Predictor Of Long-term Survival Research Articles

5951The impact of regulatory T lymphocytes on long-term survival in patients with ischemic heart failure with reduced ejection fraction

Abstract Background Heart failure with reduce ejection fraction (HFrEF) constitutes a global health issue representing a prevalent clinical syndrome. While pro-inflammatory cytokines proved to have a pivotal role in the development and progression of HFrEF, less attention has been paid to the cellular immunity. Regulatory T lymphocytes (Tregs) seem to have an important role in the induction and maintenance of immune homeostasis especially in patients after acute coronary syndrome and coronary vessel disease. Therefore, we aimed to investigate the impact of Tregs on the outcome of patients presenting with ischemic HFrEF. Methods We prospectively enrolled 112 patients with HFrEF defined by New York Heart Association (NYHA) functional class >II and left ventricular ejection fraction (LVEF) <40%. Patients were stratified in ischemic (iHFrEF, n=57) and dilated etiology (dHFrEF, n=55). Cells from fresh heparinized blood were stained and analyzed using BD FACS Canto II flow cytometry. Cox regression hazard analysis was used to assess the influence of Tregs on survival. The multivariate model was adjusted forage and gender. Results Comparing patients with iHFrEF to dHFrEF we found a significantly lower fraction of Tregs within lymphocytes in the ischemic subgroup (0.42% vs. 0.56%; p=0.009). After a mean follow-up time of 4.5 years 32 (28.6%) patients died due to cardiovascular causes. We found that Tregs were significantly associated with cardiovascular survival in the entire study cohort with an adjusted HR per one standard deviation (1-SD) of 0.60 (95% CI 0.39–0.92; p=0.017). Interestingly while there was no association with cardiovascular survival independently in the dHFrEFsubgroup (adj. HR per 1-SD of 0.62 (95% CI 0.17–2.31); p=0.486), we found a significant inverse association of Tregs and cardiovascular survival in patients with iHFrEFwith an adj. HR per 1-SD of 0.59 (95% CI 0.36–0.96; p=0.034). Figure 1. Survival Curves of Cardiovascular Mortality. Kaplan-Meier plots showing survival free of cardiovascular mortality in the total study collective (A) and patients stratified in ischemic CMP (B) as well dilative CMP (C) according to tertiles of frequencies of regulatory T cells. Tertile 1 = high; Tertile 2 = mid; Tertile 3 = low. Conclusion Our results indicate a potential influence of Tregs in the pathogenesis and progression of iHFrEF, fostering the implication of cellular immunity in iHFrEF pathophysiology and proving Tregs as a predictor for long-term survival among iHFrEF -patients.

Dynamic prediction of long-term survival in patients with primary gastric diffuse large B-cell lymphoma: a SEER population-based study

BackgroundThis study investigated a large number of patients to develop a predictive nomogram for survival and a web-based survival rate calculator that can dynamically predict the long-term survival of patients with primary gastric diffuse large B-cell lymphoma.MethodsA total of 2647 patients diagnosed with primary gastric diffuse large B-cell lymphoma from 1998 to 2014 were extracted from the SEER database. We used the Lasso Cox regression model to identify independent risk factors for long-term survival and to develop a predictive nomogram for survival and a web-based survival rate calculator.ResultsThe median (mean) follow-up time was 30 months (52.8 months). Cancer-specific survival rates decreased with time, while the 5-year conditional survival increased with time. Cancer-specific deaths were not constant. Cancer-specific deaths of patients within the first 2 years were high, while the risk remained relatively constant after 2 years. The independent risk factors included surgery, chemotherapy, tumor stage and age, according to the Lasso Cox regression analysis. We developed a predictive nomogram and a web-based survival rate calculator (https://linjuli1991.shinyapps.io/dynnomapp/). The calibration plot suggested that the actual value exhibited good agreement with the predicted value.ConclusionsWe found that patients with primary gastric diffuse large B-cell lymphoma had a high risk of death during the first 2 years. Additional active follow-up strategies should be provided during this period. This is the first study to develop a predictive nomogram and a web-based survival rate calculator that can provide evidence for individual treatment and follow-up.

