Men with metastatic castrate-resistant prostate cancer (mCRPC) may not receive docetaxel in everyday clinical practice due to comorbidities. Here we explore the impact of comorbidity on outcome in men with mCRPC treated with docetaxel in a population-based outcome study.Men with mCRPC treated with docetaxel at the Institute of Oncology Ljubljana between 2005 and 2012 were eligible. Comorbidity was assessed by the age-adjusted Charlson comorbidity index (aa-CCI) and adult comorbidity evaluation (ACE-27) index. Hospital admissions due to the toxicity and deaths during treatment with docetaxel were used as a measure of tolerability. Association between comorbidity and overall survival (OS) was tested using the Cox proportional hazards analysis.Two hundred and eight men were treated with docetaxel. No, mild, moderate and severe comorbidity was present in 2%, 32%, 53% and 13% using aa-CCI and in 27%, 35%, 29% and 8% when assessed by ACE-27. A substantial dose reduction of docetaxel occurred more often in men with moderate or severe comorbidity as compared to those with no or mild comorbidity. At all comorbidity levels about one-third of men required hospitalization or died during treatment with docetaxel. In univariate analysis a higher level of comorbidity was not associated with worse OS (aa-CCI HR 0.99; [95% CI 0.87-1.13], p = 0.93; ACE-27: HR 0.96; [95% CI 0.79-1.17], p = 0.69).Men with mCRPC, who have comorbidities may benefit from treatment with docetaxel.
Background Treatment with small molecule tyrosine kinase inhibitors (TKIs) has improved survival in many cancers, yet has been associated with an increased risk of adverse events. Warnings of cardiovascular events are common in drug labels of many TKIs. Despite these warnings, cardiovascular toxicity of patients treated with TKIs remains unclear. Here, we evaluate the cardiovascular outcomes of advanced cancer patients treated with small molecule tyrosine kinase inhibitors. Methods A population based cohort study was undertaken involving adults aged >18 years in Ontario, Canada, diagnosed with any advanced malignancy between 2006 and 2012. Data were extracted from linked administrative governmental databases. Adults with advanced cancer receiving TKIs were identified and followed throughout the time period. The main outcomes of interest were rates of hospitalization for ischemic heart disease (acute myocardial infarction and angina) or cerebrovascular accidents and death. Results 1642 patients with a mean age of 62.5 years were studied; 1046 were treated with erlotinib, 166 with sorafenib and 430 with sunitinib. Over the 380 day median follow-up period (range 6-1970 days), 1.1% of all patients had ischemic heart events, 0.7% had cerebrovascular accidents and 72.1% died. Rates of cardiovascular events were similar to age and gender-matched individuals without cancer. In a subgroup analysis of treatment patients with a prior history of ischemic heart disease, 3.3% had ischemic heart events while 1.2% had cerebrovascular accidents. Conclusions TKIs do not appear to increase the cause-specific hazard of ischemic heart disease and cerebrovascular accidents compared to age and gender-matched individuals without advanced cancer.
A number of randomized controlled trials (RCTs) have reported improvement in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial five years after diagnosis. However, the toxicity profile of extended AIs is uncertain.We identified RCTs that compared extended AIs to placebo or no treatment using MEDLINE and a review of abstracts from key conferences between 2013 and 2016. Odds ratios (ORs), 95% confidence intervals (CIs), absolute risks, and the number needed to harm (NNH) were computed for prespecified safety and tolerability outcomes including cardiovascular events, bone fractures, second cancers (excluding new breast cancer), treatment discontinuation for adverse events, and death without recurrence. All statistical tests were two-sided.Seven trials comprising 16 349 patients met the inclusion criteria. Longer treatment with AIs was associated with increased odds of cardiovascular events (OR = 1.18, 95% CI = 1.00 to 1.40, P = .05, NNH = 122), bone fractures (OR = 1.34, 95% CI = 1.16 to 1.55, P < .001, NNH = 72), and treatment discontinuation for adverse events (OR = 1.45, 95% CI = 1.25 to 1.68, P < .001, NNH = 21). Longer treatment with AIs did not influence the odds of either second malignancy (OR = 0.93, 95% CI = 0.73 to 1.18, P = .56) or deaths without breast cancer recurrence (OR = 1.11, 95% CI = 0.90 to 1.36, P = .34).Extended treatment with AIs is associated with an increased risk of cardiovascular events and bone fractures. There is no statistically significant increase in deaths without breast cancer recurrence among patients receiving longer treatment with AIs. These data should be taken into account when considering extended adjuvant AIs.
