Independent Prognostic Factor For Survival Research Articles

Prognostic factor analysis for patient outcome of PD-L1 expression in thoracic oesophageal squamous cell carcinoma

The purpose of this study was to determine the expression of PD-L1 in oesophageal squamous cell carcinoma (OSCC) and the prognostic factors. PD-L1 expression was investigated by immunohistochemical staining of resected specimens from 50 OSCC patients who were randomly selected from 104 patients with complete follow-up data. The relationships among PD-L1 expression, clinicopathological factors and prognosis were assessed by statistical analysis. The expression of PD-L1 was positive in 27 (54%, positive cells' proportion > 25%) and negative in 23 (46%, positive cells proportion ≤25%) of 50 cases, and PD-L1 expression was negative in all pericarcinomatous tissues (P > 0.05). The 5-year survival rate of patients with PD-L1-positive expression was 22.2% (6 of 27), which was less than that of patients with PD-L1-negative expression (47.8%; 11 of 23) (P < 0.05). The results showed significant differences in the depth of tumour invasion, lymph node status, postoperative pathological stage and PD-L1 expression (P < 0.05). Multivariable analysis showed that PD-L1 expression was an independent prognostic factor for survival. The depth of tumour invasion, lymph node status, postoperative pathological stage and PD-L1 expression are important factors affecting the prognosis of patients with thoracic OSCC; in particular, high PD-L1 expression was a significant independent poor prognostic factor in thoracic OSCC patients.

SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells. We observed that SMYD3 upregulated sphingosine-1-phosphate receptor 1 (S1PR1) promoter activity by methylating histone 3 (H3K4me3). S1PR1 was expressed at high levels in HCC samples, and high S1PR1 expression was associated with shorter survival. S1PR1 expression was also positively correlated with SMYD3 expression in HCC samples. We confirmed that SMYD3 promotes HCC cell growth and migration in vitro and in vivo by upregulating S1PR1 expression. Further investigations revealed that SMYD3 affects critical signaling pathways associated with the progression of HCC through S1PR1. These findings strongly suggest that SMYD3 has a crucial function in HCC progression that is partially mediated by histone methylation at the downstream gene S1PR1, which affects key signaling pathways associated with carcinogenesis and the progression of HCC.

Pathologic Lymph Node Staging of Gastric Cancer.

The TNM classification is the main tool for lymph node (LN) staging in gastric cancer (GC). However, alternative LN staging systems have been proposed, and the role of features other than the number of metastatic LNs is being investigated. Our aim is to discuss the main challenges of LN assessment in GC. Comprehensive review of the literature on alternative LN staging systems, examined LNs, sentinel LN (SLN) biopsy, LN micrometastases (LNMIs), extracapsular extension (ECE), and tumor deposits (TDs) in GC. Many controversies exist regarding LN assessment in GC. The TNM classification shows excellent prognostic performance, but alternative prognostic methods such as the LN ratio or log odds of positive LNs have demonstrated to be better than the TNM system in terms of prognostic accuracy. The value of SLN biopsy and LNMIs in GC is still unclear, and several challenges concerning their clinical impact and pathologic analysis must be overcome before their introduction in clinical practice. Most authors have identified ECE and TDs as independent prognostic factors for survival in GC. Further studies should be performed to evaluate the impact of these features on the TNM classification and patient outcomes, as well as to standardize alternative LN staging systems.

