Competing Risk Cox Regression Research Articles

Abstract 2227: Physical activity at breast cancer diagnosis and incident cardiovascular disease in the Pathways Study

Abstract Background: Breast cancer survivors are at increased risk of cardiovascular disease (CVD) compared to women without a history of breast cancer. Although cardiotoxic cancer treatments influence these risks, lifestyles that are associated with both breast cancer and CVD also contribute. With the number of breast cancer survivors expected to increase, a growing need exists to identify modifiable risk factors that protect against the development of CVD after diagnosis. Physical activity at breast cancer diagnosis is associated with lower cancer recurrence and mortality risk. However, associations between physical activity at diagnosis and incident CVD have yet to be investigated in detail. Methods: The Pathways Study is a prospective cohort study of 4,504 women who were members of Kaiser Permanente Northern California (KPNC) when diagnosed with first primary invasive breast cancer between 2005 and 2013. At enrollment, women self-reported their frequency, duration, and intensity of physical activities during the previous six months using the Arizona Activity Frequency Questionnaire. This information was used to dichotomize the women’s physical activity levels by the CDC’s Physical Activity Guidelines for Americans (≥ 150 minutes of moderate-to-vigorous physical activity per week vs less). CVD events were obtained from electronic health records as part of the Pathways Heart Study and were defined as post-diagnostic incidence of ischemic heart disease, heart failure, cardiomyopathy, and stroke. Deaths were documented through several sources, including the National Death Index. Women were followed until the first of disenrollment from the KPNC health plan, death, or December 31, 2021. Competing risk Cox regression models were used to estimate associations between meeting CDC physical activity guidelines and CVD. Results: In this cohort of breast cancer survivors, women who self-reported meeting physical activity guidelines at diagnosis experienced lower rates of post-diagnostic CVD events (8.6% vs 13.1%). After adjustment for socio-demographic factors, meeting physical activity guidelines remained associated with lower risk of CVD (HR: 0.78, 95% CI: 0.61, 0.98); this association appeared to be driven by reduced risk of heart failure (HR: 0.68, 95% CI: 0.50, 0.93) and cardiomyopathy (HR: 0.51, 95% CI: 0.28, 0.92). Approximately 15% of the CVD risk reduction in Pathways Study participants can be attributed to meeting physical activity guidelines (population attributable risk percent: 14.5%, 95% CI: 8%, 21%). Conclusions: Compared to women who did not meet CDC physical activity guidelines, women who reported meeting guidelines near the time of their breast cancer diagnosis had decreased risk of future CVD, including heart failure and cardiomyopathy. Future studies investigating changes in post-diagnostic physical activity patterns and CVD risk are warranted. Citation Format: Jacob K. Kresovich, Alicia R. Richards, Isaac J. Ergas, Cecile A. Laurent, Rikki Cannioto, Jamal S. Rana, Janise M. Roh, Catherine Thomsen, Salma Shariff-Marco, Eileen Rillamas-Sun, Richard K. Cheng, Song Yao, Christine B. Ambrosone, Lawrence H. Kushi, Heather Greenlee, Marilyn L. Kwan. Physical activity at breast cancer diagnosis and incident cardiovascular disease in the Pathways Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2227.

Upper Urinary Tract Urothelial Cancer After Radical Cystectomy for Bladder Cancer: Survival Outcomes After Radical Nephroureterectomy.

Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27-76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11-63 months), and the CSS was 34 months (IQR, 13-132 months). In the multivariable CRR, the factors predictive for CSSafter RNUincluded male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03-5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13-4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33-25.2; p < 0.001). In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender.

Attention‐deficit/hyperactivity disorder in old age and the risk of dementia: A national cohort study in Israel

AbstractBackgroundEvidence of the association between Attention‐Deficit/Hyperactivity Disorder (ADHD) and the risk of dementia is scarce, inconsistent, and subject to potential sources of bias that are as yet unconsidered. Our objective was to examine the association between ADHD and dementia risk.MethodA prospective national cohort study born 1933‐1952, without a dementia diagnosis for two years, were followed up for incident dementia from 2002‐2020. Information was from electronic health records in a healthcare maintenance organization in Israel. ADHD diagnosis was classified as present from the age of the first diagnosis, otherwise absent. Competing risk Cox regression models were fit to quantify the risk of incident dementia with the Hazard Ratio (HR) and their associated 95% Confidence Intervals (CI) with inverse probability weights, age as the underlying time‐scale, unadjusted and, in the primary analysis, adjusted by 18 covariates.ResultOf 110,196 participants aged 50‐70 years in 2002, 56,914 (51.6%) were female. During follow‐up there were a total of 746 (0.7%) cases of ADHD, and 8,339 (7.6%) of incident dementia. The percentage of incident dementia was 13.1% (N = 98) among those with ADHD present and 7.5% (N = 8,241) among those with ADHD absent. In the primary analysis, the group with ADHD was statistically significantly (P&lt;.05) associated with a higher risk of dementia (unadjusted: HR = 3.57, CI = 2.89, 4.42; adjusted HR = 2.73, CI = 2.04, 3.65) compared to the group with ADHD absent. Eight of ten sensitivity analyses replicated the statistically significant association observed in the primary analysis. Psychostimulant medication offset the association between ADHD and dementia risk to null, and evidence of reverse causation was mild.ConclusionADHD is associated with increased dementia risk. Policymakers, caregivers, patients, and clinicians may wish to monitor ADHD in old age reliably.

