Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma (uHCC). HAIC-based treatment showed great potential for treating uHCC. However, large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking. AIM: To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors, programmed cell death of protein 1 (PD-1) and its ligand (PD-L1) blockers (triple therapy) under real-world conditions. METHODS: Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis. Study-level pooled analyses of hazard ratios (HRs) and odds ratios (ORs) were performed. This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades (AIPB) at Sun Yat-sen University Cancer Center from January 2018 to April 2023. Propensity score matching (PSM) was performed to balance the bias between the groups. The Kaplan-Meier method and cox regression were used to analyse the survival data, and the log-rank test was used to compare the suvival time between the groups. RESULTS: A total of 13 randomized controlled trials were included. HAIC alone and in combination with sorafenib were found to be effective treatments (P values for ORs: HAIC, 0.95; for HRs: HAIC + sorafenib, 0.04). After PSM, 176 HCC patients were included in the analysis. The triple therapy group (n = 88) had a longer median overall survival than the AIPB group (n = 88) (31.6 months vs 14.6 months, P < 0.001) and a greater incidence of adverse events (94.3% vs 75.4%, P < 0.001). CONCLUSION: This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC. Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and hepatic artery infusion chemotherapy for hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (TRIPLET): a phase II study.

Hepatic arterial infusion chemotherapy (HAIC) using a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promise for hepatocellular carcinoma (HCC) patients classified under Barcelona Clinic Liver Cancer (BCLC) stage C. In China, the combined therapy of camrelizumab and apatinib is now an approved first-line approach for inoperable HCC. This study (NCT04191889) evaluated the benefit of combining camrelizumab and apatinib with HAIC-FOLFOX for HCC patients in BCLC stage C. Eligible patients were given a maximum of six cycles of HAIC-FOLFOX, along with camrelizumab and apatinib, until either disease progression or intolerable toxicities emerged. The primary outcome measured was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Thirty-five patients were enrolled. Based on RECIST v1.1 criteria, the confirmed ORR stood at 77.1% (95% CI: 59.9% to 89.6%), with a disease control rate of 97.1% (95% CI: 85.1% to 99.9%). The median progression-free survival was 10.38 months (95% CI: 7.79 to 12.45). Patient quality of life had a transient deterioration within four cycles of treatment, and generally recovered thereafter. The most frequent grade ≥3 or above treatment-related adverse events included reduced lymphocyte count (37.1%) and diminished neutrophil count (34.3%). The combination of camrelizumab, apatinib, and HAIC demonstrated encouraging results and manageable safety concerns for HCC at BCLC stage C.

Cost-effectiveness and prognostic model of hepatic arterial infusion chemotherapy for hepatocellular carcinoma with high tumor burden and/or Vp4 tumor thrombus compared with sorafenib: a post-hoc analysis of the FOHAIC-1 trial.

OBJECTIVES: The phase III FOHAIC-1 trial revealed that hepatic arterial infusion of chemotherapy (HAIC) improved overall survival compared to sorafenib in the high-risk hepatocellular carcinoma (HCC). This study therefore set out to evaluate the cost-effectiveness and establish a prognostic clinico-radiological score of HAIC. MATERIALS AND METHODS: A total of 409 patients with high-risk HCC who received HAIC between 2014 and 2020 were included. A Markov model was applied in the cost-effectiveness analysis using data from the FOHAIC-1 trial. In prognosis analysis, a clinico-radiological score was developed using a Cox-regression model and subsequently confirmed in the internal validation and test cohorts. The area under the curve from receiver operator characteristic analysis was used to assess the performance of the clinico-radiological score. RESULTS: HAIC resulted in an incremental cost-effectiveness ratio of $10190.41/quality-adjusted life years compared to sorafenib, which was lower than the willingness-to-pay threshold. Probabilistic sensitivity analysis predicted a ≥99.9% probability that the incremental cost-effectiveness ratio was below the willingness-to-pay. The Cox analysis identified five factors, namely extrahepatic metastasis (m), arterial enhancing type (a), tumor number (nu), albumin-bilirubin index (a), and involved lobe (l), which together comprise the clinico-radiological score (HAIC-manual). Patients were classified into three groups based on the number of factors present, with cutoffs at 2 and 4 factors. The stratified median overall survival for these groups were 21.6, 10.0, and 5.9 months, respectively ( P <0.001). These findings were verified through internal validation and test cohorts with a significance level of P ≤0.01. The time-dependent area under the curve from receiver operator characteristic for the ability of the HAIC-manual to predict survival in 1, 2, and 3 years were 0.71, 0.76, and 0.78, which significantly outperformed existing staging systems. CONCLUSION: HAIC is a promising and cost-effective strategy for patients with high-risk HCC. The clinico-radiological score may be a simple prognostic tool for predicting HAIC treatment.

