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.

Correction: Systemic Delivery of MicroRNA-101 Potently Inhibits Hepatocellular Carcinoma In Vivo by Repressing Multiple Targets.

[This corrects the article DOI: 10.1371/journal.pgen.1004873.].

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.

Radiofrequency Ablation Following Downstaging of Hepatocellular Carcinoma by Using Transarterial Chemoembolization: Long-term Outcomes.

Background Transarterial chemoembolization (TACE) is an effective downstaging procedure for hepatocellular carcinoma (HCC). However, knowledge of the effectiveness of radiofrequency ablation (RFA) after downstaging of HCC is currently lacking. Purpose To evaluate the clinical outcomes of RFA after downstaging of HCC by using TACE. Materials and Methods This retrospective study investigated a cohort of patients who underwent RFA with curative intent after downstaging with TACE to meet Milan criteria (one lesion up to 5 cm or no more than three lesions ≤3 cm without vascular invasion or extrahepatic metastasis) from January 2012 to July 2017. A control group of patients initially meeting the Milan criteria also underwent RFA as first-line treatment in the same period. Overall survival (OS), disease-free survival (DFS), and major complication rates were compared by using the log-rank test. To reduce potential bias, a propensity score analysis was also performed. Results There were 72 patients (median age, 56.5 years; range, 30-78 years; 67 men) in the downstaging group and 357 patients meeting the Milan criteria (median age, 58.0 years; range, 25-87 years; 313 men) included in this study. After propensity score matching, the 1-, 3-, and 5-year OS rates were 99%, 80%, and 66%, respectively, for the patients in the downstaging group and 94%, 84%, and 69%, respectively, for the patients in the Milan criteria group. The 1-, 3-, and 5-year DFS rate were 73%, 34%, and 24% for the downstaging group and 74%, 43%, and 37% for the Milan criteria group. There were no differences in the OS, DFS, or major complication rates between the two groups (P = .74, P = .39, P = .73, respectively). Conclusion The long-term patient survival and major complication rates of radiofrequency ablation following transarterial chemoembolization downstaging for hepatocellular carcinoma were similar to that of patients initially meeting the Milan criteria. © RSNA, 2019 See also the editorial by vanSonnenberg and Mueller in this issue.

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.

TFAP4 Promotes Hepatocellular Carcinoma Invasion and Metastasis via Activating the PI3K/AKT Signaling Pathway.

Transcription factor activating enhancer binding protein 4 (TFAP4) is established as a regulator of human cancer genesis and progression. Overexpression of TFAP4 indicates poor prognosis in various malignancies. The current study was performed to quantify TFAP4 expression as well as to further determine its potential prognostic value and functional role in patients with hepatocellular carcinoma (HCC). We identified that the expression of TFAP4 mRNA in 369 tumor tissues was higher than that in 160 normal liver tissues. Upregulated TFAP4 expressions were discovered in HCC cell lines compared to the healthy liver cell line, and similarly, the levels of TFAP4 were higher in tumor tissues than its expression in paratumor tissues. High mRNA and protein expression of TFAP4 was associated with worse overall survival (OS) and disease-free survival (DFS). Additionally, TFAP4 expression emerged as a risk factor independently affecting both OS and DFS of HCC patients. Functional studies demonstrated that TFAP4 increased HCC cell migration and invasion. Further investigations found that TFAP4 promotes invasion and metastasis by inducing epithelial-mesenchymal transition (EMT) and regulating MMP-9 expression via activating the PI3K/AKT signaling pathway in HCC. In conclusion, our study demonstrated that TFAP4 is a valuable prognostic biomarker in determining the likelihood of tumor metastasis and recurrence, as well as the long-term survival rates of HCC patients. Exploring the regulatory mechanism of TFAP4 will also contribute to the development of new prevention and treatment strategies for HCC.

A Prognostic Score for Nasopharyngeal Carcinoma with Bone Metastasis: Development and Validation from Multicenter.

