Independent Predictor Of Poor Overall Survival Research Articles

Is laparoscopic liver resection suitable for selected patients with BCLC stage B HCC? A propensity score-matched analysis

BackgroundThe optimal treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is controversial given the variability of tumour status within this group of patients. This aim of this study was to compare the outcomes of laparoscopic liver resection (LLR) to transarterial chemoembolization (TACE) in a subset of selected patients with BCLC stage B HCC. MethodsPatients with resectable BCLC stage B HCC who underwent treatment between April 2015 and October 2018 were identified for further analysis. Propensity score matching (PSM) was conducted to minimize effect of confounding factors. Perioperative and long-term outcomes were compared between the two groups and multivariate analysis was performed to identify risk factors related to the overall survival (OS). ResultsFrom a total of 224 patients 70 were included into each group after PSM. The overall and major morbidity were comparable between the LLR and TACE groups (P = 0.700 and P = 0.500 after PSM, respectively). The OS in LLR group was significantly better than that in the TACE group (P < 0.001). Tumor number ≥4, the diameter of the biggest tumor >5 cm, and patients who underwent TACE were independent predictors of poorer OS. ConclusionsLLR for selected patients with BCLC stage B HCC is safe and feasible and has improved survival as compared to TACE.

Amide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma.

To assess the utility of amide proton transfer (APT) imaging as an imaging biomarker to predict prognosis and molecular marker status in high-grade glioma (HGG, WHO grade III/IV). We included 71 patients with pathologically diagnosed HGG who underwent preoperative MRI with APT imaging. Overall survival (OS) and progression-free survival (PFS) according to APT signal, clinical factors, MGMT methylation status, and IDH mutation status were analyzed. Multivariate Cox regression models with and without APT signal data were constructed. Model performance was compared using the integrated AUC (iAUC). Associations between APT signals and molecular markers were assessed using the Mann-Whitney test. High APT signal was a significant predictor for poor OS (HR = 3.21, 95% CI = 1.62-6.34) and PFS (HR = 2.22, 95% CI = 1.33-3.72) on univariate analysis. On multivariate analysis, high APT signals were an independent predictor of poor OS and PFS when clinical factors alone (OS: HR = 2.89; PFS: HR = 2.13), or in combination with molecular markers (OS: HR = 2.85; PFS: HR = 2.00), were included as covariates. The incremental prognostic value of APT signals was significant for OS and PFS. IDH-wild type was significantly associated with high APT signals (p = 0.001) when compared to IDH-mutant; however, there was no difference based on MGMT methylation status (p = 0.208). High APT signal was a significant predictor of poor prognosis in HGG. APT data showed significant incremental prognostic value over clinical prognostic factors and molecular markers and may also predict IDH mutation status. • Amide proton transfer (APT) imaging is a promising prognostic marker of high-grade glioma. • APT signals were significantly higher in IDH-wild type compared to IDH-mutant high-grade glioma. • APT imaging may be valuable for preoperative screening and treatment guidance.

Widespread Expression of Sonic Hedgehog (Shh) and Nrf2 in Patient Treated with Cisplatin Predicts Outcome in Resected Tumors and Potential Therapeutic Target for Head and Neck Cancer

Background: Sonic hedgehog (Shh) and Nrf2 play an immense role in chemotherapeutic resistance. These genes have been found to be deregulated in head and neck squamous cell carcinoma (HNSCC). The purpose of this study is to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs). Methods: We analyzed a cohort of HNSCC patients to identify potential candidate therapeutic biomarkers correlating with overall survival (OS) and disease-free survival (DFS) from our own data and validated the results using data from TCGA. Expression of Shh and Nrf2 was silenced by siRNA and cell growth, sphere growth and chemotherapeutic resistance were evaluated. Findings: Widespread abundant expression of Shh and Nrf2 protein was associated with shorter OS and DFS. The combination of Shh and Nrf2 expression levels was found to be a mostly significant predictor of patient DFS. The tumor stromal index (SI) was correlated with Shh expression and inversely associated with shorter DFS. Inhibition of Shh by siRNA or cyclopamine resulted in the attenuation of resistant CSC self-renewal, invasion, clonogenic growth and re-sensitization to chemotherapeutic agents. Interpretation: Concomitant high expression of Shh and Nrf2 proved to be an independent predictor of poor OS and DFS in HNSCC patients. These findings suggest that Shh and Nrf2 might serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC. Funding Statement: Grant-in-Aid from Bangladesh Medical Research Council (BMRC), and University Grant Commission (UGC), Ministry of Education of Bangladesh with the assistance of the World Bank under Higher Education Quality Enhancement Project (HEQEP)– Window -4 (Grant Id. CP4023). Declaration of Interests: The authors declare that they have no conflict of interests. Ethics Approval Statement: This study was approved by the ethics committee of the University of Chittagong and Chittagong Medical Hospital, Chittagong, Bangladesh, and was performed in accordance with the ethical standards laid down in the 1964 declaration of Helsinki and all subsequent revisions. Written informed consent was obtained from all patients used in this study.