Identification and Validation of a Prognostic lncRNA Signature for Hepatocellular Carcinoma.

Background: An accumulating body of evidence suggests that long non-coding RNAs (lncRNAs) can serve as potential cancer prognostic factors. However, the utility of lncRNA combinations in estimating overall survival (OS) for hepatocellular carcinoma (HCC) remains to be elucidated. This study aimed to construct a powerful lncRNA signature related to the OS for HCC to enhance prognostic accuracy. Methods: The expression patterns of lncRNAs and related clinical data of 371 HCC patients were obtained based on The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DElncRNAs) were acquired by comparing tumors with adjacent normal samples. lncRNAs displaying significant association with OS were screened through univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. All cases were classified into the validation or training group at the ratio of 3:7 to validate the constructed lncRNA signature. Data from the Gene Expression Omnibus (GEO) were used for external validation. We conducted real-time polymerase chain reaction (PCR) and assays for Transwell invasion, migration, CCK-8, and colony formation to determine the biological roles of lncRNA. Gene set enrichment analysis (GSEA) of the lncRNA model risk score was also conducted. Results: We identified 1292 DElncRNAs, among which 172 were significant in univariate Cox regression analysis. In the training group (n = 263), LASSO regression analysis confirmed 11 DElncRNAs including AC010547.1, AC010280.2, AC015712.7, GACAT3 (gastric cancer associated transcript 3), AC079466.1, AC089983.1, AC051618.1, AL121721.1, LINC01747, LINC01517, and AC008750.3. The prognostic risk score was calculated, and the constructed risk model showed significant correlation with HCC OS (log-rank P-value of 8.489e-9, hazard ratio of 3.648, 95% confidence interval: 2.238-5.945). The area under the curve (AUC) for this lncRNA model was up to 0.846. This risk model was confirmed in the validation group (n = 108), the entire cohort, and the external GEO dataset (n = 203). GACAT3 was highly expressed in HCC tissues and cell lines. Based on online databases, GACAT3 expression independently affects both OS and disease-free survival in HCC patients. Silencing GACAT3 in vitro significantly suppressed HCC cell proliferation, invasion, and migration. Moreover, pathways related to the lncRNA model risk score were confirmed by GSEA. Conclusion: The lncRNA signature established in this study can be used to predict HCC prognosis, which could provide novel clinical evidence to guide targeted HCC treatment.

Profiles of m6A RNA methylation regulators for the prognosis of hepatocellular carcinoma.

N6-methyladenosine (m6A) RNA methylation, which is related to cancer initiation and progression, is dynamically regulated by the m6A RNA methylation regulators (including 'writers', 'erasers' and 'readers'). However, the prognostic value of m6A RNA methylation regulators involved in hepatocellular carcinoma (HCC) carcinogenesis and progression remains to be elucidated. The aim of the present study was to determine the prognostic score in predicting the prognosis of HCC patients based on these regulators. In The Cancer Genome Atlas, most of the 13 major m6A RNA methylation regulators were found to be differentially expressed between HCC and normal samples (P<0.001). In addition, two subgroups (clusters 1/2) had also been identified by applying consensus clustering in the m6A RNA methylation regulators. As compared with the cluster 1 subgroup, the cluster 2 subgroup was correlated with a poorer prognosis, as shown by the Kaplan-Meier method (P=6.197e-4). A risk signature was constructed based on these findings using six m6A RNA methylation regulators, which could not only predict the clinicopathological features of HCCs, but also serve as an independent prognostic marker, as shown by Cox regression analysis (hazard ratio=1.219, 95% confidence interval: 1.143-1.299; P<0.001). Data from the International Cancer Genome Consortium were used for external validation. In addition, gene set enrichment analysis identified several pathways that m6A RNA methylation regulators were closely associated with. In conclusion, the m6A RNA methylation regulators are the crucial participants in the malignant progression of HCCs, which are potentially useful for prognosis stratification and therapeutic strategy development for HCC.

Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets.

