Multivariate Analysis HR Research Articles

Integrating Red Blood Cell Features and Hemoglobin Levels in Metastatic Renal Cell Carcinoma Patients Treated with Pazopanib or Cabozantinib: An Easily Exploitable Prognostic Score.

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis still play a key role. The aim of the present study was to explore the prognostic performance of an integrated blood score, based on hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and red cell distribution width (RDW), in mRCC patients treated with anti-VEGF TKIs. The primary endpoint was to correlate Hb, MCV, and RDW with progression-free survival (PFS) and overall survival (OS). Our multicenter retrospective observational study involved mRCC patients treated with pazopanib or cabozantinib from January 2012 to December 2020 in nine Italian centers. Clinical records and laboratory data, including Hb levels, MCV, and RDW, were collected at baseline. Descriptive statistics and univariate and multivariate analyses were performed. We enrolled 301 mRCC patients of which 179 (59%) underwent pazopanib, and 122 (41%) cabozantinib. We considered baseline Hb ≥12 g/dL, MCV >87 fL, and RDW ≤16% as good prognostic factors; hence, developing a multiparametric score capable of delineating 4 different categories. The number of good prognostic factors was associated with significantly longer PFS and OS (p < 0.001 for both). Therefore, we developed a red blood cell-based score by stratifying cases into two groups (2-3 versus 0-1, good factors). The impact on PFS and OS was even more striking (median PFS (mPFS): 16.3 vs 7.9 months; median OS (mOS): 33.7 vs 14.1 months)), regardless of the TKI agent. When challenged with univariate and multivariate analysis, the blood score maintained its high prognostic significance in terms of OS (multivariate analysis HR for OS: 0.53, 95% CI 0.39-0.75; p < 0.001, respectively), while the impact on PFS resulted in borderline significance. Our analyses demonstrate the prognostic role of a multiparametric score based on easily exploitable blood parameters, such as Hb concentration, MCV, and RDW. The red blood cell-based score may underlie the upregulation of the HIF-1α pathway and VEGF axis, thereby identifying a selected population who is likely to benefit from TKI therapy.

Dietary Flavonoid Intake and Cancer Mortality: A Population-Based Cohort Study.

Cancer is a leading cause of death worldwide, posing a huge burden upon society and individuals. The adequate intake of fruit and vegetables is reported to be an effective strategy for primary cancer prevention. Fruits and vegetables are rich in nutrients, such as vitamins and flavonoids, which may reduce the occurrence and progression of cancers. However, the importance of each flavonoid and the sub-classes remains controversial regarding cancer mortality. The population benefiting from increased flavonoid intake has not been determined. An estimation of cancer mortality by flavonoid intake is not established. We explored the association between the intake of flavonoids and cancer mortality amongst 14,029 participants in the National Health and Nutrition Examination Survey. During a median follow-up of 117 months, 405 cancer deaths were confirmed. Being in the second, third, and fourth quartiles of flavonol intake, the cancer mortality was inversely associated with the intake of flavonols (multivariate analysis HR (95% CI] 0.58 [0.36, 0.91], p = 0.02, Q1 vs. Q2; 0.55 [0.31, 0.96], p = 0.04, Q1 vs. Q3; 0.54 [0.30, 0.99], p = 0.05, Q1 vs. Q4, respectively). Potential effects of dietary flavonol intake against cancer death was observed especially in participants aged 50 or above, males, whites, former smokers, people who used to drink or drink alcohol mildly, people without hyperlipidemia, and people with hypertension. Moreover, the dietary intakes of peonidin, naringenin, and catechin were inversely associated with cancer mortality (multivariate HR [95% CI] 0.93 [0.88,0.98], p = 0.01; 0.97 (0.95,1.00), p = 0.03; 0.98 (0.96,1.00), p = 0.05, respectively). Furthermore, a nomogram based on flavonol intake is feasible for assessing cancer mortality for each participant. Taken together, our results could improve personalized nutrition amongst cancer patients.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable PM from gastric cancer outstanding result from multicenter cohort study.

