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The prognostic analysis of different metastatic patterns in advanced liver cancer patients: A population based analysis.

ABSTRACT: The prognostic impact of different distant metastases pattern in liver cancer is unexplored still now. The aim of this study is to analyze the metastasis patterns and prognosis differences for patients with stage IV liver cancers.A SEER analysis was performed. Overall survival and cancer-specific survival were calculated by the Kaplan-Meier method. Multivariable Cox regression models were used to further analyze survival outcome and other prognostic factors.A total of 37526 eligible cases were retrieved in the Surveillance, Epidemiology, and End Results database. Among these patients, stage of IV liver cancer accounted for 14.80% (5555/37526) at initial diagnosis. Patients who suffered bone, brain or lung metastasis occupied 55.61% (3089/5555). Comparing with other two single metastases, the patients with brain metastasis exhibited worst overall survival whose mean of survival was 4.758 months. Multivariate analysis with Cox hazard regression model showed that metastatic site was an independent prognostic factor of overall survival and cancer-specific survival in patients with single metastasis (P<0.05). The results of univariate analysis showed that metastatic pattern was significantly correlated with overall survival (P = 0.038) and cancer-specific survival (P = 0.035) of patients with two sites.Lung was the most common site of single metastasis for liver cancers. Patients with bone metastasis had best survival outcome comparing with other two distant metastases. Patients with two metastatic sites, where one of them is the lung tends to have a slight trend to a worse outcome.

SUBMITTER: Chen J

PROVIDER: S-EPMC6089416 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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The prognostic analysis of different metastatic patterns in advanced liver cancer patients: A population based analysis.

Chen Jie J

PloS one 20180813 8

<h4>Background</h4>The prognostic impact of different distant metastases pattern in liver cancer is unexplored still now. The aim of this study is to analyze the metastasis patterns and prognosis differences for patients with stage IV liver cancers.<h4>Methods</h4>A SEER analysis was performed. Overall survival and cancer-specific survival were calculated by the Kaplan-Meier method. Multivariable Cox regression models were used to further analyze survival outcome and other prognostic factors.<h4 ...[more]

PMID: 30102707

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Project description:Background and objectiveOveractivation of the PI3K/AKT pathway can occur in many cancers. Capivasertib is a potent, selective pan-AKT inhibitor. The objectives of this analysis were to develop a population pharmacokinetic model for capivasertib and to quantitatively assess the impact of intrinsic and extrinsic factors on the pharmacokinetics of capivasertib.MethodsPharmacokinetic data from four phase I and II studies were combined. Capivasertib was administered orally at a dose range of 80-800 mg twice daily over 28-day and 21-day cycles as monotherapy or in combination with paclitaxel or fulvestrant, using continuous dosing or one of two intermittent dosing schedules: either 4 days on, 3 days off (4/3) or 2 days on, 5 days off (2/5). Several models and approaches were tested for their ability to describe capivasertib disposition. The covariates assessed included dose, schedule, age, body weight, race, sex, creatinine clearance, hepatic function, renal function, smoking status, food effect, formulation, and concomitant use with paclitaxel, fulvestrant, cytochrome P450, family 3, subfamily A (CYP3A) inducers, CYP3A inhibitors and acid-reducing agents.ResultsA total of 3963 capivasertib plasma concentrations from 441 patients were included. Capivasertib pharmacokinetics was adequately described by a three-compartment model where the apparent clearance (CL/F) presented a moderate time-dependent and dose-dependent clearance. Following oral administration of multiple doses of capivasertib (400 mg twice daily; [4/3]), the initial CL/F was 62.2 L/h (between-subject variability 39.3%), and after approximately 120 hours, CL/F decreased by 18%. The effective half-life was 8.34 h. Steady state was predicted to be reached on every third and fourth dosing day each week from the second week with exposure levels that produced robust inhibition of AKT but not of other related kinases. The area under the plasma concentration-time curve and maximum plasma concentration of capivasertib were proportional between the dose levels of 80-480 mg after multiple doses but more than proportional beyond 480 mg. Schedule, age, race, sex, creatinine clearance, hepatic function, renal function, smoking status and concomitant use with fulvestrant, CYP3A inducers, CYP3A inhibitors or acid-reducing agents were not significant covariates for capivasertib pharmacokinetics. Concomitant use of paclitaxel, food effect and formulation statistically significantly affected capivasertib pharmacokinetics, but the effect was low. Body weight was statistically significantly related to capivasertib CL/F, with a 12% reduction in CL/F at steady state and a 14% increase in the area under the curve for 12 hours at steady state and maximum concentration at steady state at a lower body weight (47 kg vs 67 kg reference).ConclusionsCapivasertib pharmacokinetics showed moderate between-subject variability, and most covariates assessed had no significant impact. Body weight, dose, concomitant use of paclitaxel, food effect and formulation showed statistically significant effects. However, these were predicted to impact exposure to capivasertib by <20% and were not expected to be clinically relevant. Based on the population pharmacokinetics, no a priori dose adjustment is needed for intrinsic and extrinsic factors.

