Outcome In Solid Tumors Research Articles

High CD206 levels in Hodgkin lymphoma-educated macrophages are linked to matrix-remodeling and lymphoma dissemination.

Macrophages (Mφ) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. Mφ heterogeneity, the mechanisms of their recruitment, and their differentiation into lymphoma‐promoting, alternatively activated M2‐like phenotypes are still not fully understood. Therefore, further functional studies are required to understand biological mechanisms associated with human tumor‐associated Mφ (TAM). Here, we show that the global mRNA expression and protein abundance of human Mφ differentiated in Hodgkin lymphoma (HL)‐conditioned medium (CM) differ from those of Mφ educated by conditioned media from diffuse large B‐cell lymphoma (DLBCL) cells or, classically, by macrophage colony‐stimulating factor (M‐CSF). Conditioned media from HL cells support TAM differentiation through upregulation of surface antigens such as CD40, CD163, CD206, and PD‐L1. In particular, RNA and cell surface protein expression of mannose receptor 1 (MRC1)/CD206 significantly exceed the levels induced by classical M‐CSF stimulation in M2‐like Mφ; this is regulated by interleukin 13 to a large extent. Functionally, high CD206 enhances mannose‐dependent endocytosis and uptake of type I collagen. Together with high matrix metalloprotease9 secretion, HL‐TAMs appear to be active modulators of the tumor matrix. Preclinical in ovo models show that co‐cultures of HL cells with monocytes or Mφ support dissemination of lymphoma cells via lymphatic vessels, while tumor size and vessel destruction are decreased in comparison with lymphoma‐only tumors. Immunohistology of human HL tissues reveals a fraction of cases feature large numbers of CD206‐positive cells, with high MRC1 expression being characteristic of HL‐stage IV. In summary, the lymphoma‐TAM interaction contributes to matrix‐remodeling and lymphoma cell dissemination.

271P - Association of derived neutrophil-to-lymphocyte ratio (dNLR) with pathological complete response (pCR) after neoadjuvant chemotherapy (CT)

271P - Association of derived neutrophil-to-lymphocyte ratio (dNLR) with pathological complete response (pCR) after neoadjuvant chemotherapy (CT)

Dynamic contrast-enhanced perfusion parameters in ovarian cancer: Good accuracy in identifying high HIF-1α expression.

BackgroundHypoxia significantly influences treatment response and clinical outcome in solid tumors. A noninvasive marker for hypoxia will help physicians in treatment planning and encourage the efficient use of hypoxia targeted therapies. The purpose of this study was to investigate whether pharmacokinetic dynamic contrast-enhanced (DCE) perfusion parameters are associated with a specific marker of hypoxia, hypoxia-inducible factor 1 alpha (HIF-1α) in ovarian cancer (OC).Materials and methodsThirty-eight patients with primary OC were enrolled in this prospective study approved by the local ethical committee. Patients underwent dynamic gadolinium-enhanced 3.0 T MRI as part of their staging investigations. Pharmacokinetic perfusion parameters, including a rate constant for transfer of contrast agent from plasma to extravascular extracellular space (EES) (Ktrans) and a rate constant from EES to plasma (Kep), were measured by drawing two types of regions of interest (ROIs): a large solid lesion (L-ROI) and a solid, most enhancing small area (S-ROI) (NordicICE platform). Tissue samples for immunohistochemical analysis were collected during surgery. Kruskal–Wallis, Mann–Whitney U and Chi-square tests were used in statistical analyses. Receiver Operating Characteristic curve analyzes were done for DCE parameters to discriminate high HIF-1α expression.ResultsPharmacokinetic perfusion parameters Ktrans and Kep were inversely associated with HIF-1α expression (Ktrans L-ROI P = 0.021; Ktrans S-ROI P = 0.018 and Kep L-ROI P = 0.032; Kep S-ROI P = 0.033). Ktrans and Kep showed good accuracy in identifying high HIF-1α expression (AUC = 0.832 Ktrans L-ROI; 0.840 Ktrans S-ROI; 0.808 Kep L-ROI and 0.808 Kep L-ROI).ConclusionThis preliminary study demonstrated that pharmacokinetic DCE-MRI perfusion parameters are associated with the hypoxia specific marker, HIF-1α in OC. DCE-MRI may be a useful supplementary tool in the characterization of OC tumors in a staging investigation.