Background: To establish a prognostic score based on clinical routine factors to stratify nasopharyngeal carcinoma patients with bone metastasis into risk groups with different survival rates. Materials and Methods: Total 276 patients from multicenter were retrospectively analyzed. Kaplan-Meier method and Cox regression were used to confirm independent risk factors, which were checked for internal validity by bootstrapping method. The prognostic score, deriving from the corresponding regression coefficients in Cox model, classified patients into low and high risk groups. Finally, two independent cohorts were used for external validation. Results: In development cohort, six risk factors were identified: age>46 year-old (point=1), N>0 stage (point=2), anemia (point=2), bone metastasis free interval≤12 months (point=1), without radiotherapy to primary sites (point=1), and without radiotherapy to first metastasis sites (point=1). The derived prognostic score divided patients into low (score, 0-4) and high (score, 5-8) risk groups, with highly significant differences of 5-year overall survival rates (high vs. low risk: 24.6% vs. 58.2%, HR 3.47, P<0.001). Two external validations presented congruent results. Conclusion: A feasible and applicative prognostic score was successfully established and validated to discriminate bone metastatic nasopharyngeal carcinoma into low/high risk groups, which will be useful for individual treatment.

Percutaneous CT-guided Radiofrequency Ablation for Lymph Node Oligometastases from Hepatocellular Carcinoma: A Propensity Score-matching Analysis.

Purpose To assess the effectiveness and safety of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for lymph node (LN) oligometastases from hepatocellular carcinoma (HCC). Materials and Methods This retrospective study was approved by the institutional ethics committee, and all patients provided written informed consent. From January 2004 to December 2013, 119 consecutive patients with HCC and LN oligometastases (115 men [mean age, 51.3 years; age range, 16-83 years] and four women [mean age, 38.2 years; age range, 23-47 years]) were included in this study. A matched cohort composed of 46 patients from each group was selected after adjustment with propensity score matching. The median follow-up time was 14.0 months in the RFA group and 13.8 months in the non-RFA group. The overall survival (OS), local control rate, and complications were evaluated. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results Eighty-seven patients had LN metastases located in the regional site, and 32 patients had LN metastases in the distant site. No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. The RFA group showed higher 6-month and 1-year OS rates compared with the non-RFA group (87.0% and 58.3% vs 62.4% and 17.9%, respectively; P = .001). The 3-month local control rate after RFA was 84.4%, including complete response in 71.1% of patients and partial response in 13.3%. The complications of RFA were short-term abdominal pain and self-limited local hematoma, which occurred in 10 patients (21.7%) and five patients (10.9%), respectively. Conclusion Percutaneous CT-guided RFA may be a safe and effective treatment for the LN oligometastases generated by HCC. © RSNA, 2016.

Overweight/obese status associates with favorable outcome in patients with metastatic nasopharyngeal carcinoma: a 10-year retrospective study.

BACKGROUND: Although the prognostic impact of body mass index (BMI) in patients with non-metastatic nasopharyngeal carcinoma (NPC) had been extensively studied, its effect among metastatic NPC patients remains unknown. The purpose of this study was to evaluate the prognostic effect of BMI in patients with metastatic NPC. METHODS: We retrospectively studied 819 patients who were diagnosed with distant metastasis from NPC and received treatment between 1998 and 2007. The patients were divided into three subgroups according to the World Health Organization classifications for Asian populations: underweight (BMI <18.5 kg/m(2)), normal weight (BMI 18.5-22.9 kg/m(2)), and overweight/obese (BMI ≥23.0 kg/m(2)). The associations of BMI with overall survival (OS) and progression-free survival (PFS) were determined by Cox regression analysis. RESULTS: Of the 819 patients, 168 (20.5%) were underweight, 431 (52.6%) were normal weight, and 220 (26.9%) were overweight/obese. Multivariate analysis adjusted for covariates showed that overweight/obese patients had a longer OS than underweight patients [hazard ratio (HR), 0.64; 95% confidence interval (CI), 0.49-0.84] and normal weight patients (HR, 0.72; 95% CI, 0.57-0.90); no significant difference in PFS was observed among these three groups (P = 0.407). Moreover, in stratified analysis, no statistically significant differences in the effect of overweight/obese status among different subgroups were observed. CONCLUSION: For patients with metastatic NPC, overweight/obese status was associated with longer OS but not longer PFS compared with underweight or normal weight status.

Chemolipiodolization with or without embolization in transcatheter arterial chemoembolization combined with radiofrequency ablation for hepatocellular carcinoma-propensity score matching analysis.

