Postoperative adjuvant TACE-associated nomogram for predicting the prognosis of resectable Hepatocellular Carcinoma with portal vein Tumor Thrombus after Liver Resection.
ABSTRACT: Background: To explore the effects of postoperative adjuvant transarterial chemoembolization (PA-TACE) on the prognosis of HCC patients with Portal Vein Tumor Thrombus (PVTT) undergoing resection, and to develop a PA-TACE-related nomogram for predicting survival individually. Patients and Methods: Two hundred and ninety-three consecutive HCC patients with PVTT under R0 hepatectomy were recruited. Forty-seven cases had recurrence within one month after surgery. The remaining 246 cases consisted of 90 PA-TACE and 156 non-PA-TACE cases. COX regression analysis was performed for overall survival (OS) or recurrence-free survival (RFS) of these 246 cases, allowing the derivation of independent factors that were integrated into the nomogram. C-index, calibration curves, and risk stratification were performed to evaluate the performance and discriminative power of the nomograms. Results: In 246 patients without recurrence within one month after surgery, the OS and RFS for the PA-TACE group were significantly better than those for the non-PA-TACE group (P<0.0001, P<0.0001, respectively). After Cox regression analysis of OS or RFS, PA-TACE-related nomogram models were constructed. The C-index of the PA-TACE-related nomogram for OS and RFS was 0.72 and 0.73, respectively. Calibration curves revealed a good agreement between predictions and observations for the nomograms. Based on the nomogram-related risk stratification, Kaplan-Meier curves showed powerful discriminative ability. Conclusions: PA-TACE therapy improved the survival of HCC patients with PVTT undergoing hepatectomy. Accurate nomogram models were developed for predicting the individual survival and recurrence of these patients.
Project description:BACKGROUND:The predictive model of postsurgical recurrence for solitary early hepatocellular carcinoma (SE-HCC) is not well established. The aim of this study was to develop a novel model for prediction of postsurgical recurrence and survival for patients with hepatitis B virus (HBV)-related SE-HCC ?10 cm. PATIENTS AND METHODS:Data from 1,081 patients with HBV-related SE-HCC ?10 cm who underwent curative liver resection from 2003 to 2016 in our center were collected retrospectively and randomly divided into the derivation cohort (n =?811) and the internal validation cohort (n =?270). Eight hundred twenty-three patients selected from another four tertiary hospitals served as the external validation cohort. Postsurgical recurrence-free survival (RFS) and overall survival (OS) predictive nomograms were generated. The discriminatory accuracies of the nomograms were compared with six conventional hepatocellular carcinoma (HCC) staging systems. RESULTS:Tumor size, differentiation, microscopic vascular invasion, preoperative ?-fetoprotein, neutrophil-to-lymphocyte ratio, albumin-to-bilirubin ratio, and blood transfusion were identified as the risk factors associated with RFS and OS. RFS and OS predictive nomograms based on these seven variables were generated. The C-index was 0.83 (95% confidence interval [CI], 0.79-0.87) for the RFS-nomogram and 0.87 (95% CI, 0.83-0.91) for the OS-nomogram. Calibration curves showed good agreement between actual observation and nomogram prediction. Both C-indices of the two nomograms were substantially higher than those of the six conventional HCC staging systems (0.54-0.74 for RFS; 0.58-0.76 for OS) and those of HCC nomograms reported in literature. CONCLUSION:The novel nomograms were shown to be accurate at predicting postoperative recurrence and OS for patients with HBV-related SE-HCC ?10 cm after curative liver resection. IMPLICATIONS FOR PRACTICE:This multicenter study proposed recurrence or mortality predictive nomograms for patients with hepatitis B virus-related solitary early hepatocellular carcinoma ?10 cm after curative liver resection. A close postsurgical surveillance protocol and adjuvant therapy should be considered for patients at high risk of recurrence.
