Rapid regression of advanced hepatocellular carcinoma associated with elevation of des-gamma-carboxy prothrombin after short-term treatment with sorafenib - a report of two cases

Background

Sorafenib is the first molecular-targeted agent that is effective for advanced hepatocellular carcinoma (HCC), with prolongation of survival. However, a complete response is very rare, and rapid regression of HCC after short-term treatment with sorafenib has not been reported previously.

Case Reports

We describe 2 patients with advanced multiple HCC who received sorafenib for short periods of 1 or 2 weeks, respectively. Longer treatment was precluded by the development of hepatic failure as an adverse event of sorafenib.

Results

HCC rapidly regressed, and both patients had a partial response (PR), despite short-term treatment. Furthermore, an early elevation of des-gamma-carboxy prothrombin (DCP) was temporarily seen in both patients, with no elevation of alpha-fetoprotein.

Conclusions

Sorafenib can induce rapid regression of advanced HCC even after short-term treatment, and the initial response of HCC was identical in both patients. Since early elevation of DCP was observed in our patients with PR, DCP might be a predictive biomarker of anti-tumor response. Further studies are required to clarify the mechanisms underlying the effectiveness of sorafenib, including the alteration of DCP.Key Words: Hepatocellular carcinoma, Sorafenib, Rapid regression, Des-gamma-carboxy prothrombin, Biomarker     

Multicenter Italian Experience in Liver Transplantation for Hepatocellular Carcinoma in HIV‐Infected Patients

Background.

The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine.

Patients and Methods.

We compared 30 HIV-positive patients affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden.

Results.

HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates.

Conclusion.

LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.     

An open-label,single-arm,phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma

Purpose

We conducted this phase I/II clinical trial to determine the safety and efficacy of lower-dose decitabine based therapy in pretreated patients with advanced HCC.

Experimental Design

Patients with advanced HCC were eligible. The administered dose of decitabine was 6 mg/m²/d intravenously on days 1 to 5 of a 28-day cycle. Additional therapies were given based on their disease progression status. The endpoint was to ensure the safety, hepatotoxicity, clinical responses, progression-free survival (PFS) and pharmacodynamics assay of lower-dose decitabine.

Results

Fifteen patients were enrolled. The favorable adverse events and liver function profiles were observed. The most beneficial responses were 1 complete response (CR), 6 stable disease (SD) and 8 progressive disease (PD). MRI liver scans post-treatment indicated a unique and specific characteristic. The immunohistochemistry result from the liver biopsy exhibited noteworthy CTL responses. Median PFS was 4 months (95% CI 1.7, 7), comparing favorably with existing therapeutic options. Expression decrement of DNMT1 and global DNA hypomethylation were observed in PBMCs after lower-dose decitabine treatment.

Conclusion

The lower-dose decitabine based treatment resulted in beneficial clinical response and favorable toxicity profiles in patients with advanced HCC. The prospective evaluations of decitabine administration schemes and tumor tissue-based pharmacodynamics effect are warranted in future trials.     

Combination of percutaneous radiofrequency ablation with transarterial chemoembolization for hepatocellular carcinoma： observation of clinical effects

Objective： To observe the clinical effect of radiofrequency ablation （RFA） combined with transcatheter arterial chemoembolization （TACE） for advanced hepatocellnlar carcinoma （HCC）. Methods： A total of 92 eases of advanced primary liver cancer underwent TACE and RFA treatment from June 2005 to 2011 at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College. A total of 88 cases with complete clinical treatment and follow-up data were divided into two groups： 43 patients treated with TACE （TACE group） and 45 patients that received TACE combined with RFA treatment （TACE ＋ RFA group）. After clinical data assessment, tumor size and survival status were not significantly different between the groups as determined by stratified analysis. Results： Before and after surgery, spiral CT radiography and color comparison observed ablation conditions. The tumor necrosis rates after treatment （CR ＋ PR） were 67.4% （29/43） and 91.1% （41/45） for the TACE and combined treatment groups, respectively, and the difference was statistically significant （P〈0.05）. The quality of life was significantly improved for patients undergoing TACE ~ RFA compared with the control group. Survival duration was not significantly different in patients undergoing TACE ~ RFA compared with the control group. Conclusions： In this study, the effect of RFA combined with TACE treatment was better than TACE alone in treating advanced HCC.     