To retrospectively compare the outcome of chemolipiodolization with or without embolization in transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in Patients with hepatocellular carcinoma (HCC) within the Milan criteria. From August 2002 to December 2014, 112 patients (median age, 56.7 years; age range, 22-80 years; 97 men, 15 women) underwent TACE with gelatin sponge particle embolization, and 125 patients (median age, 56.6 years; age range, 23-82 years; 109 men, 16 women) underwent TACE without embolization. RFA was performed within 2 weeks after the TACE. Cumulative overall survival (OS) and disease-free survival (DFS) rates were compared before and after propensity score matching. Before matching, the 1-, 3-, and 5-year OS rate were 96%, 80%, and 62% for embolization group and 94%, 76%, and 59% for non-embolization group . The 1-, 3-, and 5-year DFS rate were 77%, 38%, and 30% for embolization group and 75%, 35%, and 26% for non-embolization group. After matching, the 1-, 3-, and 5-year OS rate were 97%, 82%, and 62% for embolization group and 92%, 74%, and 56% for non-embolization group. The 1-, 3-, and 5-year DFS rate were 79%, 36%, and 30% for embolization group and 74%, 33%, and 26% for non-embolization group. There were no significant difference in OS and DFS rates between the two groups before matching (P =0.999 and P =0.654) and after matching (P =0.951 and P =0.670). In conclusion, embolization in TACE combined with RFA could not improve the survival for patients with HCC within the Milan criteria.

Nomograms for predicting long-term survival in patients with non-metastatic nasopharyngeal carcinoma in an endemic area.

PURPOSE: Nomogram for predicting more than a 5-year survival for non-metastatic nasopharyngeal carcinoma (NPC) was lacking. This study aimed to develop the new nomograms to predict long-term survival in these patients. RESULTS: The median follow-up time for training set and test set was 95.2 months and 133.3 months, respectively. The significant predictors for death were age, gender, body mass index (BMI), T stage, N stage, lactate dehydrogenase (LDH), and radiotherapy techniques. For predicting recurrence, age, gender, T stage, LDH, and radiotherapy techniques were significant predictors, whereas age, gender, BMI, T stage, N stage and LDH were significant predictors for distant metastasis. The calibration curves showed the good agreements between nomogram-predicted and actual survival. The c-indices for predicting death, recurrence, and distant metastases between nomograms and the TNM staging system were 0.767 VS.0.686 (P<0.001), 0.655 VS.0.585 (P<0.001), and 0.881 VS.0.754 (P<0.001), respectively. These results were further confirmed in the test set. METHODS: On the basis of a retrospective study of 1593 patients (training set) who received radiotherapy alone or concurrent chemoradiotherapy from 2000 to 2004, significant predictors were identified and incorporated to build the nomograms. The calibration curves of nomogram-predicted survival versus the actual survival were plotted and reviewed. Bootstrap validation was performed to calculate the concordance index (c-index). These models were further validated in an independent prospective trial (test set, n=400). CONCLUSION: The established nomograms suggest more-accurate long-term prediction for patients with non-metastatic NPC.

Critical weight loss predicts poor prognosis in nasopharyngeal carcinoma.

BACKGROUND: The impacts of weight loss on prognosis in nasopharyngeal carcinoma (NPC) remain unclear. The present study was therefore undertaken to investigate the association between critical weight loss and long-term survival in NPC patients. METHODS: The eligible 2399 NPC patients were reviewed. Weight change was categorized into critical weight loss (CWL) and non-critical weight loss (Non-CWL). The associations of CWL with long-term survival were analyzed by Cox regression in the entire patient and two subsets. Propensity score matching was performed to reduce the effects of confounding factors. RESULTS: CWL was defined as body weight loss of ≥4.6 %. Compared with patients without CWL, patients with CWL had significantly lower 5-year OS (72.4 vs. 79.3 %, P < 0.001), FFS (71.1 vs. 78.4 %, P <0.001), and LR-FFS (78.1 vs. 84.8 %, P <0.001), respectively. After adjustment for potential confounders, CWL remained an independence prognostic factor for OS (HR = 1.352; 95 % CI 1.160-1.576; P < 0.001), FFS (HR = 3.275; 95 % CI 1.101-9.740; P = 0.033), and LR-FFS (HR = 6.620; 95 % CI 2.990-14.658; P < 0.001), respectively. Furthermore, subgroup analysis in the cohort of patients received concurrent chemoradiotherapy or radiotherapy alone confirmed the results in the entire patient even after the propensity-score matching. In IMRT cohort, CWL was also significantly associated with a lower OS (P = 0.04) and FFS (P = 0.04). CONCLUSIONS: CWL has a significant and independent impact on long-term survival in nasopharyngeal carcinoma patients.

