Angiogenesis has been a major target of novel drug development in hepatocellular carcinoma (HCC). It is hypothesized that the combination of two antiangiogenic agents, sorafenib and bevacizumab, will provide greater blockade of angiogenesis.
Objective
To determine the optimal dose, safety, and effectiveness of dual anti-angiogenic therapy with sorafenib and bevacizumab in patients with advanced HCC.
Patients and Methods
Patients with locally advanced or metastatic HCC not amenable for surgery or liver transplant were eligible. The phase I starting dose level was bevacizumab 1.25 mg/kg day 1 and 15 plus sorafenib 400 mg twice daily (BID) days 1-28. In the phase II portion, patients were randomized to receive bevacizumab and sorafenib at the maximum tolerated dose (MTD) or sorafenib 400 mg BID.
Results
Seventen patients were enrolled in the phase I component. Dose-limiting toxicities included grade 3 hand/foot skin reaction, fatigue, hypertension, alanine/aspartate aminotransferase increase, dehydration, hypophosphatemia, creatinine increase, hypoglycemia, nausea/vomiting, and grade 4 hyponatremia. Seven patients were enrolled in the phase II component at the MTD: sorafenib 200 mg BID days 1-28 and bevacizumab 2.5 mg/kg every other week; 57% (4/7) had grade 3 AEs at least possibly related to treatment. No responses were observed in the phase II portion. Estimated median time to progression and survival were 8.6 months (95% CI: 0.4-16.3) and 13.3 months (95% CI 4.4 – not estimable), respectively.
Conclusions
The MTD of the combination is sorafenib 200 mg twice daily on days 1-28 plus bevacizumab 2.5 mg/kg on days 1 and 15 of a 28-day cycle. In the phase II portion of the trial, concerns regarding excessive toxicity, low efficacy, and slow enrollment led to discontinuation of the trial. (Clinical Trials ID: NCT00867321.)
Hepatocellular carcinoma (HCC) represents one of the most common causes of cancer-related deaths worldwide, with rising incidence in the USA. Bone metastases with HCC, in particular, have an extremely poor prognosis. We present prevalence, treatment, and survival of patients with bone and more specifically spinal metastases from HCC.
Methods
A retrospective analysis was done at a single tertiary care institution of patients with bone metastases from HCC between January 2005 and December 2015.
Results
Among 1017 patients with HCC, 20 were found to have bone metastases of which 11 had spinal metastases. Seventeen (85%) were male, with median age of 58 years at time of HCC diagnosis. Systemic chemotherapy and sorafenib were used in 12 (60%) patients, and 12 (60%) received radiation therapy. Among patients who did not receive therapy, median survival was 76 days. Median survival after diagnosis of metastasis in patients on sorafenib and radiation were 106 and 100 days, respectively.
Conclusion
Bone metastases in HCC are very rare and aggressive. Due to its rarity, optimal treatment strategies are not well defined. Early diagnosis is important for optimal therapy and improved survival.
Identification of patients with advanced HCC-deriving preferential benefit from sorafenib is desirable, and treatment-related adverse events are potential clinical biomarkers.
Methods
Survival and toxicity data for patients with HCC treated with sorafenib at the Christie NHS Foundation Trust from 11/09 to 02/15 were collected retrospectively.
Results
Eighty-five eligible patients were identified. The most common grade 3 or 4 treatment-related toxicities were hypertension (HTN, 45 %), fatigue (8 %), and hand-foot syndrome (HFS, 8 %). Any-grade HFS and/or worsening HTN (HFS/HTN) were experienced by 58 % of patients. Estimated median progression-free and overall survival (OS) were 4.6 (95 % CI 2.8–5.2) and 6.5 (95 % CI 4.9–8.01) months, respectively. Child–Pugh score (p value <0.001) and the development of HFS/HTN were independent prognostic factors impacting on OS on multivariable analysis. Patients who developed HFS/HTN had median OS of 8.2 months (95 % CI 6.5–12.4) compared with 4.1 (95 % CI 2.7–5.4) for those without this toxicity (Hazard Ratio (HR) 0.4, 95 % CI 0.2–0.7, p value 0.003). The prognostic impact of HFS/HTN was confirmed by landmark analyses limited to patients who lived a minimum of 2 months (p value 0.019) or who developed HFS/HTN in the first 3 months of treatment (p value 0.006).
