Gray Subdistribution Hazard Model Research Articles

Mortality after the 9/11 terrorist attacks among world trade center health registry enrollees with cancer.

While several studies have reported the association between 9/11 exposure and cancer risk, cancer survival has not been well studied in the World Trade Center (WTC) exposed population. We examined associations of 9/11-related exposures with mortality in WTC Health Registry enrollees diagnosed with cancer before and after 9/11/2001. This is a longitudinal cohort study of 5061 enrollees with a first-ever primary invasive cancer diagnosis between 1995 and 2015 and followed through 2016. Based on the timing of first cancer diagnosis, pre-9/11 (n=634) and post-9/11 (n=4427) cancer groups were examined separately. 9/11-related exposures included witnessing traumatic events, injury on 9/11, and 9/11-related post-traumatic stress disorder (PTSD). Associations of exposures with all-cause mortality were examined using Cox proportional hazards regression. In the post-9/11 group, cancer-specific mortality was evaluated by enrollee group (WTC rescue/recovery workers vs. non-workers) using Fine and Gray's proportional sub-distribution hazard models, adjusting for baseline covariates, tumor characteristics, and treatment. In the pre-9/11 group, 9/11-related exposures were not associated with all-cause mortality. In the post-9/11 group, increased risk of all-cause mortality was associated with PTSD (adjusted HR=1.35; 95% CI=1.11-1.65), but not with injury or witnessing traumatic events. Cancer-specific mortality was not statistically significantly associated with 9/11-related exposures. In rescue/recovery workers, increased non-cancer mortality risk was associated with PTSD (aHR=2.13, 95% CI=1.13-4.00) and witnessing ≥3 traumatic events (aHR=2.00, 95% CI=1.13-3.55). We did not observe associations between 9/11-related exposures and cancer-specific mortality. Similar to findings in the non-cancer WTC exposed population, PTSD was associated with increased risk of all-cause mortality in cancer patients.

Mortality and Conversion to Transfemoral Amputation After Transtibial Amputation in the Veterans Affairs Health System.

Transtibial below-knee amputation (BKA) is associated with considerable morbidity, particularly in the vasculopathic population. The purpose of this study was to determine the cumulative probability of undergoing transfemoral above-knee amputation (AKA) conversion within 5 years of BKA and associated risk factors while accounting for the competing risk of death. This is a retrospective, national database study with structured query of the Veterans Affairs (VA) database for patients who underwent BKA from 1999 to 2020, identified by Current Procedural Terminology codes. Above-knee amputation conversion was identified using Current Procedural Terminology codes in combination with natural language processing to match procedure laterality. After internally validating our patient identification method, risk factors were collected. Competing risk analysis estimated the cumulative incidence rate of AKA conversion and associated risk factors with death as a competing risk. Our query yielded 19,875 patients (19,640 men, 98.8%) who underwent BKA with a median age of 66 years (interquartile range, 60 to 73). The median follow-up was 951 days (interquartile range, 275 to 2,026). The crude cumulative probabilities of AKA conversion and death at 5 years were 15.4% (95% confidence interval [CI], 14.9% to 16.0%) and 47.7% (95% CI, 46.9% to 48.4%), respectively. In the Fine and Gray subdistribution hazard model, peripheral vascular disease had the highest AKA conversion risk (hazard ratio [HR] 2.66; 95% CI, 2.22 to 3.20; P < 0.001). Other factors independently associated with AKA conversion included urgent operation (HR 1.32; 95% CI, 1.23 to 1.42), cerebrovascular disease (HR 1.19; 95% CI, 1.11 to 1.28), chronic obstructive pulmonary disease (HR 1.15; 95% CI, 1.07 to 1.24), and previous myocardial infarction (HR 1.10; 95% CI, 1.02 to 1.19) (All P < 0.02). Within this predominantly male, VA population, BKA carries a high risk of conversion to AKA within 5 years, without reaching a steady risk of AKA conversion within 5 years. Peripheral vascular disease, chronic obstructive pulmonary disease, cerebrovascular disease, previous myocardial infarction, and urgent BKA increase the risk of AKA conversion. Level III.

Risk Factors of Cardiovascular Death after Venous Thromboembolism: Results from a Prospective Cohort Study.

