Multivariable Competing Risk Models Research Articles

Sex disparities in patients with symptomatic severe aortic stenosis

We evaluated whether there is equitable distribution across sexes of treatment and outcomes for aortic valve replacement (AVR), via surgical (SAVR) or transcatheter (TAVR) methods, in symptomatic severe aortic stenosis (ssAS) patients. Using de-identified data, we identified 43,822 patients with ssAS (2008-2016). Multivariate competing risk models were used to determine the likelihood of any AVR, while accounting for the competing risk of death. Association between sex and 1-year mortality, stratified by AVR status, was evaluated using multivariate Cox regression models with AVR as a time-dependent variable. Among patients with ssAS, 20,986 (47.9%) were female. Females were older (median age 81 vs. 78, P<0.001), more likely to have body mass index <20 (8.5% vs. 3.5%), and home oxygen use (4.4% vs. 3.4%, P<0001 for all). Overall, 12,129 (27.7%) patients underwent AVR for ssAS. Females were less likely to undergo AVR compared with males (24.1% vs. 31.0%, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.77-0.83), but when treated, were more likely to undergo TAVR (37.9% vs. 30.9%, adjusted HR 1.21, 95% CI 1.15-1.27). Untreated females and males had similarly high rates of mortality at 1 year (31.1% vs. 31.3%, adjusted HR 0.98, 95% CI 0.94-1.03). Among those undergoing AVR, females had significantly higher mortality (10.2% vs. 9.4%, adjusted HR 1.24, 95% CI 1.10-1.41), driven by increased SAVR-associated mortality (9.0% vs. 7.6%, adjusted HR 1.43, 95% CI 1.21-1.69). Treatment rates for ssAS patients remain suboptimal with disparities in female treatment.

Liver resection in elderly patients with hepatocellular carcinoma: age does matter.

Increasing proportions of elderly patients with hepatocellular carcinoma (HCC) requiring oncological treatment have been noted. We aim to evaluate the impact of elderly age on outcomes of liver resection (LR) for HCC. This retrospective study enrolled 1004 patients with HCC who underwent curative LR in our institution from 2007 to 2017, dividing them into three groups according to age (18-59years, n = 461; 60-74years, n = 447; ≥ 75years, n = 96). Elderly patients were defined as those ≥ 75years old. Outcomes were then compared among the three groups, with a multivariate competing risk model used to estimate cause-specific subdistribution hazard ratios (SHRs) for HCC- and non-HCC-related deaths. The OS was significantly lower in the elderly than younger patients. However, recurrence-free survival was similar among the three groups. The cumulative incidence of HCC-related death was similar among the three groups; however, the cumulative incidence of non-HCC-related death was significantly higher in the elderly than younger patients. Moreover, the multivariate analysis showed that elderly age was not an independent variable associated with HCC-related death. However, elderly age was an independent variable associated with non-HCC-related death. The 60-year SHR for non-HCC-related death increased with increasing age. The elderly patients had significantly worse OS after LR than the younger patients, possibly due to the cumulative incidence of non-HCC-related death being significantly higher among the elderly than among the younger patients. Elderly patients should be more stringently selected for LR.

Abstract PS17-02: Molecular alterations in the androgen receptor and associated clinical outcomes in hormone receptor-positive/HER2- metastatic breast cancer

