Fine-Gray Competing Risk Regression Research Articles

The Association Between Illicit Drug Use and the Duration of Renal Replacement Therapy in Patients With Acute Kidney Injury From Severe Rhabdomyolysis.

Background and Aims: Acute kidney injury is a known complication of severe rhabdomyolysis. In patients who present to hospital with rhabdomyolysis, illicit drug use is associated with a higher risk of acute kidney injury needing renal replacement therapy (RRT), independent of the peak serum creatine kinase level. The aim of this study was to assess if RRT duration and renal outcomes were also worse in illicit drug use-associated rhabdomyolysis.Methods: We conducted a cohort study of adult patients who presented to Monash Health (Jan 2011–June 2020) with rhabdomyolysis and required RRT. Patients with isolated myocardial injury and cardiac arrest were excluded. We used survival analysis to examine the time to RRT independence, utilizing the Fine-Gray competing risks regression and death as the competing event. A subdistribution hazard ratio (SHR) < 1.0 represents a relatively greater duration of RRT and a worse outcome.Results: We included 101 patients with a mean age of 58 years, of which 17% were cases associated with illicit drug use. The median peak creatine kinase level was 5,473 U/L (interquartile range, 1,795–17,051 U/L). Most patients (79%) initiated RRT within 72 h of admission, at a median serum creatinine of 537 μmol/L (interquartile range, 332–749 μmol/L). In the competing risks analysis, the estimated SHR was 1.48 (95% CI: 0.78–2.84, P = 0.23) for illicit drug use, 0.87 (95% CI: 0.76–0.99, P = 0.041) for the log-transformed peak creatine kinase, and 0.41 (95% CI: 0.25–0.67, P < 0.001) for sepsis. A 50% cumulative incidence of RRT independence occurred at 11 days (95% CI: 8–16 days). Only 5% of patients remained on RRT at 3 months.Conclusion: In rhabdomyolysis-associated acute kidney injury, it is unlikely that patients with illicit drug use-associated rhabdomyolysis require a longer duration of RRT compared to patients with rhabdomyolysis from other causes.

125I Interstitial Brachytherapy with or without Androgen Deprivation Therapy among Unfavorable Risk Prostate Cancer

To determine if patients (pts) with unfavorable-intermediate risk (UIR), high risk (HR), or very high risk (VHR) prostate cancer (PCa) treated with 125I brachytherapy benefit from androgen deprivation therapy (ADT). We reviewed an institutional database of pts with UIR, HR, or VHR PCa (per NCCN v4.2019) treated with definitive 125I interstitial brachytherapy with or without ADT from 1998-2017. Men treated with external beam radiation were excluded. Outcomes, including biochemical failure (bF), distant metastases (DM), and overall survival (OS) were analyzed with the Kaplan Meier method and Cox proportional hazards regression. PCa specific mortality (PCSM) was analyzed with Fine-Gray competing risk regression. P values <.05 were considered statistically significant. Of 1033 pts, 262 (25%) received ADT and 771 (75%) did not. Median duration of ADT was 6 months (standard deviation [SD], 3.5 months). By risk group, 764 (74%) pts had UIR PCa, 219 (21%) HR, and 50 (5%) VHR. ADT was more likely to be given to pts with HR (50%) and VHR (56%) PCa, compared to UIR (16%; p<.001). There was corresponding greater use of ADT with increasing PSA (p<.001) and Grade Group (p<.001). Pts who were older were more likely to receive ADT (median 70 years [yrs]; SD, 7.7 v median 68 yrs; SD, 7.3; p<.001). Median follow up was 4.9 yrs (range, 0.3-17.6 yrs). On univariable analysis, ADT usage was associated with worse OS (10 yr OS, 63.6% [95% CI, 54.2-73.0%) with ADT v 74.7% [68.0-81.4%] without ADT; p = .036), but there were no differences in bF, DM, or PCSM (p≥.05 each). On multivariable analysis (MVA; Table) adjusting for risk group, age, and year of treatment, ADT was not associated with bF, DM, PCSM, or OS (p≥.05 each). When stratified by risk group, ADT usage was not associated with improved bF, DM, PCSM, or OS for UIR, HR, or VHR PCa (p≥.05 each). Among pts with UIR, HR, or VHR PCa, the addition of short-term ADT to 125I brachytherapy was not associated with improved outcomes in any subgroup. Our findings do not support the use of short-term ADT in combination with 125I interstitial brachytherapy. Additional analysis is required to determine if ADT was associated with worse survival when accounting for comorbidities and cause of death, such as cardiac death.Abstract 4122; TableMVAbFDMPCSMOSHR (95% CI)pHR (95% CI)pHR (95% CI)pHR (95% CI)pADT no v yes1.03 (.74-1.44).851.39 (.86-2.25).18.92 (.31-2.67).881.03 (.70-1.51).88Risk GroupHR v UIR2.20 (1.59-3.03)<.0011.96 (1.23-3.13).0051.79 (.58-5.50).311.33 (.88-2.020.17VHR v UIR2.82 (1.57-5.07)<.0015.01 (2.48-10.11)<.0018.00 (2.23-28.67).0013.93 (2.22-6.96)<.001VHR v HR1.29 (.72-2.29).402.56 (1.27-5.15).0094.47 (1.38-14.55).0132.95 (1.64-5.29)<.001Age.99 (.97-1.01).271.01 (0.98-1.04).411.06 (1.00-1.13).071.08 (1.06-1.11)<.001Yr of Treatment1.02 (098-1.06).371.08 (1.01-1.14).018.93 (.83-1.04).20.97 (.92-1.02)0.22 Open table in a new tab