Cardiovascular deaths (CVDTs) are more frequent in patients with venous thromboembolism (VTE) than in the general population; however, risk factors associated with this increased risk of CVDT in patients with VTE are not described. To determine the risk factors of CVDT in patients with VTE from a multicenter prospective cohort study, Fine and Gray subdistribution hazard models were conducted. Of the 3,988 included patients, 426 (10.7%) died of CVDT during a median follow-up of 5 years. The risk factors of CVDT after multivariate analyses were: age of 50 to 65 years (vs. <50 years, hazard ratio [HR]: 3.22, 95% confidence interval [CI]: 1.67-6.62), age >65 years (vs. <50 years, HR: 7.60, 95% CI: 3.73-15.52), cancer-associated VTE (vs. transient risk factor-related VTE, HR: 1.73, 95% CI: 1.15-2.61), unprovoked VTE (vs. transient risk factor-related VTE, HR: 1.42, 95% CI: 1.02-2.00), past tobacco use (vs. never, HR: 1.43, 95% CI: 1.06-1.94), current tobacco use (vs. never, HR: 1.87, 95% CI: 1.15-3.01), hypertension (HR: 2.11, 95% CI: 1.51-2.96), chronic heart failure (HR: 2.28, 95% CI: 1.37-3.79), chronic respiratory failure (HR: 1.72, 95% CI: 1.02-2.89), and atrial fibrillation (HR: 1.67, 95% CI: 1.06-2.60). The risk of CVDT was significantly reduced with direct oral anticoagulants (vs. vitamin-K antagonists) and with longer duration of treatment (>3 months). Risk factors of CVDT after VTE include some traditional cardiovascular risk factors and other risk factors that are related to characteristics of VTE, and patients' comorbidities.

Comorbid Hypertension Reduces the Risk of Ventricular Arrhythmia in Chronic Heart Failure Patients with Implantable Cardioverter-Defibrillators.

Aims: Low blood pressure (BP) has been shown to be associated with increased mortality in patients with chronic heart failure. This study was designed to evaluate the relationships between diagnosed hypertension and the risk of ventricular arrhythmia (VA) and all-cause death in chronic heart failure (CHF) patients with implantable cardioverter-defibrillators (ICD), including those with preserved left ventricular ejection fraction (HFpEF) and indication for ICD secondary prevention. We hypothesized that a stable hypertension status, along with an increasing BP level, is associated with a reduction in the risk of VA in this population, thereby limiting ICD efficacy. Methods: We retrospectively enrolled 964 CHF patients, with hypertension diagnosis and hospitalized BP measurements obtained before ICD implantation. The primary outcome measure was defined as the composite of SCD, appropriate ICD therapy, and sustained VT. The secondary endpoint was time to death or heart transplantation (HTx). We performed multivariable Cox proportional hazard regression and entropy balancing to calculate weights to control for baseline imbalances with or without hypertension. The Fine–Gray subdistribution hazard model was used to confirm the results. The effect of random BP measurements on the primary outcome was illustrated in the Cox model with inverse probability weighting. Results: The 964 patients had a mean (SD) age of 58.9 (13.1) years; 762 (79.0%) were men. During the interrogation follow-up [median 2.81 years (interquartile range: 1.32–5.27 years)], 380 patients (39.4%) reached the primary outcome. A total of 244 (45.2%) VA events in non-hypertension patients and 136 (32.1%) in hypertension patients were observed. A total of 202 (21.0%) patients died, and 31 (3.2%) patients underwent heart transplantation (incidence 5.89 per 100 person-years; 95% CI: 5.16–6.70 per 100 person-years) during a median survival follow-up of 4.5 (IQR 2.8–6.8) years. A lower cumulative incidence of VA events was observed in hypertension patients in the initial unadjusted Kaplan–Meier time-to-event analysis [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.53–0.80]. The protective effect was robust after entropy balancing (HR: 0.71, 95% CI: 0.56–0.89) and counting death as a competing risk (HR: 0.71, 95% CI: 0.51–1.00). Hypertension diagnosis did not associate with all-cause mortality in this population. Random systolic blood pressure was negatively associated with VA outcomes (p = 0.065). Conclusions: In hospitalized chronic heart failure patients with implantable cardioverter-defibrillators, the hypertension status and higher systolic blood pressure measurements are independently associated with a lower risk of combined endpoints of ventricular arrhythmia and sudden cardiac death but not with all-cause mortality. Randomized controlled trials are needed to confirm the protective effect of hypertension on ventricular arrhythmia in chronic heart failure patients.

Cancer Risk and Mortality in Patients With Kidney Disease: A Population-Based Cohort Study

