Univariate Cox Proportional Hazards Analyses Research Articles

Abstract B099: Rural black cases have worsened outcomes in head and neck cancer

Abstract Background: Racial and socioeconomic disparities in head and neck cancer survival are well documented. However, rural-urban context, especially the interaction between race and rural-urban context, is understudied. The aim of this study is to examine the relationship between race and rural-urban context in HNC survival and determine factors that potentially drive this disparity. Methods: We constructed a retrospective cohort of 158,718 head and neck squamous cell cases from the National Cancer Database with the following sites: hypopharynx (9.54%), larynx (54.42%), and oral cavity (36.04%). Since we are interested in traditional head and neck cancer, oropharyngeal cases were excluded from the cohort. We used Rural-Urban Continuum Codes (RUCC) to classify cases into metro (RUCC 1-3) and non-metro subgroups (RUCC 4- 9). Risk factors were classified into demographic (age and gender), socioeconomic (insurance status), and clinical factors (site, stage, and treatment modality). Kaplan-Meier survival curves and the Cox proportional hazards regression were used to calculate adjusted hazard ratios (HR). The proportional hazards and linearity assumptions were tested and satisfied. Results: The exposure cohorts that were analyzed include black metro (N = 17,256; 10.87%), black non-metro (N = 2,501; 1.57%), white metro (N = 109,842; 69.21%), and white-non-metro cases (N = 29,119; 18.35%). Rural-urban five-year survival differences are larger between black non-metro cases (39.32%; 95% Confidence Interval (CI): 37.21-41.56%) and black metro cases (43.97%; 95% CI: 43.15-44.81%) compared with white non-metro cases (50.32%; 95% CI: 49.68-50.99%) and white metro cases (53.12%; 95% CI: 52.79-53.45%). In the univariable Cox proportional hazards analysis, compared with white metro cases, black non-metro cases have the worst survival (HR: 1.44; 95% CI: 1.36-1.15; p<.001) followed by black metro cases (HR: 1.28; 95% CI: 1.26-1.31; p<.001) and white non-metro cases (HR: 1.0,76 95% CI: 1.06-1.10; p<.001). Interestingly, there is no interaction between race and rural-urban context (p=0.18). After conducting a multivariable analysis controlling for demographic, socioeconomic, and clinical factors, the HRs were attenuated, but black non-metro cases continue to have worse survival compared with white metro cases. Conclusion: Although there is no interaction between rural-urban context and race, black HNC cases, specifically those living in non-metro areas, have worse survival. This disparity still remains after adjusting for insurance status, site, and stage. Further research should be conducted to determine other modifiable risk factors to mitigate this racial and geospatial disparity. Citation Format: Jacob A Clarke, Alyssa M Despotis, Jose P Zevallos, Angela L Mazul. Rural black cases have worsened outcomes in head and neck cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B099.

Prognostic significance of nutritional markers in metastatic gastric and esophageal adenocarcinoma.

4557 Background: Malnutrition and sarcopenia (defined as low skeletal muscle mass) are recognized as poor prognostic factors in many cancers. Studies to date in gastroesophageal cancer have largely focused on patients (pts) undergoing curative intent surgery. This study aims to evaluate the prognostic utility of nutritional markers and sarcopenia in pts with de novo metastatic gastric and esophageal adenocarcinoma (GEA). Methods: Pts with de novo metastatic GEA seen at the Princess Margaret Cancer Centre from 2010-2016 with available pre-treatment abdominal computed tomography imaging were identified from an institutional database. Nutritional index (NRI) was calculated using weight and albumin, with moderate/severe malnutrition defined as NRI < 97.5. Skeletal muscle index (SMI) normalized by height was calculated at the L3 level using Slice-O-Matic software. Sarcopenia was defined as SMI < 34.4cm2/m2 in women and < 45.4cm2/m2 in men based on previously established consensus. Results: Of 175 consecutive pts, median age was 61, 69% were male, 79% had ECOG performance status 0-1, and 71% received chemotherapy. Median BMI was 24.2 (range 15.7-39.8), 70% of pts had > 5% weight loss in the preceding 3 months, and 29% had moderate/severe malnutrition. 68 pts (39%) were sarcopenic, of whom 46% were malnourished. Median overall survival (OS) was 9.3 months (95% CI 7.3-11.4) for all pts. OS was significantly worse in malnourished pts (5.5 vs 10.9 months, p = 0.000475) and displayed a non-significant trend in sarcopenic pts (7.8 vs 10.6 months, p = 0.186). On univariable Cox proportional hazards (PH) analysis, ECOG (p < 0.001), number of metastatic sites (p = 0.029) and NRI (p < 0.001) were significant prognostic factors, while BMI (p = 0.57) and sarcopenia (p = 0.19) were not. On multivariable Cox PH analysis, ECOG (p < 0.001) and NRI (p = 0.025) remained significant as poor prognostic factors for OS. Conclusions: This study demonstrates in a large cohort of de novo metastatic GEA pts that ECOG and NRI were significantly associated with poor OS. NRI was superior to BMI alone. Early identification of malnourished pts using NRI may allow for supportive interventions to optimize nutritional status. Further study is needed to determine whether these factors can be modified to improve prognosis in these pts.