Galectin-3 as a Predictor of Long-term Survival After Isolated Coronary Artery Bypass Grafting Surgery

Galectin-3 (Gal-3) is a well-established biomarker of adverse clinical outcomes, but its prognostic value for long-term survival after cardiac surgery is not well understood. Elevated levels of Gal-3 have been found to be remarkably associated with higher risk of death in both acute decompensated and chronic heart failure populations. Its prognostic value for long-term survival after cardiac surgery is not known. A sample of patients contributing to the Northern New England Cardiovascular Disease Study Group Cardiac Surgery Registry from 2004 to 2007 were enrolled in a prospective biomarker cohort (N= 1690). Preoperative Gal-3 levels were measured and categorized by quartile. We used Kaplan-Meier survival analysis and Cox regression models, adjusting for variables in The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategy probability calculator to evaluate the association between elevated Gal-3 levels and survival to 6 years. Preoperative Gal-3 levels ranged from 1.72 to 28.89 ng/mL (mean, 8.96 ng/mL; median, 8.06 ng/mL; interquartile range, 5.42-11.08 ng/mL). Crude survival decreased by increasing quartile. After adjustment, serum levels of Gal-3 in the highest quartile of the cohort were associated with significantly decreased survival compared with the lowest quartile (hazard ratio [HR] 2.22; 95% confidence interval [CI], 1.40-3.54; P= .001). No decrease in survival was found for the middle quartiles (HR 1.36; 95% CI, 0.87-2.12; P= .177). A substantial association was found between elevated preoperative Gal-3 levels and risk of mortality after isolated coronary artery bypass grafting surgery. An assessment of the relationship between preoperative serum biomarkers and long-term survival can be used for risk stratification or estimating postsurgical prognosis.

Expression patterns of small numbers of transcripts from functionally-related pathways predict survival in multiple cancers

BackgroundGenetic profiling of cancers for variations in copy number, structure or expression of certain genes has improved diagnosis, risk-stratification and therapeutic decision-making. However the tumor-restricted nature of these changes limits their application to certain cancer types or sub-types. Tests with broader prognostic capabilities are lacking.MethodsUsing RNAseq data from 10,227 tumors in The Cancer Genome Atlas (TCGA), we evaluated 212 protein-coding transcripts from 12 cancer-related pathways. We employed t-distributed stochastic neighbor embedding (t-SNE) to identify expression pattern difference among each pathway’s transcripts. We have previously used t-SNE to show that survival in some cancers correlates with expression patterns of transcripts encoding ribosomal proteins and enzymes for cholesterol biosynthesis and fatty acid oxidation.ResultsUsing the above 212 transcripts, t-SNE-assisted transcript pattern profiling identified patient cohorts with significant survival differences in 30 of 34 different cancer types comprising 9350 tumors (91.4% of all TCGA cases). Small subsets of each pathway’s transcripts, comprising no more than 50–60 from the original group, played particularly prominent roles in determining overall t-SNE patterns. In several cases, further refinements in long-term survival could be achieved by sequential t-SNE profiling with two pathways’ transcripts, by a combination of t-SNE plus whole transcriptome profiling or by employing t-SNE on immuno-histochemically defined breast cancer subtypes. In two cancer types, individuals with Stage IV disease at presentation could be readily subdivided into groups with highly significant survival differences based on t-SNE-based tumor sub-classification.Conclusionst-SNE-assisted profiling of a small number of transcripts allows the prediction of long-term survival across multiple cancer types.

Analysis of outcomes and predictors of long-term survival following resection for retroperitoneal sarcoma