Abstract Background: Although the androgen receptor (AR) is frequently co-expressed with ER and PR in hormone receptor-positive (HR+)/HER2- breast cancer, the biological significance of detectable AR alterations (ARalt) in metastatic disease (MBC) remains poorly understood. The primary objective of this study was to evaluate the association of ARalt status with clinical outcomes among women with HR+/HER2- MBC. Methods: Retrospective review was performed on patients with HR+/HER2- MBC treated at an academic institution, for whom genotyping information was available. ARalt status was determined using Guardant360, a 73-gene next-generation sequencing assay that detects both AR mutations and amplifications in circulating tumor DNA. Women with positive or unknown HER2 status and triple-negative breast cancer were excluded from analysis, as were cases of male breast cancer. Time-to-progression on the therapy initiated immediately following Guardant testing was compared based on ARalt status, excluding patients treated with androgen-directed therapies given potential for confounding. Cumulative incidence plots were generated and analyzed by Gray’s test, and propensity score-adjusted competing risk models were generated with the probability of treatment as a function of age at metastatic diagnosis, presence of visceral metastasis, presence of de novo metastases, as well as number of prior therapies. Additional analysis was performed to assess progression stratified by treatment type (endocrine or non-endocrine based). Results: Among women with HR+/HER2- MBC (n=222), 16 patients (7%) had detectable ARalt (12 point mutations, 4 amplifications). No baseline differences were observed between women with ARalt and those without AR alterations (ARwt), with respect to age at primary or metastatic diagnosis, menopause status, time to onset of metastasis or de novo metastatic disease, presence of visceral metastases, or number of endocrine/chemotherapies received prior to Guardant testing. ARalt tumors had a higher frequency of detected mutations (14% vs. 5%, p&amp;lt;0.01), and frequently co-altered genes included TP53, PIK3CA, ERBB2, SMAD4, and NF1. Genes with a tendency towards co-alteration in ARalt but not in ARwt included MAP2K2, ARAF1, MAPK1, SMAD4, MYC, ROS1, TERT, and NRAS. In a multivariable model adjusting for age, de novo metastases, visceral metastases, and number of prior therapies, ARalt status was associated with a higher rate of progression (HR 2.5; 95% CI 1.2-5.0, p=0.01), particularly among patients treated with endocrine-based therapies following Guardant testing (HR 4.2, 95% CI 2.4-7.2, p&amp;lt;0.0005) but was not statistically different in women treated with non-endocrine based therapies (HR 1.6; 95% CI 0.5-4.9, p=0.4). Conclusions: ARalt tumors demonstrate a higher rate of progression on endocrine-based therapy as compared to ARwt tumors, highlighting a potential role of AR in mediating resistance to endocrine therapy in HR+/HER2- disease. Further translational investigations are warranted to determine whether ARalt/HR+/HER2- disease represents a unique biological subtype that predominantly relies on AR signaling and may thus benefit from blockade with AR antagonists. Table 1. Multivariable competing risks model for endocrine progression.CovariatePFSMultivariableHR95% CIP-valuePositive ARalt status4.172.43-7.17&amp;lt;0.01Age at metastatic dx1.000.97-1.020.89De novo metastasesYes1.770.96-3.260.07No[ref]Visceral metastasesYes1.250.72-2.160.43No[ref]No. of prior therapies1.060.93-1.210.98 Citation Format: Charles Dai, Andrzej Niemierko, Neelima Vidula, Laura M Spring, Seth A Wander, Arielle J Medford, Katherine A Hesler, Giuliana Malvarosa, Jeffrey Peppercorn, Dejan Juric, Steven J Isakoff, Beverly Moy, Leif W Ellisen, Aditya Bardia. Molecular alterations in the androgen receptor and associated clinical outcomes in hormone receptor-positive/HER2- metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-02.

Impact of prior cancer history on survival of patients with gastric cancer

BackgroundPatients with prior cancer history are commonly excluded from clinical trial. However, the impact of prior cancer on survival of patients with gastric cancer remains largely unknown. The aim of this study was to evaluate the prevalence of prior cancer and assess its impact on survival of patients diagnosed with gastric cancer. MethodsPatients with gastric cancer as the primary or second primary malignancies diagnosed from 2004 to 2010 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier method, multivariate Cox proportional hazard model, and multivariate competing risk model were performed for survival analysis. ResultsA total of 28,795 eligible patients with gastric cancer were included, of whom 2695 (9.35%) had a history of prior cancer. Prostate (35%), breast (12%), colon (8%), and urinary bladder (7%) malignancies were the most common prior cancer types. Patients with prior cancer history had slightly inferior overall survival (AHR = 1.06; 95% CI [1.00–1.12]; P = 0.043) but superior gastric cancer-specific survival (AHR = 0.82; 95% CI [0.76–0.88]; P < 0.001) compared with those without prior cancer. The subgroup analysis determined that a prior cancer history did not adversely affect gastric patients’ clinical outcomes, except in those with prior cancer diagnosed within one year, at distant stage, or originating from lung and bronchus. ConclusionA substantial proportion of gastric cancer patients with a history of prior cancer had non-inferior clinical outcome to those without prior cancer. These patients should be considered in clinical trials.

Survival analysis of second primary malignancies after cervical cancer using a competing risk model: implications for prevention and surveillance.

BackgroundPrevious studies have reported an increased risk for second primary malignancies (SPMs) after cervical cancer (CC). This study aims to quantify and assess the risk of developing SPMs in long-term survivors of CC.MethodsA population-based cohort of CC patients aged 20–79 years was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk model and corresponding nomogram were constructed to predict the 3-, 5-, and 10-year cumulative risks of SPMs. A Fine-Gray plot was created to validate the model. Finally, we performed decision curve analysis (DCA) to evaluate the clinical usefulness of the model by calculating the net benefit.ResultsA total of 34,295 patients were identified, and approximately 6.3% of the study participants developed SPMs. According to the multivariable competing-risk model, older black CC survivors with localized disease who were treated with radiation therapy were more susceptible to SPMs. The 3-, 5-, and 10-year cumulative incidences of SPMs were 2.5%, 3.6%, and 6.2%, respectively. Calibration curves showed good agreement between the predicted and observed models. The DCA yielded a wide range of risk thresholds at which the net benefits could be obtained from our proposed model.ConclusionsThis study provides physicians with a practical, individualized prognostic estimate to assess the risk of SPMs among CC survivors. CC survivors remain at a high risk of developing SPMs, and further surveillance should focus especially on the patients with black race, older age, localized disease, or those having received radiation therapy.