Association of intraoperative opioids with improved recurrence-free survival in triple-negative breast cancer.

542 Background: Opioid-induced immunomodulation may be of particular importance in triple negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and outcomes in a large TNBC cohort. Methods: Consecutive patients with stage I-III primary TNBC treated between 03/2010 and 12/2016 were identified from our prospectively maintained database. Total intraoperative opioid dose was extracted from anesthetic records and converted to oral morphine milligram equivalents (MME) (10 MME = 50 mcg fentanyl IV). Univariable and multivariable (MVA) Cox proportional hazards analysis (adjusting for relevant clinicopathological features, (neo)adjuvant therapy, anesthesia technique and morbidity score), were performed to quantify the association between opioid exposure and recurrence-free survival (RFS) and overall survival (OS). Results: 1143 patients were included. Median age was 54 years (IQR 45, 64). 911 (80%) had ductal histology, 359 (31%) had nodal metastases, and 1070 (94%) were poorly differentiated. 781 (68%) received adjuvant chemotherapy and 313 (27%) received neoadjuvant chemotherapy. 525 (46%) received total intravenous anesthesia and 618 (54%) had general anesthesia. Median intraoperative opioid dose was 30 MME (IQR 20, 60). 5-year RFS was 81% (95% CI 79%-84%), 5-year OS was 86% (95% CI 84%-88%). In MVA, higher opioid administration was associated with favorable RFS but did not significantly affect OS (Table). Conclusions: Our study is the first to directly evaluate intraoperative opioid administration in TNBC and suggests a protective effect on RFS. Future work will focus on elucidating the underlying mechanism for this effect, including possible modulation of endogenous opioid signaling pathways and immunologic correlates. [Table: see text]

The association of CD8+ T-cell infiltration and PD-L1 expression with prognosis of Chinese pulmonary large cell neuroendocrine carcinoma.

e21003 Background: Pulmonary large cell neuroendocrine carcinoma (LCNCE) is a high-grade neuroendocrine tumor with poor prognosis. The genomic profile and immune feature of LCNEC have been reported in many studies. However, the relationship between immune microenvironment and the prognosis of LCNEC patients is poorly understood. Our study was aimed to examine the infiltration of CD8+ T cell and PD-L1+ cells in LCNEC patients, and explore whether CD8+T cell and PD-L1+ cells are related to LCNEC patients’ prognosis. Methods: 37 eligible LCNEC patients (stage I-III) with received the treatment of surgical operation (27 among 37 patients underwent adjuvant radiochemotherapy) were included, tumor tissues were collected from the first medical center of Chinese PLA General Hospital. Multiplex immunohistochemistry (Multi IHC) was performed using the antibodies of CD8 and PD-L1. The univariate and multivariate cox proportional hazards analyses were used to assess the association between the abundance of CD8+T cell and PD-L1+ cells with the clinical outcome of LCNEC patients. Results: Patients were divided into high and low group using the median positive percentage of CD8 or PD-L1 as cutoff. The univariate analysis showed that patients with stromal high CD8+ T cell infiltration or stage I had significantly longer disease free survival (DFS) (CD8, p = 0.03; stage I, p = 0.036), and patients with high PD-L1 expression in stroma region, I stage, adjvant radiochemotherapy had notably increased overall survival (OS) (p = 0.049, p = 0.031, p = 0.023, respectively). However, the infiltration of CD8+ T cell or PD-L1 expression in total or tumor region had no correlation with survival of LCNEC patients. Furthermore, multivariate analysis demonstrated that low CD8+ T cell density in stroma region was an independent risk factor for PFS (p = 0.03), advanced TNM stage (II-III stage, p = 0.0009) and low stromal PD-L1 expression were independent risk factors for OS (p = 0.013). Conclusions: High infiltration of CD8+ T cell or PD-L1+ cell in stroma region were independent good prognosis factors of LCNEC patients. However, these findings need a larger LCNEC cohort to validate.

Transcription Factor Profiling to Predict Recurrence-Free Survival in Breast Cancer: Development and Validation of a Nomogram to Optimize Clinical Management.

Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-related death in young women. Several prognostic and predictive transcription factor (TF) markers have been reported for BC; however, they are inconsistent due to small datasets, the heterogeneity of BC, and variation in data pre-processing approaches. This study aimed to identify an effective predictive TF signature for the prognosis of patients with BC. We analyzed the TF data of 868 patients with BC in The Cancer Genome Atlas (TCGA) database to investigate TF biomarkers relevant to recurrence-free survival (RFS). These patients were separated into training and internal validation datasets, with GSE2034 and GSE42568 used as external validation sets. A nine-TF signature was identified as crucially related to the RFS of patients with BC by univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and multivariate Cox proportional hazard analysis in the training dataset. Kaplan–Meier analysis revealed that the nine-TF signature could significantly distinguish high- and low-risk patients in both the internal validation dataset and the two external validation sets. Receiver operating characteristic (ROC) analysis further verified that the nine-TF signature showed a good performance for predicting the RFS of patients with BC. In addition, we developed a nomogram based on risk score and lymph node status, with C-index, ROC, and calibration plot analysis, suggesting that it displays good performance and clinical value. In summary, we used integrated bioinformatics approaches to identify an effective predictive nine-TF signature which may be a potential biomarker for BC prognosis.

Appropriate Candidates for Salvage Esophagectomy of Initially Unresectable Locally Advanced T4 Esophageal Squamous Cell Carcinoma.

Standard treatment for unresectable locally advanced esophageal cancer is definitive chemoradiotherapy (dCRT). Although salvage esophagectomy is the only curative treatment available following dCRT failure, the appropriate candidates for salvage esophagectomy remain unclear. Three hundred seventeen patients who underwent dCRT from April 2004 to December 2016 were stratified into three study groups-a complete response (CR) group, chemotherapy or best supportive care (BSC) group, and salvage esophagectomy group-and compared. We also investigated the clinical outcomes and prognostic factors of salvage esophagectomy. Seventy-one patients (22.4%) achieved CR after dCRT, 18 patients (5.7%) underwent salvage esophagectomy, and 228 patients (71.9%) underwent palliative chemotherapy or BSC. The 5-year overall survival (OS) rates of the CR group, salvage esophagectomy group, and chemotherapy or BSC group were 83.0%, 51.6%, and 1.3%, respectively. Salvage esophagectomy recipients had a worse OS rate than CR patients (p < 0.001) but a better OS rate than those in the chemotherapy or BSC group (p < 0.001). Incomplete resection was the only significant variable associated with poor OS on univariate Cox proportional-hazards analysis (hazard ratio: 7.633, 95% confidence interval: 1.692-34.482; p = 0.008). Patients with tumors in the upper thoracic esophagus were more likely to undergo incomplete resection (p = 0.011). Patients who achieve R0 resection are good candidates for salvage esophagectomy regardless of their response to dCRT. Those with upper thoracic esophageal tumors are at risk of incomplete resection; careful attention is required when considering these patients for salvage esophagectomy.

Clinical outcomes of 168 Chinese patients after local surgery for bone metastases arising from advanced renal cell carcinoma.

The effectiveness of local surgery for bone metastases (BM) arising from renal cell carcinoma (RCC) remains uncertain. Herein, the authors performed what to the best of their knowledge is the first investigation of the outcomes of Chinese patients with RCC and BM. Data were collected for 168 patients with RCC and BM who were treated at Changzheng Hospital in Shanghai, China, between March 2009 and December 2018. All patients underwent local surgery for BM arising from RCC. Overall survival (OS) was defined as the interval between the date of local surgery and death or last follow-up and was estimated using the Kaplan-Meier method. Univariate and multivariable Cox proportional hazards analyses were used to identify significant prognostic factors. The median OS in the study cohort was 43months (range, 0-113months). The 1-year, 3-year, and 5-year survival rates after surgery were 77.4%, 55.9%, and 31.8%, respectively. Univariate analyses demonstrated significant survival differences associated with sex (P=.003), the number of preoperative metastatic sites (BM alone or BM with concomitant metastasis; P<.001), and the number of BM (single or multiple; P=.008). OS also did not appear to differ regardless of whether the patients received postsurgical targeted therapy. Multivariable Cox regression demonstrated that the following characteristics were independent predictors of OS: the number of preoperative metastatic sites, International Metastatic Renal Cell Carcinoma Database Consortium risk score, and Memorial Sloan Kettering Cancer Center score. Careful patient selection for local surgery is of paramount importance. The prognoses of patients in the Memorial Sloan Kettering Cancer Center-based and International Metastatic Renal Cell Carcinoma Database Consortium-based poor-risk groups were much worse than those of the intermediate-risk groups. In current clinical practice, "stratified treatment" can be performed according to these criteria.

