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BACKGROUND: Bacillus Calmette-Guérin (BCG) is currently the most clinically effective intravesical treatment for non-muscle-invasive bladder cancer (NMIBC), particularly for patients with high-risk NMIBC such as those with carcinoma in situ. BCG treatments could be optimized to improve patient safety and conserve supply by predicting BCG efficacy based on tumor characteristics or clinicopathological criteria. OBJECTIVE: The aim of this study is to assess the ability of specific clinicopathological criteria to predict tumor recurrence in patients with NMIBC who received BCG therapy along various treatment timelines. METHODS: A total of 1331 patients (stage Ta, T1, or carcinoma in situ) who underwent transurethral resection of a bladder tumor between 2006 and 2017 were included. Univariate analysis, including laboratory tests (eg, complete blood panels, creatinine levels, and hemoglobin A1c levels) within 180 days of BCG therapy initiation, medications, and clinical and demographic variables to assess their ability to predict NMIBC recurrence, was completed. This was followed by multivariate regression that included the elements of the Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model and variables that were significant predictors of recurrence in univariate analysis. RESULTS: BCG was administered to 183 patients classified as intermediate or high risk, and 76 (41.5%) experienced disease recurrence. An abnormal neutrophil-to-lymphocyte ratio measured within 180 days of induction BCG therapy was a significant predictor (P=.047) of future cancer recurrence and was a stronger predictor than the CUETO score or the individual variables included in the CUETO scoring model through multivariate analysis. CONCLUSIONS: An abnormal neutrophil-to-lymphocyte ratio within 180 days of BCG therapy initiation is predictive of recurrence and could be suggestive of additional or alternative interventions.
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PURPOSE: Smoking has a strong causal association with bladder cancer but the relationship with recurrence is not well established. We sought to assess the association of smoking status on recurrence of non-muscle invasive bladder cancer (NMIBC) in a contemporary cohort of patients with predominantly high-risk, recurrent NMIBC managed with photodynamic enhanced cystoscopy. MATERIALS AND METHODS: We performed a retrospective study of patients with NMIBC included in a multi-institutional registry. Our primary exposure of interest was smoking status. Our primary outcome was first recurrence of NMIBC. Kaplan-Meier analysis was used to calculate recurrence free probabilities and Cox proportional hazards regression was used to evaluate the impact of smoking status on recurrence free survival. RESULTS: Our analytic cohort included 723 adults with bladder cancer, 11.5% with primary NMIBC and 88.5% with recurrent NMIBC. The majority of patients were white, male, and had high-risk NMIBC (72.6%). 52.6% of included patients were former smokers and 12.7% were current smokers. During the three-year study period, there was a NMIBC recurrence in 259 of the 723 patients (35.8%). The 1- and 3-year probability of recurrence was 19% and 44%, respectively. The grade and stage of recurrences were 28.9% LG Ta, 34.4% HG Ta, 15.8% pure CIS, 0.3% LG T1, 15.4% HG T1, and 5.4% unknown. After adjustment for a priori clinical and demographic factors, smoking status had no significant association with recurrence. CONCLUSION: Smoking status was not significantly association with recurrence in a study of patients with predominantly high-risk recurrent NMIBC managed with photodynamic enhanced cystoscopy.
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Cistoscopía/métodos , Fumar/efectos adversos , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Humanos , Masculino , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: The risk of thromboembolism and bleeding before initiation of oral anticoagulant (OAC) in atrial fibrillation patients is estimated by CHA2DS2-VASc and HAS-BLED scoring system, respectively. Patients' socioeconomic status (SES) could influence these risks, but its impact on the two risk scores' predictive performance with respect to clinical events remains unknown. Our objective was to determine if patient SES defined by area deprivation index (ADI), in conjunction with CHA2DS2-VASc and HAS-BLED scores, could guide oral anticoagulation therapy. METHODS AND FINDINGS: The study cohort included newly diagnosed patients with AF who were treated with warfarin. The cohort was stratified by the time in therapeutic range of INR (TTR), ADI, CHA2DS2-VASc, and HAS-BLED risk scores. TTR and ischemic and bleeding events during the first year of therapy were compared across subpopulations. Among 7274 patients, those living in the two most deprived quintiles (ADI ≥60%) had a significantly higher risk of ischemic events and those in the most deprived quintile (ADI≥80%) had a significantly increased risk of bleeding events. ADI significantly improved the predictive performance of CHA2DS2-VASc but not HAS-BLED risk scores. CONCLUSION: ADI can predict increased risk for ischemic and bleeding events in the first year of warfarin therapy in patients with incident AF.