Sarcopenia Affects Systemic and Local Immune System and Impacts Postoperative Outcome in Patients with Extrahepatic Cholangiocarcinoma.

A decrease in skeletal muscle mass and function, defined as sarcopenia, is associated with poor postoperative outcome in patients with cancers. Although systemic or local immune status impacts cancer progression, the relationship between sarcopenia and these statuses remains unclear. The aim of this study is to investigate the clinical impact of sarcopenia and its relationship to immune systems in patients with extrahepatic cholangiocarcinoma (ECC). A total of 110 consecutive ECC patients with curative resection between 2005 and 2014 were enrolled. Sarcopenia was determined from skeletal muscle index, assessed by a L3 skeletal muscle mass on axial computed tomography images, and their relationships with patients' clinicopathological characteristics and survival were evaluated. Systemic immune status was calculated using preoperative laboratory data, and tumor-infiltrating (TI) immune cells (CD8+ T cells, CD66b+ neutrophils, CD163+ M2 macrophages) assayed by immunohistochemistry, and their relationship to sarcopenia were evaluated. Sarcopenia was present in 31 patients (28.2%). Patients with sarcopenia had a worse recurrence-free survival (HR 1.87, p = 0.009) and overall survival (OS) (HR 2.47, p = 0.0004) than patients without sarcopenia. Moreover, patients with sarcopenia had a higher level of platelet-lymphocyte ratio (159 vs. 119; p = 0.003) and lower number of TI CD8+ T cells (47 vs. 66 cells/spot; p = 0.03) than patients without sarcopenia. On multivariate analysis, the presence of sarcopenia (HR 2.60, p = 0.0008) was an independent predictor of poor OS. Our data showed that sarcopenia and systemic or local immune cells may interact with each other and play a pivotal role in clinical outcomes of patients with ECC.

Prognostic significance of C-reactive protein to albumin ratio in colorectal cancer patients: a meta-analysis.

Inconsistent results on the prognostic significance of C-reactive protein to albumin ratio (CAR) in colorectal cancer patients have been reported. This meta-analysis sought to assess the prognostic value of pretreatment CAR for survival outcomes in colorectal cancer patients. We conducted a systematic literature search of PubMed and Embase databases until February 16, 2019. Observational studies investigating the prognostic role of pretreatment CAR for survival outcome in patients with colorectal cancer were included. Outcome measures included overall survival (OS), disease-free survival (DFS), or progression-free survival (PFS). Pooled hazard ratio (HR) with 95% confidence interval (CI) was utilized to summarize the prognostic significance of CAR for patient survival. Nine retrospective studies involving 2492 colorectal cancer patients were identified. A fixed-effect model meta-analysis showed that high pretreatment CAR was an independent predictor of poor OS (HR 2.25; 95% CI 1.84-2.76) and DFS (HR 2.49; 95% CI 1.43-4.33). On the other hand, no significant association was observed between high CAR and PFS (HR 1.71; 95% CI 0.44-6.60). The predictive values of OS with high pretreatment CAR caused no significant changes in different sample sizes, countries, cut-off values of CAR, treatment methods, and study quality of subgroups. This meta-analysis suggests that CAR may be a powerful prognostic indicator for colorectal cancer prognosis. High pretreatment CAR is associated with poor OS and DFS in patients with colorectal cancer.

Solvent-based paclitaxel or nab-paclitaxel for heavily treated relapsed/refractory small cell lung cancer: Retrospective single-institution observational study.