Project description:This study sought to develop an effective and reliable nomogram for predictions of recurrence for postoperative adjuvant transarterial chemoembolization (PA-TACE) in patients with hepatitis B virus-related (HBV) hepatocellular carcinoma (HCC).The nomogram was established based on data obtained from a retrospective study on 235 consecutive patients with HBV HCC who received PA-TACE as an initial therapy from 2006 to 2010 in our center. Eighty-four patients who were collected at another institution between 01/2008 and 12/2010 served as an external validation set. Recurrence-free survival (RFS) was collected. The nomogram for tumor recurrence was developed based on the data obtained before the PA-TACE procedure. Predictive accuracy and discriminative ability of the nomogram were assessed by concordance index (C-index), calibration curves, and validation set.The 1, 2, 3-year RFS rates were 55.5%, 27.0%, and 14.1%, respectively, in the patients from the derivation set and 60.7%, 33.2%, and 23.8% in those from the validation set. Four risk factors (HBV-DNA level, vascular invasion, change of Child-Pugh score, and tumor diameter) in the multivariate analysis were significantly associated with RFS. The statistical nomogram incorporated these 4 factors achieved good calibration and discriminatory abilities with the c-index of 0.74 (95% CI 0.66-0.82). The findings were supported by the independent external validation set (c-index, 0.70; 95% CI 0.58-0.83). The area under the receiver operating characteristic curve in our model was greater than those of conventional staging systems in the validation patients (corresponding c-indices, 0.56-0.64).The novel nomogram may achieve an optimal prediction for recurrence outcome in HBV-related HCC with PA-TACE.
Project description:In this study, we aimed to compare and validate the prognostic abilities of preoperative systemic immune cells in hepatocellular carcinoma (HCC) after curative hepatectomy. We developed two nomograms to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) after comparisons of the systemic immune cell prognostic scores. The two nomograms were constructed based on 305 patients who underwent curative hepatectomy for HCC. The predictive accuracy and discriminative ability of the nomograms were compared with six commonly used staging systems for HCC. The results were validated using bootstrap resampling and an internal validation cohort of 142 patients and an external validation cohort of 169 patients. Necroinflammatory activity in peritumoral liver tissues in the primary cohort was evaluated by hematoxylin and eosin (H&E) staining. Neutrophil, monocyte, and lymphocyte ratio (NMLR) had a higher area under the receiver operating characteristic curves (AUROC) value at both RFS (AUC = 0.603) and OS (AUC = 0.726) compared to that of other systemic immune cell prognostic scores. The independent predictors of RFS or OS, including ?-fetoprotein (AFP), tumor size, tumor number, microvascular invasion, and NMLR, were incorporated into the two nomograms. In the primary cohort, the C-indexes of the RFS and OS nomograms were 0.705 and 0.797, respectively. The ROC analyses showed that the two nomograms had larger AUC values (0.664 for RFS and 0.821 for OS) than those of the American Joint Commission on Cancer seventh edition, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, Japan Integrated Staging Score, Okuda stage, and the Vauthey's system. These results were verified by internal and external validations. The nomogram-predicted probability of RFS was associated with peritumoral necroinflammatory activity scores (r = 0.304, P < 0.001). The proposed nomograms had accurate prognostic prediction in patients with HCC after curative hepatectomy.
Project description:Background:Both persistent inflammatory activity and liver function damage contribute to a poor prognosis of hepatocellular carcinoma (HCC). This study aimed to develop nomograms that incorporate hepatitis virus B (HBV)-related peritumoral inflammation score (PIS) and liver function based on ALBI score to predict postoperative outcomes of HCC. Methods:The prognostic roles of HBV-related preoperative PIS and ALBI scores in HCC recurrence were examined, and then two nomograms were constructed. The predictive accuracy and discriminative ability of the nomograms were compared with AJCC and BCLC staging systems of HCC. Results:PIS (HBV-PIS) and ALBI scores (HBV-ALBI) with different HBV-DNA loads had association with overall survival (OS) and/or recurrence-free survival (RFS) of HCC. The independent predictors of OS and RFS were incorporated into the corresponding nomograms. In the training cohort, the C-indexes of OS and RFS nomograms were 0.751 and 0.736, respectively. ROC analyses showed that both OS and RFS nomograms had larger AUC (0.775 and 0.739, respectively) than AJCC and BCLC staging systems. These results were verified by the internal and external validation cohorts. Conclusion:The proposed nomograms, including HBV-DNA load-related PIS and ALBI scores, were accurate in predicting survival for HCC after curative resection.
