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Introduction: Combination immunotherapy is widely used in clinical practice as the first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, predictive factors associated with long-term response to combination immunotherapy have not been well investigated. Herein, we compared the clinical findings, including systemic inflammatory nutritional biomarkers, between responders and nonresponders to combination immunotherapy. In addition, we investigated the predictive factors associated with long-term response to combination immunotherapy. Methods: This study included a total of 112 previously untreated advanced NSCLC patients who received combination immunotherapy at eight institutions in Nagano prefecture between December 2018 and April 2021. The responders were defined as those who achieved progression-free survival for 9 months or longer with combined immunotherapy. We evaluated predictive factors associated with long-term response, and the favorable prognostic predictors associated with overall survival (OS) using statistical analyses. Results: The responder and nonresponder groups included 54 and 58 patients, respectively. Compared with the nonresponder group, the responder group had significantly younger age (p = 0.046), higher prognostic nutritional index (44.8 vs. 40.7, p = 0.010), lower C-reactive protein/albumin ratio (CAR) (0.17 vs. 0.67, p = 0.001), and a higher rate of complete plus partial response (83.3% vs. 34.5%, p < 0.001). The area under the curve and optimal cut-off value for CAR were 0.691 and 0.215, respectively. The CAR and best objective response were identified as independent favorable prognostic predictors associated with OS in the multivariate analyses. Conclusion: The CAR and best objective response were suggested to be useful predictors of long-term response in NSCLC patients who received combination immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Anti-HER2 monoclonal antibody is associated with a greater risk of heart failure (HF) in female breast cancer patients. In recent years, the indication of anti-HER2 monoclonal antibodies was further expanded to stomach, colorectal, and salivary gland cancers regardless of sex in Japan. However, there have been no data on sex difference in the risk of HF after the anti-HER2 monoclonal antibody treatment. Objectives: We compared the risk of HF between male and female cancer patients treated with anti-HER2 monoclonal antibody using a nationwide population-based database. Method: We analyzed 4,608 cancer patients (230 men, median age; 52 years, breast cancer; 4,333) treated with HER2 monoclonal antibody enrolled in the JMDC Claims Database. The primary outcome was the incidence of HF. Results: Over a mean follow-up of 917 ± 835 days, 559 HF events were documented. Kaplan-Meier curves showed no significant difference in the incidence of HF between men and women. Multivariable Cox regression analysis showed that male sex was not associated with a risk of HF compared with women (HR, 0.76; 95% CI: 0.39–1.49). Conclusions: Our analysis of a nationwide population-based database firstly revealed that no significant sex difference existed in the risk of HF among cancer patients treated with anti-HER2 monoclonal antibody. Our findings suggest that the use of anti-HER2 monoclonal antibodies in male patients may be associated with similar risks observed in female patients. [ABSTRACT FROM AUTHOR]

Introduction: We investigated whether the expression of prospero homeobox protein-1 (PROX1) in gastric cancer (GC) could be a prognostic marker. We also focused on the relationship between PROX1 and LGR5 and Wnt/β-catenin activity in GC. Methods: A total of 196 patients who underwent potentially curative surgery were collected and reviewed retrospectively. Immunohistochemistry was conducted and evaluated the expression PROX1, LGR5, Wnt3a, and β-catenin expression. And we evaluated the relationship between PROX1 expression and clinicopathological features. Results: The PROX1 low-expression group consisted of 105 patients (53.6%) and the high-expression group consisted of 91 patients (46.4%). For LGR5 expression, 76 patients (38.8%) were classified as low-expression, and 120 patients (61.2%) were classified as high-expression. The PROX1 low-expression group was significantly younger (p = 0.0095), had more intestinal type (p = 0.014), and had smaller tumor size (p = 0.013). The PROX1 high-expression group was significantly correlated with high LGR5 expression (p < 0.0001) and high Wnt3a expression (p = 0.012). In addition, there were significantly more cases of postoperative recurrence in the PROX1 high-expression group (p = 0.013). Conclusion: Our findings demonstrate that PROX1 correlated with the cancer stemness markers LGR5 and Wnt3a signaling in GC and had a poor prognosis including postoperative recurrence. [ABSTRACT FROM AUTHOR]

Background: It is unclear for whom new anti-human epidermal growth factor receptor 2 (anti-HER2) agents, such as pertuzumab and T-DM1, should be considered. We investigated prognostic factors before neoadjuvant chemotherapy (NAC) among HER2-positive invasive breast cancer patients and those after NAC among patients who did not achieve pathological complete response (pCR) using conventional adjuvant trastuzumab. Methods: HER2-positive primary breast cancer patients treated using NAC containing trastuzumab were enrolled between September 2006 and June 2017 at the Osaka Breast Clinic. Patients with distant metastasis or using NAC containing pertuzumab were excluded. The main outcome was disease-free survival (DFS). We investigated pre- and post-NAC prognostic factors using the log-rank test and Cox proportional hazards model. Results: In total, 157 patients were included. Among the pre-NAC prognostic factors, younger age (under 40 years old) and positive clinical nodal status were significantly poorer prognostic factors (hazard ratio [HR] 3.47, 95% CI 1.06–10.12, p = 0.041 and HR 3.32, 95% CI 1.03–14.78, p = 0.045) by multivariate analysis. Among the post-NAC prognostic factors, patients with non-pCR (3-year DFS; 85 vs. 96%, p = 0.022) had a poorer DFS than patients with pCR. DFS was assessed for non-pCR patients (n = 64). High post-NAC Ki-67 status (≥20%; HR 6.73, 95% CI 1.82–31.93, p = 0.004) was a significant and large post-NAC tumor size (≥2 cm; HR 3.65, 95% CI 0.97–14.71, p = 0.056) was a marginally significant prognostic factor by multivariate analysis. After having combined them, high post-NAC Ki-67 status or large post-NAC tumor size was also a significant prognostic factor (HR 5.75, 95% CI 1.32–16.12, p = 0.017). Conclusions: Positive clinical nodal status and young age were found to be prognostic factors before NAC in HER2-postive invasive breast cancer patients. A high post-NAC Ki-67 status and large post-NAC tumor size were significant and marginally significant prognostic factors, respectively, after NAC in patients who did not achieve pCR. New anti-HER2 agents, such as pertuzumab and T-DM1, should be considered for the patients with those prognostic factors. [ABSTRACT FROM AUTHOR]