Prognostic significance of lymph node ratio in patients with squamous cell carcinoma of the floor of the mouth

The lymph node ratio (LNR) has been proposed as an independent prognostic factor for survival in patients with oral squamous cell carcinoma (OSCC). However, little attention has been paid to its role in the specific subsite of the floor of the mouth (FOM). The purpose of this study was to evaluate the prognostic significance of the LNR in patients with FOM SCC. A retrospective analysis of 92 patients with FOM SCC who were treated with primary curative resection and neck dissection was conducted. Overall survival (OS) and disease-free survival (DFS) were used to evaluate the prognostic significance of the LNR. Both of these parameters were significantly worse (P < 0.001) in patients with neck metastases. The mean LNR was 0.145 in patients with positive lymph nodes. A LNR <0.145 was predictive of longer DFS, while the receiver operating characteristic curve analysis demonstrated that a LNR ≥0.175 indicated a significantly lower OS. This study confirms that metastatic cervical lymph nodes correlate with an adverse prognosis in patients with FOM SCC, and specifically, a LNR ≥0.145 is predictive. Therefore, the LNR in patients with FOM SCC may be a predictor of survival in these patients.

Upregulation of FGD6 Predicts Poor Prognosis in Gastric Cancer.

Background: The aim of this study was to investigate the prognostic significance of faciogenital dysplasia 6 (FGD6) in gastric cancer (GC).Methods: The data of GC patients from The Cancer Genome Atlas (TCGA) database were used for the primary study. Then, our data were validated by the GEO database and RuiJin cohort. The relationship between the FGD6 level and various clinicopathological features was analyzed by logistic regression and univariate Cox regression. Multivariate Cox regression analysis was used to evaluate whether FGD6 was an independent prognostic factor for survival of patients with GC. The relationship between FGD6 and overall survival time was explored by the Kaplan–Meier method. In addition, gene set enrichment analysis (GSEA) was performed to investigate the possible biological processes of FGD6.Results: The FGD6 level was significantly overexpressed in GC tissues, compared with adjacent normal tissues. The high expression of FGD6 was related to a high histological grade, stage, and T classification and poor prognosis of GC. Multivariate Cox regression analysis showed that FGD6 was an independent prognostic factor for survival of patients with GC. GSEA identified that the high expression of FGD6 was mainly enriched in regulation of actin cytoskeleton.Conclusion: FGD6 may be a prognostic biomarker for predicting the outcome of patients with GC.

Genetic signature of CTLA-4, BTLA, TIM-3 and LAG-3 molecular expression in colorectal cancer patients: Implications in diagnosis and survival outcomes

ObjectiveAccumulating evidences suggest that immune checkpoints (ICs) inhibit immune response against cancerous cells and promote tumor cell survival. Up-regulation of ICs in tumor microenvironment is reported in patients with colorectal cancer (CRC). Thus, evaluating the peripheral blood expression of ICs may be used as non-invasive biomarkers for diagnosis and prognosis of CRC. MethodsThis study included 60 primary and treatment naïve CRC patients along with 15 age and sex matched healthy volunteers as a control group. Total RNA was extracted from peripheral blood samples and gene expression of cytotoxic T lymphocyte antigen-4 (CTLA-4), B and T lymphocyte attenuator (BTLA), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and Lymphocyte activation gene-3 (LAG-3) was measured by quantitative real time polymerase chain reaction (qRT-PCR). All patients were followed for 12 months to correlate the measured ICs to patients’ survival. ResultsThe gene expression of CTLA-4, BTLA, TIM-3 and LAG-3 was significantly up-regulated in CRC patients compared to the control group (p < 0.001). Individually, CTLA-4 and BTLA showed 85% sensitivity in discriminating CRC patients from control group (p < 0.001). On the other hand, TIM-3 and LAG-3 expression showed higher sensitivity (93%) for diagnosis of CRC (p < 0.001). Conversely, CTLA-4 or BTLA strongly predicted CRC patients’ survival (p < 0.001) compared to TIM-3 (p = 0.018) or LAG-3 (p = 0.035). CTLA-4, BTLA, TIM-3 and LAG-3 were independent prognostic factors of survival after adjustment for age and gender. ConclusionThe current study provided evidence that blood gene expression of ICs was up-regulated in CRC patients and associated with cancer stage and patients’ survival, which highlights the diagnostic and prognostic values of ICs expression in CRC. Further investigations and validations in larger cohorts are required.

