Dataset Information

Survival Estimates after Stopping Sorafenib in Patients with Hepatocellular Carcinoma: NEXT Score Development and Validation.

ABSTRACT:

Background/aims

Limited information is available regarding patient survival after sorafenib discontinuation in patients with hepatocellular carcinoma (HCC). Thus, we developed and validated a novel survival prediction model.

Methods

Clinical data from 409 patients with HCC who stopped taking sorafenib between September 2008 and February 2015 were reviewed.

Results

In the training cohort, four factors were independent negative predictors of survival (p<0.05). Based on the ? regression coefficient of each factor, we established the NEXT score (Survival after Stopping Nexavar Treatment), allocating 1 point each for an Eastern Cooperative Oncology Group score ?2, Child-Pugh class B or C, serum sodium ?135 mEq/L, and ?-fetoprotein ?400 ng/mL. Area under the receiver operating characteristic curve values to predict 1-, 3-, and 6-month survival rates were 0.805, 0.809, and 0.774, respectively, in the training cohort and 0.783, 0.728, and 0.673, respectively, in the validation cohort (n=137). When the training and validation cohorts were stratified into three risk groups (NEXT score 0 [low-risk] vs 1 to 2 [intermediate-risk] vs 3 to 4 [high-risk]), survival differed significantly between the groups (p?0.05, log-rank test).

Conclusions

In patients with HCC, survival after stopping sorafenib is poor. However, risk estimates based on a new "NEXT score" may help predict survival and prognosis even in patients who discontinue sorafenib treatment.

SUBMITTER: Lee HW

PROVIDER: S-EPMC5593332 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Survival Estimates after Stopping Sorafenib in Patients with Hepatocellular Carcinoma: NEXT Score Development and Validation.

Lee Hye Won HW Kim Hyun Soo HS Kim Seung Up SU Kim Do Young DY Kim Beom Kyung BK Park Jun Yong JY Ahn Sang Hoon SH Jeon Mi Young MY Heo Ja Yoon JY Park Soo Young SY Lee Yu Rim YR Jang Sun Kyung SK Lee Su Hyun SH Jang Se Young SY Tak Won Young WY Han Kwang-Hyub KH

Gut and liver 20170901 5

<h4>Background/aims</h4>Limited information is available regarding patient survival after sorafenib discontinuation in patients with hepatocellular carcinoma (HCC). Thus, we developed and validated a novel survival prediction model.<h4>Methods</h4>Clinical data from 409 patients with HCC who stopped taking sorafenib between September 2008 and February 2015 were reviewed.<h4>Results</h4>In the training cohort, four factors were independent negative predictors of survival (p<0.05). Based on the β ...[more]

PMID: 28651299

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Project description:Targeted therapy is currently the standard treatment for advanced hepatocellular carcinoma (HCC), but an effective treatment after the discontinuation of sorafenib therapy remains uncertain. We aim to investigate the survival benefits of transcatheter arterial chemoembolization (TACE) after stopping sorafenib therapy. We retrospectively analyzed all patients with advanced HCC, who had received palliative TACE after terminating sorafenib therapy, from January 2008 to June 2016. Patients who were in the terminal stage (Child-Pugh class C or performance status 3-4), who received a liver transplantation, or who had received any HCC treatment other than TACE, were excluded. Finally, 28 patients were recruited as the TACE group, and were randomly matched 1:1 by age, gender, Child-Pugh class, extrahepatic metastasis, and portal vein thrombosis with 28 controls who only received supportive care. For avoiding any immortal time bias, the index date of outcome follow-up was also matched. Cumulative incidences of, and hazard ratios (HRs) for, patient mortality were analyzed. The baseline demographic data between the TACE group and the control group were similar, but the 1-year overall survival rate in the TACE group was significantly higher than that of the control group (41.2%, 95% confidence interval [CI]: 19.4-63.0% vs. 24.5%, 95% CI: 6.3-42.7%; p < 0.01). In multivariate analysis, after adjusting for alpha-fetoprotein > 400ng/mL, Child-Pugh class B, and tumor extension > 50% of liver volume, TACE was independently associated with a decreased mortality risk(HR 0.19, 95% CI: 0.08-0.42). In addition, tumor extension > 50% of the liver was another independent prognostic factor associated with an increased mortality risk (HR 2.99, 95% CI: 1.31-6.82). Multivariate stratified analyses verified the association of TACE with a decreased mortality rate in each patient subgroup (all HR < 1.0). By controlling intrahepatic tumor growth, TACE may be a treatment option for use in improving patient survival in advanced HCC, after the termination of sorafenib therapy.

