Multivariate Cox Survival Analysis Research Articles

Abstract No. 547 Radioembolization segmentectomy and stereotactic body radiation therapy for hepatocellular carcinoma: a retrospective survival analysis

To compare outcomes among hepatocellular carcinoma (HCC) patients treated with radioembolization segmentectomy (RS) with yttrium-90 conjugated beads or stereotactic body radiation therapy (SBRT). This single-center retrospective study included all HCC patients treated with RS or SBRT from January 2010 to February 2016. Records were reviewed for sex, median age (MA), target tumor size (cm) (TS), prior local-regional therapy with transarterial chemo embolization and/or ablation (LRT), radiographic response progression, and overall survival time (OST). Kaplan Meier and Cox multivariate regression survival analysis were performed to determine time to local progression (TLP), time to overall disease progression (TOP), and OST (months) after RS or SBRT along with hazard ratio (HR). There were 51 RS patients (75% male, MA 66) and 71 SBRT patients (75% male, MA 64) included. When TS was restricted to ≤5 cm, there were 23 RS patients (78% male, MA 64) and 64 SBRT patients (72% male, MA 65). Kaplan Meier revealed for all RS and SBRT respectively: TLP (34.6 v 54.8, p<0.04), TOP (19.1 v 27.6, p = 0.15), and OST (33.4 v 55.6, p = 0.48). Mean TS for RS and SBRT was 5.4 v 3.4, p<0.01. Rates of prior LRT in RS and SBRT were 25% v 87% (p<0.01). Multivariate regression survival analysis including treatment type, sex, age, prior LRT, and TS (Table 1) demonstrated that TS was the only independent predictor of TLP, TOP, and OST. When TS for RS and SBRT was limited to ≤5 cm (mean TS 3.3 v 2.6, p = 0.13), Kaplan Meier revealed respectively: TLP (39.3 v 55.6, p = 0.47), TOP (25.3 v 27.4, p = 0.83) and OST (38.3 v 50.0, p = 0.92). Retrospective analysis demonstrates RS and SBRT have similar outcomes in HCC with TS ≤ 5 cm and the majority of SBRT patients had prior LRT. TS may be an important factor in selecting RS and SBRT with LRT.Table 1Cox Regression AnalysisTLP HR (p)TOP HR (p)OST HR (p)RS v SBRT0.4(0.14)0.6(0.15)1.7(0.40)Sex0.3(0.11)0.6(0.16)1.1(0.91)Age1.0(0.70)1.0(0.66)1.0(0.47)LRT2.2(0.24)1.9(0.15)0.4(0.16)TS1.2(<0.01)1.3(<0.01)1.2(<0.01)P model<0.01<0.03<0.05 Open table in a new tab

Circulating antithyroid antibodies contribute to the decrease of glomerular filtration rate in lithium-treated patients: a longitudinal study

BackgroundConcerns about the adverse effects of long-term treatment with lithium include reduced renal function. In the present study, we examined comorbidities which may be associated with chronic kidney disease in a cohort of patients treated with lithium for up to 41 years.MethodsWe studied 394 patients who were treated with lithium for ≥ 5 years. The potential role of comorbidities (diabetes, concurrent antihypertensive medication, treatment with l-thyroxine, and presence of antithyroid peroxidase/microsomes, anti-thyroglobulin, and/or anti-thyrotropin-receptor antibodies) was analysed. We focused on the categories of patients with an estimated glomerular filtration rate (eGFR) lower than 60 or 45 mL/min/1.73 m2 as calculated from serum creatinine according to the Modification of Diet in Renal Disease Study Group. We applied multivariate regression analysis and Cox survival analysis to study the effects exerted by sex, age, duration of lithium treatment, and comorbidities using eGFR categories as the dependent variable. Kaplan–Meier curves were generated to measure the time to decline to an eGFR lower than 45 mL/min/1.73 m2 in patients with positive or negative thyroid antibodies.ResultsAge was associated with a decline to an eGFR lower than 60 mL/min/1.73 m2 after controlling for sex, duration of lithium treatment, and comorbidities. Circulating thyroid antibodies were associated with a decline to an eGFR lower than 45 mL/min/1.73 m2.ConclusionsThe present study is the first to suggest a potential role of circulating thyroid antibodies in the severe decline of eGFR in lithium-treated patients.