Social Determinants of Health and Race Disparities in Kidney Transplant.

Black patients have a higher incidence of kidney failure but lower rate of deceased- and living-donor kidney transplantation compared with White patients, even after taking differences in comorbidities into account. We assessed whether social determinants of health (e.g., demographics, cultural, psychosocial, knowledge factors) could account for race differences in receiving deceased- and living-donor kidney transplantation. Via medical record review, we prospectively followed 1056 patients referred for kidney transplant (2010-2012), who completed an interview soon after kidney transplant evaluation, until their kidney transplant. We used multivariable competing risk models to estimate the cumulative incidence of receipt of any kidney transplant, deceased-donor transplant, or living-donor transplant, and the factors associated with each outcome. Even after accounting for social determinants of health, Black patients had a lower likelihood of kidney transplant (subdistribution hazard ratio, 0.74; 95% confidence interval, 0.55 to 0.99) and living-donor transplant (subdistribution hazard ratio, 0.49; 95% confidence interval, 0.26 to 0.95), but not deceased-donor transplant (subdistribution hazard ratio, 0.92; 95% confidence interval, 0.67 to 1.26). Black race, older age, lower income, public insurance, more comorbidities, being transplanted before changes to the Kidney Allocation System, greater religiosity, less social support, less transplant knowledge, and fewer learning activities were each associated with a lower probability of any kidney transplant. Older age, more comorbidities, being transplanted before changes to the Kidney Allocation System, greater religiosity, less social support, and fewer learning activities were each associated with a lower probability of deceased-donor transplant. Black race, older age, lower income, public insurance, higher body mass index, dialysis before kidney transplant, not presenting with a potential living donor, religious objection to living-donor transplant, and less transplant knowledge were each associated with a lower probability of living-donor transplant. Race and social determinants of health are associated with the likelihood of undergoing kidney transplant.

The Impact of Radiotherapy on the Incidence of Secondary Malignancies: A Pan-Cancer Study in the US SEER Cancer Registries.

The population of cancer patients with second primary malignancies (SPMs) is rapidly growing. The relationship between radiotherapy and SPMs for some types of tumors is unknown or debated. In this study, we identify 24 types of first primary malignancies (FPMs) between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the radiotherapy group were matched to those in the no radiotherapy group with a matching ratio of 1:1. After propensity-score matching (PSM), additional competing risk regression analyses were performed to calculate the efficacy of radiotherapy to SPMs in the PSM-adjusted population. In addition, the Fine and Gray model was utilized in the primary cohorts, and stratified analyses were performed based on surgery. This study includes a total of 2,831,789 eligible patients with tumors diagnosed from 2004 to 2015 in the SEER 18 database, amongst whom 100,194 (3.5%) patients developed SPMs. We observe higher risks of SPMs associated with radiotherapy in several types of tumors in the PSM-adjusted populations (small bowel adenocarcinoma, small cell lung carcinoma, prostate adenocarcinoma, urinary bladder transitional cell carcinoma, invasive ductal breast carcinoma, invasive lobular breast carcinoma, and Hodgkin lymphoma). The results in the PSM-adjusted populations were consistent with outcomes in the multivariable competing risk models. Meanwhile, in subgroup analyses stratified by surgery, some other types of tumor (except for those with positive results in the PSM-adjusted cohorts) with radiotherapy were also associated with a higher prevalence of SPMs in the subgroups of surgical treatment (pancreatic adenocarcinoma, rectal adenocarcinoma, lung adenocarcinoma and follicular thyroid carcinoma in the surgery subgroups). The impact of radiotherapy on the incidence of secondary malignancies is distinct in different types of cancer. These findings merit further investigation and may ultimately impact treatment decision-making for tumor management.

Cardiovascular Mortality Risk among Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Registry-Based Analysis.