Fused monochromatic imaging acquired by single source dual energy CT in hepatocellular carcinoma during arterial phase： an initial experience

Objective： To explore whether single and fused monochromatic images can improve liver tumor detection and delineation by single source dual energy CT （ssDECT） in patients with hepatocellular carcinoma （HCC） during arterial phase. Methods： Fifty-seven patients with HCC who underwent ssDECT scanning at Beijing Cancer Hospital were enrolled retrospectively. Twenty-one sets of monochromatic images from 40 to 140 keV were reconstructed at 5 keV intervals in arterial phase. The optimal contrast-noise ratio （CNR） monochromatic images of the liver tumor and the lowest-noise monochromatic images were selected for image fusion. We evaluated the image quality of the optimal-CNR monochromatic images, the lowest-noise monochromatic images and the fused monochromatic images, respectively. The evaluation indicators included the spatial resolution of the anatomical structure, the noise level, the contrast and CNR of the tumor. Results： In arterial phase, the anatomical structure of the liver can be displayed most clearly in the 65-keV monochromatic images, with the lowest image noise. The optimal-CNR monochromatic images of HCC tumor were 50-keV monochromatic images in which the internal structural features of the liver tumors were displayed most clearly and meticulously. For tumor detection, the fused monochromatic images and the 50-keV monochromatic images had similar performances, and were more sensitive than 65-keV monochromatic images. Conclusions： We achieved good arterial phase images by fusing the optimal-CNR monochromatic images of the HCC tumor and the lowest-noise monochromatic images. The fused images displayed liver tumors and anatomical structures more clearly, which is potentially helpful for identifying more and smaller HCC tumors.     

A phase I/IIa study of adjuvant immunotherapy with tumour antigen-pulsed dendritic cells in patients with hepatocellular carcinoma

Background:

To date, no adjuvant treatment has been shown to have a clear benefit in patients with hepatocellular carcinoma (HCC). In this prospective phase I/IIa study, we evaluated the safety and efficacy of adjuvant dendritic cell (DC) therapy in HCC patients who received primary treatment for HCC.

Methods:

Twelve HCC patients who had no viable tumour after primary treatments were included. Dendritic cell vaccines pulsed with cytoplasmic transduction peptide-attached alpha-fetoprotein, glypican-3 and melanoma-associated antigen 1 recombinant fusion proteins were injected subcutaneously near to inguinal lymph nodes. Adverse effects, time to progression (TTP), and associated immune responses were evaluated after DC vaccination.

Results:

Nine of 12 patients had no tumour recurrence up to 24 weeks after DC vaccination. Among a total of 144 adverse events, 129 events (89.6%) were regarded as adverse drug reactions, all of which were grade 1 or 2. The majority of patients showed enhanced anti-tumour immune responses after DC vaccination. Recurrence-free patients exhibited relatively stronger anti-tumour immune responses than patients who developed recurrence after DC vaccination, as evidenced by lymphocyte proliferation and IFN-γ ELISPOT assays. The median time of TTP was 36.6 months in the DC-vaccination group and 11.8 months in the control group (hazard ratio, 0.41; 95% confidence interval, 0.18–0.95; P=0.0031 by log-rank test).

Conclusions:

Adjuvant DC vaccine for HCC was safe and well tolerated in phase I/IIa study, and preliminary efficacy data are encouraging to warrant further clinical study in patients with HCC after primary treatments.     

A case report of HCC cutaneous metastasis

Introduction

Hepatocellular carcinoma (HCC) is one of the most common solid tumors in the world. HCC muscle and cutaneous metastases are rare and can occur by hematogenous spread or following surgical procedures performed for diagnostic or therapeutic aims.

Case study

We present a 47-year-old man underwent liver biopsy followed by surgical resection for moderately differentiated HCC in January 1999. In February 2010 the patient presented with HCC cutaneous metastases in the surgical scare and with HCC metastases of the right abdominal rectus muscle. En bloc tumor resection with the right abdominal rectus muscle was performed. In March 2011 the patient underwent resection of a locoregional muscle relapse. In November 2011 we started Sorafenib for intraepatic recurrence.

Discussion

This case suggests that in the follow-up of patients who underwent surgical resection or diagnostic and therapeutic procedures for HCC should be considered the possibility of abdominal wall metastasis even after many years, particularly in the cases with favorable evolution.     

Hepatocellular carcinoma in HIV-infected patients: check early, treat hard

Purpose.

Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era. The aims of this study were to describe HCC tumor characteristics and different therapeutic approaches, to evaluate patient survival time from HCC diagnosis, and to identify clinical prognostic predictors in patients with and without HIV infection.

