Multivariate Cox Proportional Hazards Model Research Articles

Effect of Primary Site and Treatment Modality of Patients With Head and Neck Myoepithelial Carcinoma on Survival

AimEpidemiological evidence on myoepithelial carcinoma is rare. This study aimed to investigate the effect of tumor primary site and treatment modality on survival in patients with head and neck myoepithelial carcinoma. Materials and methodsData on adult patients diagnosed with head and neck myoepithelial carcinoma between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Uni- and multivariable Cox proportional hazard models were utilized to evaluate the effects of different tumor primary sites and treatment modalities on overall survival (OS) and cancer-specific survival (CSS), and expressed as hazard ratio (HR) and 95% confidence interval (CI). ResultsA total of 415 patients were enrolled. No significant differences in OS and CSS were found between different tumor primary sites (P > 0.05). Compared with partial excision, patients with total excision (HR = 1.65, 95%CI: 1.12–2.42) (partial or total removal of the organ in which the tumor is located and complete removal of the tumor) or no surgery (HR = 3.52, 95%CI: 2.05–6.03) had worse OS. Compared with surgery only, patients with radiotherapy only had poorer OS (HR = 4.69, 95%CI: 2.32–9.46) and CSS (HR = 6.72, 95%CI: 2.59–17.46), while no significant differences in OS (P = 0.120) and CSS (P = 0.847) were found among patients who received surgery combined with radiotherapy. In patients with AJCC III/IV, patients with radiotherapy only (HR = 4.51, 95%CI: 1.61–12.62) had poorer OS compared to those with surgery only, whereas patients who received surgery combined with radiotherapy had better OS (HR = 0.50, 95%CI: 0.29–0.89). ConclusionThe tumor primary site may not affect the prognosis of patients with myoepithelial carcinoma, while the effect of treatment modality on prognosis is related to the primary site and stage of the tumor.

Hispanic Ethnicity and Fertility Outcomes

ObjectiveTo assess the association between ethnicity and fertility outcomes for men in a statewide cohort. DesignWe linked data from the Utah Population Database (UPDB) and Subfertility Health Assisted Reproduction and Environment (SHARE) database, to comprise a cohort of sub-fertile men who underwent semen analysis (SA) between 1998-2017 in Utah. A multivariable Cox proportional hazard model was constructed to understand the impact of ethnicity on fertility outcomes in our cohort. Results11,363 men were included. 1,039 (9.1%) were Hispanic. 39.7% of men in the lowest socioeconomic status group (SES) were Hispanic (p<0.001). When controlling for demographic and clinical factors, the number of live births was reduced for Hispanic men (HR=0.62 [0.57-0.67], p<0.001). Though fertility treatment (FT) had a positive effect (HR 1.242 [1.085-1.421], p<0.001), in competing risks models, Hispanic men were less likely to use FT (HR=0.633 [0.526-0.762], p<0.001). ConclusionHispanic ethnicity is significantly associated with a lower likelihood of successful fertility outcomes in Utah. Hispanic men had nearly a 40% reduced likelihood of live births when controlling for sociodemographic factors. Our results indicate that, depending on age, Hispanic men have up to approximately 14 fewer live births per 100 men per year, pointing to a significant disparity in fertility outcomes in the state of Utah. Given 15.1% of Utah’s population identifies as Hispanic and 18.7% of the United States population identifies as Hispanic on the 2020 Census, better understanding of the association of ethnicity and fertility outcomes is imperative.

Development and validation of prognostic nomographs for patients with cervical cancer: SEER-based Asian population study

To develop and validate a nomograph to predict the long-term survival probability of cervical cancer (CC) patients in Asia, Surveillance, Epidemiology, and End Results (SEER) were used to collect information about CC patients in Asia. The patient data were randomly sampled and divided into a training group and a validation group by 7:3. Least absolute shrinkage and selection operator (LASSO) regression was used to screen key indicators, and multivariate Cox regression model was used to establish a prognostic risk prediction model for CC patients. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were adopted to comprehensively evaluate the nomogram model. LASSO regression and multivariate Cox proportional hazards model analysis showed that age, American Joint Committee on Cancer (AJCC) Stage, AJCC T, tumor size, and surgery were independent risk factors for prognosis. The ROC curve results proved that the area under curve (AUC) values of the training group in 3 and 5 years were 0.837 and 0.818, The AUC values of the validation group in 3 and 5 years were 0.796 and 0.783. DCA showed that the 3- and 5-year overall survival (OS) nomograms had good clinical potential value. The nomogram model developed in this study can effectively predict the prognosis of Asian patients with CC, and the risk stratification system based on this nomogram prediction model has some clinical value for discriminating high-risk patients.

Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer.

Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P = .021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.

Value of nutritional indices in predicting survival free from pump replacement and driveline infections in centrifugal left ventricular assist devices

ObjectiveThere is a paucity of data assessing the impact of nutritional status on outcomes in patients supported with the HeartMate 3 (HM3) left ventricular assist device (LVAD). MethodsPatients ≥18 years of age who underwent HM3 LVAD implantation between 2015 and 2020 were identified from a single tertiary care center. The primary outcome assessed was death or device replacement. A secondary outcome of driveline infection was also evaluated. Kaplan-Meier survival analysis and a multivariate Cox-proportional hazards model were used to identify predictors of outcome. ResultsOf the 289 patients identified, 94 (33%) experienced a primary outcome and 96 (33%) a secondary outcome during a median follow-up time of 2.3 years. Independent predictors of the primary outcome included peripheral vascular disease (hazard ratio [HR], 3.40; 95% confidence interval [CI], 1.66-6.97, P < .01), diabetes mellitus (HR, 0.46; 95% CI, 0.27-0.80, P < .01), body mass index ≥40 kg/m2 (HR, 2.63 per 1 kg/m2 increase; 95% CI, 1.22-5.70, P < .05), preoperative creatinine level (HR, 1.86 per 1 mg/dL increase; 95% CI, 1.31-2.65, P < .01), and preoperative prognostic nutritional index (PNI) score (HR, 0.88 per 1-point increase; 95% CI, 0.81-0.96, P < .01). Independent predictors of driveline infection included age at the time of implantation (HR, 0.97; 95% CI, 0.96-0.99, P < .01) and diabetes mellitus (HR, 1.79; 95% CI, 1.17-2.73, P < .01). ConclusionsPreoperative PNI scores may independently predict mortality and the need for device replacement in patients with HM3 LVAD. Routine use of the PNI score during preoperative evaluation and, when possible, supplementation to PNI >33, may be of value in this population.

Clinical impact of malnutrition according to the Global Leadership Initiative on Malnutrition criteria combined with kidney dysfunction to determine mortality in inpatients

ObjectiveThe clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD). MethodsThis single-center retrospective cohort study included 6,712 patients aged ≥18 admitted between 2018 and 2019. The relationship between the estimated glomerular filtration rate (eGFR) groups, nutritional status based on the GLIM criteria, and incidence of all-cause mortality was evaluated using multivariate Cox proportional hazards (CPH) models. Malnutrition was defined as at least one phenotype (weight loss, low body mass index (BMI), or reduced muscle mass) and one etiological criterion (reduced intake/assimilation or disease burden/inflammation). ResultsMultivariate CPH models showed that eGFR ≤29 (vs. eGFR: 60–89, adjusted HR = 1.84, 95% CI: 1.52–2.22), 30–59 (vs. eGFR: 60–89, adjusted HR = 1.40, 95% CI: 1.20–1.64), and ≥90 (vs. eGFR: 60–89, adjusted HR = 1.40, 95% CI: 1.14–1.71), moderate and severe malnutrition (vs. without malnutrition, adjusted HR = 1.38 [1.18–1.62] and 2.18 [1.86–2.54], respectively) were independently associated with the incidence of death. The all-cause mortality rate was higher in patients with malnutrition or eGFR ≤29 (adjusted HR, 3.31; 95% CI: 2.51–4.35) than in patients without malnutrition or eGFR 60–89. Furthermore, moderate and severe malnutrition (vs. no malnutrition) was independently associated with death in patients with NKD, AKI, and CKD. ConclusionMalnutrition based on the GLIM criteria was associated with increased all-cause mortality in inpatients, and malnutrition combined with kidney dysfunction was associated with a higher risk of mortality. Furthermore, patients with NKD, AKI, and CKD showed an association between malnutrition based on GLIM criteria and mortality.

Psychological Distress, Emergency Room Utilization, and Mortality Risk Among US Adults With History of Prostate Cancer.