Risk Factors for Progression of Barrett\u2019s Esophagus to High Grade Dysplasia and Esophageal Adenocarcinoma

Barrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Methods of identifying BE patients at high risk for progression to high-grade dysplasia (HGD) or EAC are needed to improve outcomes and identify who will benefit most from intensive surveillance or ablative therapy. Clinical predictors of BE progression to HGD or EAC are poorly understood, with multiple contradictory studies. We performed a retrospective study which included 460 patients at Johns Hopkins Hospital who underwent at least 2 upper endoscopies 6 months apart showing biopsy-documented BE between 1992 and 2013. Patients with EAC or HGD at the initial endoscopy were excluded. Demographic, clinicopathological, and endoscopic data were collected. Univariate and multivariate Cox proportional hazards analyses with time to progression to HGD and EAC were performed. Among 460 patients included in the study, 132 BE patients developed HGD and 62 developed EAC. Significant EAC risk factors included age, abdominal obesity, caffeine intake, and the presence of HGD. Risk factors for HGD or EAC included age, caffeine intake, and low-grade dysplasia while colonic adenomas trended towards significance. Notably, a history of statin or SSRI usage reduced the risk of EAC or HGD by 49% or 61%, respectively. Our study validated several known and identified several novel risk factors, including a history of colonic adenomas or caffeine usage. Low-grade dysplasia was a risk factor for progression but various endoscopic characteristics were not, suggesting that screening strategies should focus on histology instead. We identified SSRIs as a new potentially chemoprotective medication.

Five-year survival following endovascular repair of ruptured abdominal aortic aneurysms is improving

ObjectiveIncreasing experience and improving technology have led to the expansion of endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysms (AAA). We investigated whether the 5-year survival after both EVAR and open repair for ruptured AAA changed over the last 14 years. MethodsWe identified repairs for ruptured infrarenal AAA within the Vascular Quality Initiative registry between 2004 and 2018. We compared the 5-year survival of both EVAR and open repair between the early (2004-2012) and late (2013-2018) cohorts. In addition, we compared EVAR with open repair in the early and late cohorts. We used propensity score modeling to create matching cohorts for each analysis. Kaplan-Meier analysis was used to estimate survival proportions and univariate Cox proportional hazards analysis was used to compare differences in hazard of mortality in the matched cohorts. ResultsWe identified 4638 ruptured AAA repairs. This included 409 EVARs in the early cohort and 2250 in the late cohort, as well as 558 open repairs in the early cohort and 1421 in the late cohort. Propensity matching resulted in 366 matched pairs of late vs early EVAR and 391 matched-pairs of late vs early open repair. When comparing EVAR with open repair, propensity matching resulted in 277 matched pairs of early EVAR versus open, and 1177 matched pairs of late EVAR versus open. In matched EVAR patients, 5-year survival was higher in the late cohort (63% vs 49%; hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.97; P = .027), whereas there was no difference between matched late vs early for open repair patients (52% vs 59%; HR, 1.04; 95% CI, 0.85-1.28; P = .69). In the early cohort, there was no survival difference between EVAR and open repair (51% vs 46%; HR, 0.88; 95% CI, 0.69-1.11; P = .28). However, in the late cohort EVAR was associated with higher survival compared with open repair (63% vs 54%; HR, 0.69; 95% CI, 0.60-0.79; P < .001). ConclusionsThe 5-year survival after EVAR for ruptured AAA has improved over time, whereas survival after open repair remained constant. Consequently, the relative survival benefit of EVAR over open repair has increased over time, which should encourage further adoption of EVAR for ruptured AAA.

Spectroscopic markers of neurodegeneration in the mesial prefrontal cortex predict survival in ALS

Background and objective: N-acetylaspartate (NAA) and myo-inositol (mIns) are spectroscopic markers of neuronal integrity and astrogliosis, respectively. We performed a survival analysis to determine the prognostic value of the NAA/mIns metabolite ratio in ALS after a period of two and five years. Methods: Twenty-four patients with ALS (two with ALS-FTD) were recruited to participate in a high-field MR spectroscopy study of the mesial prefrontal cortex. Univariate and multivariate Cox proportional hazards analyses were used to assess NAA/mIns as a predictor of survival alongside other demographic and clinical measures. Census dates were set at two and five years after the time of MR scan for each patient. Survival curves were calculated using the Kaplan–Meier method. Results: After a five-year observation period, 19 patients had died and five were still alive. Median survival time from date of scan was 1.95 years. Univariate and multivariate Cox analysis showed NAA/mIns to be a significant independent predictor of survival at two years after scanning, but not at five years. Conclusion: Cerebral degeneration in the mesial prefrontal cortex as detected by the NAA/mIns metabolite ratio is predictive of survival in ALS in a time-dependent manner.

Transcriptional profile of immune microenvironment and their prediction role for the prognosis of esophageal squamous cell carcinoma.