Patients and Methods.

A multicenter observational retrospective comparison of 104 HIV-infected patients and 484 uninfected patients was performed in four Italian centers. HCC was staged according to the Barcelona Clinic Liver Cancer (BCLC) criteria.

Results.

Tumor characteristics of patients with and without HIV were significantly different for age, Eastern Cooperative Oncology Group performance status (PS) score ≤1, and etiology of chronic liver disease. Despite the similar potentially curative option rate and better BCLC stage at diagnosis, the median survival time was significantly shorter in HIV⁺ patients. HIV⁺ patients were less frequently retreated at relapse.Independent predictors of survival were: BCLC stage, potentially effective HCC therapy, tumor dimension ≤3 cm, HCC diagnosis under a screening program, HCC recurrence, and portal vein thrombosis. Restricting the analysis to HIV⁺ patients only, all positive prognostic factors were confirmed together with HAART exposure.

Conclusion.

This study confirms a significantly shorter survival time in HIV⁺ HCC patients. The less aggressive retreatment at recurrence approach does not balance the benefit of younger age and better BCLC stage and PS score of HIV⁺ patients. Thus, considering the prognosis of HIV⁺ HCC patients, effective screening techniques, programs, and specific management guidelines are urgently needed.     

High expression of 5-hydroxymethylcytosine and isocitrate dehydrogenase 2 is associated with favorable prognosis after curative resection of hepatocellular carcinoma

Background

The expression of 5-hydroxymethylcytosine (5-hmC) and isocitrate dehydrogenase 2 (IDH2) is frequently downregulated in numerous cancers. 5-hmC and IDH2 expression in hepatocellular carcinoma (HCC) has yet to be determined.

Methods

The immunohistochemical expression of 5-hmC and IDH2 were analyzed in tissue microarrays containing samples from 646 patients who had undergone hepatectomy for histologically proven HCC. The prognostic value of 5-hmC and IDH2 were evaluated by Cox regression and Kaplan-Meier analyses.

Results

We discovered that low 5-hmC and IDH2 expression was associated with malignant behaviors. Low 5-hmC or IDH2 expression alone and combined 5-hmC and IDH2 expression were associated with lower overall survival (OS) rates and higher cumulative recurrence rates. Multivariate analysis indicated that 5-hmC or IDH2 and 5-hmC/IDH2 were independent prognostic indicators for OS and time to recurrence (TTR), which was confirmed in an independent validation cohort.

Conclusions

5-hmC and IDH2 correlate with less aggressive tumor behavior in HCC. When 5-hmC and IDH2 are considered together, they serve as a prognostic marker in patients with surgically resected HCCs.     

Hepatocellular carcinoma in a large medical center of China over a 10-year period: evolving therapeutic option and improving survival

Background

Hepatocellular carcinoma (HCC) is among the most common and lethal cancers worldwide, especially in China.

Methods

We retrospectively analyzed data from patients who were diagnosed and treated HCC between 2002 and 2011 in a large hospital in northwest China and compared the data between periods 2002–2006 (P1) and 2007–2011 (P2).

Results

2045 patients were included in analysis. The HCC stages at diagnosis according to the Barcelona clinic liver cancer staging system had no significant change. Treatment options of liver transplantation, transcatheter arterial chemoembolization and other therapy decreased while percutaneous local ablation and supportive care increased from P1 to P2. Options of surgical resection and systematic therapy had no significant change. Patient survival rates at 1, 3 and 5 years significantly improved from P1 to P2. The treatments with increasing option trend had a higher magnitude of survival increase and vise versa.

Conclusion

Over the last 10 years, the patient survival had a significant increase which was mainly a result of the optimal therapeutic selections according to disease stages in this center. However, the proportion of patients diagnosed at early stages of HCC remained low and did not increase, a result calling for implementing surveillance system for at risk patients.     

High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer

Background

To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer.

Methods

Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression.

Results

The median follow-up time was 98 months(range, 17–265 months). The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD-L1 expression. Univariate Cox proportional hazards model analysis showed that PD-L1 was an independent prognostic factor for tumor prognosis.

Conclusions

PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients.     

Phase II Study of Afatinib as Third‐Line Treatment for Patients in Korea With Stage IIIB/IV Non‐Small Cell Lung Cancer Harboring Wild‐Type EGFR

Background.

This phase II single-arm trial evaluated afatinib, an irreversible inhibitor of the ErbB receptor family as third-line treatment of Korean patients with advanced non-small cell lung cancer (NSCLC) and tumors with wild-type EGFR. Currently, no standard therapy exists for these patients.