Utilization and survival implications of a delayed approach to targeted therapy for metastatic renal cell carcinoma: A nationwide cancer registry study.

586 Background: Targeted therapy (TT) is the first-line option for metastatic renal cell carcinoma (mRCC) however, it is not curative and associated with a high-cost and adverse events. Preliminary data suggests TT may be safely delayed in appropriately selected patient, however the utilization and impact of delayed TT has not been evaluated on larger-scale. Methods: The National Cancer Database (NCDB) was queried from 2006-2012 for patients with mRCC treated with cytoreductive nephrectomy and TT. Time to initiation of TT was defined as ‘early’ (within 2 months), ‘moderately delayed’ (2-4 months), and ‘delayed’ (4-6 months), and ‘late’ ( &gt; 6 months) based on time from diagnosis to initiation of therapy. Multivariable logistic regression was performed to determine factors associated with delayed TT. The impact time to initiation of TT on OS was estimated by Kaplan-Meier and Cox multivariable survival analysis. Results: For2,716 patients in the analysis, the median (interquartile range [IQR]) follow-up was 18.8 (9.1-32.9) months, and 71.8% of patients had died at last follow-up. The median (IQR) time from diagnosis to initiation of TT was 2.1 (1.3-3.23) months, with the longest delay being 20.1 months. 1,255 patients (46.2%) had early TT, 1,072 patients (39.5%) had moderately delayed TT, 284 patients (10.5%) had delayed TT, and 105 patients (3.9%) had late TT. Delay in TT was not found to be a predictor of mortality in multivariable analysis; early TT (reference), moderately delayed TT (HR 0.98, p = 0.74), delayed TT (HR 0.95, p = 0.51), and late TT (HR 0.86, p = 0.20). Time from diagnosis to initiation of TT and time from initiation of TT to patient death were not correlated after control for covariates ( r= 0.04, p = 0.08). Conclusions: Delay in initiation of TT for mRCC was not an independent predictor of worse OS. Although this study is subject to limitations of observation study design and selection bias, the results are consistent with the notion that in carefully selected patients, outcomes might not be compromised with initial observation. Prospective, randomized evaluation is warranted.

Clinical prognostic value of the isocitrate dehydrogenase 1 single-nucleotide polymorphism rs11554137 in glioblastoma.

The presence of the single-nucleotide polymorphism (SNP) rs11554137:C>T in the IDH1 gene is associated with a significantly lower survival in acute myeloid leukemia patients. The impact of its presence in glioblastoma on patient survival is unclear. We retrospectively reviewed 171 adult (> 18years of age) patients treated at a single, tertiary academic center for supratentorial glioblastoma (WHO grade IV) between 2013 and 2017. We conducted Kaplan-Meier overall and progression free survival analyses based on the IDH1 and IDH2 gene status of patients' glioblastoma (IDH wild type, mutant, and IDH1 rs11554137:C>T SNP). Multivariate Cox survival analyses were conducted accounting for age at diagnosis, preoperative Karnofsky performance status score, treatment (extent of resection, postoperative radiotherapy, and temozolomide), IDH gene variant, and MGMT promoter methylation status. Presence of rs11554137:C>T SNP in glioblastoma samples did not correlate with presence of IDH1 mutation. Patients with rs11554137:C>T SNP did not have histories of prior lower-grade gliomas. Patients with IDH mutant glioblastoma had a distinctly higher survival profile than both rs11554137:C>T SNP and IDH wild type glioblastomas. No survival difference was noted between patients with glioblastoma harboring the SNP and patients with IDH wild type glioblastoma. In this study, clinical prognostication in glioblastoma patients was largely dependent on the classification of IDH mutant and wild type glioblastoma, and not on the presence of IDH1 rs11554137:C>T SNP in the tumor.