Adults with a history of prostate cancer experience several physical and mental stressors. However, limited information is available about the prevalence of psychological distress in this population and its association with clinical outcomes in a nationally representative sample. We identified adults with history of prostate cancer from a nationally representative cohort (2000-2018 US National Health Interview Survey) and its linked mortality files through December 31, 2019. The six-item Kessler Psychological Distress Scale (K6) was used to assess psychological distress. The associations between psychological distress severity, emergency room (ER) usage, and mortality risk were estimated using multivariable logistic and Cox proportional hazards models, which were both adjusted for age, survey year, race/ethnicity, region, education, health insurance, comorbidities, functional limitations, and time since cancer diagnosis. Among the 3,451 adults with history of prostate cancer surveyed, 96 (2.4%), 434 (11.3%), and 2,921 (86.3%) reported severe, moderate, or low/no mental distress, respectively. During the 12 months preceding the survey, 812 (22.8%) adults with history of prostate cancer visited the ER. After a median follow-up of 81 months, 937 (25.5%) deaths occurred. Compared with participants with low/no mental distress, those with severe mental distress reported the highest utilization of the ER (adjusted odds ratio [aOR], 2.57 [95% CI, 1.51 to 4.37]) and exhibited the highest all-cause mortality (adjusted hazard ratio [aHR], 1.83 [95% CI, 1.29 to 2.60]), followed by those with moderate mental distress (ER use aOR, 1.76 [95% CI, 1.29 to 2.42]; all-cause mortality aHR, 1.22 [95% CI, 0.92 to 1.62]). Among US adults with history of prostate cancer, psychological distress was associated with increased ER use and mortality risk. Notably, severe psychological distress was correlated with the highest rates of ER visits and mortality risk. However, given the retrospective nature of this study, uncontrolled confounding variables need to be considered when interpreting the findings.

Outcome of Darunavir-Cobicistat-Based Regimens in HIV-Infected People Who Have Experienced Virological Failure.

To evaluate the virological outcome of darunavir-cobicistat (DRVc)-based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination. This was a retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc-based regimen with HIV-RNA >50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV-RNA <50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA <50 copies/mL, last available visit, or lossto follow-up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS. A total of 176 individuals were included, and 120 (68.2%) achieved <50 HIV-RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004-1.038; p=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant-bearing protease inhibitor-resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (p=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months, p=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up. Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.

MGMT Methylation and Differential Survival Impact by Sex in Glioblastoma.

Introduction: Sex differences in glioblastoma (GBM) have been observed in incidence, genetic and epigenetic alterations, and immune response. These differences have extended to the methylation of the MGMT promoter, which critically impacts temozolomide resistance. However, the association between sex, MGMT methylation, and survival is poorly understood, which this study sought to evaluate. Methods: A retrospective cohort study was conducted and reported following STROBE guidelines, based on adults with newly diagnosed GBM who received their first surgical intervention at Cleveland Clinic (Ohio, USA) between 2012 and 2018. Kaplan-Meier and multivariable Cox proportional hazards models were used to analyze the association between sex and MGMT promoter methylation status on overall survival (OS). MGMT was defined as methylated if the mean of CpG 1-5 ≥ 12. Propensity score matching was performed on a subset of patients to evaluate the effect of individual CpG site methylation. Results: A total of 464 patients had documented MGMT methylation status with a mean age of 63.4 (range 19-93) years. A total of 170 (36.6%) were female, and 133 (28.7%) received gross total resection as a first intervention. A total of 42.5% were MGMT methylated, with females more often having MGMT methylation than males (52.1% vs. 37.4%, p = 0.004). In univariable analysis, OS was significantly longer for MGMT promoter methylated than un-methylated groups for females (2 yr: 36.8% vs. 11.1%; median: 18.7 vs. 9.5 months; p = 0.001) but not for males (2 yr: 24.3% vs. 12.2%; median: 12.4 vs. 11.3 months; p = 0.22, p for MGMT-sex interaction = 0.02). In multivariable analysis, MGMT un-methylated versus methylated promoter females (2.07; 95% CI, 1.45-2.95; p < 0.0001) and males (1.51; 95% CI, 1.14-2.00; p = 0.004) had worse OS. Within the MGMT promoter methylated group, males had significantly worse OS than females (1.42; 95% CI: 1.01-1.99; p = 0.04). Amongst patients with data on MGMT CpG promoter site methylation values (n = 304), the median (IQR) of CpG mean methylation was 3.0% (2.0, 30.5). Females had greater mean CpG methylation than males (11.0 vs. 3.0, p < 0.002) and higher per-site CpG methylation with a significant difference at CPG 1, 2, and 4 (p < 0.008). After propensity score matching, females maintained a significant survival benefit (18.7 vs. 10.0 months, p = 0.004) compared to males (13.0 vs. 13.6 months, p = 0.76), and the pattern of difference was significant (P for CpG-sex interaction = 0.03). Conclusions: In this study, females had higher mean and individual CpG site methylation and received a greater PFS and OS benefit by MGMT methylation that was not seen in males despite equal degrees of CpG methylation.

