Univariate Cox Proportional Hazards Analyses Research Articles

TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations

TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90–100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.

A novel autophagy-related lncRNA prognostic risk model for breast cancer.

Long non‐coding RNAs (lncRNAs) are well known as crucial regulators to breast cancer development and are implicated in controlling autophagy. LncRNAs are also emerging as valuable prognostic factors for breast cancer patients. It is critical to identify autophagy‐related lncRNAs with prognostic value in breast cancer. In this study, we identified autophagy‐related lncRNAs in breast cancer by constructing a co‐expression network of autophagy‐related mRNAs‐lncRNAs from The Cancer Genome Atlas (TCGA). We evaluated the prognostic value of these autophagy‐related lncRNAs by univariate and multivariate Cox proportional hazards analyses and eventually obtained a prognostic risk model consisting of 11 autophagy‐related lncRNAs (U62317.4, LINC01016, LINC02166, C6orf99, LINC00992, BAIAP2‐DT, AC245297.3, AC090912.1, Z68871.1, LINC00578 and LINC01871). The risk model was further validated as a novel independent prognostic factor for breast cancer patients based on the calculated risk score by Kaplan‐Meier analysis, univariate and multivariate Cox regression analyses and time‐dependent receiver operating characteristic (ROC) curve analysis. Moreover, based on the risk model, the low‐risk and high‐risk groups displayed different autophagy and oncogenic statues by principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation. Taken together, these findings suggested that the risk model of the 11 autophagy‐related lncRNAs has significant prognostic value for breast cancer and might be autophagy‐related therapeutic targets in clinical practice.

Establishment of an immune-related gene pair model to predict colon adenocarcinoma prognosis

BackgroundColon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma (COAD) is the main pathological type of colon cancer, and much evidence has supported the correlation between the prognosis of COAD and the immune system. The current study aimed to develop a robust prognostic immune-related gene pair (IRGP) model to estimate the overall survival of patients with COAD.MethodsThe gene expression profiles and clinical information of patients with colon adenocarcinoma were obtained from the TCGA and GEO databases and were divided into training and validation cohorts. Immune genes were selected that showed a significant association with prognosis.ResultsAmong 1647 immune genes, a model with 17 IRGPs was built that was significantly associated with OS in the training cohort. In the training and validation datasets, the IRGP model divided patients into the high-risk group and low-risk group, and the prognosis of the high-risk group was significantly worse (P<0.001). Univariate and multivariate Cox proportional hazard analyses confirmed the feasibility of this model. Functional analysis confirmed that multiple tumor progression and stem cell growth-related pathways were upregulated in the high-risk groups. Regulatory T cells and macrophages M0 were significantly highly expressed in the high-risk group.ConclusionWe successfully constructed an IRGP model that can predict the prognosis of COAD, providing new insights into the treatment strategy of COAD.

Tumor Response to Irinotecan is Associated with IL-10 Expression Level in Metastatic Colorectal Cancer-Results from mCRC Biomarker Study.

PurposeMetastatic colorectal cancer (mCRC) is a leading cause of cancer-related death. Resistance to chemotherapy is the main reason for the failure of the treatment of mCRC. IL-10 has been reported to decrease after surgery and increase after mCRC reoccurrence. The role of IL-10 in chemotherapy drug resistance of mCRC is not well elucidated.Patients and MethodsThe retrospective study recruited 264 mCRC patients between January 2012 and December 2016 (NCT03532711). All the enrolled patients received an oxaliplatin-containing or irinotecan-containing regimen. The expression level of IL-10 in 232 patients’ plasma and 68 patients’ tumor tissue was examined. The relationships between IL-10 and clinicopathological characteristics were analyzed. Kaplan–Meier method and Cox regression were used to evaluate the prognostic impact of IL-10.ResultsThe median concentration of IL-10 was 7.60 pg/mL before treatment and 11.08 pg/mL after treatment, which suggested that IL-10 level was significantly increased by treatment with a chemotherapeutic regimen (p = 0.000). By utilizing univariate and multivariate Cox proportional hazard analyses, we found that low IL-10 level in plasma was significantly associated with improved overall survival (OS) of mCRC patients treated with irinotecan-containing regimen-with optimal cutoff value of 5.525pg/mL, respectively (p =0.002). In addition, the low IL-10 expression level in tumor tissue was significantly associated with the improved OS for the irinotecan-containing regimen (p = 0.023).ConclusionOur study demonstrated that IL-10 could act as a prognostic biomarker for mCRC patients undergoing irinotecan-containing chemotherapy.