P-241 Metastatic lymph node ratio as an addition to the nodal evaluation of TNM staging: A new sight for prevention of stage migrations

TNM staging is a routine grading system for gastric cancer, but the survival of gastric cancer gets better with early diagnoses and a better management with the correlation of oncology and general surgery departments. Making additions to TNM classification is important in terms of clarifying surveillance and preventing stage migrations. The purpose of this study was to evaluate the metastatic lymph node ratios in locally advanced gastric cancer patients who have undergone curative gastrectomy with D2 dissection. From January 2011 to December 2015, 341 patients were diagnosed with gastric adenocarcinoma and 226 patients underwent curative gastrectomy in our hospital. As curative gastrectomies with R0 resection and patients without distant metastasis were included in the study, palliative surgeries, R1-R2 resections, emergent surgeries and surgeries with insufficient lymph node dissection are excluded. From 226 patients, 193 patients whose tumor was not T1 and whose both preoperative and postoperative data were present were included in the study. In particular, lymph node metastasis was not present in 81 patients. The ratio between the number of metastatic lymph nodes and total number of dissected lymph nodes was analysed to evaluate their influences on the disease outcome. Patients were divided into three groups according to the ratio (NR) between metastatic lymph nodes and total nodes dissected. The number of metastatic lymph nodes ranged from 0 to 43 (mean, 6.77±4.82) and the number of dissected total lymph nodes ranged from 15 to 93 (mean 27.13±6.91). There was no significant correlation between numbers of metastatic and dissected lymph nodes (p:0.142). Survival of patients at 5 years regardless of their stage was 54.1%, with a median survival of 23.24±4.18 months. According to regional nodal status (N) of the 8th edition of the AJCC, patients with N0 (n=81), pN1 (n=24), pN2 (n=31) and pN3 (n=67) showed survival rates at 5 years of 81.7%, 75.0%, 45.2% and 40.3%, respectively (p=0.009). Patients were stratified into NR0 (ratio 0%), NR1 (ratio 1-49%) and NR2 (ratio >50%). Their survival rates at 5 years were 81.7%, 53.5% and 36.1%, respectively (p=0.008). Metastatic lymph node ratio is an independent prognostic factor in survival regardless of the number dissected in the surgical process. The metastatic lymph node ratio has a more beneficial effect on disease-free and overall survival than the number of metastatic lymph nodes. If D2 dissection is done, metastatic lymph node ratio should be added to pathological TNM staging for a better foresight and for the prevention of stage migrations.

Absolute Lymphocyte Count after First Induction Is Associated with Relapse Free Survival in Acute Myeloid Leukemia

Introduction. Absolute lymphocyte count (ALC) nowadays is a well known independent prognostic factor of survival in acute lymphoblastic leukemia (ALL): higher counts of ALC in period of induction therapy predict better results. The opposite situation remains with ALC and acute myeloid leukemia. Recent researches showed inverse dependence with higher initial ALC and worse response rate or shorter remission in AML. However, there is still limited data of ALC value in AML patients (pts) after chemotherapy courses. This criterion of prognosis is quite cheap and can be widely used in almost every clinic.Aims. To explore ALC in de novo AML pts after 1 induction course and compare it with clinical outcomes.Methods. From March 2016 to March 2017 in hematology department of National Research Center for Hematology in the study included 35 pts with de novo AML. All pts were treated with standard protocol and 1 induction course included cytarabine (100mg/m2 twice/day tag 1-7) and daunorubicine (60mg/m2 tag 1-3). In period on 28th - 40th days (depends of recovery) after therapy we performed blood samples with ALC analysis using Flow Cytometry. Kaplan-Meier method with log-rank test was used for disease free survival (DFS) analysis. 8 pts had resistant leukemia after 1st course and 8 another pts had relapse in short time.Results. We found out that DFS after 1st course was associated with certain amount of ALC (pic.1). ALC more than 0,8 x109/l predicted poor DFS in contrast with pts of low ACL (<0,8x109/l)(median survival 226 days vs not reached, p=0,03) . Limitation of study was the short follow up period (under 1,5 years). Data had retrospective analysis and there were no standardized methods and time points.Conclusion. Our findingsidentify ALC after 1st induction course in AML isprobably dysfunctional and may cause worse response to leukemia and short DFS. These studies need further researches in bigger cohort of pts. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Role of FDG PET for Evaluation of Bone Marrow Status and Prognosis in T Cell Lymphomas

