Cancer Of The Liver Italian Program Score Research Articles

Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

Comparing Staging Systems for Predicting Prognosis and Survival in Patients with Hepatocellular Carcinoma in Egypt

IntroductionSeveral hepatocellular carcinoma (HCC) staging systems are available. Although the European Association for Study of Liver Diseases (EASL) and American Association for the Study of Liver Diseases (AASLD) recommended the use of Barcelona Clinic Liver Cancer (BCLC), many studies in different populations revealed heterogeneous results. The aim of this study was to compare different staging systems for predicting prognosis and survival, and for stratifying HCC patients for treatment at a national referral centre for liver disease in Egypt.Methods2000 Patients were included in this study. Baseline demographic, clinical, laboratory, and radiological data were determined at diagnosis. Patients were stratified using the Okuda, BCLC, Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS). Patients’ survival in different stages within each staging system and the validity of the system in predicting survival were compared.ResultsThe overall survival was 15 months. The 1-, 2-, 3- and 4-year survival of the entire cohort was 56%, 34%, 25% and 15% respectively. The presence of ascites, multiple focal lesions, large tumour size >5 cm, portal vein thrombosis, extra-hepatic spread, AFP≥200 ng/ml and poor Child score were independent predictors of survival (p<0.001). All staging systems were significant in determining overall survival in univariate and multivariate analyses. BCLC was the most predictive staging system for the whole cohort (p<0.001). Among the subgroup of patients offered potentially curative therapy, BCLC was the most informative system in predicting patient survival (p<0.001). For patients with advanced HCC not amenable for specific therapy, CLIP was the best staging system for predicting prognosis (p<0.001).ConclusionBCLC staging system provided the best prognostic stratification for HCC patients. However, CLIP score has the highest stratification ability in patients with advanced HCC highlighting the importance of including AFP in best staging system.

Diagnostic and prognostic significance of cell death and macrophage activation markers in patients with hepatocellular carcinoma

The serum cell death parameters M30 and M65 and the macrophage activation marker sCD163 (soluble CD163) are elevated in patients with acute and chronic liver diseases. However, their diagnostic and prognostic potential in patients with hepatocellular carcinoma (HCC) has not yet been investigated. Serum levels of M30, M65, and sCD163 were measured in two cohorts of HCC patients and a cohort of cirrhotic patients. The parameters were compared between patients with and without HCC and the overall survival (OS) times according to M30, M65, and sCD163 were assessed. M30 and M65 levels were higher in HCC patients than in cirrhotic patients (both p < 0.001). M65 was an independent parameter for non-invasive identification of HCC patients by logistic regression analysis and could supplement AFP (alpha-fetoprotein) and abdominal ultrasound in non-invasive detection of HCC patients. High M65 serum levels as well as high sCD163 concentrations were associated with an impaired prognosis in univariate Cox regression analysis. The sCD163 level was associated with OS independently of the CLIP (Cancer of the Liver Italian Program) score, the BCLC (Barcelona Clinic Liver Cancer) stage, and the CRP (C-reactive protein) level in a multivariate Cox regression model. Serum M65 has the potential as a new diagnostic parameter for HCC and serum sCD163 is a new prognostic parameter in HCC patients.

High Serum Levels of the Interleukin-33 Receptor Soluble ST2 as a Negative Prognostic Factor in Hepatocellular Carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor, usually arises in the setting of liver cirrhosis (LC), and has a poor prognosis. The recently discovered Th2-cytokine interleukin-33 (IL-33) is a possible mediator in pancreatic and gastric carcinogeneses. IL-33 binds to its receptor and to soluble ST2 (sST2), which thereby acts as a regulator. The role of IL-33 and sST2 in HCC has not been elucidated yet. METHODS: We conducted a case-control study with 130 patients and 50 healthy controls (HCs). Sixty-five patients suffered from HCC and 65 patients had LC without HCC. We assessed serum IL-33 and sST2 levels and their association with established prognostic scores, liver function parameters, and overall survival (OS). RESULTS: No significant difference in IL-33 serum levels was found in HCC compared to LC and HCs. IL-33 levels did not correlate with OS, liver function parameters, the Model for End-Stage Liver Disease (MELD) score, or the Cancer of the Liver Italian Program (CLIP) score. sST2 levels were significantly elevated in LC and HCC patients compared to HCs (P < .0001). Mean sST2 levels in LC were higher than in HCC (P < .0001), but a significant association with OS was only observed in the HCC group (P = .003). sST2 in HCC correlated with the CLIP score, the MELD score, and liver function parameters. CONCLUSION: In the present study, the serum concentration of sST2 was associated with OS of HCC. Therefore, sST2 may be considered as a new prognostic marker in HCC and is worth further evaluation.