Project description:WW domain-containing oxidoreductase (WWOX), which has a protein-interaction domain and is regarded to be a tumor suppressor, has been known to play an important role in anti-angiogenesis and cancer progression. This study aimed to investigate prognostic values of WWOX expression in hepatocellular carcinoma (HCC) patients after hepatectomy. Additionally, we intended to formulate a valuable prognostic nomogram for HCCs. 182 HCC patients who underwent hepatectomy from January 2009 to January 2010 were enrolled in our study. qRT-PCR, Western blot, and immunohistochemistry on tissue microarrays were then used to determine the expression levels of WWOX. An evaluation of the role of WWOX expression levels in the prognosis and outcome of patients was established. A decrease in the expression of WWOX was found when compared to adjacent tumor-free tissues, which led to worse overall survival (OS) and recurrence-free survival (RFS) and, therefore, was considered as an independent negative factor in the prognosis of HCC. Two nomograms, comprising WWOX, alpha-fetoprotein (AFP), tumor size, and ?-glutamyltransferase (?-GT), were constructed to obtain superior discriminatory abilities than conventional staging systems in terms of C-index and clinical net benefit on decision curve analysis (DCA) for OS and RFS. Our data suggest that WWOX expression is strongly related to HCC post-resection aggressiveness and recurrence. Additional advanced and accurate predictive model through the incorporation of WWOX into nomogram could help predict OS or RFS for HCC patients.
Project description:Precise predictive tools are critical for choosing the individualized treatment protocols and follow-up procedures for patients with gastric cancer (GC). In this study, we aimed to evaluate and validate the prognostic abilities of preoperative nutrition and immunity parameters in GC after curative R0 resection.We established two nomograms based on 437 patients who underwent curative radical gastrectomy for gastric cancer to predict the postoperative overall survival (OS) and recurrence-free survival (RFS), and then compared the predictive accuracy and discriminative ability of the nomograms with the TNM stage systems for GC. An internal validation cohort of 141 patients and an external validation cohort of 116 patients were used to validate the result.The independent predictive factors for OS or RFS, including T stage, N stage, differentiated degree, neutrophil monocyte lymphocyte ratio (NMLR) and albumin globulin ratio (AGR) were used to establish the 2 nomograms. The C-index of the OS nomogram was 0.802, which was higher than that of the AGR, the NMLR and the TNM stage. The C-index of the RFS nomogram was 0.850, which was higher than that of the AGR, the NMLR and the TNM stage. Analogously, the areas under the receiver operating characteristics curves (AUROCs, 0.920 for OS and 0.897 for RFS, respectively) of the two nomograms were higher than that of the NMLR, the AGR and the TNM stage. In the internal validation cohort, the C-indexes of the OS and RFS nomograms were 0.812 and 0.826, respectively. In the external validation cohort, the C-indexes of the OS and RFS nomograms were 0.866 and 0.880, respectively.The proposed nomograms including nutrition and immunity parameters were proved to have excellent predictive ability in survival and recurrence for patients with GC after R0 resection.
Project description:Patients with hepatocellular carcinoma (HCC) accompanying portal vein tumor thrombosis (PVTT) have relatively few therapeutic options and an extremely poor prognosis. These patients are classified into barcelona clinic liver cancer stage C and sorafenib is suggested as the standard therapy of care. However, overall survival (OS) gain from sorafenib is unsatisfactory and better treatment modalities are urgently required. Therefore, we critically appraised recent data for the various treatment strategies for patients with HCC accompanying PVTT. In suitable patients, even surgical resection can be considered a potentially curative strategy. Transarterial chemoembolization (TACE) can be performed effectively and safely in a carefully chosen population of patients with reserved liver function and sufficient collateral blood flow nearby the blocked portal vein. A recent meta-analysis demonstrated that TACE achieved a substantial improvement of OS in HCC patients accompanying PVTT compared with best supportive care. In addition, transarterial radioembolization (TARE) using yttrium-90 microspheres achieves quality-of-life advantages and is as effective as TACE. A large proportion of HCC patients accompanying PVTT are considered to be proper for TARE. Moreover, TACE or TARE achieved comparable outcomes to sorafenib in recent studies and it was also reported that the combination of radiotherapy with TACE achieved a survival gain compared to sorafenib in HCC patients accompanying PVTT. Surgical resection-based multimodal treatments, transarterial approaches including TACE and TARE, and TACE-based appropriate combination strategies may improve OS of HCC patients accompanying PVTT.