Platelet-to-lymphocyte ratio in peripheral blood: A novel independent prognostic factor in patients with melanoma

ObjectivesThis retrospective study aimed to investigate the prognostic value of pre-treatment platelet-to-lymphocyte ratio (PLR), which is an inflammatory indicator, in patients with melanoma. MethodsPatients in this retrospective analysis were admitted between January 1, 2010 and December 31, 2015 in Henan Cancer Hospital. Receiver operating characteristic (ROC) curve was performed the optimal cut-off value for PLR. The 140 patients were divided into two groups: high PLR group and low PLR group. The relationship between PLR and overall survival (OS) was analyzed. The Kaplan-Meier and Log rank tests were used for univariate survival analysis and Cox proportional hazards regression model for multivariate analysis. ResultsThe optimal cut-off value of PLR determined by ROC curve was 120.15. Univariate and Cox multivariate survival analysis all showed that PLR and clinical stage were factors affecting OS in melanoma patients (P < 0.05). The overall median OS was 21.0 months (95% confidence interval (CI): 18.1–23.9), for 17.0 months in the high PLR group, and 34.0 months in the low PLR group (hazard ratio: 0.436, 95% CI: 0.291–0.652, P < 0.001), respectively. Clinical subgroup analysis showed that PLR was a risk factor in patients with stage II, III, and IV disease (P < 0.05). ConclusionThe elevated PLR was an independent prognostic predictor for OS in patients with melanoma.

Clinical Prognostic Value of the Isocitrate Dehydrogenase 1 Single-Nucleotide Polymorphism RS11554137 in Glioblastoma

The presence of the single-nucleotide polymorphism (SNP) rs11554137:C>T in the IDH1 gene is associated with a significantly lower survival in acute myeloid leukemia patients. The impact of its presence in glioblastoma on patient survival is unclear. We retrospectively reviewed 171 adult (> 18 years of age) patients treated at a single, tertiary academic center for supratentorial glioblastoma (WHO grade IV) between 2013 and 2017. We conducted Kaplan–Meier overall and progression free survival analyses based on the IDH1 and IDH2 gene status of patients’ glioblastoma (IDH wild type, mutant, and IDH1 rs11554137:C>T SNP). Multivariate Cox survival analyses were conducted accounting for age at diagnosis, preoperative Karnofsky performance status score, treatment (extent of resection, postoperative radiotherapy, and temozolomide), IDH gene variant, and MGMT promoter methylation status. Presence of rs11554137:C>T SNP in glioblastoma samples did not correlate with presence of IDH1 mutation. Patients with rs11554137:C>T SNP did not have histories of prior lower-grade gliomas. Patients with IDH mutant glioblastoma had a distinctly higher survival profile than both rs11554137:C>T SNP and IDH wild type glioblastomas. No survival difference was noted between patients with glioblastoma harboring the SNP and patients with IDH wild type glioblastoma. In this study, clinical prognostication in glioblastoma patients was largely dependent on the classification of IDH mutant and wild type glioblastoma, and not on the presence of IDH1 rs11554137:C>T SNP in the tumor.

Overexpression of FNDC1 in Gastric Cancer and its Prognostic Significance.