Clinical Characteristics of Hepatocellular Carcinoma in Elderly Patients

The average age of patients with hepatocellular carcinoma (HCC) has been increasing worldwide. This study aimed to clarify the aged-specific clinical characteristics of HCC among elderly patients. We retrospectively analyzed 1123 patients with HCC treated between 2003 and 2006 at the Mackay Memorial Hospital in Taiwan. Patients aged more than 75 years of age at the time of diagnosis of HCC were defined as the elderly group. According to the Kaplan–Meier method, survival curves were compared between patients receiving treatment and those receiving supportive care. A total of 169 patients (16.9%) were included in the elderly group. The mean age of the patients at the time of diagnosis was 80 ± 3.6 years. The sex ratio (male to female) was 1:0.72. The proportion of patients positive for hepatitis C virus antibody (HCVAb) and hepatitis B surface antigen (HBsAg) were 49.1% and 19.5%, respectively. The percentages of patients in the Cancer of the Liver Italian Program (CLIP) score categories 0–1, 2–3, and 4–6 were 44%, 39%, and 17 %, respectively. Of the 169 patients, 114 patients (67.5%) underwent treatment—transcatheter arterial embolization (TAE, n = 52, 45.7%), being the predominant treatment method—while 55 patients (32.5%) received supportive care. There cumulative survival curves of the treated group and the supportive care group differed significantly for HCC patients in the CLIP score categories 0–1 ( p < 0.001) and 2–3 ( p = 0.021), while there was no difference in these survival curves for HCC patients in the CLIP score category 4–6. Most elderly patients at the time of diagnosis of HCC were in CLIP score category 0–1. Transcatheter arterial embolization was the predominant treatment method at our hospital. Aggressive treatment for HCC, especially in CLIP score category 0–3, might improve the survival rate.

Factors Affecting Survival following Chemoembolization with Doxorubicin-eluting Microspheres for Inoperable Hepatocellular Carcinoma

PurposeTo assess factors associated with better overall survival (OS) and progression-free survival (PFS) following chemoembolization with doxorubicin-eluting microspheres for inoperable hepatocellular carcinoma (HCC) Materials and MethodsData of 130 patients (104 men; median age, 62 y) with inoperable HCC who underwent successful DEB chemoembolization with 100–300 -μm LC Bead particles loaded with 50 mg doxorubicin per vial were reviewed following human research committee approval. Effects of various clinical, imaging, and response factors on OS and PFS were assessed by univariate Kaplan–Meier survival analysis. Multiple Cox regression with backward elimination was performed for terms found significant (P≤.05) on univariate analysis. ResultsThe number of DEB chemoembolization procedures per patient ranged from one to four (mean, 2±1). The median PFS and OS were 5.7 months (95% confidence interval, 4.6–7.6 mo) and 14.7 months (95% confidence interval, 12.3–19.7 mo), respectively. On multivariate Cox regression, Cancer of the Liver Italian Program (CLIP) score of 1 or lower, necrosis of more than 50%, and response or stable disease per Response Evaluation Criteria In Solid Tumors after DEB chemoembolization were associated with better PFS. CLIP score of 1 or lower, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or lower, absence of portal vein (PV) thrombosis, and necrosis greater than 50% following DEB chemoembolization were associated with better OS. ConclusionsCLIP score of 1 or lower and necrosis of more than 50% are independent variables affecting PFS and OS after DEB chemoembolization, whereas absence of PV thrombosis and ECOG PS of 1 or lower affected OS but not PFS.