Objective: We investigated clinical value of FDG PET for evaluation of bone marrow (BM) tumor involvement status in peripheral T cell lymphoma (PTCL) or extranodal NK/T cell lymphoma (NKTCL).Methods: Patients with PTCL or NKTCL, who underwent initial staging with FDG PET and BM biopsy were analyzed. PET BM uptake was analyzed visually and quantitatively (bone marrow-to-liver ratio; MLR). Receiver-operating-characteristic (ROC) analysis was performed to evaluate the usefulness of FDG PET for predicting BM tumor involvement. Prognostic implication of FDG PET finding was also assessed.Results: A total of 109 (63 PTCL and 46 NKTCL) patients were analyzed. BM biopsy revealed tumor involvement in 64.2% of cases. In the ROC curve analysis for determining visually positive BM involvement by MLR, the area under curve (AUC) was 0.948 with sensitivity 90.2% and specificity 91.2%. The AUC using visual analysis was 0.76 (sensitivity 82.1% and specificity 38.6%). Predicting power of FDG PET for BM involvement was not different across lymphoma subtypes. Multivariate survival analysis revealed that BM FDG PET finding was an independent prognostic factor for survival in PTCL and NKTCL. Moreover, MLR was a significant prognostic factor for both PFS and OS (P = 0.001 and 0.005) in BM involvement-negative patients by BM biopsy.Conclusion: Although FDG PET findings fairly correlates with BM biopsy findings, FDG PET could not replace BM biopsy in PTCL and NKTCL. Rather, BM finding on FDG PET is an independent prognostic factor in these tumors, suggesting further biologic relevance of FDG PET findings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Survival and treatment of cranial and spinal chordomas: a population-based study.

Chordomas are rare, slow-growing malignant tumors. Given the paucity of data of the disease, the treatment strategies are disputed. We collected clinical and survival information of patients with chordoma diagnosed between 1975 and 2016 from the Surveillance, Epidemiology, and End Results database. A total of 1797 patients were initially enrolled, including 762 (42.4%) cranial and 1035 (57.6%) spinal chordoma. A total of 1504 patients were further evaluated after screening. In the cranial group, the surgery (gross total resection (GTR): p = 0.001 for overall survival (OS); p = 0.009 for cancer-specific survival (CSS)), tumor extension (distant metastasis: p = 0.001 for OS; p = 0.002 for CSS), and the age (p < 0.001 for OS) were independent prognostic factors for survival. In the spinal group, theage (p = 0.004), location (p < 0.001), GTR (p < 0.001), and tumor extension (distant metastasis, p < 0.001) were independent prognostic factors for OS; the age (p = 0.007), histological type (p < 0.001), GTR (p < 0.001), radiation (p = 0.018), chemotherapy (p = 0.006), and tumor extension (p < 0.001) were independent prognostic factors for CSS. In this large cohort, a significant association was noted between extent of resection and outcome. Even though adjuvant radiation or chemotherapy did not benefit patients with chordoma, the effect on prognosis can be explored in a further studybased on our findings.