331 Background: PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal metastasis (PM). It is a safe and well-tolerated treatment. Our aim was to report oncological outcomes after PIPAC for gastric PM. Methods: International retrospective cohort study of consecutive patients with gastric PM. Outcome measures were overall survival (OS), radiological response (RECIST), histological response by use of Peritoneal regression grading system (PRGS) and cytology, peritoneal cancer index (PCI) and symptoms. Results: 586 non-selected patients with a median age of 56 (47-64) years, 54% of them were female and underwent a total of 1566 PIPAC procedures. 37% of patients were treated with 2 or more lines of IV chemotherapy, median PCI at first PIPAC was 14 (7-24) and 63% of them were with signet ring adenocarcinoma. Grade III-IV morbidity was 5.1 % and 1.9% died within 30 days from PIPAC procedure. Median OS was 15.4 months from diagnosis and 20.1 months for patient with more than 3 PIPAC. 263/586 patients (44.9%) had ≥3 procedures ( pp: per protocol) with the following outcomes: RECIST: 4.3% complete response 11% partial remission, 44% stable; PRGS1 39% at PIPAC3 and negative cytology at PIPAC3 in 16% of patient. In multivariate analysis, 3 PIPAC or more HR 0.3 (95% CI 0.27-0.51), 2nd and 3rd line of chemotherapy HR 0.48 (95% CI 0.25-0.92) and CRS&amp;HIPEC after PIPAC HR 0.3 (95% CI 0.18-0.51) were predictors for survival. Conclusions: Based on this large multicentre cohort study, PIPAC could be considered as an option for the treatment of PM from gastric cancer. More prospective study will validate this indication in the near future.

Prognostic Role of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma: A Large, Multicenter, Prospective Trial.

Circulating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC). We designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression. One hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p=.002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16-3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p=.003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95-2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five. We provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC. This prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.

MICROENVIRONMENT IMMUNE CELLS IN BONE MARROW AND LYMPH NODE MEASURED BY FLOW CYTOMETRY CAN PREDICT SURVIVAL IN DIFFUSE LARGE B CELL LYMPHOMA

Introduction: Tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL) has recently been in the spotlight. The predictive role of immune cells (IC) in peripheral blood (PB), bone marrow (BM) and lymph nodes (LN) has been individually assessed, often using techniques not widely available. However, data regarding the relative prognostic impact of TME in each compartment evaluated simultaneously in DLBCL is still lacking. Aims: To determine the prognostic impact on survival of the Monocyte-Lymphocyte prognostic score (MLS) in PB and the percentage (%) of IC in the BM and LN measured by flow cytometry (FC) in DLBCL. Methods: We retrospectively collected information of patients (pts) with DLBCL and available BM aspiration and LN FC data at diagnosis, treated at our center between 2012 and 2019. Pts were stratified according to the MLS (Wilcox et al, leukemia 2011) in two groups: low (PB monocyte counts <630/ml and lymphocyte counts ≥1000/ml) and intermediate-high. FC analysis was performed with 8-color panels according to Euroflow protocols. % of BM and LN IC by FC were compared to normal values determined by Matarraz (Cytometry part B 2010) and Battaglia et al (Immunology 2003), and analyzed in 3 categories: low, normal and high. Survival analysis was performed with Kaplan-meier (variables compared with log-rank) and Cox regression. Results: 71 pts were included with a median age of 59 years. 49.3% had poor R-IPI. All pts received immunochemotherapy. Complete remission rate was 82%. Median overall survival (OS) was 120.5 months (m), with a median follow up time of 34.7 m. On univariate analysis TME variables from all the compartments showed prognostic impact on OS. BM IC levels did not statistically differ in involved vs not involved BM. Both low LN TL % and high and low BM Mo % remained independent predictors of survival on multivariate analysis. Moreover, pts with both of these unfavorable variables had a HR for death of 40.22 (CI 95% 5.16-313.04, p < 0.001) with a median OS of only 22.19 m. Variables Univariate analysis Multivariate analysis HR (95% CI) P-value HR (95% CI) P-value LN T lymphocytes (TL) low 3.98 (1.31-12.06) 0.014 5.44 (1.48-20.04) 0.011 BM B lymphocytes low 4.73 (1.62-13.79) 0.004 3.36 (0.99-11,34) 0.0501 BM Monocytes (Mo) High 10.53 (3.66-30.26) <0.001 4.66 (1.34-16.25) 0.015 BM Monocytes Low 3.87 (1.28-11.7) 0.016 3.40 (1.05-10.99) 0.04 PB MLS intermediate-high 2.59 (1.12-6) 0.02 1.05 (0.4-2.77) 0.91 Conclusion: Abnormal BM Mo % and low LN TL % measured by FC were associated with inferior OS in our cohort of DLBCL pts. These two TME variables presented at diagnosis could be easily translated into prognostic biomarkers in DLBCL, identifying a subgroup of pts with a dismal short term prognosis. In the future, therapies that target the crosstalk between lymphoma cells and the LN and BM ME might represent an encouraging strategy to improve outcomes in this high risk subset of pts. Kaplan-meler estimates of overall survival stratified by number of adverse prognosis tumor microenviroment varaibles present(low lymph node T-lymphocytes and high low bone marrow monocytes) Keywords: Diagnostic and Prognostic Biomarkers No conflicts of interests pertinent to the abstract. On univariate analysis TME variables from all the compartments showed prognostic impact on OS. BM IC levels did not statistically differ in involved vs not involved BM. Both low LN TL % and high and low BM Mo % remained independent predictors of survival on multivariate analysis. Moreover, pts with both of these unfavorable variables had a HR for death of 40.22 (CI 95% 5.16-313.04, p<0.001) with a median OS of only 22.19 m. Variables Univariate analysis Multivariate analysis HR (95% CI) P-value HR (95% CI) P-value LN T lymphocytes (TL) low 3.98 (1.31-12.06) 0.014 5.44 (1.48-20.04) 0.011 BM B lymphocytes low 4.73 (1.62-13.79) 0.004 3.36 (0.99-11,34) 0.0501 BM Monocytes (Mo) High 10.53 (3.66-30.26) <0.001 4.66 (1.34-16.25) 0.015 BM Monocytes Low 3.87 (1.28-11.7) 0.016 3.40 (1.05-10.99) 0.04 PB MLS intermediate-high 2.59 (1.12-6) 0.02 1.05 (0.4-2.77) 0.91

