastases have been reported, only few data from brain metastasis specific trails are available so far. The following review will provide an overview on the currently available data on targeted therapies, remaining questions and the most important side effects in the special clinical situation of melanoma brain metastases.
| S-EPMC5378732 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2014-05-08 | GSE50496 | GEO
Project description:A recent meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases. The "minimum standard" recommended pulse sequences include: (i) parameter matched pre- and post-contrast inversion recovery (IR)-prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); (ii) axial 2D T2-weighted turbo spin echo acquired after injection of gadolinium-based contrast agent and before post-contrast 3D T1-weighted images; (iii) axial 2D or 3D T2-weighted fluid attenuated inversion recovery; (iv) axial 2D, 3-directional diffusion-weighted images; and (v) post-contrast 2D T1-weighted spin echo images for increased lesion conspicuity. Recommended sequence parameters are provided for both 1.5T and 3T MR systems. An "ideal" protocol is also provided, which replaces IR-GRE with 3D TSE T1-weighted imaging pre- and post-gadolinium, and is best performed at 3T, for which dynamic susceptibility contrast perfusion is included. Recommended perfusion parameters are given.
| S-EPMC7283031 | biostudies-literature