Objectives: The aims of this study were to compare the expression of fibronectin type III domain containing 1 (FNDC1) in gastric cancer (GC) and normal gastric tissue, to explore the prognostic significance of FNDC1 expression in patients with gastric adenocarcinoma, and to analyze FNDC1-related signaling pathways.Methods: The expression level of FNDC1 was initially predicted using the Oncomine and Cancer Genome Atlas databases. A Kaplan-Meier plotter database was mined to examine the clinical prognostic significance of FNDC1 mRNA in patients with GC. Subsequently, immunohistochemistry was used to measure FNDC1 protein expression levels in tissue from 90 cases of GC and paired adjacent normal tissue. Kaplan-Meier univariate and Cox multivariate survival analyses were used to determine the prognostic role of FNDC1 expression.Results: Bioinformatic data indicated that FNDC1 mRNA expression levels were significantly highly expressed in GC compared with normal gastric tissue (all P < 0.05), and patients with GC with high FNDC1 mRNA expression levels had remarkably lower overall survival (all P < 0.01). Immunohistochemical results revealed that expression levels of FNDC1 protein were significantly increased in GC compared with normal gastric tissue (P < 0.001). Additionally, Kaplan-Meier univariate and Cox multivariate survival analyses indicated that increased expression of FNDC1 was an independent predictor of poor prognosis in patients with GC (all P < 0.05).Conclusions: FNDC1 was highly expressed in GC, and high expression of FNDC1 was an independent predictor of poor prognosis in patients with GC. FNDC1 co-expressed genes were largely enriched in extracellular matrix-receptor interactions, which are closely related to tumor metastasis.

Prognostic significance of combined fibrinogen concentration and neutrophil-to-lymphocyte ratio in patients with resectable non-small cell lung cancer.

Objective:Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival. In this study, we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio (NLR) in predicting the survival of patients with non-small cell lung cancer (NSCLC).Methods:We retrospectively enrolled 589 patients with NSCLC who underwent surgery. The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including the combination of fibrinogen and NLR (F-NLR). The cut-off values for fibrinogen, NLR, and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis. According to the ROC curve, the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30, respectively. Patients with both a high NLR (≥ 2.30) and hyperfibrinogenemia (≥ 3.48 g/L) were given a score of 2, whereas those with one or neither were scored as 1 or 0, respectively.Results:Our results showed that F-NLR was an independent prognostic indicator for disease-free survival (DFS) [hazard ratio (HR), 1.466; 95% confidence interval (CI), 1.243–1.730; P < 0.001] and overall survival (OS) (HR, 1.512; 95% CI, 1.283–1.783; P < 0.001). The five-year OS rates were 66.1%, 53.5%, and 33.3% for the F-NLR = 0, F-NLR = 1, and F-NLR = 2, respectively ( P < 0.001). Correspondingly, their five-year DFS rates were 62.2%, 50.3%, and 30.4%, respectively ( P < 0.001). In the subgroup analyses of the pathological stages, the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers. Conclusions:Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.

Prognostic Dynamic Nomogram Integrated with Inflammation-Based Factors for Non-Small Cell Lung Cancer Patients with Chronic Hepatitis B Viral Infection.

Chronic inflammation plays an important role in tumor progression. The aim of this study was to develop an effective predictive dynamic nomogram integrated with inflammation-based factors to predict overall survival (OS) of non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. We retrospectively analyzed NSCLC patients with HBV infection from Sun Yat-sen University Cancer Center between 2008 and 2010. Univariate and multivariate Cox survival analyses were performed to identify prognostic factors associated with OS of patients. All of the independent prognostic factors were utilized to build the dynamic nomogram. The predictive accuracy of the dynamic nomogram was evaluated concordance index (C-index), decision curve analysis and were compared with previous reported model and traditional TNM staging system. According to the total points (TPS) by dynamic nomogram, we further stratified patients into different risk groups. A total of 203 patients were included. Multivariate Cox analysis showed TNM stage (P = 0.019), treatment (P < 0.001), C-reactive protein (P = 0.020) and platelet (P = 0.012) were independent prognostic factors of OS. The dynamic nomogram was established by involving all the factors above. The C-index of dynamic nomogram for predicting OS was 0.76 (95%CI: 0.72-0.80), which was statistically higher than that of traditional TNM staging system (0.70, 95%CI: 0.66-0.74, P<0.001). Decision curve analysis demonstrated that the dynamic nomogram was better than the TNM staging system. The predictive accuracy of the current model keeping almost the same accuracy as previous one. Based on the total points (TPS) of dynamic nomogram, we divided the patients into 3 subgroups: low risk (TPS ≤ 107), intermediate risk (107< TPS ≤ 149), and high risk (TPS > 149). The differences of OS rates were significant in the subgroups. We propose a novel dynamic nomogram model based on inflammatory prognostic factors that is highly predictive of OS in NSCLC patients with HBV infection and outperforms the traditional TNM staging system.

