Therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Immune checkpoint inhibitor therapy is the backbone of numerous combination regimens for improving the therapeutic response of patients with hepatocellular carcinoma (HCC). We aimed to investigate the therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable HCC. METHODS: Patients with unresectable HCC who received sorafenib and followed at Taipei Tzu Chi Hospital from January 2016 to May 2022 were selected for this study, and those treated with nivolumab plus sorafenib and those with sorafenib alone were propensity score matched. The primary outcome was overall survival (OS) presented as a hazard ratio calculated using Cox proportional hazards regression models. RESULTS: In the analysis, 36 patients receiving nivolumab plus sorafenib and 36 receiving sorafenib alone were propensity score matched. The median OS for those receiving nivolumab plus sorafenib and sorafenib alone were 3.6 years and 1.2 years, respectively (p = 0.031). The hazard ratio of OS for nivolumab plus sorafenib compared to sorafenib alone was 0.36 (95 %CI, 0.19-0.70; p = 0.003). Furthermore, patients receiving nivolumab plus sorafenib with a baseline α-fetoprotein(AFP) < 10 ng/mL and early reduction in AFP had a 100 % objective response rate and disease control rate. CONCLUSION: In patients with unresectable HCC, nivolumab plus sorafenib resulted in better OS outcomes than sorafenib.

Transarterial chemoembolization with or without sorafenib for hepatocellular carcinoma: A real-world propensity score-matched study.

Objectives: Transarterial chemoembolization (TACE) or sorafenib may prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, whether their combination prolongs survival than TACE alone remains controversial. We aimed to compare the overall survival (OS) of patients with unresectable HCC treated with TACE plus sorafenib (TACE-S) versus TACE alone. Materials and Methods: All patients with unresectable HCC who received TACE as the initial therapy between January 2006 and January 2017 at Taipei Tzu Chi Hospital were enrolled. We matched patients treated with TACE-S and those treated with TACE alone (TACE) by performing propensity score matching at a 1:2 ratio. Our primary outcome was OS during a 10-year follow-up period, and represented as a hazard ratio calculated using Cox proportional hazard regression models. Results: Among 515 patients with unresectable HCC were treated initially with TACE, 56 receiving TACE-S group and 112 receiving TACE alone (TACE group) were included in the primary outcome analysis. The TACE-S group had significantly longer median OS than did the TACE group (1.55 vs. 0.32, years; P < 0.001), and the 5-year OS rates was 10.7% in the TACE-S group and 0.9% in the TACE group (P < 0.001). In multivariate analyses, patients with a lower Child-Pugh score, tumor size ≤5 cm, and no extrahepatic metastasis before treatment and those receiving antiviral agents and receiving TACE-S had longer OS (all P < 0.001). Conclusion: Antiviral agents and the combination of TACE with sorafenib may improve the OS of patients with unresectable HCC.

Radiofrequency ablation versus surgical resection for the treatment of solitary hepatocellular carcinoma 2 cm or smaller: A cohort study in Taiwan.

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) is increasingly being used instead of surgical resection for the treatment of hepatocellular carcinoma (HCC) tumor measuring ≦2 cm. However, the long-term outcomes of RFA, especially in comparison to surgical resection, are still debated. We compared the outcomes of surgical resection and RFA in patients with a solitary HCC tumor measuring ≦2 cm from a 10-year cohort study. METHODS: From Jan 2006 to Dec 2016, 156 patients with a resectable HCC measuring ≦2 cm who underwent surgical resection (n = 83) or RFA (n = 73) at the Buddhist Tzu Chi Medical Foundation were enrolled. Patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were retrospectively examined, and comparisons were made between the two groups and through subgroup analyses. RESULTS: The 1-year, 3-year, 5-year, and 7-year OS outcomes were comparable between the surgical resection group and the RFA group (P = 0.193), but the surgical resection group had significantly higher 1-year, 3-year, 5-year, 7-year, and 10-year RFS than the RFA group (P = 0.018). Multivariate analysis revealed that patients with lower age, Child-Turcotte-Pugh score, or albumin-bilirubin score before treatment had better OS, and patients with an HCV infection or receiving RFA treatment had higher HCC recurrence rates. CONCLUSION: The liver reserve determined the long-term OS of patients with an HCC tumor ≦ 2 cm, and surgical resection offered better RFS than RFA (ClinicalTrials.gov number, NCT04525833.).

Daily activity, mood, and quality of life in colorectal cancer patients with chemotherapy-induced peripheral neuropathy: A mediation effect analysis.