Patients with chronic kidney disease (CKD) may be at increased risk for cancer. CKD may also be associated with worse cancer outcomes. This study examined cancer incidence and mortality across the spectrum of CKD. Population-based cohort study. All adult Ontario residents with data on estimated glomerular filtration rate (eGFR) or who were receiving maintenance dialysis or had received a kidney transplant (2007-2016). Patients were categorized as of the first date they had 2 eGFR assessments or were registered as receiving maintenance dialysis or having received a kidney transplant. eGFR levels were further categorized as≥60, 45-59, 30-44, 15-29, and<15 mL/min/1.73 m2; the latter 4 groups are consistent with KDIGO (Kidney Disease: Improving Global Outcomes) CKD categories G3a, G3b, G4, and G5, respectively. Overall and site-specific cancer incidence and mortality. Fine and Gray subdistribution hazard models. Among 5,882,388 individuals with eGFR data, 29,809 receiving dialysis, and 4,951 having received a kidney transplant, there were 325,895 cancer diagnoses made during 29,993,847 person-years of follow-up. The cumulative incidence of cancer ranged between 10.8% and 15.3% in patients with kidney disease. Compared with patients with eGFR≥60 mL/min/1.73 m2, adjusted hazard ratios (AHRs) for a cancer diagnosis among patients with CKD G3a, G3b, G4, and G5 were 1.08 (95% CI, 1.07-1.10), 0.99 (95% CI, 0.97-1.01), 0.85 (95% CI, 0.81-0.88), and 0.81 (95% CI, 0.73-0.90), respectively. The AHRs for patients receiving dialysis and who had received a transplant were 1.01 (95% CI, 0.96-1.07) and 1.25 (95% CI, 1.12-1.39), respectively. Patients with kidney disease had higher proportions of stage 4 cancers at diagnosis. Patients with CKD G3a, G3b, and G4 and transplant recipients had increased risks of cancer-specific mortality (AHRs of 1.27 [95% CI, 1.23-1.32], 1.29 [95% CI, 1.24-1.35], 1.25 [95% CI, 1.18-1.33], and 1.48 [95% CI, 1.18-1.87], respectively). The risks of bladder and kidney cancers and multiple myeloma were particularly increased in CKD, and mortality from these malignancies increased with worsening kidney function. Possible unmeasured confounding and limited ability to infer causal associations. Cancer incidence in the setting of kidney disease is substantial. Cancer risk was increased in mild to moderate CKD and among transplant recipients, but not in advanced kidney disease. Cancer-related mortality was significantly higher among patients with kidney disease, particularly urologic cancers and myeloma. Strategies to detect and manage these cancers in the CKD population are needed.

Second primary malignancies in oral tongue cancer: A Surveillance, Epidemiology, and End Result–based analysis evaluating the basic characteristics, survival outcomes, and predictive factors

AbstractThe purpose of this study is to evaluate the risk of developing a second primary malignancy (SPM) in oral tongue cancer (OTC) patients, and identify the characteristics and survival outcomes of OTC patients with an SPM. Patients with first primary OTC were identified from the Surveillance, Epidemiology, and End Result (SEER) database, and were further divided into the only one primary malignancy (OOPM) group and SPM group. Baseline characteristics and survival outcomes between patients in two groups were compared. Furthermore, a Fine and Gray subdistribution hazard model was utilized to investigate the cumulative risk of developing an SPM in OTC patients. Then, a multivariate competing‐risk model was performed to explore risk predictors. Patients in the SPM group had older age and lower tumor stage than those in the OOPM group. Moreover, the proportion of receiving surgery in the SPM group was significantly higher than that in the OOPM group. Lung was the most common site of SPMs in whole patients. In male patients, the second common site of SPMs was prostate, while in female patients, it was female breast. OTC patients with an SPM of lung and bronchus had the worst overall survival. Finally, older age, male sex, primary site of ventral surface and anterior 2/3 of tongue, localized diseases, and the administration of surgery were considered as risk predictors of developing an SPM in OTC patients. OTC survivors had high risk of developing an SPM, and subsequent malignancy was an important COD. Careful monitoring is warranted in OTC survivors due to the high SPM‐specific mortality.

Ankylosing Spondylitis: A Risk Factor for Parkinsonism-A Nationwide Population-Based Study.

Ankylosing spondylitis (AS) is an immune-mediated, chronic inflammatory rheumatic disorder. The etiology of Parkinson's disease (PD) is multifactorial; however, inflammation is receiving an increasing amount of attention as an underlying cause of the neurodegenerative process of PD. We performed a nationwide longitudinal, population-based matched cohort study to assess the association with the later development of parkinsonism in Korea. This study was conducted using records from the Health Insurance Review and Assessment Service database. The cumulative incidence rate of PD was estimated. Fine-Gray subdistribution hazard models were used to identify hazards associated with PD development based on the presence of AS. Exposure to anti-inflammatory drugs was measured and analyzed to determine the protective effect of these medications. Additionally, the hazard ratio (HR) for atypical parkinsonism was estimated. The results of the Fine-Gray subdistribution hazard model revealed that the HR for PD development in the AS group was 1.82 (95%confidence interval [CI], 1.38-2.39, p < 0.001). A significant decrease in PD development was observed in patients with AS taking non-steroidal anti-inflammatory drugs (NSAIDs). The HR for atypical parkinsonism in the AS group was 3.86 (95%CI, 1.08-13.78, p < 0.05). We found that AS was associated with an increased risk of PD and atypical parkinsonism. NSAIDs used for AS control have some protective effects against PD. Further studies assessing whether biological treatment mitigates PD risk in patients with high activity are warranted.