Types of peripherally inserted central catheters and the risk of unplanned removals in patients: A prospective cohort study

BackgroundPeripherally inserted central catheters are widely used in clinical practice. Despite the many advantages of peripherally inserted central catheters, unplanned removals can occur owing to irreversible complications and may have adverse consequences for patients. However, the relationship between peripherally inserted central catheter type and the incidence of unplanned removal is unclear. ObjectiveTo investigate the association between the type of peripherally inserted central catheter and unplanned catheter removal. DesignA multicenter prospective cohort study. SettingsSixty hospitals located in 30 cities across seven provinces in China. ParticipantsThree thousand two hundred and twenty-two patients aged 18 years or older with one peripherally inserted central catheter inserted for treatment were enrolled, and 3166 (98.3 %) patients with follow-up data were included in the final analysis. MethodsThe included participants had peripherally inserted central catheters that either had a proximal valve (n = 2436) or were open-ended (n = 730). A competing risk Cox regression model was used, and both univariate and multivariate analyses were conducted. A sub-distribution hazard model was applied to test the validity of the results. ResultsOf the 2436 peripherally inserted central catheters with a proximal valve and 730 that were open-ended, 272 (11.2 %) and 46 (6.3 %) were removed unplanned, respectively. The whole incidence of unplanned removal was 10.04 %; multivariate Cox regression was conducted and it was determined that unplanned removal was statistically significantly associated with the proximal valve peripherally inserted central catheter type (hazard ratio: 1.86, 95 % confidence interval: 1.28 to 2.70, p = 0.001). In patients without cancer, the risk of unplanned removal of peripherally inserted central catheters with a proximal valve was 8.14 times higher than that of open-ended peripherally inserted central catheters (p < 0.001). ConclusionsIn this study, peripherally inserted central catheters with a proximal valve had a higher risk of unplanned removals, especially in patients without cancer. The peripherally inserted central catheter type should be considered in advance, and clinical staff should take appropriate measures to prevent unplanned removals after insertion.

Prepayment and Default Risks of Mortgage-Backed Security Collateral Pools

Mortgage-backed securities (MBS) are structured financial products that are produced via securitization of mortgage loans. Due to the nature of securitization, all risks of mortgage loans are transferred from originators to MBS investors. Prepayment and default risks of mortgages lead to uncertainty in MBS cash flows and create a complex problem for valuation of these instruments. Therefore, estimating these mortgage termination risks has become the focus of valuation of MBS collateral pools. This study explores two questions by using a publicly open dataset provided by Fannie Mae. First, two machine learning algorithms (Random Forest and Multinomial Logit Regression) are used for classification to predict whether a mortgage loan is likely to be prepaid, defaulted or current. Afterwards, Competing Risks Cox Regression Analysis is performed to see determinants of when mortgage termination risks are likely to happen. It is found that not all mortgage borrowers behave optimally in their prepayment and default decisions. Therefore, in addition to refinancing incentive and negative equity which depend on variations in prevailing mortgage interest rates and housing prices, heterogeneity in mortgage borrowers’ behaviors and loan characteristics, and also local economic factors are significantly important in estimating mortgage termination risks. It is worth noting that prominence role of mortgage payment delinquencies in particularly predicting defaults emphasizes the essential need of monitoring payments by servicers to keep safety of MBS investors and financial markets.

Association of Body Mass Index and Cardiometabolic Factors With Elderly Suicide: A Cohort Study of 101,518 Older Taiwanese

Older people have the highest suicide rate across age groups in most countries. The prevalence of cardiometabolic risk factors also increases with age. We investigated the association between body mass index (BMI), cardiometabolic risk factors, and suicide in a large cohort of older people in Taiwan. We conducted a cohort study using data from an elderly health examination program in Taipei City, Taiwan (2005-2010), linked to the national cause-of-death data files. We used competing risk Cox regression models to investigate the associations of BMI (kg/m2) and cardiometabolic factors with suicide after adjusting for sex, age, socioeconomic variables, chronic diseases, psychological distress, and cognitive function. Among 101,518 individuals aged ≥ 65 years, 92 died by suicide during an average follow-up of 3.9 years. Underweight (BMI<18.5) was associated with increased suicide risk (adjusted hazard ratio [aHR]=2.33, 95% confidence interval [CI] 1.20-4.52) (reference: normal weight). Low diastolic blood pressure was associated with increased suicide risk - aHR was 0.51 (95% CI 0.29-0.91) and 0.55 (95% CI 0.31-0.99) for the third and fourth quartiles of diastolic blood pressure (reference: the lowest quartile), respectively. Older people with a higher waist circumference (aHR per 1-standard-deviation increase=0.60 [95% CI 0.37-0.98]) and a higher number of metabolic syndrome criteria (aHR per 1-criterion increase=0.65 [95% 0.46-0.92]) had lower suicide risk. Systolic blood pressure, pulse rate, fasting blood glucose, and lipid profiles were not associated with suicide risk. Underweight, low diastolic blood pressure, and low waist circumference may be markers of increased suicide risk in older people.

