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Purpose: The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy., Materials and Methods: Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed., Results: A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS., Conclusion: Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials., Competing Interests: relevant to this article was not reported.

Background: Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI. Methods: L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable. Results: Patients with low ALI (cut-off, 31.1, n = 94) had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p < 0.001), and patients with low mALI (cut-off 67.7, n = 94) had shorter OS than patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001). There was no significant difference in estimates of median survival time between low ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z = 0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p < 0.001), supportive care only (HR, 7.86, p < 0.001), and elevated LDH (HR, 1.45, p = 0.037). Furthermore, goodness of fit of this prognostic model was not significantly increased by adding mALI as an extra variable (LR difference = 2.220, p = 0.136). Conclusion: The present study confirms mALI using CT-determined L3MI has no additional prognostic value beyond original ALI using BMI. ALI is a simple and useful prognostic indicator in SCLC. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of sarcopenia, an important component of cancer cachexia, has been demonstrated in oncologic patients. Catabolic drivers have been suggested to be key features of cancer cachexia. Objective: To determine the relationship between systemic inflammatory markers and CT-determined muscle mass in patients with SCLC. Methods: Cross-sectional muscle areas were evaluated at the level of the third lumbar vertebra (L3) using baseline CT images in 186 SCLC patients. Sarcopenia was defined as a L3 muscle index (L3MI, muscle area at L3/height2) of < 55 cm2/m2 for men and of < 39 cm2/m2 for women. Systemic inflammatory markers investigated included serum white blood cell count (WBC), neutrophil: lymphocyte ratio (NLR), C-reactive protein (CRP), and albumin. Results: Mean L3MI was 47.9 ± 9.7 cm2/m2 for men and 41.6 ± 7.0 cm2/m2 for women. Sarcopenia was present in 128 patients (68.8%), and sarcopenic patients had significant serum lymphocyte counts and albumin levels (p = 0.002 and 0.041, respectively), and higher NLRs and CRP levels (p = 0.011 and 0.026) than non-sarcopenic patients. Multivariable analysis revealed that CRP independently predicted L3MI (β = -0.208; 95% CI, -0.415 to -0.002; p = 0.048), along with gender and BMI (p values < 0.001) and performance status (p = 0.010). Conclusion: The present study confirms a significant linear relationship exists between CT-determined muscle mass and CRP in SCLC patients. This association might provide a better understanding of the mechanism of cancer cachexia. [ABSTRACT FROM AUTHOR]

Purpose: With the exception of temsirolimus, clinical trials in metastatic renal cell carcinoma (mRCC) with poor-risk features are lacking. We previously showed that vascular endothelial growth factor receptor tyrosine kinase inhibitors are active and well tolerated by poor-risk group. This study evaluated and compared the efficacy and safety of pazopanib and sunitinib in this group.Methods: We reviewed the medical records of all patients with mRCC who had received pazopanib or sunitinib at Asan Medical Center. We only assessed patients who had three or more poor-risk features as determined in the advanced renal cell carcinoma trial.Results: Between December 2006 and April 2015, a total of 172 patients who met the inclusion criteria received pazopanib (n = 72) or sunitinib (n = 100). The clinical characteristics were as follows in the pazopanib/sunitinib groups: median age = 60/57 years (range 34-80/17-83); clear cell type = 65/80 (90/80 %); and prior nephrectomy = 46/56 (64/56 %). The disease control rates in the pazopanib/sunitinib groups were 82/60 % (p = 0.002). With a median follow-up duration of 14.2 months (range 1.6-65.0), the median overall survival and progression-free survival in the pazopanib/sunitinib groups were 14.4/8.9 (p = 0.030) and 9.8/4.3 months (p = 0.040), respectively. The common all-grade toxicities for pazopanib/sunitinib were anemia (32 vs. 77 %), neutropenia (33 vs. 56 %), increased aspartate aminotransferase or alanine aminotransferase levels (36 vs. 35 %), fatigue (38 vs. 55 %), and hand-foot syndrome (17 vs. 51 %).Conclusions: Pazopanib and sunitinib are both active and well tolerated in mRCC patients with poor-risk features, but pazopanib might be more effective in this group. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment strategy for cholangiocarcinoma (CC) after curative resection remains controversial. The aim of this study was to analyze the role of adjuvant therapy in R0-resected distal CC.Methods: We retrospectively reviewed the medical records of patients who underwent R0 resection for distal CC at six cancer centers in Korea. Adjuvant therapy consisted of chemotherapy (CT), chemoradiotherapy (CRT), or radiotherapy (RT). The outcomes of the study were overall survival (OS) and recurrence-free survival (RFS).Results: A total of 158 patients were included in the analysis; 47 patients (29.7 %) had lymph node involvement. Fifty-six patients (35.4 %) received adjuvant therapy (CT/CRT/RT: 27/20/9, respectively). Patients with advanced TNM stage (P < 0.001), T3/T4 disease (P = 0.009), positive lymph nodes (LN; P = 0.052), and elevated baseline carbohydrate antigen 19-9 (P = 0.071) were more likely to receive adjuvant therapy. The effect of adjuvant therapy varied according to treatment modality. A multivariable analysis showed a significant improvement in OS after CT [hazard ratio (HR) 0.21, 95 % confidence interval (CI) 0.08-0.53, P = 0.001] and CRT (HR 0.25, 95 % CI 0.08-0.83, P = 0.024). However, RT alone was associated with shorter OS (HR 2.38, P = 0.040), along with T3/T4 disease (HR 2.12, P = 0.012) and positive LN (HR 2.30, P = 0.008). RFS benefited from adjuvant treatment with CT (HR 0.34, P = 0.002) and CRT (HR 0.33, P = 0.004), but not with RT alone (HR 1.42, P = 0.361). In the subset analysis according to LN status, adjuvant therapy not including RT alone was associated with a significant OS and RFS advantage in both LN-negative and LN-positive patients.Conclusions: Our results show that patients receiving CT or CRT had significant improvements in OS and RFS. In addition, a benefit of adjuvant therapy (except RT alone) was observed even in LN-negative patients. [ABSTRACT FROM AUTHOR]

In metastatic renal cell carcinoma (mRCC), the prognostic role of several tumor tissue biomarkers has been evaluated, but the results were controversial. This study aims to verify the prognostic importance of selected tumor tissue biomarkers in patients with mRCC. The clinicopathological features, immunohistochemical staining and scoring for select tissue biomarkers, treatment, and outcome of patients with mRCC treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) between July 2006 and March 2011 at Asan Medical Center in Seoul, South Korea, were reviewed. In total, 123 patients met the inclusion criteria. Most patients had clear-cell carcinoma (107 patients, 87.0 %). First-line VEGFR TKIs were sunitinib (97 patients, 78.9 %), sorafenib (23 patients, 18.7 %), and pazopanib (3 patients, 2.4 %). With a median follow-up period of 60.0 months (95 % confidence interval (CI), 56.3-63.6), median overall survival (OS) and progression-free survival (PFS) were 25.6 months (95 % CI, 19.2-32.0) and 12.2 months (95 % CI, 8.1-16.3), respectively. In the multivariable analysis for OS, carbonic anhydrase IX (CAIX; 47.5 % or less vs. more than 47.5 %, p = 0.014), sarcomatoid change (40 % or less vs. more than 40 %, p < 0.001), tumor necrosis (20 % or less vs. more than 20 %, p = 0.006), and Heng's risk group (good vs. intermediate vs. poor, p = 0.011) were identified as independent prognostic factors. In the multivariable analysis for PFS, CAIX ( p < 0.001), phosphatase and tensin homolog (PTEN; 45 % or less vs. more than 45 %, p = 0.004), sarcomatoid change ( p = 0.002), and tumor necrosis ( p = 0.001) were identified as independent factors affecting PFS. CAIX and PTEN had prognostic importance for mRCC patients receiving first-line VEGFR TKI. Future validation and mechanistic studies are required. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the current study was to evaluate the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) who interrupted vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy.Methods: A retrospective analysis of medical records was performed on all patients with mRCC treated with VEGFR-TKIs between January 2008 and July 2014 (n = 505). Patients who achieved stable disease (SD) or a better response under TKI and later discontinued TKI treatment for any reason with the exception of disease progression were included in the analysis.Results: We identified 32 patients (sunitinib = 20, sorafenib = 7, and pazopanib = 5). The responses to VEGFR-TKIs were complete response (CR, n = 4), partial response (PR, n = 11), SD (n = 15), and controlled but nonmeasurable response (n = 2). Median time to TKI discontinuation from the initiation of VEGFR-TKI therapy was 16.6 months (95 % CI 12.8-20.3), and the main cause of VEGFR-TKI discontinuation was toxicity (n = 19, 59.4 %). At the time of analysis, 16 patients had disease progression and one patient died. With a median follow-up duration of 51.7 months (range 11.5-87.6), median progression-free survival (PFS) after TKI discontinuation was 20.2 months (95 % CI 6.4-34.0). In multivariate analysis, the duration of TKI therapy (<1 year) before TKI discontinuation was an independent significant prognostic factor of poor PFS (p = 0.045). Among 11 patients who were retreated with the same TKI, two patients (18.2 %) achieved PR and nine achieved SD (81.8 %).Conclusions: VEGFR-TKI could be interrupted at least temporarily when clinically warranted in patients with mRCC sufficiently controlled by TKIs. [ABSTRACT FROM AUTHOR]

Background: The therapeutic benefit of adjuvant chemotherapy has not been proven in stage I gastric cancer (GC). The aim of this study was to identify stage I GC patients at high risk of recurrence or death. Methods: We retrospectively reviewed the medical records of 2,783 patients with pathologically confirmed stage I GC who underwent curative surgical resection alone at Asan Medical Center between 2003 and 2007. The clinicopathologic parameters explored included age, sex, histologic differentiation, Lauren classification, size, location, multiplicity, stage, lymphovascular or perineural invasion, preoperative serum levels of tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4), and type of surgery. Results: With a median follow-up of 54 months (range 0-60 months), 212 patients (7.6 %) experienced recurrence or death, and the 5 -year recurrence-free survival (RFS) rate and overall survival rate were 89.9 and 93.4 %, respectively. With a multivariate analysis, six factors (age over 65 years, male gender, stage IB GC, lymphovascular invasion, perineural invasion, and elevated level of carcinoembryonic antigen) were independent poor prognostic factors for RFS ( p < 0.05). Patients with more than two of six poor risk factors had a 5-year RFS rate of 79 %, whereas patients with fewer risk factors had a 5-year RFS rate of 97 % ( p <0.001). Conclusions: In this study cohort, we identified six independent risk factors for RFS. The patients with more than two risk factors are expected to have significant risk of recurrence or death after curative resection and should be considered as candidates for adjuvant treatment. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer, with an increasing mortality rate. Aberrant expression of fibroblast growth factor 19–fibroblast growth factor receptor 4 (FGF19–FGFR4) is reported to be an oncogenic-driver pathway for HCC patients. Thus, the FGF19–FGFR4 signaling pathway is a promising target for the treatment of HCC. Several pan-FGFR (1–4) and FGFR4-specific inhibitors are in different phases of clinical trials. In this review, we summarize the information, recent developments, binding modes, selectivity, and clinical trial phases of different available FGFR4/pan-FGF inhibitors. We also discuss future perspectives and highlight the points that should be addressed to improve the efficacy of these inhibitors. [ABSTRACT FROM AUTHOR]