Project description:Background and aimsInflammation affects progression of hepatocellular carcinoma (HCC). We therefore postulate that systemic inflammatory markers could help to predict prognosis in HCC patients receiving sorafenib therapy.MethodsOverall survival (OS) of HCC patients receiving palliative sorafenib treatment was correlated with the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and the modified GPS (mGPS) along with clinicopathological parameters. Predictors of OS were assessed by multivariable Cox regression and receiver operating characteristics and area under the curve (ROC-AUC) analyses.ResultsPatients receiving sorafenib (n = 120) for advanced HCC (Barcelona Clinic Liver Cancer stage C) were explored by retrospective analysis. Findings were subsequently validated by a second HCC cohort (n = 113) receiving sorafenib at two independent treatment centers. Multivariable assessment across these HCC cohorts confirmed a stable association of CAR (p ≤ 0.001), GPS (p ≤ 0.01) and mGPS (p ≤ 0.004) with OS. This study also identified Eastern Cooperative Oncology Group (ECOG) performance score (p < 0.001) and portal thrombosis (p = 0.002) as prognostic factors and uncovered an inconsistent OS association of NLR and PLR in HCC patients. Additional combined analysis of ECOG, portal thrombosis and GPS within an extended score (GPS-EP) was associated with OS (p = 0.021), which was confirmed within the validation cohort (p = 0.001). In sorafenib-treated HCC, the ROC-AUC value for the prediction of 12-month survival was 0.761 (CAR >/≤0.37 cut-off, p < 0.001), 0.766 (GPS, p < 0.001) and 0.754 (mGPS, p < 0.001), respectively. In comparison to this, GPS-EP achieved a higher AUC of 0.826 (0.746-0.907) for the 12-month survival prediction, resulting in a 64.4% sensitivity and 83.3% specificity at a > 2 point cut-off.ConclusionsInflammatory scores obtained before sorafenib treatment initiation are associated with OS in advanced HCC. Their combination with other risk factors improves prediction of 3- and 12-month survival, which could guide treatment decisions in selected patient subgroups.

Project description:Background: There is not yet an effective marker in predicting the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC) patients. The Gustave Roussy Immune Score (GRIm-Score) based on three objective variables, namely, neutrophil-to-lymphocyte ratio (NLR), serum albumin level (ALB), and lactate dehydrogenase (LDH), was developed as feasible prognostic indication in lung cancer patients receiving ICIs therapies. Our study aimed to adapt the GRIm-Score (HCC-GRIm-Score) in HCC patients who received ICIs therapies and thus improving the predictive ability. Methods: From January 2018 to September 2020, 261 patients who received ICIs therapy were retrospectively included and divided into training and validation groups. After determining the factors for HCC-GRIm-Score by multivariable analysis from training group, the optimized HCC-GRIm-Score was validated and compared to the original GRIm-Score and the Barcelona clinic liver cancer (BCLC) staging system. Results: One hundred sixty-one and 80 patients were assigned into the training and validation groups, respectively. Two more factors, aspartate transaminase-to-alanine transaminase ratio [hazard ratio (HR), 1.51; 95% confidence interval (CI), 0.94-2.42] and total bilirubin (HR, 1.76; 95% CI, 1.07-2.88), were identified as independent prognostic factors for overall survival (OS) and integrated in the HCC-GRIm-Score system according to the multivariable analysis. A risk score based on the HCC-GRIm-Score indicated that patients presenting high score (>2) suffered from significantly shorter median OS of 10.3 months compared to those with a low score (not reached; HR, 2.99; 95% CI, 1.89-4.75; p < 0.001). In the validation group of 80 patients, the patients presenting a high score showed an inferior OS (HR 5.62, 95% CI, 1.25-25.24; p = 0.024). HCC-GRIm-Score had the highest area under curve of 0.719 (95% CI, 0.661-0.773) compared to original GRIm-Score and BCLC staging system. Conclusion: The present study confirmed that the modified HCC-GRIm-Score system provided superior predictive ability in identifying the HCC patients potentially benefit from ICIs therapies, compared to the original GRIm-Score and the BCLC staging system.