Background This research is aimed to explore mortality patterns and quantitatively assess the risks of cardiovascular mortality (CVM) in patients with primary gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Methods We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with GEP-NENs between 2000 and 2015. The standardized mortality ratio (SMR) and the absolute excess risk were obtained based on the reference of the general US population. The cumulative incidence function curves were constructed for all causes of death. Predictors for CVM were identified using a multivariate competing risk model. Results Overall, 42027 patients were enrolled from the SEER database, of whom 1598 (3.8%) died from cardiovascular disease (CVD). The SMR for CVM was 1.20 (95% CI: 1.14-1.26) among GEP-NEN patients. The cumulative mortality of CVD was the lowest among all causes of death, including primary cancer, other cancer, and other noncancer diseases. Furthermore, age at diagnosis, race, Hispanic origin, sex, marital status, year of diagnosis, grade, education level, region, SEER stage, primary site, surgery, and chemotherapy were identified as independent predictors of CVM in GEP-NEN patients. Conclusions GEP-NEN patients have a significantly increased risk of CVM relative to the general population. Cardioprotective interventions might be considered a preferred method for these patients.

Long-term survival trend after primary total laryngectomy for patients with locally advanced laryngeal carcinoma.

Purpose: To evaluate long-term survival trends after primary total laryngectomy (TL) for locally advanced laryngeal carcinoma (LC).Methods: A total of 2094 patients diagnosed with locally advanced LC and underwent primary TL (1992-2011, at least 5-year follow-up) in the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. Besides the traditional overall survival (OS) and cancer-specific survival (CSS) by using Kaplan-Meier curves, the 3-year conditional survival analysis was also performed to describe the long-term trends in these patients. Time-dependent multivariate competing-risk models were constructed to assess the persistent sub-distribution hazard of prognostic factors. Finally, a nomogram was developed to predict conditional cancer-specific survival.Results: The curves of overall hazard and cancer-specific hazard both quickly reached the apex within the first year since TL, then decreased thereafter. In general, the CS3 steadily increased from within 5 years after TL. In the stratified CS3 analysis, the increments in patients with adverse characteristics were more pronounced. 4 years after TL, the probability of surviving the next year exceeded 90%. The time-dependent multivariate competing-risk models indicated that age and lymph node ratio (LNR) persistently contributed to the cancer-specific outcome. The nomogram based on the competing-risk model was constructed to estimate CSS probability conditional upon 3 years for advanced LC patients having survived 1, 2, and 3 years.Conclusion: Most patients achieved a substantially improved survival rate after surviving a long period after primary TL. Patients diagnosed at older age and with higher LNR should receive more effective follow-up. The predictive nomogram can provide significant evidence for clinical research and practice.

Impact of prior cancer history on the survival of patients with larynx cancer

BackgroundPatients with a prior history of cancer are commonly excluded from clinical trial. Increasing number of studies implied that a prior cancer did not adversely affect the clinical outcome among various types of cancer patients. However, the impact of prior cancer on survival of larynx cancer patients remains largely unknown. The aim of this study was to evaluate the prevalence of prior cancer and assess its impact on survival of patients diagnosed with larynx cancer.MethodsPatients with larynx cancer as the first or second primary malignancy diagnosed from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier method, multivariate Cox proportional hazard model, and multivariate competing risk model were performed for survival analysis.ResultsA total of 24,812 eligible patients with larynx cancer were included in the study, wherein a total of 2436 patients (9.8%) had a prior history of cancer. Prostate (36%), lung and bronchus (10%), urinary bladder (7%), and breast (6%) were the most common types of prior cancer. A prior cancer history served as a risk factor for overall survival (AHR =1.30; 95% CI [1.21–1.41]; P < 0.001) but a protective factor for cancer-specific mortality (AHR = 0.83; 95% CI [0.72–0.94]; P = 0.004) in comparison with those without prior cancer. The subgroup analysis showed that a prior history of cancer adversely affected overall survival of patients with larynx cancer in most subgroups stratified by timing and types of prior cancer, as well as by different clinicopathologic features.ConclusionOur study indicated an adverse survival impact of a prior history of cancer on patients with larynx cancer. Except for a few particular prior cancer, clinical trials should be considered prudently for laryngeal cancer patients with prior cancers.

Impact of Primary Site and Era of Diagnosis on Mortality in Patients with Extranodal Marginal Zone Lymphoma in the United States: A Population-Based Study