Conclusion(s)
The development of toxicities specific to sorafenib is associated with prolonged survival in a UK-based HCC patient series; prospective assessment of their significance is required.
Patients with diabetes are at increased risk of developing hepatocellular carcinoma (HCC) and have a poorer prognosis as compared to non-diabetics when HCC occurs. Diabetics with non-HCC cancers are at higher risk of toxicity related to systemic therapy, but data on HCC are lacking.
Objective
The aim of this study was to evaluate safety and effectiveness of sorafenib in HCC patients according to the presence/absence of diabetes.
Patients and Methods
From October 2008 to June 2014, 313 patients with HCC treated with sorafenib were enrolled. The patients were staged according to the BCLC system. Treatment response was evaluated according to the mRECIST criteria. The main evaluated outcomes were the overall survival and the safety in the two groups.
Results
Patients were divided in two groups: 80 diabetics (DIAB) and 233 nondiabetics (nDIAB). The median treatment duration was 4 months in DIAB and 3 months in nDIAB. Main adverse events occurred with comparable frequency in both groups, with the exception of rash, that was more frequent among DIAB than in nDIAB: 27.5 % vs 17.6 % (P?=?.047). The median overall survival was 9 months in nDIAB and 10 months in DIAB group (P?=?.535). Median time-to-progression (TTP) was longer the in DIAB than the nDIAB group (P?=?.038).
Conclusions
Sorafenib was as safe as effective in DIAB and in nDIAB patients. The longer TTP observed among DIAB than in nDIAB patients might suggest a better anticancer effect of sorafenib in patients with diabetes.
Hepatocellular carcinoma (HCC), a primary neoplasm derived from hepatocytes, is the second leading cause of cancer mortality worldwide. Previous work has shown that fibroblast growth factor 19 (FGF19), an oncogenic driver, acts as a negative regulator of the therapeutic efficacy of the tyrosine kinase inhibitor sorafenib in HCC cells. The FGF19-mediated mechanism affecting sorafenib treatment, however, still remains to be resolved. Here, we hypothesize that the FGF19-FGFR4 axis may affect the effectiveness of sorafenib in the treatment of HCC.
Methods
FGF19 and FGFR4 cDNAs were cloned into a pcDNA3.1 vector and subsequently used for exogenous over-expression analyses. FGF19 knockdown cells were generated using a lentiviral-mediated short hairpin RNA (shRNA) methodology and FGFR4 knockout cells were generated using a CRISPR-Cas9 methodology. FGFR4 activation in HCC cells was inhibited by BLU9931. The effects of exogenous gene over-expression, expression knockdown and knockout, as well as drug efficacies in HCC cells, were validated using Western blotting. HCC cell proliferation was assessed using a CellTiter 96® AQueous One Solution Cell Proliferation Assay, whereas NO levels were assessed using DAF-FM DA staining in conjunction with electrochemical biosensors.
Results
We found that FGF19, when exogenously overexpressed, results in a reduced sorafenib-induced NO generation and a decreased proliferation of HCC cells. In contrast, we found that either FGF19 silencing or knockout of its receptor FGFR4 sensitized HCC cells to sorafenib through the induction of NO generation. Concordantly, we found that inactivation of FGFR4 by BLU9931 enhanced the sensitivity of HCC cells to sorafenib.
Conclusion
From our data we conclude that the FGF19-FGFR4 axis may play a critical role in the effects elicited by sorafenib in HCC cells. Blocking the FGF19-FGFR4 axis may provide novel opportunities to improve the efficacy of sorafenib in the treatment of patients with HCC.
Although hepatocellular carcinoma (HCC) is one of the most common malignant tumors, its molecular mechanism is still unknown. Dishevelled 2 (Dvl2) is one of the downstream targets of non-canonical Wnt signaling, which has been demonstrated to be of great importance in the progression of cancers. Nevertheless, the expression mechanisms and physiological significance of Dvl2 in HCC remain unclear.
Methods
Western blotting and immunohistochemistry were used to measure Dvl2 protein expression in HCC and adjacent normal tissues of 101 patients. Wound healing and transwell assays were used to determine cell migration and invasion.