Statin use associated with lower mortality in very elderly patients with peripheral arterial disease

Abstract Introduction Given the potential side effects and the lack of data on its efficacy, the role of statins in the very elderly (age 75+) with peripheral arterial disease (PAD) is uncertain. Previous studies have shown significant mortality benefit in very elderly patients with coronary artery disease, but the effect in PAD has not been evaluated. Methods Very elderly patients aged 75 to 80 with at least five years of follow-up who underwent ankle-brachial index (ABI) measurement were included. PAD was defined as either low ABI &amp;lt;0.90 or high ABI &amp;gt;1.40. Demographic, medication use, comorbidity and mortality data was obtained using the electronic medical record. Univariate and multivariate Cox proportional hazard analyses were performed. Results In total, 4,560 very elderly subjects with PAD were included in the analysis. The median age was 77 (interquartile range 76–79) and 39% were female. 3,462 (76%) had low ABI while 1098 (24%) had high ABI. Univariate analysis showed that patients on statins were more likely to be male, have diabetes, have coronary artery disease, and have hyperlipidemia. Overall, 1,355 (30%) patients died in the five-year period. Unadjusted all-cause mortality hazard ratios for patients with low or high ABI with statin use was 0.66 (95% confidence interval [CI]: 0.57–0.75) and 0.80 (95% CI: 0.66–0.97), respectively. After adjusting for age, sex, coronary artery disease and diabetes, statin use in low and high ABI was still associated with significant reductions in risk of all-cause mortality of 0.59 (95% CI: 0.51–0.67) and 0.66 (95% CI: 0.54–0.80), respectively. The survival curve for very elderly patients with PAD by statin use is shown in Figure 1. Conclusion Statin use in the very elderly was associated with lower risk of all-cause mortality in the five-year period after diagnosis of PAD. There appears to be a mortality benefit with statin use in the very elderly with PAD, though careful consideration of benefits and side effects should be individualized in this age group. Figure 1 Funding Acknowledgement Type of funding source: None

Predictive role of serum cholesterol and triglycerides in cervical cancer survival

ObjectiveLipids have been evaluated for their possible role in cancer survival prediction. The aim of the current study was to investigate the prognostic value of lipids on overall survival for...

Radiomics may increase the prognostic value for survival in glioblastoma patients when combined with conventional clinical and genetic prognostic models.

To evaluate the additional prognostic value of multiparametric MR-based radiomics in patients with glioblastoma when combined with conventional clinical and genetic prognostic factors. In this single-center study, patients diagnosed with glioblastoma between October 2007 and December 2019 were retrospectively screened and grouped into training and test sets with a 7:3 distribution. Segmentations of glioblastoma using multiparametric MRI were performed automatically via a convolutional-neural network. Prognostic factors in the clinical model included age, sex, type of surgery/post-operative treatment, and tumor location; those in the genetic model included statuses of isocitrate dehydrogenase-1 mutation and O-6-methylguanine-DNA-methyltransferase promoter methylation. Univariate and multivariate Cox proportional hazards analyses were performed for overall survival (OS) and progression-free survival (PFS). Integrated time-dependent area under the curve (iAUC) for survival was calculated and compared between prognostic models via the bootstrapping method (performances were validated with prediction error curves). Overall, 120 patients were included (training set, 85; test set, 35). The mean OS and PFS were 25.5 and 18.6 months, respectively. The prognostic performances of multivariate models improved when radiomics was added to the clinical model (iAUC: OS, 0.62 to 0.73; PFS, 0.58 to 0.66), genetic model (iAUC: OS, 0.59 to 0.67; PFS, 0.59 to 0.65), and combined model (iAUC: OS, 0.65 to 0.73; PFS, 0.62 to 0.67). In the test set, the combined model (clinical, genetic, and radiomics) demonstrated robust validation for risk prediction of OS and PFS. Radiomics increased the prognostic value when combined with conventional clinical and genetic prognostic models for OS and PFS in glioblastoma patients. • CNN-based automatic segmentation of glioblastoma on multiparametric MRI was useful in extracting radiomic features. • Patients with glioblastoma with high-risk radiomics scores had poor overall survival (hazards ratio 8.33, p < 0.001) and progression-free survival (hazards ratio 3.76, p < 0.001). • MR-based radiomics improved the survival prediction when combined with clinical and genetic factors (overall and progression-free survival iAUC from 0.65 to 0.73 and 0.62 to 0.67, respectively; both p < 0.001).