Improved Metastatic-Free Survival after Systematic Re-Excision Following Complete Macroscopic Unplanned Excision of Limb or Trunk Soft Tissue Sarcoma.

Whether re-excision (RE) of a soft tissue sarcoma (STS) of limb or trunk should be systematized as adjuvant care and if it would improve metastatic free survival (MFS) are still debated. The impact of resection margins after unplanned macroscopically complete excision (UE) performed out of a NETSARC reference center or after second resection was further investigated. This large nationwide series used data from patients having experienced UE outside of a reference center from 2010 to 2019, collected in a French nationwide exhaustive prospective cohort NETSARC. Patient characteristics and survival distributions in patients reexcised (RE) or not (No-RE) are reported. Multivariate Cox proportional hazard model was conducted to adjust for classical prognosis factors. Subgroup analysis were performed to identify which patients may benefit from RE. Out of 2371 patients with UE for STS performed outside NETSARC reference centers, 1692 patients were not reviewed by multidisciplinary board before treatment decision and had a second operation documented. Among them, 913 patients experienced re-excision, and 779 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, size, depth, grade and histotype in patients re-excised (RE) or not (No-RE). In univariate analysis, final R0 margins are associated with a better MFS, patients with R1 margins documented at first surgery had a better MFS as compared to patients with first R0 resection. The study identified RE as an independent favorable factor for MFS (HR 0.7, 95% CI 0.53-0.93; p = 0.013). All subgroups except older patients (>70 years) and patients with large tumors (>10 cm) had superior MFS with RE. RE might be considered in patients with STS of limb or trunk, with UE with macroscopic complete resection performed out of a reference center, and also in originally defined R0 margin resections, to improve LRFS and MFS. Systematic RE should not be advocated for patients older than 70 years, or with tumors greater than 10 cm.

ZIP Code to Genomic Code: Neighborhood Disadvantage, Aggressive Breast Cancer Biology, and Breast Cancer Outcomes.

To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer (BCa) tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. ND is associated with shorter BCa recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity (NF-kB, AP-1), sympathetic nervous system (SNS) activity (CREB), and protective cellular responses (IRF, STAT). To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB, AP-1, down-regulated IRF, STAT) and SNS activation (up-regulated CREB). Increasing subjective ND (e.g., threat to safety), was associated with up-regulated NF-kB and CREB and down-regulated IRF. These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

Comparison of β-blocker agents and mortality in maintenance hemodialysis patients: an international cohort study

ABSTRACT Background Despite a lack of clinical trial data, β-blockers are widely prescribed to dialysis patients. Whether specific β-blocker agents are associated with improved long-term outcomes compared with alternative β-blocker agents in the dialysis population remains uncertain. Methods We analyzed data from an international cohort study of 10 125 patients on maintenance hemodialysis across 18 countries that were newly prescribed a β-blocker medication within the Dialysis Outcomes and Practice Patterns Study (DOPPS). The following β-blocker agents were compared: metoprolol, atenolol, bisoprolol and carvedilol. Multivariable Cox proportional hazards models were used to estimate the association between the newly prescribed β-blocker agent and all-cause mortality. Stratified analyses were performed on patients with and without a prior history of cardiovascular disease. Results The mean (standard deviation) age in the cohort was 63 (15) years and 57% of participants were male. The most commonly prescribed β-blocker agent was metoprolol (49%), followed by carvedilol (29%), atenolol (11%) and bisoprolol (11%). Compared with metoprolol, atenolol {adjusted hazard ratio (HR) 0.77 [95% confidence interval (CI) 0.65–0.90]} was associated with a lower mortality risk. There was no difference in mortality risk with bisoprolol [adjusted HR 0.99 (95% CI 0.82–1.20)] or carvedilol [adjusted HR 0.95 (95% CI 0.82–1.09)] compared with metoprolol. These results were consistent upon stratification of patients by presence or absence of a prior history of cardiovascular disease. Conclusions Among patients on maintenance hemodialysis who were newly prescribed β-blocker medications, atenolol was associated with the lowest mortality risk compared with alternative agents.