Association Between T-Stage and Cancer-Specific Mortality among Men with High-Risk Prostate Adenocarcinoma

Risk group stratification identifies men with high-risk prostate adenocarcinoma (Gleason 8-10, PSA > 20 ng/mL, or cT3-T4) who benefit from more intense treatment. However, many patients are classified as high-risk with only one high-risk feature. Although many trials that are the basis for 2-3 years of androgen deprivation therapy (ADT) studied patients with mostly cT3/T4 disease, PSA-detected, non-palpable T1c disease is currently the most commonly detected. We assessed whether within localized high-risk prostate cancer, survival differences existed based on T-stage. Data from men with high-risk N0M0 prostate adenocarcinoma from the 2004 to 2015 Surveillance, Epidemiology, and End Results database were used. Ten-year PCSM was estimated using Fine-Gray competing-risk regression. The independent variable of interest was clinical T-stage (cT1/2 vs. cT3/4); adjustments were made for PSA, Gleason score, treatment with radical prostatectomy (RP) and radiation (RT), and relevant demographic factors. A second analysis assessed PCSM only among men who received RP, with pathologic T-stage as co-variate (pT2 vs. pT3/4). The average of 12 prostate cancer prognostic signatures, including Decipher prostate cancer signature, compared genomic risk score by pT-stage. For 63,319 men included (median follow-up 6.4 years, median age 68 years), 56,322 (89.0%) had cT1/2, and 6,997 (11.1%) had cT3/4 disease. Ten-year PCSM for men with cT1/2 disease was 12.5%, and for men with cT3/4 disease was 17.5% (competing risk regression HR 0.55, 95CI 0.51—0.60, P<0.001). Greater PSA and greater Gleason score were associated with greater PCSM; receipt of RP, RT, being married, greater income, and later year of diagnosis were associated with lower PCSM. African American and Other race were also associated with lower PCSM. Of the 20,409 men who received radical prostatectomy, 9,953 (48.8%) had pT2 disease and 10,456 (51.2%) had pT3/4 disease. Ten-year PCSM for post-RP men with pT2 disease was 3.5%, and for men with pT3/4 disease was 11.9% (competing risk regression HR 0.29, 95CI 0.24—0.35, P<0.001). Greater PSA, Gleason score, receipt of radiation, and earlier year of diagnosis were associated with worse PCSM. Within a high-risk prospective RP cohort (n = 10,419) from the Decipher GRID registry (NCT02609269), patients with pT3/4 had significantly higher genomic risk scores than patients with pT2 (p<0.001). Men with cT1/2 disease had improved cancer-specific outcomes compared to men with cT3/4. Among men treated with RP, pT2 disease was associated with lower PCSM compared to pT3/4. Genomic risk scores validated these findings. Therefore, treatment paradigms given clinically relevant sub-classification of high-risk tumors based on size merit further study, with a focus on shorter-duration ADT among men with high-risk but T1/2 disease. As cT1c disease is most commonly diagnosed, more men with smaller tumors should be included in trials.

Characteristics of Radiation-Associated Bladder Cancer Compared To Primary Bladder Cancer

Radiation-associated muscle-invasive bladder cancer (RA-MIBC) has been suggested to represent a more aggressive disease variant compared to primary (non-radiation associated) MIBC. We sought to characterize the presentation, patterns of care, and outcomes of RA-MIBC compared to primary MIBC. We identified 60,117 patients diagnosed with non-metastatic or metastatic MIBC between 1988 and 2015 using the Surveillance, Epidemiology, and End Results (SEER) database and stratified patients based on whether radiation had been administered to a pelvic primary prior to the development of bladder cancer. We used logistic regression to compare rates of chemotherapy, surgery, or radiation for patients with RA-MIBC compared to primary MIBC. We used Fine-Gray competing risks regression to compare adjusted bladder cancer-specific mortality (BCSM) for RA-MIBC compared to primary MIBC. There were 1,093 patients with RA-MIBC and 59,024 patients with primary MIBC. Patients with RA-MIBC were older compared to patients with primary MIBC (mean age 77.4 years vs 72.4 years, p < 0.001) and more likely to be male (86.8% vs 73.3%, p<0.001). RA-MIBCs were more likely to be high-grade (57.5% vs 47.6%, p<0.001) more likely to have T4 disease at diagnosis (21.0% vs 17.3%, p<0.001), and less likely to be node-positive (4.2% vs 8.1%, p < 0.001). In terms of treatment, primary MIBC patients with non-metastatic disease were more likely to undergo radiation (14.0% vs 3.1%, p<0.001) as well as radiation with cystectomy (1.9% vs 0.8%, p<0.001) compared to those with RA-MIBC. Median survival was significantly shorter for patients with RA-MIBC (13 mo. vs 19 mo.; p<0.001). RA-MIBCs tend to present with higher grade and higher stage disease and are less likely to receive curative treatment. Even when adjusting for stage, grade, and receipt of treatment, patients with RA-MIBC have worse survival compared to those with primary MIBC. These findings raise the possibility that RA-MIBC represents a biologically more aggressive disease compared to primary MIBC. Future research is needed to better understand biological differences between RA-MIBC and primary MIBC and develop improved therapeutics for radiation-associated cancers.