BACKGROUND: Hepatitis B virus, together with hepatitis C virus, has been recognized as the leading causes of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have been suggested in increasing studies to be the potential prognostic factors for HCC. However, the role of combined application of lncRNAs in estimating overall survival (OS) for hepatitis virus positive HCC (VHCC) is uncertain. AIM: To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction. METHODS: The expression patterns of lncRNAs, as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database. The R package was adopted to obtain the differentially expressed lncRNAs (DElncRNAs). LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis, so as to construct a least absolute shrinkage and selection operator (LASSO) model. Subsequently, the constructed lncRNA signature was developed and validated. Afterwards, the prognostic nomogram was established, which combined the as-established lncRNA signature as well as the clinical features. Meanwhile, subgroup analysis stratified by the virus type was also performed. Finally, the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly co-expressed genes. RESULTS: A total of 1420 DElncRNAs were identified, among which 406 were significant in univariate Cox regression analysis. LASSO regression confirmed 8 out of the 406 lncRNAs, including AC005722.2, AC107959.3, AL353803.1, AL589182.1, AP000844.2, AP002478.1, FLJ36000, and NPSR1-AS1. Then, the prognostic risk score was calculated. Our results displayed a significant association between the risk model and the OS of VHCC [hazard ratio = 1.94, 95% confidence interval (CI): 1.61-2.34, log-rank P = 2e-10]. The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC. Furthermore, a nomogram was plotted, and the concordance index of internal validation was 0.763 (95%CI: 0.700-0.826). Moreover, the subgroup analysis regarding etiology confirmed this risk model. In addition, the Wnt signaling pathway, angiogenesis, the p53 pathway, and the PI3 kinase pathway were the remarkably enriched pathways. CONCLUSION: An eight-lncRNA signature has been established to predict the prognosis for VHCC, which contributes to providing a novel foundation for the targeted therapy of VHCC.

Efficacy of treatment regimens for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials.

BACKGROUND: This study aimed to perform a network meta-analysis to evaluate the therapeutic effect and safety of various modalities in treating advanced hepatocellular carcinoma (HCC). Typically, the modalities of interest were comprised of sorafenib, transarterial chemoembolization (TACE), sorafenib combined with TACE, TACE combined with traditional Chinese medicine (TCM), and sorafenib combined with hepatic arterial infusion chemotherapy (HAIC). METHODS: Potentially eligible studies were systemically retrieved from the electronic databases (including PubMed and Cochrane Library) up to September 2018. The overall survival (OS) associated with the 5 modalities of interest enrolled in this study was compared by means of network meta-analysis. Meanwhile, major adverse events (AEs) were also evaluated. RESULTS: The current network meta-analysis enrolled 7 published randomized controlled trials (RCTs), and the pooled results indicated that the TACE-TCM regimen displayed the highest efficacy in treating advanced HCC, followed by HAIC-sorafenib. By contrast, the TACE alone and sorafenib alone regimens had the least efficacy. Relative to other regimens of interest, the TACE-TCM regimen was associated with less incidence of treatment-associated AEs. CONCLUSION: The TACE-TCM regimen was associated with higher treatment responses in advanced HCC patients than those of the other regimens of interest.

Significance of tumor-infiltrating immunocytes for predicting prognosis of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Hepatitis B virus (HBV) has been recognized as a leading cause of hepatocellular carcinoma (HCC). Numerous reports suggest that immune infiltration can predict the prognosis of HCC. Nonetheless, no creditable markers for prognosis of HBV-related HCC have been established by systematically assessing the immune-related markers based on tumor transcriptomes. AIM: To establish an immune-related marker based on the cell compositions of immune infiltrate obtained based on tumor transcriptomes, so as to enhance the prediction accuracy of HBV-related HCC prognosis. METHODS: RNA expression patterns as well as the relevant clinical data of HCC patients were obtained from The Cancer Genome Atlas. Twenty-two immunocyte fraction types were estimated by cell type identification by estimating relative subsets of RNA transcripts. Subsequently, the least absolute shrinkage and selection operator (LASSO) Cox regression model was employed to construct an immunoscore based on the immunocyte fraction types. Afterwards, the receiver operating characteristic (ROC) curve, Kaplan-Meier, and multivariate Cox analyses were performed. Additionally, a nomogram for prognosis that integrated the immunoscore as well as the clinical features was established. Meanwhile, the correlation of immunoscore with immune genes was also detected, and gene set enrichment analysis (GSEA) of the immunoscore was conducted. RESULTS: A total of 22 immunocyte fraction types were predicted and compared among the tumor as well as non-tumor samples. An immunoscore was constructed through adopting the LASSO model, which contained eight immunocyte fraction types. Meanwhile, the areas under the ROC curves for the immunoscore biomarker prognostic model were 0.971, 0.912, and 0.975 for 1-, 3-, and 5-year overall survival (OS), respectively. Difference in OS between the high-immunoscore group and the low-immunoscore group was statistically significant [hazard ratio (HR) = 66.007, 95% confidence interval (CI): 8.361-521.105; P < 0.0001]. Moreover, multivariable analysis showed that the immunoscore was an independent factor for predicting the prognosis (HR = 2.997, 95%CI: 1.737-5.170). A nomogram was established, and the C-index was 0.757 (95%CI: 0.648-0.866). The immunoscore showed a significant negative correlation with the expression of PD-1 (P = 0.024), PD-L1 (P = 0.026), PD-L2 (P = 0.029), and CD27 (P = 0.033). Eight pathways were confirmed by GSEA. CONCLUSION: The established immunoscore can potentially serve as a candidate marker to estimate the OS for HBV-related HCC cases.