416 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancer in China. The genetic characterizations have already been described in many studies, but the immune microenvironment features were seldom reported. Our study was aimed to explore the relationship between the immune profile in stage IIIa ESCC and patients’ prognosis. Methods: 20 eligible stage IIIa ESCC patients with received surgery and radiotherapy (19 with and 1 without radiotherapy). RNA targeted sequencing was performed on 20 primary tumor specimens. Transcripts of 395 immune-related genes expressed in tumor were analyzed. The univariate and multivariate Cox proportional hazards analyses were examined the relations of 395 genes’ expression and the prognosis. Results: Patients were divided into two groups based on the median expression values of 395 genes. The univariate analyses showed 20 genes were significantly associated with overall survival (OS). Unsupervised hierarchical clustering analysis using 20 gene expression data revealed two distinct clusters (cluster 1 and 2). The cluster1 patients had high level expression of AXL, ADGRE5, CD40, CXCR6, MPO, etc., which were associated with tumor proliferation and migration. However, the cluster2 patients expressed higher NOS2, IL15, IKZF2, TNFRSF18 which were related with T lymphocyte activated. Therefore, the cluster2 patients had significantly longer OS than cluster 1. Moreover, the combined expression of 10 genes (CD40, ADGRE5, CSF1R, CCR1, IGSF6, MPO, MRC1, SRGN, CD63, LRP1) which had high correlation among 20 genes were significantly related to OS and DFS (disease free survival) in univariate analysis. The multivariate analyses demonstrated that 10 genes signature expression was the independent high risk factor for OS, and the low signature value was associated with better prognosis. Conclusions: In IIIa ESCC, the 20 genes can profile the tumor immune microenvironment, and were independently associated with the patients’ OS. The 10 genes’ signature which represents the malignancy and immune activation of tumor was an independent predictive factor for OS, which can identify the patients with favorable or poor prognosis.

Hospitalization for Patients on Combination Therapy With Peritoneal Dialysis and Hemodialysis Compared With Hemodialysis

IntroductionCombination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used for PD patients with decreased residual kidney function in Japan; however, hospitalization for this combined dialysis has not been investigated so far. We compared the risk of hospitalization for PD+HD with that for HD.MethodsA multicenter, prospective observational study was conducted on 42 PD+HD and 42 HD patients matched for age and diabetic nephropathy. The main outcome measure was the cumulative incidence of hospitalization for any cause assessed with the Kaplan-Meier method. Hospitalization rates (the number of admissions per 100 patient-years) associated with dialysis modality were also calculated. The impact of dialysis modality on time to hospitalization was analyzed using the Cox proportional hazard model.ResultsThere was no significant difference between groups in terms of age, sex, dialysis vintage, diabetic nephropathy, and comorbidities. The cumulative incidence of hospitalization did not significantly differ between the groups (log-rank test, P = 0.36). Although total hospitalization rates were 66.0 in PD+HD and 59.2 in HD, hospitalization rates for the sum of PD-related infections (a composite of catheter-related infection and peritonitis) and vascular access troubles were 21.7 in PD+HD and 7.2 in HD. On univariate Cox proportional hazard analysis, dialysis modality had no significant impact on time to hospitalization.ConclusionThe risk of hospitalization was not significantly different between PD+HD and HD, although PD+HD patients had a higher risk of dialysis access–related complications than HD patients.

Platelets reflect the fate of type II endoleak after endovascular aneurysm repair

ObjectiveThe management of type II endoleak (T2E) remains controversial because of the heterogeneous outcome. For blood-based screening to detect malignant T2E, we focused on platelets after endovascular aneurysm repair (EVAR) and compared them with the prognosis of T2Es. MethodsFrom 2007 to 2015, there were 249 patients treated with EVAR for abdominal aortic aneurysm who were evaluated retrospectively. The mean follow-up period was 3.5 ± 0.2 years. T2Es that had aneurysm sac enlargement or converted to type I or type III endoleak were defined as malignant; the other T2Es were considered benign. Cases without any complications, including T2E, were defined as completed. We compared the platelet count on postoperative days (PODs) 1 to 7 with preoperative baseline values among the three groups. Sequentially, we calculated the cutoff of the platelet ratio on POD 7 to the baseline value in relation to malignant T2E using receiver operating characteristic analysis, and the cutoff ratio was 113% (sensitivity, 79%; specificity, 58%). We then reclassified T2E patients into T2E-high platelet (T2E-HP; ≥113%) or T2E-low platelet (T2E-LP; <113%) groups. The influence of platelets on T2E was evaluated with reintervention rate and cumulative aneurysm sac enlargement rate using the Kaplan-Meier method. ResultsT2Es were found in 70 patients (28%), and 179 patients were assigned to the completed group. Malignant and benign T2Es were found in 33 and 37 patients, respectively. No difference was found in the preoperative baseline values. On POD 7, the platelet count in the malignant T2E group was significantly lower than that in the completed and benign T2E groups (168 × 103/μL vs 207 × 103/μL and 201 × 103/μL; P = .0124). Then, 27 and 43 patients were assigned to the T2E-HP and T2E-LP groups, respectively. The reintervention-free survival rate in the T2E-LP group was lower than that in the completed group (at 3 years, 66.4% ± 8.0% vs 71.9% ± 4.0%; P = .0031). Among T2E patients, the cumulative aneurysm sac enlargement rates in the T2E-LP group were significantly higher than those in the T2E-HP group (at 3 years, 34.6% ± 8.2% vs 20.6% ± 8.2%; P = .0105). Univariate Cox proportional hazards analysis for the cumulative aneurysm sac enlargement rates among T2E patients showed that sex, dual antiplatelet therapy, and lower platelet ratio (<113%) were significant predictors; multivariate analysis showed that T2E-LP was the only significant predictor (hazard ratio, 2.60; P = .0355). ConclusionsThe platelet count of patients with malignant T2Es on POD 7 was definitively lower than that of patients with completed EVAR or with benign T2Es. The lower platelet count on POD 7 could be a risk factor for aneurysm sac enlargement among patients with T2Es.