Patterns of Clinical Progression in Radiorecurrent High Risk Prostate Cancer and Impact of Initial Treatment Selection

The natural history of radiorecurrent of high-risk prostate cancer (HRPCa) is poorly understood, despite the proportionally higher rates of BCR in this risk group. Treatment HRPCa with external beam radiotherapy (EBRT) plus brachytherapy (BT) boost (EBRT+BT) has been associated with lower rates of BCR, distant metastasis (DM), and PCa-specific mortality (PCSM) compared to EBRT alone. However, it is unclear whether patients who develop BCR following either approach have similar downstream oncologic outcomes. To understand the clinical course of HRPCa patients who develop BCR after initial RT, and to evaluate how initial upfront treatment intensification with EBRT+BT may affect clinical outcomes after BCR compared to initial treatment with EBRT. We identified 706 out of 3820 men with HRPCa treated at 13 institutions from 1998-2015 with EBRT (n=468/2134) or EBRT+BT (n=238/1686) who developed BCR. We compared rates of DM, PCSM, and all-cause mortality (ACM) after BCR between treatment groups using Fine-Gray competing risk regression. Models were adjusted for age, Gleason grade group, initial PSA (iPSA), clinical T stage, time-dependent use of systemic salvage, and interval to BCR using inverse probability of treatment weighting. Two-tailed chi-square testing was used to evaluate the relationship between early BCR (≤3 years from RT) and DM. Median follow-up was 9.9 years from RT and 4.8 years from BCR. Groups were similar in age, iPSA, presence of ≥2 HR features, and median interval to BCR (3.3 years). Most men received neoadjuvant/concurrent androgen deprivation therapy (ADT), 92.5% and 91.0% for EBRT and EBRT+BT, respectively, though for a longer duration with EBRT (median 14.7 vs. 9.0 months, p=0.0012). Early BCR occurred in 44.3% of men and was associated with a higher risk of DM compared to BCR at >3 years (62.0% vs. 36.1%, p < 0.0001). Among all DM events, 60.4% occurred within 1 year of BCR (median 29 days) and 39.6% occurred after 1 year (median 968 days). Local and systemic salvage rates were 2.4% and 37.2% after EBRT, and 3.4% and 42.9% after EBRT+BT, respectively. Initial EBRT+BT was associated with significantly lower rates of DM after BCR (HR 0.48, 95% CI 0.36-0.64, p < 0.001). Rates of PCSM and ACM did not significantly differ (HR 0.93, 95% CI 0.67-1.30, p=0.93, and HR 0.8, 95% CI 0.6-1.1, p=0.11, respectively). In this large retrospective series of radiorecurrent HRPCa, initial treatment with EBRT+BT was associated with significantly lower rates of DM after BCR compared with EBRT, despite shorter ADT use and a similar median interval to BCR. Local salvage was rarely utilized in both groups. Early BCR was associated with increased DM, and though over half of DMs occurred early, there was a sizeable wave of late DMs. In the absence of salvage for local failure after EBRT, upfront treatment intensification with BT may reduce DM, though not PCSM or ACM, even after development of BCR.

Disparities in Mortality from Larynx Cancer: Implications for Reducing Racial Differences.

Race predicts overall mortality (OM) of laryngeal squamous cell carcinoma (LSCC) in the United States (US). We assessed whether racial disparities affect cancer-specific mortality (CSM) using the Surveillance, Epidemiology, and End Results (SEER) database. Adults with LSCC from 2004 to 2015 were selected. Univariable and multivariable Cox proportional hazards and Fine-Gray competing-risks regression analysis adjusted for clinicodemographic factors defined hazard ratios (aHR). We identified 14,506 patients. The median age was 63 years. Most were male (11,725, 80.8%) and white (11,653, 80.3%), followed by Black (2294, 15.8%). Most had early-stage disease (7544, 52.0%) and received radiotherapy only (4107, 28.3%), followed by chemoradiation (3748, 25.8%). With median follow-up of 60 months, overall 3- and 5-year OM were 34.0% and 43.2%; CSM were 16.0% and 18.9%, respectively. Black patients had higher OM than white patients on univariable (HR 1.35, 95% CI, 1.26-1.44, P < .001) and multivariable (aHR 1.10, 95% CI, 1.02-1.18, P = .011) analyses. Black patients had higher CSM on univariable analysis (HR 1.22, 95% CI, 1.09-1.35, P < .001) but not on multivariable CSM analysis (aHR 1.01, 95% CI, 0.90-1.13, P = .864). On multivariable analysis, year of diagnosis, age, disease site, stage, treatment, nodal metastasis, marital status, education, and geography significantly predicted CSM. On multivariable analyses controlling for sociodemographic, clinical, and treatment characteristics, Black and white patients differed in OM but not in CSM. However, Black patients presented with greater proportions of higher stage cancers and sociodemographic factors such as income and marital status that were associated with worse outcomes. Efforts to target sociodemographic disparities may contribute to the mitigation of racial disparities in LSCC. 4 Laryngoscope, 131:E1147-E1155, 2021.

Ethnicity and Insurance-Specific Disparities in the Model for End-Stage Liver Disease Score at Time of Liver Transplant Waitlist Registration and its Impact on Mortality