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Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Hemorragia/inducido químicamente , Accidente Cerebrovascular/inducido químicamente , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Clase Social , Factores SocioeconómicosRESUMEN
PURPOSE: We evaluated the AUA (American Urological Association)/SUO (Society of Urologic Oncology) nonmuscle invasive bladder cancer risk model to predict nonmuscle invasive bladder cancer recurrence and progression prior to death. MATERIALS AND METHODS: We performed a retrospective analysis using electronic medical records and cancer registry data of patients with nonmuscle invasive bladder cancer in a multicenter United States patient population. We evaluated recurrence-free and progression-free survival according to the AUA/SUO nonmuscle invasive bladder cancer risk model. We then assessed discriminative performance with the c-index and compared the cumulative incidence of recurrence, progression and death across 4 age groups. RESULTS: We identified 1,297 patients with nonmuscle invasive bladder cancer. Median followup in the cohort was 3.2 years. The c-index of the AUA/SUO recurrence model was 0.62 and for progression it was higher at 0.77. Patients younger than 60 years had a 40% greater probability of recurrent nonmuscle invasive bladder cancer vs death while patients 84 years old or older had a 12% greater probability of death prior to recurrence at 5 years. This study was limited by its retrospective design. CONCLUSIONS: The AUA/SUO nonmuscle invasive bladder cancer risk model provides predictive performance of recurrence and progression similar to that of previous similar risk models, such as the models of the European Organization for Research and Treatment of Cancer, the Club Urológico Español de Tratamiento Oncológico and the National Comprehensive Cancer Network®. This work illustrates the need to consider age in predictive tools for clinicians who treat patients with nonmuscle invasive bladder cancer.
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Recurrencia Local de Neoplasia/diagnóstico , Neoplasias de la Vejiga Urinaria/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Supervivencia sin Progresión , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Estados Unidos/epidemiología , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
We apply a treatment simulation and optimization approach to develop decision support guidance for warfarin precision treatment plans. Simulation include the use of â¼1,500,000 clinical avatars (simulated patients) generated by an integrated data-driven and domain-knowledge based Bayesian Network Modeling approach. Subsequently, we simulate 30-day individual patient response to warfarin treatment of five clinical and genetic treatment plans followed by both individual and subpopulation based optimization. Sub-population optimization (compared to individual optimization) provides a cost effective and realistic means of implementation of a precision-driven treatment plan in practical settings. In this project, we use the property of minimal entropy to minimize overall adverse risks for the largest possible patient sub-populations and we temper the results by considering both transparency and ease of implementation. Finally, we discuss the improved outcome of the precision treatment plan based on the sub-population optimized decision support rules.
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Anticoagulantes/uso terapéutico , Warfarina/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Ensayos Clínicos como Asunto/estadística & datos numéricos , Biología Computacional/métodos , Simulación por Computador , Técnicas de Apoyo para la Decisión , Sistemas Especialistas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Farmacogenómica/estadística & datos numéricos , Medicina de Precisión/estadística & datos numéricos , Factores de Riesgo , Warfarina/administración & dosificación , Warfarina/efectos adversosRESUMEN
BACKGROUND: Clinical trials testing pharmacogenomic-guided warfarin dosing for patients with atrial fibrillation have demonstrated conflicting results. Non-vitamin K antagonist oral anticoagulants are expensive and contraindicated for several conditions. A strategy optimizing anticoagulant selection remains an unmet clinical need. METHODS AND RESULTS: Characteristics from 14 206 patients with atrial fibrillation were integrated into a validated warfarin clinical trial simulation framework using iterative Bayesian network modeling and a pharmacokinetic-pharmacodynamic model. Individual dose-response for patients was simulated for 5 warfarin protocols-a fixed-dose protocol, a clinically guided protocol, and 3 increasingly complex pharmacogenomic-guided protocols. For each protocol, a complexity score was calculated using the variables predicting warfarin dose and the number of predefined international normalized ratio (INR) thresholds for each adjusted dose. Study outcomes included optimal time in therapeutic range ≥65% and clinical events. A combination of age and genotype identified different optimal protocols for various subpopulations. A fixed-dose protocol provided well-controlled INR only in normal responders ≥65, whereas for normal responders <65 years old, a clinically guided protocol was necessary to achieve well-controlled INR. Sensitive responders ≥65 and <65 and highly sensitive responders ≥65 years old required pharmacogenomic-guided protocols to achieve well-controlled INR. However, highly sensitive responders <65 years old did not achieve well-controlled INR and had higher associated clinical events rates than other subpopulations. CONCLUSIONS: Under the assumptions of this simulation, patients with atrial fibrillation can be triaged to an optimal warfarin therapy protocol by age and genotype. Clinicians should consider alternative anticoagulation therapy for patients with suboptimal outcomes under any warfarin protocol.
