Long-term outcome and prognostic nomogram for intrahepatic cholangiocarcinoma after thermal ablation: a retrospective study
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ABSTRACT: Background
To evaluate the efficacy of thermal ablation and transcatheter arterial chemoembolization (TACE) in treating intrahepatic cholangiocarcinoma (ICC), and to propose a prognostic nomogram to predict overall survival (OS) after ablation. Methods
ICC patients (n=58) undergoing percutaneous CT-guided ablation with or without pre-ablation TACE at our institute from 2009 to 2013 were enrolled in the primary cohort. All treatments were performed under conscious sedation and local anesthesia. Prognostic factors for OS were identified to establish the nomogram. The nomogram was accessed by the concordance index (C-index) and calibration curve, and compared with 11 currently available prognostic systems. The nomogram was further evaluated in a validation cohort (n=19) of patients with ICC who underwent thermal ablation and TACE from 2014 to 2016. Results
In the primary cohort, the median OS was 17.9 months and the 1-, 3-, 5-year OS rates were 69.6%, 29.5%, 23.6%, respectively. Three single independent predictors (number of tumors, vascular invasion and lymph node metastasis) for OS were identified by multivariate analysis and used to formulate the nomogram. The C-index of the nomogram was 0.834 [95% confidence interval (CI), 0.765 to 0.904], significantly higher than that of ten current prognostic systems for ICC, and similar with that of the Wang nomogram. The performance of the proposed nomogram was also confirmed in the validation cohort (C-index, 0.839). Conclusions
Thermal ablation appears to be effective for ICC patients. The proposed nomogram is helpful for predicting patient survival after ablation treatment.
SUBMITTER: Wang Y
PROVIDER: S-EPMC8797463 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and Aims: Despite resection being considered the treatment of choice for intrahepatic cholangiocarcinoma (ICC), percutaneous thermal ablation can be an alternative treatment for patients unfit for surgery. Our aim was to compare long-term results of percutaneous sonographically-guided radiofrequency ablation (RFA) with high-powered microwave ablation (MWSA) in treatment of ICC. Methods: Results of 71 ICC patients with 98 nodules treated with RFA (36 patients) or MWSA (35 patients) between January 2008 and June 2018 in 5 Interventional Ultrasound centers of Southern Italy were retrospectively reviewed. Cumulative overall survival curves were calculated with the Kaplan-Meyer method and differences with the log-rank test. Eleven possible factors affecting survival were analyzed. Results: Overall survival of the entire series was 88%, 65%, 45% and 34% at 12, 36, 60 and 80 months, respectively. Patients treated with MWSA survived longer than patients treated with RFA (p < 0.005). The MWSA group with ICC nodules ≤3 cm or nodules up to 4 cm survived longer than the RFA group (p < 0.0005). In patients with nodules >4 cm, no significant difference was found. Disease-free survival and progression-free survival were better in the MWSA group compared to the RFA group (p < 0.005). Diameter of nodules and MWSA were independent factors predicting a better survival. No major complications were observed. Conclusions: MWSA is superior to RFA in treating ICC unfit for surgery, achieving better long-term survival in small (≤3 cm) ICC nodules as well as nodules up to 4 cm of neoplastic tumors and should replace RFA.
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Project description:BackgroundCumulating evidence indicates that the systemic inflammatory response (SIR) plays a crucial role in the prognosis of various cancers. We aimed to generate a preoperative risk grade (PRG) by integrating SIR markers to preoperatively predict the long-term prognosis of intrahepatic cholangiocarcinoma (ICC).Methods468 consecutive ICC patients who underwent hepatectomy between 2010 and 2017 were enrolled. The PRG and a nomogram were generated and their predictive accuracy was evaluated.ResultsThe PRG consisted of two non-tumor-specific SIR markers platelet-to-lymphocyte ratio (PLR) and albumin (ALB), which were both the independent predictors of overall survival (OS). Multivariate analysis showed that the PRG was significantly associated with OS (PRG = 1: hazard ratio (HR) = 3.800, p < 0.001; PRG = 2: HR = 7.585, p < 0.001). The C-index of the PRG for predicting survival was 0.685 (95% CI 0.655 to 0.716), which was statistically higher than that of the following systems: American Joint Committee on Cancer (AJCC) 8th edition (C-index 0.645), Liver Cancer Study Group of Japan (LCSGJ) (C-index 0.644) and Okabayashi (C-index 0.633) (p < 0.05). Besides, the C-index of the nomogram only consisting of the tumor-specific factors (serum carcinoembryonic antigen, carbohydrate antigen 19-9, tumor number) could be improved to 0.737 (95% CI 0.062-0.768) from 0.625 (95% CI 0.585-0.665) when the PRG was incorporated (p < 0.001).ConclusionsThe PRG integrating two non-tumor-specific SIR markers PLR and ALB was a novel method to preoperative predicting the prognosis of ICC.