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Prognosis of advanced hepatocellular carcinoma patients enrolled in clinical trials can be classified by current staging systems

Background:Patients enrolled in clinical trials of advanced hepatocellular carcinoma (HCC) are usually required to have good liver reserve and organ function. However, their outcomes are still highly variable. We aimed to examine whether current staging systems can predict the survival of these highly selected patients.Methods:Patients from clinical trials involving first-line anti-angiogenic therapy were assigned to different stage groups using the American Joint Committee on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC), China integrated score, Cancer of the Liver Italian Program (CLIP) score, Chinese University Prognostic Index (CUPI), Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire (GETCH), Japan Integrated Staging (JIS) score, Okuda, Tokyo score, and a new staging system recently proposed. Survival prediction by the 10 systems was then compared by both univariate and multivariate analyses.Results:A total of 157 patients were selected for this study. In univariate analysis, all staging systems can predict patient survival except AJCC, BCLC, and JIS score. Concordance indexes for CLIP score, CUPI, and GETCH (0.752, 0.775, and 0.791, respectively) were significantly higher than those obtained for other staging systems. In multivariate analysis, the CLIP score and CUPI (P<0.001 and 0.009, respectively) predicted survival more accurately than did the other tested staging systems. Hepatitis B infection and poor performance status were also associated with poor survival.Conclusion:Several HCC staging systems, especially the CLIP score and CUPI, can predict prognosis of patients who are enrolled in clinical trials of advanced HCC.

A novel and validated prognostic index in hepatocellular carcinoma: The inflammation based index (IBI)

Outcome prediction is uniquely different in hepatocellular carcinoma (HCC) as the progressive functional impairment of the liver impacts patient survival independently of tumour stage. As chronic inflammation is associated with the pathogenesis of HCC, we explored the prognostic impact of a panel of inflammatory based scores, including the modified Glasgow Prognostic Score (mGPS), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), in independent cohorts. Inflammatory markers, Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) scores were studied in a training set of 112 patients with predominantly unresectable HCC (75%). Independent predictors of survival identified in multivariate analysis were validated in an independent cohort of 466 patients with an overall lower tumour burden (BCLC-A, 56%). In both training and validation sets, mGPS and CLIP scores emerged as independent predictors of overall survival. The predictive accuracy of the combined mGPS and CLIP score (c score 0.7, 95% CI 0.6-0.8) appeared superior to that of the CLIP score alone (c score 0.6, 95% CI 0.5-0.7). Systemic inflammation as measured by the mGPS, independently predicts overall survival in HCC. We have validated a novel, easy to use inflammatory score that can be used to stratify individuals. These data enable formulation of a new prognostic system, the inflammation based index in HCC (IBI). Further validation of the IBI considering treatment allocation and survival is warranted in an independent patient cohort.

Abstract No. 199: Hepatocellular carcinoma (HCC) treatment with radiolabelled lipiodol embolization versus ytrrium-90 radioembolization: comparative survival analysis

lona Clinic Liver Cancer (BCLC), Okuda classification, Cancer of the Liver Italian Program (CLIP), Groupe d‘Etude et de Traitement du Carcinome Hepatocellulaire (GRETCH), Chinese University Prognostic Index (CUPI) and the Japan Integrated System score (JIS). Staging systems were compared using cox-regression model, linear trend test and Akaike information criterion. Uni/ Multivariate analyses were employed to assess independent predictors of survival. Results: When tested independently, all staging systems provided significant ability to progressively discriminate patients with early disease and better survival from patients with advanced disease and worse survival. When staging systems were compared, they were found to be most accurate in predicting survival outcome in following order: CLIP, JIS, UNOS, GRETCH, BCLC, CUPI, Okuda and CTP. Independent predictors of survival outcomes on multivariate analyses were ECOG 0 (HR: 0.56, CI: 0.34 0.93); non-infiltrative tumors (HR: 0.62, CI: 0.44 0.89); absence of portal venous thrombosis (HR: 0.60, CI: 0.40 0.89); absence of ascites (HR: 0.56, CI: 0.40 0.76); albumin 2.8 g/dL (HR: 0.72, CI: 0.55 0.94); alkaline phosphatase 200 U/L (HR: 0.68, CI: 0.50 0.92); and AFP 200 ng/dL (HR:0.67, CI: 0.51 0.86). Conclusion: CLIP score is the most accurate in predicting survival outcomes after Y-90 therapy for HCC. Multivariate analyses demonstrated that tumor characteristics, liver function and performance status of the patient are independent predictors of survival outcomes.