Tumor budding is a prognostic factor linked to epithelial mesenchymal transition in pancreatic ductal adenocarcinoma. Study report and literature review

BackgroundPancreatic ductal adenocarcinoma (PDAC) has a devastatingly poor prognosis. Surgical resection is undertaken in only 20% of patients. Most of well-known prognostic factors reflect tumor stage more than its biology. So it is important to identify new biological indicators related to survival in order to develop new therapies. ObjectiveTo determine the relation between tumor budding and Epithelial Mesenchymal Transition (EMT) and to evaluate their impact on survival for patients after resection of PDAC. MethodsWe herein report a retrospective study of 50 patients with resected PDAC. Tumor budding, immunohistochemical expression of vimentin and other standard factors were correlated with survival using the Kaplan-Meier method and Cox multivariable survival analysis. For tumor budding assessment, an inter-observer variability study was performed using 100 images of tumor slides stained with Hematoxylin & Eosin and Pan-Cytokeratin. ResultsTumor budding was present in all tumors. A substantial agreement between six pathologists was established in distinguishing high-grade from low-grade budding (κ = 0.6 and 0.73 for H&E and PCK images respectively). High-grade budding was identified in 56% of tumors (28/50). It was an adverse prognostic factor independent of tumor size, resection margins status, nodal status and vascular invasion (p = 0.008). Tumor budding was significantly associated with vimentin expression (p = 0.002). ConclusionsThe association of tumor budding with vimentin expression supported the idea that EMT is a key process in PDAC responsible for progression and drug resistance. Consequently, the elucidation of EMT molecular biology and development of new targeted therapy may improve disease outcome.

Kidney transplantation in Romania: two transplant centers experience.

Kidney graft survival rates improved from decade to decade, but data about factors that affect patient and graft survival remain challenging and even controversial. We analyzed retrospectively data from kidney transplanted patients followed in two Romanian transplant centers (Iasi and Bucharest)-new programmes specifically developed after 1989 to cover transplantation requirements for two-thirds of Romania. We used a composite survival outcome defined as 50% reduction in estimated glomerular filtration rate (eGFR), return to dialysis or death. Survival analysis was performed using uni- and multivariable Cox regression with baseline and time-updated covariates. From the entire cohort of 365 patients, 243 had the outcome of interest. In the univariable Cox survival analysis, age, hemoglobin, eGFR, cholesterol, AST and transplant center were associated with the outcome. The multivariable Cox analysis reveals that only cholesterol (HR 0.97, 95% CI 0.94-0.99 per 10mg/dL increase) and transplant center (HR 3.64, 95% CI 2.67-4.97) remain associated. For the time-updated Cox survival analysis we found that eGFR (HR 0.91, 95% CI 0.87-0.96 per 10ml/min/1.73m2 increase) and cholesterol are associated with the outcome in the univariable analysis and only eGFR and transplant center in the multivariable Cox survival analysis. Our study reports data from two distinct transplant centers from a developing country. Our results are similar to the current literature data, but also reveal that the approach of a center to the transplantation management is an independent factor associated with graft survival.

Clinicopathologic significance of ROCK2 expression in oral squamous cell carcinomas.