BackgroundRetroperitoneal sarcomas (RPS) include a heterogeneous group of rare malignant tumours, and various treatment algorithms are still controversially discussed until today. The present study aimed to examine postoperative and long-term outcomes after resection of primary RPS.Patients and methodsClinicopathological data of patients who underwent resection of primary RPS between 2005 and 2015 were assessed, and predictors for overall survival (OS) and disease-free survival (DFS) were identified.ResultsSixty-one patients underwent resection for primary RPS. Postoperative morbidity and mortality rates were 31 and 3%, respectively. After a median follow-up time of 74 months, 5-year OS and DFS rates were 58 and 34%, respectively. Histologic high grade (5-year OS: G1: 92% vs. G2: 54% vs. G3: 43%, P = 0.030) was significantly associated with diminished OS in univariate and multivariate analyses. When assessing DFS, histologic high grade (5-year DFS: G1: 63% vs. G2: 24% vs. G3: 22%, P = 0.013), positive surgical resection margins (5-year DFS: R0: 53% vs. R1: 10% vs. R2: 0%, P = 0.014), and vascular involvement (5-year DFS: yes: 33% vs no: 39%, P = 0.001), were significantly associated with inferior DFS in univariate and multivariate analyses.ConclusionsHigh-grade tumours indicated poor OS, while vascular involvement, positive surgical resection margins, and histologic grade are the most important predictors of DFS. Although multimodal treatment strategies are progressively established, surgical resection remains the mainstay in the majority of patients with RPS, even in cases with vascular involvement.

Management trends for anaplastic meningioma with adjuvant radiotherapy and predictors of long-term survival.

OBJECTIVEThe purpose of this study was to describe effects of adjuvant radiotherapy (RT) for anaplastic meningiomas (AMs) on long-term survival, and to analyze patient and RT characteristics associated with long-term survival.METHODSThe authors queried a retrospective cohort of patients with AM from the National Cancer Database (NCDB) diagnosed between 2004 and 2015 to describe treatment trends. For outcome analysis, patients with at least 10 years of follow-up were included, and they were stratified based on adjuvant RT status and propensity matched to controls for covariates. Survival curves were compared. A data-driven approach was used to find a biologically effective dose (BED) of RT with the largest difference between survival curves. Factors associated with long-term survival were quantified.RESULTSThe authors identified 2170 cases of AM in the NCDB between 2004 and 2015. They observed increased use of adjuvant RT in patients treated with higher doses. A total of 178 cases met the inclusion criteria for outcome analysis. Forty-five percent (n = 80) received adjuvant RT. Patients received a BED of 80.23 ± 16.6 Gy (mean ± IQR). The median survival time was not significantly different (32.8 months for adjuvant RT vs 38.5 months for no RT; p = 0.57, log-rank test). Dichotomizing the patients at a BED of 81 Gy showed maximal difference in survival distribution with a decrease in median survival in favor of no adjuvant RT (31.2 months for adjuvant RT vs 49.7 months for no RT; p = 0.03, log-rank test), but this difference was not significant after false discovery rate correction. Age was a significant predictor for long-term survival.CONCLUSIONSAMs are aggressive tumors that carry a poor prognosis. Conventional adjuvant RT improves local control. However, the effect of adjuvant radiation on overall survival is unclear. Further investigation into this area is warranted.

The psoas muscle index as a predictor of long-term survival after cardiac surgery for hemodialysis-dependent patients.

Sarcopenia represented by skeletal muscle depletion is closely related to frailty and predicts prognoses in the general population. However, its predictive value for hemodialysis (HD)-dependent patients undergoing cardiac surgery has not been fully investigated. We aimed to clarify the impact of sarcopenia on the outcomes of HD-dependent patients after cardiac surgery. We retrospectively reviewed 138 HD-dependent patients who underwent cardiac surgery between January 2006 and December 2017. Sarcopenia was assessed using the psoas muscle index (PMI), which was calculated using values measured on preoperative computed tomography images and the following formula: cross-sectional area of bilateral psoas muscle/height2. Patients were divided into two groups according to the PMI: the sarcopenia group (≤ 443mm2/m2 for men and ≤ 326mm2/m2 for women; n = 35) and the non-sarcopenia group (> 443mm2/m2 for men and > 326mm2/m2 for women; n = 103). Preoperative characteristics and surgical outcomes were compared. Overall in-hospital mortality did not differ between the sarcopenia and non-sarcopenia groups. However, the patients with sarcopenia had significantly decreased long-term survival. Multivariate analysis revealed that low PMI was a significant independent predictor of long-term mortality (hazard ratio, 1.92; 95% confidential interval, 1.19-3.17; p < 0.01). Long-term survival rates in HD-dependent patients undergoing cardiac surgery are severely affected by the presence of preoperative sarcopenia defined by PMI. Preoperative risk analysis using the PMI might contribute to risk stratification of and decision-making for HD-dependent patients undergoing cardiac surgery.