Methods.

Eligible patients had stage IIIB/IV wild-type EGFR lung adenocarcinoma and had failed to benefit from two previous lines of chemotherapy but had not received anti-EGFR treatment. Patients received oral afatinib at 40 mg per day until disease progression or occurrence of intolerable adverse events (AEs). The primary endpoint was confirmed objective tumor response (OR) rate (confirmed complete response [CR] or partial response [PR]). Secondary endpoints included disease control rate (DCR; OR or stable disease for ≥6 weeks), progression-free survival (PFS), and safety.

Results.

Forty-two patients received afatinib treatment, and 38 of those were included in efficacy analyses. No confirmed CRs or PRs were reported. DCR was 24% (9 of 38 patients), with a median disease control duration of 19.3 weeks. Median PFS was 4.1 weeks (95% confidence interval: 3.9–8.0). Frequently reported AEs (mainly grades 1 and 2) were rash/acne (88%), diarrhea (62%), and stomatitis (57%).

Conclusion.

Heavily pretreated patients with wild-type EGFR NSCLC treated with afatinib monotherapy did not experience an objective response and only 24% had disease stabilization lasting more than 6 weeks. AEs were manageable and consistent with the expected safety profile.     

Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease

Background:

α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients.

Methods:

We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-γ.

Results:

Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P=0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child–Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child–Pugh A score and in 46% with a B or C score.

Conclusion:

These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more likely to be present in patients with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC.     

A Phase II Trial of Neoadjuvant Chemotherapy with Genexol? (Paclitaxel) and Epirubicin for Locally Advanced Breast Cancer

Purpose

Neoadjuvant chemotherapy (NC) is yet to be established as the definitive treatment regimen for locally advanced breast cancer (LABC). The aim of this study was to determine the efficacy and toxicity of NC with epirubicin and paclitaxel.

Methods

Between March 2007 and January 2009, 50 patients with LABC were enrolled in an open-label, phase II, multicenter study carried out at five distinct institutions. All patients were scheduled to receive four cycles of 60 mg/m² epirubicin and 175 mg/m² paclitaxel every 3 weeks, preoperatively, unless they developed profound side effects or disease progression. After curative surgery, two additional cycles of chemotherapy were administered to patients who had shown a positive response to NC.

Results

In all, 196 cycles of chemotherapy were administered preoperatively; 47 of the 50 patients (94%) underwent all four cycles of designated treatment. Complete disappearance of invasive foci of the primary tumor, and negative axillary lymph nodes were confirmed in eight patients (16.0%), post operation. The cumulative 5-year disease-free survival rate was 70.0% for patients with complete remission (CR) and partial remission (PR), and 33.3% for patients with stable disease (SD) and progressive disease (PD) (p=0.018). The cumulative 5-year overall survival was 90.0% for patients who achieved CR and PR and 55.6% for patients who had SD and PD (p=0.001). Neutropenia (42.0%) was the most common grade 3/4 toxicity. However, none of the toxicities resulted in cessation of the treatment.

Conclusion

The encouraging pathologic response observed in the patients treated with epirubicin plus paclitaxel NC in this study suggests that epirubicin could be a substitute for doxorubicin, which is the most cardiotoxic agent.     

Efficacy of capecitabine-based combination therapy and single-agent capecitabine maintenance therapy in patients with metastatic breast cancer

Objective

The purpose of this study was to observe the efficacy and toxicities of capecitabine-based chemotherapy and capecitabine monotherapy as maintenance therapy in the treatment of metastatic breast cancer (MBC).

Patients and methods

A total of 98 MBC patients were treated with capecitabine combined with vinorelbine (NX).

Results

The median number of treatment was 6 cycles (1-7 cycles). There were two cases of complete remission (CR), 58 partial remission, 27 stable disease (SD), 11 progression disease. The overall response rate (ORR) (CR + PR) was 61.2%. The clinical benefit rate (CBR) was 75.5%. Fifty of effective patients received with capecitabine monotherapy as maintenance therapy. The ORR (CR + PR) was 4%. The CBR was 48%. The median progression-free survival (PFS) was 12 months. In maintenance therapy or not, the median post metastasis survival rate (MSR) was 63 and 28 months, respectively. In the combination therapy group, the major grade 3/4 toxicities included hand-foot syndrome (3.1%), skin pigmentation (2.0%), diarrhoea and abdominal distension (5.1%), stomatitis (1.0%), and leukopenia (20.4%).