Treatment options for patients with relapsed/refractory small cell lung cancer (R/R SCLC) are limited, and the efficacy of salvage therapies for heavily treated patients should be assessed. Here, we evaluated the efficacy of paclitaxel (PTX) in R/R SCLC patients.A single-institute retrospective chart review was conducted. The primary endpoint was overall survival (OS), whereas the secondary endpoints were progression-free survival (PFS), overall response rate, disease control rate (DCR), and safety.Thirty-one patients (median age, 69 [range, 56–80] years) were analyzed. The median follow-up period was 122 (range, 28–1121) days. The median OS and PFS were 4.4 and 2.2 months, respectively. Adverse events of grade 3 or higher, other than hematological toxicity, were febrile neutropenia and neuropathy. Multivariate analyses identified the following independent predictors of poor OS: performance status and lactate dehydrogenase at the upper limit of normal.PTX monotherapy showed moderate efficacy with acceptable toxicity in heavily treated patients with R/R SCLC patients.

Preoperative C-reactive protein to albumin ratio is a predictor of survival after pancreatic resection for pancreatic ductal adenocarcinoma.

Systemic inflammation and nutritional status are associated with clinical outcomes of cancer patients. We investigated the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in patients with pancreatic ductal adenocarcinoma (PDA) after pancreatic resection. One-hundred and thirty-six PDA patients who underwent pancreatic resection between January 2005 and June 2017 were retrospectively enrolled. Preoperative inflammation-based scores including CAR, modified Glasgow prognostic score (mGPS), neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI) were evaluated as potential predictor of overall survival (OS) using Cox regression models. An optimal cutoff value for the continuous variable was estimated by receiver-operating characteristic (ROC) analysis. Patients were categorized by CAR using a cutoff value of 0.09. High CAR was associated with advanced stage, increased mGPS and decreased LMR and PNI, but not with other factors such as tumor location, preoperative biliary drainage or preoperative chemotherapy. In univariate analysis, patients with high CAR had poor OS compared with those with low CAR (P=0.01). Multivariate analysis indicated that high CAR was an independent predictor of poor OS (P=0.03) in addition to advanced stage and residual tumors. The predictive ability of CAR evaluated by area under the ROC curve was consistently higher than that of other inflammation-based factors. Preoperative CAR was an independent and superior predictor of survival after pancreatic resection in patients with PDA. [Correction added on 17 January 2019, after first online publication: In Conclusion, "in" has been corrected to "independent" for clarity.].

Prognostic Significance of Pretreatment Lymphocyte-to-Monocyte Ratio in Patients with Tongue Cancer.

Low pre-operative lymphocyte-to-monocyte ratio (LMR) is associated with worse outcomes in several malignancies. The aim of this study was to determine the prognostic value of LMR in tongue cancer. A total of 103 patients with pathologically-proven tongue cancer were retrospectively analyzed. The peripheral LMR and the ratio of CD8-positive to CD14-positive (CD8+/CD14+) tumor-infiltrating cells were determined by immunohistochemical staining. Receiver operating characteristic curve analysis, log-rank test, and Cox proportional hazards regression models were used for statistical analysis. There was a significant difference in overall survival (OS) between low LMR and high LMR, and low CD8+/CD14+ tumor-infiltrating cells and high CD8+/CD14+ tumor infiltrating cells. For the clinical analysis, multivariate analysis showed that clinical ocular inspection type and low LMR were independent predictors for poor OS. Concerning the immunohistochemical analysis, monocyte count was independent predictor of poor OS. Pre-operative LMR and CD8+/CD14+ tumor-infiltrating cells serve as independent prognostic biomarkers.

Preoperative sarcopenia is a predictor of poor prognosis of esophageal cancer after esophagectomy: a comprehensive systematic review and meta-analysis.

The impact of preoperative sarcopenia on long-term survival of esophageal cancer patients after esophagectomy remains unclear. We conducted an updated meta-analysis focusing on current topic comprehensively. We systematically searched relevant studies investigating the impact of preoperative sarcopenia on survival of patients with surgically treated esophageal cancer in PubMed, Embase, and Web of Science up to July 20, 2018. Data of 3-year and 5-year overall survival (OS) rates as well as hazard ratio (HR) of OS and disease-free survival (DFS) were collected for analysis by using the STATA 12.0 package. Finally, a total of 11 cohort studies consisting of 1520 patients (795 sarcopenic patients and 725 nonsarcopenic patients) were included for analysis. Our meta-analysis showed that patients with sarcopenia had a significantly lower 3-year (51.6% vs. 65.4%, P<0.001) and 5-year OS rate (41.2% vs. 52.2%, P=0.018) than those without sarcopenia. Sarcopenia was found to be an independent predictor of poor OS (HR=1.58; 95% confidence interval (CI)=[1.35, 1.85]; P<0.001) and DFS (HR=1.46; 95% CI=[1.12, 1.90]; P=0.005) in esophageal cancer patients after esophagectomy. No obvious heterogeneities or publication bias were observed during analysis. Therefore, patients with sarcopenia had a significantly worse prognosis than those without after surgical resection of esophageal cancer. Preoperative sarcopenia is an independent unfavorable prognostic factor for esophageal cancer patients after esophagectomy. However, high-quality studies with appropriate adjustments for confounding factors are needed to confirm our conclusions.