Results
Dvl2 expression was upregulated in HCC tissues compared to the adjacent normal tissues. Moreover, its expression level was significantly correlated with histological grade (P = 0.042), metastasis (P = 0.005) and vein invasion (P = 0.009) in patients with HCC. Wound healing and transwell assays showed that knockdown of Dvl2 reduced cell migration and invasion in HepG2 cells. Finally, we confirmed that Dvl2 could regulate the migration and invasion of HCC cells by interacting with P62 in non-canonical Wnt signaling.
Conclusions
Our data showed that Dvl2 was overexpressed in HCC tissues and was also correlated with poor prognosis, suggesting that Dvl2 is a novel therapeutic target for HCC.
Several prognostic models have been developed to assess the efficacy and safety of sorafenib for metastatic renal cell carcinoma (mRCC), but few studies have validated its use in Chinese patients. The objective of this single center, single arm retrospective study was to examine the efficacy and safety of sorafenib and its related prognostic clinico-pathologic factors in Chinese mRCC patients.
Methods
One hundred thirty four mRCC patients were enrolled. All patients received 400 mg of sorafenib orally twice daily. The dose was subsequently adjusted in the event of treatment-induced toxicity. Tumor response, progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were determined.
Results
The median PFS and OS were 10 months (1–36 months) and 22 months (2–37 months), respectively. Complete, partial, and stable disease were observed in two (1.49 %), 24 (17.91 %), and 99 (73.88 %) patients, respectively. Hand/foot skin reactions, diarrhea and fatigue were the most commonly observed AEs following sorafenib treatment. Among the AEs, only 13 grades 3 and 4 were observed. Multivariate analysis revealed that independent predictive factors for PFS included Eastern Cooperative Oncology Group (ECOG) status, Memorial Sloan-Kettering Cancer Center (MSKCC) risk status, and bone metastasis (all p?<?0.05). Factors associated with OS included MSKCC risk values, bone metastasis and sorafenib-induced hypertension (all p?<?0.05).
Conclusion
The introduction of sorafenib therapy for mRCC in Chinese patients may lead to a favorable disease control with acceptable tolerability. In addition, the parameters predicting favorable outcomes, including ECOG status, MSKCC risk status and bone metastasis, may have prognostic value in clinical practice.
Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis.
Purpose
To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management.
Materials and methods
Retrospective review of 145 pts bNLR, overall toxicity, early toxicity rates and overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the coefficients found in the Cox analysis. ROC curves and pseudoR2 index were used for internal validation. Discrimination ability and calibration were tested by Harrel’s c-index (HCI) and Akaike criteria (AIC).
Results
The optimal bNLR cut-off for the prediction of OS was 4 (AUC 0.62). Independent prognostic factors in multivariate analysis for OS were performance status (PS) (p < .0001), Child–Pugh (C–P) score (p = 0.005), early-onset diarrhoea (p = 0.006) and BNLR (0.011). The prognostic score based on these four variables was found efficient (HCI = 0.659; AIC = 1.180). Four risk groups for OS could be identified: a very low-risk (median OS = 48.6 months), a low-risk (median OS = 11.6 months), an intermediate-risk (median OS = 8.3 months) and a high-risk group (median OS = 4.4 months).
Conclusions
PS and C–P score were the main prognostic factors for OS, followed by early-onset diarrhoea and bNLR. We identified four risk groups for OS depending on these parameters. This prognostic model could be useful for patient stratification, but an external validation is needed.
In this study, we aim to report the efficacy of using the anterior approach (AA) versus the conventional approach (CA), in surgical resection for large hepatocellular carcinoma (HCC) (≥7 cm) of the right hepatic lobe in terms of surgical and long-term outcomes.
Materials and Methods
Between 2000 and 2006, 138 consecutive patients who underwent hepatic resection with curative intent for large right lobe HCC ≥7 cm were identified from a retrospective database. The 40 patients who had AA were compared with the remaining 98 patients who had CA. Clinicopathological features and surgical results were analyzed and prognostic factors were evaluated by multivariate analysis.
Results
There was no significant difference between the two groups as regards clinical, laboratory, and pathological parameters. The operative results had shown a comparable proportion of patients who experienced massive operative blood loss and postoperative complications in the two groups. The AA group had a lower recurrence rate (P = 0·015), better disease-free survival (DFS) (P = 0·001), and overall survival than the CA group. Our study identified that AA is a prognostic factor of both overall survival and disease-free survival for large HCC ≥7 cm.