Staging of advanced hepatocellular carcinoma patients in the targeted therapy era.

209 Background: Several hepatocellular carcinoma (HCC) staging systems are currently available. However, they were all developed before the targeted therapy era prevailed in the last decade which has changed the natural history of the disease. Our study goal was to test the performance of different HCC staging systems in patients with HCC who were treated at our institution during the last decade. Methods: We prospectively enrolled 438 patients from early 2000 to late 2009. Baseline clinicopathologic parameters and staging were available, including the TNM, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), Okuda, and Chinese University Prognostic Index (CUPI). We performed survival and cox-regression analyses, and compared the staging systems’ predictive ability using Harrell's C-index. Finally, we performed a subgroup analysis of 3 independent cohorts based on whether or not they received sorafenib, whether or not they had hepatitis, and whether or not they had cirrhosis. Results: The overall survival was 13.9 months. Overall, CLIP score was the most predictive staging system with a C-index of 0.71. 187 patients were treated with targeted therapies and 138 were treated with sorafenib after it was approved in 2007. CLIP score was the most predictive staging system with a C-index of 0.71 in the no sorafenib group, and 0.74 in the sorafenib group. In hepatitis patients, CLIP topped amongst all staging systems with a C-index of 0.75, and in patients without hepatitis, despite all staging systems having a poor predictive ability, CLIP score still had the highest C-index of 0.67. Similarly, CLIP score had the best predictive ability in patients with and without pre-existing liver cirrhosis, with C-indices of 0.73 and 0.68 respectively. There was no statistically significant interaction between CLIP score and hepatitis status, and CLIP score and liver cirrhosis. Thus, overall the CLIP score was the best predictive system in all cohorts. Conclusions: Our results suggest that the CLIP score has the highest stratification ability in our advanced HCC patient population, including several subgroups. Our study confirms the utility of the CLIP score to stratify advanced HCC patients in clinical trials.

I-CLIP: Improved Stratification of Advanced Hepatocellular Carcinoma Patients by Integrating Plasma IGF-1 into CLIP Score

Objective: Improving the prognostic stratification of unresectable hepatocellular carcinoma (HCC) patients is critically needed. Since patients’ survival is closely linked to the severity of the underlying liver disease, and insulin-like growth factor-1 (IGF-1) is produced predominantly in the liver, we hypothesized that IGF-1 may correlate with patients’ survival and hence improve the prognostic ability of the Cancer of the Liver Italian Program (CLIP) score. Methods: Baseline plasma IGF-1 and clinicopathologic parameters were available from 288 patients. Multivariate Cox regression models, Kaplan-Meier curves, and the log-rank test were applied. Recursive partitioning was used to determine the optimal cut point for IGF-1 using training/validation samples. Prognostic ability of the I-CLIP (I = IGF) was compared to CLIP using C-index. Results: IGF-1 significantly correlated with the clinicopathologic features. With an optimal IGF-1 cut point of 26 ng/ml, the overall survival of patients with IGF-1 >26 was 17.7 months (95% CI 13.6–22.8), and with IGF-1 ≤26 was 5.8 months (95% CI 4.0–12.5), p < 0.0001. The concordance probabilities for CLIP and I-CLIP were 0.7037 and 0.7096, respectively (p < 0.0001). Conclusions: Our preliminary results indicate that I-CLIP significantly improved prognostic stratification of patients with advanced HCC. However, independent validation of our study is warranted.