Head and Neck Cancer Survival Disparities by Race and Rural-Urban Context.

This study aims to examine the relationship between race and rural-urban context in head and neck cancer (HNC) survival and determine factors that potentially drive this disparity. Using the National Cancer Database from 2004 to 2015, we identified a retrospective cohort of 146,256 patients with HNC. Kaplan-Meier survival curves and the Cox proportional hazards regression were used to calculate adjusted HRs. Median survival by patient subgroup was as follows: White urban [67 months; 95% confidence interval (CI), 66.0-67.9], White rural (59.1 months; 95% CI, 57.2-60), Black urban (43.1 months; 95% CI, 41.1-44.5), and Black rural (35.1 months; 95% CI, 31.9-39.0). The difference in 5-year survival, stratified by rural-urban context, was greater among Black patients [Δ restricted mean survival time (ΔRMST) 0.18; 95% CI, 0.10-0.27] than White patients (ΔRMST 0.08; 95% CI, 0.06-0.11). In the univariate Cox proportional hazards analysis with White urban patients as reference group, Black rural patients had the worst survival (HR, 1.45; 95% CI, 1.43-1.48; P < 0.001), followed by Black urban patients (HR, 1.29; 95% CI, 1.28-1.30; P < 0.001), and White rural patients (HR, 1.08; 95% CI, 1.07-1.09; P < 0.001). This disparity persisted when controlling for demographic, socioeconomic, and clinical factors. Black patients with HNC, specifically those living in rural areas, have decreased survival. Survival differences by rural-urban status are greater among Black patients than White patients. We have shown that race and rural-urban status impact HNC survival outcomes. Our findings will help future researchers to better frame approaches to address this disparity.

Identification and validation of stemness-related lncRNA prognostic signature for breast cancer

BackgroundLong noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs). LncRNAs are closely associated with the prognosis of breast cancer patients. It is critical to identify BCSC-related lncRNAs with prognostic value in breast cancer.MethodsA co-expression network of BCSC-related mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were used to identify a stemness risk model with prognostic value. Kaplan–Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation were conducted to analyze the risk model.ResultsIn this study, BCSC-related lncRNAs in breast cancer were identified. We evaluated the prognostic value of these BCSC-related lncRNAs and eventually obtained a prognostic risk model consisting of 12 BCSC-related lncRNAs (Z68871.1, LINC00578, AC097639.1, AP003119.3, AP001207.3, LINC00668, AL122010.1, AC245297.3, LINC01871, AP000851.2, AC022509.2 and SEMA3B-AS1). The risk model was further verified as a novel independent prognostic factor for breast cancer patients based on the calculated risk score. Moreover, based on the risk model, the low- risk and high-risk groups displayed different stemness statuses.ConclusionsThese findings suggested that the 12 BCSC-related lncRNA signature might be a promising prognostic factor for breast cancer and can promote the management of BCSC-related therapy in clinical practice.