The effects of hemoglobin levels and their interactions with cigarette smoking on survival in nasopharyngeal carcinoma patients.

There is very little published information regarding the prognostic value of hemoglobin (Hb) levels combined with smoking on the survival of patients with nasopharyngeal carcinoma (NPC), and the interactions between them remain unclear. A total of 2440 NPC patients were confirmed, and multivariate analysis was performed to identify valuable prognostic Hb levels in the entire population and in the cohort of smokers. The survival differences were compared using log-rank tests. The multiplicative and additive interactions were assessed using Cox regression and a Microsoft Word Excel spreadsheet. Postradiotherapy (RT) Hb was an independent prognostic factor for overall survival (OS) (HR = 0.797; P = 0.006), failure-free survival (FFS) (HR=0.811; P = 0.010), and loco-regional failure-free survival (LR-FFS) (HR = 0.725; P = 0.000). In the cohort of smokers, pack-years was also an independent predictor of OS (HR = 0.673; P < 0.001) and FFS (HR = 0.681; P < 0.001), LR-FFS (HR = 0.663; P = 0.001). A significant positive additive effect was found for the interaction between low post-RT Hb and high SI on OS, with RERI = 5.616, AP = 0.665, and S = 4.078. Stratified analyses demonstrated that heavy smokers with low post-RT Hb had HRs of 2.295 (P < 0.001) for death, 2.222 (P < 0.001) for disease failure, and 2.267 (P < 0.001) loco-regional recurrence compared with light smokers with high post-RT Hb levels, and post-RT Hb level is an important predictor of survival in patients with NPC. The positive interaction between post-RT Hb level and pack-years contributes to the elevated risk of poor survival. Oncologists should devote particular attention to heavy smokers with low post-RT Hb levels in the future.

The utility of breast cone-beam computed tomography, ultrasound, and digital mammography for detecting malignant breast tumors: A prospective study with 212 patients.

PURPOSE: Breast cone-beam computed tomography (BCBCT) is a flat-panel detector (FPD)-based X-ray imaging system that provides high-quality images of the breast. The purpose of this study was to investigate the ability to detect breast abnormalities using non-contrast BCBCT and contrast-enhanced BCBCT (BCBCT and CE-BCBCT) compared to ultrasound (US) and digital mammography (MG). MATERIALS AND METHODS: A prospective study was performed from May 2012 to August 2014. Ninety-two patients (172 lesions) underwent BCBCT alone, and 120 patients (270 lesions) underwent BCBCT and CE-BCBCT, all the patients underwent US and MG. RESULTS: Cancer diagnosis was confirmed pathologically in 102 patients (110 lesions). BCBCT identified 97 of 110 malignant lesions, whereas 93 malignant lesions were identified using MG and US. The areas under the receiver operating curves (AUCs) for breast cancer diagnosis were 0.861 (BCBCT), 0.856 (US), and 0.829 (MG). CE-BCBCT improved cancer diagnostic sensitivity by 20.3% (78.4-98.7%). The AUC values were 0.869 (CE-BCBCT), 0.846 (BCBCT), 0.834 (US), and 0.782 (MG). CONCLUSION: In this preliminary study, BCBCT was found to accurately identify malignant breast lesions in a diagnostic setting. CE-BCBCT provided additional information and improved cancer diagnosis in style c or d breasts compared to the use of BCBCT, US, or MG alone.

Subdivision of M category for nasopharyngeal carcinoma with synchronous metastasis: time to expand the M categorization system.