Predictive factors for survival following stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumour thrombosis and construction of a nomogram

BackgroundWe evaluated the treatment response and predictive factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT), who underwent stereotactic body radiotherapy (SBRT). Additionally, we developed and validated a personalised prediction model for patient survival.MethodsClinical information was retrospectively collected for 80 patients with HCC and PVTT, who were treated with SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) between December 2015 and June 2019. A multivariate Cox proportional hazard regression model was used to identify the independent predictive factors for survival. Clinical factors were subsequently presented in a nomogram. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the accuracy of the model and the net clinical benefit.ResultsAll patients completed the planned radiotherapy treatment, and the median follow-up duration was 10 months (range, 1–35.3 months). The median survival duration was 11.5 months, with 3-, 6-, and 12-month survival rates of 92.5, 74.5, and 47.5%, respectively. The multivariable Cox regression model indicated that the following were significant independent predictors of OS: clinical T stage (p = 0.001, hazard ratio [HR] = 3.085, 95% confidence interval [CI]: 1.514–6.286), cirrhosis (p = 0.014, HR = 2.988, 95% CI: 1.246–7.168), age (p = 0.005, HR = 1.043, 95% CI: 1.013–1.075), alpha-fetoprotein level (p = 0.022, HR = 1.000, 95% CI: 1.000–1.000), and haemoglobin level (p = 0.008, HR = 0.979, 95% CI: 0.963–0.994). A nomogram based on five independent risk factors and DCA demonstrated a favourable predictive accuracy of patient survival (AUC = 0.74, 95% CI: 0.63–0.85) and the clinical usefulness of the model.ConclusionsSBRT is an effective treatment for patients with HCC with PVTT. Notably, clinical T stage, presence of cirrhosis, age, alpha-fetoprotein levels, and haemoglobin levels are independent prognostic factors for survival. The presented nomogram can be used to predict the survival of patients with HCC and PVTT, who underwent SBRT.

Association of preoperative serum HE4 levels on the survival of patients with endometrial cancer.

To evaluate the association between preoperative serum human epididymis protein 4 (HE4) levels and survival outcomes in endometrial cancer (EC) patients. A retrospective cohort study was conducted of EC patients who were scheduled for surgery between September 2013 and May 2014 at Rajavithi Hospital. Association between preoperative serum HE4 levels and clinicopathological characteristics were evaluated. Cox proportional-hazards model was used to compare overall survival (OS) and recurrence-free survival (RFS) between EC patients who had high serum HE4 levels and those who did not. A total of 86 EC patients were enrolled. Serum HE4 levels was significantly associated with older age (p < 0.001), postmenopausal women (p = 0.001), large tumor size (p < 0.001), presence of lymphovascular invasion (p = 0.022), deep myometrial invasion (p = 0.001), lymph node metastasis (0.017), high-risk group (p < 0.001), and death status (p = 0.002). With a median follow-up of 53months, the 3-years OS and PFS of EC patients who had high serum HE4 levels were significantly poorer than those who did not (71% vs 95.8%, and 67.7% vs 91.7%, respectively). A high serum HE4 level was a significant prognostic factor for OS and RFS from the univariate analysis. However, it was not a significant prognostic factor in the multivariate analysis. Preoperative high serum HE4 levels were significantly associated with the worse clinicopathological characteristic of EC patients and decreased OS and RFS. Although there was no strong independent prognostic factor for survival, serum HE4 levels could be used in an algorithm for stratifying high-risk EC patients with more proper management.

Treatment response measurements and survival outcomes in a cohort of newly diagnosed AL amyloidosis

Introduction The assessment of AL amyloidosis response is based on serum free light chains (sFLC) levels, and serum and urine monoclonal protein investigations. Recently, difference between involved and uninvolved free light chains (dFLC), involved free light chain (iFLC) and complete response (CR) has been reported as independent predictor of survival and a refinement of the hematological response criteria has been proposed by several groups. Methods In the current study, all consecutive newly diagnosed symptomatic AL amyloidosis patients were evaluated. The primary objective of the study was to assess hematological and organ response after first line of treatment. Results A cohort of 76 cases with upfront treatment was used for this analysis. After a median of 3 months post-therapy, hematological response was seen in 88% of cases including CR in 26.3%, VGPR in 38.2% and PR in 23.7%. Median OS was longer in patients with dFLC < 10 mg/L at 3 months, iFLC <20 mg/L at 1 and 3 months, and those achieving CR. Multivariate analysis showed presence of CR as the most important independent prognostic factors for survival. Conclusions Our study suggests that maximal sFLC response and CR are potential endpoints to define clinical outcomes. Large collaborative studies are required to validate and optimize response criteria.