Prognostic factors and survival according to tumor subtype in newly diagnosed breast cancer with liver metastases: A competing risk analysis.

Population-based study for predicting the prognosis for breast cancer liver metastasis (BCLM) is lacking at present. Therefore, the present study aimed to evaluate newly diagnosed BCLM patients of different tumor subtypes and assess potential prognostic factors for predicting the survival for BCLM patients. Specifically, data were collected from the Surveillance, Epidemiology and End Results program from 2010 to 2014, and were assessed, including the data of patients with BCLM. Differences in the overall survival (OS) among patients was compared via Kaplan-Meier analysis. Other prognostic factors of OS were determined using the Cox proportional hazard model. In addition, the breast cancer-specific mortality was assessed using the Fine and Gray's competing risk model. A nomogram was also constructed on the basis of the Cox model for predicting the prognosis of BCLM cases. A total of 2,098 cases that had a median OS of 20.0 months were included. The distribution of tumor subtypes was as follows: 42.2% with human epidermal growth factor receptor 2 (Her2; -)/hormone receptor (HR; +), 12.8% with Her2(+)/HR(-), 19.1% with Her2(+)/HR(+) and 13.5% with triple negative breast cancer (TNBC). Kaplan-Meier analysis revealed that older age (>64 years), unmarried status, larger tumor, higher grade, no surgery, metastases at other sites, and TNBC subtype were associated with shorter OS. Additionally, multivariate analysis revealed that older age (>64 years), unmarried status, no surgery, bone metastasis, brain metastasis and TNBC subtype were significantly associated with worse prognosis. Thus, age at diagnosis, marital status, surgery, bone metastasis, brain metastasis and tumor subtype were confirmed as independent prognosis factors from a competing risk model. We also constructed a nomogram, which had the concordance index of internal validation of 0.685 (0.650-0.720). This paper had carried out the population-based prognosis prediction for BCLM cases. The survival of BCLM differed depending on the tumor subtype. More independent prognosis factors were age at the time of diagnosis, surgery, marital status, bone metastasis, as well as brain metastasis, in addition to tumor subtype. Notably, the as-constructed nomogram might serve as an efficient approach to predict the prognosis for individual patients.

Alternative splicing events are prognostic in hepatocellular carcinoma.

Alternative splicing events (ASEs) play a role in cancer development and progression. We investigated whether ASEs are prognostic for overall survival (OS) in hepatocellular carcinoma (HCC). RNA sequencing data was obtained for 343 patients included in The Cancer Genome Atlas. Matched splicing event data for these patients was then obtained from the TCGASpliceSeq database, which includes data for seven types of ASEs. Univariate and multivariate Cox regression analysis demonstrated that 3,814 OS-associated splicing events (OS-SEs) were correlated with OS. Prognostic indices were developed based on the most significant OS-SEs. The prognostic index based on all seven types of ASEs (PI-ALL) demonstrated superior efficacy in predicting OS of HCC patients at 2,000 days compared to those based on single ASE types. Patients were stratified into two risk groups (high and low) based on the median prognostic index. Kaplan-Meier survival analysis demonstrated that PI-ALL had the greatest capacity to distinguish between patients with favorable vs. poor outcomes. Finally, univariate Cox regression analysis demonstrated that the expression of 23 splicing factors was correlated with OS-SEs in the HCC cohort. Our data indicate that a prognostic index based on ASEs is prognostic for OS in HCC.