Effect of smoking cessation on psoriasis vulgaris, palmoplantar pustulosis, and generalized pustular psoriasis.

Smoking is a known risk factor for psoriasis; however, the impact of smoking cessation on psoriasis has seldom been evaluated. We aimed to examine the effects of smoking cessation on the development of psoriasis vulgaris (PsV), palmoplantar pustulosis (PPP), and generalized pustular psoriasis (GPP). Using the Korean National Health Insurance Service database, we retrospectively compiled a cohort of 5,784,973 participants without psoriasis, analysed their changes in smoking status from 2004 to 2007 and followed up new cases of psoriasis until 2021. The psoriasis risks were compared with those of sustained smokers, smoking quitters, sustained ex-smokers, and never smokers using multivariate Cox proportional hazards models. The mean age of the participants was 47.1 years (standard deviation, 13.5), and 3,092,426 (53.5%) were male. During 77,990,688 person-years, 67,364 psoriasis cases were identified. Compared with sustained smokers, smoking quitters showed a reduced risk of developing psoriasis (adjusted hazard ratio [aHR] 0.91; 95% confidence interval [CI] 0.87-0.95), specifically PsV (aHR 0.92; 95% CI 0.88-0.97) and PPP (aHR 0.71; 95% CI 0.63-0.79). The reduction in risk due to smoking cessation was more prominent in sustained ex-smokers (psoriasis: aHR 0.77, 95% CI 0.74-0.79; PsV: aHR 0.76, 95% CI 0.73-0.79; PPP: aHR 0.56, 95% CI 0.51-0.61; GPP: aHR 0.64; 95% CI 0.52-0.78). When conducting sensitivity analyses to address the potential for changes in smoking habits after 2007, the results and trends were consistent with the main findings, and a more pronounced significance was observed. Compared with continuous smoking, smoking cessation was associated with a decreased risk of developing psoriasis. The risk-reducing effect of smoking cessation was more pronounced in those maintaining a smoke-free status. Smoking cessation and the maintenance of a smoke-free status should be encouraged to prevent the development of psoriasis and all other smoking-related diseases.

Association of spironolactone use with risk of urinary tract cancer in the general population: A matched population-based cohort study.

The correlation between spironolactone usage and cancer risk has sparked interest. The objective of this study is to examine the association between spironolactone use and the incidence of urinary tract cancer in the general population. We conducted a matched population-based cohort study. The study population was obtained from the Taiwan National Health Insurance Research Database (TNHIRD) during the period from 2000 to 2016. The multivariate Cox proportional hazard model was performed to examine the impact of spironolactone use on the risk of urinary tract cancer. A total of 8,608 individuals exposed to spironolactone were exact matched by 1:1 ratio with unexposed controls on factors including age, gender, comorbidities, CCI scores and socioeconomic status. The incidences of urinary tract cancer, including prostate, renal and bladder cancer, were estimated in both spironolactone exposed and non-exposed cohorts. After adjusting for confounding variables, the multivariate Cox regression analysis showed no significant association between spironolactone exposure and urinary tract cancer incidence, including bladder (adjusted hazard ratio [aHR] = 1.19, 95% confidence interval [CI] = 0.72-1.96, p = 0.50), renal (aHR = 1.75, 95% CI = 0.99-3.07, p = 0.053), and prostate cancer (aHR = 0.67, 95% CI = 0.43-1.04, p = 0.07). When the population was stratified into low (cumulative dose < = 29,300 mg) and high (cumulative dose >29,300 mg) dose of spironolactone, only high dose of spironolactone use was significantly associated with a reduced risk of prostate cancer (aHR = 0.45, 95% CI = 0.23-0.89, p = 0.02), while being associated with an elevated risk of renal cancer (aHR = 2.09, 95% CI = 1.07-4.08, p = 0.03). However, no clear cumulative dose-response relationship was observed in theses associations. High cumulative dose of spironolactone may be potentially associated with a decreased incidence of prostate cancer and an increased incidence of renal cancer, while no significant association was observed with bladder cancer incidence. However, given the lack of support from the dose-response pattern, the available evidence is inconclusive to establish a definitive association between spironolactone use and urinary tract cancer.