Rho-associated coiled-coil kinase 2 (ROCK2) is an oncoprotein that controls cytoskeleton organization and acts as prognostic marker in different types of solid tumors. ROCK2 overexpression is also observed in cancer-associated fibroblasts (CAF), which suggests its relevance within the tumor microenvironment. This study aimed to access the prognostic value of ROCK2 in oral squamous cell carcinomas (OSCCs) and its association with CAF density. Rho-associated coiled-coil kinase 2 immunohistochemical analysis was applied in 93 OSCC samples from 2 centers in Brazil and Finland. The samples were also stained for isoform α of smooth muscle actin (α-SMA) to characterize the presence of CAF in the tumor stroma. Clinicopathological associations were analyzed using Chi-squared test, survival curves were constructed according to the Kaplan-Meier method, and Cox proportional hazard model was applied for multivariate survival analysis. Advanced clinical stage (P = .002) and increased density of CAF (P = .002) were significantly associated with high ROCK2 expression. The high expression of ROCK2 was also associated with shortened disease-specific survival (HR: 2.22, 95% CI: 1.15-4.38, P = .04), but the association did not withstand the Cox multivariate survival analysis. The findings suggest that high ROCK2 expression in OSCC is associated with advanced disease and follows the increase in CAF density, which may be important for tumor progression.

Treatment with Allopurinol is Associated with Lower Risk of Acute Kidney Injury in Patients with Gout: A Retrospective Analysis of a Nested Cohort.

IntroductionGout is characterized by recurrent episodes of acute inflammation of joint structures, called gout flares, and flares are commonly treated with nonsteroidal anti-inflammatory drugs (NSAIDs). The objective of the study was to evaluate risk factors associated with acute kidney injury (AKI) attributed to NSAIDs in a cohort of patients who were exposed to NSAIDs to treat gout flares prior to urate-lowering therapy.MethodsRetrospective analysis of a nested cohort of 983 gout patients in whom general variables (age, gender, renal function, ethanol intake, hypertension, hyperlipidemia, diabetes, vascular events, diuretic use) and also variables related to gout and severity of gout (serum urate levels, number for flares per year, presence of tophi, joint distribution, X-ray involvement, previous urate-lowering therapy) were available for analysis. Outcomes considered were loss of renal function attributed to NSAID prescription following the RIFLE classification for (risk, injury, and failure) for acute renal events. Variables associated with increased risk in Kaplan–Meier survival analysis were tested with multivariable Cox survival analysis, using time from onset of gout to the event as time exposed to NSAIDs.ResultsOf 983 patients, 55 (5.6%) experienced AKI; the number of flares in the year previous to the renal event and polyarticular joint distribution were associated with higher risk of renal events. Other variables previously described in the literature, such as previous chronic renal disease, use of diuretics, and presence of previous vascular events, were also independently associated with increased risk of AKI. Interestingly, patients who had been previously prescribed allopurinol showed a lower risk of acute renal events.ConclusionIn addition to classic risk factors, the number of flares and extensive joint distribution were associated with higher risk for renal injury in patients with gout, while previous prescription of allopurinol was associated with lower risk.

Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma.

Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte–monocyte ratio (LMR), and neutrophil–platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma.

Disparities in care for elderly women with endometrial cancer adversely effects survival.

Elderly women with endometrial cancer are at increased risk of local recurrence and cancer-specific death compared to younger women. We sought to investigate adjuvant radiotherapy (RT) practice patterns and effects on survival in elderly women with endometrial cancer. Women from the National Cancer Data Base (NCDB) with FIGO IA grade 3 to FIGO IVA endometrial cancer diagnosed from 2004-2013 were included. Chi square analysis was used to compare the elderly (80+) and non-elderly women (18-79) and women who received RT and those that did not. Univariate and multivariate logistic regression were used to determine predictors of receipt of oncologic surgery and adjuvant RT. Univariate and multivariate Cox survival analyses were performed to examine the effect of radiotherapy on survival. Propensity score matching and shared frailty analysis were done in the elderly cohort. We identified 48,871 women for analysis. Rates of oncologic surgery were higher in the women 80+ compared with rates of adjuvant RT (95% versus 34%). Rates of RT receipt were higher in non-elderly women (48% versus 34%, p<0.001). Age over 80 was a negative predictive factor (OR 0.62, p<0.001) for receipt of adjuvant RT and oncologic surgery (OR 0.81, p=0.03). Adjuvant RT was associated with a decreased risk of death in elderly (HR 0.79, p<0.001) and non-elderly women (HR 0.77, p<0.001). Endometrial cancer patients over age 80 have similar rates of oncologic surgery as younger women but are significantly less likely to receive adjuvant RT, and this negatively impacts their survival.

