A Simple Implement for Assessing the Survival of Elderly Patients With Melanoma Irradiated for Cerebral Metastases.
Ontology highlight
ABSTRACT:
SUBMITTER: Nguyen T
PROVIDER: S-EPMC7279822 | biostudies-literature | 2020 May-Jun
REPOSITORIES: biostudies-literature
Publications
A Simple Implement for Assessing the Survival of Elderly Patients With Melanoma Irradiated for Cerebral Metastases.
Nguyen Trang T Janssen Stefan S Schild Steven E SE Rades Dirk D
In vivo (Athens, Greece) 20200501 3
<h4>Background/aim</h4>Secondary brain lesions occur commonly in patients with advanced melanoma. Despite increasing use of local therapies, many elderly patients qualify for whole-brain radiotherapy (WBRT). For these patients, a survival score was created.<h4>Patients and methods</h4>Seven characteristics were retrospectively investigated in 35 elderly (≥65 years) patients with melanoma, namely WBRT regimen, age, gender, Karnofsky performance score (KPS), number of brain lesions, non-cerebral m ...[more]
Similar Datasets
Project description:BackgroundPrognostic estimates for patients with brain metastases (BM) stem from younger, healthier patients enrolled in clinical trials or databases from academic centers. We characterized population-level prognosis in elderly patients with BM.MethodsUsing Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified 9882 patients ≥65 years old with BM secondary to lung, breast, skin, kidney, esophageal, colorectal, and ovarian primaries between 2014 and 2016. Survival was assessed by primary site and evaluated with Cox regression.ResultsIn total, 2765 versus 7117 patients were diagnosed with BM at primary cancer diagnosis (synchronous BM, median survival = 2.9 mo) versus thereafter (metachronous BM, median survival = 3.4 mo), respectively. Median survival for all primary sites was ≤4 months, except ovarian cancer (7.5 mo). Patients with non-small-cell lung cancer (NSCLC) receiving epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)-based therapy for synchronous BM displayed notably better median survival at 12.5 and 20.1 months, respectively, versus 2.8 months exhibited by other patients with NSCLC; survival estimates in melanoma patients based on receipt of BRAF/MEK therapy versus not were 6.7 and 2.8 months, respectively. On multivariable regression, older age, greater comorbidity, and type of managing hospital were associated with poorer survival; female sex, higher median household income, and use of brain-directed stereotactic radiation, neurosurgical resection, or systemic therapy (versus brain-directed non-stereotactic radiation) were associated with improved survival (all P < 0.05).ConclusionsElderly patients with BM have a poorer prognosis than suggested by prior algorithms. If prognosis is driven by systemic and not intracranial disease, brain-directed therapy with potential for significant toxicity should be utilized cautiously.
| S-EPMC8041328 | biostudies-literature
Project description:OBJECTIVES:The main objective of this study was to analyze treatment patterns of elderly patients with breast cancer brain metastases (BCBM), evaluate characteristics associated with treatment selection, and to analyze trends in overall survival (OS) over time. MATERIALS AND METHODS:We included women with BCBM reported to the Surveillance, Epidemiology, and End Results Medicare Program from 1992 to 2012. Treatments were recorded from Medicare claims from the date of brain metastases diagnosis until 60 days after. Treatments included resection, radiation, and chemotherapy. Cochran-Armitage tests were used for analysis of treatment patterns. Multinomial logistic regression was applied to determine factors associated with treatment selection. Cox regression modelled OS trends within each treatment modality across time. RESULTS:Among 5969 patients included, treatment rates increased from 50% in 1992 to 64.1% in 2012 (P<0.01). Therapy combining radiation, resection, and/or chemotherapy also increased from 8.8% to 18% over the same period (P<0.01). Combined therapy was significantly more likely among patients with extracranial metastases, those with estrogen-negative tumors, younger age at diagnosis, no comorbidities and more recently diagnosed brain metastases. OS improved over time for patients who received a combination of ?2 treatments (hazard ratio, 0.89 per every 5 more recent diagnosis years; P<0.05). Older patients, those with extracranial metastases, or estrogen/progesterone-negative tumors showed significantly shorter OS. CONCLUSIONS:We observed substantial changes in treatment patterns and OS over time in patients with BCBM. We identified several factors associated with specific treatment use. Patients who underwent a combination of ?2 treatments experienced a significant improvement in OS over time.