A QSP Model for Predicting Clinical Responses to Monotherapy, Combination and Sequential Therapy Following CTLA-4, PD-1, and PD-L1 Checkpoint Blockade

Over the past decade, several immunotherapies have been approved for the treatment of melanoma. The most prominent of these are the immune checkpoint inhibitors, which are antibodies that block the inhibitory effects on the immune system by checkpoint receptors, such as CTLA-4, PD-1 and PD-L1. Preclinically, blocking these receptors has led to increased activation and proliferation of effector cells following stimulation and antigen recognition, and subsequently, more effective elimination of cancer cells. Translation from preclinical to clinical outcomes in solid tumors has shown the existence of a wide diversity of individual patient responses, linked to several patient-specific parameters. We developed a quantitative systems pharmacology (QSP) model that looks at the mentioned checkpoint blockade therapies administered as mono-, combo- and sequential therapies, to show how different combinations of specific patient parameters defined within physiological ranges distinguish different types of virtual patient responders to these therapies for melanoma. Further validation by fitting and subsequent simulations of virtual clinical trials mimicking actual patient trials demonstrated that the model can capture a wide variety of tumor dynamics that are observed in the clinic and can predict median clinical responses. Our aim here is to present a QSP model for combination immunotherapy specific to melanoma.

Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia

BackgroundAberrant metabolism is a hallmark of cancer cells. Recently, ATP citrate-lyase (ACLY) expression was demonstrated as an independent predictor of clinical outcome in solid tumors. However, no systematic study was conducted to explore the prognostic impact of ACLY on acute myeloid leukemia (AML).MethodsTo assess the prognostic value of ACLY transcript, we conducted a study with a discovery and validation design. We measured ACLY transcript by real-time quantitative PCR in 274 AML patients, and validated the prognostic value in the two independent cohorts using published data. Meta-analysis of gene-expression profile and inhibition ACLY expression in leukemia cell lines were conducted to help us understand the biological insight of low ACLY expression.ResultsLow ACLY expression is less common amongst AMLs with DNMT3A mutations, but coexisted in double allele CEBPA mutations. Moreover, low ACLY expression is associated with favorable overall survival in AML patients and is involved in multiple pathways. These results are also validated in two independent cohorts of AML patients. Moreover, ACLY silencing induces proliferation arrest in THP-1 and MOLM-13 leukemia cell lines.ConclusionWe found low ACLY expression is associated with favorable overall survival in AML patients.

Comparison of the Prognostic Value of Systemic Inflammation Response Markers in Small Cell Lung Cancer Patients.

Increasing evidences support that systemic inflammation-based prognostic scores, modified Glasgow Prognostic Score (mGPS), C-reactive Protein/Albumin (CRP/ALB), Albumin/Globulin (AGR), Prognostic Nutritional Index (PNI) and Advanced Lung cancer Inflammation index (ALI), are key determinants of patients' outcome in solid tumors. However, in small cell lung cancer (SCLC), there have been no direct comparisons of them. Thus, the aim of this study was to compare the prognostic value of these markers in SCLC, and select a most appropriative one. The patients with confirmed SCLC were screened between 2006 and 2011, and inflammation-based prognostic factors (mGPS, CRP/ALB, AGR, PNI, ALI) were examined. Kaplan-Meier and Cox regression analysis were performed to assess these inflammation-based prognostic scores associated with overall survival (OS). Subsequently, we compared the prognostic value of these inflammation-based prognostic scores using the area under the curve (AUC). In 451 patients, on univariate analysis, mGPS (P<0.001), CRP/ALB (P<0.001), AGR (P<0.001), PNI (P<0.001) and ALI (P<0.001) were the strongest predictors of OS. Further multivariate analysis confirmed mGPS (P<0.001), CRP/ALB (P=0.007), AGR (P=0.034) and PNI (P=0.026) as independent markers associated with OS. Further subgroup analysis revealed CRP/ALB was able to predict outcome in both limited (P=0.005) and extensive disease (P=0.013). The CRP/ALB had higher AUC values compared with other inflammation-based prognostic socres (0.566). The CRP/ALB was characterized as best, in comparison to other systemic inflammation-based prognostic scores, for its predictive power of SCLC patients' survival, and had the potential to be hierarchical factor in future clinical trials.

Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant melanoma

BackgroundMetformin is one of the biguanides commonly used in patients with type II Diabetes Mellitus. Apart from its hypoglycemic properties, metformin also inhibits the cell cycle by restricting protein synthesis and cell proliferation via regulating the LKB1/AMPL pathway. Furthermore, it also enhances the PD-1 blockade through a reduction of tumor hypoxia. Metformin has shown a significant favorable impact on treatment-related outcomes in solid tumors, but these outcomes have not been replicated in the limited clinical studies done on malignant melanoma. Moreover, none of these studies have reported on the efficacy of the combined use of metformin and immune checkpoint inhibitors (ICIs).MethodsThis is a retrospective cohort study that includes patients diagnosed with metastatic malignant melanoma and treated with ipilimumab, nivolumab, and/or pembrolizumab (Cohort A); or ipilimumab, nivolumab, and/or pembrolizumab plus metformin (Cohort B) between January 1st 2011 through December 15th 2017. In this study, patients are stratified based on anti-PD-1 only and anti-CTLA4/anti-PD-1 combination therapies in each cohort. Objective response rate (ORR) is the primary endpoint. Disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) are the secondary endpoints.ResultsCohort A had 33 patients (60%), while cohort B had 22 (40%). Overall patient characteristics were similar between both cohorts. ORR was higher in cohort B (68.2% vs. 54.5%, P = 0.31). The DCR was higher in cohort B as well (77.3% vs. 60.6%, P = 0.19). Median OS (46.7 months vs. 28 months), and median PFS (19.8 months vs. 5 months) were longer in cohort B. However, on univariate and multivariate analyses, none of these differences were statistically significant. The mean number of new metastatic sites which appeared during therapy were significantly higher in cohort A (A:1.51 vs. B:0.59, P = 0.009).ConclusionWe have observed favorable treatment-related outcomes (ORR, DCR, median PFS and median OS) in patients who have received metformin in combination with ICIs without reaching significance, probably, due to small sample size. Hence, large prospective clinical trials are required to study the synergistic effect of metformin in combination with ICIs before it can be recommended as routine additive therapy.

Galectin-9 Expression Predicts Favorable Clinical Outcome in Solid Tumors: A Systematic Review and Meta-Analysis

Background and Objective: Galectin-9 (Gal-9) is one of the galectin family members which are known as proteins with β-galactoside-binding affinity. Accumulative evidence suggest that Gal-9 plays multifaceted roles in tumor biology. However, the prognostic significance of Gal-9 in solid cancer patients remains controversial. The objective of the study was to clarify the prognostic significance of Gal-9 in solid tumors via meta-analysis.Methods: We searched PubMed, Embase and the Cochrane library for studies that report the correlation between Gal-9 expression and prognosis or clinicopathological parameters in solid cancer patients from inception to October 2017, with no language restriction. We calculated pooled hazard ratio (HR) and 95% confidence interval (CI) to investigate the prognostic significance of Gal-9 expression in solid tumors. We also calculated Odds ratio (OR) to explore the association between Gal-9 expression and clinicopathological features.Results: We included Fourteen studies with 2326 patients in our meta-analysis. The synthetic results revealed that high Gal-9 expression indicated improved overall survival (OS; HR = 0.70, 95% CI = 0.51–0.71, P = 0.006) but had no correlation with disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 0.85, 95% CI = 0.51–1.41, P = 0.527) in solid tumors. In stratified analyses, high Gal-9 expression was significantly correlated with improved OS in hepatocellular carcinoma and colon cancer and with improved DFS/RFS in gastric cancer and non-small cell lung cancer. In addition, ethnicity and the method of data extraction didn’t affect the positive prognostic values of high Gal-9 expression. Moreover, high Gal-9 expression was significantly correlated with a smaller depth of invasion (TI/TII vs. TIII/TIV, OR = 2.80, 95% CI = 1.97–3.96, P < 0.001), an earlier histopathological stage (I/II vs. III/IV, OR = 3.00, 95% CI = 2.04–4.42, P < 0.001), negative lymph node metastasis (Presence vs. Absence, OR = 0.47, 95% CI = 0.25–0.89, P = 0.020) and negative distal tumor metastasis (Presence vs. Absence, OR = 13.85, 95% CI = 3.50–54.76, P < 0.001).Conclusion: Gal-9 expression indicates beneficial outcome in patients with solid tumors and is correlated with the pathogenesis of solid tumors. Gal-9 may serve as a prognostic biomarker and an emerging therapeutic target against solid tumors.

