Predictor Of Shorter Survival Research Articles

Genomic and biomarker analysis of immunotherapy combined with chemotherapy treated for patients with metastatic BTC cancer: A real world study.

e16373 Background: Biliary tract cancer (BTC) is a heterogeneous group of diseases with dismal prognosis. The TOPAZ-1 phase III trial and KENOTE 966 reported a survival benefit with the immune checkpoint inhibitor (ICI) plus chemotherapy (GemCis,GC) in patients with advanced BTC. Consequently, immunotherapy plus chemotherapy has become a new standard care for advanced BTC. Understanding the association between genomic alterations and immunotherapy outcomes of BTC could further improve the clinical benefits. Therefore, we conducted this real-world study in China. Methods: This study included 47 patients with metastatic BTC treated with PD-1/PD-L1(ICI) antibodies in combination with chemotherapy from January 2019 to January 2023 in Medical Oncology department of Chinese PLA General Hospital. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall response rate (ORR), disease control rate (DCR). The exploration endpoint was genomic and biomarker analysis. Genomic tumor DNA was isolated from 30 patients and used for targeted next-generation sequencing genes to identify the genomic profiles. Results: 47 patients received immune checkpoint inhibitor (ICI) plus with chemotherapy in first line were enrolled in this study. The median PFS were 5.4m (95%CI,4.4-6.3), ORR and DCR was 21.3% and 83.0%, respectively. Patients were grouped into two group:AS+PD1(n=34) group and GC+ICI(n=13) group. In the AS(Albumin paclitaxel+S1)+PD1 group, mPFS was 5.0m (95%CI 3.8-6.1), ORR were 20.6% and DCR were 79.4% as we reported previously. In the GC+ ICI, mPFS was 7.9m (95%CI 4.7-11.1), ORR was 23.1% and DCR was 92.3%. There was no difference in terms of PFS, ORR and DCR between two groups. With regard to biomarker analysis, PD-L1 expression positive were 16 patients, which of mPFS were 4.2m and ORR were 18.8%, otherwise 12 patients were PDL1 expression negative, of whom mPFS were 9.1m and 33.3% as unexpected. Average TMB were 4.5mt/MB for MSS type patients. There is no difference of PFS between TMB high(>4.5mt/MB) or low(<4.5mt/MB). As for genomic analysis, the most common gene alterations were TP53(N=13, 43%))KRAS(N=8, 26.7%), NTRK1\2\3(N=8, 26.7%), IDH1/2(N=6, 20%), PIK3CA(N=6, 20%), BRCA2(N=5, 16.7%). MDM2(N=5,16.7%), BRAF(N=4,13.3%). The mutations are mainly concentrated in the DDR (20) pathway followed by the RTK-RAS (16), TP53 (13), CPF (9), FA (9), HRR (9), and PI3K (8) pathways. Compared between long term survival(PFS>5.4m)and short term survival(PFS<5.4m), MDM2 was only predictor for short survival(p<0.05). Conclusions: Compared to AS+pd-1, patients received GP+ ICI numerically had better outcomes. It seems PD-L1 and TMB were not good predictors to select patients who can more benefit from immunotherapy plus chemotherapy. MDM2 mutation suggest patients tend to less active to immunotherapy-based modality.

“Post-renal acute kidney injury in patients with cancer: Clinical presentation and kidney and patient outcomes”