Prediction of Postoperative Outcomes and Long-Term Survival in Cardiac Surgical Patients Using the Intensive Care National Audit & Research Centre Score

Scoring systems used in cardiac surgery, such as the European System for Cardiac Operative Risk Evaluation and the Society of Thoracic Surgeons scoring systems, do not adjust for events that take place intraoperatively. The authors hypothesized that intensive care unit scoring systems such as the Intensive Care National Audit & Research Centre (ICNARC) could predict accurately not only in-hospital mortality, but also other significant complications, as well as long-term survival after cardiac surgery. Prospective cohort study using perioperative data from the ICNARC Audit and Dendrite database. Single tertiary referral cardiac surgery center. A total of 4,446 consecutive cardiac surgical patients who had surgery between January 2011 and April 2018. Comparison of scoring systems to predict postoperative outcomes. Receiver operating curves (ROCs) were used to evaluate how well the ICNARC scores predicted in-hospital mortality and postoperative complications (renal failure, pulmonary complications, gastrointestinal complications, and multiorgan failure). Cox regression analysis was used to determine factors affecting long-term survival. The C-indices for the ROC graphs for the ICNARC score were 0.840 for in-hospital mortality, 0.858 for renal failure, 0.665 for pulmonary complications, 0.764 for gastrointestinal complications, 0.702 for neurological complications in general and 0.654 for confusion, and 0.885 for multiorgan failure. From Cox regression analysis, the significant (p < 0.05) predictors of midterm mortality (5 years) were a higher ICNARC score, a higher age at surgery, chronic obstructive pulmonary disease, preoperative renal failure, preoperative neurological comorbidity, arteriopathy, and non-coronary artery bypass graft surgery. The ICNARC scoring system is simple and can be used as an early warning screening tool to predict which patients are at higher risk for postoperative organ failure.

Predictors of Long-Term Survival among High-Grade Serous Ovarian Cancer Patients.

Relatively little is known about factors associated with long-term survival (LTS) following a diagnosis of ovarian cancer. We conducted a retrospective study of high-grade serous ovarian cancer (HGSOC) to explore predictors of LTS (defined as ≥7 years of survival) using electronic medical record data from a network of integrated health care systems. Multivariable logistic regression with forward selection was used to compare characteristics of women who survived ≥7 years after diagnosis (n = 148) to those who died within 7 years of diagnosis (n = 494). Our final model included study site, age, stage at diagnosis, CA-125, comorbidity score, receipt of chemotherapy, BMI, and four separate comorbid conditions: weight loss, depression, hypothyroidism, and liver disease. Of these, only younger age, lower stage, and depression were statistically significantly associated with LTS. We did not identify any new characteristics associated with HGSOC survival. Prognosis of ovarian cancer generally remains poor. Large, pooled studies of ovarian cancer are needed to identify characteristics that may improve survival.

Axitinib-Induced Hypothyroidism as a Predictor of Long-Term Survival in Patients with Metastatic Renal Cell Carcinoma

Background: The side effects of sunitinib, namely onset of hypertension and hypothyroidism, have been reported to be predictive biomarkers of treatment efficacy. However, the relationship between hypothyroidism and prolongation of survival in treatment with axitinib, a drug similar to sunitinib, has not yet been reported. Objective: In this study, we examined the relationship between the onset of hypothyroidism caused by axitinib and overall survival (OS) and progression-free survival (PFS). Methods: In this retrospective study, 44 Japanese patients, including 30 men and 14 women, were enrolled. The average age of subjects in this study was 67 years. Results: During treatment, 68% of patients developed hypothyroidism, with an average peak thyroid-stimulating hormone (TSH) value of 15.7 mIU/L. Patients with TSH > 4 mIU/L and required thyroid hormone regulation with levothyroxine had prolonged PFS (11.1 vs. 3.5 months; p = 0.002) and OS (26.4 vs. 15.6 months; p = 0.02). Hypothyroidism was found to be a significant side effect of axitinib in patients with metastatic renal cell carcinoma (mRCC). Patients with hypothyroidism had significantly longer PFS and OS. Conclusion: Our findings indicate that hypothyroidism may be a predictive marker of therapeutic effect of axitinib against mRCC.