| S-EPMC6309246 | biostudies-literature
Project description:Importance:Melanoma treatment has been revolutionized with the development of immune-based therapies that offer durable clinical responses in a subset of patients. Clinical outcomes after treatment by immunotherapy can be influenced by the host's immune system. The immune system is modified with age by age-related immune dysfunction. Objective:To evaluate if age influences clinical outcome and immune adverse events in patients treated by immunotherapy for metastatic melanoma. Design, Setting, and Participants:This was a single-center cohort analysis in patients treated with immunotherapy for metastatic melanoma between January 2007 and February 2016, in the Lyon Sud Hospital, France. A total of 92 patients with metastatic melanoma treated with ipilimumab, nivolumab, or pembrolizumab were retrospectively analyzed. Main Outcomes and Measures:Overall survival, progression-free survival, and immune-related adverse events were evaluated for each treatment line according to the patients' age. Results:A total of 92 patients were eligible and included in this study for a total of 120 lines of treatment. Fifty-four patients were included in the cohort that was 65 years or younger (24 [44%] were female; mean [SD] age, 48.1 [12.5] years), and 38 patients were included in the cohort that was older than 65 years (12 [34%] were female; mean [SD] age, 74.8 [6.9] years). Mean follow-up duration starting at treatment initiation was 12.5 months. Patients older than 65 years treated with immunotherapy had a better mean progression-free survival (4.8 vs 3.4 months; P?=?.04) and overall survival (not reached vs 10.1 months; P?=?.009) than younger patients in univariate analysis, and after adjusting on prognosis covariates. This was particularly true with patients treated with anti-programmed cell death protein 1. Common immune-related adverse effects were similar in both cohorts. Conclusions and Relevance:Age might be associated with a better clinical outcome after treatment with immunotherapy in the real-life setting. In our cohort, older patients did not have more immune-related adverse events. Further studies are warranted to confirm our results and describe the underlying mechanisms involved.
| S-EPMC5833580 | biostudies-literature
Project description:BACKGROUND:Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT). METHODS:This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (?30?days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS. RESULTS:One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8?months, median OS was 8.4?months (0-40?months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5?months, respectively (p?=?0.001 and 0.03). CONCLUSION:The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.
| S-EPMC7268472 | biostudies-literature
Project description:BACKGROUND/AIM:Cancer patients with metastatic disease require personalized treatment regimens. This study was performed to identify prognostic factors for overall survival (OS) following irradiation of bone metastases from kidney cancer. PATIENTS AND METHODS:Data of 29 patients irradiated for bone metastases from kidney cancer were retrospectively evaluated. Ten factors were analyzed, including age, gender, performance score, interval from diagnosis of kidney cancer until radiotherapy for bone metastases, visceral metastases, other bone metastases, metastatic sites, number of irradiated sites, surgery of irradiated sites and systemic treatment prior to radiotherapy. RESULTS:Using univariate analyses, a longer interval from diagnosis of kidney cancer radiotherapy was associated with better OS (p=0.012). Using Cox regression analysis, this factor remained significant (risk ratio=3.54, p=0.012). CONCLUSION:The interval from diagnosis of kidney cancer until radiotherapy is an independent prognostic factor associated with OS following irradiation of bone metastases from kidney cancer. This type of data can help personalize radiation programs.