Background: Post-renal acute kidney injury (PR–AKI) is frequent in patients with cancer requiring emergent intervention. With our study we aimed to describe the clinical features and prognostic factors for kidney and overall survival (OS) in cancer patients with PR–AKI. Methods: This is a single-center retrospective study that included 306 cancer patients with PR–AKI admitted from January 2011 to December 2021. Previous kidney function, AKI episode, and progression to end-stage kidney disease (ESKD) were compared. Kaplan Meier and Cox proportional regression methods were used for survival analyses. Results: The most frequent type of malignancy was the prostate (52, 17%) followed by the uterus (50, 16.3%). The mean baseline eGFR was 62 ml/min/1.73 m2. AKI stage 3 was present in 157 patients (51.3%) and renal replacement therapy (RRT) was performed in 19 patients (6%). At discharge, 197 patients (64.4%) had a quick recovery, and during follow-up 8 (2.6%) patients progressed to ESKD. The risk factors associated with ESKD were previous decreased kidney function (eGFR<30 ml min 1.73m2) (HR 33.275, [95% CI, 3.997–277.002], p = 0.001); glomerular disease, (HR 8.353, [95%CI, 1.022–68.279], p=0.048); concomitant prerenal AKI (HR 5.670, [95% CI, 1.143–28.131], p = 0.034); and need of RRT (HR 19.519, [95% CI, 4.871–78.215], p < 0.001). Median OS was 6 months (IQR 1–24 months). We found differences in the global survival over 60 months, with longtime survivors including patients with Bricker (42.6% vs16.4%) and genito-urinary cancer (27.6% vs 11.7%). Gastric cancer (HR 2.943, [95%CI, 1.837–4.714], p<0.001), metastatic disease (HR 1.913, [95%CI, 1.464–2.499], p < 0.001), and direct tumoral invasion (HR 1.519, [95%CI, 1.115–2.070], p = 0.008) were related with a decreased survival. Conclusions: Gastric cancer, metastatic disease, and direct tumoral invasion were predictors of short survival. The main predictors of evolution to ESKD were previous kidney function, concomitant glomerular disease, and the need for RT.

Depressive symptoms and shorter survival in lung cancer: the role of leukocyte telomere length

Objective To examine the association between depressive symptoms, leukocyte telomere length–a marker of cellular ageing, and survival amongst lung cancer patients. Design Patients with non-small cell lung cancer were recruited from a university-affiliated cancer center clinic. Main Outcome Patients (N = 67) reported on depressive symptoms and provided a blood sample for leukocyte telomere length assessment at baseline and at a 3-month follow-up. Survival status was tracked over 3 years. Results Age at diagnosis and depressive symptoms, as measured by the CES-D, were associated with shorter leukocyte telomere length (p < .05), although only age at diagnosis contributed statistical significance to the model. Depressive symptoms predicted shorter survival from date of diagnosis (p < .01). Patients who reported experiencing clinically meaningful levels of depressive symptoms (CES-D scores ≥ 16) demonstrated shorter survival than those who reported sub-clinical levels of depressive symptoms (p < .05). Leukocyte telomere length did not emerge as a predictor of shorter survival. Conclusion Clinically meaningful levels of depressive symptoms are associated with shorter survival amongst lung cancer patients. These findings support the on-going efforts to screen all cancer patients for low mood and to investigate mechanisms linking depressive symptoms and shorter survival in cancer contexts.

10-year survival in patients undergoing cardiac resynchronization therapy

Abstract Background Advanced heart failure with reduced ejection fraction (HFrEF) is associated with poor prognosis. Cardiac resynchronization therapy (CRT) is an effective method of treatment for advanced HFrEF to reduce HF hospitalizations and mortality. Nonetheless, very long-term observation of HF patients undergoing CRT implantation is scarce. Aim To assess very long-term survival (≥10 years) and predictors of shorter survival (death within 10 years from CRT implantation). Methods We screened a large dataset of CRT population from a tertiary care university hospital comprising consecutive HF patients implanted with CRT from 2002 through 2019 to select those who were alive ≥10 years and those who died within 10 years since device implantation. We analyzed various patients' baseline, clinical and procedural characteristics and sought for predictors of mortality within 10 years from CRT implantation. Results Of 1059 CRT patients, 143 (13.5%) were alive ≥10 years since CRT implantation. On multivariable regression analysis the independent predictors for all-cause death up to 10 years from CRT implantation were as follows: age, HR 1.02, 95% CI 1.01–1.31; male sex, 1.27, 95% CI 1.01–1.60; primary prevention of sudden cardiac death (SCD), HR 0.72, 95% CI 0.58–0.89; ischemic cardiomyopathy, HR 1.41, 95% CI 1.76–1.70; NYHA class at implantation, HR 1.38, 95% CI 1.17–1.62; baseline left ventricle ejection fraction (EF), HR 0.97, 95% CI 0.96–0.98; severe mitral regurgitation, HR 1.38; 95% CI 1.08–1.75; baseline NT-proBNP concentration, HR 1.00, 95% CI 1.00–1.00; and creatinine level, HR 1.00, 95% CI 1.00–1.01. Conclusions In a real-life patient population with CRT only 13.5% survived over 10 years since device implantation. Independent predictors for death within 10 years since CRT implantation were older age, male sex, secondary prevention of SCD, ischemic and more advanced heart failure along with renal impairment. Funding Acknowledgement Type of funding sources: None.