Predictors of long-term survival after hip fractures?-5-year results of a prospective study in Germany.

The incidence of hip fractures is increasing due to demographic transition. Until now, they are associated with poor results and high mortality rates. Data on long-term survival and influencing factors are sparse. Therefore, a prospective observational study was conducted. Patients ≥ 60years with hip fracture were included in this prospective study between 2009 and 2011. Demographic parameters, as well as ASA Score, pre-fracture Barthel Index and EQ-5D, Mini-Mental State Examination, Charlson Comorbidity Score, fracture type, type of surgical treatment, place of discharge, and arising complications were registered. Outcome parameter was survival during a 5-year follow-up period. A total of 539 patients attended to our emergency room during the period of recruitment. The recruitment rate was 75%. A total of 402 patients were included; 7 were lost to follow-up, and 152 (38%) survived the study period. The mortality was more than 25% in the first year after fracture. Subsequently, it was between 7 and 9% per year. In the multivariate analysis, significant risk factors for dying were male gender (p = 0.002), higher age (p < 0.001), lower Charlson Comorbidity Score (p = 0.033), lower Barthel Index (p = 0.024), lower Mini-Mental State Examination (p = 0.002), and occurrence of delirium during hospitalization (p = 0.008). Our results confirm poor results of geriatric patients after hip fracture. While early results might be influenced by optimal fracture care, long-term results seem to be determined by not changeable patient factors. Nevertheless, more than one third of surviving patients after 5years justify the elaborate treatment algorithms for these fragile patients.

Associations between Self-Reported Physical Function and Exercise Capacity in De Novo Heart Transplant Recipients

Purpose Physical capacity, as assessed by peak oxygen consumption (VO2peak ) or self-reported physical function (PF) from Short Form-36 (SF-36), is a strong predictor of long-term survival in heart transplant (HTx) recipients. VO 2peak and SF36-PF are highly correlated in maintenance HTx, but their association has previously not been examined in de novo HTx recipients. Methods Seventy-eight patients who completed the HITTS study (High-intensity Interval Training in de novo heart Transplant recipients in Scandinavia) were included in the analyses. Patients were tested at baseline (mean 11 weeks after surgery) and at 12 months follow-up, with self-reported PF (SF-36v2), cardiopulmonary exercise test with measurement of VO 2peak, and lower limb isokinetic muscle strength. Pearson´s correlation was used to compare the association between PF and VO2peak (L/min) and PF and muscular strength; early (mean 11 weeks after HTx) and later (1 year after HTx). Results Mean ± SD age was 49 ± 13 years, 73% were men. Both at 11 weeks and after 1 year, there were statistically significant positive correlations indication moderate association between PF and VO2peak (r=0.482 vs. 0.401) (Fig 1), PF and muscular exercise capacity (r= 0.494 vs. 0.388), and PF and maximal muscular strength (r = 0.443 vs. 0.414). Conclusion De novo HTx patients´ self-reported PF is associated with both VO2peak and muscular strength, also found 1 year after HTx. While measuring VO2peak is the preferred method of examining physical capacity and prognosis, self-reported PF is an easy, less resource-demanding assessment that could be considered as a clinical substitute.

Predictors of long-term survival in patients treated with targeted temperature management after cardiac arrest.

Predictors of long-term survival in patients treated with targeted temperature management after cardiac arrest.

Abstract P2-08-48: Features associated with long-term survival in metastatic breast cancer