| S-EPMC7936481 | biostudies-literature
Project description:BackgroundAblation has been recommended by worldwide guidelines as first-line treatment for hepatocellular carcinoma (HCC), while evidence regarding its efficacy for primary intrahepatic cholangiocarcinoma (iCCA) is lacking. We aimed to study the efficacy of ablation in treating iCCA by comparing its prognosis with surgery.MethodsIn this real-world multicenter cohort study from January 2009 to June 2022, 10,441 iCCA patients from ten tertiary hospitals were identified. Patients who underwent curative-intent microwave ablation (MWA) or liver resection (LR) for tumors within Milan criteria were included. One-to-many propensity score matching (PSM) at variable ratios (1:n ≤4) was used to balance baseline characteristics. Mediation analysis was applied to identify potential mediators of the survival difference.Findings944 patients were finally enrolled in this study, with 221 undergoing MWA and 723 undergoing LR. After PSM, 203 patients in the MWA group were matched with 588 patients in the LR group. The median follow-up time was 4.7 years. Compared with LR, MWA demonstrated similar overall survival (5-year 44.8% versus 40.4%; HR 0.96, 95% CI 0.71-1.29, P = .761). There was an improvement in the 5-year disease-free survival rate for MWA from 17.1% during the period of 2009-2016 to 37.3% during 2017-2022, becoming comparable to the 40.8% of LR (P = .129). The proportion of ablative margins ≥5 mm increased from 25% to 61% over the two periods, while this proportion of surgical margins was 62% and 77%, respectively. 34.5% of DFS disparity can be explained by the mediation effect of margins (P < .0001). Similar DFS was observed when both ablative and surgical margins exceeded 5 mm (HR 0.83, 95% CI 0.52-1.32, P = .41).InterpretationMWA may be considered as a viable alternative to LR for iCCA within Milan criteria when an adequate margin can be obtained.FundingNational Natural Science Foundation of China.
| S-EPMC10796969 | biostudies-literature
Project description:Background: The prognosis of patients with post-operative recurrent intrahepatic cholangiocarcinoma (ICC) is at great variance. We aimed to propose a novel efficient prognostic nomogram in facilitating the risk stratification for post-operative recurrent ICC patients. Methods: From 2000 to 2016, a total of 237 post-operative recurrent ICC patients were enrolled in this study, and randomly divided into training (n = 178) and validation cohorts (n = 59) at a ratio of 3:1. The performance of this nomogram was assessed by discrimination, calibration, and clinical usefulness, and the results were compared with four other currently used ICC staging systems. Results: On multivariate analysis of the training cohort, serum CA 19-9, albumin-bilirubin grade at recurrence, time from primary resection to recurrence, tumor number at recurrence, and treatment for recurrence were selected for the model. The concordance index (C-index) of our model was 0.791 [95% confidence interval (CI), 0.736-0.846], which was statistically higher than the values of the following systems: American Joint Committee on Cancer (AJCC) 8th edition (0.610), Liver Cancer Study Group of Japan (0.613), Nathan (0.582), and Okabayashi (0.600; P < 0.001 for all). The nomogram performed well in terms of calibration when compared with actual observation. The findings were supported by the validation cohort. Conclusions: Compared with four currently used staging systems for ICC, our nomogram showed more promising clinical utility in improving individualized predictions of survival for post-operative recurrent ICC patients.