Impact of an inflammation-based prognostic system on patients undergoing surgery for hepatocellular carcinoma: a retrospective study of 398 Japanese patients

Background Few studies have investigated the Glasgow Prognostic Score (GPS) in patients with hepatocellular carcinoma (HCC). Methods This study compared the prognostic value of the GPS and Cancer of the Liver Italian Program (CLIP) score in patients undergoing surgery for HCC. Results A total of 398 patients were evaluated retrospectively. Kaplan–Meier analyses revealed that GPS ( P < .001) and CLIP score ( P < .001) were associated with overall survival. GPS could classify patients with low CLIP score (0 or 1) into 3 independent groups ( P < .001). Univariate analyses selected GPS ( P = .006) and CLIP score ( P = .002) as the predictive factors associated with overall survival. Multivariate analysis using these 2 scoring systems disclosed that both GPS ( P = .025) and CLIP score ( P = .010) were associated with overall survival. Conclusions GPS is not only an important predictor of overall survival after surgical treatment of HCC as well as CLIP score, but also is able to clearly divide patients with low CLIP score into 3 independent groups.

Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib: A comparison with previously known prognostic models.

323 Background: Sorafenib, a multiple-targeted tyrosine kinase inhibitor, is now the treatment of choice for systemic therapy of patients with advanced hepatocellular carcinoma (HCC). Herein we present the clinical characteristics and outcomes of patients with advanced HCC who were treated with sorafenib. Methods: Data of 201 sorafenib-treated, metastatic HCC patients were collected from a single institution tumor registry. The primary and secondary endpoints were overall survival (OS) and failure-free survival (FFS). Results: Chronic hepatitis B was the predominant cause of HCC (84%).Of 162 evaluable patients, four partial responses were recorded. With a median follow-up of 15.7 months, the median FFS and OS were 2.5 months (95% confidence interval [CI], 2.3-2.7 months) and 5.3 months (95% CI, 4.4-6.3 months), respectively. In multivariate analysis, the prognostic factors associated with FFS were the presence of ascites, portal venous thrombosis, serum alpha- fetoprotein (AFP) ≥400 ng/mL, albumin, bilirubin, tumor size and number, and performance status. Likewise, the presence of ascites, portal venous thrombosis, tumor size and number, performance status, and baseline levels of AFP, albumin and bilirubin were significantly related with OS. After adjusting for performance status, the Cancer of the Liver Italian Program (CLIP) scoring system and Okuda stages can better predict the hazard of failure or death than Child-Pugh classification. Conclusions: Our results suggest that CLIP scores or Okuda stages, along with performance status, can be useful in stratifying patients with advanced HCC treated with sorafenib. No significant financial relationships to disclose.

Usefulness of a modified inflammation‐based prognostic system for predicting postoperative mortality of patients undergoing surgery for primary hepatocellular carcinoma

To assess and compare the predictive values of the hepatic Glasgow Prognostic Score (hGPS) and Cancer of the Liver Italian Program (CLIP) score in patients undergoing surgery for primary hepatocellular carcinoma (HCC). The hGPS was calculated as follows: patients with an elevated level of C-reactive protein (CRP) (>0.3 mg/dl) were allocated a hGPS of 1 or 2 depending on the absence or presence of hypoalbuminemia (<3.5 g/dl), and patients without an elevation of the CRP level (≤ 0.3 mg/dl) were allocated a hGPS of 0. Three hundred patients were evaluated. The hGPS divided patients into three independent groups, and that a hGPS of 2 predicted a higher mortality rate (P < 0.001) than a hGPS of 0 or 1. Univariate analysis demonstrated that hGPS (0, 1/2) (P = 0.010) was one of the factors predictive of postoperative mortality, along with the CLIP score (0, 1/≥ 2) (P = 0.021). Comparative analysis using these two factors showed that the hGPS was predictively superior to the CLIP score (P = 0.033). The hGPS is able to divide patients undergoing surgery for primary HCC into three independent groups, and is considered to be an important factor predictive of postoperative mortality in such patients.