Hepatoma upregulated protein and Ki-67 expression in resectable hepatocellular carcinoma.

Hepatoma upregulated protein (HURP) and Ki-67 have been identified as cancer-related genes involved in cell growth and proliferation. Previous experimental studies have suggested an essential role for HURP expression in liver carcinogenesis. However, data regarding HURP expression in hepatocellular carcinoma (HCC) and its correlation with patient outcomes are limited. In this study, we examined the clinicopathologic features associated with HURP expression in HCC, and compared them to the results of the Ki-67 study. Eighty-seven resected HCC at tumor, node, metastasis (TNM) stages I (n = 28), II (n = 29), and III (n = 30) were evaluated. HURP and Ki-67 expression were assessed by immunohistochemistry. Multivariate analysis was used to examine the prognostic significance of HURP and Ki-67 expression. HURP expression in HCC tissue was observed in 59% of patients and associated with female sex, low white blood cell count, and low platelet count. Ki-67 expression was observed in 67% of patients and associated with younger age, higher serum α-fetoprotein (AFP) levels, and frequent microvascular invasion. Univariate analysis showed that factors related to overall survival were: age >55 years, AFP >20 ng/mL, indocyanine green retention rate at 15 minutes (ICG-15) >15%, tumor size >5 cm, multiple tumors, macrovascular invasion, microvascular invasion, Ki-67 expression, and serum vascular endothelial growth factor >170 pg/mL. HURP expression was not associated with postresection survival. Multivariate analysis indicated that macrovascular invasion, multiple tumors, ICG-15 >15%, and Ki-67 expression were independent factors for overall survival. Multiple tumors and Ki-67 expression were independent factors related to recurrence-free survival. In our study, HURP expression in HCC tissue was not associated with post-resection survival. Ki-67 expression was an independent prognostic factor for survival. Our results suggest that the effect of HURP activity on growth, invasion, and postresection outcome of HCC in actual patients is less than previously demonstrated in experimental studies.

Value of total lesion glycolysis and cell-of-origin subtypes for prognostic stratification of diffuse large B-cell lymphoma patients.

This study aimed to explore the added prognostic value of baseline metabolic volumetric parameters and cell of origin subtypes to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in nodal diffuse large B-cell lymphoma (DLBCL) patients. A total of 184 consecutive de novo nodal DLBCL patients who underwent baseline positron emission tomography/computed tomography (PET/CT) were included in this study. Kaplan-Meier estimates were generated to evaluate the clinical, biological, and PET/CT parameters' prognostic value. The Cox proportional hazards model was performed to examine the potential independent predictors for progression-free survival (PFS) and overall survival (OS). With a median follow-up of 35 months, the 3-year PFS and OS were 65.2% and 73.0%, respectively. In univariate analysis, total lesion glycolysis (TLG), cell-of-origin subtypes, and NCCN-IPI were both PFS and OS predictors. High TLG (≥1,852), non-germinal center B (non-GCB), as well as high NCCN-IPI (≥4), were shown to be independently significantly associated with inferior PFS and OS after multivariate analysis. Based on the number of risk factors (high TLG, non-GCB, and high NCCN-IPI), a revised risk model was designed, and the participants were divided into four risk groups with very different outcomes, in which the PFS rates were 89.7%, 66.2%, 51.7%, and 26.7% (χ2=30.179, P<0.001), and OS rates were 93.1%, 73.8%, 56.7%, and 43.3%, respectively (χ2=23.649, P<0.001), respectively. Compared with the NCCN-IPI alone, the revised risk model showed a stronger ability to reveal further discrimination among subgroups, especially for participants with very unfavorable survival outcomes (PFS: χ2=9.963, P=0.002; OS: χ2=4.166, P=0.041, respectively). The TLG, cell-of-origin subtypes, and NCCN-IPI are independent prognostic survival factors in DLBCL patients. Moreover, the revised risk model composed of the number of risk factors (high TLG, non-GCB, and high NCCN-IPI) can stratify patients better than the NCCN-IPI, especially for patients at high risk, which suggests its potential integration into decision making for personalized medicine.