INTRODUCTION: The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a "catch-all" classification, covering a heterogeneous group of tumors ranging from potentially curable to incurable. The aim of this study was to design an M categorization system that could be applied in planning the treatment of NPC with synchronous metastasis. METHODS: A total of 505 NPC patients diagnosed with synchronous metastasis at Sun Yat-sen University Cancer Center between 2000 and 2009 were involved. The associations of clinical variables, metastatic features, and a proposed M categorization system with overall survival (OS) were determined by using Cox regression model. RESULTS: Multivariate analysis showed that Union for International Cancer Control (UICC) N category (N1-3/N0), number of metastatic lesions (multiple/single), liver involvement (yes/no), radiotherapy to primary tumor (yes/no), and cycles of chemotherapy (>4/≤4) were independent prognostic factors for OS. We defined the following subcategories based on liver involvement and the number of metastatic lesions: M1a, single lesion confined to an isolated organ or location except the liver; M1b, single lesion in the liver and/or multiple lesions in any organs or locations except the liver; and M1c, multiple lesions in the liver. Of the 505 cases, 74 (14.7%) were classified as M1a, 296 (58.6%) as M1b, 134 (26.5%) as M1c, and 1 was not specified. The three M1 subcategories showed significant difference in OS [M1b vs. M1a, hazard ratio (HR) = 1.69, 95% confidence interval (CI) = 1.16-2.48, P = 0.007; M1c vs. M1a, HR = 2.64, 95% CI = 1.75-3.98, P < 0.001]. CONCLUSIONS: We developed an M categorization system based on the independent factors related to the prognosis of patients with metastatic NPC. This system may be helpful to further optimize individualized care for NPC patients.

Transcatheter arterial chemoembolization combined with CT-guided percutaneous thermal ablation versus hepatectomy in the treatment of hepatocellular carcinoma.

INTRODUCTION: Transcatheter arterial chemoembolization (TACE) plus thermal ablation has been widely used recently in the treatment of hepatocellular carcinoma (HCC). In this study, we aimed to compare results of the combination of TACE and percutaneous thermal ablation with those of hepatectomy in patients with HCC. METHODS: The clinical data of 137 HCC patients who sequentially received TACE and computed tomography (CT)-guided percutaneous thermal ablation as an initial curative treatment (combination group) and 148 matched HCC patients who received hepatectomy (surgery group) between 2004 and 2011 were collected and analyzed. After TACE, multiphase contrast-enhanced CT was performed to identify the total number of tumors as well as lipiodol deposition in the liver. Survival was calculated by using the Kaplan-Meier method and compared by using the log-rank test. The prognostic factors were assessed with multivariate Cox proportional hazards regression analysis. RESULTS: Of all 285 patients, 225 (79.0%) had cancerous lesions≤5 cm in diameter. In preoperative contrast-enhanced CT or magnetic resonance imaging, the number of tumors was 1-4 for each patient. The 1-, 3-, and 5-year overall survival rates were 95, 74%, and 67% in the combination group and 88, 66, and 47% in the surgery group, respectively (P=0.004); the corresponding recurrence-free survival rates for the two groups were 92, 69, and 61% and 75, 58, and 44%, respectively (P=0.001). In the multivariate analysis, treatment allocation was an independent prognostic factor for survival. Only 60 patients in the combination group had sufficient imaging data, and 135 new lesions with lipiodol deposition were diagnosed as malignancies in 22 of 60 patients, whereas 20 new lesions were found in 11 of 148 patients in the surgery group. CONCLUSION: The combination of TACE and CT-guided percutaneous thermal ablation for HCC improves survival of HCC patients compared with hepatectomy.

Ten-year outcomes of a randomised trial for locoregionally advanced nasopharyngeal carcinoma: A single-institution experience from an endemic area.