Conclusion
The AA is a safe and effective technique for right hepatic resection for large HCC and achieves more advantageous long survival outcome over the CA.
Prognosis of synchronous hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) was poor, while aggressive intrahepatic therapies remained controversial. This study aimed to investigate the significance of aggressive intrahepatic therapies for synchronous PM–HCC.
Methods
Synchronous PM–HCC patients were retrospectively enrolled from Sun Yat-sen Memorial Hospital of Sun Yat-sen University during January 2000 and December 2015. Univariate and multivariate analysis were performed to investigate the prognostic factors. Patients were grouped according to different HCC treatment modalities including liver resection (LR), ablation, transarterial chemoembolization (TACE), systemic therapy (ST, systemic chemotherapy or sorafenib) and supportive care (SC). Case control studies were achieved using propensity score matching (PSM) analysis to further investigate the significance of LR, ablation and TACE.
Results
Eighty-one patients were enrolled, and the median overall survival (OS) was 4.5 months. Serum alpha fetal protein (AFP) ≥ 400 ng/ml, multiple HCC lesions and no intrahepatic therapies (LR/Ablation/TACE) were inferior independent prognostic factors. Patients were divided into LR group (n = 9), Ablation/TACE group (n = 24) and ST/SC group (n = 48). After PSM analysis, survival outcome was superior in LR group compared to Ablation/TACE group (19.6 vs. 6.9 months) (p = 0.023) or ST/SC group (19.6 vs. 2.8 months) (p = 0.034), while no significant difference was found between -Ablation/TACE and ST/SC group (5.1 vs. 3.2 months) (p = 0.338).
Conclusions
Prognosis of synchronous PM–HCC patients was poor. Serum AFP ≥ 400 ng/ml, multiple HCC lesions and no aggressive intrahepatic therapies were inferior prognostic factors. LR might provide survival benefits in well-selected patients, while the significance of ablation or TACE remained to be further investigated.
Microwave ablation (MWA) is an emerging treatment for treatment of patients with hepatocellular carcinoma (HCC) not amenable of surgical resection.
Patients and Methods
We searched for patients diagnosed as having small-, medium-, and large HCCs treated with MWA under CT guidance between 2010 and 2014. The main outcomes of interest were rates of complete ablation, complications, and overall survival. Rates of complete ablation were compared with Chi-square test, and estimated survival rates were calculated by means of Kaplan-Meier method.
Results
Thirty-two patients with 45 HCC nodules received MWA. Seventeen (37.8%) nodules were <3 cm (small), 15 (33.3%) between 3 and 5 cm (medium), and 13 (28.9%) > 5 cm (large). Complete ablation was obtained in 94.1% of small tumors, 80% of medium tumors, and 53.8% of large tumors (p = 0.03). Two patients had HCC located in risk area (paracardiac position). Minor complications occurred after seven procedures (15.5%). Estimated median survival was 37 months (95% confidence interval 11.97–62.02). One-year OS was 82.7%, 2-year survival 68.9%, and 3-year survival 55.2%.
Conclusion
MWA is a versatile ablative method that can be applied in HCC at various stages, and also in lesions located in risk areas.
Sorafenib is recommended for the treatment of advanced-stage hepatocellular carcinoma (HCC). Nonetheless, it is expensive, effective in few patients, and may cause significant adverse effects. Therefore, accurate selection of patients is needed. In a previous study, we constructed a simple scoring system to predict patients’ outcomes based on the occurrence of sorafenib adverse effects.
Objective
The present study aimed to validate this scoring system in a real-life cohort of HCC patients.
Patients and Methods
Clinical records of 279 outpatients treated with sorafenib in eight Italian centers were retrospectively analyzed. Adverse effects considered to calculate the score were skin toxicity, diarrhea, and arterial hypertension, occurring during the first month of therapy. For each adverse effect, 1 point was assigned if present; and 0 points if absent (resulting in a total score between 0 and 3).