Introduction: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL) is the most common subtype of MZL. EMZL can affect multiple organs throughout the body, and the management depends on the primary site of involvement and extent of disease. The most common primary site is the stomach, but other sites can be involved including the breasts, eyes, lungs, salivary glands, and skin. The last population-based survival analysis of EZML included follow-up through 2009 (Olszewski and Castillo, 2013). Given the paucity of population-based analyses of EMZL in the contemporary time-period, we sought to provide an updated analysis of disease-specific mortality and site-associated mortality using the Surveillance, Epidemiology, and End Results (SEER)-18 database. Method: We included adult patients with EMZL diagnosed between 2000-2017 who were 18-84 years old at the time of diagnosis. We excluded patients with a history of malignancy prior to EMZL, those with missing survival times and those with central nervous system involvement. Patients were divided into two cohorts based on period of diagnosis (era-1: 2000-2008, and era-2: 2009-2017). Five-year relative survival (RS) was estimated using the Pohar-Perme method. The risk of EMZL-specific death was estimated by calculating the cumulative incidence function (CIF). The difference between CIF distributions was tested with the Pepe-Mori test. The competing risks of EMZL-specific death and death from other causes were modeled using Fine and Gray regression. All tests of differences were performed at a two-sided alpha of 0.05. Results: We included a total of 11,597 patients with EMZL. Table 1 shows the baseline characteristics. Among the entire cohort, the median age at diagnosis was 63 years (IQR = 53-72). There was a slight female predominance (55%), and most patients were Non-Hispanic White (65%). Five-year RS was 95% (95% CI = 94-96%) during era-1 and 96% (95-97%) during era-2. There was a significant reduction in the cumulative incidence of EMZL-specific death between era-1 and era-2 (p &amp;lt; 0.001, Figure 1A) but not death from other causes (p = 0.35, Figure 1B). The cumulative incidence of EMZL-specific death varied according to EMZL subtype (Figure 2). In our multivariable competing risks model after adjusting for confounders (Table 2), EZMLs arising from the genitourinary (GU) tract had the worst prognosis [subhazard ratio (SHR) = 2.06, 95% CI=1.30-3.27, p=0.002], whereas EZMLs arising from the skin and connective tissue had the best prognosis [SHR = 0.66, 95% CI = 0.48 - 0.91, p = 0.01]. Conclusion: In this updated population-based analysis of EZML that includes patients treated in the contemporaneous time-period, we found that patients diagnosed with EZML in the most recent era had a significantly better prognosis. Additionally, we noted that the outcomes varied depending on primary site of involvement. Patients with EZMLs involving the GU tract had the worst prognosis, whereas patients with primary sites in the skin and connective tissue had the best prognosis. It is important to study the biology of EMZL involving the GU tract to design better therapeutic options to improve the outcomes. Disclosures Epperla: Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau.

Decreased Lymphoma-Specific Mortality in Patients with Splenic Marginal Zone Lymphoma in the United States

Introduction: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non-Hodgkin lymphoma that usually presents in elderly patients with splenomegaly, lymphocytosis, and cytopenias (either due to hypersplenism or autoimmune phenomena). Treatment of SMZL has advanced over the past decade including identification of better tolerable chemotherapy regimens (such as rituximab and bendamustine) and the advent of novel agents (such as ibrutinib and lenalidomide). We sought to determine whether advances in treatment and supportive care over the past decade have translated to decreased lymphoma-specific mortality among patients with SMZL. Method: We used the population-based Surveillance, Epidemiology, and End Results (SEER)-18 database. We included adult patients with SMZL diagnosed between 2000-2017 who were 18-84 years old at the time of diagnosis. We excluded patients with a history of malignancy prior to SMZL, those with missing survival times and those with central nervous system involvement. Patients were divided into two cohorts based on period of diagnosis (era-1: 2000-2008, and era-2: 2009-2017). Five-year relative survival (RS) was estimated using the Pohar-Perme method. Differences between RS distributions was tested with a log-rank-type test. The risk of SMZL-specific death was estimated by calculating the cumulative incidence function (CIF). The difference between CIF distributions was tested with the Pepe-Mori test. The competing risks of SMZL-specific death and death from other causes were modeled using Fine and Gray regression. All tests of differences were performed at a two-sided alpha of 0.05. Results: We included 1,548 patients with SMZL. Table 1 shows the baseline characteristics. The median age at diagnosis was 66 years (IQR = 57-74) years. Most patients were non-Hispanic White (81%) with advanced stage at diagnosis (stage III-IV, 70%). Five-year RS was 84% (95% CI = 80-87%) during era-1 and 89% (95% CI = 85-92%) during era-2 (p = 0.21. The CIF distributions for SMZL-specific death and death from other causes are shown in Figure 1A and Figure 1B, respectively (Pepe-Mori p = 0.02). In our multivariable competing risks model, the period of diagnosis, age, and stage at diagnosis were significant predictors of SMZL-specific death (Table 2). Patients in era-2 had significantly lower risk of SMZL-specific death [subhazard ratio (SHR) = 0.30, 95% CI = 0.22-0.41), while the cumulative incidence of mortality significantly increased with age (SHR = 1.39 per decade, 95% CI = 1.24-1.56) and advanced stage (SHR = 1.55, 95% CI= 1.04-2.13). Conclusion: There has been a significant reduction in the risk of SMZL-specific death for patients with SMZL in the most recent era possibly due to advances in therapy. This reduction in mortality persists even after accounting for competing risks of mortality from other causes. Disclosures Olszewski: Spectrum Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding; Genentech, Inc.: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria.

