Westmont, IL, United States
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Huynh M.A.,Brigham and Women's Hospital | Chen M.-H.,University of Connecticut | Wu J.,University of Connecticut | Braccioforte M.H.,Prostate Cancer Foundation of Chicago | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2016

Purpose To explore whether a subgroup of men with unfavorable-risk prostate cancer (PC) exists in whom high-dose radiation therapy (RT) alone is sufficient to avoid excess PC death due to competing risk from cardiometabolic comorbidity. Methods and Materials This was a cohort study of 7399 men in whom comorbidity (including congestive heart failure, diabetes mellitus, or myocardial infarction) was assessed and recorded with T1-3NxM0 PC treated with brachytherapy with or without neoadjuvant RT, October 1997 to May 2013 at a single providing institution. Cox and competing risks regression analyses were used to assess whether men with unfavorable-intermediate/high-risk versus favorable-intermediate/low-risk PC were at increased risk of PC-specific, all-cause, or other-cause mortality (PCSM, ACM, OCM), adjusting for number of comorbidities, age at and year of brachytherapy, RT use, and an RT treatment propensity score. Results After a median follow-up of 7.7 years, 935 men died: 80 of PC and 855 of other causes. Among men with no comorbidity, PCSM risk (adjusted hazard ratio [AHR] 2.74 [95% confidence interval (CI) 1.49-5.06], P=.001) and ACM risk (AHR 1.30 [95% CI 1.07-1.58], P=.007) were significantly increased in men with unfavorable-intermediate/high-risk PC versus favorable-intermediate/low-risk PC, with no difference in OCM (P=.07). Although PCSM risk was increased in men with 1 comorbidity (AHR 2.87 [95% CI 1.11-7.40], P=.029), ACM risk was not (AHR 1.03 [95% CI 0.78-1.36], P=.84). Neither PCSM risk (AHR 4.39 [95% CI 0.37-51.98], P=.24) or ACM risk (AHR 1.43 [95% CI 0.83-2.45], P=.20) was increased in men with 2 comorbidities. Conclusions To minimize death from PC, high-dose RT alone may be sufficient treatment in men with 2 or more cardiometabolic comorbidities and unfavorable-intermediate- and high-risk PC. © 2016 Elsevier Inc.


D'Amico A.V.,Dana-Farber Cancer Institute | Braccioforte M.H.,Prostate Cancer Foundation of Chicago | Moran B.J.,Prostate Cancer Foundation of Chicago | Chen M.-H.,University of Connecticut
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: To determine whether prevalent diabetes mellitus (pDM) affects the presentation, extent of radiotherapy, or prostate cancer (PCa)-specific mortality (PCSM) and whether PCa aggressiveness affects the risk of non-PCSM, DM-related mortality, and all-cause mortality in men with pDM. Methods: Between October 1997 and July 2907, 5,279 men treated at the Chicago Prostate Cancer Center with radiotherapy for PCa were included in the study. Logistic and competing risk regression analyses were performed to assess whether pDM was associated with high-grade PCa, less aggressive radiotherapy, and an increased risk of PCSM. Competing risks and Cox regression analyses were performed to assess whether PCa aggressiveness described by risk group in men with pDM was associated with the risk of non-PCSM, DM-related mortality, and all-cause mortality. Analyses were adjusted for predictors of high-grade PCa and factors that could affect treatment extent and mortality. Results: Men with pDM were more likely (adjusted hazard ratio [AHR], 1.9; 95% confidence interval [CI], 1.3-2.7; p = .002) to present with high-grade PCa but were not treated less aggressively (p = .33) and did not have an increased risk of PCSM (p = .58) compared to men without pDM. Among the men with pDM, high-risk PCa was associated with a greater risk of non-PCSM (AHR, 2.2; 95% CI, 1.1-4.5; p = .035), DM-related mortality (AHR, 5.2; 95% CI, 2.0-14.0; p = .001), and all-cause mortality (AHR, 2.4; 95% CI, 1.2-4.7; p = .01) compared to favorable-risk PCa. Conclusion: Aggressive management of pDM is warranted in men with high-risk PCa. Copyright © 2010 Elsevier Inc.