Incidence and Survival of Hepatocellular Carcinoma in Type 2 Diabetes Patients with Cirrhosis Who Were Treated with and without Metformin.

PurposeTo evaluate metformin’s benefit on the incidence and survival of hepatocellular carcinoma (HCC) in cirrhosis with type 2 diabetes mellitus (T2DM) patients.Patients and MethodsWe conducted a retrospective study from 2006 to 2019. The patients were assigned to metformin exposure if they administered metformin at least 3 months after diagnosis of cirrhosis. The outcomes were incidence and survival of HCC in T2DM with cirrhosis treated with metformin compared with those who were not treated with metformin. For the incidence of HCC, the follow-up time was 5 years after cirrhosis was diagnosed. For the survival of HCC, we censored for vital status in June 2019.ResultsOf 1061 patients, the patients were divided into 719 patients with metformin exposure and 342 in metformin non-exposure. In metformin exposure, 125 patients (17.4%) developed HCC. In metformin non-exposure, 128 patients (37.4%) developed HCC. Metformin exposure had a significantly lower risk of developing HCC in multivariate analysis HR 0.48 (0.36–0.61); P<0.001. For the survival of HCC, 327 patients were recruited. One-hundred and sixty-two patients were in metformin exposure and 165 patients were in metformin non-exposure. Sixty patients (37%) in metformin exposure died, while 84 patients (50.9%) in metformin non-exposure died. The median survival of metformin exposure and metformin non-exposure were 6.9 years and 3.88 years, respectively; P=0.003. In univariate analysis, the metformin exposure was significantly associated with better survival than in the non-exposure group, HR 0.63 (0.45–0.88); P=0.006. No significant difference was observed in multivariate analysis between two groups, HR 1.07 (0.74–1.54); P=0.72.ConclusionMetformin exposure was associated with a lower incidence of HCC in cirrhosis with T2DM patients and seemed to extend survival. Continuing metformin in patients with cirrhosis with T2DM should be considered if there was no contraindication.

Factors related to the discontinuation and mortality rates of a cardiac rehabilitation programme in patients with Chagas disease: a 6-year experience in a Brazilian tertiary centre.

To describe the clinical and sociodemographic characteristics of participants as well as discontinuation and mortality rates in a cardiac rehabilitation programme (CRP) tailored to Chagas disease (CD). Participants underwent functional capacity, anthropometry and cardiac function evaluations before beginning a CRP. Univariate and multivariate Cox proportional hazards models were performed to investigate the associations between clinical and sociodemographic characteristics at baseline with discontinuation rates and deaths. Forty-two patients were enrolled in the CRP (61.9% men, mean age of 58.1±11.8years). During a median follow-up period of 10.8months, 74% discontinued and 14% died while enrolled in CRP. 34% of the patients who discontinued CRP died during follow-up. White race (HR=0.09; 95% CI 0.01-1.00), right ventricular systolic dysfunction (HR=10.54; 95% CI 1.24-89.50) and oxygen pulse (HR=0.69; 95% CI 0.48-0.99) were independently associated with death while enrolled in CRP. Married status (HR=0.44; 95% CI 0.21-0.95) was independently associated with discontinuation rates from CRP. VO2 peak (HR=0.85; 95% CI 0.74-0.98) and CRP discontinuation due to CD-related reasons (HR=8.33; 95% CI 1.91-36.27) were the variables independently associated with death after discontinuation of CRP. In this population, sociodemographic aspects and severity of CD were important determinants of CRP discontinuation and mortality.