| S-EPMC7157884 | biostudies-literature
Project description:There is an urgent need to identify more accurate prognostic biomarkers in melanoma patients, particularly in those with metastatic disease. This study aimed to identify melanoma and leukocyte surface antigens predictive of survival in a prospective series of AJCC stage IIIb/c melanoma patients (n = 29). Live cell suspensions were prepared from melanoma metastases within lymph nodes (LN). The suspensions were immuno-magnetically separated into CD45(+) (leukocyte) and CD45(-) (non-hematopoietic, enriched melanoma cell) fractions. Surface antigens on CD45(-) and CD45(+) cell populations were profiled using DotScan™ microarrays (Medsaic Pty. Ltd.) and showed differential abundance levels for 52 and 78 antigens respectively. Associations of the surface profiles with clinicopathologic and outcome data (median follow-up 35.4 months post LN resection) were sought using univariate (log-rank test) and multivariate (Wald's test; modelled with patient's age, gender and AJCC staging at LN recurrence) survival models. CD9 (p = 0.036), CD39 (p = 0.004) and CD55 (p = 0.005) on CD45(+) leukocytes were independently associated with distant metastasis-free survival using multivariate analysis. Leukocytes with high CD39 levels were also significantly associated with increased overall survival (OS) in multivariate analysis (p = 0.016). LNs containing leukocytes expressing CD11b (p = 0.025), CD49d (p = 0.043) and CD79b (p = 0.044) were associated with reduced OS on univariate analysis. For enriched melanoma cells (CD45(-) cell populations), 11 surface antigens were significantly correlated with the disease-free interval (DFI) between diagnosis of culprit primary melanoma and LN metastasis resection. Nine antigens on CD45(+) leukocytes also correlated with DFI. Following validation in independent datasets, surface markers identified here should enable more accurate determination of prognosis in stage III melanoma patients and provide better risk stratification of patients entering clinical trials.
| S-EPMC3973954 | biostudies-literature
Project description:The management of melanoma patients with nodal metastases has undergone dramatic changes over the last decade. In the past, the standard of care for patients with a positive sentinel lymph node biopsy (SLNB) was a completion lymph node dissection (CLND), while patients with palpable macroscopic nodal disease underwent a therapeutic lymphadenectomy in cases with no evidence of systemic spread. However, studies have shown that SLN metastases present as a spectrum of disease, with certain SLN-based factors being prognostic of and correlated with outcomes. Furthermore, the results of key clinical trials demonstrate that CLND provides no survival benefit over nodal observation in positive SLN patients, while other clinical trials have shown that adjuvant immune checkpoint inhibitor therapy or targeted therapy after CLND is associated with a recurrence-free survival benefit. Given the efficacy of these systemic therapies in the adjuvant setting, these agents are now being evaluated and utilized as neoadjuvant treatments in patients with regionally-localized or resectable metastatic melanoma. Multiple options now exist to treat melanoma patients with nodal disease, and determining the best treatment course for a particular case requires an in-depth knowledge of current data and an informed discussion with the patient. This review will provide an overview of the various options for treating melanoma patients with nodal metastases and will discuss the data that supported the development of these treatment options.
| S-EPMC8102663 | biostudies-literature
Project description:ObjectIn the light of an aging population and ongoing advances in cancer control, the optimal management in geriatric patients with brain metastases (BM) poses an increasing challenge, especially due to the scarce data available. We therefore analyzed our institutional data with regard to factors influencing overall survival (OS) in geriatric patients with BM.MethodsBetween 2013 and 2018, patients aged ≥ 65 years with surgically treated BM were included in this retrospective analysis. In search of preoperatively identifiable risk factors for poor OS, in addition to the underlying cancer, the preoperative frailty of patients was analyzed using the modified Frailty Index (mFI).ResultsA total of 180 geriatric patients with surgically treated BM were identified. Geriatric patients categorized as least-frail achieved a median OS of 18 months, whereas frailest patients achieved an OS of only 3 months (p<0.0001). Multivariable cox regression analysis detected "multiple intracranial metastases" (p=0.001), "infratentorial localization" (p=0.011), "preoperative CRP >5 mg/l" (p=0.01) and "frailest patients (mFI ≥ 0.27)" (p=0.002) as predictors for reduced OS in older patients undergoing surgical treatment for BM.ConclusionsIn this retrospective series, pre-operative frailty was associated with poor survival in elderly patients with BM requiring surgery. Our analyses warrant thorough counselling and support of affected elderly patients and their families.