ABDOMINAL AORTA CALCIFICATION PRIOR TO KIDNEY TRANSPLANTATION: THE ASSOCIATION WITH PATIENT AND GRAFT SURVIVAL

Dutch Kidney Transplant Study Group. Introduction: A high degree of vascular calcification is commonly encountered in patients undergoing kidney transplantation, especially in those who were on long-term hemodialysis. The prognostic value of pre-transplant vascular calcification for patient and graft survival is unclear. Therefore, this study focused on the association of abdominal aortic calcification (AAC) prior to kidney transplantation and both all-cause mortality and graft failure. Materials and Methods: From 2005 to 2018, renal transplant recipients referred for a nonenhanced CT procedure within 3 years prior to kidney transplantation, were included in a dual-centre study. Primary endpoints were all-cause mortality and graft failure after kidney transplantation. AAC was retrospectively quantified using a semiautomated tool, as a modified Agatston score. Patients were stratified into three groups based on the AAC quantification results. A Kaplan-Meier curve, with Log Rank analysis, and a Cox proportional hazards model were used for time-to-event analysis. Multivariate analysis included the AAC score in quartiles, recipient age, sex and Body Mass Index (BMI) at moment of transplantation, duration of dialysis prior to transplantation and history of smoking. Results: We evaluated 547 patients, 461 (84.3%) had detectable calcifications and the median time between CT and transplantation was 1.0 (IQR 0.5 – 1.4) years. Sixty-nine (12.6%) patients died and 84 (15.4%) had graft failure during a median follow-up of 2.5 (IQR 1.0 – 4.3) years. Kaplan-Meier curves indicate that a higher AAC score was associated with a higher all-cause mortality (p < 0.001) (Figure 1.) and higher rate of graft failure (p = 0.009) (Figure 2.). Similarly, in univariate Cox proportional hazard analysis a high AAC score was associated with a higher all-cause mortality (HR 4.3 (95% CI 2.2 – 8.4, p < 0.001) and a higher rate of graft failure (HR 2.1 (95% CI 1.3 – 3.6, p < 0.004). These associations remained significant upon multivariate analysis, with HR 3.1 (95% CI 1.3 – 7.0), p = 0.008) and (HR 2.0 (95% CI 1.2 – 3.5, p < 0.00) for mortality and graft failure, respectively. Fig. 1.Fig. 2.Conclusion: A significant association between the degree of AAC, assessed by nonenhanced CT-based quantification, and both all-cause mortality and graft failure was identified. A validated scoring system for AAC could guide clinicians in decision-making with regard to risk stratification and expected patient-related outcomes after kidney transplantation.

Elevated tumor-to-liver standardized uptake value ratio (TLR) from preoperative 18F-FDG PET/CT predicts poor prognosis of patients with clear cell renal cell carcinoma after nephrectomy

AimTo assess the potential of using preoperative 18F-FDG PET/CT to predict the prognosis of patients with clear cell renal cell carcinoma (ccRCC) after nephrectomy. MethodsSixty-nine patients with newly diagnosed ccRCC who underwent 18F-FDG PET/CT prior to surgery were retrospectively reviewed. The metabolic parameters of maximum standardized uptake value (SUVmax) and tumor-to-liver ratio (TLR) from 18F-FDG PET/CT were obtained. Clinicopathological characteristics, including the World Health Organization/the International Society of Urological Pathology (WHO/ISUP) grade, pathological tumor node metastasis (pTNM) stage, venous tumor thrombus, and so on, were acquired. Univariate and multivariate Cox proportional hazards analyses were performed to identify the prognostic factors for disease-free survival (DFS). ResultsOf the 69 patients, 25 patients (36.2%) experienced disease progression during the follow-up period. In univariate analysis, the primary tumor size (>4.85 cm), pTNM stage (Ⅲ/Ⅳ), WHO/ISUP grade (G3/4), venous tumor thrombus, adjuvant therapy, SUVmax (>3.55), and TLR (>1.66) were found to correlate with the incidence of decreased DFS (P < 0.05). In multivariate analysis, TLR (P = 0.007, HR: 5.489, 95%CI: 1.605-18.774) and pTNM stage (P = 0.024, HR: 10.385, 95%CI: 1.361-79.238) were revealed to serve as independent prognostic predictors for DFS after adjustment for other variables. Only 3 cases (8.3%) with normal TLR showed disease progression, while 22 cases (66.7%) with elevated TLR experienced disease progression. ConclusionccRCC patients with preoperatively elevated TLR (>1.66) and high pTNM stages (Ⅲ/Ⅳ) had significantly unfavorable survival outcomes. These patients should be carefully monitored to detect the possibility of disease progression after nephrectomy as early as possible.

Abstract 5912: YTHDF1 amplification associates with clinicopathological featuresand predicts worse survival in breast cancer