Rapidly declining skeletal muscle mass predicts poor prognosis of hepatocellular carcinoma treated with transcatheter intra-arterial therapies

BackgroundThe impact of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) who receive transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, remains unclear. We investigated the prognostic value of skeletal muscle loss (SML) stratified by cutoffs for sarcopenia and rate of change in skeletal muscle mass over 6 months.MethodsWe retrospectively evaluated 102 patients with HCC treated with transcatheter intra-arterial therapies between 2005 and 2015. Computed tomography images of the third lumbar vertebra (L3) were analyzed to obtain the skeletal muscle area normalized for the height squared, defined as the skeletal muscle index at L3 (L3 SMI), before and 6 months after treatment. Low or high SMI was defined using cutoff values of 42 cm2/m2 in men and 38 cm2/m2 in women. The rate of change in skeletal muscle mass (ΔL3 SMI) over 6 months was calculated. Overall survival (OS) was compared in groups classified by baseline L3 SMI and ΔL3 SMI; prognostic significance was assessed with univariate and multivariate analyses, using Cox proportional hazards models.ResultsOS did not differ significantly between groups with low (n = 31) and high (n = 71) SMI at baseline (P = 0.172), but OS was significantly poorer in patients with SML (n = 41), defined as ΔL3 SMI < − 4.6% over 6 months than in those without SML (n = 61, P = 0.018). On multivariate analysis, SML (hazard ratio [HR], 1.675; 95% confidence interval [CI], 1.031–2.721; P = 0.037), serum alpha-fetoprotein ≥20 ng/mL (HR, 2.550; 95% CI, 1.440–4.515; P = 0.001), and maximum tumor diameter ≥ 30 mm (HR, 1.925; 95% CI, 1.166–3.179; P = 0.010) were independent predictors of poor OS. Baseline L3 SMI was not significantly associated with OS (HR, 1.405; 95% CI, 0.861–2.293; P = 0.174).ConclusionsΔL3 SMI was an independent prognostic factor in patients with HCC treated with transcatheter intra-arterial therapies. Further study is required to reveal whether prevention of skeletal muscle depletion might be a new therapeutic strategy to contribute to improved clinical outcomes in patients with HCC.

Prognostic value of pretreatment PET/CT lean body mass-corrected parameters in patients with hepatocellular carcinoma.

This study was designed to investigate whether pretreatment fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) lean body mass-corrected parameters could predict the overall survival (OS) better than the established predictors in patients with hepatocellular carcinoma (HCC). We retrospectively analyzed 61 patients with HCC with pretreatment F-FDG-PET/CT. Besides obtaining clinical factors, we measured both lean body mass-corrected and body weight-corrected PET/CT parameters, including metabolic tumor volume, maximal standardized uptake value of the tumor, total lesion glycolysis, tumor-to-normal liver uptake ratio, and so on. The prognostic value of those factors for OS was assessed by statistical software. In the univariate analysis, PET/CT parameters, ascites, serum α-fetoprotein, alkaline phosphatase, aspartate transaminase (AST), tumor number, tumor size of the maximal one, vascular invasion, TNM stage, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) staging, and Okuda staging were significant predictors of OS. In multivariate and Kaplan-Meier analyses, lean body mass-corrected maximum standardized uptake value (lbmSUVmax) more than 3.35 g/ml, AST more than 42.00 U/l, and BCLC staging B-C were significant independent predictors of poor OS. When BCLC staging variable was stratified by four categories instead of two in the multivariate analysis, it was not the statistically significant independent predictor anymore, but lbmSUVmax and AST still were. Pretreatment F-FDG-PET/CT lean body mass-corrected parameters can predict the OS in patients with HCC. Moreover, lbmSUVmax and AST, as the independent predictors of OS, could supplement the prognostic value of the BCLC staging system.