Fat mass loss correlates with faster disease progression in amyotrophic lateral sclerosis patients: Exploring the utility of dual-energy x-ray absorptiometry in a prospective study.

Weight loss is a predictor of shorter survival in amyotrophic lateral sclerosis (ALS). We performed serial measures of body composition using Dual-energy X-ray Absorptiometry (DEXA) in ALS patients to explore its utility as a biomarker of disease progression. DEXA data were obtained from participants with ALS (enrollment, at 6- and 12- months follow ups) and Parkinson's disease (enrollment and at 4-month follow up) as a comparator group. Body mass index, total lean mass index, appendicular lean mass index, total fat mass index, and percentage body fat at enrollment were compared between the ALS and PD cohorts and age-matched normative data obtained from the National Health and Nutrition Examination Survey database. Estimated monthly changes of body composition measures in the ALS cohort were compared to those of the PD cohort and were correlated with disease progression measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). The ALS cohort (N = 20) had lower baseline total and appendicular lean mass indices compared to the PD cohort (N = 20) and general population. Loss in total and appendicular lean masses were found to be significantly associated with follow-up time. Low baseline percentage body fat (r = 0.72, p = 0.04), loss of percentage body fat (r = 0.81, p = 0.01), and total fat mass index (r = 0.73, p = 0.04) during follow up correlated significantly with monthly decline of ALSFRS-R scores in ALS cohort who had 2 or more follow-ups (N = 8). Measurement of body composition with DEXA might serve as a biomarker for rapid disease progression in ALS.

Clinical Determinants of Disease Progression in Amyotrophic Lateral Sclerosis-A Retrospective Cohort Study.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is ultimately fatal but characterized by substantial phenotypic heterogeneity, which is known to impact long-term course and survival. This study investigated clinical determinants of disease progression and outcome in a large cohort of patients with ALS. Methods: Retrospective analysis included comprehensive data from 625 patients who attended a tertiary ALS centre at least twice. Patients were stratified according to five distinct clinical phenotypes: classical ALS; bulbar ALS; ALS with frontotemporal dementia (ALS-FTD); upper motor neuron predominant (UMNP); and lower motor neuron predominant (LMNP). Results: This study confirmed higher age at symptom onset, shorter latency to diagnosis and more rapid decline in the revised ALS Functional Rating Scale sum score as predictors of poor prognosis. Hazard ratios for shorter survival were higher in patients with ALS-FTD versus classical ALS, and in patients with versus without chronic obstructive pulmonary disease (COPD). Mean survival was longest in the UMNP phenotype group. Conclusions: This study confirmed established predictors of shorter survival in ALS and showed that concomitant COPD in particular relates to poor outcome.

Is presymptomatic ALS perivascular?

Increased activity in perivascular fibroblasts could precede motor-neuron degeneration and be a predictor of shorter survival in amyotrophic lateral sclerosis.

Prevalence, median time, and associated factors with the likelihood of initial antidepressant change: a cross-sectional study in Qatar

BackgroundMajor Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change.MethodsThis was a retrospective study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using several cox regression models.ResultsA total of 487 patients met the inclusion criteria of the study, 431 (88%) of them had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. The factors statistically associated with higher hazard of IAD change were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety.ConclusionsBecause almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. Our findings offered some clues to help clinicians identify the high-risk predictors of short survival and subsequent failure of IAD.

Long-Term Survival Following Sepsis.