Salvage high-intensity focused ultrasound (S-HIFU) for recurrence after primary radiotherapy of prostate cancer

ObjectivesTo evaluate functional and oncological outcomes of salvage high-intensity focal ultrasound (S-HIFU) after external beam radiotherapy (EBRT) failure in prostate cancer (PCa) patients. MethodsThis single-center study included patients who underwent S-HIFU for local recurrence after EBRT between 2006 and 2023. Cancer-specific survival, metastasis-free survival and progression-free survival were illustrated using Kaplan–Meier curves. Disease progression was defined by one of the following criteria: increase of 2ng/mL or more above the PSA nadir, positive post-S-HIFU biopsy or initiation of androgen deprivation therapy (ADT). Multivariable Cox proportional hazards model was used to identify predictors of disease progression after S-HIFU. ResultsA total of 52 S-HIFU sessions for 48 patients were performed. Median time between EBRT and S-HIFU was 6.5 years. Median PSA before S-HIFU was 3.2ng/mL and median PSA nadir after S-HIFU was 0.58ng/mL. A total of 39 (81.3%) complications was recorded, including 3 (6.3%) high grade complications according to the Clavien-Dindo classification. After a median follow-up period of 6 years, 14 (29.2%) patients developed metastatic disease. Eighteen (37.5%) patients had no recurrence, whereas 30 (62.5%) patients received ADT for disease progression. The estimated 5-yr cancer-specific survival (CSS), metastasis-free survival (MFS) and progression-free survival rates (PFSR) were 100%, 79.9% (95% CI 67–92) and 41.2% (95% CI 74–96), respectively. The estimated 10-yr CSS, MFS and PFSR were 80% (95% CI 45–100), 50.7% (95% CI 19.4–82.1) and 14% (95% CI 10.8–45), respectively. The hazard of progression increased with the intermediate (HR 3.8; 95% CI 0.99 to 15; p=0.049) and high pre-EBRT d’Amico-s risk group (HR 4.1; 95% CI 0.98 to 16.2; p=0.050). Also, the time between EBRT and S-HIFU was significantly associated with risk of progression (HR 0.61; 95% CI 0.43 to 0.86; p=0.004). No significant difference linked to the disease progression (DP) risk was found between focal vs whole-gland treatment (p=0.70). ConclusionPhysicians should consider HIFU as a local salvage treatment after failed EBRT, thus avoiding or delaying palliative androgen deprivation therapy. Further studies are needed to improve patient selection for this therapy. Level of evidence4.

Nomogram for customized recurrence prediction in primary non-muscle-invasive bladder cancer based on routine blood and urine parameters

PurposeA prevalent condition with a high probability of recurrence, non-muscle invasive bladder cancer (NMIBC) necessitates lifetime surveillance. In patients with pathologically confirmed NMIBC, our goal was to create a unique nomogram to predict recurrence after transurethral resection of bladder tumor (TURBT).MethodsOur institution’s 91 NMIBC patients with complete follow-up data between January 2017 and February 2021 were included in the retrospective analysis. The nomogram predicting the 0.5, 1, 2 and 3-year likelihood of recurrence was created using multivariate Cox proportional hazard models to find the significant determinants of recurrence. Using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA), we internally validated the nomogram.ResultsThe significant factors related to NMIBC recurrence were age, blood platelet count, especially for the urine leukocyte count and mucus filament. The constructed nomogram performed well in the customized prediction of NMIBC recurrence at 6th, 12th, 24th and 36th month, of which the C-index was 0.724. The calibration curve and the ROC curve both validated the prediction accuracy. On DCA, the nomogram presented good net benefit gains across a wide range of threshold probabilities. Furthermore, the Nomogram-related risk score was used to divide the patient population into two groups with significant recurrence disparities.ConclusionFor the prediction of NMIBC recurrence, our unique nomogram demonstrated a respectable degree of discriminative capacity, sufficient calibration, and considerable net benefit gain. There will be a need for additional internal and external validation.

Gene Expression Patterns Associated with Survival in Glioblastoma.

