Impact of comorbidity on survival by tumour location: Breast, colorectal and lung cancer (2000–2014)

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Oleguer Parés-Badell, Marta Banqué, Francesc Macià, Xavier Castells, Maria Sala
BackgroundTo assess the impact of comorbidity, measured by the Charlson Comorbidity Index (CCI), on survival in breast, colorectal and lung cancer.MethodsWe identified 3455 breast cancer, 3336 colorectal cancer and 2654 lung cancer patients through the Hospital del Mar cancer registry. The prevalence of comorbidities according to the CCI was calculated. Kaplan-Meier curves and the log-rank test were used to compare survival curves for each cancer location. Cox regression was used to calculate survival hazard ratios and 1-, 3- and 5-year mortality rate ratios adjusted by age, sex, CCI, place of first consultation, stage, treatment and period of diagnosis.ResultsThe overall unadjusted 5-year follow-up survival proportion was 82.6% for breast cancer, 55.7% for colorectal cancer, and 16.3% for lung cancer. Overall survival was associated with CCI≥3 in breast cancer (HR: 2.33 95%CI: 1.76–3.08), colorectal cancer (HR: 1.39; 95%CI: 1.13–1.70) and lung cancer (HR: 1.22; 95%CI: 1.06–1.40). In breast cancer, the higher the CCI, the higher the adjusted mortality rate ratio and differences were greater in 5-year than in 1-year follow-up survival.ConclusionsComorbidity is a significant predictor of overall survival in cancer patients; however, it has a stronger impact on survival in breast cancer than in colorectal and lung cancer.



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Impact of comorbidity on survival by tumour location: Breast, colorectal and lung cancer (2000–2014)

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Oleguer Parés-Badell, Marta Banqué, Francesc Macià, Xavier Castells, Maria Sala
BackgroundTo assess the impact of comorbidity, measured by the Charlson Comorbidity Index (CCI), on survival in breast, colorectal and lung cancer.MethodsWe identified 3455 breast cancer, 3336 colorectal cancer and 2654 lung cancer patients through the Hospital del Mar cancer registry. The prevalence of comorbidities according to the CCI was calculated. Kaplan-Meier curves and the log-rank test were used to compare survival curves for each cancer location. Cox regression was used to calculate survival hazard ratios and 1-, 3- and 5-year mortality rate ratios adjusted by age, sex, CCI, place of first consultation, stage, treatment and period of diagnosis.ResultsThe overall unadjusted 5-year follow-up survival proportion was 82.6% for breast cancer, 55.7% for colorectal cancer, and 16.3% for lung cancer. Overall survival was associated with CCI≥3 in breast cancer (HR: 2.33 95%CI: 1.76–3.08), colorectal cancer (HR: 1.39; 95%CI: 1.13–1.70) and lung cancer (HR: 1.22; 95%CI: 1.06–1.40). In breast cancer, the higher the CCI, the higher the adjusted mortality rate ratio and differences were greater in 5-year than in 1-year follow-up survival.ConclusionsComorbidity is a significant predictor of overall survival in cancer patients; however, it has a stronger impact on survival in breast cancer than in colorectal and lung cancer.



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Retrospective Evaluation of Thromboembolism Risk in Ovarian Cancer Patients Treated with Bevacizumab

Abstract

Background

Bevacizumab is used in addition to standard, platinum-based chemotherapy to treat advanced-stage ovarian cancer patients. Thrombosis is a well-documented adverse effect of bevacizumab.

Objective

The aim of this study was to identify predictive parameters for thromboembolic events in ovarian cancer patients and to explain how bevacizumab increases the risk of these events.

Patients and Methods

Fifty-seven FIGO stage III ovarian cancer patients who underwent cytoreductive surgery and chemotherapy were identified and included in this retrospective study. Twenty-six patients were treated with carboplatin and paclitaxel (CP) only (control group), and 31 patients received CP with bevacizumab (study group). The two groups were compared with regard to thrombosis risk factors and laboratory parameters (total leukocytes, platelet count, hemoglobin, APTT, prothrombin time, INR, fibrinogen levels, D-dimer concentration) before treatment, after each course of chemotherapy, and during thromboembolic events.

Results

Only patients in the group receiving bevacizumab experienced venous thromboembolism (VTE) (p=0.03, χ² test). VTE occurred on average at the 13th cycle of chemotherapy. Patients who experienced VTE had increased BMI before chemotherapy as compared to patients with no thromboembolic event (27.2 vs. 23.3, p=0.005, Mann-Whitney test). D-dimer concentration before treatment was also elevated more in patients affected by VTE (3132.5) than in the non-VTE group (956.43) (p=0.0007, Mann-Whitney test). During the first four administrations of chemotherapy in patients with future VTE, there was a reduction in D-dimer concentration and an extension of APTT. A D-Dimer level higher than 485 ng/mL prior to first chemotherapy indicates for a risk of VTE with 94% sensitivity and 36% specificity.

Conclusions

An elevated D-dimer level and high BMI before chemotherapy are risk factors for VTE in ovarian cancer patients receiving bevacizumab. Bevacizumab possibly increases the risk for VTE.

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Retrospective Evaluation of Thromboembolism Risk in Ovarian Cancer Patients Treated with Bevacizumab

Abstract

Background

Bevacizumab is used in addition to standard, platinum-based chemotherapy to treat advanced-stage ovarian cancer patients. Thrombosis is a well-documented adverse effect of bevacizumab.

Objective

The aim of this study was to identify predictive parameters for thromboembolic events in ovarian cancer patients and to explain how bevacizumab increases the risk of these events.