Survival Analysis of Ovarian Cancer Patients based on Age at The Dr. Wahidin Sudirohusodo Makassar Hospital in 2014-2018

Background. Generally, a younger age at diagnosis indicates a better prognosis, with younger women having an average survival of at least 2 years longer than older women. It is estimated that in young women the disease is diagnosed more quickly in the early stages when compared to older women. Method. A cohort retrospective study. This research was conducted at the Dr. Wahidin Sudirohusodo Makassar Hospital by taking the medical records of ovarian cancer patients from January 2014 to December The study subjects were 263 patients. The Kaplan-Meier method was used to estimate survival rate and Cox Regression to investigate the effect of variable. Results. The survival of ovarian cancer patients within 30 months is 78%. Ovarian cancer patients who survived to the 30th month based on age ? 60 years were 79% whereas &gt; 60 years to 30th month none had survived with an HR score of 2.74 (95% CI: 1.09-6.88 ). Multivariate analysis HR values were obtained for age 2.65 (95% CI: 1,07-6,52) after being controlled by stage, and performance status. Conclusion. Age affects the survival of ovarian cancer patients. Patients aged&gt; 60 years are more at risk of dying compared to patients aged ? 60 years

Early biochemical predictors of survival in intermediate and high-risk prostate cancer treated with radiation and androgen deprivation therapy

Background and purposeTo identify early biochemical predictors of survival in intermediate- and high-risk prostate cancer patients with a pre-treatment PSA <20 ng/mL following definitive radiation therapy (RT) and androgen deprivation therapy (ADT). Materials and methodsA single-institution review of 2566 intermediate and high-risk prostate cancer patients treated with definitive RT and neoadjuvant and concurrent ADT from 1990 to 2012 was performed. The first prostate-specific antigen (PSA) value within three months of ADT initiation (post-ADT PSA) and the first PSA within three months after RT completion (post-RT PSA) were recorded. 1275 had baseline PSA <20 ng/mL and either post-ADT or post-RT PSA available. Median follow-up was 7.6 years. The relationship between post-treatment PSA kinetics and biochemical relapse (BR), distant metastasis (DM), prostate cancer specific death (PCSD) and overall survival (OS) was modeled using Cox regression univariate and multivariate analysis (MVA). ResultsMVA demonstrated a strong association between a post-RT PSA ≥0.09 ng/mL and a significantly higher risk of BR (HR: 1.93; 95% CI: 1.45–2.57; p < 0.001), DM (HR: 2.97; 95% CI: 2.01–4.39; p < 0.001), PCSD (HR: 2.99; 95% CI: 1.73–5.15; p < 0.001) and OS (HR: 1.49; 95% CI: 1.18–1.86; p < 0.001). Post-RT PSA reduction of ≥95% relative to the baseline PSA was associated with a significantly lower risk of BR (MVA HR: 0.58; 95% CI: 0.41–0.83; p = 0.003) and DM (MVA HR: 0.47; 95% CI: 0.30–0.76; p = 0.002). ConclusionA PSA value ≥0.09 ng/mL early after RT completion is associated with significantly worse prognosis across all clinical outcomes, and an early PSA reduction of ≥95% is associated with reduced risk of BR and DM. These findings may identify patients who require early aggressive systemic management for high-risk disease.

Fragmented QRS Complex as a Predictor of High Risk in Acute Coronary Syndrome

Background: To detect the potential in hospital prognostic value of fQRS complex in patients with acute coronary syndrome (ACS) & investigate whether FQRS complex can be used to distinguish patients with early NSTEMI from those with unstable angina. Methods: It included 150 patients with acute NSTEMI and unstable angina. All patients were subjected to Grace score calculation, ECG to detect ischemic changes and detect presence or absent of fQRS, transthoracic echo to detect LV ejection fraction and recording in-hospital outcome. Results: Patients with fQRS have significant higher Killip class>2, higher troponin &CKMB levels, higher grace score, increased LVEDD & LVESD and significantly lower LVEF%. LVEF is significantly lower among patients with fQRS than patients with not fQRS in NSTEMI patients while there is no significant difference of LVEF % between both groups in unstable angina patients. There is significant association between fQRS and higher prevalence of NSTEMI and higher incidence of heart failure, arrhythmia and bad outcome. By multivariate analysis, NSTEMI (p =0.003) and high HR (p =0.004) and fragmented QRS (p =0.00) were the only significant predictors for bad outcome. FQRS have the ability to diagnose NSTEMI in 47.9% of cases, fQRs can truly exclude NSTEMI in 72.7% of case. Conclusion: Among patients with ACS, the presence of fQRS was associated with an increase incidence of complication, worse outcome, larger LV dimensions, and lower LVEF. The presence of fQRS in acute coronary syndrome patients could predict the presence of NSTEMI with fair diagnostic value.