A systematic review of the influence of radiation-induced lymphopenia on survival outcomes in solid tumors.

Lymphopenia is a common accompaniment of multimodal cancer therapy. As the most radiosensitive cells of the hematopoietic system, lymphocytes residing within or circulating through a radiation portal are frequently depleted by radiation therapy. The recognition that radiation-induced reduction of circulating lymphocyte counts and eventual lymphocyte infiltration of tumors have a tangible impact on overall survival outcomes has revived the interest in understanding the causes of treatment-associated lymphopenia and developing strategies to predict, prevent and ameliorate this well-documented phenomenon. In this systematic review, we have performed a comprehensive search of the literature to elucidate the studies that document a correlation between radiation-associated lymphopenia and survival outcomes in solid malignancies. We also summarize potential unifying paradigms that account for radiation-induced lymphopenia across studies and lay the groundwork for attempting to explain and/or counter this phenomenon.

Tumor-Infiltrating Podoplanin+ Fibroblasts Predict Worse Outcome in Solid Tumors

Background/Aims: Tumor-infiltrating fibroblasts are a heterogeneous population, and different subpopulations play differential roles in tumor microenvironment. However, the prognostic role of podoplanin⁺ fibroblasts in human solid tumors still remains controversial. Therefore, we performed the meta-analysis to better understand the role of this subpopulation in prognosis prediction for patients with solid tumor. Methods: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral podoplanin⁺ fibroblast density detected by immunohistochemical method and overall survival (OS) and/or disease-free survival (DFS) in patients with solid tumor, then computed extracted data into hazard ratios for OS, DFS and clinicopathological features with STATA 12.0. Results: A total of 4883 patients from 29 published studies were incorporated into this meta-analysis. We found that podoplanin⁺ fibroblast infiltration significantly decreased OS and DFS in all types of solid tumors. In stratified analyses, podoplanin⁺ fibroblast infiltration was significantly associated with worse OS in cholangiocarcinoma, breast, lung and pancreatic cancer. And these cells were inversely associated with DFS in breast, lung and pancreatic cancer. In addition, high density of these cells significantly correlated with unfavorable clinicopathological features such as lymph node metastasis, TNM stage, lymphatic and vascular invasion of solid tumor. Conclusion: Podoplanin⁺ fibroblast infiltration leads to worse clinical outcome in solid tumors, implicating that it is a valuable prognostic biomarker and targeting it may have a potential for effective treatment.