The prognostic value of tumor markers in patients (pts) with resectable gastric cancer (GC) receiving perioperative therapy in the CRITICS trial.

4024 Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are well-known tumor markers. Most studies on CEA and CA 19-9 in pts with GC were performed in Asia, and/or in the metastatic setting. The aim of this study was to investigate the prognostic value of blood derived laboratory parameters in a cohort of European pts with resectable non-metastatic GC. Methods: In the CRITICS trial, 788 pts with resectable GC underwent perioperative therapy (preoperative chemotherapy plus either postoperative chemotherapy or postoperative chemoradiotherapy). Blood levels of CEA, CA 19-9, alkaline phosphatase (AP), creatinine, neutrophils, hemoglobin (Hb) and lactate dehydrogenase (LDH) were determined prior to treatment. Data for these variables were available for at least 89% of the pts. Factors significant on univariable cox regression analysis were further explored in multivariable analysis. Probabilities to undergo potentially curative surgery was investigated for factors significant on multivariable analysis. The relationship between tumor markers and the presence of circulating tumor DNA (ctDNA) was explored in 50 pts with available ctDNA data. Results: CEA and CA 19-9 were identified as independent prognostic factors for survival (Table). Probabilities to undergo potentially curative surgery were 86%, 77% and 60% for pts with no elevated tumor makers versus those with elevated CEA or elevated CA 19-9 versus those with both tumor markers elevated, respectively (p&lt;0.001). No relationship was found between elevated tumor marker(s) and the presence of ctDNA neither pretreatment nor preoperatively. Conclusions: Pretreatment blood levels of CEA and CA 19-9 were identified as prognostic factors for overall survival in a large cohort of European GC pts with potentially curable disease. These factors may guide treatment choices at an early phase and should be included in future trials to determine their role in clinical decision making.[Table: see text]

Prognostic value of pre-treatment systemic immune-inflammation index in patients with endometrial cancer.

The systemic immune-inflammation index (SII), which is calculated using absolute platelet, neutrophil, and lymphocyte counts, has recently attracted attentions as a prognostic indicator in patients with solid malignancies. In the current study, we retrospectively investigated the prognostic significance of pre-treatment SII among patients with endometrial cancer. Endometrial cancer patients treated at Nara medical university hospital between 2008 and 2018 were included in the current study. Receiver operating characteristic (ROC) curve was used to find the optimal SII cut-off values for 3-years progression free survival (PFS) and overall survival (OS). Then, the predictive abilities of SII and its superiority over neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were investigated. Kaplan-Meier method was used to calculate the OS and PFS rates, and log-rank test was used to compare the survival rate between two groups. Univariate and multivariate Cox regression analysis were performed to identify risk factors for PFS and OS. A total of 442 patients were included in the current study. The cut-off value of SII for predicting PFS and OS were defined by ROC analysis as 931 and 910, respectively. Univariate analyses showed that elevated SII was associated with significantly shorter survival (p <0.001 for both PFS and OS). Cox regression analyses revealed that an advanced FIGO stage (p <0.001 for both PFS and OS) and an elevated SII (p = 0.014 for PFS, p = 0.011 for OS) are the independent prognostic factors for survival. When SII was compared with NLR and PLR, SII showed greater area under curve for predicting survival. The SII is an independent prognostic factor in endometrial cancer patients, allowing more precise survival estimation than PLR or NLR.

Skeletal system as a rare metastatic site in patients with ovarian carcinoma

ObjectiveTo evaluate the frequency and predictors of bone metastasis in patients with ovarian cancer and to determine prognostic factors associated with this finding.MethodsPatients diagnosed with ovarian cancer between January 2009...