Survival in males with glioma and gastric adenocarcinoma correlates with mutant p53 residual transcriptional activity.

There is currently no clinical distinction between different TP53 mutations, despite increasing evidence that not all mutations have equally deleterious effects on the activity of the encoded tumor suppressor protein p53. The objective of this study was to determine whether these biological differences have clinical significance. This retrospective cohort analysis included 2,074 patients with sporadic TP53 mutations (403 unique mutations) and 1,049 germline TP53 mutation carriers (188 unique mutations). Survival was projected by stratifying patients according to their p53 mutant-specific residual transcriptional activity scores. Pan-cancer survival analyses revealed a strong association between increased mutant p53 residual activity and improved survival in males with glioma and gastric adenocarcinoma (P = 0.002 and P = 0.02) that was not present in the female cohorts (P = 0.16 and P = 0.50). Male glioma and gastric cancer patients with TP53 mutations resulting in >5% transcriptional activity had 3.1-fold (95% CI, 2.4-3.8; P = 0.002; multivariate analysis hazard ratio [HR]) and 4.6-fold (95% CI, 3.7-5.6; P = 0.001; multivariate analysis HR) lower risk of death as compared with patients harboring inactive (0% activity) p53 mutants. The correlation between mutant p53 residual activity with survival was recapitulated in the dataset of germline TP53 mutation carriers (HR = 3.0, 95% CI, 2.7-3.4, P < 0.001 [females]; HR = 2.2, 95% CI, 1.8-2.6, P < 0.001 [males]), where brain and gastric tumors were more common among males (P < 0.001 and P = 0.001, respectively). The retention of mutant p53 transcriptional activity prognosticates superior survival for men with glioma and gastric adenocarcinoma harboring sporadic TP53 mutations. Among germline TP53 mutation carriers, increased residual transcriptional activity is correlated with prolonged lifetime cancer survival and delayed tumor onset, and males are more prone to develop brain and gastric tumors. Canadian Institutes of Health Research (no. 148556).

Age-not Charlson Co-morbidity Index-predicts for mortality after stereotactic ablative radiotherapy for medically inoperable stage I non-small cell lung cancer

PurposeIn this single institution retrospective study of patients with stage I medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) we attempt to model overall survival (OS) using initial prognostic variables with specific attention on the Charlson co-morbidity index (CCI). MethodsBetween 2008 and 2013, 335 patients with medically inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy (50–60Gy in at least 5Gy or 4Gy fractions respectively) at our institution. Medical comorbidities and Charlson scores were determined by individual chart review. Patients were stratified into 3 groups based on the CCI score (0–1, 2–3, 4–9) and again based on the age-adjusted Charlson Comorbidity score (aCCI). Cumulative survival for each stratum was determined using the Kaplan-Meier method. Non-significant and confounding variables were identified and discounted from survival modeling. 3 sex stratified Cox regression models were tested: (1) aCCI with age and comorbidity combined; (2) age and CCI; (3) age alone, comorbidity removed. ResultsThe median survival was 4.4years and the median follow up 4.7years. The median CCI and aCCI scores were 2 and 5 respectively. Patients with aCCI 7–12 had an increased hazard of death on univariate analysis HR 2.45 (1.15–5.22 95%CI, p=0.02) and -excluding age as a competing variable- on multivariate analysis HR 2.25 (1.04–4.84 95%CI, p=0.04). Patients with CCI 4-9 had an increased hazard of death on univariate analysis HR 1.57(1.30–2.90) but not on multivariate analysis. On formalized testing – with either continuous or categorical variables- all three survival models yielded similar coefficients of effect. ConclusionWe identify male gender, weight loss greater than 10% and age as independent prognostic factors for patients treated with medically inoperable NSCLC treated with SABR or hypofractionated radiotherapy. Based on our survival models, age alone can be used interchangeably with aCCI or CCI plus age with the same prognostic value. Age is more reliably recorded, less prone to error and therefore a more useful metric than Charlson score in this group of patients.