Prognostic Role of Pretreatment Plasma D-Dimer in Patients with Solid Tumors: a Systematic Review and Meta-Analysis

Background/Aims: Elevated pretreatment plasma D-dimer level has been reported as an unfavorable prognostic indicator in several malignancies. The aim of this meta-analysis was to evaluate the prognostic value of elevated D-dimer level in solid tumors. Methods: A comprehensive search of electronic databases up to June 10, 2017 was carried out by two independent reviewers. We included studies exploring the association between pretreatment plasma D-dimer level and patients’ survival outcomes in solid tumors. Overall survival (OS) was regarded as primary outcome and progression-free survival (PFS), disease-free survival (DFS) as well as cancer-specific survival (CSS) were chosen as secondary outcomes. Hazard ratio and 95% confidence interval (CI) were extracted directly or indirectly from included studies. Results: 49 studies with 13001 patients were included in our meta-analysis. Elevated D-dimer was markedly associated with poor OS (pooled HR = 1.90, 95% CI = 1.63 - 2.20, P < 0.001). The effect was observed in all different tumor sites, disease stages, cut-off values and ethnicities. Meanwhile, patients with a high plasma D-dimer had a shorter PFS (HR = 1.46, 95% CI = 1.22–1.76; P < 0.001), DFS (HR = 2.02, 95% CI = 1.56–2.62) and CSS (HR = 2.04, 95% CI= 1.58 – 2.64). Conclusions: Analysis of the pretreatment plasma D-dimer might provide useful information to predict prognosis in patients with solid tumors.

Repolarizing heterogeneous leukemia-associated macrophages with more M1 characteristics eliminates their pro-leukemic effects

ABSTRACT Macrophages exhibit phenotypic heterogeneity under both physiological and pathological conditions. Applications targeting M2-like tumor-associated macrophages (TAMs) improve outcome in solid tumors. Considerable differences are detected between leukemia-associated macrophages (LAMs) and TAMs. However, application to induce M1 characteristics in heterogeneous LAMs has not been established. Here we analyzed clinical relevance of macrophage phenotypes in human acute myeloid leukemia (AML), studied phenotypic evolution of bone marrow (BM) and spleen (SP) LAMs in mouse AML and T cell acute lymphoblastic leukemia (T-ALL) models, explored mechanism leading to different LAM phenotypes and tried to eliminate pro-leukemic effects by inducing M1 characteristics. The results showed that more M2-like LAMs but not total LAMs correlated with worse prognosis in AML patients. Heterogeneity of LAM activation in tissue-specific leukemic microenvironments was observed in both AML and ALL models, i.e. SP LAMs evolved with more M2 characteristics while BM LAMs with more M1 characteristics. Furthermore, IRF7 contributed to M1 characteristics through the activation of SAPK/JNK pathway. Moreover, targeting IRF7-SAPK/JNK pathway to induce M1 characteristics in LAMs contributed to prolonged survival in leukemia mice. Our study provides the potential target for macrophage based immuno-therapy strategy against leukemia.

Prognostic role of tumor-infiltrating CD57-positive lymphocytes in solid tumors: a meta-analysis.

The prognostic role of tumor-infiltrating CD57-positive lymphocytes (CD57+ lymphocytes) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 26 published studies with 7656 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD57+ lymphocytes in human solid tumors. We found that CD57+ lymphocyte infiltration significantly improved overall survival (OS) including 1 – year, 3 – year and 5 – year survival, and disease – free survival (DFS) in all types of solid tumors. In stratified analyses, CD57+ lymphocyte infiltration was significantly associated with better OS in hepatocellular, esophageal, head and neck carcinoma, non-small cell lung cancer, 5 – year survival in colorectal cancer, and 3 – year and 5 – year survival in gastric cancer, but not with 1 – year survival in gastric cancer, or 1 – year or 3 – year survival in colorectal cancer. In addition, high density of intratumoral CD57+ lymphocytes was significantly inversely correlated with lymph node metastasis and TNM stage of solid tumor. In conclusion, CD57+ lymphocyte infiltration leads to a favorable clinical outcome in solid tumors, implicating that it is a useful biomarker for prognosis and adoptive immunotherapy based on these cells may be a promising choice for treatment.

Tumor-infiltrating tryptase+ mast cells predict unfavorable clinical outcome in solid tumors.