There have not yet been any prospective registry studies in Germany with active investigation of the long-term survival of patients with sepsis. The Jena Sepsis Registry (JSR) included all patients with a diagnosis of sepsis in the four intensive care units of Jena University Hospital from January 2011 to December 2015. Long-term survival 6-48 months after diagnosis was documented by asking the treating general practitioners. The survival times were studied with Kaplan-Meier estimators. Cox regressions were calculated to show associations between possible predictors and survival time. 1975 patients with sepsis or septic shock were included. The mean time of observation was 730 days. For 96.4% of the queries to the general practitioners, information on long-term survival was available. Mortality in the intensive care unit was 34% (95% confidence interval [32; 37]), and in-hospital mortality was 45% [42; 47]. The overall mortality six months after diagnosis was 59% [57; 62], the overall mortality 48 months after diagnosis was 74% [72; 78]. Predictors of shorter survival were age, nosocomial origin of sepsis, diabetes, cerebrovascular disease, duration of stay in the intensive care unit, and renal replacement therapy. The nearly 75% mortality four years after diagnosis indicates that changes are needed both in the acute treatment of patients with sepsis and in their multi-sector long-term care. The applicability of these findings may be limited by their having been obtained in a single center.

Significance of Pretreatment C-Reactive Protein, Albumin, and C-Reactive Protein to Albumin Ratio in Predicting Poor Prognosis in Epithelial Ovarian Cancer Patients

To investigate the prognostic significance of pretreatment C-reactive protein (CRP), albumin, and the CRP to albumin ratio (CRP/Alb) in epithelial ovarian cancer (EOC) patients. Clinical data from 308 EOC patients between April 2007 and March 2016 were collected and retrospectively reviewed. The cutoff values for CRP, albumin, and CRP/Alb were defined by receiver operating characteristics (ROC) analyses. Univariate or multivariate analysis was conducted to evaluate the prognostic significance of these factors for disease-specific survival. The cutoff values for CRP, albumin, and CRP/Alb were 0.76, 3.8, and 0.048 by ROC analysis, respectively. Cox regression analyses demonstrated that an elevated CRP/Alb is an independent predictor of short disease-specific survival irrespective of clinical stage or optimal surgery rate. When examined according to clinical stage, elevated CRP/Alb was associated with short disease-specific survival in both early-stage and advanced-stage patients. Cox regression analyses demonstrated that an elevated CRP, but not lower albumin, is also an independent predictor of short disease-specific survival. When two prognosticators were compared, CRP/Alb was found to be superior to CRP for predicting disease-specific survival in EOC patients. Pretreatment elevated CRP/Alb is a predictor of shorter survival in EOC patients regardless of clinical stage.

Diagnostic and Prognostic Value of Conventional Brain MRI in the Clinical Work-Up of Patients with Amyotrophic Lateral Sclerosis.

Clinical signs of upper motor neuron (UMN) involvement are important in the diagnosis of amyotrophic lateral sclerosis (ALS) though are often difficult to analyze. Many studies using both qualitative and quantitative evaluations have reported abnormal Magnetic Resonance Imaging (MRI) findings at the level of the pyramidal pathway in patients with ALS. Although the most interesting results were obtained by quantitative studies using advanced MR techniques, the qualitative evaluation of MRI images remains the most-used in clinical practice. We evaluated the diagnostic and prognostic contribution of conventional 3T-MRI in the clinical work-up of ALS patients. Two neuroradiologists retrospectively assessed 3T-MRI data of 93 ALS patients and 89 controls. The features of interest were corticospinal tract (CST) T2/FLAIR hyperintensity, motor cortex (MC) T2*/SWI hypointensity, and selective MC atrophy. All MRI features were significantly more prevalent in ALS patients than in controls. The simultaneous presence of CST FLAIR hyperintensity and MC SWI hypointensity was associated with the highest diagnostic accuracy (sensitivity: 70%; specificity: 81%; positive predictive value, PPV: 90%; negative predictive value, NPV: 51%; accuracy: 73%) and a shorter survival (HR: 6.56, p = 0.002). Conventional 3T-MRI can be a feasible tool to detect specific qualitative changes based on UMN involvement and to support clinical diagnosis of ALS. Importantly, CST FLAIR hyperintensity and MC SWI hypointensity are predictors of shorter survival in ALS patients.

Clinical implications of hyperprogression with immune checkpoint inhibitors in patients with head and neck squamous cell carcinoma (HNSCC).