| S-EPMC7142225 | biostudies-literature
Project description:Background and aimGenetic alterations in intrahepatic cholangiocarcinoma (iCCA) are increasingly well characterized, but their impact on outcome and prognosis remains unknown.Approach and resultsThis bi-institutional study of patients with confirmed iCCA (n = 412) used targeted next-generation sequencing of primary tumors to define associations among genetic alterations, clinicopathological variables, and outcome. The most common oncogenic alterations were isocitrate dehydrogenase 1 (IDH1; 20%), AT-rich interactive domain-containing protein 1A (20%), tumor protein P53 (TP53; 17%), cyclin-dependent kinase inhibitor 2A (CDKN2A; 15%), breast cancer 1-associated protein 1 (15%), FGFR2 (15%), polybromo 1 (12%), and KRAS (10%). IDH1/2 mutations (mut) were mutually exclusive with FGFR2 fusions, but neither was associated with outcome. For all patients, TP53 (P < 0.0001), KRAS (P = 0.0001), and CDKN2A (P < 0.0001) alterations predicted worse overall survival (OS). These high-risk alterations were enriched in advanced disease but adversely impacted survival across all stages, even when controlling for known correlates of outcome (multifocal disease, lymph node involvement, bile duct type, periductal infiltration). In resected patients (n = 209), TP53mut (HR, 1.82; 95% CI, 1.08-3.06; P = 0.03) and CDKN2A deletions (del; HR, 3.40; 95% CI, 1.95-5.94; P < 0.001) independently predicted shorter OS, as did high-risk clinical variables (multifocal liver disease [P < 0.001]; regional lymph node metastases [P < 0.001]), whereas KRASmut (HR, 1.69; 95% CI, 0.97-2.93; P = 0.06) trended toward statistical significance. The presence of both or neither high-risk clinical or genetic factors represented outcome extremes (median OS, 18.3 vs. 74.2 months; P < 0.001), with high-risk genetic alterations alone (median OS, 38.6 months; 95% CI, 28.8-73.5) or high-risk clinical variables alone (median OS, 37.0 months; 95% CI, 27.6-not available) associated with intermediate outcome. TP53mut, KRASmut, and CDKN2Adel similarly predicted worse outcome in patients with unresectable iCCA. CDKN2Adel tumors with high-risk clinical features were notable for limited survival and no benefit of resection over chemotherapy.ConclusionsTP53, KRAS, and CDKN2A alterations were independent prognostic factors in iCCA when controlling for clinical and pathologic variables, disease stage, and treatment. Because genetic profiling can be integrated into pretreatment therapeutic decision-making, combining clinical variables with targeted tumor sequencing may identify patient subgroups with poor outcome irrespective of treatment strategy.
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Project description:ObjectivesTo establish a nomogram based on preoperative laboratory study variables using least absolute shrinkage and selection operator (LASSO) regression for differentiating combined hepatocellular cholangiocarcinoma (cHCC) from intrahepatic cholangiocarcinoma (iCCA).MethodsWe performed a retrospective analysis of iCCA and cHCC patients who underwent liver resection. Blood signatures were established using LASSO regression, and then, the clinical risk factors based on the multivariate logistic regression and blood signatures were combined to establish a nomogram for a differential preoperative diagnosis between iCCA and cHCC. The differential accuracy ability of the nomogram was determined by Harrell's index (C-index) and decision curve analysis, and the results were validated using a validation set. Furthermore, patients were categorized into two groups according to the optimal cut-off values of the nomogram-based scores, and their survival differences were assessed using Kaplan-Meier curves.ResultsA total of 587 patients who underwent curative liver resection for iCCA or cHCC between January 2008 and December 2017 at West China Hospital were enrolled in this study. The cHCC score was based on the personalized levels of the seven laboratory study variables. On multivariate logistic analysis, the independent factors for distinguishing cHCC were age, sex, biliary duct stones, and portal hypertension, all of which were incorporated into the nomogram combined with the cHCC-score. The nomogram had a good discriminating capability, with a C-index of 0.796 (95% CI, 0.752-0.840). The calibration plot for distinguishing cHCC from iCCA showed optimal agreement between the nomogram prediction and actual observation in the training and validation sets. The decision curves indicated significant clinical usefulness.ConclusionThe nomogram showed good accuracy for the differential diagnosis between iCCA and cHCC preoperatively, and therapeutic decisions would improve if it was applied in clinical practice.
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Project description:Introduction: The emerging field of "radiomics" has considerable potential in disease diagnosis, pathologic grading, prognosis evaluation, and prediction of treatment response. We aimed to develop a novel radiomics nomogram based on radiomics features and clinical characteristics that could preoperatively predict early recurrence (ER) of intrahepatic cholangiocarcinoma (ICC) after partial hepatectomy. Methods: A predictive model was developed from a training cohort comprising 139 ICC patients diagnosed between January 2010 and June 2014. Radiomics features were extracted from arterial-phase image of contrast-enhanced magnetic resonance imaging. Feature selection and construction of a "radiomics signature" were through Spearman's rank correlation and least absolute shrinkage and selection operator (LASSO) logistic regression. Combined with clinical characteristics, a radiomics nomogram was developed with multivariable logistic regression. Performance of the nomogram was evaluated with regard to discrimination, calibration, and clinical utility. An independent validation cohort involving 70 patients recruited from July 2014 to March 2016 was used to evaluate the utility of the nomogram developed. Results: The radiomics signature, consisting of nine features, differed significantly between ER patients and non-ER patients in training and validation cohorts. The area under the curve (AUC) of the radiomics signature in training and validation cohorts was 0.82 (confidence interval [CI], 0.74-0.88) and 0.77 (95% CI, 0.65-0.86), respectively. The AUC of the radiomics nomogram combining the radiomics signature and clinical stage in the two cohorts was 0.90 (95%CI, 0.83-0.94) and 0.86 (95% CI, 0.76-0.93), respectively. Decision curve analysis confirmed the clinical usefulness of the radiomics nomogram. Conclusion: The non-invasive radiomics nomogram developed using the radiomics signature and clinical stage could be used to predict ER of ICC after partial hepatectomy.