Results
Median overall survival (OS) was 10.8 months and median time to progression (TTP) was 5.1 months. At multivariate analysis, performance status, α-fetoprotein (AFP), and Child-Pugh score were independently associated with TTP and OS. A progressive increase of OS and TTP was observed in patients with scores from 0 to 3 (p < 0.001). Six-, 12-, and 24-month survival probabilities were 55.1, 24.5, and 7.9% in score 0 patients, and 100, 80.9, and 46.2% in score 3 patients, respectively. Complete response was observed in one patient (0.4%), partial responses in 41 (15.2%), and stable disease in 117 (43.5%). The disease control rate in patients with scores of 0, 1, 2, and 3 was 34.3, 51.6, 80.9, and 96.3%, respectively (p < 0.001). Complete or partial responses were not observed in score 0 patients.
Conclusions
We have validated a useful scoring system to predict outcomes in sorafenib-treated HCC patients. This score is easy to calculate and suitable for implementation in daily clinical practice.
Venous thromboembolism (VTE) is a common complication in cancer patients, and is associated with worse prognosis in such population. Hepatocellular carcinoma (HCC) poses high risk for VTE; however, data is scarce regarding the characteristics and consequences of VTE in HCC patients.
Method
We retrospectively reviewed the electronic medical records (EMR) of 270 patients diagnosed with HCC from 2000 to 2015 in Cook County Health and Hospitals System. We report the cumulative incidence of VTE in the present cohort, and identified through multivariate logistic regression the independent risk factors of the development of VTE. Overall prognosis of patients with and without VTE were presented and compared.
Results
Sixteen cases (5.93%) of VTE were documented in the present study. In multivariate analysis, obesity, Child B cirrhosis, intra-hepatic lesions more than 3, and multi-organ extrahepatic metastasis were significantly associated with VTE development (p < 0.05). The presence of VTE was an independent risk factor for mortality in multivariate analysis (HR = 3.62, p = 0.021), together with male gender, Child C cirrhosis, and extrahepatic metastasis.
Conclusions
Obesity, Child B cirrhosis, more intra-hepatic lesions, and multi-organ extrahepatic metastasis are associated with cancer-associated VTE. VTE will adversely affect the prognosis of patients with HCC; therefore, primary thromboprophylaxis may be warranted in such population.
Little information has been published on the use of tyrosine kinase inhibitors for treatment of patients undergoing hemodialysis (HD). We investigated the efficacy and safety of sorafenib for metastatic renal cell carcinoma (mRCC) patients undergoing HD.
Methods
Twenty patients undergoing HD were treated with sorafenib as first-line therapy for mRCC at our hospital between April 2008 and August 2014. Patient medical records were retrospectively reviewed to evaluate the response to sorafenib and treatment-related toxicity.
Results
Fifteen and 5 patients were classified in the intermediate and poor risk groups, respectively, of the Memorial Sloan–Kettering Cancer Center risk model. Eighteen patients had 3 or more metastatic lesions, and 7 patients had metastases in 2 or more organs. Of 16 patients who had previously undergone nephrectomy, 8 were pathologically diagnosed with non-clear-cell carcinoma. The median duration of sorafenib therapy was 4.7 months. Sorafenib was discontinued owing to progressing disease for 15 patients and because of serious adverse events (AE) (≥grade 3) for 4 patients, i.e. subarachnoid hemorrhage, cerebral hemorrhage, sepsis, and syncope for 1 patient each. Median time to progression was 6.3 months, and median overall survival was 14.2 months.
Conclusions
In this study, many patients had unfavorable clinical features, for example poor risk classification and metastases in multiple organs. Although sorafenib treatment of HD patients seems feasible, careful monitoring is needed because of the tendency for a high incidence of serious AE, even when a reduced dose is administered.
The study aimed to evaluate stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) in patients not eligible for liver transplant (LT).
Methods
We retrospectively identified transplant-ineligible HCC patients treated with SBRT to the liver between 2004 and 2013. Our primary endpoint was overall survival (OS). We also report treatment toxicities using CTCAE 3.0, radiographic response, and patterns of failure.
Results
We identified 93 patients with median age at SBRT of 65.8 years. Forty-six percent were classified as Child-Pugh B or C and 85% had an Eastern Cooperative Oncology Group performance status of 1–2. After SBRT, 86% of patients experienced no or mild treatment-related adverse events. Only 8% of patients experienced grade 3 and 2% of patients experienced grade 4 adverse events. Overall radiographic response was complete in 1.2%, partial in 35.4%, stable in 43.9%, and progressive disease in 19.5%. Median OS was 8.8 months with 1-, 2-, and 3-year OS rates of 38.0, 29.8 and 21.2%, respectively. The Cancer of the Liver Italian Program (CLIP) score was found to strongly correlate with survival. Median OS for patients with CLIP scores of 0, 1, 2, and 3 was 21.1, 8.5, 5.1, and 7.1 months, respectively (p = 0.003).