6034 Background: Hyperprogressive disease (HPD) refers to paradoxical acceleration of tumor growth kinetics (TGK) after initiation of treatment with anti- PD-1/PD- L1 agents and has been reported across tumor types in 4-29% of patients using different definitions. Preliminary data suggest that HPD might affect response to subsequent therapies. Methods: We compared TGK prior and TGK upon immunotherapy (IO) in 62 patients (pts) with recurrent/metastatic (R/M) HNSCC treated with PD-1/PD-L1 inhibitors. The TGK ratio (TGKR, ratio of tumor growth velocity before and upon treatment) was calculated. The first imaging assessment was performed 3 months (mo) after IO initiation. HPD was defined as 1. Radiological HPD (TGKR≥2) or 2. Clinical HPD (Disease-related rapid clinical deterioration post IO). Results: After median follow-up of 12.3 mo (range, 0.4-28.1), 43 pts progressed and 38 died. Median PFS was 2.8 mo (95%CI, 2.2-3.4) and median OS 8.6 mo (95%CI, 4.2-12.9). HPD was observed in 16 pts (25.8%), while 15 pts had early PD (Time to Treatment failure, TTF &lt; 3 mo) and 31 late PD (TTF &gt; 3mo). Among 16 pts with HPD, 11 had radiological HPD and 10 had clinical HPD. 4 pts had both clinical and radiological HPD. Pts with late PD had median OS 11.3 mo (95%CI, 9.3-13.3), those with early PD 5.2 mo (95%CI, 3.1-7.3 months) and those with HPD 5.1 mo (95%CI, 4.4-5.9) (p &lt; 0.005). Regarding post-progression OS, pts with late PD had median 11.3 mo (95%CI 0-22.8), those with early PD 2.5 mo (95%CI 0.6-4.4) and those with HPD 4.2 mo (95%CI 1.7-6.7) (p = 0.001). Pts with HPD had a trend for longer median post-progression OS compared to pts with early PD (p = 0.121). Median PFS with chemotherapy after immunotherapy failure was 3.0 mo (95%CI 2.4-3.6) for pts with late PD, 2.1 mo (95%CI 0.9-3.4) for pts with early PD and 6.1 mo (95%CI 3.0-9.3) for those with HPD (p = 0.040). HPD was associated with longer median PFS with chemotherapy compared to pts with early PD (p = 0.016), while the difference in median PFS with chemotherapy between pts with HPD and late progressors was non-statistically significant (p = 0.260). Conclusions: Radiological or clinical HPD was observed in 25.8% of patients with R/M HNSCC treated with IO. Early progression to immunotherapy is an important predictor of short survival, while HPD was associated with improved PFS to subsequent chemotherapy.

Expression and Clinical Significance of Protein Kinase RNA-Like Endoplasmic Reticulum Kinase and Phosphorylated Eukaryotic Initiation Factor 2α in Pancreatic Ductal Adenocarcinoma.

Endoplasmic reticulum stress and subsequent phosphorylation of eukaryotic initiation factor 2α (eIF2α) by protein kinase R-like endoplasmic reticulum kinase (PERK) plays an important role in the development and chemoresistance of pancreatic ductal adenocarcinoma (PDAC). However, the expression and significance of phosphorylated eIF2α (p-eIF2α) and PERK in PDAC have not been examined. We examined p-eIF2α and PERK expression in 84 PDAC and paired normal pancreas samples by immunohistochemistry and Western blotting and correlated the results with clinicopathologic parameters and survival. Mean PERK H score was 140.8 in PDAC compared with 82.1 in normal pancreas (P < 0.001). High p-eIF2α expression was present in 56% of PDACs versus 7.6% of normal pancreases (P < 0.001). High PERK and p-eIF2α expression correlated with shorter overall survival (P = 0.048 and P = 0.03, respectively). By multivariate analysis, high p-eIF2α (P = 0.01), positive margin (P = 0.002), and lymph node metastasis (P = 0.01) were independent prognosticators for survival. The expression levels of PERK and p-eIF2α are higher in PDAC than those in normal pancreas. High levels of PERK and p-eIF2α are predictors of shorter survival in PDAC patients, suggesting that PERK and eIF2α could be promising targets in PDAC.