Disparities in timely referral to liver transplantation (LT) evaluation persist. We aim to examine race/ethnicity and insurance-specific differences in the Model for End-Stage Liver Disease (MELD) score at time of waitlist (WL) registration and its impact on WL survival. We retrospectively evaluated U.S. adults listed for LT using 2005-2018 United Network for Organ Sharing LT registry. Multiple linear regression methods examined factors associated with MELD at listing, and Fine-Gray competing risks regression were used to analyze WL mortality. Among 144,163 WL registrants (median age= 56 years, 65.3% male, 56.4% private insurance, 23.3% Medicare, 15.7% Medicaid), mean WL MELD at listing was higher in African Americans versus non-Hispanic whites (2.57 points higher, 95%CI: 2.40-2.74, P < 0.001). Compared with patients with private insurance, adjusted mean WL MELD was higher among those with no insurance, Medicare, or Medicaid (P < 0.001 for all). After correcting for differences in MELD at listing, Asians had lower risk of WL death versus non-Hispanic whites (subhazard ratio (SHR): 0.92, 95% CI: 0.86-1.00, P= 0.04), but no difference was observed in African Americans or Hispanics. Compared with patients with private insurance, higher risk of WL death was observed in patients with no insurance (SHR: 1.33, 95%CI: 1.14-1.56, P < 0.001), Medicare (SHR: 1.20, 95%CI: 1.16-1.25, P < 0.001), or Medicaid (SHR: 1.22, 95%CI: 1.17-1.27, P < 0.001). Higher MELD scores at listing among African Americans did not translate into increased WL mortality. Patients with Medicare, Medicaid, or uninsured had significantly higher WL mortality than privately insured patients, even after correcting for disparities in MELD scores at listing.

Impact of chronic kidney disease on oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who underwent adjuvant bacillus Calmette-Guérin therapy

ObjectivesTo investigate the impact of chronic kidney disease (CKD) on oncological outcomes in patients with high-risk non-muscle invasive bladder cancer (NMIBC) who underwent adjuvant induction bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT). Materials and MethodsWe conducted a multi-institutional retrospective study assessing 209 patients with high-risk NMIBC who underwent TURBT and subsequent adjuvant induction BCG therapy from December 1998 to April 2019. Patients were divided into 2 groups: those with preoperative estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 (non-CKD group), and those with eGFR < 60 ml/min/1.73 m2 (CKD group). Primary endpoints were intravesical recurrence-free survival (RFS) and muscle-invasive bladder cancer (MIBC)-free survival. Background-adjusted multivariate analyses with the inverse probability of treatment weighting (IPTW) method using the propensity score were performed to evaluate the impact of CKD on intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. Moreover, multivariable analyses were performed to assess the impact of CKD on intravesical recurrence and MIBC progression, adjusting for the competing risk of death using the Fine-Gray competing risk regression model. ResultsMedian age and follow-up period after TURBT were 72 years and 45 months, respectively. Of 209 patients, 71 (34%) were diagnosed with CKD before TURBT. Background-adjusted multivariate analyses with the IPTW method indicated that CKD was significantly associated with shorter intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. In the Fine-Gray competing risk regression model, CKD showed significantly higher probabilities of intravesical recurrence and MIBC progression, with an adjusted subdistribution hazard ratio of 1.886 (95% confidence interval 1.069–3.330, P = 0.028) and 3.740 (95% confidence interval 1.060–13.20, P = 0.040), respectively. ConclusionsCKD presents a risk factor of poor oncological outcomes in patients with high-risk NMIBC who underwent adjuvant induction BCG therapy after TURBT.

Long-term Implications of Tracheostomy in Cardiac Surgery Patients: Decannulation and Mortality

The long-term implications of tracheostomy in cardiac surgical patients are largely unknown. We sought to investigate outcomes including decannulation and long-term mortality in a population of post-cardiac surgery patients. All patients undergoing cardiac surgery at a single institution between 1997 and 2016 were evaluated for postoperative tracheostomy placement, time to decannulation, and mortality. Patients were stratified by tracheostomy placement, as well as by successful decannulation for comparison. Kaplan-Meier analysis identified time to decannulation and mortality and a Fine-Gray's competing risk regression, accounting for mortality, identified predictors of time to decannulation. Of 14,600 total cardiac surgery patients, only 309 required tracheostomy. Patients with tracheostomy had high rates of perioperative comorbidities, including 60% with heart failure and 24% with postoperative stroke. Tracheostomy patients had high short-term and long-term mortality, with a median survival of 152 days, 1-year survival of 41%, and 5-year survival of 29.1%. Patients remained with tracheostomy in place for a median of 59 days, with a 1-year decannulation rate of 80% in living patients. Patients with older age (hazard ratio 0.98, P= .01), chronic lung disease (hazard ratio 0.66, P= .03), and preoperative or postoperative dialysis (hazard ratio 0.45, P < .01) were less likely to have their tracheostomy removed. Tracheostomy is associated with poor long-term survival of cardiac surgery patients. However, patients who do survive have a short duration of tracheostomy with almost all surviving patients eventually decannulated. This finding provides valuable information for pre-procedural counseling for these high-risk patients and their families.

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease.

The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer. Cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure. We identified 69,984 patients with localized prostate cancer diagnosed from 2001 to 2015 treated with surgery or radiation. We coded receipt of TT after treatment as a time-dependent covariate; used the National Death Index to identify cause of death; and defined biochemical recurrence as PSA > 0.2 ng/mL after surgery and nadir + 2 ng/mL after radiation. We analyzed recurrence and mortality using cumulative incidence curves, Fine-Gray competing risk regression, and Cox regression. This cohort included 28,651 surgery patients and 41,333 radiation patients, of whom 469 (1.64%) and 543 (1.31%), respectively, received TT with a median follow-up of 6.95 years. Comparing testosterone users to nonusers, there were no between-group differences in biochemical recurrence, prostate cancer-specific mortality, or overall mortality after surgery [hazard ratios (HR): 1.07; HR: 0.72 (p = 0.43); and HR: 1.11 (p = 0.43), respectively] or radiation [HR: 1.07; HR: 1.02 (p = 0.95); and HR: 1.02 (p = 0.86), respectively]. Limitations included lack of detailed data on TT duration and serum testosterone concentrations. In this multi-ethnic national cohort, TT did not increase the risks of biochemical recurrence or prostate cancer-specific or overall mortality after surgery or radiation. These data suggest that TT is safe in appropriate men after definitive treatment of localized prostate cancer.