The expression profile and prognostic value of APE/Ref-1 and NPM1 in high-grade serous ovarian adenocarcinoma.

To analyze the expression trends and clinical significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APE1/Ref-1) and Nucleophosmin (NPM1) proteins in high-grade serous ovarian adenocarcinoma (HGSC). The expressions of APE1/Ref-1 and NPM1 proteins in 94 patients with HGSC were determined using the immunohistochemical (IHC) method, and their relationships with clinicopathological features were analyzed by the χ2 test or Fisher's exact test. The follow-up data, Cox proportional hazards univariate and multivariate survival analyses were integrated to evaluate the prognostic factors affecting patients with HGSC. In the normal fallopian tubes, APE1/Ref-1 and NPM1 protein were mainly distributed in the nuclear. The HGSC experienced changes in the cellular localization of APE1/Ref-1 and NPM1 protein expressions, which were abnormally expressed in the cytoplasm. The rates of abnormal cytoplasmic expression of APE1/Ref-1 and NPM1 proteins in 94 patients with HGSC were 69.1% and 73.4%, respectively, which were significantly higher than the normal fallopian tube tissues (p < 0.05). The abnormal cytoplasmic APE1/Ref-1 and NPM1 are significantly correlated with the lymph node metastasis, chemosensitivity, FIGO staging, and prognosis. The COX multivariate survival analysis showed that the abnormal expression of APE1/Ref-1 protein, FIGO staging, and lymph node metastasis are independent prognostic factors. Collectively, the abnormal cytoplasmic APE1/Ref-1 and NPM1 proteins are associated with the oncogenic progression and chemoresistance of HGSC, and predict a poor prognosis.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals

Prognostic implication of aquaporin 1 overexpression in resected lung adenocarcinoma.

Aquaporins (AQPs) are a group of transmembrane water-selective channel proteins thought to play a role in the regulation of water permeability for plasma membranes. Indeed, high AQP levels have been suggested to promote the progression, invasion and metastasis of tumours. Specifically, AQP1 and AQP5 overexpression in lung adenocarcinoma (AC) have been suggested to be involved in molecular mechanisms in lung cancer. The aim of this retrospective cohort single-centre study was to assess both the levels of expression and therein the prognostic significance, regarding outcome of AQP1 and AQP5 in resected AC patients. Patients with histological diagnoses of lung AC submitted to pulmonary resection were included in this cohort study. Tissue microarrays containing cores from 185 ACs were prepared. AQP1 and AQP5 expressions were assessed by immunohistochemistry. Results were scored as either low (Score 0-2) or high (Score 3-9). Clinical data, pathological tumour-node-metastasis staging and follow-up were recorded. Multivariate Cox survival analysis and Fisher's t-test were performed. AQP1 overexpression was detected in 85 (46%) patients, while AQP5 overexpression was observed in 45 (24%) patients. AQP1 did not result being significantly correlated with clinical and pathological parameters, while AQP5 resulted more expressed in AC with mucinous and papillary predominant patterns. Patients with AQP1 overexpression had shorter disease-free survival (P = 0.001) compared with patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter disease-free survival (P = 0.001). Our results evidenced that AQP1 overexpression resulted in a shorter disease-free survival in lung AC patients. Being so, AQP1 overexpression might be an important prognostic marker in lung AC.