Microwave ablation versus radiofrequency ablation as bridge therapy in potentially transplantable patients with single HCC ≤ 3 cm: A propensity score-matched study

ObjectivesThe efficacy of microwave ablation (MWA) for hepatocellular carcinoma (HCC) as bridge therapy has been gradually confirmed. We aimed to compare the recurrence beyond the Milan criteria (RBM) rates in potentially transplantable patients with HCC receiving MWA or radiofrequency ablation (RFA) as bridge therapy. MethodsIn total, 307 potentially transplantable patients with single HCC ≤ 3 cm who initially received MWA (n = 82) or RFA (n = 225) were included. RBM, recurrence-free survival (RFS), and overall survival (OS) were compared between MWA and RFA groups by using propensity score matching (PSM). Competing risks Cox regression was used to identify predictors of RBM. ResultsAfter PSM, the 1-, 3-, and 5-year cumulative RBM rates were 6.8%, 18.3%, and 39.3% in the MWA group (n = 75), and 7.4%,18.5%, and 27.7% in the RFA group (n = 137), respectively, with no significant difference (p = 0.386). MWA and RFA were not the independent risk factors of RBM, and patients with higher alpha-fetoprotein, non-antiviral treatment, and higher MELD score were at greater risk of RBM. Neither corresponding RFS rates (66.7%, 39.2% and 21.4% vs. 70.8%, 47% and 34.7%, p = 0.310) nor OS rates (97.3%, 88.0%, and 75.4% vs. 97.8%, 85.1%, and 70.7%, p = 0.384) for 1-, 3- and 5-years were significantly different between the MWA and RFA groups. The MWA group showed more frequent major complications (21.4% vs. 7.1%, p = 0.004) and longer hospital stays (4 days vs. 2 days, p < 0.001) compared with the RFA group. ConclusionMWA showed comparable RBM, RFS, and OS rates to RFA in potentially transplantable patients with single HCC ≤ 3 cm. Compared to RFA, MWA might provide the same effect as bridge therapy.

PD29-05 ASSOCIATION OF AGE WITH NON-MUSCLE INVASIVE BLADDER CANCER: A BIOLOGICAL BASIS FOR EPIDEMIOLOGICAL DISPARITIES?