The Impact of Neutrophil to Lymphocytic Ratio (NLR) as a Predictor of Treatment Outcomes in Rectal Carcinomas: A Retrospective Cohort Study

Background and aim: The prognostic role of neutrophil to lymphocyte ratio (NLR) has been shown in many solid tumors included in a recent meta-analysis of one hundred studies. We aimed to evaluate the prognostic value of neutrophil to lymphocyte ratio in treatment outcomes; response and survival of patients with different stages of rectal cancers. Patients and methods: All patients with pathologically confirmed cancer rectum presented to our department during the period from January 2012 to the end of 2014 were included in this retrospective study, these recruited patients were evaluated through their files to determine different objectives of our study. Results: The median overall survival was 31 ± 4.676 months while disease free survival was 40 ± 2.346 for the whole study group; neutrophil to lymphocyte ratio was negatively correlated with overall survival with r = –0.743, P disease free survival with r = –0.717, P total number of lymph nodes dissected ratio with r = +0.254, P = 0.028. Roc curve was used to find the accurate cut point of NLR for these patients and was found to be of 4.5. Conclusion: Elevated pre-treatment NLR is an independent predictor of shorter survival in patients with rectal cancer. This parameter is a simple, easily accessible laboratory test for identifying patients with poorer prognosis.

Vascular and tumor cell expression of VEGFR2 and molecular subtyping: An innovative biomarker approach in bladder cancer.

497 Background: Treatment approaches combining anti-angiogenic therapy with chemotherapy have shown promising clinical results in metastatic bladder cancer (BC). In order to interrogate the potential clinico-pathologic and molecular basis of these findings, we evaluated VEGFR2, vascular density and molecular subtyping in a series of BC patients. Methods: A custom-TMA with primary BC tissues from 117 patients (mean age 71 yrs; range 38-99 yrs; M:F = 83:34) treated at a single institution, was stained and scored (0-3) for CD34 (vascular density) and for VEGFR2 on tumor vessels and cells. CK5/6 and GATA3 IHC was scored by a pathologist to identify main molecular classes of BC. The association between clinico-pathologic variables, VEGFR2, CD34 and molecular subtypes was analyzed by Fisher’s exact test and ANOVA. Univariate and multivariate Cox proportional models were used for survival analysis. Results: Of 112 analyzable BC tissues, 41% were muscle-invasive (MIBC) vs. 56% non-muscle invasive (NMIBC) and 3% undetermined. Compared to NMIBC patients those with MIBC had shorter overall survival (p &lt; 0.001). The main molecular subtypes included basal (11%), mixed baso-luminal (28%) and luminal (61%). Compared to luminal and baso-luminal subtypes, the majority of basal BCs were muscle invasive (p = 0.036). VEGFR2 expression was higher in tumor vessels but variable in tumor cells. 74% of BCs showed high-medium levels of VEGFR2 (scores 3-2) in tumor vessels and 88% had high-medium levels of tumor vascular density. Within basal, luminal and baso-luminal subtypes, 58%, 78% and 71% had high-medium levels of vascular VEGFR2 (p = 0.52), while 83%, 91% and 82% had high-medium levels of tumor vascular density (p = 0.08). Survival analyses showed increasing patient age, higher stage and lower VEGFR2 levels as independent predictors of shorter survival. Conclusions: Given the observed complexity of BC regarding VEGFR2 expression and vascular density across molecular subtypes, further investigation is warranted to understand how the frequent expression of VEGFR2 on tumor vasculature and variable expression in tumor cells relates to the efficacy of anti-angiogenic agents across these subtypes in bladder cancer.

Long-term outcomes of postoperative taxane/platinum chemotherapy for early stage cervical cancer: a retrospective study.

Taxane/platinum (TP)-based combination chemotherapy is standard for the treatment of metastatic or recurrent cervical cancer. The aim of this study was to investigate the efficacy of postoperative TP therapy in early stage cervical cancer. A retrospective review of patients with FIGO IB-IIB stage cervical cancer who were treated with radical hysterectomy and displayed surgical-pathological risk factors was performed. 122 patients were identified between 2003 and 2012. Survival was analyzed by Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used to investigate predictors of survival. The median follow-up period was 82.4months. The postoperative adjuvant therapy was TP in 82 (67.2%) patients, other chemotherapies in 10 (8.2%), radiotherapy (RT) in 25 (20.5%), and no further therapy (NFT) in 5 (4.1%). Survival was analyzed using 4 subgroups according to the postoperative adjuvant therapy. The estimated 5-year overall survival was 95.1% in the TP group, 90.0% in the other chemotherapy group, 78.9% in the RT group, and 100% in the NFT group. No significant difference of survival was observed in the subgroups. However, when analyzing only patients who displayed high-risk factors, non-TP adjuvant therapy (including RT and other chemotherapies) was independently associated with shorter survival on multivariate analysis. In the TP group, multivariate analysis revealed that a positive surgical margin was a significant predictor of shorter survival. Postoperative TP is effective in patients with surgically treated early stage cervical cancer. In these populations, a positive surgical margin could be associated with poor prognosis.