Very High High-Density Lipoprotein Cholesterol Levels and Cardiovascular Mortality

Previous studies have shown reduced cardiovascular risk with increasing high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high concentrations of HDL-C. Thus, we aimed to study the gender-specific relation between very high HDL-C levels (>80, >100mg/100ml) and adverse cardiovascular outcomes and the genetic basis in the general population enrolled in the United Kingdom Biobank. A total of 415,416 participants enrolled in the United Kingdom Biobank without coronary artery disease were included in this prospective cohort study, with a median follow-up of 9years. A high HDL-C level >80mg/100ml was associated with increased risk of all-cause death (Hazard ratio [HR] 1.11, confidence interval [CI] 1.03 to 1.20, p=0.005) and cardiovascular death (HR 1.24, CI 1.05 to 1.46, p=0.01) after adjustment for age, gender, race, body mass index, hypertension, smoking, triglycerides, LDL-C, stroke history, heart attack history, diabetes, eGFR, and frequent alcohol use (defined as ≥3 times/week) using Cox proportional hazard and Fine and Gray's subdistribution hazard models, respectively. In gender-stratified analyses, such associations were only observed in men (all-cause death HR 1.79, CI 1.59 to 2.02, p <0.0001; cardiovascular death HR 1.92, CI 1.52 to 2.42, p <0.0001), but not in women (all-cause death HR 0.97, CI 0.88 to 1.06, p=0.50; cardiovascular death HR 1.04, CI 0.83 to 1.31, p=0.70). The findings persisted after adjusting for the genetic risk score comprised of known HDL-C-associated single nucleotide polymorphisms. Very high HDL-C levels are associated with an increased risk of all-cause death and cardiovascular death among men but not in women in the general population free of coronary artery disease.

Non-Hispanic Black and Hispanic Patients Have Worse Outcomes Than White Patients Within Similar Stages of Peripheral Artery Disease.

BackgroundRacial and ethnic disparities in outcomes following lower limb revascularization for peripheral artery disease have been ascribed to disease severity at presentation for surgery.Methods and ResultsWe calculated 1‐year risk of major adverse limb events (MALEs), major amputation, and death for patients undergoing elective revascularization for claudication or chronic limb‐threatening ischemia in the Vascular Quality Initiative data (2011–2018). We report hazard ratios according to race and ethnicity using Cox (death) or Fine and Gray subdistribution hazards models (MALE and major amputation, treating death as a competing event), adjusted for patient, treatment, and anatomic factors associated with disease severity. Among 88 599 patients (age, 69 years; 37% women), 1‐year risk of MALE (major amputation and death) was 12.8% (95% CI, 12.5–13.0) in 67 651 White patients, 16.5% (95% CI, 5.8–7.8) in 15 442 Black patients, and 17.2% (95% CI, 5.6–6.9) in 5506 Hispanic patients. Compared with White patients, we observed an increased hazard of poor limb outcomes among Black (MALE: 1.17; 95% CI, 1.12–1.22; amputation: 1.52; 95% CI, 1.39–1.65) and Hispanic (MALE: 1.22; 95% CI, 1.14–1.31; amputation: 1.45; 95% CI, 1.28–1.64) patients. However, Black and Hispanic patients had a hazard of death of 0.85 (95% CI, 0.79–0.91) and 0.71 (95% CI, 0.63–0.79) times the hazard among White patients, respectively. Worse limb outcomes were observed among Black and Hispanic patients across subcohorts of claudication and chronic limb‐threatening ischemia.ConclusionsBlack and Hispanic patients undergoing infrainguinal revascularization for chronic limb‐threatening ischemia and claudication had worse limb outcomes compared with White patients, even with similar disease severity at presentation. Additional investigation aimed at eliminating disparate limb outcomes is needed.

Risk of dementia in colorectal cancer patients receiving chemotherapy: A nationwide cohort study

BackgroundStudies have reported conflicting evidence regarding whether chemotherapy leads to dementia. This study aimed to determine whether chemotherapy increases dementia risk in Taiwanese patients with colorectal cancer (CRC). MethodsData from the Taiwan Cancer Registry and National Health Insurance Research Database were used. Patients newly diagnosed as having CRC between 2007 and 2015 without prior history of dementia or neurodegenerative disorders were identified. Based on whether they underwent chemotherapy, patients were divided into chemotherapy and non-chemotherapy groups. Those who later developed dementia were identified using validated diagnostic codes. The Fine and Gray subdistribution hazard model for all-cause dementia with competing risk of death was applied for all patients or each stratified group. ResultsA total of 76,130 patients with CRC were included, with 45,872 (60.25%) in the chemotherapy group and 30,258 (39.75%) in the non-chemotherapy group. A higher incidence of dementia was observed in the non-chemotherapy group compared with the chemotherapy group (3.75% vs. 2.40%, p < 0.0001), but the risk of dementia did not differ between the groups (adjusted subdistribution hazard ratio [HRSD] = 0.97, 95% confidence interval [CI]: 0.88–1.06, p = 0.492). In the stratified analysis, chemotherapy was a risk factor for dementia in patients aged > 80 years (adjusted HRSD = 1.20, 95% CI: 1.03–1.40, p = 0.0190), whereas gender, clinical cancer stage, comorbidities, surgery, and radiation therapy had no impact on the risk of dementia. ConclusionChemotherapy increased the risk of dementia in elderly patients with CRC, highlighting the necessity to monitor their cognitive function after chemotherapy.