V‐CLIP: Integrating plasma vascular endothelial growth factor into a new scoring system to stratify patients with advanced hepatocellular carcinoma for clinical trials

Several staging systems have been proposed for hepatocellular carcinoma (HCC); however, none has incorporated circulating angiogenic biomarkers. The purpose of this study was to determine whether vascular endothelial growth factor (VEGF) could independently predict overall survival in patients with HCC, and whether adding VEGF level into the Cancer of the Liver Italian Program (CLIP) score could improve patient stratification and prediction of overall survival. Between 2001 and 2008, baseline plasma VEGF levels were available from 288 patients, and multivariate Cox regression models and median survival (95% confidence intervals) were calculated. Recursive partitioning was used to determine the optimal cutpoint for VEGF, using 10 repeated training/validation samples, each using two-thirds of the data to determine the best cutpoint and the remaining one-third to validate it. Prognostic ability of CLIP and V-CLIP was compared using the concordence index. Plasma VEGF was a significant independent predictor of overall survival, with an optimal VEGF cutpoint of 450 pg/mL. After CLIP validation in our patients, we added VEGF to the CLIP score and found that the new V-CLIP score better separates patients into homogenous prognostic groups (P = .005). The assessment of baseline plasma VEGF levels increases the precision of the CLIP scoring system for predicting HCC prognosis, which may assist in equally randomizing patients with HCC in clinical trials. Prospective validation of the V-CLIP scoring system is warranted.

Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma and Renal Insufficiency

Renal dysfunction is often present in patients with cirrhosis and hepatocellular carcinoma (HCC). Acute renal failure (ARF) may occur after transarterial chemoembolization (TACE) owing to radiocontrast agent. This study investigated the incidence and risk factors of ARF and prognostic predictors in HCC patients with preexisting renal insufficiency undergoing TACE. A total of 566 HCC patients undergoing TACE were enrolled. Renal insufficiency was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m. In a mean follow-up duration of 18+/-16 months, 231 (40.8%) patients undergoing TACE died. Renal insufficiency that was present in 134 (23.7%) patients at baseline, independently predicted a poor prognosis in the Cox proportional hazards model [risk ratio (RR): 1.47, P=0.012]. Of them, 13 (10%) and 6 (5%) patients had transient and prolonged ARF after TACE, respectively. Post-TACE gastrointestinal bleeding [odds ratio (OR): 16.54, P=0.001] and higher Cancer of the Liver Italian Program (CLIP) scores (> or =2; OR: 4.22, P=0.02) were independent risk factors for ARF in the multivariate logistic regression analysis. In the Cox model, prolonged ARF (RR: 3.28, P<0.001) and higher CLIP scores (> or =2; RR: 2.13, P<0.001) were independent poor prognostic predictors for HCC patients with renal insufficiency receiving TACE. Gastrointestinal bleeding and higher CLIP scores are associated with the development of ARF in patients with HCC and renal insufficiency undergoing TACE. Higher CLIP scores and renal insufficiency, either preexisting before TACE or as a complication of TACE, are poor prognostic predictors in HCC patients receiving TACE.

A new classification for hepatocellular carcinoma with portal vein tumor thrombus

We aimed to correlate the survival of patients with hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT) who underwent partial hepatectomy with or without portal thrombectomy with our PVTT classification. Currently, different staging systems for HCC are widely used in clinical practice. However, they lack the refinement in giving prognosis and guiding surgical treatment once macroscopic PVTT is present. A retrospective study was carried out, in a single tertiary center, from January 2001 to December 2004 on 441 patients who underwent partial hepatectomy with or without portal thrombectomy for HCC with macroscopic PVTT. Overall survival was examined to determine whether it was correlated with our PVTT classification, and with the TNM staging, Cancer of the Liver Italian Program (CLIP) scoring system, and the Japan Integrated Staging (JIS) scoring system. With our PVTT classification, the numbers (percentages) of patients with types I, II, III, and IV PVTT were 144 (32.7%), 189 (42.9%), 86 (19.5%), and 22 (5.0%), respectively. The corresponding 1-, 2-, and 3-year overall survival rates for types I to IV PVTT were 54.8, 33.9, and 26.7%; 36.4, 24.9, and 16.9%; 25.9, 12.9, and 3.7%; and 11.1, 0, and 0%, respectively (log-rank of the survival curves P < 0.0001). Using the TNM system, the majority of patients were classified as stage III (n = 379 or 85.9%). Similarly, the majority of patients (n = 388 or 88.0%) were classified as having CLIP scores of 2 (n = 143, or 32.4%), 3 (n = 171, or 38.8%), and 4 (n = 74, or 16.8%). The 1-, 2-, and 3-year overall survivals for these 3 CLIP scores were very similar. Using the JIS score, the majority of patients (n = 372 or 84.4%) were classified with a JIS score of 2. The 1-, 2-, and 3-year overall survivals of patients with a JIS score of 2 were worse than those of the patients with a JIS score of 1 (this was expected) as well as being worse than those with a JIS score of 3 (this was unexpected). Thus, the latter 3 systems of classification were not refined enough, and they were inadequate for stratifying HCC with macroscopic PVTT treated with partial hepatectomy with or without thrombectomy. In patients with HCC with macroscopic PVTT treated by partial hepatectomy with or without thrombectomy, our PVTT classification better stratified and predicted prognosis than the TNM staging, CLIP scoring system, and JIS scoring system, which were unrefined and inadequate for this group of patients.