The aim of this study was to investigate gene expression alterations associated with overall survival (OS) in glioblastoma (GBM). Using the Nanostring nCounter platform, we identified four genes (COL1A2, IGFBP3, NGFR, and WIF1) that achieved statistical significance when comparing GBM with non-neoplastic brain tissue. The four genes were included in a multivariate Cox Proportional Hazard model, along with age, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation, to create a unique glioblastoma prognostic index (GPI). The GPI score inversely correlated with survival: patient with a high GPI had a median OS of 7.5 months (18-month OS = 9.7%) whereas patients with a low GPI had a median OS of 20.1 months (18-month OS = 54.5%; log rank p-value = 0.004). The GPI score was then validated in 188 GBM patients from The Cancer Genome Atlas (TCGA) from a national data base; similarly, patients with a high GPI had a median OS of 10.5 months (18-month OS = 12.4%) versus 16.9 months (18-month OS = 41.5%) for low GPI (log rank p-value = 0.0003). We conclude that this novel mRNA-based prognostic index could be useful in classifying GBM patients into risk groups and refine prognosis estimates to better inform treatment decisions or stratification into clinical trials.

Novel Echocardiogram Analysis of Cardiac Dysfunction is Associated with Mortality in Pediatric Sepsis.

The objective of our study was to semi-automatically generate echocardiogram indices in pediatric sepsis using novel algorithms and determine which indices were associated with mortality. We hypothesized that strain and diastolic indices would be most associated with mortality. Retrospective cohort study of children with sepsis from 2017-2022. Survivors and non-survivors were compared for echocardiogram indices. Multivariate Cox proportional hazard models were constructed for our primary outcome of in-hospital mortality. Linear regression was performed for secondary outcomes, which included multiple composite 28-day outcomes. Of the 54 patients in the study 9 (17%) died. Multiple echocardiogram indices of both right (RV) and left ventricles (LV) were associated with in-hospital mortality [RV GLS adjusted hazard ratio (aHR): 1.16 (1.03-1.29), p-value 0.011; RV global longitudinal early diastolic strain rate (GLSre) aHR:0.24 (0.07 to 0.75), p-value 0.014; LV GLSre aHR: 0.33 (0.11-0.97), p-value 0.044]. Impairment in GLS was associated with fewer ventilator-free days [RV GLS β-coefficient: -0.47 (-0.84 to -0.10), p-value 0.013; LV GLS β-coefficient -0.62 (-1.07 to -0.17), p-value 0.008], organ-support free days [RV GLS β-coefficient: -0.49 (-0.87 to -0.11), p-value 0.013; LV GLS β-coefficient: -0.64 (-1.10 to -0.17), p-value 0.008], and days free from ICU [RV GLS β-coefficient: -0.42 (-0.79 to -0.05), p-value 0.026; LV GLS β-coefficient:-0.58 (-1.03 to -0.13), p-value 0.012]. Systolic indices were not associated with mortality in this cohort. Our study demonstrates the feasibility of obtaining echocardiogram indices in a semi-automatic method using our algorithms. We showed that abnormal strain is associated with worse outcomes in a cohort of children with sepsis.

Abstract 4812: Evaluating racial and ethnic differences in advanced-stage laryngeal cancer treatment and outcomes in Florida: Unmasking the inequities

Abstract Purpose: To evaluate the association between race/ethnicity, treatment, and mortality among individuals with advanced-stage laryngeal cancer in Florida. Methods: We obtained data from the Florida Cancer Data System (FCDS) on non-Hispanic (NH)-White (the reference group), Hispanic, and NH-Black patients with advanced-stage (regional and distant) laryngeal cancer from 2009 to 2020. Sociodemographic factors were obtained from FCDS (age, marital status, and insurance) and the United States Census at the county level (education, household income, and rurality). Treatment strategies included chemoradiation, surgery followed by chemoradiation, chemotherapy, radiation, surgery, and surgery followed by chemotherapy. The primary outcome was overall mortality. Multivariable Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) and to examine the association of race/ethnicity with treatment and survival, while adjusting for sociodemographic factors. Results: There were 4,522 participants with advanced-stage laryngeal cancer (57.9% &amp;lt;65 years, 79.5% male, 75.4% NH-White, 13.1% Hispanic, and 11.5% NH-Black) included in the analysis. Compared to NH-White patients, NH-Black patients were less likely to be married, have private insurance, and live in an urban county. Moreover, NH-Black individuals were less likely to receive chemoradiation alone and were more likely to receive surgery followed by chemoradiation. Government insurance was highly associated with chemoradiation receipt. In age-adjusted models, NH-Black patients with advanced-stage laryngeal cancer had a higher risk of death compared to NH-White patients (HR: 1.19; 95% CI: 1.06, 1.32), while Hispanic patients had a lower risk of death compared to NH-White patients (HR: 0.80; 95% CI: 0.71, 0.89). After adjusting for sociodemographic factors, there was no statistically significant difference in overall mortality in NH-Black patients compared to NH-White patients (HR: 1.07; 95% CI: 0.96, 1.20). However, among individuals who received chemoradiation, NH-Black patients had a higher risk of mortality, even after adjusting for sociodemographic factors, compared to NH-White patients (HR: 1.27; 95% CI: 1.04, 1.55). Conclusions: Among patients with advanced-stage laryngeal cancer in Florida, NH-Black patients experienced a higher risk of overall mortality compared to other racial and ethnic groups, but this discrepancy was primarily among those who received chemoradiation, even after accounting for sociodemographic factors. This study emphasizes the urgency of expanding laryngeal cancer care access for NH-Black individuals and investigating possible biological variations in their response to chemoradiation and subsequent survival outcomes. Citation Format: Caretia J. Washington, Chayil Lattimore, Dejana Braithwaite, Kristianna Fredenburg, Shama Karanth. Evaluating racial and ethnic differences in advanced-stage laryngeal cancer treatment and outcomes in Florida: Unmasking the inequities [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 4812.