Development of a competing risk nomogram for the prediction of cause-specific mortality in patients with thymoma: a population-based analysis.

BackgroundThis study was developed to assess the odds of cause-specific mortality and other types of mortality in thymoma patients. In addition, these analyses were leveraged to develop a comprehensive competing risk model-based nomogram capable of predicting cause-specific mortality as a result of thymoma.MethodsThymoma patients included within the Surveillance, Epidemiology, and End Results (SEER) database from 2004–2016 were identified, and the odds of cause-specific mortality due to thymoma and other forms of mortality for these patients were estimated. In addition, Fine and Gray’s proportional subdistribution hazard model was constructed, and a competing risk nomogram was developed using this model that was capable of predicting the odds of 3-, 5-, and 10-year cause-specific mortality in thymoma patients.ResultsIn total, 1,591 relevant cases in the SEER database were selected for analysis. In this patient cohort, the respective 5-year cumulative incidence rates for cause-specific mortality and mortality attributable to other causes were 12.4% and 8.2%. Variables significantly associated with cause-specific mortality included age, chemotherapy, surgery, and Masaoka stage. Additionally, the odds of other-cause-specific mortality rose with increasing patient age, and chemotherapy was correlated with other-cause-specific mortality. The competing risk nomogram that was developed exhibited good discriminative ability as a means of predicting cause-specific mortality, as evidenced by a concordance index (C-index) value of 0.84. Calibration curves further revealed excellent consistency between predicted and actual mortality when using this nomogram.ConclusionsIn summary, we herein assessed the odds of cause-specific and other-cause-specific mortality among thymoma patients, and we designed a novel nomogram capable of predicting cause-specific mortality for thymoma, providing a promising tool that may be of value in the context of individualized patient prognostic evaluation.

Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative.

BackgroundMany individuals take long-term immunosuppressive medications. We evaluated whether these individuals have worse outcomes when hospitalised with COVID-19 compared with non-immunosuppressed individuals.MethodsWe conducted a retrospective cohort study using data from the National COVID Cohort Collaborative (N3C), the largest longitudinal electronic health record repository of patients in hospital with confirmed or suspected COVID-19 in the USA, between Jan 1, 2020, and June 11, 2021, within 42 health systems. We compared adults with immunosuppressive medications used before admission to adults without long-term immunosuppression. We considered immunosuppression overall, as well as by 15 classes of medication and three broad indications for immunosuppressive medicines. We used Fine and Gray's proportional subdistribution hazards models to estimate the hazard ratio (HR) for the risk of invasive mechanical ventilation, with the competing risk of death. We used Cox proportional hazards models to estimate HRs for in-hospital death. Models were adjusted using doubly robust propensity score methodology.FindingsAmong 231 830 potentially eligible adults in the N3C repository who were admitted to hospital with confirmed or suspected COVID-19 during the study period, 222 575 met the inclusion criteria (mean age 59 years [SD 19]; 111 269 [50%] male). The most common comorbidities were diabetes (23%), pulmonary disease (17%), and renal disease (13%). 16 494 (7%) patients had long-term immunosuppression with medications for diverse conditions, including rheumatological disease (33%), solid organ transplant (26%), or cancer (22%). In the propensity score matched cohort (including 12 841 immunosuppressed patients and 29 386 non-immunosuppressed patients), immunosuppression was associated with a reduced risk of invasive ventilation (HR 0·89, 95% CI 0·83–0·96) and there was no overall association between long-term immunosuppression and the risk of in-hospital death. None of the 15 medication classes examined were associated with an increased risk of invasive mechanical ventilation. Although there was no statistically significant association between most drugs and in-hospital death, increases were found with rituximab for rheumatological disease (1·72, 1·10–2·69) and for cancer (2·57, 1·86–3·56). Results were generally consistent across subgroup analyses that considered race and ethnicity or sex, as well as across sensitivity analyses that varied exposure, covariate, and outcome definitions.InterpretationAmong this cohort, with the exception of rituximab, there was no increased risk of mechanical ventilation or in-hospital death for the rheumatological, antineoplastic, or antimetabolite therapies examined.FundingNone.