Is There An Association Between Use Of Androgen Deprivation Therapy And Acute Kidney Injury In Prostate Cancer Patients Treated With Definitive Radiotherapy?

Androgen Deprivation Therapy (ADT) has been demonstrated to improve survival in men with prostate cancer undergoing definitive radiotherapy. However, ADT may have deleterious effects on cardiovascular, metabolic, bone, and mental health. Little is known about possible effects of ADT on renal function. Recent observational studies have demonstrated an association between ADT use and Acute Kidney Injury (AKI). These studies have included heterogeneous populations undergoing a variety of treatments, which may predispose to selection bias, and do not reflect recent changes in the definition of AKI. We sought to investigate the incidence of AKI in a large cohort of US veterans receiving definitive radiotherapy +/- ADT for prostate cancer. We investigated the prevalence of AKI through the Veterans Affairs Informatics and Computing Infrastructure (VINCI) platform. Our cohort consists of 44,246 veterans diagnosed with nonmetastatic prostate cancer between January 1st 2001 and October 31st 2015. All were treated with definitive radiotherapy. Exposure was defined as initiation of ADT within one year of diagnosis. The primary outcome was the incidence of AKI, defined via ICD codes. Covariates included in the multivariable regression model were: Age, Charlson Comorbidity Index score, race, smoking status, region, income, education, marital status, and year of diagnosis. Within the study population, 16,275 patients (37%) received RT+ADT and 27,971 (62%) received RT alone. With a median follow up of 6.8 years, there were 3,853 patients diagnosed with an AKI during the study period including 1,753 ADT users (10.8%) and 2,100 non-ADT users (7.5%). The overall cumulative incidence of AKI at 10 years was 11.4% including 14.1% for ADT users and 9.8% for non-ADT users. In the multivariable competing risks model, there was a significant association between ADT and AKI (subdistribution hazard ratio (SHR) = 1.28, 95% CI = 1.20-1.37, p<0.01). The use of ADT was associated with an increased risk of AKI in a large, modern cohort of US veterans undergoing definitive radiotherapy for prostate cancer. These findings warrant prospective confirmation, but suggest that renal function may be an important consideration when assessing the risks and benefits of ADT use. Further study will be useful to investigate if particular subgroups of patients receiving ADT are more susceptible to AKI and if the increased rate of AKI is associated with any long-term effects on renal function.

Prognostic validation and treatment decision making of the 8th edition of the American Joint Committee on Cancer pathological staging system for elderly women with early-stage breast cancer.

Purpose: To determine the prognostication and treatment decision making of the American Joint Committee on Cancer (AJCC) 8th pathological staging system in elderly women (aged ≥65 years) with T1-2N0M0 breast cancer (BC).Results: We included 67699 patients, and patients were restaged into stage IA (84.9%), IB (8.9%), and IIA (6.2%) using the 8th AJCC edition criteria. Overall, 69.4% and 30.6% of them underwent breast-conservation surgery (BCS) and mastectomy (MAST), respectively. In patients who received BCS, 30.3% of them underwent postoperative radiotherapy (RT). Patients with a higher pathological stage were more likely to receive MAST. The 5-year breast cancer-specific mortality rate was 2.2%, 6.5% and 13.7% in stage IA, IB, and IIA, respectively. Patients treated with BCS and RT had significantly lower risk of breast cancer-specific mortality compared to those treated with MAST or with BCS alone regardless of the pathological prognostic stages (P<0.001).Conclusions: The 8th AJCC pathological prognostic staging system provides accurate risk stratification and impacts the treatment decision making for elderly women with early-stage BC.Methods: We identified stage T1-2N0M0 BC patients using the Surveillance, Epidemiology, and End Results database. Statistical analyses were used binomial logistic regression, and multivariable competing risk models in the Cox model framework.

Risk of recurrent hepatic encephalopathy in patients with liver cirrhosis: a German registry study

Patients with hepatic encephalopathy (HE) show low quality of life, recurrent hospitalizations and an increased mortality. We aimed to assess the natural course of patients after a recent episode of overt HE and to identify risk factors for HE recurrence in Germany. Fifteen sites took part in a prospective, observational study including patients with liver cirrhosis who had been hospitalized for HE within 3 months before recruitment. Clinical data, psychometric hepatic encephalopathy score (PHES) and critical flicker frequency were assessed quarterly for 1 year. Primary endpoint was HE recurrence requiring hospitalization, all-cause-mortality was treated as a competing risk factor. From January 2014 to March 2016, a total of 115 patients were recruited. Overall 14 premature deaths were documented. For 78 subjects follow-up data were available in accordance with the protocol. After a median of 118 days, more than half of the per-protocol cohort was readmitted to hospital due to HE (N = 34) or died (N = 11). The risk for hospitalization was significantly increased in patients who had been recruited by liver transplant centers (P = 0.003), had had frequent HE relapses prior to recruitment (P = <0.0001) or an abnormal PHES result of <-4 (P = 0.044). Abnormal PHES results barely missed level of significance as an independent risk factor for re-hospitalization in a multivariable competing risk model (P = 0.093). Patients with a history of HE are at high risk for the development of recurrent overt HE demanding hospitalization. The PHES test may aid in detection, monitoring and risk stratification of recurrent HE.