Conclusions

Capecitabine-based combination therapy and single-agent capecitabine maintenance therapy were well tolerated and effective to MBC.     

Radioembolization with Yttrium-90 microspheres for patients with unresectable hepatocellular carcinoma

Background

Hepatocellular carcinoma (HCC) is aggressive primary malignancy of the liver that most commonly presents late in the disease course. As a result, the majority of patients are not candidates for curative therapies. Locoregional therapies including Yttrium-90 (Y-90) radioembolization play an important role in management of the vast majority of patients with HCC.

Methods

Patients with unnresectable HCC (n=17) treated with Y-90 radioembolization from 2005 to 2014 were evaluated retrospectively. Data was abstracted from medical records including patient charts, laboratory data, and imaging. Toxicities were recorded using Common Terminology Criteria 3.0. Response was recorded according to modified RECIST (mRECIST) criteria.

Results

Seventeen patients received 33 treatments with Y-90 radioembolization. A majority (65%) received TheraSphere with a minority (35%) receiving SIR-Spheres. The median treatment activity delivered was 1.725 gBq (range, 1.4-2.5 gBq). The median treatment dose delivered was 100 Gy (range, 90-120 Gy). The median lung shunt fraction was 2.02% (range, 1.5-4.1%). The most common clinical toxicity among all patients was nausea and vomiting (59%), primarily grade 1 and 2. Other post-treatment findings included abdominal pain (29%), fatigue (53%), and weight loss (18%). One patient developed a grade 5 gastric ulcer after the treatment. A clinical benefit, defined as patients achieving complete response (CR), partial response (PR) or stable disease (SD), was seen in 48% of patients. PR was seen in 24% of cases; progressive disease (PD) was noted in 35%. Patients survived for a median of 8.4 months (range, 1.3 to 21.1 months) after the first radioembolization treatment. Median survival after Y-90 treatment was 8.4 months among patients treated TheraSphere as compared with 7.8 months in patients treated with SIR-Spheres. The mean overall survival from the time of diagnosis was 11.7 months (range, 3.4 to 43.2 months).

Conclusions

For patients with unresectable HCC, Y-90 radioembolization is a safe and well-tolerated procedure. Our experience suggests that a significant percentage of patients achieve clinical benefit including many with PR. Survival after treatment from this single-center, transplant center is in line with prior reports. Prospective, randomized data is required to compare radioembolization with other therapies including chemoembolization and systemic therapy with sorafenib.     

Diabetes mellitus is associated with increased mortality in patients receiving curative therapy for hepatocellular carcinoma

Background.

Diabetes mellitus (DM) is closely associated with hepatocarcinogenesis. This study explores the prognostic impact of DM in patients who received curative therapy for localized hepatocellular carcinoma (HCC).

Methods.

Patients who had been diagnosed with stage I or II HCC in 2003 and 2004 and received surgical resection or local ablation therapy were identified from the population-based Taiwan National Cancer Registry. Data pertaining to DM and other comorbidities were retrieved from the Taiwan National Health Insurance database. Liver cancer-specific survival (LCS), liver disease-related survival (LDS) and overall survival (OS) rates were compared between patients with and without DM. The presence of other comorbidities and tumor status were adjusted using multivariate analysis.

Results.

A total of 931 patients who fulfilled the study criteria were analyzed; 185 (20%) of them had DM (type 1 or type 2). The LCS, LDS, and OS rates were significantly worse for patients with DM than patients without DM (all p < .001). After adjusting for age, sex, tumor stage, treatment, and the presence of other comorbidities, DM remained an independent predictor of poorer LCS (hazard ratio [HR] = 1.57; p < .001), LDS (HR = 1.70; p < .001), and OS (HR = 1.69; p < .001). The associations between DM and mortality were consistent among subgroups, irrespective of tumor size, stage, treatment modality, and liver cirrhosis.

Conclusions.

DM is an independent factor for poorer prognosis in patients who received curative therapy for localized HCC.     

FOXP3 gene polymorphism is associated with hepatitis B-related hepatocellular carcinoma in China

Background

Previous evidence has shown that the FOXP3 gene was involved in the pathogenesis of several tumors; however, the correlation between single nucleotide polymorphisms (SNPs) in the FOXP3 gene and the susceptibility to hepatitis B-related hepatocellular carcinoma (HCC) remains unclear.