Letter Re: Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

We read with interest the article by Geocadin et al.1 and found the conclusion of importance. Over the last 2 years, we observed a group of 32 patients treated with mild therapeutic hypothermia after an out-of-hospital nontraumatic cardiac arrest. When considering the effect of the cardiac arrest on the patients' subsequent outcomes in the short and middle term, a sharp difference between 2 conditions was observed. A cardiac arrest complicated by a not-shockable rhythm and a circulatory instability is usually accompanied by a worsening cerebral edema. These 2 signs, clearly connected to each other, are strong predictors of short survival and of poor neurologic outcome, independent from any treatment. On the contrary, in the case of cardiac arrest followed by a shockable rhythm, mild therapeutic hypothermia is directly indicated for the greater possibility of a good outcome.2–4 In these patients, any early invasive treatment of the acute cardiac pathology, or of any other intervening complication, is not contraindicated.

Comparison of clinical utility between neutrophil count and neutrophil-lymphocyte ratio in patients with ovarian cancer: a single institutional experience and a literature review.

We retrospectively investigated the prognostic significance and clinical utility of pretreatment neutrophilia and elevated neutrophil-lymphocyte ratio (NLR) in patients with epithelial ovarian cancer. Clinical data were collected from 344 surgically staged ovarian cancer patients between April 2007 and March 2016 and retrospectively reviewed. Neutrophilia and elevated NLR were defined as a neutrophil count ≥ 8,000/μl and an NLR ≥ 4.0, respectively. Univariate or multivariate analysis was conducted to evaluate the association between pretreatment neutrophilia or elevated NLR and clinicopathological characteristics, optimal surgery rate, progression-free survival (PFS) and disease-specific survival (DSS). Finally, we compared the clinical utility between neutrophil count and NLR by receiver operating characteristic (ROC) analysis. Pretreatment neutrophilia and elevated NLR were observed in 24 (7.0%) and 142 (41.3%) patients, respectively. In univariate analysis, both neutrophilia and elevated NLR were found to be associated with short PFS and DSS (p<0.005). Multivariate analysis showed that neutrophilia and elevated NLR were predictors for shorter survival. In ROC analysis, the NLR tended to have a greater area under the ROC curve (AUC) value than the neutrophil count in predicting recurrence (0.7011 vs 0.6516, p=0.0546) and had a significantly greater AUC value in predicting DSS (0.7249 vs 0.6379, p=0.0182). Finally, based on the neutrophil count and NLR, we divided the patients into 3 prognostic groups-high-risk group (elevated NLR with neutrophilia), intermediate-risk group (elevated NLR without neutrophilia), and low-risk group (normal NLR), which allows for individualized and accurate survival estimates. Pretreatment neutrophilia and elevated NLR are independent poor prognostic factors in epithelial ovarian cancer patients. The NLR was superior to neutrophil count in predicting the survival of epithelial ovarian cancer patients.

Cortactin is a prognostic marker for oral squamous cell carcinoma and its overexpression is involved in oral carcinogenesis.

EMS1 (chromosome eleven, band q13, mammary tumor and squamous cell carcinoma-associated gene 1) gene amplification and the concomitant cortactin overexpression have been reported to associate with poor prognosis and tumor metastasis. In this study, we examined cortactin expression by immunohistochemistry in human oral tumors and murine tongue tumors which were induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO). The immunostaining results show over- to moderate expression of cortactin in 85% (104/122) of oral squamous cell carcinoma (OSCC) tissues and in all 15 leukoplakia tissues examined. Further, statistical analysis indicates that cortactin overexpression appears to be a predictor for shorter survival and poorer prognosis in OSCC patients. In an animal model, cortactin is shown to upregulate in infiltrating squamous cell carcinoma, papilloma, and epithelia with squamous hyperplasia, indicating that cortactin induction is an early event during oral carcinogenesis. It is suggested that cortactin expression is mediated in the progression of pre-malignancy to papilloma, based on earlier cortactin induction in pre-malignancy preceding cyclin D1 in papilloma. In conclusion, cortactin overexpression is frequently observed in human OSCC and mouse tongue tumors. Thus, cortactin may have an important role in the development of oral tumors in human and mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 799-812, 2017.