Abstract N6-methyladenosine (m6A) is a common RNA modification on eukaryotic mRNA and several m6a regulatory proteins, which plays a crucial part in breast cancer. But the copy number variations (CNVs) for m6a regulatory proteins and their role in pathogenesis and progression in breast cancer is still unclear. By analyzing the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and the cancer genome atlas (TCGA database), we screened CNVs of ten m6A regulatory genes, including YTHDF3, YTHDF1, FTO, YTHDC1, ALKBH5, METTL3, WTAP, METTL14, YTHDF2, YTHDC2. Among them, YTHDF3 and YTHDF1 amplification had higher alteration rates among ten m6A regulatory genes. YTHDF1 and YTHDF3 amplification resulted in higher mRNA expression (P&amp;lt;0.001). We found that YTHDF1 and YTHDF3 amplification presented a high correlation with worse cinlicopathological characteristics and overall survival (OS) in breast cancer patients. COX regression analysis showed YTHDF1 amplification was an independent risk factor for 10-year OS in breast cancer (HR=1.549, 95% CI: 1.408-1.705, P&amp;lt;0.001, Table). Moreover, GSEA analysis revealed the downstream target of YTHDF1 may be related to MYC signaling regulation and T cell differentiation. In conclusion, we illustrated genetic alteration of m6A regulatory genes in breast cancer patients and found significant relationship between YTHDF1 amplification and worse clinical characteristics, indicating it a potential target for breast cancer treatment in epigenetic modification. Univariate and multivariate Cox proportional hazard analysis for 10-year overall survivalUnivariateUnivariateHR95% CIP valueHR95% CIP valueNode status1.7181.566-1.885&amp;lt;0.0011.5491.408-1.705&amp;lt;0.001Tumor Size1.0161.013-1.019&amp;lt;0.001ER status0.6200.530-0.725&amp;lt;0.0010.5260.440-0.629&amp;lt;0.001PR status0.6120.531-0.707&amp;lt;0.001HER2 status1.7471.445-2.112&amp;lt;0.0011.5171.234-1.866&amp;lt;0.001Age1.0241.018-1.030&amp;lt;0.0011.0331.026-1.039&amp;lt;0.001YTHDF11.8111.419-2.313&amp;lt;0.0011.5491.408-1.705&amp;lt;0.001 Citation Format: Cheukfai Li, Guochun Zhang, Yulei Wang, Bo Chen, Kai Li, Li Cao, Chongyang Ren, Lingzhu Wen, Minghan Jia, Hsiaopei Mok, Jianguo Lai, Weikai Xiao, Xuerui Li, Ning Liao. YTHDF1 amplification associates with clinicopathological featuresand predicts worse survival in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5912.

Lumbar Puncture Increases Risk of Lumbar Degenerative Disc Disease: Analysis From the Rochester Epidemiology Project.

A population-based, retrospective cohort study. To determine whether Lumbar puncture (LP) is associated with risk of degenerative disc disease (DDD) progression. Etiology of DDD is poorly understood and has been suggested to be multifactorial, with pro-inflammatory cytokine mediators playing a pathophysiological role. While it is known that LP is associated with local inflammation, a clear link has not been previously established between LP and DDD. In this study, we performed a population-based matched cohort analysis using the medical records linkage system of the Rochester Epidemiology Project to investigate this possible association. Between 2004 and 2009, a total of 950 cases who underwent LP and 1876 referent subjects (who did not undergo an LP procedure), matched by age, sex and BMI were identified. Univariate and multivariable Cox proportional hazards analyses were used to estimate the risk of DDD among patients undergoing LP. The cumulative probability of developing DDD from the time of LP procedure was 13.8% among LP cases (95% CI 11.5%-16.1%) vs. 9.4% among controls (95%CI 8.1%-10.8%) at 5 years. On multivariable Cox regression analysis, patients undergoing an LP were found to have a significantly higher risk of developing DDD (HR 1.33; 95%CI 1.10-1.60; p = 0.003). Use of fluoroscopic guidance while performing an LP was associated with a significantly lower risk of DDD (OR 0.55, 95% CI 0.30, 1.00, p value = 0.049) when compared to patients who did underwent LP without fluoroscopy. This investigation is the first to demonstrate a possible link between LP and higher risk of developing DDD. In addition, we show that using image-guided LP might attenuate that risk. 4.

The Impact of Severe Infectious Complications on Long-term Prognosis for Gastric Cancer.