Clinical, genetic, and pathologic determinants of prostate cancer brain metastasis.

5536 Background: Prostate cancer (PCa) brain metastasis (BM) is a rare event occurring in 0.16-0.63% of PCa patients. Current clinical data on this phenomenon is limited to small retrospective cohorts and our understanding of it is incomplete. We sought to identify clinical and molecular predictors of PCa BM in a large retrospective cohort treated at our institution. Methods: Men diagnosed with Pca from 1995-2017 with ≥6 months of follow-up were included. Data was collected on clinical and tumor characteristics at diagnosis, PCa treatment, brain and bone metastasis, and tumor genetic profile based on Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) analysis. Results were examined using Kyoto Encyclopedia of Genes and Genome (KEGG) pathway. Genes altered in ≥5% of patients were included. Time to brain metastasis (TTBM) and overall survival (OS) were analyzed with univariable (UVA) Fine-Gray competing risks regression and Cox proportional hazards. TTBM and OS were landmarked at 6 months after PCa diagnosis. False discovery rate (FDR) adjustment accounted for multiple comparisons. Results: 27,887 men met inclusion criteria; 74 developed BM. Clinical variables associated with increased hazard of TTBM in UVA were high-clinical and pathologic-* (p&lt;.001) T stage, node-positive disease* (p&lt;.001), primary* and total* Gleason (p&lt;.001), receipt of abiraterone* (HR 52.51 (95% CI 7.1-389.8), p&lt;.001), and receipt of leuprolide* (HR 3.0 (95% CI 1.7-5.4), p&lt;.001). Tumor alterations associated with BM include mutations in BRCA2 (HR 2.94 (95% CI 1.1-8.0), p=.04), MYC (HR 3.41 (95% CI 1.2-9.5), p=.02), PTEN (HR 2.90 (95% CI 1.2-6.9), p=.02), RB1 (HR 3.09 (95% CI 1.2-8.0), p=.02), and pathways involving homologous recombination (HR 2.70 (95% CI 1.1-6.4), p=.02), Fanconi anemia* (HR 4.22 (95% CI 1.8-10.0), p&lt;.001), Ras signaling* (HR 4.6 (95% CI 1.5-13.9), p=.006), mTOR signaling (HR 2.88 (95% CI 1.1-7.9), p=.04), VEGF signaling* (HR 3.60 (95% CI 1.5-8.8), p=.005), and GnRH signaling* genes (HR 3.93 (95% CI 1.6-9.6), p0.003). Variables associated with increased hazard of BM after FDR adjustment are denoted with an asterisk. Variables associated with reduced OS after FDR adjustment were neuroendocrine or blastoma histology, node-positive disease, high-T stage, high initial PSA, receipt of leuprolide, and alterations in AR, TP53, and CDK12 genes. Conclusions: PCa BM is significantly associated with high-stage and grade disease, receipt of androgen deprivation agents such as abiraterone and leuprolide, and alterations in the Fanconi anemia, Ras, VEGF, and GnRH pathways.

Incidence and risk factors for pneumonitis associated with immune checkpoint inhibitors in advanced-stage non-small cell lung cancer: A single center experience.

e15089 Background: Conventional treatments for advanced-stage non-small cell lung cancer (NSCLC) confer a progression-free survival of only about 6 months. Immune checkpoint inhibitors (ICIs) have become standard therapies in the management of advanced NSCLC, but are associated with a variety of immune-related adverse events that may be dose-limiting (irAEs). Risk factors for ICI-related pneumonitis, a potentially fatal irAE, have not been well established. We sought to determine the incidence and risk factors for ICI-related pneumonitis in NSCLC in a cohort of patients treated with ICIs as standard of care or as part of a clinical trial. Methods: We performed a retrospective review of 525 patients with advanced NSCLC who received ICI therapy with PD-1 inhibitors, with or without CTLA-4 inhibitors, at MD Anderson Cancer Center between 2015 and 2018. Patients with incomplete data were excluded from the study. Clinical data was collected at the time of ICI therapy and at the time of irAE. The diagnosis of pneumonitis was based on clinical presentation, imaging findings, and microbiological results. We constructed a Fine-Gray competing risks regression model with pneumonitis as the outcome of interest and all-cause mortality as the competing risk. Results: In our initial data analysis based on available data shows a 9.7% raw incidence of pneumonitis (17/177). We found no association between age, race, gender, type of anti-PD-1 therapy, concurrent use of CTLA-4 inhibitors, tumor histology, cumulative radiation dose, or smoking pack-years with the risk for pneumonitis. Patients who were therapy-naïve at the initiation of ICI therapy (hazard ratio [HR] 3.3, 95% confidence interval [CI] 1.0-10.6, p = 0.04), and patients with prior lung disease (HR 2.7, 95% CI 0.8-8.5, p = 0.1) had around a three-fold increase in the risk for pneumonitis after accounting for the competing risk of mortality. Conclusions: NSCLC patients who are therapy-naïve or have prior lung disease on initiation of ICI therapy have a higher risk for pneumonitis. Other studies have shown an increase in pneumonitis in therapy-naïve patients, but the association with prior lung disease is novel. Further analysis on this cohort is ongoing.

PD63-03 TREATMENT INTENSIFICATION AND OUTCOME IN HIGH-RISK PROSTATE CANCER:A MULTI-INSTITUTIONAL CONSORTIUM ANALYSIS

INTRODUCTION AND OBJECTIVE:External beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), EBRT with a brachytherapy boost (EBRT+BT) with ADT, and radical prostatectomy (RP) with or with...