Objectives: Radiofrequency ablation plays a key role in the treatment of early-stage hepatocellular carcinoma. However, it is not recommended for intermediate-stage hepatocellular carcinoma. The objective of this study was to clarify the efficacy and safety of radiofrequency ablation for treating intermediate-stage hepatocellular carcinoma. Methods: We examined the outcome of 65 consecutive patients who were treated with radiofrequency ablation with or without transarterial chemoembolization for intermediate-stage hepatocellular carcinoma. Results: With a median follow-up of 37 months, overall survival rates of 65 cases at 1, 3, 5, and 7 years were 90, 70, 51, and 36%, respectively. Multivariate analysis of clinical parameters revealed that the multicentric occurrence (MC)/intrahepatic metastasis (IM) was the only significant prognostic factor for overall survival (hazard ratio, 4.9; 95% confidence intervals, 2.1-11.4). Tumor size and tumor number were not significant factors for survival. The overall survival rates of patients with MC (n = 33) at 1, 3, 5, and 7 years were 97, 90, 80, and 59%, respectively; those for patients with IM (n = 32) were 86, 55, 14, and 8%, respectively (p < 0.0001). Two cases (4.9%) had complications of hemothorax and diaphragmatic burn; however, no major complications were observed. Conclusion: Radiofrequency ablation is safe and effective for the treatment of intermediate-stage hepatocellular carcinoma, especially for patients with MC. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objecitive: Fucosyltransferase 8 (FUT8), the only enzyme responsible for the core α1,6-fucosylation of asparagine-linked oligosaccharides of glycoproteins, is a vital enzyme in cancer development and progression. We examined FUT8 expression in non-small cell lung cancers (NSCLCs) to analyze its clinical significance. We also examined the expression of guanosine diphosphate-mannose-4,6-dehydratase (GMD), which is imperative for the synthesis of fucosylated oligosaccharides. Methods: Using immunohistochemistry, we evaluated the expression of FUT8 and GMD in relation to patient survival and prognosis in potentially curatively resected NSCLCs. Results: High expression of FUT8 was found in 67 of 129 NSCLCs (51.9%) and was significantly found in non-squamous cell carcinomas (p = 0.008). High expression of FUT8 was associated with poor survival (p = 0.03) and was also a significant and independent unfavorable prognostic factor in patients with potentially curatively resected NSCLCs (p = 0.047). High expression of GMD was significantly associated with high FUT8 expression (p = 0.04). Conclusions: High expression of FUT8 is associated with an unfavorable clinical outcome in patients with potentially curatively resected NSCLCs, suggesting that FUT8 can be a prognostic factor. The analysis of FUT8 expression and its core fucosylated products may provide new insights for the therapeutic targets of NSCLCs. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify the prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who are refractory or intolerant to sorafenib and to exclude unsuitable candidates from subsequent therapy. Methods: The study cohort consisted of 111 patients who had discontinued sorafenib therapy. Uni- and multivariate analyses were conducted to identify the prognostic factors for survival after discontinuation of sorafenib therapy. Results: The median age of the patients was 70 years, and 96 of them (86%) were male. The Eastern Cooperative Oncology Group performance status was 0-1 in 94 patients (85%). Forty patients (36%) were classified as Child-Pugh class A and 57 (51%) as Child-Pugh class B. The median survival time after discontinuation of sorafenib therapy was 146 days. Hepatitis C viral antibody negativity, presence of ascites, absence of a history of previous treatment excluding sorafenib, elevated serum total bilirubin level, and elevated serum α-fetoprotein level were identified as the independent unfavorable prognostic factors by multivariate analysis. The median survival time of the patients with 4 or 5 unfavorable prognostic factors was 59 days. Conclusions: We should judge the indication of any subsequent therapy carefully in patients with 4 or 5 of the aforementioned factors. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Exon 19 deletion and L858R point mutation of the epidermal growth factor receptor (EGFR) are the most commonly encountered EGFR mutations in non-small cell lung cancer (NSCLC), and predict higher clinical outcomes following treatment with gefitinib. The objective of this study was to evaluate the differential clinical outcomes of gefitinib in patients with NSCLC according to the type of active EGFR mutation, i.e. exon 19 deletion or L858R point mutation. Methods: We identified patients with advanced NSCLC harboring the exon 19 deletion or the L858R point mutation of EGFR who were on gefitinib treatment. The clinical outcomes were evaluated. Results: Of the 124 patients with NSCLC harboring active EGFR mutations, the overall response rate, progression-free survival and overall survival were 60.5%, 11.3 and 27.3 months, respectively, and did not differ significantly between patients with the exon 19 deletion (61.8%, 11.3 and 32.2 months, respectively) and those with the L858R point mutation (58.9%, 9.0 and 27.7 months, respectively). Conclusion: It may be considered that there is no difference in the clinical efficacy of gefitinib between NSCLC patients who harbor the exon 19 deletion and those with the L858R point mutation. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]