Chemotherapy-induced peripheral neuropathy (CIPN) with restriction of daily activity (RDA) was common consequence of oxaliplatin-based chemotherapy in colorectal cancer patients. CIPN with RDA and negative mood may impact the quality of life (QoL). However, the relationships among RDA, mood, and QoL remain unclear. This was a cross-sectional relative study in which four instruments were used: the Neuropathic Pain Symptom Inventory was used to measure the severity of CIPN; the Screening of Activity Limitation and Safety Awareness scale was used to evaluate RDA; the Profile of Mood States Short Form was used to assess negative mood; and the Functional Assessment Cancer Center Therapy-Colorectal scale version 4 was used to evaluate QoL. Relationships among the variables were analyzed by bivariate correlation, hierarchical multiple linear regression, and Baron and Kenny's mediation testing. One hundred three colorectal adenocarcinoma patients with CIPN after receiving oxaliplatin-based chemotherapy were enrolled. Patients had mild-to-moderate CIPN and mild RDA. Significant correlations were found between CIPN and mood (r = 0.425, P < 0.001), between RDA and mood (r = 0.343, P < 0.001), and between RDA and QoL (r = 0.285, P < 0.01). RDA and mood may impact QoL. Under mediation effect analysis, mood mediated 38.48% of the effect of RDA on QoL (P < 0.001). Negative mood is the major factor impacting QoL in colorectal cancer patients with CIPN. Although the management of CIPN and RDA can prevent irreversible functional problems, enhancing the adaption of mood disturbance can strongly promote their QoL.

Reliability and validity of the Chinese version neuropathic pain symptom inventory in patients with colorectal cancer.

BACKGROUND/PURPOSE: Chemotherapy-induced peripheral neuropathy is a common consequence of chemotherapeutic treatments in patients with cancer. This study evaluated the validity and reliability of a Chinese version of the Neuropathic Pain Symptom Inventory (C-NPSI) in patients with colorectal cancer and chemotherapy-induced peripheral neuropathy. METHODS: This cross-sectional study recruited 106 patients from a cancer center in Northern Taiwan. The C-NPSI was obtained through the translation and back-translation of the original NPSI. Content validity was evaluated by 10 experts. Internal consistency reliability was assessed through Pearson correlation analysis. Construct validity was conducted by confirmed factor analysis. Convergent validity was examined using the Chinese version of Profile of Mood States-Short Form (POMS-SF). RESULTS: The item-level and average scale-level content validity indices were 0.80 and 0.90, respectively. Internal consistency reliability was acceptable (Cronbach's α coefficient = 0.9). A parsimonious goodness-of-fit model was supported by the normed chi-square (x2/df = 2.74), root mean square error of approximation (RMSEA; 0.10) and root mean square error with respect to the mean (RMSEM; 0.126, 90% confidence interval [CI], 0.093-0.16); partial indices were acceptable (goodness-of-fit index [GFI] = 0.90; comparative fit index [CFI] = 0.89; incremental fit index [IFI] = 0.90). Additional model modifications demonstrated goodness of fit (x2/df = 1.78; RMSEA = 0.08; RMSEM = 0.085, 90% CI, 0.041-0.12; GFI = 0.92; CFI = 0.96; IFI = 0.96). Convergent validity showed most coefficients between the C-NPSI and POMS-SF Chinese version have a significant positive correlation (p < 0.05-0.005). CONCLUSION: The C-NPSI has satisfactory reliability and validity. Clinicians and physician can use it to evaluate and manage oxaliplatin-induced peripheral neuropathy.

NKX6.1 hypermethylation predicts the outcome of stage II colorectal cancer patients undergoing chemotherapy.

Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the same stage often present with dramatically different clinical scenarios. Thus, robust prognostic biomarkers are urgently needed to guide therapies and improve treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation marker in cervical cancer, functioning as a metastasis suppressor by regulating epithelial-mesenchymal transition. Here, we investigated whether hypermethylation of NKX6.1 might be a prognostic biomarker for CRC. By analyzing the methylation and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using methylation-specific polymerase chain reaction analysis and found that NKX6.1 was hypermethylated in 35 of 151 CRC tissues (23%). NKX6.1 gene expression was inversely correlated with the DNA methylation level in CRC cell lines in vitro. Then, we analyzed the association of NKX6.1 methylation with clinical characteristics of these CRC patients. Our data demonstrated that patients with NKX6.1 methylation presented poorer 5-year overall survival (P = 0.0167) and disease-free survival (P = 0.0083) than patients without NKX6.1 methylation after receiving adjuvant chemotherapy. Most importantly, these data revealed that stage II CRC patients with NKX6.1 methylation had poorer 5-year disease-free survival (P = 0.0322) than patients without NKX6.1 methylation after adjuvant chemotherapy. Our results demonstrate that methylation of NKX6.1 is a novel prognostic biomarker in CRC and that it may be used as a predictor of the response to chemotherapy.