| S-EPMC8350563 | biostudies-literature
Project description:Background:MAP kinase inhibitor (MAPKi) therapy for BRAF mutated melanoma is characterized by high response rates but development of drug resistance within a median progression-free survival (PFS) of 9-12 months. Understanding mechanisms of resistance and identifying effective therapeutic alternatives is one of the most important scientific challenges in melanoma. Using proteomics, we want to specifically gain insight into the pathophysiological process of cerebral metastases. Methods:Cerebral metastases from melanoma patients were initially analyzed by a LC-MS shotgun approach performed on a QExactive HF hybrid quadrupole-orbitrap mass spectrometer. For further validation steps after bioinformatics analysis, a targeted LC-QQQ-MS approach, as well as Western blot, immunohistochemistry and immunocytochemistry was performed. Results:In this pilot study, we were able to identify 5977 proteins by LC-MS analysis (data are available via ProteomeXchange with identifier PXD007592). Based on PFS, samples were classified into good responders (PFS???6 months) and poor responders (PFS [Formula: see text] 3 months). By evaluating these proteomic profiles according to gene ontology (GO) terms, KEGG pathways and gene set enrichment analysis (GSEA), we could characterize differences between the two distinct groups. We detected an EMT feature (up-regulation of N-cadherin) as classifier between the two groups, V-type proton ATPases, cell adhesion proteins and several transporter and exchanger proteins to be significantly up-regulated in poor responding patients, whereas good responders showed an immune activation, among other features. We identified class-discriminating proteins based on nearest shrunken centroids, validated and quantified this signature by a targeted approach and could correlate parts of this signature with resistance using the CPL/MUW proteome database and survival of patients by TCGA analysis. We further validated an EMT-like signature as a major discriminator between good and poor responders on primary melanoma cells derived from cerebral metastases. Higher immune activity is demonstrated in patients with good response to MAPKi by immunohistochemical staining of biopsy samples of cerebral melanoma metastases. Conclusions:Employing proteomic analysis, we confirmed known extra-cerebral resistance mechanisms in the cerebral metastases and further discovered possible brain specific mechanisms of drug efflux, which might serve as treatment targets or as predictive markers for these kinds of metastasis.
| S-EPMC5844114 | biostudies-literature
Project description:Stereotactic radiosurgery (SRS) alone is an increasingly common treatment strategy for brain metastases. However, existing prognostic tools for overall survival (OS) were developed using cohorts of patients treated predominantly with approaches other than SRS alone. Therefore, we devised novel risk scores for OS and distant brain failure (DF) for melanoma brain metastases (MBM) treated with SRS alone.We retrospectively reviewed 86 patients treated with SRS alone for MBM from 2009-2014. OS and DF were estimated using the Kaplan-Meier method. Cox proportional hazards modeling identified clinical risk factors. Risk scores were created based on weighted regression coefficients. OS scores range from 0-10 (0 representing best OS), and DF risk scores range from 0-5 (0 representing lowest risk of DF). Predictive power was evaluated using c-index statistics. Bootstrapping with 200 resamples tested model stability.The median OS was 8.1 months from SRS, and 54 (70.1 %) patients had DF at a median of 3.3 months. Risk scores for OS were predicated on performance status, extracranial disease (ED) status, number of lesions, and gender. Median OS for the low-risk group (0-3 points) was not reached. For the moderate-risk (4-6 points) and high-risk (6.5-10) groups, median OS was 7.6 months and 2.4 months, respectively (p?<?.0001). Scores for DF were predicated on performance status, ED status, and number of lesions. Median time to DF for the low-risk group (0 points) was not reached. For the moderate-risk (1-2 points) and high-risk (3-5 points) groups, time to DF was 4.8 and 2.0 months, respectively (p?<?.0001). The novel scores were more predictive (c-index?=?0.72) than melanoma-specific graded prognostic assessment or RTOG recursive partitioning analysis tools (c-index?=?0.66 and 0.57, respectively).We devised novel risk scores for MBM treated with SRS alone. These scores have implications for prognosis and treatment strategy selection (SRS versus whole-brain radiotherapy).
| S-EPMC4666036 | biostudies-literature