MP79-09 ANTI-ANDROGEN THERAPY OVERCOMES THE TIME-DELAY IN INITIATION OF SALVAGE RADIATION THERAPY AND RESCUES ONCOLOGICAL OUTCOMES IN MEN WITH RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) IV (MP79)1 Apr 2020MP79-09 ANTI-ANDROGEN THERAPY OVERCOMES THE TIME-DELAY IN INITIATION OF SALVAGE RADIATION THERAPY AND RESCUES ONCOLOGICAL OUTCOMES IN MEN WITH RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY Akshay Sood*, Jacob Keeley, Deepansh Dalela, Sohrab Arora, Isaac Palma-Zamora, Marcus Jamil, Natalija Kovacevic, Guillaume Farah, Philip Olson, Wooju Jeong, Quoc-Dien Trinh, Craig G. Rogers, James O. Peabody, Mani Menon, and Firas Abdollah Akshay Sood*Akshay Sood* More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Deepansh DalelaDeepansh Dalela More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Isaac Palma-ZamoraIsaac Palma-Zamora More articles by this author , Marcus JamilMarcus Jamil More articles by this author , Natalija KovacevicNatalija Kovacevic More articles by this author , Guillaume FarahGuillaume Farah More articles by this author , Philip OlsonPhilip Olson More articles by this author , Wooju JeongWooju Jeong More articles by this author , Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author , Craig G. RogersCraig G. Rogers More articles by this author , James O. PeabodyJames O. Peabody More articles by this author , Mani MenonMani Menon More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000971.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To examine whether the addition of anti-androgen therapy (AAT) to ‘late’ salvage radiation therapy (sRT) can lead to oncological outcomes similar to that of early sRT in men with recurrent prostate cancer after radical prostatectomy. METHODS: Data on 670 men who participated in the RTOG 9601 trial and experienced biochemical recurrence were extracted using the NCTN data archive platform. Patients were stratified into four treatment groups: early sRT (pre-sRT PSA <0.7 ng/mL) with/without concomitant AAT and late sRT (pre-sRT PSA ³0.7 ng/mL) with/without concomitant AAT, based on the cut-offs reported in the original trial. Cox proportional hazards and Fine-Gray competing-risk regression analyses assessed the adjusted hazards of overall mortality, CaP specific mortality and metastatic/local disease progression among the four treatment groups. RESULTS: Patients were well-matched in baseline characteristics. The median follow-up was 12 years. At 10-years, for patients treated with early sRT, early sRT with AAT, late sRT and late sRT with AAT, the overall mortality, CaP specific mortality and metastasis rates were 14%, 16%, 31% and 17% (Log-rank p=0.0001), 7%, 3%, 16% and 4% (Gray’s p=0.0001) and 12%, 9%, 26% and 12% (Gray’s p=0.0003), respectively (Figure). Adjusted analysis demonstrated increased hazards of overall mortality in patients receiving delayed sRT versus early sRT, HR 1.62 (95% CI: 1.11 - 2.37). However, no difference remained after addition of concomitant AAT to late sRT ¾ referent early sRT, HR 0.89 (95% CI: 0.58 - 1.39). Similarly, the hazards of cancer-specific mortality and metastatic progression were worse for late sRT, when compared to early sRT, but were no different after addition of AAT to late sRT. CONCLUSIONS: Poorer outcomes associated with late sRT may be rescued with delivery of concomitant AAT. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1218-e1219 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akshay Sood* More articles by this author Jacob Keeley More articles by this author Deepansh Dalela More articles by this author Sohrab Arora More articles by this author Isaac Palma-Zamora More articles by this author Marcus Jamil More articles by this author Natalija Kovacevic More articles by this author Guillaume Farah More articles by this author Philip Olson More articles by this author Wooju Jeong More articles by this author Quoc-Dien Trinh More articles by this author Craig G. Rogers More articles by this author James O. Peabody More articles by this author Mani Menon More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

Long Term Employment Following Heart Transplantation in the United States

Employment is an important metric of post-transplant functional status and quality of life, yet remains poorly described after heart transplant. We sought to characterize the prevalence of employment following heart transplantation and identify patients at risk for post-transplant unemployment. Adults undergoing single-organ heart transplantation (2007-2016) were evaluated using the UNOS database. Univariate analysis was stratified by employment status at one year post-transplant. A Kaplan-Meier analysis evaluated time to start of employment while Fine-Gray competing risk regression was used for risk adjustment. Of 11,088 heart transplant recipients, 22.0% of survivors were employed and 71.3% unemployed one year post-transplant. Overall employment rate of survivors increased to 32.9% by year two. Employed individuals were more likely white (70.9% vs. 60.4%, p<0.01), male (79.6% vs. 70.7% p<0.01), held a job at listing/transplant (37.6% vs. 7.6%, p<0.01), and have private insurance (79.1% vs. 49.5%, p<0.01). After risk-adjustment, several characteristics were independently associated with time to employment (Table). Of the 1,657 (14.0%) patients employed prior to transplant, 58% were working at one year and 79% returned to work by 4 years (Figure). Over 20% of heart transplant patients are employed at one year and 30% at two years, while 60% of those working pre-transplant return to work. Postoperative complications, race, education and insurance status are all drivers of employment. Quality improvement focused on addressing socioeconomic disparities may maximize functional status post-transplant.

Impact of initial treatment selection on clinical outcomes after biochemical failure in radiorecurrent high-risk prostate cancer.