Patients and Methods

Fifty-seven FIGO stage III ovarian cancer patients who underwent cytoreductive surgery and chemotherapy were identified and included in this retrospective study. Twenty-six patients were treated with carboplatin and paclitaxel (CP) only (control group), and 31 patients received CP with bevacizumab (study group). The two groups were compared with regard to thrombosis risk factors and laboratory parameters (total leukocytes, platelet count, hemoglobin, APTT, prothrombin time, INR, fibrinogen levels, D-dimer concentration) before treatment, after each course of chemotherapy, and during thromboembolic events.

Results

Only patients in the group receiving bevacizumab experienced venous thromboembolism (VTE) (p=0.03, χ² test). VTE occurred on average at the 13th cycle of chemotherapy. Patients who experienced VTE had increased BMI before chemotherapy as compared to patients with no thromboembolic event (27.2 vs. 23.3, p=0.005, Mann-Whitney test). D-dimer concentration before treatment was also elevated more in patients affected by VTE (3132.5) than in the non-VTE group (956.43) (p=0.0007, Mann-Whitney test). During the first four administrations of chemotherapy in patients with future VTE, there was a reduction in D-dimer concentration and an extension of APTT. A D-Dimer level higher than 485 ng/mL prior to first chemotherapy indicates for a risk of VTE with 94% sensitivity and 36% specificity.

Conclusions

An elevated D-dimer level and high BMI before chemotherapy are risk factors for VTE in ovarian cancer patients receiving bevacizumab. Bevacizumab possibly increases the risk for VTE.

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Blood assessment of the expression levels of matrix metalloproteinase 9 ( MMP9 ) and its natural inhibitor, TIMP1 genes in Iranian schizophrenic patients

Abstract

Schizophrenia (SCZ) is the most severe chronic mental disorder characterized by abnormal social behavior and disrupted emotions and thought. Like other complex neuropsychological disease, SCZ is caused by a combination of genetic and environmental factors but with a high concordance rate. So far, different genetic factors are revealed to be associated with increased risk of developing SCZ. One of the best ways to investigate the genetic basis of the complex disease is to discover the genetic underlying mechanisms of the defective clinical aspects of the patients. In this regard, genes involved in the developmental mechanisms of the brain such as long-term potentiation (LTP) process that is the basis of synaptic plasticity, memory and learning are considered as strong candidates for SCZ. The aim of the present study was to evaluate the expression levels of two genes that are involved in the LTP regulation in the developing and adult brain, Matrix metallopeptidase9 (MMP9) and TIMP metallopeptidase inhibitor 1 (TIMP1) genes in a blood assessment of schizophrenic patients in comparison to healthy controls by means of quantitative real time PCR. The results of the study showed a significant difference in MMP9/TIPM1 ratio between SCZ patients and healthy controls (P = 0.01). However, no significant difference was detected in the expression level of individual MMP9 and TIMP1 genes in SCZ patients versus healthy controls either in total numbers of subject or in sex based subgroups. Considering the relatively small sample size of the current study, there is a need to replicate this study with further investigations about the mechanism of association of these genes and their functions in the pathogenesis of the SCZ.

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A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors [Research Briefs]

Larotrectinib, a selective TRK tyrosine kinase inhibitor (TKI), has demonstrated histology-agnostic efficacy in patients with TRK fusion-positive cancers. While responses to TRK inhibition can be dramatic and durable, duration of response may eventually be limited by acquired resistance. LOXO-195 is a novel, selective TRK TKI designed to overcome acquired resistance mediated by recurrent kinase domain (solvent front and xDFG) mutations identified in multiple patients who have developed resistance to TRK TKIs. Activity against these acquired mutations was confirmed in enzyme and cell-based assays and in vivo tumor models. As clinical proof of concept, the first two patients with TRK fusion-positive cancers that developed acquired resistance mutations on larotrectinib were treated with LOXO-195 on a first-in-human basis, utilizing rapid dose titration guided by pharmacokinetic assessments. This approach led to rapid tumor responses and extended the overall duration of disease control achieved with TRK inhibition in both patients.

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Blood assessment of the expression levels of matrix metalloproteinase 9 ( MMP9 ) and its natural inhibitor, TIMP1 genes in Iranian schizophrenic patients

Abstract

Schizophrenia (SCZ) is the most severe chronic mental disorder characterized by abnormal social behavior and disrupted emotions and thought. Like other complex neuropsychological disease, SCZ is caused by a combination of genetic and environmental factors but with a high concordance rate. So far, different genetic factors are revealed to be associated with increased risk of developing SCZ. One of the best ways to investigate the genetic basis of the complex disease is to discover the genetic underlying mechanisms of the defective clinical aspects of the patients. In this regard, genes involved in the developmental mechanisms of the brain such as long-term potentiation (LTP) process that is the basis of synaptic plasticity, memory and learning are considered as strong candidates for SCZ. The aim of the present study was to evaluate the expression levels of two genes that are involved in the LTP regulation in the developing and adult brain, Matrix metallopeptidase9 (MMP9) and TIMP metallopeptidase inhibitor 1 (TIMP1) genes in a blood assessment of schizophrenic patients in comparison to healthy controls by means of quantitative real time PCR. The results of the study showed a significant difference in MMP9/TIPM1 ratio between SCZ patients and healthy controls (P = 0.01). However, no significant difference was detected in the expression level of individual MMP9 and TIMP1 genes in SCZ patients versus healthy controls either in total numbers of subject or in sex based subgroups. Considering the relatively small sample size of the current study, there is a need to replicate this study with further investigations about the mechanism of association of these genes and their functions in the pathogenesis of the SCZ.

http://ift.tt/2sCConY