Galectin-3 Levels Are Elevated and Predictive of Mortality in Pulmonary Hypertension

Galectin-3, a novel binding-lectin involved in inflammation and fibrosis, is elevated in heart failure and is independently predictive of mortality in this condition. We sought to evaluate galectin-3 levels and its prognostic value in patients with pulmonary hypertension (PH), a known inflammatory state, in the setting of pulmonary arterial hypertension (PAH) and in heart failure with preserved ejection fraction-associated PH (HFpEF-PH). We measured galectin-3 levels in 76 patients with PH; 37 patients with PAH and 39 patients with HFpEF-PH. Baseline characteristics, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels were assessed. Univariate and multivariate analyses were used to assess the prognostic value of galectin-3. Median (IQR) galectin-3 (ng/mL) for the entire cohort was 24.65 (IQR=10.39, 32.90); 22.33 (IQR=18.94, 27.30) and 28.94 (IQR=21.67, 39.85) in the PAH and HFpEF-PH, respectively (p=0.07). After evaluation of the galectin-3 levels by tertile, mortality rates were 16% (4/25), 34.6% (9/26), and 48% (12/25) in tertiles 1-3, respectively, and Kaplan-Meier analysis revealed a significant increase in mortality across increasing galectin-3 tertiles (log-rank p=0.014). On Cox regression analysis, galectin-3 was a strong predictor of mortality on both univariate HR=2.09 per tertile (95% CI=1.21, 3.62 per tertile; p-trend=0.008) and multivariate analysis HR=2.19 per tertile (95% CI=1.06, 4.54; p-trend=0.035) after adjusting for age, sex, race, glomerular filtration rate (eGFR), NT-proBNP, medications, and aetiology of PH (PAH vs. HFpEF-PH). Galectin-3 is a strong, independent prognostic marker in PH, regardless of aetiology. Larger studies should further evaluate the role of galectin-3 as a prognostic biomarker and possible therapeutic target in PH.

Primary Tumor Characteristics Are Important Prognostic Factors for Sorafenib-Treated Patients with Metastatic Renal Cell Carcinoma: A Retrospective Multicenter Study.

We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS (p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS (p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients.

Extrahepatic cancer risk among patients with liver cirrhosis in Taiwan: A nationwide population-based study.

1564 Background: Cirrhosis is a well-known risk factor of hepatocellular carcinoma. However, the risk of extra-hepatic cancers (EHCs) is not clear in cirrhotic patients. This study is aimed to identify the risk and sites of EHCs among cirrhotic patients. Methods: Newly diagnosed cirrhotic patients between 2000 and 2011 were recruited from Taiwan's nationwide health insurance database. Patients aged < 20 years and those with antecedent malignancies were excluded. To avoid surveillance bias, EHCs that developed within one year were also excluded in further analysis. Standardized incidence ratios (SIRs) of EHCs in these patients were calculated by comparing to the EHC incidence in the general population. Univariate and multivariate Cox proportional hazards models were applied to find the predictors of EHCs development among patients with cirrhosis. Results: During the 12-year study period, 859 EHCs developed among 13,729 cirrhotic patients, with a median follow-up period of 4.44 years. The SIR for all patients was 2.17 (95% confidence interval [CI] 2.03-2.32), for cirrhosis due to alcohol 3.43 (95% CI 3.02-3.89), for hepatitis B 1.81 (95% CI 1.51-2.15) and for hepatitis C 1.83 (95% CI 1.52-2.19). The SIRs for cancers of esophagus (4.60), head and neck (2.43), skin (1.99), stomach (1.95), bladder (1.66), breasts (1.46), and lung and mediastinum (1.42) were significantly increased. Multivariate analysis showed that age ≥ 50 years (adjusted hazard ratio [HR] 2.26, 95% CI 1.85-2.75), being male (HR 1.57, 95% CI 1.29-1.90), and chronic obstructive pulmonary disease (HR 1.29, 95% CI 1.06-1.56) were independent factors. Conclusions: This largest cohort study demonstrated an increasing risk of EHCs among cirrhotic patients, especially cirrhosis due to alcohol. Risk factors for cancer development in patients with cirrhosis. Variables Multivariate analysis HR (95% CI) P Value Age ≥ 50 2.26 (1.85-2.75) < 0.001 Sex (male) 1.57 (1.29-1.90) < 0.001 Comorbidities Diabetes mellitus 1.15 (0.94-1.40) 0.165 COPD 1.29 (1.06-1.56) 0.011 Autoimmune diseases 0.86 (0.61-1.21) 0.382 Dyslipidemia 1.00 (0.82-1.22) 0.998 Chronic kidney disease 0.95 (0.74-1.21) 0.658 COPD: chronic obstructive pulmonary disease

Improved Overall Survival With Adjuvant Radiation on Resected Pancreatic Tail Adenocarcinoma