Predictors of Residential Care Admission in Community-Dwelling Older People With Dementia

ObjectivesThe objectives of this study were to identify variables associated with dementia and entry into aged residential care (ARC) and derive and validate a risk prediction model for dementia and entry into ARC. DesignThis was an observational study of prospectively collected Home Care International Residential Assessment Instrument (interRAI-HC) assessment data. Setting and ParticipantsParticipants included all people age ≥65 years who had completed an interRAI-HC assessment between July 1, 2012 and June 30, 2018. Exclusion criteria included death or entry into ARC within 30 days of assessment and not living at home at the time of the assessment. MeasuresInterRAI data from 94,202 older New Zealanders were evaluated for presence or absence of dementia. A multivariable competing-risks model for entry into ARC with death as the competing event was used to estimate subdistribution hazard ratios (SHR). ResultsIn total, there were 18,672 (19.8%) persons with dementia (PWD). PWD were almost twice as likely to enter ARC as persons without dementia [42.8% vs 25.3%; difference 17.5% (95% confidence interval 16.7%‒18.2%)]. PWD at highest risk of entering ARC were those where there was a desire to live elsewhere (SHR 1.44), depression (indicated, SHR 1.15), poor cognitive performance (Cognitive Performance Scale minimal SHR 1.32 and severe plus SHR 1.91), and wandering (SHR 1.19). Factors associated with reduced risks of PWD entering ARC were living with a child or relative, alcohol consumption, and comorbidities. Conclusions and ImplicationsA desire to live elsewhere, social isolation, independent activities of daily living, and depression were independently associated with entry into ARC. Supporting caregivers may improve outcomes for PWD that delay entry into ARC. Future revisions of the interRAI questionnaire could provide more insight on this matter.

Association of Premorbid Blood Pressure with Vasopressor Infusion Duration in Patients with Shock.

Rationale: Guidelines for vasopressor titration suggest a universal target-mean arterial pressure (MAP) >65 mm Hg. The implications for patients with premorbid low/high blood pressure are unknown.Objectives: To investigate the relationship between premorbid blood pressure and vasopressor duration for patients with shock.Methods: We performed a retrospective cohort study of adults admitted with shock to Calgary ICUs (June 2012-December 2018). The primary exposure was premorbid blood pressure: low (systolic <100); normal (systolic 100-139 and diastolic <90); and high (systolic ≥140 or diastolic ≥90). The primary outcome was vasopressor duration; secondary outcomes included ICU/hospital length of stay and ICU/hospital mortality. We examined associations of premorbid blood pressure with vasopressor duration and length of stay using multivariable competing risk models and mortality using multivariable mixed-effects logistic regression.Measurements and Main Results: Of 3,542 admissions with shock, 177 (5.0%) had premorbid low, 2,887 (81.5%) normal, and 478 (13.5%) high blood pressure. Premorbid low admissions had lower MAPs (vs. normal or high premorbid admissions) over the duration of vasopressor use (P = 0.003) and were maintained nearest premorbid MAPs while receiving vasopressors (P < 0.001). After adjustment, premorbid low admissions had longer vasopressor use (median, 1.35 d vs. 1.04 d for normal; hazard ratio for discontinuation vs. normal, 0.78 [0.73-0.85]; P < 0.001) and premorbid high admissions had shorter use (median, 0.84 d; hazard ratio, 1.22 [1.12-1.33]; P < 0.001). Premorbid low admissions had longer adjusted length of stay and higher adjusted mortality than premorbid normal admissions.Conclusions: Premorbid blood pressure was inversely associated with vasopressor duration.