Methods

We analyzed two SNPs in the FOXP3 gene, rs2280883 and rs3761549, in 392 patients with HCC, 344 patients with chronic hepatitis B (CHB) and 372 matched healthy controls. Genotyping was performed by MALDI-TOF Mass Spectrometry for all donors.

Results

Compared to healthy controls, HCC patients had higher frequencies of the TT genotype (79.6%) at rs2280883 and the CC genotype (77.6%) at rs3761549 of the FOXP3 gene; CHB patients also had higher frequencies of the TT genotype (74.1%) at rs2280883 and the CC genotype (74.6%) at rs3761549. There were no significant differences in the distribution of FOXP3 genotypes between CHB donors and HCC donors. The TT genotype at rs2280883 was more frequent in patients with HCC than healthy donors (P = 0.01), but no significant difference was observed in this genotype between CHB and healthy donors (P = 0.479). C allele frequency at rs3761549 was higher in HCC patients than healthy donors (P = 0.03), but distribution of this allele was not significantly different between CHB patients and healthy donors (P = 0.11). Stratified analysis showed that the CC genotype at rs3761549 was significantly associated with a high incidence of portal vein tumor thrombus (P = 0.02) and that the TT/CT genotype at rs3761549 was significantly associated with an increased rate of tumor recurrence in HCC patients (P = 0.001).

Conclusions

Our results suggested that the FOXP3 gene polymorphisms at rs2280883 and rs3761549 may be associated with hepatitis B-related HCC. At rs3761549, the CC genotype and the TT/CT genotype were associated with a high incidence of portal vein tumor thrombus and tumor recurrence, respectively.     

Clinical features,survival and prognostic factors of primary testicular diffuse large B-cell lymphoma

Objective： To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma （DLBCL）. Methods： A retrospective study of 37 patients with primary testicular DLBCL was carried out from November 2003 to May 2012. Their clinical features, survival and prognostic factors were analyzed. Results： During a median follow-up period of 39.8 months （5.4-93.0 months）, the median progression-free survival （PFS） was 26.2 months （95% CI：0-65 months） and the 3-year overall survival （OS） rate was 78.4%. Within the whole cohort, the factors significantly associated with a superior PFS were limited stage （stage Ⅰ/Ⅱ）, lactate dehydrogenase （LDH） ≤245 U/L, international prognostic index （IPI） ≤1, primary tumor diameter 〈7.5 cm, and patients who had complete response （CR） and received doxoruhicin-contained chemotherapy （P〈0.05）. There was a trend toward superior outcome for patients who received combined therapy （surgery/ chemotherapy/radiotherapy） （P=0.055）. Patients who had CR, primary tumor diameter 〈7.5 cm and IPI score ≤1 were significantly associated with longer PFS at multivariate analysis. Conclusions： Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of orchectomy, doxorubicin-contained chemotherapy and contralateral testicular radiotherapy （RT） seemed to improve survival.     

Sorafenib continuation or discontinuation in patients with unresectable hepatocellular carcinoma after a complete response

Aims

To assess the efficacy of continued administration of sorafenib for patients with unresectable hepatocellular carcinoma (HCC) treated with local regional therapy (LRT) after a complete response (CR), also, the adverse events of sorafenib after discontinuation of administration were observed.

Methods

Between April 2008 and May 2012, 956 consecutive patients with unresectable HCC treated with LRT (transarterial chemoembolization, radiofrequency ablation) combined with sorafenib were retrospectively investigated. Of these, 157 patients with a CR were enrolled: 102 of them continued to receive sorafenib (test group) and the other 55 stopped receiving sorafenib (control group).

Results

The median recurrence-free survival (RFS), post-complete response overall survival (pOS) and overall survival (OS) in the test and control groups were 11 months (95% CI: 6.1, 15.9), 25 months (95% CI: 20.7, 29.3) and 33 months (95% CI: 29.2, 36.8) and 12 months (95% CI: 10.4, 13.6), 28 months (95% CI 24.2, 31.8) and 34 months (95% CI: 30.8, 37.2) respectively. The differences in RFS, pOS and OS between the groups were not significant (P = 0.768, 0.797 and 0.730, respectively). The adverse events related to sorafenib resolved after discontinuation of administration and the quality of life (QoL) scores improved.

Conclusions

Patients with unresectable HCC who achieved a CR did not benefit from continued sorafenib in terms of RFS, pOS or OS. The adverse events of sorafenib were reversible, and discontinuation of sorafenib may improve the QoL of patients who have achieved a CR.