Samuel Swisher-McClure

Androgen Deprivation Therapy and Future Alzheimer’s Disease Risk

PURPOSE To test the association of androgen deprivation therapy (ADT) in the treatment of prostate cancer with subsequent Alzheimers disease risk. METHODS We used a previously validated and implemented text-processing pipeline to analyze electronic medical record data in a retrospective cohort of patients at Stanford University and Mt. Sinai hospitals. Specifically, we extracted International Classification of Diseases-9th revision diagnosis and Current Procedural Terminology codes, medication lists, and positive-present mentions of drug and disease concepts from all clinical notes. We then tested the effect of ADT on risk of Alzheimers disease using 1:5 propensity score-matched and traditional multivariable-adjusted Cox proportional hazards models. The duration of ADT use was also tested for association with Alzheimers disease risk. RESULTS There were 16,888 individuals with prostate cancer meeting all inclusion and exclusion criteria, with 2,397 (14.2%) receiving ADT during a median follow-up period of 2.7 years (interquartile range, 1.0-5.4 years). Propensity score-matched analysis (hazard ratio, 1.88; 95% CI, 1.10 to 3.20; P = .021) and traditional multivariable-adjusted Cox regression analysis (hazard ratio, 1.66; 95% CI, 1.05 to 2.64; P = .031) both supported a statistically significant association between ADT use and Alzheimers disease risk. We also observed a statistically significant increased risk of Alzheimers disease with increasing duration of ADT (P = .016). CONCLUSION Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of Alzheimers disease in a general population cohort. This study demonstrates the utility of novel methods to analyze electronic medical record data to generate practice-based evidence.

Dose-Escalated Irradiation and Overall Survival in Men With Nonmetastatic Prostate Cancer

IMPORTANCE In 5 published randomized clinical trials, dose-escalated external-beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, scarce evidence addresses whether dose escalation improves overall survival. OBJECTIVE To examine the association between dose-escalated EBRT and overall survival among men with nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective, nonrandomized comparative effectiveness study of dose-escalated vs standard-dose EBRT for prostate cancer diagnosed from 2004 to 2006 using the National Cancer Database (NCDB), which includes data from patients treated at Commission on Cancer-accredited community, academic, and comprehensive cancer facilities. Three cohorts were evaluated: men with low-risk (n = 12,229), intermediate-risk (n = 16,714), or high-risk (n = 13,538) prostate cancer. EXPOSURES We categorized patients in each risk cohort into 2 treatment groups: standard-dose (from 68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT (1 Gy = 100 rad). MAIN OUTCOMES AND MEASURES We compared overall survival between treatment groups in each analytic cohort using Cox proportional hazard models with an inverse probability weighted propensity score (IPW-PS) approach. In secondary analyses, we evaluated dose response for survival. RESULTS Dose-escalated EBRT was associated with improved survival in the intermediate-risk (IPW-PS adjusted hazard ratio [HR], 0.84; 95% CI, 0.80-0.88; P < .001) and high-risk groups (HR, 0.82; 95% CI, 0.78-0.85; P < .001) but not the low-risk group (HR, 0.98; 95% CI, 0.92-1.05; P = .54). For every incremental increase of about 2 Gy in dose, there was a 7.8% (95% CI, 5.4%-10.2%; P < .001) and 6.3% (95% CI, 3.3%-9.1%; P < .001) reduction in the hazard of death for intermediate- and high-risk patients, respectively. CONCLUSIONS AND RELEVANCE Dose-escalated EBRT is associated with improved overall survival in men with intermediate- and high-risk prostate cancer but not low-risk prostate cancer. These results add to the evidence questioning aggressive local treatment strategies in men with low-risk prostate cancer but supporting such treatment in men with greater disease severity.

Low rates of adjuvant radiation in patients with nonmetastatic prostate cancer with high‐risk pathologic features

The 2013 American Urological Association/American Society for Radiation Oncology consensus guidelines recommend offering adjuvant radiotherapy (RT) after radical prostatectomy in patients with high‐risk pathologic features for recurrence. In the current study, the authors examined practice patterns of adjuvant RT use in patients with elevated pathologic risk factors over a time period spanning the publication of supporting randomized evidence.

Association Between Androgen Deprivation Therapy and Risk of Dementia

Importance A growing body of evidence supports a link between androgen deprivation therapy (ADT) and cognitive dysfunction, including Alzheimer disease. However, it is currently unknown whether ADT may contribute to the risk of dementia more broadly. Objective To use an informatics approach to examine the association of ADT as a treatment for prostate cancer with the subsequent development of dementia (eg, senile dementia, vascular dementia, frontotemporal dementia, and Alzheimer dementia). Design, Setting, and Participants In this cohort study, a text-processing method was used to analyze electronic medical record data from an academic medical center from 1994 to 2013, with a median follow-up of 3.4 years (interquartile range, 1.0-7.2 years). We identified 9455 individuals with prostate cancer who were 18 years or older at diagnosis with data recorded in the electronic health record and follow-up after diagnosis. We excluded 183 patients with a previous diagnosis of dementia. Our final cohort comprised 9272 individuals with prostate cancer, including 1826 men (19.7%) who received ADT. Main Outcomes and Measures We tested the effect of ADT on the risk of dementia using propensity score–matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results Among 9272 men with prostate cancer (mean [SD] age, 66.9 [10.9] years; 5450 [58.8%] white), there was a statistically significant association between use of ADT and risk of dementia (hazard ratio, 2.17; 95% CI, 1.58-2.99; P < .001). In sensitivity analyses, results were similar when excluding patients with Alzheimer disease (hazard ratio, 2.32; 95% CI, 1.73-3.12; P < .001). The absolute increased risk of developing dementia among those who received ADT was 4.4% at 5 years (7.9% among those who received ADT vs 3.5% in those who did not receive ADT). Analyses stratified by duration of ADT found that individuals with at least 12 months of ADT use had the greatest absolute increased risk of dementia (hazard ratio, 2.36; 95% CI, 1.64-3.38; P < .001). Kaplan-Meier analysis demonstrated that ADT users 70 years or older had the lowest cumulative probability of remaining dementia free (log-rank P < .001). Conclusions and Relevance Androgen deprivation therapy in the treatment of prostate cancer may be associated with an increased risk of dementia. This finding should be further evaluated in prospective studies.

Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes

PURPOSE To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national cancer registry. METHODS AND MATERIALS Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score-adjusted and inverse probability of treatment-weighted Cox proportional hazards methods. Sensitivity analyses were performed to account for unmeasured confounders. RESULTS A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio [OR] 0.52, 95% confidence interval [CI] 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment-weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses. CONCLUSIONS Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL may not apply to T4a disease, and patients should be counseled accordingly.

Radical Cystectomy versus Bladder-Preserving Therapy for Muscle-Invasive Urothelial Carcinoma: Examining Confounding and Misclassification Biasin Cancer Observational Comparative Effectiveness Research

OBJECTIVES Radical cystectomy (RC) is the standard treatment for muscle-invasive urothelial carcinoma of the bladder. Trimodality bladder-preserving therapy (BPT) is an alternative to RC, but randomized comparisons of RC versus BPT have proven infeasible. To compare RC versus BPT, we undertook an observational cohort study using registry and administrative claims data from the Surveillance, Epidemiology and End Results-Medicare database. METHODS We identified patients age 65 years or older diagnosed between 1995 and 2005 who received RC (n = 1426) or BPT (n = 417). We examined confounding and stage misclassification in the comparison of RC and BPT by using multivariable adjustment, propensity score-based adjustment, instrumental variable (IV) analysis, and simulations. RESULTS Patients who received BPT were older and more likely to have comorbid disease. After propensity score adjustment, BPT was associated with an increased hazard of death from any cause (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.05-1.53) and from bladder cancer (HR 1.31; 95% CI 0.97-1.77). Using the local area cystectomy rate as an instrument, IV analysis demonstrated no differences in survival between BPT and RC (death from any cause HR 1.06; 95% CI 0.78-1.31; death from bladder cancer HR 0.94; 95% CI 0.55-1.18). Simulation studies for stage misclassification yielded results consistent with the IV analysis. CONCLUSIONS Survival estimates in an observational cohort of patients who underwent RC versus BPT differ by analytic method. Multivariable and propensity score adjustment revealed greater mortality associated with BPT relative to RC, while IV analysis and simulation studies suggest that the two treatments are associated with similar survival outcomes.

Risk of fatal cerebrovascular accidents after external beam radiation therapy for early‐stage glottic laryngeal cancer

This study compared the risk of fatal cerebrovascular accidents (CVAs) in patients with early‐stage glottic laryngeal cancer receiving surgery or external beam radiation therapy (EBRT).

Patterns of care and perioperative outcomes in transoral endoscopic surgery for oropharyngeal squamous cell carcinoma.

Transoral endoscopic surgery is a promising new treatment for oropharyngeal squamous cell carcinoma (SCC).

Clinical impact of prolonged diagnosis to treatment interval (DTI) among patients with oropharyngeal squamous cell carcinoma

PURPOSE/OBJECTIVE(S) We examined practice patterns using the National Cancer Data Base (NCDB) to determine risk factors for prolonged diagnosis to treatment interval (DTI) and survival outcomes in patients receiving chemoradiation for oropharyngeal squamous cell carcinoma (OPSCC). METHODS AND MATERIALS We identified 6606 NCDB patients with Stage III-IV OPSCC receiving chemoradiation from 2003 to 2006. We determined risk factors for prolonged DTI (>30days) using univariate and multivariable logistic regression models. We examined overall survival (OS) using Kaplan Meier and multivariable Cox proportional hazards models. RESULTS 3586 (54.3%) patients had prolonged DTI. Race, IMRT, insurance status, and high volume facilities were significant risk factors for prolonged DTI. Patients with prolonged DTI had inferior OS compared to DTI⩽30days (Hazard Ratio (HR)=1.12, 95% CI 1.04-1.20, p=0.005). For every week increase in DTI there was a 2.2% (95% CI 1.1-3.3%, p<0.001) increase in risk of death. Patients receiving IMRT, treatment at academic, or high-volume facilities were more likely to experience prolonged DTI (High vs. Low volume: 61.5% vs. 51.8%, adjusted OR 1.38, 95% CI 1.21-1.58; Academic vs. Community: 59.5% vs. 50.6%, adjusted OR 1.26, 95% CI 1.13-1.42; non-IMRT vs. IMRT: 53.4% vs. 56.5%; adjusted OR 1.17, 95% CI 1.04-1.31). CONCLUSIONS Our results suggest that prolonged DTI has a significant impact on survival outcomes. We observed disparities in DTI by socioeconomic factors. However, facility level factors such as academic affiliation, high volume, and IMRT also increased risk of DTI. These findings should be considered in developing efficient pathways to mitigate adverse effects of prolonged DTI.

Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

PURPOSE To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. METHODS AND MATERIALS We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. RESULTS Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. CONCLUSIONS Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.