Comparable prevalence of distant metastasis and survival of different primary site for LN\u2009+\u2009pancreatic tumor

BackgroundFew studies have delved into the prevalence of distant metastasis (DM +) and survival for patients with lymph node metastases (LN +) by primary site. We aimed to detect differences in distant metastasis and prognosis between pancreatic head and bodytail tumors for LN + patients.MethodsPatients with chemotherapy, histologically diagnosed, primary site between 2004 and 2016 were included from the SEER (Surveillance, Epidemiology, and End Results) database. Pancreatic head tumors were compared with pancreatic bodytail tumors using the odds ratio (OR) for rates of distant metastasis, hazard ratios (HR) for overall survival (OS) and cancer-specific survival (CSS). The competing risk model and propensity score matching (PSM) were performed to further explore.ResultsOf 5726 LN + patients identified from the SEER database, pancreatic head tumors account for 85.2% (4877 of 5726) and 14.8% (849 of 5726) were pancreatic bodytail tumors. The incidence of DM was lower in pancreatic head than in pancreatic bodytail tumors (OR, 0.29; 95% CI 0.23–0.37; P < 0.001). The multivariate Cox regression show pancreatic head tumors have a significantly shorter survival rate relative to pancreatic bodytail (HR, 1.12; 95% CI 1.03–1.22; P = 0.008), but the primary site was not a significant independent risk factor for prognosis by log-rank test (P = 0.39) and multivariate competing risk model [subdistribution HR (SHR), 1.08; 95% CI 0.98–1.19; P = 0.087].We then examined our conclusion by 1:1 propensity score matching, and the result reflected pancreatic head tumors have a lower risk of DM compared with pancreatic bodytail tumors (OR, 0.22; 95% CI 0.15–0.34; P < 0.001), but the primary site of pancreatic tumors was not associated with LN + patient survival based on univariate Cox regression (HR, 1.04; 95% CI 0.93–1.17; P = 0.435) and competing risk analysis (SHR, 1.01; 95% CI 0.89–1.12; P = 0.947).ConclusionsLN + pancreatic head tumors were significantly lower risk of DM relative to pancreatic bodytail tumors. Survival outcome in LN + pancreatic tumors didn’t exist significant differences split by primary site, which indicates that the prognosis of LN + patients with chemotherapy isn’t associated with the primary site of metastasis, but with the occurrence of metastasis.

Real-world patterns of treatment and recurrence by frailty status among older women with HR-positive, HER2-negative early breast cancer.

535 Background: Frail health status impacts clinical decision making for older cancer patients and their families, and frailty is independently associated with increased risks of mortality. Our objective was to describe differences in treatment and rates of recurrence by frailty status among older women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. Methods: We performed a large, population-based retrospective cohort study of women aged 65 years and older diagnosed with first primary stage I-III HR+/HER2-breast cancer using the Surveillance, Epidemiology, and End Results Medicare-linked database between 2007 and 2015. Using administrative health claims, we ascertained information on breast cancer treatment and utilized validated claims-based algorithms to determine frailty status (robust, pre-frail, and frail) and identify subsequent invasive breast cancer recurrences. Relative hazards of recurrence were determined using Fine and Gray competing risks regression models with estimated subdistribution hazard ratios (SHR) and robust 95% confidence intervals (CI). Results: From an overall cohort of 46,027 women, most women (56%) were classified as robust at breast cancer diagnosis, whereas 37% and 7% were identified as pre-frail and frail, respectively. Compared to robust patients, frail patients were more likely to have stage III disease (10% vs. 7%) and receive mastectomy (27% vs. 18%), and less likely to receive radiation (35% vs. 57%) or chemotherapy (5% vs. 9%). Five-year cumulative incidences of recurrence were 15%, 18% and 22% among robust, pre-frail, and frail women, respectively. In multivariable competing risks models adjusted for age, race, stage, and treatment, frail (SHR 1.28, 95%CI 1.17-1.41) and pre-frail (SHR 1.15, 95%CI 1.09-1.21) women had a significantly increased risk of breast cancer recurrence. Conclusions: Independent of differences in treatment, frailty was associated with increased breast cancer recurrence risk in this population-based cohort of older women. However, the vast majority of older women living with HR+/HER2- early breast cancer were not identified as frail. These study results suggest that age alone is not an adequate indicator of physical resilience and underscores the need to consider additional factors when assessing the benefits and risks of treatments for the prevention of recurrence among HR+/HER2- early breast cancer patients.

Aspirin and pre-eclampsia: the heart of the matter?

Ling and colleagues (BJOG 2020 xxxx) have contributed important information on cardiovascular (CV) assessment over the course of pregnancy, with and without aspirin treatment, associated with risk of pre-term pre-eclampsia, as assessed by the multivariable competing risks model at 11-13 weeks. There are a number of important messages in these data. First, women at low- (vs. high-) risk of preterm pre-eclampsia appear to have lower cardiac output (CO), stroke volume (SV), and blood pressure (BP) in early pregnancy, consistent with the hypothesis that maternal CV predisposition plays a major role in pre-eclampsia risk (Ridder A et al. Int J Mol Sci. 2019;20(13)).