208 Background: Treatment of high risk prostate cancer (HRPCa) with external beam radiotherapy (EBRT) plus brachytherapy (BT) boost (EBRT+BT) has been prospectively associated with lower rates of BCR, albeit potentially with increased toxicity, and retrospectively linked to decreased distant metastasis (DM) and PCa-specific mortality (PCSM) compared to EBRT alone. However, it is unclear whether patients who develop BCR following either approach have similar downstream oncologic outcomes. Methods: We identified 706 out of 3820 men with HRPCa treated at 13 institutions from 1998-2015 with EBRT (n=468/2134) or EBRT+BT (n=238/1686) who developed BCR. We compared rates of DM, PCSM, and all-cause mortality (ACM) after BCR between treatment groups using Fine-Gray competing risk regression. Models were adjusted for age, Gleason grade group, initial PSA (iPSA), clinical T stage, time-dependent use of systemic salvage, and interval to BCR using inverse probability of treatment weighting. Results: Median follow-up was 9.9 years from RT and 4.8 years from BCR. Groups were similar in age, iPSA, presence of ≥2 HR features, and median interval to BCR (3.3 years). Most men received neoadjuvant/concurrent androgen deprivation therapy (ADT), 92.5% and 91.0% for EBRT and EBRT+BT, respectively, though for a longer duration with EBRT (median 14.7 vs. 9.0 months, p=0.0012). Local and systemic salvage rates were 2.3% and 36.3% after EBRT, and 2.6% and 43.6% after EBRT+BT, respectively. Initial EBRT+BT was associated with significantly lower rates of DM after BCR (HR 0.48, 95% CI 0.36-0.64, p&lt;0.001). Rates of PCSM and ACM did not significantly differ (HR 0.93, 95% CI 0.67-1.30, p=0.93, and HR 0.8, 95% CI 0.6-1.1, p=0.11, respectively). Conclusions: In this large retrospective series of radiorecurrent HRPCa, initial treatment with EBRT+BT was associated with significantly lower rates of DM after BCR compared with EBRT, despite shorter ADT use and a similar median interval to BCR. Local salvage was widely underutilized in both groups. In the absence of salvage for local failure after EBRT, upfront treatment intensification with BT may reduce DM, though not PCSM or ACM, even after development of BCR.

Characteristics of radiation-associated bladder cancer compared to primary bladder cancer

582 Background: Radiation-associated muscle-invasive bladder cancer (RA-MIBC) has been suggested to represent a more aggressive disease variant compared to primary (non-radiation associated) MIBC. We sought to characterize the presentation, patterns of care, and outcomes of RA-MIBC compared to primary MIBC. Methods: We identified 60,117 patients diagnosed with non-metastatic or metastatic MIBC between 1988 and 2015 using the Surveillance, Epidemiology, and End Results (SEER) database and stratified patients based on whether radiation had been administered to a pelvic primary prior to the development of bladder cancer. We used logistic regression to compare rates of chemotherapy, surgery, or radiation for patients with RA-MIBC compared to primary MIBC. We used Fine-Gray competing risks regression to compare adjusted bladder cancer-specific mortality (BCSM) for RA-MIBC and primary MIBC. Results: There were 1,093 patients with RA-MIBC and 59,024 patients with primary MIBC. Patients with RA-MIBC were older compared to patients with primary MIBC (mean age 77.4 years vs 72.4 years, p &lt; 0.001) and more likely to be male (86.8% vs 73.3%, p&lt;0.001). RA-MIBCs were more likely to be high-grade (57.5% vs 47.6%, p&lt;0.001), more likely to have T4 disease at diagnosis (21.0% vs 17.3%, p&lt;0.001), and less likely to be node-positive (4.2% vs 8.1%, p &lt; 0.001). In terms of treatment, non-metastatic primary MIBC patients were more likely to undergo radiation (14.0% vs 3.1%, p&lt;0.001) as well as radiation with cystectomy (1.9% vs 0.8%, p&lt;0.001) compared to those with RA-MIBC. Median survival was significantly shorter for patients with RA-MIBC (13 mo. vs 19 mo.; p&lt;0.001). Conclusions: RA-MIBCs tend to present with higher grade and higher stage disease and are less likely to receive curative treatment. Even when adjusting for stage, grade, and receipt of treatment, patients with RA-MIBC have worse survival compared to those with primary MIBC. These findings raise the possibility that RA-MIBC represents a biologically more aggressive disease compared to primary MIBC. Future research is needed to better understand biological differences between RA-MIBC and primary MIBC and develop improved therapeutics for radiation-associated cancers.

Outcomes of HPV-Associated Squamous Cell Carcinoma of the Head and Neck: Impact of Race and Socioeconomic Status.

Socioeconomic factors affecting outcomes of HPV-associated squamous cell carcinoma of the head and neck (SCCHN) are poorly characterized. A custom SEER database identified adult patients with primary nonmetastatic SCCHN and known HPV status diagnosed in 2013 through 2014. Multivariable logistic regression defined associations between patient characteristics and HPV status, with adjusted odds ratios (aORs) and 95% confidence intervals reported. Fine-Gray competing risks regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals for cancer-specific mortality (CSM), including a disease subsite * HPV status * race interaction term. A total of 4,735 patients with nonmetastatic SCCHN and known HPV status were identified. HPV-associated SCCHN was positively associated with an oropharyngeal primary, male sex, and higher education, and negatively associated with uninsured status, single marital status, and nonwhite race (P≤.01 for all). For HPV-positive oropharyngeal SCCHN, white race was associated with lower CSM (aHR, 0.55; 95% CI, 0.34-0.88; P=.01) and uninsured status was associated with higher CSM (aHR, 3.12; 95% CI, 1.19-8.13; P=.02). These associations were not observed in HPV-negative or nonoropharynx SCCHN. Accordingly, there was a statistically significant disease subsite * HPV status * race interaction (Pinteraction<.001). Nonwhite race and uninsured status were associated with worse CSM in HPV-positive oropharyngeal SCCHN, whereas no such associations were observed in HPV-negative or nonoropharyngeal SCCHN. These results suggest that despite having clinically favorable disease, nonwhite patients with HPV-positive oropharyngeal SCCHN have worse outcomes than their white peers. Further work is needed to understand and reduce socioeconomic disparities in SCCHN.