Patterns of Treatment Failure in Patients with Sinonasal Mucosal Melanoma.

Head and neck mucosal melanoma is a locally aggressive tumor with a high recurrence rate. The paranasal sinuses and nasal cavity are the most common primary tumor sites. The purpose of this retrospective study was to identify independent predictors of outcome in sinonasal mucosal melanoma (SNMM) and characterize the patterns of treatment failure. This study included 198 patients with SNMM who had been treated at The University of Texas MD Anderson Cancer Center from 1 January 1991 through 31 December 2016. The survival outcomes included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local recurrence-free survival, and distant metastasis-free survival. A stepwise regression analysis was used to assess associations in the multivariate models. The 5-year OS, DSS, and DFS rates were 38, 58, and 27%, respectively. Independent predictors of poor OS and DSS were the paranasal sinuses as the primary tumor site [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.11-2.66; and HR 2.12, 95% CI 1.21-3.74, respectively] and the presence of distant metastases at presentation (HR 4.53, 95% CI 2.24-7.83; and HR 3.6, 95% CI 1.12-7.1). Recurrence occurred in 96 patients (48%). The most common cause of treatment failure was distant metastasis in 69 of 198 patients (35%), followed by local [36 (18%)] and regional [22 (11%)] recurrence. The most common cause of treatment failure in SNMM is distant metastasis. The tumor site and the presence of metastatic disease at presentation were the only independent predictors of survival. These data can be used to inform quality improvement efforts and the counseling of high-risk SNMM patients.

Abstract P2-03-04: Lymphovascular invasion in breast carcinoma following neodjuvant chemotherapy is a strong prognosis factor

Abstract Purpose : Lymphovascular invasion (LVI) is a poor prognosis factor in breast cancer (BC), but data on its value in the neoadjuvant setting is scarce. This study evaluates the relationships between post-NAC LVI and prognosis in BC. Methods: We identified 1197 patients with primary BC receiving NAC +/- trastuzumab between 2002 and 2011. Information on LVI in post-NAC surgical specimen was retrieved from review of medical charts. Univariate and multivariate analyses were performed to assess the association of clinical, pathological factors with disease free survival (DFS) and overall survival (OS) was assessed using a cox proportional hazard model. Results: On 1197 tumors, 528 were luminal (44.1%), 375 were triple negative breast cancer (TNBC) (31.3%) and 294 were HER2-positive (24.6%). On post-NAC surgical specimens, LVI was present in 302 (25.2%), absent in 531 (44.4%), and was not mentionned in 364 cases (30.4%). The presence of post-NAC LVI was associated with an impaired DFS (HR=2.17, 95 CI [1.65 - 2.86], p&amp;lt;0.001) and the magnitude of this impact varied by BC subtype (p-value for interaction=0.02), (luminal BC: HR=1.75, p=0.006; TNBC : HR=2.77, p&amp;lt;0.001 ; HER2-positive BC : HR=5.12, p&amp;lt;0.001). Table 1 Univariate analysis and multivariate analysis on DFS (whole population) Univariate Multivariate VariableClassHRClpHRCIpAge&amp;lt; 451 0.35 45-550.82[0.62 - 1.08] &amp;gt;550.87[0.64 - 1.19] Menopausal statuspremenopausal1.04[0.81 - 1.34]0.75 postmenopausal1 BMI class19-251 &amp;lt; 191.24[0.75 - 2.05]0.41 &amp;gt; 251.36[1.06 - 1.75]0.01 Tumor sizeT1-T21 T31.77[1.38 - 2.27]&amp;lt;0.011.77[ 1.32 - 2.38 ]&amp;lt;0.001Clinical nodal statusN01 N1-N2-N31.35[1.05 - 1.72]0.021.43[ 1.07 - 1.91 ]0.016HistologyDuctal1 Other1.24[0.87 - 1.78]0.24 GradeGrade I-II1 III1.24[0.87 - 1.78]0.07 Ki 67&amp;lt;201 &amp;gt;201.54[1.06 - 2.22]0.02 Mitotic index≤221 &amp;gt;221.18[0.9 - 1.53]0.23 DCIS componentno1 yes1.33[0.88 - 2.01]0.18 Pre-NAC LVIno1 yes1.35[0.88 - 2.01]0.09 ER statusnegative1 positive0.72[0.56 - 0.91]&amp;lt;0.01 PR statusnegative1 positive0.66[0.51 - 0.85]&amp;lt;0.01 HER2 statusnegative1 positive0.84[0.62 - 1.14]0.26 BC subtypeluminal1 TNBC1.53[1.17 - 2]&amp;lt;0.012.67[ 1.93 - 3.69 ]&amp;lt;0.001 HER20.99[0.72 - 1.38]0.971.25[ 0.82 - 1.88 ]0.299Post NAC parametersPost-NAC LVI (breast)no1 yes2.17[1.65 - 2.86]&amp;lt;0.012.3[ 1.72 - 3.08 ]&amp;lt;0.001pCRNo pCR1 pCR0,4[0.27 - 0.59]&amp;lt;0.01 Pathological nodal involvement0 1-31.48[1.11 - 1.97]&amp;lt;0.01 ≥4 N+3.13[2.34 - 4.19]&amp;lt;0.01 RCB class01 10.97[0.36 - 2.64]0.96 22.88[1.69 - 4.89]&amp;lt;0.01 35.21[3.01 - 9.02]&amp;lt;0.01 ER: oestrogene receptor PR: progesteron receptor RCB: residual cancer burden Post-NAC LVI was an independent predictor of poor DFS, that overwhelmed the prognostic impact of pathological complete response in all 3 BC subtypes. Post-NAC LVI was also an independent predictor of poor OS in the whole cohort and in all BC subtypes. Table 1 resumes univariate and multivariate analysis on DFS in whole population. Conclusion: Post-NAC LVI is a strong independent prognostic factor associated with poor DFS and OS, that (i) should be systematically mentioned in pathological reports following NAC and (ii) could be used to select high risk patients candidates to second line trials in the post-neoadjuvant window. Citation Format: Hamy-Petit A-S, Lam G-T, Laas E, Darrigues L, Balezeau T, Guerin J, Livartowski A, Sadacca B, Pierga J-Y, Vincent-Salomon A, Bidard F-C, Lerebours F, Brain E, Becette V, Rouzier R, Lae M, Reyal F. Lymphovascular invasion in breast carcinoma following neodjuvant chemotherapy is a strong prognosis factor [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-04.