The aim of this study was to evaluate the impact of postoperative infectious complications on long-term outcomes after curative resection of gastric cancer. Patients who underwent curative gastrectomy with lymphadenectomy for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015 were retrospectively selected from medical records. Clinicopathological factors between patients with and without infectious complications were compared. Prognostic factors of long-term survival were analyzed by univariate and multivariate Cox proportional hazards analyses. A total of 2,254 patients were eligible for inclusion in the present study. Fifty-eight patients had postoperative infectious complications (IC group); 2,196 had no postoperative infectious complications (NC group). In the IC group, the median age (p=0.031), body mass index (p=0.004), American Society of Anesthesiologists physical status (p=0.006) and percentage of male patients (p<0.001) were higher in comparison to the NC group. The operation time was longer (p<0.001) and the incidence of intestinal-type histology was higher (p=0.017) in the IC group. The 5-year overall survival rates of the IC and NC groups were 59.8% and 83.2%, respectively (p<0.001). Univariate and multivariate analyses demonstrated that postoperative infectious complications were a significant risk factor for poorer overall survival (hazard ratio=2.38; 95% confidence interval=1.47-3.85, p<0.001). Perioperative management is necessary to reduce the incidence of postoperative infectious complications and improve the survival of patients after curative resection of gastric cancer.

DNA methylation profiling to predict recurrence risk in stage Ι lung adenocarcinoma: Development and validation of a nomogram to clinical management.

Increasing evidence suggested DNA methylation may serve as potential prognostic biomarkers; however, few related DNA methylation signatures have been established for prediction of lung cancer prognosis. We aimed at developing DNA methylation signature to improve prognosis prediction of stage I lung adenocarcinoma (LUAD). A total of 268 stage I LUAD patients from the Cancer Genome Atlas (TCGA) database were included. These patients were separated into training and internal validation datasets. GSE39279 was used as an external validation set. A 13‐DNA methylation signature was identified to be crucially relevant to the relapse‐free survival (RFS) of patients with stage I LUAD by the univariate Cox proportional hazard analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multivariate Cox proportional hazard analysis in the training dataset. The Kaplan‐Meier analysis indicated that the 13‐DNA methylation signature could significantly distinguish the high‐ and low‐risk patients in entire TCGA dataset, internal validation and external validation datasets. The receiver operating characteristic (ROC) analysis further verified that the 13‐DNA methylation signature had a better value to predict the RFS of stage I LUAD patients in internal validation, external validation and entire TCGA datasets. In addition, a nomogram combining methylomic risk scores with other clinicopathological factors was performed and the result suggested the good predictive value of the nomogram. In conclusion, we successfully built a DNA methylation‐associated nomogram, enabling prediction of the RFS of patients with stage I LUAD.

Posttreatment Lymphopenia Is Associated With an Increased Risk of Redeveloping Nontuberculous Lung Disease in Patients With Mycobacterium avium Complex Lung Disease.

Lymphopenia has been reported as a risk factor for poor prognosis in various infectious diseases, including Mycobacterium avium complex lung disease (MAC-LD), and recurrence in several infectious diseases. However, the association between lymphopenia and the risk of redeveloping nontuberculous lung disease (NTM-LD) after completed treatment for MAC-LD is unknown. We performed a retrospective cohort study with 147 patients with MAC-LD who successfully completed guideline-based therapy. Lymphopenia was defined as an absolute lymphocyte count (ALC) <1000 cells/μL based on commonly accepted reference values. During the median follow-up period of 41.9 months after treatment completion, 59 (40.1%) patients redeveloped NTM-LD. Patients with NTM-LD redevelopment had significantly lower posttreatment ALCs (median, 1260 vs 1420 cells/μL) than those without, and the univariate Cox proportional hazard analysis identified posttreatment ALC as a predictive factor for redevelopment (hazard ratio, .94 [95% confidence interval, .89-.99] for every increase of 100 cells/μL; P = .04). In the multivariate analysis, posttreatment ALC and the extent of bronchiectasis were independently associated with NTM-LD redevelopment. The cumulative rate of NTM-LD redevelopment was significantly higher in patients with posttreatment lymphopenia than in those without (P = .008). Posttreatment lymphopenia could predict an increased risk of NTM-LD redevelopment after completed treatment for MAC-LD.

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&amp;lt;.001) followed by black metro cases (HR: 1.28; 95% CI: 1.26-1.31; p&amp;lt;.001) and white non-metro cases (HR: 1.0,76 95% CI: 1.06-1.10; p&amp;lt;.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 &lt; 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 &lt; 34.4cm2/m2 in women and &lt; 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 &gt; 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 &lt; 0.001), number of metastatic sites (p = 0.029) and NRI (p &lt; 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 &lt; 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.