Nasopharyngeal carcinoma patients with retropharyngeal lymph node metastases: a minimum axial diameter of 6 mm is a more accurate prognostic predictor than 5 mm.

OBJECTIVE: The criteria for the diagnosis of metastatic retropharyngeal lymph nodes (RLNs) have not yet been resolved and are not included in the current edition of the American Joint Committee on Cancer (AJCC) staging system (seventh edition) for the staging of nasopharyngeal carcinoma (NPC). The aim of this study was to use MRI to identify an RLN size criterion that can accurately predict prognosis in patients with NPC. MATERIALS AND METHODS: Eight hundred seventeen patients with newly diagnosed localized NPC were identified. All of the patients underwent MRI before treatment with definitive radiation therapy. All the MRI studies and medical records were reviewed retrospectively. Overall survival (OS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS) were assessed using SPSS software (version 17.0). RESULTS: RLN size cutoffs of ≥ 5 mm and of ≥ 6 mm were used. There was no significant difference in OS (p = 0.216), DMFS (p = 0.081), or LRFS (p = 0.067) in patients with RLNs ≥ 5 mm and in those with RLNs < 5 mm. When 6 mm was used as a size cutoff, significant differences in OS (p = 0.000) and DMFS (p = 0.001) were identified; there was no significant difference observed for LRFS (p = 0.380). CONCLUSION: A minimum axial RLN diameter of 6 mm was a more accurate prognostic predictor in NPC patients with RLN metastases than 5 mm.

Efficacy of minimally invasive therapies on unresectable pancreatic cancer.

For patients with unresectable pancreatic cancer, current chemotherapies have negligible survival benefits. Thus, developing effective minimally invasive therapies is currently underway. This study was conducted to evaluate the efficacy of transarterial chemoembolization plus radiofrequency ablation and/or 125I radioactive seed implantation on unresectable pancreatic cancer. We analyzed the outcome of 71 patients with unresectable pancreatic carcinoma who underwent chemoembolization plus radiofrequency ablation and/or radioactive seed implantation. Of the 71 patients, the median survival was 11 months, and the 1-, 2-, and 3-year overall survival rates were 32.4%, 9.9%, and 6.6%, respectively. Patients who had no metastasis, who had oligonodular liver metastases (≤3 lesions), and who had multinodular liver metastases (>3 lesions) had median survival of 12, 18, and 8 months, respectively, and 1-year overall survival rates of 50.0%, 68.8%, and 5.7%, respectively. Although the survival of patients without liver metastases was worse than that of patients with oligonodular liver metastasis, the result was not significant (P = 0.239). In contrast, the metastasis-negative patients had significantly better survival than did patients with multinodular liver metastases (P < 0.001). Patients with oligonodular liver lesions had a significant longer median survival than did patients with multinodular lesions (P < 0.001). In conclusion, combined minimally invasive therapies had good efficacy on unresectable pancreatic cancer and resulted in a good control of liver metastases. In addition, the number of liver metastases was a significant factor in predicting prognosis and response to treatment.

Nasopharyngeal cancer: impact of skull base invasion on patients prognosis and its potential implications on TNM staging.

PURPOSE: To evaluate patterns of skull base invasion and its possible impact on tumor (T)-staging in nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI). MATERIALS AND METHODS: 838 consecutive newly diagnosed by biopsy proven and untreated patients with NPC underwent MRI. The skull-base invasion of NPC was classified according to their incidence from proximal sites to more distant sites surrounding the nasopharynx as: high (≥35%), medium (≥5-35%), and low (<5%) groups. A retrospective analysis of data consisting of a 5-year follow-up was carried out. The skull base invasion was related to their tumor (T) staging and prognosis at the 5-year follow-up after treatment with definitive radiation therapy. In addition, a survival health-related quality of life (QOL), overall survival (OS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were also assessed among the three groups. RESULTS: The total incidence of skull-base invasion was 65.51% (549/838). The differences in T-stage distribution, and the total survival health-related QOL, among the three groups were statistically significant (χ(2)=160.45, p<0.005; χ(2)=38.43, p<0.005, respectively). The differences between any two of the three groups were also significant, except when the medium grade was compared to the low grade. Significant differences were observed with regard to 5-year OS (83.2%, 74.7%, 59.2%, p=0.000) and DMFS (95.0%, 88.0%, 88.0%, p=0.016); no significant difference was observed in LRFS (95.3%, 95.6%, 91.23%, p=0.450). CONCLUSIONS: The results indicate that medium and low group displayed similar findings of skull base invasion, and survival status. We, therefore, propose that patients in these two groups be grouped under T4 in the TNM classification that might have a bearing in implementing optimum treatment.