Conclusion
Our series demonstrates that SBRT is generally safe for HCC patients, even those with advanced liver failure. Although survival is generally poor, we were able to identify a group of patients with good liver function and early tumor stage who can achieve median OS of close to 2 years with SBRT.
Small-sized HCC can be effectively cured by surgery with good clinical outcomes. A highly sensitive HCC α-fetoprotein routine test (HCC-ART) for HCC diagnosis as well as a simplied form of the HCC-ART were reported in the British Journal of Cancer. Here, we verified and studied the applicability of the HCC-ART to the detection of early-stage HCC.
Methods
341 cirrhotic patients and 318 HCC patients were included in this study. For each, the HCC-ART score was calculated, and then the sensitivity, specificity, and results of an ROC curve analysis were compared between the HCC-ART and AFP when these biomarkers were used to detect small-sized HCC.
Results
Different HCC-ART cutoffs were set for the detection of different tumor sizes. The HCC-ART (AUC = 0.871, 70% sensitivity, 97% specificity) and the simplified HCC-ART (AUC = 0.934, 82% sensitivity, 100% specificity) were found to have high predictive power when attempting to separate cirrhotic patients from those with small-sized HCC. The simplified HCC-ART score was superior to AFP for determining stages according to the early Okuda (0.950 AUC, 84% sensitivity, 99% specificity), CLIP (0.945 AUC, 84% sensitivity, 99% specificity), and BCLC (1.000 AUC, 100% sensitivity, 99% specificity) staging systems. The simplified HCC-ART score was more strongly correlated than AFP and other staging systems with HCC tumor size (P < 0.0001; r = 0.8).
Conclusion
The HCC-ART is superior to AFP for diagnosing early-stage HCC. Due to its advantages of minimal variability and a wide continuous scale for assessing HCC severity, the simplified HCC-ART has the potential to be more widely used than the original HCC-ART.
Several studies have found benefits of radiotherapy for adrenal metastasis from hepatocellular carcinoma (HCC). However, the efficacy, safety and outcome issues have not yet been fully addressed. Therefore, we performed this study to further elucidate the feasibility and outcome of radiotherapy in treating adrenal metastasis from HCC.
Methods
We retrospectively analyzed 81 patients with adrenal metastasis from HCC between 2001 and 2015. Eighteen patients received helical tomotherapy and 63 patients received conventional radiotherapy, including two-dimensional (2-D) or three-dimensional conformal radiotherapy (3-D CRT). The median radiation dose was 50 Gy (range 26–64 Gy) with median fraction size of 2.0 Gy (range 2.0–5.0 Gy). Tumor responses, adverse effects, patient outcomes and prognostic factors were analyzed.
Results
An objective response (complete and partial response) was achieved in 55.6% patients. The helical tomotherapy group showed higher objective response rate than the conventional radiotherapy group (P = 0.031). The major adverse effects were anorexia (51.8%), nausea (41.9%), and fatigue (35.8%). Similar toxicity profile occurred in the 2-D, 3-D CRT and helical tomotherapy groups. The overall survival (OS) rate at 1, 2 and 5 years was 59.9, 35.0, and 12.9%, respectively, with a median survival of 15 months. Patients who received helical tomotherapy achieved a better OS compared to the conventional radiotherapy group (P = 0.047). However, multivariate analysis indicated that radiotherapy technique was not an independent prognostic factor for patient outcome.
Conclusion
These results suggest that radiotherapy offers a noninvasive approach in controlling adrenal metastasis from HCC with promising local control and acceptable tolerability.
Extremely poor prognosis in hepatocellular carcinoma (HCC) patients with progressing disease was denoted by vascular invasion. Cytokeratin 18 (CK18) has been shown to be overexpressed in hepatocellular carcinoma so it is a valuable tumor marker; however, its role in vascular invasion is still unclear. This study aimed to predict CK18 as a predictive marker for macrovascular malignant invasion.