Prospective longitudinal quality of life and survival outcomes in patients with advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated with Yttrium-90 radioembolization

BackgroundTo determine the effect of Yttrium-90 (Y90) radioembolization on health-related quality of life (HRQOL) and its effect on overall survival advanced, unresectable infiltrative hepatocellular carcinoma (HCC) patients with concurrent portal vein thrombosis (PVT).MethodsConsecutive patients with unresectable infiltrative HCC and PVT were recruited. The Short-Form 36 (SF-36) questionnaire was used to assess HRQOL for consecutive patients treated with glass-based Y90 based on a prospective phase II trial. MR imaging was used to determine tumor progression every 3 months post-treatment. Overall survival (OS) from treatment and time to progression (TTP) was analyzed using Kaplan-Meier estimation and log-rank test.ResultsThirty patients were treated and followed for 17.4 months; physical and mental component summary scores (PCS & MCS) remained unchanged at one, three, and six months. While no difference was observed in baseline SF-36 scores for patients with prolonged TTP (≥4 months) and OS (≥ 6 months), corresponding 1-month PCS were significantly higher than those with TTP < 4 months and OS < 6 months. At 1 month, patients with normalized Physical Function (PF), Role Physical (RP) and PCS within 2 standard deviations (SD) of US normalized baseline scores had a significantly prolonged median OS (15.7 vs. 3.7 months; p < 0.001) and TTP (12.4 vs. 1.8 mo; p < 0.001) compared those with physical component scores greater than 2SD below normalized US population values.ConclusionY90 radioembolization for HCC demonstrated long-term preservation of HRQOL. Lower baseline HRQOL scores were predictive of poorer OS. Early (1 month post-treatment) significant decreases in PCS were independent predictors of poorer OS and TTP.Trial registrationClinicalTrials.gov identifier NCT01556282, registered March 16, 2012.

Prognostic Impact of Splenectomy in Patients with Esophagogastric Junction Carcinoma.