Localized DLBCL of the Tonsil: A U.S. Population-Based Survival Analysis

INTRODUCTION: The Waldeyer ring represents a common location of diffuse large B-cell lymphoma (DLBCL) arising in the head and neck. Within the Waldeyer ring, tonsils are the most common site. Chemotherapy with or without consolidation with radiotherapy are the most common approaches. However, the benefit of radiotherapy over chemotherapy as a single approach in patients with localized DLBCL remains unclear. In this study we analyzed the survival effect of different treatment modalities along with clinical variables in two cohorts of patients with stage I DLBCL involving either the tonsils or the neck lymph nodes (LN).METHODS: This is a retrospective analysis of patients with stage I DLBCL with primary involvement of the tonsil or neck lymph nodes derived from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2015 with follow up through 2017. We concentrated our analysis on patients with Ann Arbor stage I and treated with chemotherapy and/or radiotherapy. We excluded cases without histologic confirmation, untreated, incomplete survival data or unknown cause of death. The major end-points of this study were overall survival (OS) and lymphoma-specific survival (LSS). Kaplan-Meier and log-rank test were used in the OS analysis with Cox proportional hazard regression model to assess predictors of OS. LSS was evaluated using competing risk analysis. The Fine and Gray subdistribution hazard model was used to assess the effect of demographic and treatment related variables on the risk of lymphoma-specific death. We reported subdistribution hazard ratios (SHR) with corresponding 95% confidence intervals.RESULTS: 1978 (tonsil: 311 and neck LN: 1667) patients with DLBCL met the inclusion criteria. Overall, most patients were ≥ 60 years (n=1130, 57.1%), male (n=1101, 55.7%), white (n=1631, 82.5%), non-Hispanic (n=1775, 89.7%), and treated with chemotherapy (n=935, 47.3%) followed by chemotherapy/radiotherapy (n=929, 47%). Patients <60 years (48.9% vs 41.8%; P=0.019), non-White race (21.9% vs 16.7%; P=0.029) and Hispanic origin (14.1% vs 9.5%; P=0.013) were more common in DLBCL in tonsil compared to neck LN.Patients with tonsil DLBCL exhibited longer median OS compared to neck LN (16.2 vs. 14.2 years; P=0.033) (Figure 1A). In patients with tonsil DLBCL, consolidation with radiation did not lead to longer median 5-year OS (83.9%, 95%CI 76.7-89% vs 81.8%, 95%CI 74.1-87.4%; P=0.523) or LSS (HR=0.73, 95%CI 0.37-1.42; P=0.350) compared to chemotherapy (Figure 1B and Table 1). Contrary, patients with neck LN demonstrated better OS (5-year OS 82.6%, 95% 79.7-85.1 vs 72.2% 95%CI 68.9-75.2%; P<0.001) and LSS (HR=0.55, 95%CI 1.51-3.14; P<0.001) if they received consolidation with radiotherapy compared to chemotherapy only (Figure 1C and Table 2).CONCLUSION: Based on our analysis consolidation with radiotherapy does not improve OS or LSS in patients with stage I tonsil DLBCL treated with chemotherapy. Conversely, consolidation with radiation significantly improves survival in patients with localized LN DLBCL. [Display omitted] DisclosuresLossos: NCI: Research Funding; Seattle Genetics: Consultancy; Stanford University: Patents & Royalties; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment. Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Puma Biotechnology: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member.

Clinical outcomes of Sacubitril/Valsartan in patients with acute heart failure: A multi-institution study.

BackgroundThe effectiveness and safety of initiating sacubitril/valsartan therapy among patients who are hospitalized for acute heart failure (HF) is unclear.MethodsA cohort of 3736 patients with HF with reduced ejection fraction (HFrEF) hospitalized for acute HF was identified from Chang Gung Research Database between January 1, 2016 and August 31, 2019. The risks of rehospitalization for HF and death associated with sacubitril/valsartan therapy compared to angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy were evaluated. We used stabilized inverse probability of treatment weighting to balance the baseline covariates. The risks of fatal and non-fatal outcomes between the groups were compared using a Cox proportional hazard model and Fine and Gray subdistribution hazard model, respectively.FindingsThe composite of rehospitalization for HF and death occurred in 22.9% of the patients in the sacubitril/valsartan group compared to 32.6% in the ACEI/ARB group (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52–0.97) after a mean follow-up period of 11.8 months. The sacubitril/valsartan group had a lower risk of rehospitalization for HF (subdistribution HR 0.83, 95% CI 0.74–0.92) and all-cause death (HR 0.51, 95% CI 0.27–0.94). There were no significant differences in the rates of worsening renal function or severe hyperkalemia between the two groups.InterpretationIn real-world practice, initiating sacubitril/valsartan therapy among patients with HFrEF who were hospitalized for acute HF was associated with a lower rate of rehospitalization for HF and death compared with ACEI/ARB therapy.FundingThis study was supported by Novartis Pharmaceuticals.

Major adverse limb events in type 2 diabetes patients receiving glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: A retrospective multi-institutional study

AimsTo compare the risk of incident major adverse limb events (MALEs) between patients with type 2 diabetes (T2DM) who initiated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or sodium-glucose cotransporter-2 Inhibitors (SGLT2Is). MethodsT2DM patients with prescriptions of GLP-1 RAs or SGLT2Is between January 1, 2016 and December 31, 2018 were retrospectively identified from a multi-institutional database. We used inverse probability of treatment weighting (IPTW) to balance covariates, and compared MALEs between GLP-1 RAs and SGLT2Is initiators using Fine and Gray subdistribution hazard model. ResultsThere were 3,087 patients in the GLP-1 RAs group and 19,101 patients in the SGLT2Is group. After IPTW adjustment, the mean ages were 59.0 and 58.8 years, mean durations of diabetes were 6.4 years and 6.1 years, and 25.4% and 28.4% of the patients had cardiovascular disease, respectively. Lower extremity arterial disease was uncommon in both groups (2%).Those who initiated GLP-1 RAs treatment were associated with reduced rate of MALEs (adjusted subdistribution hazard ratio [HR] 0.62, 95% confidence interval 0.46–0.83). ConclusionsT2DM patients who received GLP-1 RAs treatment were associated with lower risk of MALEs compared to those who received SGLT2Is treatment.