Challenges in the modification of the M1 stage of the TNM staging system for nasopharyngeal carcinoma: A study of 1027 cases and review of the literature.

A series of modifications have been introduced to the TNM staging system over time for nasopharyngeal carcinoma (NPC), mainly focused on the T (primary tumor) and N (local node) components of the system. The M1 stage is a 'catch all' classification, covering a group of patients whose outlook ranges from potentially curable to incurable. Since the current M1 stage does not allow clinicians to stratify patients according to prognosis or guide therapeutic decision-making and allow comparison of results of radical and non-radical treatments, we aimed to subdivide the M1 stage according to a retrospective study of 1027 metastatic NPC patients and to review the relevant literature. Between 1995 and 2007, 1027 inpatients with distant metastasis from NPC were retrospectively analyzed. Various possible subdivisions of the M1 stage were considered, looking at different metastatic sites, the number of metastatic organs and the number of metastases. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. The most frequently involved metastatic sites were the bone, lung and liver. The incidence rates of solitary metastatic lesions and pulmonary metastasis were 16.2 and 41.3%. Despite the poor survival of these patients with a median survival of 30.8 months, patients in the metachronous metastatic group with metastases to the lung and/or solitary lesions, were defined as M1a, and were significantly associated with favorable median survival of 41.5 and 49.1 months in the univariate and multivariate analysis, respectively. Patients in the metachronous metastatic group with metastasis to the lung and/or solitary lesions (M1a) have a more favorable prognosis compared with those patients with multiple metastases located in other anatomic sites (M1b). These data, in one of the largest reported metastatic NPC cohorts, are the first to show the prognostic impact of metastatic status in NPC. As a powerful predictor, the potential clinical value of a modified M1 of the TNM system for NPC will facilitate patient counseling and individualize management.

CT-guided radiofrequency ablation after with transarterial chemoembolization in treating unresectable hepatocellular carcinoma with long overall survival improvement.

PURPOSE: To assess the time to disease progression (TTP), long-term survival benefit and safety of patients with unresectable hepatocellular carcinoma (HCC) treated with computed tomography (CT)-guided radiofrequency ablation (RFA) with transarterial chemoembolization chemoembolization (TACE). METHODS: This study was approved by the institutional review board. We reviewed the records of patients with intermediate and advanced HCC treated with CT-guided RFA with TACE between January 2000 and December 2009. Median TTP, overall survival (OS) and hepatic function were analyzed with the Kaplan-Meier method and log-rank tests. RESULTS: One hundred and twenty-two patients (112 men and 10 women, mean age 53 years, range 18-86 years) were included in the study. The median follow-up time was 42 months (range 6-89 months), TTP was 6.8 months, the median OS was 31 months, and the 1-, 3-, and 5-year OS were 88.5%, 41.0%, and 10.7%. The results of the univariate analysis revealed that intrahepatic lesion, AJCC stage, and Child-Pugh stage were predictors of OS (P<0.01). In the multivariate analysis, the AJCC stage system showed a statistically significant difference for prognosis. Procedure-related death was 0.21% (1/470) within 1 month, and a statistical difference was found between the TACE and RFA of liver decompensation and Child-Pugh stage (P<0.05). CONCLUSIONS: The survival probabilities of OS increased with CT-guided RFA with TACE, as observed in randomized studies from Europe and Asia. The longest TTP was observed for the intermediate stage HCC. The procedures were well tolerated with acceptable minor and major complications in unresectable HCC patients.

[Value of CIK in the treatment of TACE combined with RFA for HCC in long-term survival and prognostic analysis].