| S-EPMC6131601 | biostudies-literature
Project description:Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary epithelial tumor with poor prognosis. There are increasing evidences that long non-coding RNAs (lncRNAs) are dysregulated in multifarious tumors, revealing potential significant role of lncRNAs in tumorigenesis.We used the ICC dataset retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus database to obtain the lncRNAs expression profiles and identify potential prognostic lncRNAs for predicting the prognosis in ICC. Univariate and multivariate Cox regression analyses were performed to construct a prognostic index (PI). Furthermore, coexpression analysis and functional assessment were performed to initially investigate the function of these prognostic lncRNAs.A total of 255 differentially expressed lncRNAs (DElncRNAs) were identified among two RNA sequencing dataset of a total 63 ICC patients with 98 samples using R platform. Thirteen of 255 DElncRNAs were identified as prognostic lncRNAs and used for a PI. Patients with high PI were associated with poor prognostic (P = .0064), and the Cox regression showed consistent result (P = .042). The time-dependent receiver operating characteristic analysis showed the PI performed well in ICC survival prediction with an area under curve of 0.921, 0.801, and 0.717 for 1-, 3-, and 5-year survival, respectively.In conclusion, we included 13 identified prognostic DElncRNAs and constructed a prognostic signature/PI. ICC patient with higher PI was associated with poorer prognosis. However, the clinical role as well as biological functions of constructed PI and these prognostic DElncRNAs need to be verified in future study.
| S-EPMC7220432 | biostudies-literature
Project description:BackgroundThe relationship between tumor size and survival in intrahepatic cholangiocarcinoma (ICC) is still controversial. This study aimed to evaluate the prognostic ability of tumor size for solitary ICC after resection and explore optimal cut-off values in different subgroups.MethodsPatients with solitary ICC who underwent liver resection from the Surveillance, Epidemiology, and End Results Program and Shandong Provincial Hospital were retrospectively analyzed. Kaplan-Meier and Cox regression analysis were used to assess the prognostic ability of tumor size. The log-rank test was used to determine the optimal cut-off values, and a minimum P was regarded as the optimal one in different subgroups.ResultsLarge tumor size groups had worse overall survival (OS) than small tumor size groups. Cox regression analysis suggested that tumor size was an independent prognostic factor for OS for solitary ICC after resection. Subgroup analysis showed tumor size was associated with OS for both solitary ICC with and without vascular invasion (VI). Furthermore, the optimal cut-off values for solitary ICC with and without VI were found to be 8 and 3 cm, respectively, which could divide the patients into two groups with significant differences in OS.ConclusionTumor size was an independent prognostic factor for solitary ICC after resection. The existing American Joint Committee on Cancer (AJCC) staging system could be improved if the cut-off value of the T1 stage was changed to 8 cm and if the T2 stage incorporated a tumor size with a cut-off value of 3 cm. Further studies with more cases are needed to validate these findings.
| S-EPMC7859518 | biostudies-literature
Project description:BackgroundCalpain small subunit 1 (Capn4) has been shown to correlate with the metastasis/invasion of hepatocellular carcinoma. This study aimed to investigate the role of Capn4 in intrahepatic cholangiocarcinoma (ICC).MethodsCapn4 expression was measured in 33 ICC tissues by quantitative real-time polymerase chain reaction and western blot. The role of Capn4 in the migration, invasion and proliferation of ICC cells and matrix metalloproteinase 2 (MMP2) expression were assessed after Capn4 depletion by specific small interfering RNA. Capn4 expression was further examined by immunohistochemistry in a tissue microarray consisting of 140 ICC patients and 13 normal liver tissues, and the prognostic role of Capn4 in ICC was evaluated by Kaplan-Meier and Cox regression analyses.ResultsCapn4 expression was significantly higher in the ICC tissues compared to the peritumor tissues. Capn4 down-regulation impaired the migration/invasion ability of HCCC-9810 and QBC939 cells in vitro and decreased MMP2 expression. Capn4 overexpression significantly correlated with the presence of lymphatic metastasis of ICC (p = 0.026) and the tumor-node-metastasis (TNM) stage (p = 0.009). The postoperative 2- and 5-year overall survivals in patients with Capn4(low) were higher than those in the Capn4(high) group. The cumulative recurrence rate in patients with Capn4(low) was much lower than in the Capn4(high) group. Multivariate analysis showed that Capn4 overexpression was an independent prognostic marker in ICC.ConclusionsCapn4 overexpression was implicated in ICC metastasis/invasion, and Capn4 overexpression may be used as a molecular therapeutic target for ICC.
| S-EPMC3551843 | biostudies-literature