Abstract Background: There is an increasing body of evidence that the host inflammatory response plays an important prognostic role in cancer. High level of the neutrophil/lymphocyte ratio (NLR) has been associated with poor prognosis in many cancers. The association of NLR with survival in breast cancer and its different subtypes remains unclear. Methods: A literature review of electronic databases was conducted to identify studies exploring the prognostic role of NLR in breast cancer. Data were extracted from individual publications or estimated from associated figures. Where possible, data were included in a meta-analysis. The association of high NLR with other classical prognostic factors (e.g. tumor size, histological grade, nodal metastasis, and estrogen receptor or HER2/neu expression) was evaluated using the Mantel-Haenszel odds ratio (OR). Both univariable and multivariable analyses of NLR with overall survival (OS) were assessed using generic inverse variance. Subgroup analysis was conducted to assess the effect of different cut-offs to define high versus low NLR. Breast cancer-specific survival was assumed to be equivalent to OS if non-breast cancer deaths contributed to <5% of evaluable patients. Results: The analysis included a total of 5 retrospective studies comprising of 3,449, predominantly early-stage, breast cancer patients. Three studies defined high NLR based on the most discriminating cut-off evaluated by receiver operator characteristic (ROC) analysis, while two studies compared upper to lower quartiles for NLR. The mean age was 56.9 and there were no differences in age between those with high and low NLR (mean difference +1.54 years, 95% confidence intervals [CI] -0.17-3.24, P = 0.08). Compared with low NLR, patients with high NLR were more likely to have tumors larger than 2cm (OR 1.69, 95% CI 1.23-2.32, P = 0.001), nodal metastases (OR 1.65, 95% CI 1.21-2.23, P = 0.001) and HER2/neu overexpression or amplification (OR 1.77, 95% CI 1.20-2.62, P = 0.004). There were no differences in the proportion of tumors that were high grade (OR 1.27, 95% CI 0.90-1.79, P = 0.18) or estrogen receptor positive (OR 0.76, 95% CI 0.54-1.09, P = 0.13) between those with high and low NLR. High NLR showed an association with worse OS (univariable hazard ratio [HR] 3.42, 95% CI 2.75-4.24, P<0.001). This association was retained in multivariable analyses (HR 3.16, 95% CI 2.13-4.68, P<0.001). There was no difference in this association with worse survival when NLR was assessed based on a single cut-off or when compared between upper and lower quartiles (subgroup difference P = 0.68, table). Conclusion: High NLR is associated with various poor prognostic factors, but despite this appears to be an independent factor for worse survival from breast cancer. These findings may be explained by an adverse host response to cancer. SubgroupNumber of studiesHR for OS95% CIPCut-off determined by ROC analysis33.362.64-4.29<0.001Upper versus lower quartile23.872.08-7.23<0.001 Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-12.