Abstract C75: Correlation of nephrectomy status and race with overall survival in patients with metastatic renal cell carcinoma

Abstract Introduction: In most settings median overall survival (OS) is longer for non-Hispanic whites when compared to non-Hispanic blacks with metastatic renal cell carcinoma (mRCC). However, the clinical outcome has been equally poor for both groups in patients who do not undergo nephrectomy. The primary objectives of this study were to explore the reasons why patients with mRCC do not undergo nephrectomy and to evaluate the impact of nephrectomy status and race on OS. Methods: After obtaining approval from the Institutional Review Board of Emory University and the Atlanta Research and Education Foundation, a retrospective chart review was conducted at the Atlanta VA Medical Center in conjunction with a longitudinal biomarker study of patients with mRCC. Patients who were treated with targeted therapy between 2005 and 2015 were eligible for inclusion. Nephrectomy status was assessed and the reasons for not undergoing nephrectomy were documented. Descriptive statistics were employed along with Kaplan-Meier survival analysis. Results: Forty four of the 46 patients from the biomarker study were included in the analysis of nephrectomy status (31 non-Hispanic whites and 13 non-Hispanic blacks; 2 Hispanics were not included). Of the non-Hispanic patients, 39 had unilateral disease and 5 had bilateral disease for a total of 49 primary tumors. Nephrectomy rates with respect to the number of primary tumors were 59% for non-Hispanic whites (n=20 of 34) and 53% for non-Hispanic blacks (n=8 of 15) for an overall rate of 57% (n=28 of 49). There was no significant difference in OS by race with a median of 29.5 months (2.42 years) for non-Hispanic blacks (95% C.I. 7.4 – 56.9 months) and 35.6 months (2.92 years) for non-Hispanic whites (95% C.I. 19.4 – 61.4 months) with a log-rank p-value of 0.88. Metastasis was present at the time of nephrectomy in 14 cases while the remaining 15 cases were the result of recurrence after nephrectomy with curative intent. Of the 21 primary tumors that were not resected in 19 non-Hispanic patients, metastases were present in most instances at the time decisions were made regarding nephrectomy (n=17 of 21; 81%). There were relative or absolute contraindications to nephrectomy for 12 of the primary tumors that were not resected (57%). These included unresectable tumors and patients with poor performance status, chronic kidney disease or other significant medical comorbidities. For the 9 remaining unresected primary tumors, no contraindications to surgery were identified, yet some patients declined of their own volition, others were not referred or re-referred to urology and some did not keep their follow up appointments with urology. Also, some surgeons did not recommend nephrectomy. As such, no predominant reason for absence of nephrectomy was identified for the group as a whole or by race. However, in the absence of nephrectomy, the median OS was only 15.5 months (1.27 years) with a 95% C.I. of 8.5 to 29.5 months, versus 45.2 months (3.71 years) for patients who had undergone nephrectomy with a 95% C.I. of 30.3 to 100.9 months and a log-rank p-value of 0.0002. Summary: No racial disparity in OS was observed in this retrospective study of a small number of patients at a single institution. However, absence of nephrectomy may be a significant confounding factor since it is a strong predictor of short survival irrespective of race. Larger studies are required. Of note, a nephrectomy was much less likely to have been performed in patients who had metastatic disease at the time of diagnosis. Though no predominant reason for absence of nephrectomy was found, key factors were identified such as unresectability, poor performance status, significant medical comorbidities, the failure to schedule or keep appointments with surgical staff, and patient choice to forego nephrectomy. Citation Format: Dale Kesley Robertson, Yuan Liu, Chao Zhang, Theresa Gillespie, John Petros, Muta Issa, Maria Ribeiro, Wayne B. Harris. Correlation of nephrectomy status and race with overall survival in patients with metastatic renal cell carcinoma. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C75.