Project description:BackgroundPhase III trials show sorafenib improves survival in advanced hepatocellular carcinoma (HCC). Because of narrow trial eligibility, results may not be generalizable to a broader HCC population. We sought to evaluate the effectiveness of initial sorafenib versus no treatment among Medicare beneficiaries with advanced HCC.Materials and methodsPatients with advanced HCC diagnosed from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Eligible patients received initial sorafenib or no therapy and were covered by Medicare parts A, B, and D. Sorafenib use and outcomes were described in this population. Using a propensity score (PS)-matched sample, we compared the effectiveness of sorafenib versus no treatment by Cox proportional hazards and binomial regression, using a landmark requiring all patients to survive ?60 days after diagnosis.ResultsOf 1,532 patients, 27% received initial sorafenib. Median duration of sorafenib use was 60 days (interquartile range [IQR], 30-107 days), and median survival from first prescription was 3 months (IQR, 1-8 months). In the PS-matched cohort, median survival was 3 months from the 60-day landmark in sorafenib-treated (n = 223) and 2 months in untreated (n = 223) patients (adjusted hazard ratio, 0.95 [95% confidence interval (CI), 0.78-1.16]). Sorafenib was associated with a nonsignificant reduction in mortality at 3 months (44% versus 51%; adjusted risk ratio, 0.88 [95% CI, 0.72-1.07]), but no reduction thereafter.ConclusionSurvival after sorafenib initiation in newly diagnosed Medicare beneficiaries with HCC is exceptionally short, suggesting trial results are not generalizable to all HCC patients. The downsides of sorafenib use-high drug-related symptom burden and high drug cost-must be considered in light of this minimal benefit.Implications for practiceThe findings of a median survival of only 3 months in Medicare beneficiaries with HCC prescribed sorafenib as first-line therapy highlight the questionable value of sorafenib in this population. Patients should be cautioned that outside of the narrow confines of randomized trials, their life expectancy may be very short, and any benefit of sorafenib is likely to be quite small. Given that sorafenib causes considerable adverse effects and offers no symptom palliation, supportive care should be discussed as a reasonable alternative to sorafenib, particularly for patients who have a poor performance status or advanced cirrhosis.

Project description:AimTo investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis.MethodsFrom October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled. According to the Barcelona Clinic Liver Cancer (BCLC) classification, patients were in the advanced stage (BCLC-C) or in the intermediate stage (BCLC-B) but unfit or unresponsive to other therapeutic strategies. Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo, and analyzed according to the modified Response Evaluation Criteria in Solid Tumors. Sorafenib was administered at 800 mg/d, until radiological progression or occurrence of unacceptable adverse events (AEs). Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.ResultsForty-four patients were enrolled, 15 had intermediate HCC and 14 a Child-Pugh score of B7. AEs caused treatment interruption in 19 patients (43%), and median treatment duration was shorter in this subset (5 wk vs 19 wk, P < 0.001) and in the BCLC-C subgroup (13 wk vs 40 wk, P = 0.015). No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years. After 16 wk of treatment, 18 patients (41%) had stable disease or partial response. Patients with viral infection or BCLC-C were at higher risk of disease progression. ECOG, extrahepatic spread, macrovascular invasion, alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.ConclusionIn patients with cirrhosis and HCC treated with sorafenib, AEs are a common cause of early treatment withdrawal. Vascular invasion and extrahepatic spread condition early response to treatment and survival. Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter overall survival.

Dataset Information

Survival Estimates after Stopping Sorafenib in Patients with Hepatocellular Carcinoma: NEXT Score Development and Validation.

Background/aims

Methods

Results

Conclusions

Publications

Survival Estimates after Stopping Sorafenib in Patients with Hepatocellular Carcinoma: NEXT Score Development and Validation.

Similar Datasets

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