The prognostic role of tumor-infiltrating tryptase+ mast cells in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 28 published studies with 4224 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating tryptase+ mast cells in human solid tumors. We found that tryptase+ mast cell infiltration significantly decreased overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, tryptase+ mast cell infiltration was significantly associated with worse OS in non-small cell lung cancer, hepatocellular carcinoma and 5-year survival in colorectal cancer. And these cells were inversely associated with DFS in hepatocellular and colorectal cancer. In addition, high density of intratumoral tryptase+ mast cells significantly correlated with lymph node metastasis of solid tumor. In conclusion, Tryptase+ mast cell infiltration leads to an unfavorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances and targeting it may have a potential for effective treatment.

Tumor-infiltrating CD45RO+ Memory T Lymphocytes Predict Favorable Clinical Outcome in Solid Tumors

The prognostic role of tumor-infiltrating CD45RO+ memory T lymphocytes (CD45RO+ T cells) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 25 published studies with 4720 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD45RO+ T cells in human solid tumors. We found that CD45RO+ T cell infiltration was significantly associated with improved overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, CD45RO+ T cell infiltration significantly improved 1-year, 3-year and 5-year OS in colorectal, gastric and esophageal cancer, but only 5-year OS in hepatocellular carcinoma. And these cells were positively associated with 1-year, 3-year and 5-year DFS in hepatocellular, colorectal and esophageal cancer. In addition, high density of intratumoral CD45RO+ T cells inversely correlated with TNM stage of solid tumor. In conclusion, CD45RO+ memory T lymphocyte infiltration leads to a favorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances.

Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors.

The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors.

Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis.

BackgroundInflammation may play an important role in cancer progression, and a higher systemic immune-inflammation index (SII) has been reported to be a poor prognostic marker in several malignancies. However, the results of published studies are inconsistent.Materials and MethodsA systematic review of databases was conducted to search for publications regarding the association between blood SII and clinical outcome in solid tumors with a date up to February 12, 2017. The primary outcome was overall survival (OS) and the secondary outcomes were progression-free survival (PFS) and cancer-specific survival (CSS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the strength of the association between blood SII and clinical outcome in solid tumors.ResultsA total of 15 articles were included in the analysis. Overall, systemic immune-inflammation index greater than the cutoff predicted poor overall survival (HR = 1.55, 95% CI = 1.27–1.88; P < 0.001). Subgroup analyses revealed that high systemic immune-inflammation index indicated a worse overall survival in hepatocellular carcinoma (P < 0.001), urinary cancers (P < 0.001), gastrointestinal tract cancers (P = 0.02), small cell lung cancer (P < 0.05) and acral melanoma (P < 0.001). Hazard ratio for systemic immune-inflammation index greater than the cutoff for cancer-specific survival was 1.44 (P < 0.05).ConclusionsElevated systemic immune-inflammation index is associated with a worse overall survival in many solid tumors. The systemic-inflammation index can act as a powerful prognostic indicator of poor outcome in patients with solid tumors.

Hyperglycemia and survival in solid tumors: A systematic review and meta-analysis.

e18158 Background: Diabetes is associated with adverse cancer outcomes. However, the effect of hyperglycemia independent of diabetes is unclear. Here we report on a meta-analysis exploring the effect of hyperglycemia on outcomes of solid tumors, and the influence of clinical factors on this association. Methods: A systematic search of electronic databases identified publications exploring the effect of hyperglycemia on overall (OS), disease-free (DFS) or progression-free survival (PFS). Definitions of hyperglycemia (fasting blood glucose, random blood glucose or HbA1c) and cut-offs varied between studies. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) or a p -value were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on method of hyperglycemia measurement (HbA1c, other) and tumor stage (early, advanced, mixed). Meta-regression was performed to evaluate the influence of clinical characteristics including baseline diabetes status on the HR for OS. All statistical tests were two-sided. Results: Eight studies comprising a total of 4342 patients were included. All studies reported HRs for OS. Two studies reported DFS outcomes, and two reported PFS. Hyperglycemia was associated with worse OS (HR 2.07, 95% CI = 1.70 - 2.52; P &lt; 0.001) and DFS (HR 1.61, 95% CI = 1.04 - 2.49; P &lt; 0.001), but did not decrease PFS (HR 1.08, 95% CI = 0.72 - 1.62; P = 0.71). The association with worse OS maintained in subgroups based on method of hyperglycemia measurement (subgroup difference P = 0.65) and tumor stage ( P= 0.47). Meta-regression analyses did not identify any factors significantly altering the magnitude of association between hyperglycemia and OS (see Table). Conclusions: Hyperglycemia is associated with adverse OS and DFS in patients with cancer, and the therapeutic role of optimal glycemic control warrants further investigation. [Table: see text]