DOP41 Low-grade dysplasia prognosis and predictive factors for advanced neoplasia progression in the 21st century: A large multi-centre retrospective cohort study

Abstract Background Recent advances in ulcerative colitis (UC) endoscopic surveillance such as high-definition imaging and greater chromoendoscopy (CE) use have led to an increase in detection and resection of visible dysplasia. An updated study of prognosis of low-grade dysplasia (LGD) is needed to address uncertainty as to the accuracy of progression rates based on historical studies. Methods This retrospective cohort study involved four UK IBD centres. Hospital and endoscopy pathology databases were searched between 1 January 2001 and 30 December 2018 to identify adult patients with UC who had their first LGD diagnosis diagnosed within the extent of colitis. Only patients followed up with at least one colonoscopy or colectomy by 30 August 2019 were included. The study endpoint was time to high-grade dysplasia (HGD) or cancer (CRC), i.e. advanced neoplasia (AN), or end of follow-up. Survival analyses were performed using Kaplan–Meier estimation and Cox proportional hazards (PH) models. Results In total, 460 patients met the inclusion criteria and were followed up for a median of 4.1 years (IQR 6), equating to 2,232 patient-years. A mean of 3.7 (range 0–17) subsequent colonoscopies was performed per patient. Seventy-seven per cent of patients had CE surveillance. Complete endoscopic resection was achieved in 94% and 64% of the polypoid and non-polypoid LGD, respectively. There was progression to AN in 88 cases (19%) during follow-up. There was no significant difference in AN progression between centres. Unresectable non-polypoid or invisible LGD carried the greatest risk of AN development (Figure 1). On univariate Cox PH analysis, CE use was protective against AN progression (HR 0.5; 95% CI 0.3–1.0; p = 0.04). However, only highly significant predictors of LGD progression to AN on univariate analysis (Bonferroni adjusted p &amp;lt; 0.003), were entered into the multivariate model: Cumulative risk of AN increased with the number of risk factors (Figure 2). Conclusion This is the largest study examining prognosis of LGD, based on endoscopic features, in this century. Five-year cumulative incidence of AN is low after complete endoscopic resection of visible LGD without surrounding dysplasia. Lesion size of 1 cm or more, invisibility, multifocality and unresectability of LGD are significant risk factors for progression to AN. These factors should be taken into consideration when discussing management options with patients.

Improved risk stratification in younger IDH wild-type glioblastoma patients by combining a 4-miRNA signature with MGMT promoter methylation status.

BackgroundThe potential benefit of risk stratification using a 4-miRNA signature in combination with MGMT promoter methylation in IDH1/2 wild-type glioblastoma patients was assessed.MethodsPrimary tumors from 102 patients with comparable treatment from the LMU Munich (n = 37), the University Hospital Düsseldorf (n = 33), and The Cancer Genome Atlas (n = 32) were included. Risk groups were built using expressions of hsa-let-7a-5p, hsa-let-7b-5p, hsa-miR-615-5p, and hsa-miR-125a-5p to assess prognostic performance in overall survival (OS). MGMT promoter methylation and age were considered as cofactors. Integrated miRNA, DNA methylome, and transcriptome analysis were used to explore the functional impact of signature miRNAs.ResultsThe 4-miRNA signature defined high-risk (n = 46, median OS: 15.8 months) and low-risk patients (n = 56, median OS: 20.7 months; univariable Cox proportional hazard analysis: hazard ratio [HR]: 1.8, 95% confidence interval [CI]: 1.14–2.83, P = .01). The multivariable Cox proportional hazard model including the 4-miRNA signature (P = .161), MGMT promoter methylation (P < .001), and age (P = .034) significantly predicted OS (Log-rank P < .0001). Likewise to clinical routine, analysis was performed for younger (≤60 years, n = 50, median OS: 20.2 months) and older patients (>60 years, n = 52, median OS: 15.8) separately. In younger patients, the 4-miRNA signature had prognostic value (HR: 1.92, 95% CI: 0.93–3.93, P = .076). Particularly, younger, MGMT methylated, 4-miRNA signature low-risk patients (n = 18, median OS: 37.4 months) showed significantly improved survival, compared to other younger patients (n = 32, OS 18.5 months; HR: 0.33, 95% CI: 0.15–0.71, P = .003). Integrated data analysis revealed 4-miRNA signature-associated genes and pathways.ConclusionThe prognostic 4-miRNA signature in combination with MGMT promoter methylation improved risk stratification with the potential for therapeutic substratification, especially of younger patients.