Methods
The present study was conducted on three groups of patients: group I included 91 HCC patients without macrovascular invasion, group II included 34 HCC patients with radiological evidence of vascular invasion, and group III included 110 control individuals subdivided into IIIA as healthy blood donors and IIIB as post-HCV cirrhotic patients without HCC.
Results
ROC curve of M30 fragments of CK18 was constructed for discrimination between HCC with and without macrovascular invasion. Optimum cutoff value was 304.5 ng/mL (AUC = 0.997, P < 0.001), sensitivity (100%) and specificity (98.8%). Regression analysis was conducted for prediction of macrovascular invasion within HCC patients. The following variables: higher levels of AST, M30, bilirubin, and AFP, lower levels of serum albumin, larger tumor size, child B score, and multiple lesions were associated with vascular invasion in univariate analysis. While in multivariate analysis, higher levels of AST and bilirubin and elevated levels of M30 and AFP serum were considered independent predictors for macrovascular invasion in HCC patients.
Conclusion
The present study suggests that increased M30 fragments of CK18 levels may be useful as a possible marker of early tumor invasiveness.
Application of the Milan criteria is an effective strategy to select patients with hepatocellular carcinoma (HCC) for liver transplantation, but HCC recurrence is still a major concern. The aim of this study was to determine whether interleukin 6 (IL6) polymorphisms and clinical variables are potential predictors for HCC recurrence and prognosis after transplantation.
Methods
A total of 110 consecutive patients with HCC undergoing liver transplantation were enrolled in the study. Six tag single nucleotide polymorphisms in IL6 were genotyped in both the donors and recipients. Demographic characteristics, HCC features, and IL6 polymorphisms were assessed against HCC recurrence.
Results
Pretransplant hepatitis B virus DNA (P = 0.014), pretransplant serum alpha-fetoprotein (P = 0.035), number of nodules (P = 0.011), diameter of main nodule (P = 0.001), macrovascular invasion (P = 0.001), microvascular invasion (P = 0.001), HCC exceeding the Milan criteria (P < 0.001), and donor rs2069852 AA genotype (P = 0.010) were associated with HCC recurrence. Recurrence-free survival rate and overall survival rate were significantly lower (P = 0.011 and P = 0.026, respectively) in patients whose donor had the rs2069852 AA genotype than in those whose donor had the AG and GG genotypes. Independent risk factors for recurrence-free survival and overall survival were microvascular invasion (P = 0.003; P = 0.002), HCC exceeding the Milan criteria (P < 0.001; P = 0.001), and donor rs2069852 AA genotype (P = 0.002; P = 0.010).
Conclusions
Our data suggest that donor IL6 rs2069852 polymorphisms may be a potential genetic marker for HCC recurrence after liver transplantation in the Han Chinese population.
Indications for resection of hepatocellular carcinoma (HCC) remain controversial. This study aimed to identify prognostic factors that affect overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatectomy.
Methods
From 2004 to 2010, 601 patients with HCC who underwent resection were enrolled. Factors stratified into the host, biochemical, surgical treatment and tumor-related features in terms of recurrence and overall survival were analyzed. Prognostic factors were evaluated by univariate and multivariate analyses, with Kaplan–Meier survival analyses and Cox proportional hazard model.
Results
The overall survival rates of 1-, 3- and 5- year were 79, 62, and 54 %, and the corresponding DFS rates were 51, 38 and 31 %, respectively. In a multivariate analysis, Child–Pugh, serum AFP level, ALT level, time for hepatic resection, tumor differentiation, maximum size of tumors, local necrosis, portal vein tumor thrombus, and TNM Stage were correlated significantly with patients’ OS. Gender (P = 0.046), cigarette smoking (P = 0.007), serum AFP level (P = 0.001), GGT level (P = 0.002), maximum size of tumors (P = 0.009), liver cirrhosis (P = 0.025), portal vein tumor thrombus (P = 0.022), microvascular tumor thrombus (P = 0.007) and TNM Stage (P = 0.001) were significantly affected DFS.
Conclusion
Preoperative AFP level, maximum size of tumors, portal vein tumor thrombus and TNM Stage were revealed as important prognostic factors for OS and DFS through follow-up of a relatively large cohort of Chinese HCC patients.