Abstract Background: 5-10% of women with metastatic breast cancer (MBC) survive ≥5 years. Predictors of long-term survival are not clearly elucidated. We used data from 122 long-term MBC survivors (≥5-year survival from date of MBC diagnosis) and 191 short-term MBC survivors (≤2-year survival from date from MBC diagnosis) to identify clinico-pathologic and socioeconomic features associated with MBC survival. Methods: Women initially diagnosed with breast cancer (BC) in or after 1999, and diagnosed with MBC at Magee Women's Cancer Program of UPMC were included (N=313). Data abstracted from medical records included: stage at initial BC diagnosis, body mass index (BMI), Charlson Comorbidity Index (CCI), age, menopausal status at initial BC diagnosis, tumor receptor status at initial BC diagnosis, site of initial metastases, time to recurrence between initial diagnosis and MBC, household income, race, employment status, and partner status. Differences between groups were assessed using t-tests and Chi-square or Fisher's exact tests. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression models. Results: Long-term survivors were significantly (P&amp;lt;0.05) younger, had more ER positive, PR positive, and Her2 positive disease, lower CCI, more often premenopausal at initial diagnosis, lower rates of visceral metastases, higher household income, and more often partnered than short-term survivors. The association of premenopausal status at initial diagnosis with long-term survival remained significant after adjustment for stage at initial diagnosis, tumor receptor status, and CCI (OR: 1.96, 95% CI 1.02- 3.79). Long-term term survivors were also significantly more often diagnosed with de novo MBC compared to short-term survivors. The association of de novo MBC with long-term survival remained significant after adjustment for age, tumor receptor status, and CCI (OR: 3.0, 95% CI 1.6-5.4). Time to recurrence between initial diagnosis and MBC, BMI, race, and employment status were not associated with survival. Conclusions: Diagnosis of de novo MBC, ER-, PR- and/or Her2-positive primary tumor, lower rates of visceral metastases, higher household income, younger age, lower CCI, premenopausal status, and having a partner are associated with long-term survival after diagnosis of MBC. This is one of the first studies to show a survival benefit in MBC for patients with de novo MBC, premenopausal status at initial diagnosis, positive partner status, and higher household income. Citation Format: Klar NJ, Rosenzweig M, Diergaarde B, Brufsky A. Features associated with long-term survival in metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-48.

Effect of the Selective NLRP3 Inflammasome Inhibitor mcc950 on Transplantation Outcome in a Pig Liver Transplantation Model With Organs From Donors After Circulatory Death Preserved by Hypothermic Machine Perfusion.

We investigated whether the outcome of organs from donors after circulatory death (DCD) can be improved by the addition of mcc950 to the perfusate of the hypothermic machine perfusion (HMP) system and intravenous mcc950 injection after transplantation in a pig liver transplantation model. Thirty-six healthy Bama mini pigs randomized into 3 groups. All the DCD livers were preserved in an HMP system after 2 hours of simple cold storage. In HMP-Postop group, mcc950 was added to the perfusate; in the control group and Postop group, the perfusate was normal LPS. After transplantation, the pigs in the Postop group and HMP-Postop group were intravenously administered 3 mg/kg mcc950, at the time of reperfusion and on day 2 and day 3 after transplantation. During the 3-day follow-up period, general operative characteristics, and serological markers and histological features related to ischemia reperfusion injury were examined. The HMP-Postop group suffer the lightest ischemia reperfusion injury (IRI), and functioned best after transplantation. Model for the Early Allograft Function Score (predictor of long-term survival), degree of injury in the hepatocytes and rate of apoptosis was lowest in the HMP-Postop group. Further, in the HMP-Postop group, the nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 inflammasome pathway activation was lowest, and the level of IL-1β was lowest. Postop group functioned better than control group, but not comparable with HMP-Postop group. The outcome of DCD organs can be improved by the addition of mcc950 to the perfusate of the HMP system and intravenous injection of mcc950 after transplantation.

Prognostic factors associated with long term survival in chemotherapy-treated advanced pancreatic cancer: A Canadian multicenter analysis.