Peripheral arterial disease diagnosed by ankle–brachial index: Predictor for early renal replacement therapy in chronic kidney disease

Our study aimed to investigate the relationship between ankle-brachial index (ABI) and need for early renal replacement therapy (RRT) in predialysis patients with chronic kidney disease (CKD). A total of 112 patients (62% men) with pre-dialysis CKD, seen in the outpatient clinic, were included, and ABI was obtained as per standard protocol. Peripheral arterial disease (PAD) was defined as ABI <0.9 or >1.3 in either leg. The clinical data were analyzed, and the risk factors for early RRT were determined by multivariate logistic regression analysis. The prevalence of PAD was 44% in predialysis CKD patients. Over three years' follow- up, 14.2% required RRT; 11.3% developed major cardiovascular event (myocardial infarction, stroke, or death). A total of 26 events occurred. The incidence of all events was significantly higher in patients with abnormal ABI than in those with normal ABI (34.7% vs. 12.7%; log rank P = 0.02). PAD was associated with all events [hazard ratio (HR): 2.72; 95% CI: 1.04-7.17; P = 0.042] as also the need for RRT (HR 3.2; 95% Cl: 1.005-10.23; P = 0.049), on univariate cox proportional hazard analysis. Multivariate logistic regression analysis adjusted for other risk factors identified that PAD remained an independent predictor for the need for early RRT (HR: 12.2; 95%Cl: 2.2-66.5; P = 0.004) and all events (HR: 3.5; 95% Cl: 0.9-13.5; P = 0.032). PAD was an independent predictor for RRT requirement in predialysis CKD.

Development and Validation of a Prognostic Nomogram Based on Clinical and CT Features for Adverse Outcome Prediction in Patients with COVID-19.

ObjectiveThe purpose of our study was to investigate the predictive abilities of clinical and computed tomography (CT) features for outcome prediction in patients with coronavirus disease (COVID-19).Materials and MethodsThe clinical and CT data of 238 patients with laboratory-confirmed COVID-19 in our two hospitals were retrospectively analyzed. One hundred sixty-six patients (103 males; age 43.8 ± 12.3 years) were allocated in the training cohort and 72 patients (38 males; age 45.1 ± 15.8 years) from another independent hospital were assigned in the validation cohort. The primary composite endpoint was admission to an intensive care unit, use of mechanical ventilation, or death. Univariate and multivariate Cox proportional hazard analyses were performed to identify independent predictors. A nomogram was constructed based on the combination of clinical and CT features, and its prognostic performance was externally tested in the validation group. The predictive value of the combined model was compared with models built on the clinical and radiological attributes alone.ResultsOverall, 35 infected patients (21.1%) in the training cohort and 10 patients (13.9%) in the validation cohort experienced adverse outcomes. Underlying comorbidity (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.67–6.71; p < 0.001), lymphocyte count (HR, 0.12; 95% CI, 0.04–0.38; p < 0.001) and crazy-paving sign (HR, 2.15; 95% CI, 1.03–4.48; p = 0.042) were the independent factors. The nomogram displayed a concordance index (C-index) of 0.82 (95% CI, 0.76–0.88), and its prognostic value was confirmed in the validation cohort with a C-index of 0.89 (95% CI, 0.82–0.96). The combined model provided the best performance over the clinical or radiological model (p < 0.050).ConclusionUnderlying comorbidity, lymphocyte count and crazy-paving sign were independent predictors of adverse outcomes. The prognostic nomogram based on the combination of clinical and CT features could be a useful tool for predicting adverse outcomes of patients with COVID-19.

Correlation of the ORBIT Score With 30-Day Mortality in Patients With ST-Segment Elevation Myocardial Infarction.

A new scoring system Outcomes Registry for Better Informed Treatment (ORBIT) score is used to assess the bleeding risk in anticoagulated patients with atrial fibrillation (AF). Our aim is to investigate the possible correlations of the ORBIT score with 30-day mortality in patients with ST-segment elevation myocardial infarction (STEMI). A total of 639 patients with STEMI were enrolled in this study. The ORBIT, HAS-BLED, and TIMI scores were recorded during admission. After 30 days’ follow-up, 639 patients were divided into 2 groups: the survival group and the nonsurvival group. Different clinical parameters were compared. The predictive values of the ORBIT, HAS-BLED, and TIMI scores for 30-day mortality were assessed from receiver operating characteristic (ROC) analyses. The univariate and multivariate Cox proportional hazards analyses were applied to evaluate the relationships between variables and 30-day mortality. Sixty-seven deaths occurred after a 30-day follow-up. The ORBIT, HAS-BLED, and TIMI scores in the death group were higher than those in the survival group (P < .05). The areas under the ROC curve for the ORBIT, HAS-BLED, and TIMI scores to predict the occurrence of 30-day mortality were 0.811 (95% CI: 0.779-0.841, P < .0001), 0.717 (95% CI: 0.680-0.752, P < .0001), and 0.844 (95% CI: 0.813-0.871, P < .0001), respectively. In multivariate Cox proportional hazards modeling, the high ORBIT score was positively associated with 30-day mortality (hazard ratio: 1.309, 95% CI: 1.101-1.556, P = .013) after adjustment. A graded relation is found in the elevated ORBIT score and 30-day mortality in patients with STEMI. Thus, the ORBIT score can be an independent predictor of 30-day mortality in patients with STEMI.