OBJECTIVE: To assess the long-term efficacy and investigate the prognostic factors of cytokine-induced killer (CIK) combined with the sequential transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC). METHOD: A total of 95 HCC patients with the informed consents received TACE combined with RFA, 48 cases of which accepted the CIK via intravenous drop infusion for more than 6 times (study group) while the other 47 cases were enrolled in control group. The following-up duration was more than 3 years. Primary endpoint was the overall survival (OS) and the secondary endpoint was the disease-free survival (DFS). RESULTS: 76 patients in all (38 in study group, 38 in control group) complied with the study and follow-up (44 months in median, 10-88 months). No mortality and serve complications were observed in both groups. The ratio for patients with DFS over 1-year, 3-year and 5-year were 79%, 26% and 16% (28 months in median and 32.3 months in mean) while 71%, 21% and 8% (22 months in median and 23.1 months in mean) for the control group. There was significant difference between the two groups (P=0.001). For the OS, the ratio for 1-year, 3-year and 5-year in the study group were 92%, 53% and 26% (38 months in median and 42.5 in mean) and 89%, 42% and 24% (35 months in median and 37 in mean). No significant difference was observed in both groups. ECOG performance status, Hepatitis B virus infection and treatment were the prognostic factors for DFS while ECOG performance status was the only prognosis for OS. CONCLUSION: CIK infusion basing on the TACE combined with RFA can control the recurrence of HCC, decrease the times of TACE or RFA.

Magnetic resonance imaging features of nasopharyngeal carcinoma and nasopharyngeal non-Hodgkin's lymphoma: are there differences?

PURPOSE: To describe differences in the primary tumour and distribution of cervical lymphadenopathy for cases of nasopharyngeal carcinoma (NPC) and nasopharyngeal non-Hodgkin's lymphoma (NPNHL) using magnetic resonance (MR) imaging. MATERIALS AND METHODS: MR images of patients with NPC (n = 272) and NPNHL (n = 118) were independently reviewed by two experienced radiologists. RESULTS: NPC had a higher incidence of tumour invasion associated with the levator and tensor muscles of the velum palatine, the longus colli and medial pterygoid muscles, the base of the pterygoid process, the clivus, the base and greater wing of the sphenoid bone, the petrous apex, the foramen lacerum, the foramen ovale, the hypoglossal canal, and intracranial infiltration. In contrast, NPNHL had a higher incidence of tumour invasion associated with the hypopharynx, the palatine and lingual tonsils, as well as the ethmoid and maxillary sinuses. NPNHL also had a higher incidence of extensive and irregular bilateral lymphadenopathy, and lymphadenopathy in the parotid. CONCLUSIONS: NPC more often involved an unsymmetrical tumour with a propensity to invade both widely and deeply into muscle tissue, the fat space, the neural foramen, and the skull base bone. In contrast, NPNHL tended to be a symmetrical and diffuse tumour with a propensity to spread laterally through the fat space and along the mucosa to the tonsils of the oropharynx and hypopharynx. These differences facilitate a differentiation of these diseases using MR images, and enhance our understanding of the biological behavior of these malignant tumours of the nasopharynx.

Comparative survival analysis in patients with pulmonary metastases from nasopharyngeal carcinoma treated with radiofrequency ablation.

PURPOSE: The aim of this retrospective study was to evaluate technical efficacy and the impact of CT-guided pulmonary radiofrequency ablation (RFA) on survival in patients with pulmonary metastases from nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Between 2000 and 2009, 480 patients were pathologically or clinically confirmed pulmonary metastases from NPC. And ten included patients of them had a total of 23 pulmonary metastases treated with percutaneous RFA under the real-time CT fluoroscopy. Safety, local tumor progression, and survival were evaluated in our institutions. Matched-pair survival was compared using Kaplan-Meier analysis. RESULTS: A total of 25 ablations were performed to 23 pulmonary metastases in 13 RFA sessions. Pneumothorax requiring chest tube placement developed in 3 of 13 (23.1%) RFA sessions. The median metastatic overall survival was 36.1 months for all the 480 NPC patients with pulmonary metastases. Furthermore, matched-pair analysis demonstrated patients with RFA treatment had a greater metastatic overall survival than patients without RFA treatment (77.1 months vs 32.4 months, log-rank test, p=0.009). There were no statistically significant differences in the survival probability of patients with RFA treatment (n=10) and surgical resection of pulmonary metastases (n=27) (log-rank test, p=0.75). CONCLUSION: CT-guided pulmonary RFA is safe and offers a treatment alternative for local tumor control, providing promising survival in selected patients with pulmonary metastases from NPC.

[Comparison of safety and efficacy for transcatheter arterial chemoembolization alone and plus radiofrequency ablation in the treatment of single branch portal vein tumor thrombus of hepatocellular carcinoma and their prognosis factors].