OBJECTIVE: We previously reported the five-year results of a randomised trial that compared induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) with induction chemotherapy plus radiotherapy (IC+RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was to report the ten-year results and to explore potential prognostic factors. METHODS: From August 2002 to April 2005, 408 patients with locoregionally advanced NPC were randomly assigned to receive either IC (carboplatin and floxuridine)+CCRT (carboplatin) or IC+RT. The survival rates were analysed using the Kaplan-Meier method and compared using the log-rank test. Multivariable analysis was performed to identify valuable prognostic factors. RESULTS: The ten-year overall survival, failure-free survival, locoregional failure-free survival and distant failure-free survival rates for the entire patient cohort were 49.5%, 48.0%, 80.8% and 66.9%, respectively. No significant survival differences were found between the IC+CCRT and IC+RT arms. By 3 years from the date of randomisation, 62.5% of the relapses had been detected; no recurrence occurred after 8 years. Within 3 years after randomisation, 77.0% of the metastases were detected; 0.8% was identified after 8 years. Age, Union for International Cancer Control (UICC) N-stage, serum lactate dehydrogenase (LDH) and body mass index (BMI) were independent prognostic factors that predicted death. Smoking status and total radiotherapy dose were independent prognostic factors that predicted locoregional recurrence. UICC N-stage, LDH and BMI were independent prognostic factors that predicted distant metastasis. CONCLUSIONS: Concurrent carboplatin chemotherapy did not significantly improve the long-term survival after inductive carboplatin and floxuridine chemotherapy in locoregionally advanced nasopharyngeal carcinoma. In addition to patient and tumour characteristics, LDH, BMI and smoking status were important baseline prognostic factors for tumour recurrence or distant metastasis; these are worthy of further prognostic investigation in future studies.

Anomalous gray matter structural networks in patients with hepatitis B virus-related cirrhosis without overt hepatic encephalopathy.

BACKGROUND AND PURPOSE: Increasing evidence suggests that cirrhosis may affect the connectivity among different brain regions in patients before overt hepatic encephalopathy (OHE) occurs. However, there has been no study investigating the structural reorganization of these altered connections at the network level. The primary focus of this study was to investigate the abnormal topological organization of the structural network in patients with hepatitis B virus-related cirrhosis (HBV-RC) without OHE using structural MRI. METHODS: Using graph theoretical analysis, we compared the global and regional topological properties of gray matter structural networks between 28 patients with HBV-RC without OHE and 30 age-, sex- and education-matched healthy controls. The structural correlation networks were constructed for the two groups based on measures of gray matter volume. RESULTS: The brain network of the HBV-RC group exhibited a significant decrease in the clustering coefficient and reduced small-worldness at the global level across a range of network densities. Regionally, brain areas with altered nodal degree/betweenness centrality were observed predominantly in association cortices (frontal and temporal regions) (p < 0.05, uncorrected), including a significantly decreased nodal degree in the inferior temporal gyrus (p < 0.001, uncorrected). Furthermore, the HBV-RC group exhibited a loss of association hubs and the emergence of an increased number of non-association hubs compared with the healthy controls. CONCLUSION: The results of this large-scale gray matter structural network study suggest reduced topological organization efficiency in patients with HBV-RC without OHE. Our findings provide new insight concerning the mechanisms of neurobiological reorganization in the HBV-RC brain from a network perspective.

A matched cohort study of standard chemo-radiotherapy versus radiotherapy alone in elderly nasopharyngeal carcinoma patients.

The impact of standard chemo-radiotherapy (CRT) as preferred therapy for elderly patients (age≥60 years) with nasopharyngeal carcinoma (NPC) remains unclear. Therefore, a strict matched cohort study was conducted to compare the survival and treatment toxicity of standard chemo-radiotherapy in the elderly NPC patients with those of radiotherapy (RT) alone. From 1998 to 2003, total 498 newly diagnosed elderly non-metastatic NPC patients were abstracted and classified into two groups by the treatments they received. For each patient in the CRT group, a matched pair in RT group was identified by matching for gender, age, histological type, T and N classifications, RT dose to primary tumor and neck nodes, and days of radiotherapy. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared between the two groups. Two groups were well balanced in clinical characteristics because of the strict matching conditions. Totally 87 pairs can be assessed according to the criteria. The 5-year OS, CSS, FFS, and LR-FFS for CRT and RT groups were 62% versus 40% (P=0.013), 67% versus 47% (P=0.018), 65% versus 53% (log-rank: P=0.064, Breslow: P=0.048), and 88% versus 72%, (P=0.019), respectively. There was no significant difference in 5-year D-FFS between the two groups (75% vs. 73%, P=0.456). The CRT group experienced significantly more Grade ≥3 acute mucositis (46.0% vs. 28.7%, P= 0.019). We concluded that standard chemo-radiotherapy can achieve a reasonable local and regional control in elderly NPC patients with acceptable and reversible acute toxicity. However, distant metastasis remains the dominant failure pattern. When the elderly NPC patients are in good performance status following a complete evaluation of overall functional status and comorbidity conditions, standard chemo-radiotherapy is worthy of recommendation.