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Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/genética , Medicina de Precisión/métodos , Warfarina/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Teorema de Bayes , Ensayos Clínicos como Asunto/métodos , Simulación por Computador , Femenino , Genotipo , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Farmacogenética/métodos , Warfarina/farmacocinéticaRESUMEN
PURPOSE: We assessed the performance of the EORTC (European Organisation for Research and Treatment of Cancer) and CUETO (Club Urológico Español de Tratamiento Oncológico) nonmuscle invasive bladder cancer predictive models compared to current United States NCCN Guidelines® in an American population. MATERIALS AND METHODS: We retrospectively analyzed the electronic medical records of patients with nonmuscle invasive bladder cancer in a multicenter population in the United States. We evaluated recurrence-free and progression-free survival according to EORTC and CUETO, and assessed discriminative performance with the c-index at 1 and 5 years. We then compared the discrimination of EORTC and CUETO to the discrimination of the 4 nonmuscle invasive bladder cancer treatment groups described in NCCN Guidelines. RESULTS: We identified 1,333 patients with nonmuscle invasive bladder cancer and a median followup of 37 months. At 5 years the recurrence c-index of EORTC and CUETO was 0.59 and 0.56 while for progression it was higher at 0.74 and 0.72, respectively. NCCN Guidelines demonstrated a similar c-index of 0.56 and 0.75, respectively. The discrimination of all 3 risk models decreased in patients who received bacillus Calmette-Guérin. EORTC was better able to identify patients at low risk for recurrence or progression but it overestimated the 5-year risk of progression in patients at high risk. This study was limited by its retrospective design. CONCLUSIONS: Our work illustrates the need for improved predictive tools for clinicians who treat patients with nonmuscle invasive bladder cancer. However, until new tools are developed NCCN Guidelines are a simple option for clinicians who treat patients with nonmuscle invasive bladder cancer. Those guidelines provide predictive power comparable to that of the EORTC and CUETO models.
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Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/patología , Recurrencia Local de Neoplasia/diagnóstico , Medición de Riesgo/métodos , Neoplasias de la Vejiga Urinaria/patología , Administración Intravesical , Anciano , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/terapia , Cistectomía , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Guías de Práctica Clínica como Asunto , Valor Predictivo de las Pruebas , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos , Medición de Riesgo/normas , Estados Unidos , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
We tested optimization-based approaches to generate decision support rules used to improve personalized warfarin treatment based on clinical and genetic characteristics. Our approach simulated warfarin treatment outcomes using five existing treatment plans for clinical avatars (virtual patients). We used individual clinical avatar Time-in-Therapeutic-Range to represent the two-sided adverse risk to bleeding (over dosed - above therapeutic range) and thrombosis (under dosed - below therapeutic range) and as the objective function in the optimization to minimize overall risk. A series of optimization approaches demonstrate that correctly selected decision rules matched to particularly characterized patients produce treatment plans that minimize risk. Finally, a decision tree algorithm was used to produce decision rules, each of which indicated a specific treatment plan that optimally reduce risks for a patient subgroup. The optimization approach minimizes entropy/impurity property thus producing rules that identify treatment plans that minimize overall adverse risks for the largest possible patient subgroups.