OBJECTIVE: To compare the transcatheter arterial chemoembolization (TACE) alone or plus radiofrequency ablation (RFA) in the treatment of single branch portal vein tumor thrombus(PVTT)in patients with hepatocellular carcinoma (HCC) so as to evaluate the safety, control rate, prognostic factors and overall survival. METHODS: From January 2004 to December 2007, 50 HCC patients (< 5 cm in diameter and 3 parenchymal lesions) with concurrent PVTT were enrolled and treated by TACE alone or TACE plus RFA randomly (TACE, n = 25; TACE-RFA, n = 25). In TACE group, the intra-hepatic lesions received TACE sequentially with RFA; in TACE-RFA group, PVTT and intra-hepatic lesions were treated with TACE sequentially with RFA separately. Strict follow-up was conducted by computed tomography and alpha-fetoprotein (AFP) assay. The survival time was analyzed by the Kaplan-Meier method and Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Of all 50 HCC patients with single branch PVTT with TACE or RFA, 47 patients (TACE, n = 24; TACE-RFA, n = 23) received all the scheduled procedures and completed the follow-up. Two patients (8.3%) in TACE group had liver dysfunction versus none in TACE-RFA group, 2 patients (8.7%) developed bile duct injury in TACE-RFA group related with the RFA procedure. The OR (overall response) for PVTT was 54.2% (complete response (CR) 8.3%, partial response (PR) 45.8%) in TACE group while 87.0% (CR 60.9%, PR 26.1%) in TACE-RFA group during the follow-up. From the definite diagnosis of HCC, the median survival was 8 months. And the 1-, 2- & 3-year survival rates were 33.3%, 12.5%, 8.3% in TACE group. And 26 months, 65.2%, 47.8%, 30.4% in TACE-RFA group respectively. The difference between two groups was significant. From the definite diagnosis of PVTT, the respective data were 7 months, 12.5% and 4.2%, 0 in TACE group versus 22 months, 52.2%, 34.8%, and 8.7% in TACE-RFA group with a significant P value. In multivariate analysis, only therapy (TACE or TACE-RFA) showed a protective value (hazard rate 0.430 vs 0.345, P < 0.05). Survival was not correlated with age, intra-hepatic tumor status, liver functions and AFP level for all patients. CONCLUSION: RFA is both safe and efficacious to prolong survival in the treatment of single branch PVTT plus TACE in selected HCC patients. It may provide rationales for further studies of evaluating the outcome of RFA plus other therapies in the treatment of HCC with single branch PVTT.

[Significance and prognostic factors in 84 patients with colorectal liver metastases treated with radiofrequency ablation].

OBJECTIVE: To investigate the prognostic factors and significance of patients with colorectal liver metastases (CLM) treated with radiofrequency ablation (RFA). METHODS: A retrospective study was conducted for the clinic outcomes, follow-up data and survival status in 84 patients with CLM undergoing RFA between January 2000 and December 2008. Univariate and multivariate analyses were performed by log-rank test and Cox's proportional hazard model respectively. RESULTS: A total of 265 lesions in 84 patients received RFA with a follow-up of 1-10 years. The median survival was 29 months, 1-year survival rate 98%, 3-year survival rate 27% and 5-year survival rate 7%. For those lesion < or = 4 cm and lesion number < 3, the median survival time was 30 months, 1-year survival rate 100%, 3-year survival rate 31% and 5-year survival rate 16%. For those with lesions > 4 cm or lesion number > 3, the median survival time was 28 months, 1-year survival rate 96%, 3-year survival rate 21% and 5-year survival rate 0. For those receiving RFA combined with chemotherapy, the median survival time was 32 months, three-year survival rate 29% and five-year survival rate 8%. For those on molecular-target therapy, the median survival time was 41 months, 3-year survival rate 60% and 5-year survival rate 20%. The multivariate statistical analysis showed that the influences of lesion number and size (P = 0.004), chemotherapeutic agents and timing (P = 0.004) and extra-liver metastases (P = 0.097) had statistic significance to the survival rate. CONCLUSIONS: RFA has a favorable outcome in the treatment of CLM patients. The prognostic factors of overall survival are correlated with the lesion size and presence or absence of extra-hepatic metastasis. It may effectively improve the patient prognosis by RFA in combination with chemotherapy and especially molecular-target therapy.