To determine the effects of adjuvant treatment on survival in patients with pancreatic tail lesions. An analysis of patients with upfront surgically resected pancreatic tail cancer treated at our institution between 2000 and 2012 was performed to compare OS outcomes of patients treated with and without adjuvant radiation therapy (RT). The majority of patients received chemotherapy (83%), either alone or concurrent with RT. Survival curves were calculated according to the Kaplan-Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using the Cox proportional hazards model. We identified 34 patients who met inclusion criteria. The only difference in patient and tumor characteristics between those treated with and without adjuvant RT was patient sex. There was no difference in age, pathologic tumor size, nodes positive, nodes removed, nodal stage, tumor grade, surgical margins or post-op CA19-9 levels between the groups. On both UVA and MVA there was significantly worse survival in patients with a post-op CA19-9 >90 (MVA Hazard Ratio [HR] 5.55 95% Confidence Interval [CI] 1.20-25.7, p=0.03) and improved survival in patients treated with adjuvant RT (MVA HR 0.15 95% CI 0.04-0.58, p=0.006). There was no difference based on sex, pathologic T stage, tumor grade, or surgical margins. The median and 2-year OS was 21.6 months and 47% for patients treated with adjuvant RT compared with 11.3 months and 21% for those treated without RT (p=0.03). Although small patient numbers, this data suggests integration of adjuvant RT in resected pancreatic tail adenocarcinoma may improve OS compared to chemotherapy alone.

Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study

Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort [MSKCC] cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment. Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio [HR] 4·5 [95% CI 2·1-9·8]; p=0·00013; area under the receiver operator curve [AUC] 0·70 [95% CI 0·65-0·76]) and radical prostatectomy (4·0 [1·6-9·7]; p=0·0024; AUC 0·57 [0·52-0·61]) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 [1·2-12]; p=0·019; AUC 0·67 [0·61-0·73]). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 [95% CI 2·0-19]; p=0·0015; AUC 0·74 [95% CI 0·65-0·83]). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 [95% CI 1·4-6·0]; p=0·0039; AUC 0·68 [95% CI 0·63-0·73]), and was better at predicting biochemical relapse than 23 previously published RNA signatures. This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials. Movember Foundation, Prostate Cancer Canada, Ontario Institute for Cancer Research, Canadian Institute for Health Research, NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cancer Research UK, Cambridge Cancer Charity, Prostate Cancer UK, Hutchison Whampoa Limited, Terry Fox Research Institute, Princess Margaret Cancer Centre Foundation, PMH-Radiation Medicine Program Academic Enrichment Fund, Motorcycle Ride for Dad (Durham), Canadian Cancer Society.

PT041 Applicability of BNP as a Biomarker of Prognosis in Long-Term Mortality in a Cohort of Elderly Patients in South Brazil

Introduction: The BNP is used as a biomarker of prognosis, in the short term, in patients with heart failure (HF). The prognostic role of the long-term mortality is not enough studied. Objectives: To validate the BNP test as a biomarker of long-term prognosis in patients with suspected HF. Methods: Three hundred eighteen patients, who presented at the emergency room, from March 2003 through September 2009, with suspected HF, took part of this study. The accuracy of BNP to identify patients with heart failure and the search from the association with the level of BNP (POCT Biosite) and with the long-term prognosis were evaluated. The cause of death was identified through the search of death certificates in registries, informed by the Brazilian Information Service of Mortality. Results: Most of the patients were white (93.1%), female (63.8%), and aged 77.3 8.6 years. HF was diagnosed based in a new gold standard that considered the Framingham and Boston criteria plus echocardiography and ECG. HF was present in 170 pt (53.5%). Most of these 108 pt (63.5%) had HF with Preserved Ejection Fraction (HFPEF). The functional class III and IV NYHA was present in 87%. The BNP presented AUC 0.93 (CI 95%, 0.88 to 0.97). The best cutoff of BNP was 180 pg/ml with S 0.83 (CI 95%, 66.7 to 80.4) and Sp 0.90 (CI 95%, 76.7 to 95.4). LR + 6.7 (95 %, 3.1 to 14.3), accuracy of 77.7. In the bivariate analysis BNP> 180pg/ml was associated with a higher risk of mortality. In multivariate analysis HR BNP> 180pg/ml remained associated with increased risk of mortality HR 3.4 (HF 1.2 to 9.6 p 50% and mortality of 26%. The comparison HFS group and NHF showed RRR 0,21 (CI 95% 0,05 – 0,38) p<0,001. Betwin HFPEF group and N-HF group RRR 0,12 (CI 95% -0,02 0,27). HFS and HFPEF the RRR 0,089 (CI 95% -0,67 – 0,24). Ninety nine 99 deaths were recorded in the total group. Conclusion: The level of the BNP showed association with mortality index. The BNP is an independent prognostic biomarker of long-term mortality in patients with HF. Disclosure of Interest: None Declared