Project description:The optimal treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains controversial. We aimed to investigate the best treatment for patients with HCC with PVTT. From January 2002 to January 2014, the data from all consecutive patients with HCC with PVTT who underwent surgical treatment (ST),TACE,TACE combined with sorafenib (TACE-Sor), or TACE combined with radiotherapy (TACE-RT) in the 4 largest tertiary hospitals in China were analyzed retrospectively. The patients were divided into 3 subtypes according to the extent of PVTT in the portal vein (type I-III). The primary endpoint was overall survival (OS). A total of 1580 patients with HCC with PVTT were included in the study. The median survival times (MST) for ST (n?=?745) for type I, II, and III patients (95% CI) were 15.9 (13.3-18.5), 12.5 (10.7-14.3), and 6.0 (4.3-7.7) months, respectively. The corresponding figures for patients after TACE (n?=?604) were 9.3 (5.6-12.9), 4.9 (4.1-5.7), and 4.0 (3.1-4.9), respectively; for patients after TACE-Sor (n?=?113) 12.0 (6.6-17.4), 8.9 (6.7-11.1), and 7.0 (3.0-10.9), respectively; and for patients after TACE-RT (n?=?118) 12.2 (0-24.7), 10.6 (6.8-14.5), and 8.9 (5.2-12.6), respectively. Comparison among the different treatments for the 3 subtypes of PVTT patients after propensity score (PS) matching showed the effectiveness of ST to be the best for type I and type II PVTT patients, and TACE-RT was most beneficial for type III patients. Treatment was an independent risk factor of OS. ST was the best treatment for type I and II PVTT patients with Child-Pugh A and selected B liver function. TACE-RT should be given to type III PVTT patients.
Project description:<h4>Objective</h4>To investigate the impact of menopausal status on the prognosis for sex-classified Hepatocellular carcinoma (HCC) and to establish prognostic nomograms for patients after liver resection.<h4>Results</h4>After propensity score matching (PSM), statistically significant differences in both overall survival (OS) and recurrence-free survival (RFS) were found between men and women HCC patients. Based on Cox regression analysis, these differences were evident in the normal menstruation (N) group expanded with male patients, but not in either the expanded postmenopausal (P) or intermediate (I) groups. Sex disparity was also apparent in the recurrence-free survival (RFS) of the total HCC patients. Integrated with independent factors, nomograms for the OS and RFS of the expanded N group showed higher C-indices of 0.773 and 0.724, respectively, than those of nomograms for the total patients and BCLC stage (P<0.001).<h4>Conclusion</h4>Sex disparity appears to affect both the survival and recurrence of HCC only in normal menstruation women and their matched men. For predicting survival, prognostic nomograms derived from the expanded N group of HCC patients were more accurate for patients with the same clinical conditions.<h4>Methods</h4>The patients (390 females and 1920 males), who underwent curative liver resection for HCC during 2008 to 2012, were screened. The 390 women were divided into three groups: normal menstruation, intermediate, and postmenopausal. To overcome selection bias, the three groups of females were matched with males at a ratio of 1:2, using propensity score matching. Based on further Cox regression analysis, independent factors were integrated into nomograms for OS and RFS by R rms. The accuracy and discrimination of the nomograms were evaluated by the C-index, calibration curve, and decision curve analysis.
Project description:A combination of transarterial chemoembolization (TACE) plus sorafenib or radiotherapy (RT) has demonstrated efficacy in patients with advanced hepatocellular carcinoma (HCC). Here, the two combined treatment approaches were compared in patients with HCC and portal vein tumor thrombus (PVTT). Data from 307 patients treated with TACE plus RT (n = 203) or TACE plus sorafenib (n = 104) as first-line treatment for HCC with PVTT were retrospectively evaluated. Using the propensity model to correct selection bias, 87 patients were included from each treatment group. During follow up (median, 12 months) in the entire study population, the median progression-free survival (PFS) and overall survival (OS) were significantly longer in the TACE plus RT group than in the TACE plus sorafenib group (6.5 vs. 4.3 months, respectively; p = 0.017 and 16.4 vs. 12 months, respectively; p = 0.007). Following propensity score matching, the median PFS and OS in the two groups showed no statistically significant difference. Multivariable analysis found no significant association between PFS or OS and the treatment type. In conclusion, this retrospective study of data from patients with advanced HCC with PVTT shows that PFS and OS did not differ significantly in patients treated with TACE plus RT and TACE plus sorafenib.