Abstract 848: Influence of young age at diagnosis on the clinical presentation of disease and survival among patients with multiple myeloma

Abstract Background: Age is an important prognostic factor for multiple myeloma (MM). We evaluated the influence of age on the clinical presentation and outcomes among newly diagnosed patients with MM to optimize risk stratification. Methods: In 850 patients with first primary confirmed MM prospectively enrolled in the Integrative Molecular And Genetic Epidemiology (IMAGE) study (2009-2020), we evaluated the presence of diagnostic myeloma-defining events (MDE), progression free survival (PFS) and overall survival (OS) by young age at diagnosis (≤50 years). We evaluated the association of young age with the prevalence of diagnostic MDE, clinical features and chromosomal abnormalities using the prevalence odds ratio (OR) and corresponding 95% confidence interval (CI) calculated from multivariable logistic regression. Median PFS and OS were graphically examined using Kaplan-Meier survival curves with log-rank tests used to compare survival by diagnostic age group. Risks of disease progression and all-cause mortality were estimated using hazard ratios (HR) and corresponding 95% CI calculated from multivariable Cox proportional hazard models. Results.: Of the 850 patients, 15.4% were diagnosed at ≤50 years of age, 54% were male and 40% self-identified as Black. Compared to patients diagnosed with MM over the age of 50, young patients were more likely to self-identify as Black (59.5% vs 40.5%; P&amp;lt;0.0001) and to report a negative smoking history (66.2% v 56.4%; P=0.01), and less likely to present with age-dependent comorbidities including hypertension, hyperlipidemia and diabetes mellitus type II (P≤0.0001). In multivariable analyses, young patients, compared to older patients, were more likely to present at diagnosis with higher median percent bone marrow plasma cells (70% v 55%; P=0.02) and to undergo autologous stem cell transplant (ASCT) as part of their first-line treatment (82.0% v 67.6%; P=0.01) after controlling for sex, race, body mass index, smoking status and comorbidities. We did not observe significant associations of young age with the prevalence of any other MDE, clinical feature or chromosomal abnormality evaluated. The median OS was 106.9 months (range, 0.23-356.1). OS was significantly longer in young patients with MM compared to patients aged greater than 50 years (159 v 99 months, respectively; P&amp;lt;0.001) leading to a suggestive 1.5-fold decreased risk of mortality among younger newly diagnosed patients (HR=0.67, 95% CI 0.39-1.14; P=0.14) after adjusting for sex, International Staging System-stage, adverse cytogenetic abnormalities, and ASCT. We did not observe associations with age and PFS (P=0.81). Conclusions: Findings suggest that newly diagnosed younger patients with MM are more likely to self-identify as Black, present with more bone marrow plasma cells, have less age-dependent comorbidities, and undergo ASCT leading to a suggestive survival advantage. Citation Format: Krystle L. Ong, Kevin D. Arnold, Gayathri Ravi, Luciano J. Costa, Elizabeth E. Brown. Influence of young age at diagnosis on the clinical presentation of disease and survival among patients with multiple myeloma [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 848.