Project description:ObjectiveBased on a large public cohort, we aimed to investigate the prevalence of distant metastases in patients with osteosarcoma, to evaluate the survival of patients with different metastases and to reveal the related risk and prognostic factors for distant metastases.MethodsThe information of osteosarcoma patients with or without distant metastases was retrospectively extracted from the Surveillance, Epidemiology, and End Result database from January 2010 to December 2015. Patients were excluded if they were diagnosed at autopsy or via death certification. The Kaplan-Meier method was used to calculate the overall survival in the entire cohort and across patients with metastases to different organs. The related prognostic factors were investigated by univariate and multivariate Cox proportional hazard regression analysis. The logistic regression method was used to reveal the risk factors for the development of different metastases. The effects of different variables on the survival and prevalence of distant metastases were compared using subgroup analysis. Variables with P < 0.05 in the univariate regression analysis were further examined using multivariate regression analysis.ResultsIn total, 1470 osteosarcoma patients (mean age 30 ± 22 years) were included, among which 278 patients (18.9%) were initially diagnosed with distant metastasis. The median follow-up duration was 33.0 (30.2-35.8) months. The lung was the most common metastatic site (83.8%), followed by the bone (21.9%), liver (2.9%), and brain (2.2%). A total of 232 patients (83.5%) presented only one distant metastatic site, while the other 46 patients showed two or more metastatic sites. A lower proportion of metastasis was observed in patients aged from 25 to 59 years [odds ratio (OR) = 0.59; 95% confidence interval (CI): 0.37-0.95]. More metastases were noted in patients with T2/T1 (OR = 1.91; 95% CI: 1.28-2.84), T3/T1 (OR = 4.48; 95% CI: 1.78-11.30) and N1/N0 stages (OR = 6.66; 95% CI: 2.68-16.56). The 1-, 3-, and 5-year overall survival rates for metastatic patients were 57.3% (95% CI: 50.8%-63.8%), 25.3% (95% CI: 18.8%-31.9%), and 18.1% (95% CI: 10.2%-26.0%), respectively. Metastatic patients older than 25 years were prone to have poor survival and a relatively better prognosis (hazard ratio = 0.41; 95% CI: 0.25-0.69) was noticed among those who underwent surgery on the primary site. Different metastatic organs have homogeneous and heterogeneous risk and prognostic factors.ConclusionThe high incidence of initial distant metastasis in osteosarcoma and the inconsistent predictive factors should be given more attention in the clinical management of patients with osteosarcoma.

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The prognostic analysis of different metastatic patterns in advanced liver cancer patients: A population based analysis.

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The prognostic analysis of different metastatic patterns in advanced liver cancer patients: A population based analysis.

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