416 Background: The outcomes of patients (pts) with advanced pancreatic cancer (APC) are poor. With the use of currently available multi-agent regimens, median overall survival (mOS) remains &lt; 12 months. Select pts, however, experience a protracted survival. Little is known about the clinical, pathologic and treatment characteristics associated with long term survival (LTS) in APC. Methods: Pooled individual level data from six Canadian cancer centers of pts diagnosed with APC from 2012 to 2016 who received at least one cycle of chemotherapy (CT) were analyzed. Clinical, pathologic and treatment characteristics, as well as survival, were compared between pts who lived &lt; and ≥ 18 months. Multivariable logistic regression was used to identify independent predictors of survival. Results: Of 455 pts, 96% had metastatic disease and 88 (19%) survived ≥ 18 months. Compared to pts who survived &lt; 18 months, those with LTS had lower WBC (p = 0.0025), CA 19-9 (p &lt; 0.001), ALP (p &lt; 0.001) and LDH (p = 0.007) at baseline. Pts with LTS also had higher albumin (p &lt; 0.001) and BMI (p = 0.0268). In addition, they had better ECOG (p &lt; 0.001) and were more likely to have tumors in the head of the pancreas (p = 0.0204). LTS pts were more likely to have a complete response (CR) or partial response (PR) to 1L CT (p &lt; 0.001). The mOS seen with LTS was 29.2 months, compared to 4.3 months (p &lt; 0.001). On multivariable logistic regression, independent predictors of LTS included: primary tumor in the head of the pancreas (OR 3.42 95% CI 1.2-9.76); experiencing a CR or PR to 1L CT (OR 9.19 95% CI 3.78-22.32); and receipt of 2L doublet CT (OR 2.72 95% CI 1.05 to 7.08). Conversely, factors associated with lower likelihood of LTS included: ECOG ≥ 2 (OR 0.32 95% CI 0.11-0.95); and elevated CA 19-9 (OR 0.43 95% CI 0.21-0.9). Conclusions: A select proportion of pts with APC experience LTS and have clinical features which differentiate them from those without LTS. The use of performance status, primary tumor location, pre-treatment CA 19-9, 2L CT type and radiologic response may help identify LTS and inform discussions regarding treatment and prognosis.

Impact of Individual Vs. Composite Endpoints for Prediction of Long-Term Survival in Gvhd Clinical Trials Research

INTRODUCTION The composite endpoint of GVHD-free, relapse-free survival (GRFS), defined as survival free from grade 3–4 acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic immunosuppressive therapy (IST), or relapse has emerged as an outcome to capture clinically meaningful events. In the present study, we validated GRFS as a useful surrogate endpoint by examining the relative importance of individual events and the GRFS composite itself on overall survival (OS) at 5-years after allogeneic HCT. METHODS We conducted an IRB-approved retrospective cohort study on 565 consecutive patients (age ≥18 years) undergoing first-time allogeneic HCT for hematologic malignancy (January 2007–March 2013). Data abstraction of GRFS events was performed through chart review of the EHR. To determine the impact of each event of the GRFS composite endpoint, we accounted for competing risks using Fine and Gray methods, and correlated each event with OS using Kaplan-Meier methods. Using statistical simulations, the relative consequences of successfully modulating individual or composite endpoints on OS were examined to further elucidate the role of GRFS in clinical trials research. RESULTS The median age of the cohort was 54 years (18–73 years), comprised predominantly of males (58%) and Caucasians (94%). The most common indication for transplant was AML (41%), followed by lymphoma (21%) and MDS/MPD (14%). Patients received HLA-matched related (47%), and matched unrelated (53%) donors, and mostly peripheral blood stem cells (90%) and myeloablative conditioning (68%). Relapse conferred the greatest risk for death (HR 7.89; 95% CI:5.83–10.69). Grade 3–4 aGVHD was associated with HR 6.16 (95%CI:4.42–8.56), while cGVHD requiring IST was associated with lower HR 1.69 (95%CI:1.16–2.46). Indeed, the GRFS composite correlated with less HR 4.81 (95% CI:3.61–6.41) compared with either relapse or grade 3–4 aGVHD events. To determine the impact of hypothetical improvements on individual events or combined events (composite) on OS, we next performed Monte Carlo simulations. Compared with individual events, modulating composite endpoints predicted the greatest change in 5-year OS (Figure 1). The greatest gain in OS was seen by proportionally reducing both grade 3–4 aGVHD and relapse (modified GRFS). Reducing chronic GVHD requiring IST proportionally with grade 3–4 aGVHD and relapse events (conventional GRFS) did not change 5-year OS. CONCLUSION These findings highlight the importance of influencing OS by targeting the major early adverse post-HCT events (i.e., grade 3–4 acute GVHD and relapse). Moreover, the simulations herein suggest that GRFS as currently defined may be less optimal for predicting OS than using early grade 3–4 aGVHD and relapse as composite endpoints. Importantly, further refinement of these endpoints will depend on the a priori defined study population as well as intervention.