You have accessJournal of UrologyCME1 Apr 2023PD29-05 ASSOCIATION OF AGE WITH NON-MUSCLE INVASIVE BLADDER CANCER: A BIOLOGICAL BASIS FOR EPIDEMIOLOGICAL DISPARITIES? Niyati Lobo, Akshay Sood, Zhigang Duan, Wei Shen Tan, Valentina Grajales, Sia Viborg Lindskrog, Lars Dyrskjøt, Aarhus, Denmark, Hui Zhao, Sharon Giordano, Stephen B. Williams, and Ashish M. Kamat Niyati LoboNiyati Lobo More articles by this author , Akshay SoodAkshay Sood More articles by this author , Zhigang DuanZhigang Duan More articles by this author , Wei Shen TanWei Shen Tan More articles by this author , Valentina GrajalesValentina Grajales More articles by this author , Sia Viborg LindskrogSia Viborg Lindskrog More articles by this author , Lars DyrskjøtLars Dyrskjøt More articles by this author , Aarhus Aarhus More articles by this author , Denmark Denmark More articles by this author , Hui ZhaoHui Zhao More articles by this author , Sharon GiordanoSharon Giordano More articles by this author , Stephen B. WilliamsStephen B. Williams More articles by this author , and Ashish M. KamatAshish M. Kamat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003315.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Age disparity in patients with non-muscle-invasive bladder cancer (NMIBC) exists. Whether this is due to differences in cancer care or tumour biology is unclear. We sought to investigate age disparities in NMIBC using individual patient-level data from two cohorts: the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and the publicly available UROMOL dataset. METHODS: SEER-Medicare linked data was used to identify patients, aged ≥66 years, with clinical stage Ta, Tis and T1 NMIBC between 2005-2019 (n=32 225). Multivariable competing-risks Cox regression analyses were used to examine the association between age and recurrence (defined as receipt of TURBT ≥3 months after index diagnosis of NMIBC or progression), progression (defined as receipt of definitive treatment for bladder cancer) and bladder cancer-specific mortality rates after adjusting for demographic-, cancer- and treatment-related variables. Using the UROMOL cohort (n=834), age disparities across transcriptomic, genomic and spatial proteomic domains were assessed. Differences between groups were testing using Pearson’s Chi-square test or Fisher’s test for categorical variables. RESULTS: Analysis of the SEER-Medicare cohort revealed 10-year recurrence rates of 60.9%, 61.1% and 60.4% in patients aged 66-70 yrs, 71-80 yrs and ≥81 yrs, respectively; 10-year progression rates of 29.3%, 32.2% and 38.2%, respectively; and 10-year bladder-cancer specific mortality rates of 5.5%, 7.9% and 14.3%, respectively. Age ≥ 81 yrs was associated with a higher risk of progression (HR 1.32, 95% CI 1.25-1.40, p<0.001) and bladder cancer-specific mortality (HR 2.58, 95% CI 2.27-2.95, p<0.001). Analysis of UROMOL 2021 transcriptomic classes revealed that Class 2a was more frequently observed in older patients (34% in >75 yrs vs. 22% in ≤65 yrs; p=0.004). Compared to patients <65 yrs, those aged >75 yrs were more likely to have TP53 pathway change (54% vs. 38%; p=0.032). UROMOL genomic class 3 was more frequently observed in patients >75 yrs (42% vs. 24%; p=0.001), who also had higher amounts of altered genome (median: 337.7Mb vs. 168.2Mb; p<0.001). No significant differences were observed in immune cell infiltration scores between age groups. CONCLUSIONS: Among SEER-Medicare patients with NMIBC, advanced age is associated with higher risks of progression and bladder-cancer specific mortality. These results reflect age-related molecular biological differences observed across transcriptomic and genomic domains. Source of Funding: Niyati Lobo was supported by The Urology Foundation-Fulbright Scholar Award © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e826 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Niyati Lobo More articles by this author Akshay Sood More articles by this author Zhigang Duan More articles by this author Wei Shen Tan More articles by this author Valentina Grajales More articles by this author Sia Viborg Lindskrog More articles by this author Lars Dyrskjøt More articles by this author Aarhus More articles by this author Denmark More articles by this author Hui Zhao More articles by this author Sharon Giordano More articles by this author Stephen B. Williams More articles by this author Ashish M. Kamat More articles by this author Expand All Advertisement PDF downloadLoading ...

Radiation after radical prostatectomy in elderly patients - a SEER database-derived competing-risk survival analysis of propensity score-matched age groups.

This study aimed to evaluate cancer-specific (CSM) and other-cause mortality (OCM) in elderly patients with prostate cancer treated with radical prostatectomy (RP) and postoperative radiotherapy (RT). The Surveillance, Epidemiology, and End Results (SEER) database was searched for clinically non-metastatic prostate cancer (PCa) treated with RT after RP between 2010 and 2015. Patients were stratified according to age groups and underwent propensity score (PS) matching. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for survival analysis. In total, 5385 patients were analysed, including 738 (13.7%) elderly patients (≥70 years old) and 4647 (86.29%) younger individuals. A total of 54 (7.32%) and 69 (9.35%) patients aged ≥70 years died due to PCa and competing reasons, respectively. Among younger patients these included 275 (5.92%) and 208 (4.48%) deaths, respectively. At a median follow-up of 80 months, patients ≥70 years old had significantly shorter OCM (p <0.0001) than PS-matched younger controls without significant impairment of cancer-specific survival when compared to controls (p = 0.19). In CRR analysis older patients were at significantly higher risk of OCM (HR = 2.24, p = 0.0002 and HR = 3.3, p = 0.011 for patients aged ≥70 and ≥75 years, respectively). Simultaneously, the CRR revealed no increased risk of CSM for patients older than 70 and 75 years (HR = 1.2, p = 0.33 and HR = 1.53, p = 0.29, respectively). Elderly patients with PCa are at high risk of dying due to competing reasons, which might prevent the survival benefit of RT after RP. Selection for salvage and adjuvant RT in these individuals should be cautious.

Are Undernutrition and Obesity Associated with Post-Discharge Mortality and Re-Hospitalization after Hospitalization with Community-Acquired Pneumonia?

Undernutrition is associated with increased mortality after hospitalization with community-acquired pneumonia (CAP), whereas obesity is associated with decreased mortality in most studies. We aimed to determine whether undernutrition and obesity are associated with increased risk of re-hospitalization and post-discharge mortality after hospitalization. This study was nested within the Surviving Pneumonia cohort, which is a prospective cohort of adults hospitalized with CAP. Patients were categorized as undernourished, well-nourished, overweight, or obese. Undernutrition was based on diagnostic criteria by the European Society for Clinical Nutrition and Metabolism. Risk of mortality was investigated using multivariate logistic regression and re-hospitalization with competing risk Cox regression where death was the competing event. Compared to well-nourished patients, undernourished patients had a higher risk of 90-day (OR 3.0, 95% CI 1.0; 21.4) mortality, but a similar 30-day and 180-day mortality risk. Obese patients had a similar re-hospitalization and mortality risk as well-nourished patients. In conclusion, among patients with CAP, undernutrition was associated with increased risk of mortality. Undernourished patients are high-risk patients, and our results indicate that in-hospital screening of undernutrition should be implemented to identify patients at mortality risk. Studies are required to investigate whether nutritional therapy after hospitalization with CAP would improve survival.