Prognostic factor analysis of patients with small cell lung cancer: Real-world data from 988 patients.

BackgroundSmall cell lung cancer (SCLC) is characterized by aggressive spread and poor prognosis, but has limited treatment options. Results of prognostic factors from randomized trials on treatment arrangement are conflicting and large‐scale real‐world analysis is lacking.MethodsPatients diagnosed SCLC between 2008 and 2018 in Peking University Cancer Hospital were included in this study. Kaplan–Meier methods were adopted, and univariate analysis and multivariate Cox regression models were constructed to analyze prognostic factors.ResultsAmong 1045 patients who presented to our center, 988 eligible patients were identified. Median overall survival (OS) was 16.0 months for the whole group, 24.0 months and 11.0 months for limited stage small cell lung cancer (LS‐SCLC) and extensive stage small cell lung cancer (ES‐SCLC), separately. Limited‐stage, good performance status (PS) (ECOG 0–1), response to primary systemic treatment, and patients who received initiative irradiation and three or more lines of chemotherapy were predicted to have better OS in the whole group. Only response to first‐line systemic therapy and prophylactic cranial irradiation (PCI) were independent prognostic factors of survival in LS‐SCLC; while good PS (ECOG 0–1), without liver, bone, or subcutaneous metastases, response to first‐line therapy, initial local irradiation, and three or more lines of systemic therapy predicted a favorable prognosis in ES‐SCLC.ConclusionsThe present study retrieved from large real–world data suggested that response to primary systemic therapy and aggressive radiotherapy are independent prognostic factors for SCLC. PCI and initiative irradiation for original or metastatic sites improved the OS in LS‐SCLC and ES‐SCLC, respectively.

V-Domain Ig Suppressor of T Cell Activation (VISTA) Expression Is an Independent Prognostic Factor in Multiple Myeloma.

Simple SummaryMultiple myeloma (MM) is characterized by loss of anti-tumor T-cell immunity. The precise mechanisms by which malignant plasma cells escape T-cell immunity are unknown, although upregulation of checkpoint molecules is seen in progressive disease. The aim of our study was to investigate mechanisms of escape from T-cell immunity. We observed that the expression of V-domain Ig suppressor of T cell activation (VISTA) in the tumor microenvironment is an independent prognostic factor for survival in MM and its major cellular source is tumor infiltrating CD11B+ cells. The combination of high VISTA expression in the tumor combined with low infiltration of CD8+ cells compared to the surrounding stromal tissue is significantly associated with poor survival. These finding have identified VISTA as an interesting target for inhibition to circumvent escape of T-cell immunity.Multiple myeloma (MM) is characterized by loss of anti-tumor T cell immunity. Despite moderate success of treatment with anti-PD1 antibodies, effective treatment is still challenged by poor T cell-mediated control of MM. To better enable identification of shortcomings in T-cell immunity that relate to overall survival (OS), we interrogated transcriptomic data of bone marrow samples from eight clinical trials (n = 1654) and one trial-independent patient cohort (n = 718) for multivariate analysis. Gene expression of V-domain Ig suppressor of T cell activation (VISTA) was observed to correlate to OS [hazard ratio (HR): 0.72; 95% CI: 0.61–0.83; p = 0.005]. Upon imaging the immune contexture of MM bone marrow tissues (n = 22) via multiplex in situ stainings, we demonstrated that VISTA was expressed predominantly by CD11b+ myeloid cells. The combination of abundance of VISTA+, CD11b+ cells in the tumor but not stromal tissue together with low presence of CD8+ T cells in the same tissue compartment, termed a high VISTA-associated T cell exclusion score, was significantly associated with short OS [HR: 16.6; 95% CI: 4.54–62.50; p < 0.0001]. Taken together, the prognostic value of a combined score of VISTA+, CD11b+ and CD8+ cells in the tumor compartment could potentially be utilized to guide stratification of MM patients for immune therapies.