Long-term outcomes in chronic hypersensitivity pneumonitis.

The objective of this study was to analyze mortality, possible predictors of long-term survival, and health-related quality of life of a large chronic hypersensitivity pneumonitis (CHP) patient sample. Longitudinal study in patients diagnosed with CHP during 2004-2013, followed for at least 1year. Patients remaining alive and consenting to participate had a follow-up visit during 2015, including a complete pulmonary function study and the EuroQol-5D and Beck Depression and Anxiety Inventories. Out of the 160 patients finally included, 87 remained alive. Seventy-three had died or underwent lung transplantation at the time of the study with a median survival of 7.0 (4.4-14.5) years. A Cox proportional risk model showed that factors associated with lower survival were as follows: increased age, a low percentage of lymphocytes in bronchoalveolar lavage (BAL), a decreased transfer factor of the lung for carbonmonoxide (DLCO), presence of honeycomb in the high-resolution chest scan (HRCT), and the usual interstitial pneumonia (UIP) histologic pattern. At follow-up, all patients presented an EuroQol-5D score <0.8 and 21(50%) and 9(28.6%) subjects presented a probable anxiety and depressive syndrome, respectively. CHP is a severe disease with a bad mid-term prognosis. Lymphocyte values in BAL and DLCO values at baseline, presence of honeycomb in HRCT, and UIP histologic pattern were found to be predictors of survival. Early accurate diagnosis of the disease is fundamental for prompt initiation of antigen avoidance.

Tumor-specific intraoperative detection of pancreatic ductal adenocarcinoma using multimodal molecular imaging

Background: Two major predictors of long term survival of pancreatic cancer are the ability to resect tumor with cancer free margins and absence of systemic metastases. Unfortunately, margin positive resections are a frequent phenomenon as is the emergence of distant metastases soon after surgery. The use of tumor targeted molecular imaging has the potential to provide crucial information to surgeon, both in the form of fluorescent and photoacoustic imaging. Here, we report the use of Cetuximab-IRDye800, a near-infrared fluorescent agent, that binds to EGFR for intraoperative detection of pancreatic cancer. Methods: A dose escalation study of Cetuximab conjugated to IRDye800 was performed in patients (n=7) undergoing surgical resection of pancreatic cancer. Safety and pharmacokinetic data were obtained up to 30 days after infusion. Multi-instrument fluorescence and photoacoustic imaging was performed both in the operating room and ex vivo. Results: There were no grade 2 or higher adverse events attributable to the intravenous injection of cetuximab-IRDye800. Fluorescence imaging successfully differentiated tumor and positive lymph nodes from normal tissue during resection with average tumor-to-background ratio of 8.7. Ex vivo fluorescence, photoacoustic and pathologic examination confirmed correlation between tumor and fluorescent and photoacoustic signal. Conclusion: This study demonstrates safety and feasibility of tumor-specific Cetuximab-IRDye800 for multimodal molecular intraoperative imaging of pancreatic cancer.

Thromboelastography Parameters as Predictors for Long-Term Survival in Critically Ill Patients.

Thromboelastography (TEG) is used for monitoring abnormal blood coagulation in critically ill patients. However, the correlation between TEG parameters and long-term survival in these patients is unknown. We aimed to quantify the effect of TEG on long-term survival of critically ill patients. Critically ill patients undergoing TEG were retrospectively examined. Baseline patient characteristics and coagulation function indexes were compared. Cox regression, receiver–operating characteristic curve analysis, and Kaplan-Meier survival estimate curve were performed. We included 167 critically ill patients. Clot formation speed (K) and reaction time (R) were higher, whereas maximum amplitude (MA) and angle were lower in the mortality group than in the survival group (P < .01). All TEG parameters were risk factors for 2-year survival in critically ill patients (P < .01). The area under the curve of MA for predicting 2-year survival was 0.756 (95% confidence interval: 0.670-0.841). The Kaplan-Meier survival estimate curve analysis showed that MA predicted 2-year survival of critically ill patients(P < .01). Maximum amplitude can effectively predict 2-year survival of critically ill patients, indicating the influence of the coagulation system on these patients.