Proton Therapy for Uveal Melanoma: A Single-Institution Experience

<h3>Purpose/Objective(s)</h3> Uveal melanoma (UM) is the most common intraocular malignancy in adults. Eye-preserving approaches like episcleral plaque brachytherapy are common but limited in patients (pts) with large tumors or those adjacent to the optic nerve. Proton therapy (PT) offers an alternative eye-preserving treatment option. We report a single-institution experience utilizing PT to treat UM. We hypothesized that PT would provide excellent local control (LC) and eye preservation (EP) with acceptable toxicity and visual outcomes across all patients, including those with large tumors in adverse locations. <h3>Materials/Methods</h3> We reviewed the records of treatment-naive pts who received PT for non-metastatic UM between June 2012 and December 2020. All pts had ≥ 6 months of follow-up. Treatment planning was performed in EyePlan (Clatterbridge, UK) based on eye/tumor measurements and 3-4 implanted scleral fiducial markers, registered fundus photographs, and confirmed by CT/MRI. Pts were set-up in a seated position with gaze fixation and real-time image guidance using a single en face beam to a total 50-60 Gy RBE in 4-5 consecutive daily fractions. We estimated disease control and survival, including LC, EP, distant metastasis-free survival (DMFS), cause-specific survival (CSS), overall survival (OS), and grade 3+ toxicity as defined by CTCAEv5 using the cumulative incidence method. Regression of multiple variables simultaneously was accomplished with competing-risks Cox regression. <h3>Results</h3> 120 pts met inclusion criteria; 33 had a biopsy of their lesion; 9.2% were class 2. Moreover, 47.5% had COMS medium while 35.8% had large tumors. Median tumor thickness was 5.0 mm (0.5 – 13.0) and median basal dimension was 13.0 mm (4.0 – 25.0). Median distance to the fovea and optic disc was 3.5 mm. 38% had retinal detachment with 47% having significantly impaired visual acuity at baseline (worse than Snellen 20/40). 98.3% received 60 Gy RBE over 4 daily fractions. Median follow-up was 31 months (6 – 104). The 2-year estimates (95% CI) for LC, EP, DMFS, CSS, and OS were 94% (88-97%), 95% (90-98%), 88% (81-93%), 94% (88-97%), and 90% (83-95%), respectively. 9 pts underwent enucleation following PT (5 for recurrent/persistent disease). Retinopathy (5%), neovascular glaucoma (3.3%), and optic nerve disorder (2.5%) were the most common severe toxicities. 60% of toxicity resolved during follow-up. 38% had functional vision (20/40 or better) at last follow-up. Pretreatment visual acuity had a substantial impact on post-treatment vision. Tumor size was an independent prognostic factor for OS (p=0.01), CSS (p<0.01), EP (p=0.02), and DMFS (p<0.01). No prognostic factor was associated with LC. <h3>Conclusion</h3> Our experience using PT for UM is consistent with previously reported outcomes demonstrating high rates of LC and EP with acceptable toxicity despite a significant percentage of patients with large tumors and/or adverse location near the optic nerve.

Associations between patient and disease characteristics and severe adverse events during immune checkpoint inhibitor treatment: An observational study

AimWith increasing use of immune checkpoint inhibitors (ICIs) more patients will develop severe and potentially life-threatening immune-related adverse events (irAEs). So far, predictive models for the occurrence of grade ≥3 irAEs are lacking. Therefore, we analysed associations between patient and disease characteristics, and the occurrence of grade ≥3 irAEs. MethodsPatients with cancer who were treated with anti-PD-1 (+/−anti-CTLA-4) between July 2015 and February 2020, and who were prospectively included in the MULTOMAB-trial, were eligible for this cohort study. Time to and occurrence of grade ≥3 irAEs according to CTCAE v5.0 were retrospectively registered. The associations between patient and disease characteristics and irAE occurrence were analysed using the competing risk cox-regression model of Fine and Gray. Analyses were performed separately in patients treated with monotherapy (anti-PD-1) and combination therapy (anti-PD-1 + anti-CTLA-4). Subgroup analyses were performed in tumour types with the highest number of patients; melanoma and NSCLC. ResultsOut of 641 patients, 106 patients (17%) experienced grade ≥3 irAEs. None of the analysed factors were associated with grade ≥3 irAE occurrence in the monotherapy (n = 550) or the combination therapy (n = 91) groups, nor in the subgroup analyses. Of interest, none of the patients with NSCLC with a WHO performance status of 0 (n = 34) experienced grade ≥3 irAEs. Most common NSCLC histology types were adenocarcinoma (n = 99/55%) and squamous cell carcinoma (n = 39/22%). Concluding statementThis study shows that patient and disease characteristics are not able to predict the occurrence of serious AEs in patients treated with ICIs.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