A nationwide cohort investigation on pay-for-performance and major adverse limb events in patients with diabetes

A retrospective cohort study was conducted using claims data from Taiwan's National Health Insurance program to assess the effect of diabetic pay-for-performance (P4P) program on major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). This study included patients with T2DM who had completed or not completed a 1-year P4P program from 2002 to 2013. Propensity-score matching was used to balance the baseline characteristics between groups. The Cox proportional-hazard model and Fine and Gray subdistribution hazard model were used to examine the association between P4P and the risks of MALE, MACE, systemic thromboembolism (ST), heart failure (HF) hospitalization, and all-cause mortality. Patients who underwent the P4P program had a significantly decreased incidence of MALE (2.0% vs. 2.6%, subdistribution hazard ratio [SHR] 0.73, 95% CI 0.71–0.76). Regarding the individual components, the P4P group demonstrated lower risks for foot ulcer (1.1% vs 1.3%, SHR 0.80, 95% CI 0.77–0.84), gangrene (0.57% vs 0.93%, SHR 0.59, 95% CI 0.56–0.63), percutaneous transluminal angioplasty (0.61% vs 0.79%, SHR 0.72, 95% CI 0.68–0.77), and amputation (0.46% vs 0.75%, SHR 0.58, 95% CI 0.55–0.62). In addition, the risks of MACE, ST, HF hospitalization, and all-cause mortality were remarkably lower in the P4P group. The P4P program might significantly reduce critical events of MALE, MACE, ST, HF, and mortality in the diabetic population.

Immune-related adverse events and kidney function decline in patients with genitourinary cancers treated with immune checkpoint inhibitors

BackgroundIn patients with genitourinary cancers, the effect of immune checkpoint inhibitors (ICIs) on kidney function is unknown. Patients and methodsThis is a retrospective cohort study of patients with renal cell carcinoma (RCC) and urothelial carcinoma who received ICIs at two major cancer centers between 2012 and 2018. Cumulative incidence and Fine and Gray subdistribution hazard models were performed to determine predictors of the co-primary outcomes, (1) acute kidney injury (AKI) and (2) sustained estimated glomerular filtration rate (eGFR) loss, defined as a >20% decline in eGFR sustained ≥90 days. We also determined the association between immune-related adverse events (irAE) and adverse kidney outcomes among patients surviving ≥1 year. Results637 patients were included; 320 (50%) patients had RCC and 317 (50%) patients had urothelial carcinoma. Half of the cohort had eGFR<60 mL/min/1.73 m2 at baseline. irAEs, AKI, and sustained eGFR loss were common, occurring in 33%, 25% and 16%, respectively. Compared to patients with urothelial carcinoma, patients with RCC were more likely to develop irAEs (aHR 1.61, 95% CI 1.20–2.18) and sustained eGFR loss (aHR 1.97, 95% CI 1.24–3.12), but not AKI (aHR 1.53, 95% CI 0.97–2.41). Among patients surviving ≥1 years, experiencing a non-renal irAE was associated with a significantly higher risk of sustained eGFR loss (aHR 1.71, 95% CI 1.14–2.57). ConclusionAKI and sustained eGFR loss are common in patients with genitourinary cancers receiving ICIs. irAEs may be a novel risk factor for kidney function decline among patients receiving ICIs.

Ovarian cancer incidence and death in average-risk women undergoing bilateral oophorectomy at benign hysterectomy

Objectives: Opportunistic bilateral oophorectomy (BO) is often considered in patients undergoing benign hysterectomy, but the degree to which BO reduces the incidence of ovarian cancer in this population remains unclear and is important for patient decision-making. Methods: We performed a population-based cohort study of all women (≥20 years) undergoing hysterectomy for benign indications from 1996-2015 in Ontario, Canada, followed to December 2019. Patients with ovarian pathology at hysterectomy, previous breast or gynecologic cancer, or evidence of genetic susceptibility to malignancy were excluded. Ovarian cancers and deaths were ascertained from the Ontario Cancer Registry. Inverse probability of treatment weighted Fine & Gray subdistribution hazard models were used to examine the effect of BO on ovarian cancer incidence and death, while accounting for competing risks and adjusting for demographic factors, gynecologic conditions, and comorbidities. Results: We identified 249,924 patients (BO 61,203 [25%]; ovarian conservation 188,721 [75%]) with median age 45 years (interquartile range [IQR] 40-52). Over median follow-up of 14 years (IQR 9-19), 584 women developed ovarian cancer (0.2%) and 17,052 died (6.8%) from any cause. Baseline characteristics were balanced after IPT weighting (standardized differences Conclusions: BO results in a small absolute reduction in incident ovarian cancer among women undergoing benign hysterectomy. Population-average risk estimates derived in this study are generalizable, directly address the limitations of previous work, and should be used to counsel patients preoperatively.