Use of Yttrium-90 Microspheres in Patients with Advanced Hepatocellular Carcinoma and Portal Vein Thrombosis

Patients with portal vein thrombosis (PVT) and hepatocellular carcinoma (HCC) have limited treatment options because of increased disease burden and diminished hepatic perfusion. Yttrium-90 ((90)Y) microspheres may be better tolerated than chemoembolization in these patients. The present study reviews the safety and efficacy of (90)Y microspheres in HCC with major PVT. A retrospective review of HCC with main (n = 10) or first-branch (n = 12) PVT treated with (90)Y microspheres (N = 22) was conducted. Cancer of the Liver Italian Program (CLIP) scores ranged from 2 to 5, with 18% of patients having a score of 4 or greater. Imaging response at 8-12 was based on Response Evaluation Criteria In Solid Tumors. Overall survival (OS) was estimated by the Kaplan-Meier method. A total of 32 microsphere treatments (26 glass, six resin) were administered to 22 patients. Common grade 1/2 toxicities included abdominal pain (38%), nausea (28%), and fatigue (22%). Four posttreatment hospitalizations occurred, all less than 48 hours in duration. One death occurred 10 days after therapy. The partial response rate was 8% and progressive disease was seen in 42% of patients. Stable disease was achieved in 50% of treatments. Median OS was 7 months from initial treatment. Patients with Child-Pugh class A disease had a median OS of 7.7 months; those with class B/C disease had an OS of 2.7 months (P = .01). Median OS for patients with CLIP scores of 2/3 was 7 months, versus 1.3 months for those with scores of 4/5 (P = .04). Yttrium-90 microspheres are tolerated in patients with HCC and major PVT. Compared with chemoembolization, rates of severe adverse events appear low. Radiographic response rates are low. The median OS of 7 months is promising and warrants further study versus systemic therapy.

Locoregional therapies for hepatocellular carcinoma: Which patients are most likely to gain a survival advantage?

Locoregional therapies for hepatocellular carcinoma (HCC) are considered to confer a survival advantage, however, the patient group that should be targeted is not clearly defined. This study aimed to determine the impact on survival of locoregional therapies compared with supportive care, within prognostic categories as stratified by the Cancer of the Liver Italian Program (CLIP) scoring system. A prospective database was used to identify those patients who were treated with either locoregional therapy (n = 128) or supportive care (n = 92). Survival analysis was performed for groups matched by CLIP score at presentation. Comparison of important prognostic factors was undertaken and univariate and multivariate analysis was performed to assess determinants of survival. Use of locoregional therapies was only associated with a survival benefit in patients with a CLIP score of 1 or 2. In this group, the median survival in patients who received locoregional therapies was 25.0 months (95% confidence interval 22.7-27.4) compared with 8.9 months (95% confidence interval 7.3-10.5) for supportive care (P = 0.001). For patients with CLIP scores of 3 or greater, no survival benefit of locoregional therapies was observed. Multivariate analysis revealed locoregional intervention, CLIP score, tumor symptoms, alpha-fetoprotein level, bilirubin and alkaline phosphatase level as independent prognostic indicators. Locoregional therapies should be targeted specifically to patients with non-advanced hepatocellular carcinoma as assessed by validated scoring systems. Use of these therapies in patients with advanced disease does not appear to be associated with a survival benefit and may expose patients to unnecessary harm.