Background & AimsInformation about the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population.MethodsMulticentre retrospective, cross‐sectional, international study of liver cancer patients with SARS‐CoV‐2 infection registered between February and December 2020. Clinical data at SARS‐CoV‐2 diagnosis and outcomes were registered.ResultsTwo hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS‐CoV‐2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow‐up of 7.20 (IQR: 1.84–11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS‐CoV‐2‐related. Forty (18.4%) HCC patients died within 30‐days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24–12.74], 11.76% [95% CI 4.73–22.30], 20.69% [95% CI 11.35–31.96] and 34.52% [95% CI 17.03–52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49–4.31; p = .5032) in BCLC‐B versus 0/A, and 3.13 (95% CI 1.29–7.62; p = .0118) in BCLC‐C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS‐CoV‐2 infection.ConclusionsThis is the largest cohort of liver cancer patients infected with SARS‐CoV‐2. It characterizes the 30‐day mortality risk of SARS‐CoV‐2 infected patients with HCC during this period.

Association between Body Mass Index and Renal Outcomes Modified by Chronic Kidney Disease and Anemia: The Obesity Paradox for Renal Outcomes.

Obesity-related nephropathy is associated with renal function progression. However, some studies have associated a high body mass index (BMI) with improved renal outcomes—this is referred to as the obesity paradox for renal outcomes, especially in relation to advanced chronic kidney disease (CKD). Central obesity can explain the obesity paradox in all-cause mortality. However, whether obesity or central obesity is associated with renal outcomes (renal replacement therapy or a 50% decline in the estimated glomerular filtration rate) in patients with advanced CKD remains unclear. Our study included 3605 Asian patients with CKD stages 1–5 divided into six groups according to their BMI (between 15 and 35 kg/m2). Through linear regression, BMI was positively associated with hemoglobin and albumin at CKD stages 4 and 5. In the competing risk Cox regression model, a high BMI (27.5–35 kg/m2) was associated with renal outcomes at CKD stages 1–3, but not stages 4 and 5. A high BMI was associated with renal outcomes in patients with hemoglobin ≥11 g/dL, but not <11 g/dL. A high waist-to-hip ratio was not associated with renal outcomes. We conclude that the CKD stage and anemia may explain the obesity paradox in renal outcomes in patients with CKD.

Low Intestinal IL22 Associates With Increased Transplant-Related Mortality After Allogeneic Stem Cell Transplantation.

The role of IL-22 in adult patients undergoing allogeneic stem cell transplantation (SCT) is of major interest since animal studies showed a protective and regenerative effect of IL-22 in graft versus host disease (GvHD). However, no clinical data exist on the tissue expression. Here we demonstrate that patients not suffering from transplant-related mortality (TRM) show significantly upregulated IL22 expression during histological and clinical GI-GvHD (p = 0.048 and p = 0.022, respectively). In contrast, in GvHD patients suffering from TRM, IL22 was significantly lower (p = 0.007). Accordingly, lower IL22 was associated with a higher probability of TRM in survival analysis (p = 0.005). In a multivariable competing risk Cox regression analysis, low IL22 was identified as an independent risk factor for TRM (p = 0.007, hazard ratio 2.72, 95% CI 1.32 to 5.61). The expression of IL22 seemed to be microbiota dependent as broad-spectrum antibiotics significantly diminished IL22 expression (p = 0.019). Furthermore, IL22 expression significantly correlated with G-protein coupled receptor (GPR)43 (r = 0.263, p = 0.015) and GPR41 expression (r = 0.284, p = 0.009). In conclusion, our findings reveal an essential role of IL22 for the prognosis of patients undergoing allogeneic SCT.

Optimized medial unicompartmental knee arthroplasty outcome: learning from 20 years of propensity score matched registry data.

Background and purposeUnicompartmental knee arthroplasty (UKA) has increased in use. We investigated changes to UKA revision risk over the last 20 years compared with total knee arthroplasty (TKA), examined external and patient factors for correlation to UKA revision risk, and described the survival probability for current UKA and TKA practice.Patients and methodsAll knee arthroplasties reported to the Danish Knee Arthroplasty Register from 1997 to 2017 were linked to the National Patient Register and the Civil Registration System for comorbidity, emigration, and mortality information. All primary UKA and TKA patients with primary osteoarthritis were included and propensity score matched 4 TKAs to 1 UKA. Revision and mortality were analyzed using competing risk cox regression with a shared gamma frailty component.ResultsThe matched cohort included 48,195 primary knee arthroplasties (9,639 UKAs). From 1997–2001 to 2012–2017 the 3-year hazard ratio decreased from 5.5 (95% CI 2.7–11) to 1.5 (CI 1.2–1.8) due to increased UKA survival. Cementless fixation, a high percentage usage of UKA, and increased surgical volume decreased UKA revision risk, and increased in occurrence parallel to the decreasing revision risks. Current UKA practice using cementless fixation at a high usage unit has a 3-year implant survival of 96% (CI 97–95), 1.1% lower than current TKA practice.InterpretationUKA revision risk has decreased over the last 20 years, nearing that of TKA surgery. High usage rates, surgical volume, and the use of cementless fixation have increased during the study and were associated with decreased UKA revision risks.