The Cancer Care Treatment Outcomes Ontology (CCTO): A computable ontology for profiling treatment outcomes of patients with solid tumors.

e18137 Background: Systematic enhancement of knowledge about outcomes of cancer therapy is a central goal for oncology research, practice and audit. However, there is no resource standardizing the disparate vocabulary used to describe treatment outcomes, which prevents translating the data acquired into value-adding information for better cancer care. Methods: To build an application ontology that organizes high-level concepts describing treatment outcomes in solid tumors, provisionally named Cancer Care Treatment Outcomes (CCTO), we extracted all trial endpoints listed in ClinicalTrials.gov, queried it using the keyword ‘cancer’, followed by an expert appraisal. Term definitions and synonyms were automatically imported from the National Cancer Institute thesaurus, and extra terms were imported from Common Toxicity Criteria for Adverse Events. Logical relationships between concepts were represented by forward chaining rules, aiding conversion between concepts. The coverage of CCTO was tested against MEDLINE abstracts, and the applicability of 1825 rules was tested in a case of metastatic colon cancer (index case). Results: After removing duplicated terms from 54705 trial entries, an ontology (CCTO), holding 1145 terms and organized into 13 concept groups (including but not limited to efficacy, safety, and quality of life), was built. CCTO not only captures a comprehensive taxonomic hierarchy (through is_a relationships) but also an evaluative hierarchy ( is_assessed_by) to aid the acquisition of treatment outcome data. At least one CCTO term was mentioned in 29493 of 29951 (98%) MEDLINE abstracts on phase 1-3 cancer trials; concepts about efficacy were mentioned in 7208 (79%) phase 1, 15051 (92%) phase 2, and 3884 (86%) phase 3 trials. We show that, by applying the relationship rules in an expert system shell, the event sequence of the index case can be readily converted into a comprehensive profile that incorporates survival measures, treatment responses, and adverse events. Conclusions: CCTO efficiently captures and categorizes high-level concepts of treatment endpoints in oncologic practice and enables rapid profiling of clinical outcomes for cancer patients.

Glucose transporter GLUT1 expression and clinical outcome in solid tumors: a systematic review and meta-analysis.

Glucose transporter 1 (GLUT1), the uniporter protein encoded by the SLC2A1 gene, is a key rate-limiting factor in the transport of glucose in cancer cells, and frequently expressed in a significant proportion of human cancers. Numerous studies have reported paradoxical evidence of the relationship between GLUT1 expression and prognosis in solid human tumors. To address this discrepancy, we conducted a thorough search of Pubmed and Web of Science for studies evaluating the expression of GLUT1 and overall survival (OS) and disease-free survival (DFS) in patients with solid cancer from 1993 to April 2016. Data from published researches were extracted and computed into odds ratio (OR). A total of 26 studies including 2948 patients met our search criteria and were evaluated. Overexpression of GLUT1 was found to significantly correlate with poor 3-year OS (OR: 2.86; 95% CI, 1.90–4.32, P < 0.00001) and 5-year OS (OR: 2.52; 95% CI, 1.75–3.61, P < 0.00001) of solid tumors. Similar results were observed when analysis of DFS was performed. Subgroup analysis revealed that elevated GLUT1 expression was associated with worse prognosis of oral squamous cell carcinoma and breast cancer. Taken together, overexpression of GLUT1 is correlated with poor survival in most solid tumors, suggesting that the expression status of GLUT1 is a vital prognostic indicator and promising therapeutic target in solid tumors.