<p>Supplementary Figure 1: Forest plot showing the pooled odds ratio (OR) for overall survival at 1 year for circulating tumor DNA. Supplementary Figure 2: Forest plot showing the pooled odds ratio (OR) for overall survival at 1 year for total circulating DNA. Supplementary Figure 3: Forest plot showing A: pooled hazard ratio (HR) for overall survival for total tumor circulating DNA based on method of collection (plasma versus serum) and B: pooled hazard ratio (HR) for overall survival for t total circulating DNA based on method of collection (plasma versus serum).</p>
•Terminally ill cancer patients may be aggressively treated due to the growing possibilities of anticancer treatment.•A probability of receiving anticancer treatment at the EoL increased over time.•There was an increased use of novel, very costly systemic therapies in the last 2 weeks of life.•Younger patients and those not enrolled into the SPC are at particular risk to receive anticancer treatment at the EoL. BackgroundThere is a concern that terminally ill cancer patients may be aggressively treated due to the rapidly growing possibilities of anticancer treatment. The aim of this study was to evaluate the use of anticancer treatment at the end of life (EoL).Materials and methodsThis retrospective study included adult patients with advanced solid cancers who were treated at the Institute of Oncology Ljubljana and died of cancer between January 2015 and December 2019. A multiple logistic regression model was used to assess an association between the aggressiveness of anticancer treatment (i.e. systemic therapy, radiotherapy and surgery) in the last 2 weeks of life and year of death, age at death, sex, prognosis of cancer and enrolment into the specialist palliative care (SPC).ResultsWe included 1736 patients in our analysis. Overall, 13.7% of patients were enrolled into the SPC and 14.4% received anticancer treatment in the last 2 weeks of life. The odds of receiving anticancer treatment significantly increased over time [odds ratio (OR) 1.15, 95% confidence interval (CI) 1.04-1.27]. There was an increased use of novel systemic therapy (e.g. small-molecule targeted therapy and immunotherapy) at the EoL. Older patients had significantly lower odds to receive anticancer treatment in the last 2 weeks of life as compared to younger patients (OR 0.96, 95% CI 0.95-0.98). As compared to patients receiving only a standard oncology care, those also enrolled into the SPC had significantly lower odds for anticancer treatment in the last 2 weeks of life (OR 0.22, 95% CI 0.12-0.43).ConclusionsTerminally ill cancer patients have increased odds for receiving anticancer treatment, especially novel systemic therapies, in the last 2 weeks of life. Younger patients and those not enrolled into the SPC are at particular risk for anticancer treatment at the EoL. There is a concern that terminally ill cancer patients may be aggressively treated due to the rapidly growing possibilities of anticancer treatment. The aim of this study was to evaluate the use of anticancer treatment at the end of life (EoL). This retrospective study included adult patients with advanced solid cancers who were treated at the Institute of Oncology Ljubljana and died of cancer between January 2015 and December 2019. A multiple logistic regression model was used to assess an association between the aggressiveness of anticancer treatment (i.e. systemic therapy, radiotherapy and surgery) in the last 2 weeks of life and year of death, age at death, sex, prognosis of cancer and enrolment into the specialist palliative care (SPC). We included 1736 patients in our analysis. Overall, 13.7% of patients were enrolled into the SPC and 14.4% received anticancer treatment in the last 2 weeks of life. The odds of receiving anticancer treatment significantly increased over time [odds ratio (OR) 1.15, 95% confidence interval (CI) 1.04-1.27]. There was an increased use of novel systemic therapy (e.g. small-molecule targeted therapy and immunotherapy) at the EoL. Older patients had significantly lower odds to receive anticancer treatment in the last 2 weeks of life as compared to younger patients (OR 0.96, 95% CI 0.95-0.98). As compared to patients receiving only a standard oncology care, those also enrolled into the SPC had significantly lower odds for anticancer treatment in the last 2 weeks of life (OR 0.22, 95% CI 0.12-0.43). Terminally ill cancer patients have increased odds for receiving anticancer treatment, especially novel systemic therapies, in the last 2 weeks of life. Younger patients and those not enrolled into the SPC are at particular risk for anticancer treatment at the EoL.
Cancer burden is increasing in the world and also in our country. Research work in oncology is of prime importance for successful cancer control. Despite all the advances in research, further efforts will be required in the future to ensure successful cancer control. The key here is knowing the obstacles of research in oncology and how to overcome them.
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