We evaluated the survival benefit of splenectomy in patients with esophagogastric junction (ECJ) carcinoma. We retrospectively examined clinicopathological and survival data for 60 surgically-treated patients with ECJ carcinoma. The 5-year overall survival (OS) rate was 47%. Splenectomy was performed in 20 patients (30%). Multivariate Cox regression analysis revealed splenectomy (odds ratio (OR), 2.70; 95% confidence interval (CI)=1.06-7.17; p=0.04) and venous invasion (OR=3.03; 95%CI=1.20-9.27; p=0.02) as significant independent predictors of poorer OS. Splenic hilar lymph node metastasis was not observed. Multivariate logistic regression analysis identified perioperative blood transfusion (BTF) as a significant independent factor associated with splenectomy. The survival benefit of splenectomy in ECJ carcinoma patients may decrease with increasing frequency of perioperative BTF for blood loss. We recommend that splenectomy should be performed carefully when indicated by the extent or invasion of EGJ carcinoma.

The high stromal SPARC expression is independently associated with poor survival of patients with resected pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine in combination with S-1 or adjuvant gemcitabine alone

BackgroundAlthough postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival, its efficacy varies among individuals. Identification of biomarkers that can predict the efficacy of adjuvant chemotherapy for PDAC is essential. ObjectivesTo investigate the predictive value of secreted protein acidic and rich in cysteine (SPARC) expression in patients with PDAC treated with adjuvant gemcitabine in combination with S-1 (adjuvant GS) or adjuvant gemcitabine alone (adjuvant G alone). MethodsStromal SPARC and cytoplasmic SPARC were examined immunohistochemically in 211 PDAC patients treated with adjuvant GS or G alone after resection. The association of SPARC expression with clinicopathological factors, disease-free survival (DFS) and overall survival (OS) were analyzed. ResultsIn multivariate analysis, borderline resectable with arterial contact (BR-A) (P = .002), higher preoperative CA 19-9 level (≥91 U/ml) (P = .005), moderately or poorly (P = .003), presence of lymph node metastasis (P = .012) and high stromal SPARC expression (P = .013) were independent predictors of poor DFS. Moreover, BR-A (P = .003), higher preoperative CA 19-9 level (≥91 U/ml) (P = .007) and high stromal SPARC expression (P < .001) were identified as independent predictors of poor OS. In contrast, cytoplasmic SPARC expression did not affect DFS and OS. ConclusionsHigh stromal SPARC expression was an independent predictor of poor DFS and OS in patients treated with adjuvant GS or G alone. Stromal SPARC expression could be a relevant biomarker for prediction of prognosis in PDAC patients after resection treated with adjuvant GS or G alone.

High SLC4A11 expression is an independent predictor for poor overall survival in grade 3/4 serous ovarian cancer.

In this study, we aimed to examine the expression of SLC4A11 in ovarian cancer and in normal ovarian tissues, its prognostic value and the possible mechanism of its dysregulation. Bioinformatic analysis was performed by using data from the GEO datasets, the Cancer Genome Atlas-Ovarian Cancer (TCGA-OV) and the Human Protein Atlas (HPA). Results showed that SLC4A11 was upregulated in ovarian cancer compared with normal ovarian epithelial tissues. In patients with primary serous ovarian cancer in TCGA-OV, the cases with lymphatic invasion (N = 133) had significantly higher SLC4A11 expression than those without lymphatic invasion (N = 77) (p = 0.0069). High SLC4A11 expression was consistently associated with worse overall survival (OS). Univariate and multivariate analysis confirmed that high SLC4A11 expression was an independent prognostic factor for poor OS in grade 3/4 (G3/G4) tumors (HR = 1.416, 95%CI: 1.098–1.824, p = 0.007). 320 out of 578 (55.4%) ovarian cancer cases had SLC4A11 amplification. High methylation group had a significantly lower level of SLC4A11 expression. Based on these findings, we infer that high SLC4A11 expression is an independent predictor for poor OS in grade 3/4 serous ovarian cancer. Both DNA amplification and hypomethylation contribute to its upregulation in ovarian cancer.

High plasma interleukin-6 levels associated with poor prognosis of patients with advanced hepatocellular carcinoma.