Incremental Prognostic Utility of Left Ventricular Global Longitudinal Strain in Asymptomatic Patients With Significant Chronic Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction

ObjectivesThis study sought to examine the prognostic utility of left ventricular (LV) global longitudinal strain (GLS) in asymptomatic patients with ≥III+ aortic regurgitation (AR), an indexed LV end-systolic dimension of <2.5 cm/m2, and preserved left ventricular ejection fraction (LVEF). BackgroundManagement of asymptomatic patients with severe chronic AR and preserved LVEF is challenging and is typically based on LV dimensions. MethodsWe studied 1,063 such patients (age 53 ± 16 years; 77% men) seen between 2003 and 2010 (excluding those with symptoms, obstructive coronary artery disease, acute AR/dissection, aortic/mitral stenosis, more than moderate mitral regurgitation, and previous cardiac surgery). Society of Thoracic Surgeons (STS) score was calculated. The primary endpoint was mortality. Average resting LV-GLS was measured offline on 2-, 3-, and 4-chamber views using Velocity Vector Imaging (Siemens, Malvern, Pennsylvania). ResultsMean STS score, LVEF, LV-GLS, and right ventricular systolic pressure were 4.4 ± 5.0%, 57.0 ± 4.0%, −19.5 ± 0.2%, and 31.0 ± 9.0 mm Hg, respectively. In total, 671 patients (63%) underwent aortic valve surgery at a median of 42 days after the initial evaluation. At 6.8 ± 3.0 years, 146 patients (14%) had died. On multivariable Cox survival analysis, LV-GLS (hazard ratio [HR]: 1.11), STS score (HR: 1.51), indexed LV end-systolic dimension (HR: 0.50), right ventricular systolic pressure (HR: 1.33), and aortic valve surgery (HR: 0.35) were associated with longer term mortality (all p < 0.001). Sequential addition of LV-GLS and aortic valve surgery improved the C-statistic for longer term mortality for the clinical model (STS score + right ventricular systolic pressure + indexed LV end-systolic dimension) from 0.61 (95% confidence interval [CI]: 0.51 to 0.72) to 0.67 (95% CI: 0.54 to 0.87) and to 0.77 (95% CI: 0.63 to 0.90), respectively (p < 0.001 for both). A significantly higher proportion (log-rank p = 0.01) of patients with LV-GLS worse than median (−19.5%) died versus those with an LV-GLS better than median (86 of 513 [17%] vs. 60 of 550 [11%]). The risk of death at 5 years significantly increased with an LV-GLS of worse than −19%. ConclusionsIn asymptomatic patients with ≥III+ chronic AR and preserved LVEF, worsening LV-GLS was associated with longer term mortality, providing incremental prognostic value and improved reclassification.

Immune-mediated therapy of pancreatic carcinoma: strategies to prevail over T cell exhaustion

Pyroptosis, a type of regulated cell death controlled by the gasdermin family of proteins to form plasma membrane pores is known. Nonetheless, the function of pyroptosis-related long non-coding RNAs (lncRNAs) in this process still lacks exhaustive elucidation in head and neck squamous cell carcinoma (HNSCC). Other attributes encompassing the function of such lncRNAs in the immune microenvironment and potential prognosis for HNSCC are yet to see the light of the day. This work was designed to probe the possible prognostic worth of pyroptosis-related lncRNAs along with their impact on the immune microenvironment in the case of HNSCC.The Cancer Genome Atlas (TCGA) database was the source of RNA-sequencing data of HNSCC patients. Pearson correlation analysis was employed to scour for lncRNAs linked to pyroptosis based on 40 genes related to the process. Following the construction of a pyroptosis-related lncRNA signature employing univariate, Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, survival and nomogram analyses ensued to scrutinize the predictive value of the prognostic signature.The segregation of patients into two risk groups was done by the constructed pyroptosis-related-lncRNA signature (encompassing 14 lncRNAs). The prognosis was poorer for individuals of the high-risk group versus (vs.) the low-risk group with the risk score emerging as an independent prognostic factor by regression analyses. The accuracy of this signature was corroborated by Receiver operating characteristic curve (ROC) analysis with the three-years area under time-dependent ROC curve (AUC) reaching 0.767. Further analyses unveiled a conspicuous enrichment of immune-related pathways in the low-risk group. The high-risk group demonstrated an immunologically “cold” profile based on the immune cell infiltration landscape.The lncRNA signature encompassing 14 pyroptosis-related lncRNAs could be a prognostic marker for HNSCC, suggesting pyroptosis might be a promising therapeutic target in HNSCC.