Identification of microRNAs in skeletal muscle associated with lung cancer cachexia.

BackgroundCachexia, highly prevalent in patients with non‐small cell lung cancer (NSCLC), impairs quality of life and is associated with reduced tolerance and responsiveness to cancer therapy and decreased survival. MicroRNAs (miRNAs) are small non‐coding RNAs that play a central role in post‐transcriptional gene regulation. Changes in intramuscular levels of miRNAs have been implicated in muscle wasting conditions. Here, we aimed to identify miRNAs that are differentially expressed in skeletal muscle of cachectic lung cancer patients to increase our understanding of cachexia and to allow us to probe their potential as therapeutic targets.MethodsA total of 754 unique miRNAs were profiled and analysed in vastus lateralis muscle biopsies of newly diagnosed treatment‐naïve NSCLC patients with cachexia (n = 8) and age‐matched and sex‐matched healthy controls (n = 8). miRNA expression analysis was performed using a TaqMan MicroRNA Array. In silico network analysis was performed on all significant differentially expressed miRNAs. Differential expression of the top‐ranked miRNAs was confirmed using reverse transcription–quantitative real‐time PCR in an extended group (n = 48) consisting of NSCLC patients with (n = 15) and without cachexia (n = 11) and healthy controls (n = 22). Finally, these miRNAs were subjected to univariate and multivariate Cox proportional hazard analysis using overall survival and treatment‐induced toxicity data obtained during the follow‐up of this group of patients.ResultsWe identified 28 significant differentially expressed miRNAs, of which five miRNAs were up‐regulated and 23 were down‐regulated. In silico miRNA‐target prediction analysis showed 158 functional gene targets, and pathway analysis identified 22 pathways related to the degenerative or regenerative processes of muscle tissue. Subsequently, the expression of six top‐ranked miRNAs was measured in muscle biopsies of the entire patient group. Five miRNAs were detectable with reverse transcription–quantitative real‐time PCR analysis, and their altered expression (expressed as fold change, FC) was confirmed in muscle of cachectic NSCLC patients compared with healthy control subjects: miR‐424‐5p (FC = 4.5), miR‐424‐3p (FC = 12), miR‐450a‐5p (FC = 8.6), miR‐144‐5p (FC = 0.59), and miR‐451a (FC = 0.57). In non‐cachectic NSCLC patients, only miR‐424‐3p was significantly increased (FC = 5.6) compared with control. Although the statistical support was not sufficient to imply these miRNAs as individual predictors of overall survival or treatment‐induced toxicity, when combined in multivariate analysis, miR‐450‐5p and miR‐451a resulted in a significant stratification between short‐term and long‐term survival.ConclusionsWe identified differentially expressed miRNAs putatively involved in lung cancer cachexia. These findings call for further studies to investigate the causality of these miRNAs in muscle atrophy and the mechanisms underlying their differential expression in lung cancer cachexia.

T1‑2N1M0 triple‑negative breast cancer patients from the SEER database showed potential benefit from post‑mastectomy radiotherapy

The effects of post-mastectomy radiotherapy (PMRT) on different subtypes of T1-2N1M0 breast cancer remain controversial. Patients with T1-2N1M0 breast cancer treated by mastectomy or mastectomy and PMRT were identified from the 2010–2013 dataset from the Surveillance, Epidemiology and End Results (SEER) registry. A total of 7,466 patients with the 7th American Joint Committee on Cancer stage (Tumor-Node-Metastasis stages 1–2, 1 and 0, respectively) including 2,760 cases (36.97%) treated by mastectomy and PMRT and 4,706 cases (63.03%) treated by mastectomy alone were analyzed in this study. The follow-up time for patients in the dataset used from the SEER registry was 0–59 months. The breast cancer-specific survival (BCSS) of the patients was derived from the SEER dataset and stratified by treatment approach. A propensity score matching (PSM) analysis (experimental group: Control group ratio, 1:1) was conducted. Using univariate and multivariate analyses Cox proportional hazards analyses, PMRT was identified as an independent prognostic factor for triple-negative breast cancer (TNBC). Before PSM analysis, the BCSS favored PMRT in the hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)+ (P=0.025) and HR−/HER2− groups (P=0.010) but not in the HR+/HER2− (P=0.346) and HR−/HER2+ (P=0.288) groups. Following PSM analysis, BCSS favored PMRT alone in the TNBC (HR−/HER2−) group (P=0.025). Patients with T1-2N1M0 TNBC may benefit from radiotherapy post-mastectomy.