Effect of chemotherapy and radiotherapy on cognitive impairment in colorectal cancer: evidence from Korean National Health Insurance Database Cohort.

OBJECTIVESWe investigated the risk of chemotherapy-related and radiotherapy-related cognitive impairment in colorectal cancer patients.METHODSMedical use data of colorectal cancer patients were obtained from the Korean National Health Insurance Database from 2004 to 2018. We randomly selected 40% of all colorectal cancer patients (n=148,848). Cognitive impairment was defined as having 1 or more International Classification of Diseases, 10th revision diagnostic codes for dementia or mild cognitive impairment. Patients aged 18 years or younger, patients diagnosed with cognitive impairment before colorectal cancer diagnosis (n=8,225), and patients who did not receive primary resection (n=45,320) were excluded. The effects of individual chemotherapy regimens on cognitive impairment were estimated. We additionally estimated the effect of radiotherapy in rectal cancer patients. Time-dependent competing risk Cox regression was conducted to estimate the overall and age-specific hazard ratios (HR) separately for colon and rectal cancer. Landmark analyses with different lag times were conducted as sensitivity analyses.RESULTSChemotherapy did not increase the risk of cognitive impairment in colorectal cancer patients (colon cancer: HR, 0.92; 95% confidence interval [CI], 0.83 to 1.03; rectal cancer: HR, 0.88; 95% CI, 0.75 to 1.04), while radiotherapy was negatively associated with cognitive impairment in rectal cancer patients (HR, 0.01; 95% CI, 0.84 to 0.99). Varying directions of the associations between regimens and cognitive impairment were detected. The adverse effect of certain chemotherapy regimens on cognition was more prominent in older adults.CONCLUSIONSChemotherapy and radiotherapy did not increase the risk of cognitive impairment. Older patients with low cognitive reserve could be affected by the adverse cognitive effects of chemotherapy.

Coronary artery disease and cardiovascular outcomes in patients with type 2 myocardial infarction

Abstract Purpose To evaluate the role of coronary disease in predicting adverse cardiovascular events in patients with type 2 myocardial infarction. Background Type 2 myocardial infarction occurs due to imbalance in myocardial oxygen supply or demand without atherothrombosis. There is currently no consensus on how patients with type 2 myocardial infarction should be investigated or treated. Although non-cardiovascular mortality is common in this population, the incidence of future cardiovascular events is similar to those with myocardial infarction due to plaque rupture. Observational data suggest patients with type 2 myocardial infarction and underlying coronary artery disease may be at higher risk of cardiovascular events, but to date, most findings have been observed in selected rather than consecutive patient cohorts. Methods We conducted a secondary analysis of a multi-centre randomised controlled trial of 48,282 consecutive patients attending hospital with suspected acute coronary syndrome. In 9,115 patients, high-sensitivity cardiac troponin concentrations were &amp;gt;99th centile, and the diagnosis was adjudicated in line with the Fourth Universal Definition. Patients with type 2 myocardial infarction were stratified by the presence of previous coronary artery disease and evaluated for a primary outcome of cardiovascular death or Type 1 or 4b myocardial infarction at one year. Competing risk cox regression models were used to evaluate predictors of the primary outcome selected a priori on the basis of clinical importance, with adjustment for the competing risk of non-cardiovascular death. Results The diagnosis of type 1 and type 2 myocardial infarction was made in 55% (4,981) and 12% (1,121) of patients, respectively. Compared to patients without a previous diagnosis of coronary artery disease, those with coronary disease were older (78 vs 71) and more likely to be female (54% vs 46%). The incidence of future cardiovascular death or myocardial infarction was highest in patients with type 2 myocardial infarction and previous coronary disease (20%, 91/454), compared to those with type 2 myocardial infarction without known coronary disease (10%, 69/667, P&amp;lt;0.001), and was similar to patients with type 1 myocardial infarction (17%, 863/4981, Figure 1). After adjusting for cardiovascular risk factors, the presence of known coronary disease remained an important predictor for future cardiovascular death or myocardial infarction (adjusted Hazard Ratio 1.45, 95% confidence interval 1.03 to 2.03; Figure 2). Conclusion Coronary artery disease is an independent predictor of cardiovascular outcomes in patients with type 2 myocardial infarction. Further research is required to evaluate whether systematic investigation for coronary artery disease and targeted secondary prevention could improve outcomes in patients with type 2 myocardial infarction. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Figure 1Figure 2