Antiangiogenic therapy is crucial for advanced hepatocellular carcinoma (HCC) treatment. Interleukin (IL)-6 is an inflammatory response mediator that can promote angiogenesis. We explored its prognostic role in patients with advanced HCC. We had two patient cohorts, both comprising patients who received sorafenib-containing therapy as the first-line treatment for advanced HCC. We explored the best cut point for pretreatment plasma IL-6 levels in the exploration cohort and then confirmed it in the validation cohort. In total, 55 and 73 patients constituted the exploration and validation cohorts, respectively. In the exploration cohort, a cut point of 4.28 pg/ml was the best for defining high and low IL-6 levels because it could most effectively differentiate overall survival (OS). On application of this cut point to the validation cohort, patients with high plasma IL-6 levels, compared with patients with low IL-6 levels, exhibited significantly poorer OS (median, 8.0 vs 13.9 months, P = 0.031) but similar progression-free survival or treatment response. After adjusting for patient demographics and tumor characteristics, a high plasma IL-6 level remained an independent predictor of poor OS (hazard ratio 2.594, P = 0.005). High pretreatment plasma IL-6 levels were associated with poor prognosis of patients with advanced HCC.

Abstract 4728: Plasma interleukin-6 level predicts prognosis of patients who received sorafenib for advanced hepatocellular carcinoma

Abstract Background: No biomarker has been proven to predict the treatment outcomes of sorafenib, the only approved first-line therapy for advanced hepatocellular carcinoma (HCC). We explored predictive and prognostic values of plasma interleukin (IL)-6 levels for patients who received sorafenib as first-line therapy for advanced HCC. Methods: This study had 2 patient cohorts. The exploration cohort consisted of patients who were previously enrolled in a phase 2 clinical trial that examined sorafenib with tegafur/uracil as first-line therapy for advanced HCC. The validation cohort consisted of patients who received sorafenib alone as first-line therapy for advanced HCC under reimbursement of National Health Insurance of Taiwan. Pretreatment plasma IL-6 levels were determined. We used the receiver operating characteristic (ROC) curve in the exploration cohort to determine the best cut point for IL-6 levels to predict overall survival (OS). We then confirmed the cut point in the validation cohort. Results: There were 55 and 73 patients in the exploration and validation cohort, respectively. In the exploration cohort, there was no complete response but 3 (6%) partial response. The median OS was 8.1 months. In the validation cohort, there was no complete response but 7 (10%) partial response. The median OS was 10.3 months. In the exploration cohort, we found 4.28 pg/ml was the best cut point in defining high and low IL-6 levels because it could differentiate OS (p = 0.042) with the best sensitivity and specificity. Applying the cut point on the validation cohort, patients with high pretreatment plasma IL-6 levels, compared with patients with low IL-6 levels, exhibited significantly poorer OS (median, 8.0 vs. 13.9 months, p = 0.031). After adjusting for age, gender, hepatitis etiology, tumor characteristics, α-fetoprotein level, performance status, and prior treatment, a high plasma IL-6 level remained an independent predictor for poor OS (hazard ratio 2.594, p = 0.005). By contrast, the plasma IL-6 level was not associated with progression-free survival, treatment response, disease control, or other patient characteristics. Conclusion: High pretreatment plasma IL-6 level predicted prognosis of patients who received sorafenib as first-line therapy for advanced HCC. Citation Format: Yu-Yun Shao, Hang Lin, Yong-Shi Li, Ying-Hui Lee, Ho-Min Chen, Ann-Lii Cheng, Chih-Hung Hsu. Plasma interleukin-6 level predicts prognosis of patients who received sorafenib for advanced hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4728. doi:10.1158/1538-7445.AM2017-4728

Prognostic value of candidate microRNAs in gastric cancer: A validation study.

Studies have reported the prognostic value of dysregulated microRNAs (miRNAs) in gastric cancer (GC). However, the results demonstrated so far are inconsistent. To better understand the miRNAs with prognostic relevance. Evaluable miRNAs were selected based on our selection criteria and further analyzed in formalin-fixed paraffin-embedded (FFPE) tissue samples of 169 GC patients using quantitative real-time polymerase chain reaction (qRT-PCR). A total of 19 miRNAs were selected as candidate miRNAs. Among those miRNAs identified, high expression of miR-21-5p was related to poor overall survival (OS) and disease free survival (DFS) and was identified as an independent prognostic factor. Cases with high level of miR-200c-3p showed poor DFS. Subgroup analysis revealed that high expression of miR-21-5p and miR-222-3p was associated with poor OS and DFS in GC patients not received adjuvant chemotherapy. In male patients, high expression level of miR-21-5p was related to poor OS and DFS. The present study confirmed that elevated level of miR-21-5p could serve as an independent predictor for poor OS and DFS of GC patients. Moreover, miR-200c-3p, miR-222-3p might also play important roles in the prognosis of GC patients. Further studies are warranted to validate our findings and identify the functions and mechanisms of these miRNAs.