Radiomics Analysis of Computed Tomography helps predict poor prognostic outcome in COVID-19.

Rationale: Given the rapid spread of COVID-19, an updated risk-stratify prognostic tool could help clinicians identify the high-risk patients with worse prognoses. We aimed to develop a non-invasive and easy-to-use prognostic signature by chest CT to individually predict poor outcome (death, need for mechanical ventilation, or intensive care unit admission) in patients with COVID-19.Methods: From November 29, 2019 to February 19, 2020, a total of 492 patients with COVID-19 from four centers were retrospectively collected. Since different durations from symptom onsets to the first CT scanning might affect the prognostic model, we designated the 492 patients into two groups: 1) the early-phase group: CT scans were performed within one week after symptom onset (0-6 days, n = 317); and 2) the late-phase group: CT scans were performed one week later after symptom onset (≥7 days, n = 175). In each group, we divided patients into the primary cohort (n = 212 in the early-phase group, n = 139 in the late-phase group) and the external independent validation cohort (n = 105 in the early-phase group, n = 36 in the late-phase group) according to the centers. We built two separate radiomics models in the two patient groups. Firstly, we proposed an automatic segmentation method to extract lung volume for radiomics feature extraction. Secondly, we applied several image preprocessing procedures to increase the reproducibility of the radiomics features: 1) applied a low-pass Gaussian filter before voxel resampling to prevent aliasing; 2) conducted ComBat to harmonize radiomics features per scanner; 3) tested the stability of the features in the radiomics signature by several image transformations, such as rotating, translating, and growing/shrinking. Thirdly, we used least absolute shrinkage and selection operator (LASSO) to build the radiomics signature (RadScore). Afterward, we conducted a Fine-Gray competing risk regression to build the clinical model and the clinic-radiomics signature (CrrScore). Finally, performances of the three prognostic signatures (clinical model, RadScore, and CrrScore) were estimated from the two aspects: 1) cumulative poor outcome probability prediction; 2) 28-day poor outcome prediction. We also did stratified analyses to explore the potential association between the CrrScore and the poor outcomes regarding different age, type, and comorbidity subgroups.Results: In the early-phase group, the CrrScore showed the best performance in estimating poor outcome (C-index = 0.850), and predicting the probability of 28-day poor outcome (AUC = 0.862). In the late-phase group, the RadScore alone achieved similar performance to the CrrScore in predicting poor outcome (C-index = 0.885), and 28-day poor outcome probability (AUC = 0.976). Moreover, the RadScore in both groups successfully stratified patients with COVID-19 into low- or high-RadScore groups with significantly different survival time in the training and validation cohorts (all P < 0.05). The CrrScore in both groups can also significantly stratify patients with different prognoses regarding different age, type, and comorbidities subgroups in the combined cohorts (all P < 0.05).Conclusions: This research proposed a non-invasive and quantitative prognostic tool for predicting poor outcome in patients with COVID-19 based on CT imaging. Taking the insufficient medical recourse into account, our study might suggest that the chest CT radiomics signature of COVID-19 is more effective and ideal to predict poor outcome in the late-phase COVID-19 patients. For the early-phase patients, integrating radiomics signature with clinical risk factors can achieve a more accurate prediction of individual poor prognostic outcome, which enables appropriate management and surveillance of COVID-19.

The Association between Earlobe Creases and Cardiovascular Events in Japanese Hemodialysis Patients: A Prospective Cohort Study.

Objective The earlobe crease, a wrinkle extending from the tragus to the outer border of the earlobe, is a well-known surrogate marker for a high risk of cardiovascular disease. However, information is lacking about its association with cardiovascular events among hemodialysis patients, who already have an increased risk of cardiovascular disease. We tested the hypothesis that earlobe creases are independently associated with the risk of cardiovascular events among Japanese hemodialysis patients. Methods This prospective cohort study followed 247 adult hemodialysis patients with no history of cardiovascular disease for 4 years. The presence of earlobe creases was defined by two researchers using photos of patients' earlobes on both sides while blinded to one another's assessments and clinical data. The primary outcome was defined as the first fatal or nonfatal cardiovascular event (myocardial infarction, ischemic or hemorrhagic stroke, or peripheral vascular disease requiring aortic or peripheral vascular bypass surgery or below- or above-the-knee amputation). A Fine-Gray competing risks regression model was used to examine the association between earlobe creases and cardiovascular events. Results During the 4-year follow-up period, 43 patients suffered cardiovascular events. After the competing risk of non-cardiovascular death was accounted for, patients with earlobe creases had an increased cumulative incidence of cardiovascular events compared to those without earlobe creases (subhazard ratio =2.04, 95% confidence interval: 1.09 to 3.82). This association was no longer significant after adjusting for age. Conclusion Earlobe creases were not independently associated with cardiovascular events among Japanese hemodialysis patients, suggesting that these marks are simply indicative of advanced age.