Longitudinal Outcomes from Conservative Management of Cervical Cancer Associated Ureteral Obstruction

To identify predictors of hydronephrosis (HN) resolution and HN treatment failure. HN is a common comorbid condition with cervical cancer (CCa). Treatments for CCa continue to improve and long-term management strategies of HN are becoming increasingly necessary. A query of a single hospital (2004 - 2019) ICD-9 and CPT codes was made to develop a cohort of CCa patients with HN. A retrospective review was performed. The effects of patient, renal/HN, and cancer covariates on time to HN treatment failure, treatment complications and time to HN resolution were evaluated using logistic regression and competing risk Cox regression models. Of the 1670 women treated for CCa during the study period, 179 (10.7%) developed HN (n=72 (40%) bilateral), 78 (44%) at time of CCa diagnosis and 101 (56%) as a result of treatment, of which 145 (81%) underwent initial treatment with a PCN (n=77, 53%) or US (n=68, 47%). Complication rates were similar between PCN (56%) and US (61%) when adjusting for treatment time. Initial treatment failure was more likely with US vs PCN (HR 3.2, P <0.01). HN resolution (n=32, 22%) without reconstruction was predicted by HN concurrent with CCa diagnosis (HR 3.1, P <0.01) and bilateral HN (HR 0.2, P <0.01). CCa associated HN has a resolution rate of only 19% at 12 months. Those presenting with HN after CCa treatment are less likely to resolve without reconstruction. PCN and US have similar complication rates but initial US placement has a nearly three times increased risk of failing than PCN.

MP25-20 NATURAL HISTORY OF CERVICAL CANCER ASSOCIATED URETERAL OBSTRUCTION

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP25)1 Sep 2021MP25-20 NATURAL HISTORY OF CERVICAL CANCER ASSOCIATED URETERAL OBSTRUCTION Hannah E. Botkin, Kathryn N. Faidley, Sarah L. Mott, Bradley T. Loeffler, Emily K. Hill, and Bradley A. Erickson Hannah E. BotkinHannah E. Botkin More articles by this author , Kathryn N. FaidleyKathryn N. Faidley More articles by this author , Sarah L. MottSarah L. Mott More articles by this author , Bradley T. LoefflerBradley T. Loeffler More articles by this author , Emily K. HillEmily K. Hill More articles by this author , and Bradley A. EricksonBradley A. Erickson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002022.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The proximity of the cervix to the trigone makes hydronephrosis (HN) a common comorbid condition with cervical cancer (CCa). Treatments for CCa continue to improve and accordingly, long-term management strategies of ureteral obstruction are becoming increasingly necessary. Here, we report the natural history of treated and untreated HN associated with CCa and identify predictors of HN resolution, HN management complications and treatment failures. METHODS: We queried a single university hospital's (2004-2019) ICD-9 (CCa, HN) and CPT (ureteral stent (US), percutaneous nephrostomy (PCN)) codes to develop a cohort of CCa patients with comorbid HN. An EPIC/Care Everywhere retrospective review was performed focusing on HN management outcomes, complications (requiring intervention) and resolution time. The effects of patient, renal/HN, and cancer covariates on time to initial HN treatment failure, treatment complications and time to HN resolution were evaluated using logistic regression and competing risk Cox regression models. Time-dependent treatment covariates were included. RESULTS: Of the 1670 women treated for CCa during the study period, 179 (10.7%) developed HN (n=72 (40%) bilateral); 78 (44%) at time of CCa diagnosis and 101 (56%) as a result of treatment. 145 (81%) underwent initial treatment; 77 (53%) with a PCN and 68 (47%) with US. Overall complication rates were similar between PCN (56%) and US (61%) when adjusting for treatment time (p=0.67), the most common being infection (29 v 27%), dysuria (19 v 30%) and hematuria (24 v 22%). Initial treatment failure was more likely with US v PCN (HR 3.2, p <0.01) (Figure 1). HN resolution (n=32, 22%) without reconstruction was predicted by HN concurrence with CCa diagnosis (HR 3.1, p <0.01) and bilateral HN (HR 0.2, p<0.01). CONCLUSIONS: CCa associated HN has a resolution rate of only 19% at 12 months (Figure 2). Those presenting with HN after CCa treatment are less likely to resolve without reconstruction. PCN and US have similar complication rates but initial US placement has a nearly three times increased risk of failing than PCN. Source of Funding: NA © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e461-e461 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hannah E. Botkin More articles by this author Kathryn N. Faidley More articles by this author Sarah L. Mott More articles by this author Bradley T. Loeffler More articles by this author Emily K. Hill More articles by this author Bradley A. Erickson More articles by this author Expand All Advertisement Loading ...