Traumatic injury and atrial fibrillation among deployed service members.

Atrial fibrillation and atrial flutter (AF/AFL), the most common atrial arrhythmias, have never been examined in combat casualties. In this study, we investigated the impact of traumatic injury on AF/AFL among service members with deployment history. Sampled from the Department of Defense (DoD) Trauma Registry (n = 10,000), each injured patient in this retrospective cohort study was matched with a non-injured service member drawn from the Veterans Affairs/DoD Identity Repository. The primary outcome was AF/AFL diagnosis identified using ICD-9-CM and ICD-10-CM codes. Competing risk regressions based on Fine and Gray subdistribution hazards model with were utilized to assess the association between injury and AF/AFL. There were 130 reported AF/AFL cases, 90 of whom were injured and 40 were non-injured. The estimated cumulative incidence rates of AF/AFL for injured was higher compared to non-injured patients (hazards ratio [HR] = 2.04; 95% confidence interval [CI] = 1.44, 2.87). After adjustment demographics and tobacco use, the association did not appreciably decrease (HR = 1.90; 95% CI = 1.23, 2.93). Additional adjustment for obesity, hypertension, diabetes, and vascular disorders, the association between injury and AF/AFL was no longer statistically significant (HR = 1.51; 95% CI = 0.99, 2.52). Higher AF/AFL incidence rate was observed among deployed service members with combat injury compared to servicemembers without injury. The association did not remain significant after adjustment for cardiovascular-related covariates. These findings highlight the need for combat casualty surveillance to further understand the AF/AFL risk within the military population and to elucidate the potential underlying pathophysiologic mechanisms.

Abstract 2531: Function-related indicator and outcomes of screening mammography in older women from the BCSC-Medicare Cohort

Abstract Background: Although there is evidence pointing to the role of comorbidity and age in screening mammography outcomes among older women, the impact of functional decline on mortality in this population is unknown. Methods: We used data from 238,849 women in the Breast Cancer Surveillance Consortium-Medicare (BCSC) linked database from 1999-2015 who had at least one screening mammogram at ages 66-94 years. We estimated the 10-year cumulative incidence of breast cancer, breast cancer death, and non-breast cancer death by function-related indicator (FRI) which incorporated 16 claims-based items reflecting functional or health status in older people. In the analysis, FRI score was categorized as an ordinal variable (0, 1, and 2+) and a higher score indicated a higher burden of functional limitations. Fine and Gray proportional sub-distribution hazards models were applied with incident breast cancer and death treated as competing events. Risk estimates by FRI scores (0, 1, and 2+) were adjusted by age and NCI comorbidity index separately and stratified by these factors. Results: During a median follow-up of 101 months, 9,252 women were diagnosed with breast cancer. During follow-up, 406 women died of breast cancer and 41,640 died from non-breast cancer causes. The 10-year age-adjusted cumulative incidence of invasive breast cancer slightly decreased with increasing FRI score (FRI=0: 4.0%, 95% CI=3.8%-4.1%; FRI=1: 3.9%, 95% CI=3.7%-4.2%; FRI=2+: 3.5%, 95% CI=3.1%-3.9%). Risk of death from non-breast cancer causes increased with FRI score (FRI=0: 18.8%, 95% CI=18.5%-19.1%; FRI=1: 24.4%, 95% CI=23.9%-25.0%; FRI=2+: 39.8%, 95% CI=38.8%-40.9%). Risk of breast cancer death was low with minimal risk differences across FRI scores (FRI=0: 0.24%, 95%CI=0.20%-0.28%; FRI=1: 0.20%, 95%CI=0.14%-0.26%; FRI=2+: 0.30%, 95% CI=0.18%-0.42%). Risk estimates in NCI comorbidity index-adjusted models were largely similar to outcomes in age-adjusted models. Stratified analyses suggested similar patterns of risk estimates by FRI. Conclusion: Cumulative risk of death from non-breast cancer causes substantially increases with FRI score, suggesting that the potential of screening mammography to benefit older women is low among those with a high burden of functional limitation. Citation Format: Dongyu Zhang, Linn Abraham, Joshua Demb, Diana L. Miglioretti, Shailesh Advani, Brian L. Sprague, Louise M. Henderson, Tracy Onega, Karen Wernli, Louise C. Walter, Karla Kerlikowske, John T. Schousboe, Ellen S. O'Meara, Dejana Braithwaite. Function-related indicator and outcomes of screening mammography in older women from the BCSC-Medicare Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2531.