PT043 Diagnostic and prognostic value of the B-type natriuretic peptide in elderly patients, in south Brazil, with suspected heart failure in the emergency room

Introduction: The BNP is used as a biomarker of prognosis, in the short term, in patients with heart failure (HF). The prognostic role of the long-term mortality is not enough studied. Objectives: To validate the BNP test as a biomarker of long-term prognosis in patients with suspected HF. Methods: Three hundred eighteen patients, who presented at the emergency room, from March 2003 through September 2009, with suspected HF, took part of this study. The accuracy of BNP to identify patients with heart failure and the search from the association with the level of BNP (POCT Biosite) and with the long-term prognosis were evaluated. The cause of death was identified through the search of death certificates in registries, informed by the Brazilian Information Service of Mortality. Results: Most of the patients were white (93.1%), female (63.8%), and aged 77.3 8.6 years. HF was diagnosed based in a new gold standard that considered the Framingham and Boston criteria plus echocardiography and ECG. HF was present in 170 pt (53.5%). Most of these 108 pt (63.5%) had HF with Preserved Ejection Fraction (HFPEF). The functional class III and IV NYHA was present in 87%. The BNP presented AUC 0.93 (CI 95%, 0.88 to 0.97). The best cutoff of BNP was 180 pg/ml with S 0.83 (CI 95%, 66.7 to 80.4) and Sp 0.90 (CI 95%, 76.7 to 95.4). LR + 6.7 (95 %, 3.1 to 14.3), accuracy of 77.7. In the bivariate analysis BNP> 180pg/ml was associated with a higher risk of mortality. In multivariate analysis HR BNP> 180pg/ml remained associated with increased risk of mortality HR 3.4 (HF 1.2 to 9.6 p 50% and mortality of 26%. The comparison HFS group and NHF showed RRR 0,21 (CI 95% 0,05 – 0,38) p<0,001. Betwin HFPEF group and N-HF group RRR 0,12 (CI 95% -0,02 0,27). HFS and HFPEF the RRR 0,089 (CI 95% -0,67 – 0,24). Ninety nine 99 deaths were recorded in the total group. Conclusion: The level of the BNP showed association with mortality index. The BNP is an independent prognostic biomarker of long-term mortality in patients with HF. Disclosure of Interest: None Declared

PT042 Impact of the extracardiac variables on BNP cut-offs within a cohort of patients with suspected heart failure in a tertiary referral hospital

Introduction: The BNP is used as a biomarker of prognosis, in the short term, in patients with heart failure (HF). The prognostic role of the long-term mortality is not enough studied. Objectives: To validate the BNP test as a biomarker of long-term prognosis in patients with suspected HF. Methods: Three hundred eighteen patients, who presented at the emergency room, from March 2003 through September 2009, with suspected HF, took part of this study. The accuracy of BNP to identify patients with heart failure and the search from the association with the level of BNP (POCT Biosite) and with the long-term prognosis were evaluated. The cause of death was identified through the search of death certificates in registries, informed by the Brazilian Information Service of Mortality. Results: Most of the patients were white (93.1%), female (63.8%), and aged 77.3 8.6 years. HF was diagnosed based in a new gold standard that considered the Framingham and Boston criteria plus echocardiography and ECG. HF was present in 170 pt (53.5%). Most of these 108 pt (63.5%) had HF with Preserved Ejection Fraction (HFPEF). The functional class III and IV NYHA was present in 87%. The BNP presented AUC 0.93 (CI 95%, 0.88 to 0.97). The best cutoff of BNP was 180 pg/ml with S 0.83 (CI 95%, 66.7 to 80.4) and Sp 0.90 (CI 95%, 76.7 to 95.4). LR + 6.7 (95 %, 3.1 to 14.3), accuracy of 77.7. In the bivariate analysis BNP> 180pg/ml was associated with a higher risk of mortality. In multivariate analysis HR BNP> 180pg/ml remained associated with increased risk of mortality HR 3.4 (HF 1.2 to 9.6 p 50% and mortality of 26%. The comparison HFS group and NHF showed RRR 0,21 (CI 95% 0,05 – 0,38) p<0,001. Betwin HFPEF group and N-HF group RRR 0,12 (CI 95% -0,02 0,27). HFS and HFPEF the RRR 0,089 (CI 95% -0,67 – 0,24). Ninety nine 99 deaths were recorded in the total group. Conclusion: The level of the BNP showed association with mortality index. The BNP is an independent prognostic biomarker of long-term mortality in patients with HF. Disclosure of Interest: None Declared