Nanda A.,Anderson Cancer Center Orlando | Chen M.-H.,University of Connecticut | Moran B.J.,Prostate Cancer Foundation of Chicago | Braccioforte M.H.,Prostate Cancer Foundation of Chicago | D'Amico A.V.,Dana-Farber Cancer Institute
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose: To assess the impact of coronary artery disease (CAD) risk factors and sequelae on the risk of all-cause mortality (ACM) in men treated for prostate cancer (PC). Methods and Materials: The study cohort comprised 5077 men with PC consecutively treated with curative intent between 1997 and 2006 at the Chicago Prostate Cancer Center. Cox and Fine and Gray's competing risks regression multivariable analyses were performed, assessing whether cardiovascular comorbidity impacted the risk of ACM and PC-specific mortality, respectively, adjusting for CAD risk factors (diabetes mellitus, hypercholesterolemia, or hypertension) and sequelae (congestive heart failure or myocardial infarction), age, year and type of treatment, and known PC prognostic factors. Results: When compared with men with no comorbidity there was a significantly increased risk of ACM in men with congestive heart failure or myocardial infarction (adjusted hazard ratio [AHR] 1.96, P<.001) and in men with diabetes mellitus (AHR 1.60, P=.03) and hypertension (AHR 1.25, P=.04). In contrast, men with hypercholesterolemia had a similar risk of ACM (AHR 0.68, P=.17) when compared with men with no comorbidity. Other factors associated with a significantly increased risk of ACM included age (AHR 1.09, P<.001), prostate-specific antigen level (AHR 1.25, P=.008), and Gleason score 8-10 disease (AHR 1.71, P=.003). Cardiovascular comorbidity did not impact the risk of PC-specific mortality. Conclusions: In addition to age and unfavorable PC prognostic factors, select CAD risk factors and sequelae are associated with an increased risk of ACM in men treated for PC. These comorbidity prognostic factors predict time courses of mortality from competing causes, which may be factored into the decision-making process when considering management options for PC in a given individual. © 2013 Elsevier Inc.


Wattson D.A.,Brigham and Women's Hospital | Chen M.-H.,University of Connecticut | Moul J.W.,Duke University | Moran B.J.,Prostate Cancer Foundation of Chicago | And 6 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To determine whether an increasing number of high-risk factors is associated with higher prostate cancer-specific mortality (PCSM) among men treated with brachytherapy (BT)-based treatment, and whether supplemental therapy has an impact on this risk. Methods and Materials: We analyzed the cases of 2234 men with localized prostate cancer treated between 1991 and 2007 with low-dose rate BT monotherapy (n = 457) or BT with supplemental external-beam radiotherapy (EBRT, n = 229), androgen suppression therapy (AST, n = 424), or both (n = 1124). All men had at least one high-risk factor (prostate-specific antigen >20 ng/mL, biopsy Gleason score 8-10, or clinical stage ≥T2c). Competing-risks multivariable regressions were performed to determine whether the presence of at least two high-risk factors was associated with an increased risk of PCSM, with adjustment for age, comorbidity, and the type of supplemental treatment. Results: The median follow-up time was 4.3 years. The number of men with at least two high-risk factors was highest in the group treated with BT, EBRT, and AST (21%), followed by BT plus EBRT or AST (13%), and BT alone (8%) (p trend < 0.001). The adjusted hazard ratio (AHR) for PCSM for those with at least two high-risk factors (as compared with one) was 4.8 (95% confidence interval [CI], 2.8-8.0; p < 0.001). The use of both supplemental EBRT and AST was associated with a decreased risk of PCSM (AHR 0.5; 95% CI, 0.2-0.9; p = 0.03) compared with BT alone. When the high-risk factors were analyzed separately, Gleason score 8-10 was most significantly associated with increased PCSM (AHR 6.2; 95% CI, 3.5-11.2; p < 0.001). Conclusions: Men with high-risk prostate adenocarcinoma treated with BT have decreased PCSM if they receive trimodailty therapy that includes EBRT and AST. This benefit is likely most important in men with multiple determinants of high risk. © 2012 Elsevier Inc.


Kang J.,Brigham and Women's Hospital | Chen M.-H.,University of Connecticut | Zhang Y.,University of Connecticut | Moran B.J.,Prostate Cancer Foundation of Chicago | And 6 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: It has been recently shown that diabetes mellitus (DM) is significantly associated with the likelihood of presenting with high-grade prostate cancer (PCa) or Gleason score (GS) 8 to 10; however, whether this association holds for both Type 1 and 2 DM is unknown. In this study we evaluated whether DM Type 1, 2, or both are associated with high-grade PCa after adjusting for known predictors of high-grade disease. Methods and Materials: Between 1991 and 2010, a total of 15,330 men diagnosed with PCa and treated with radiation therapy were analyzed. A polychotomous logistic regression analysis was performed to evaluate whether Type 1 or 2 DM was associated with odds of GS 7 or GS 8 to 10 compared with 6 or lower PCa, adjusting for African American race, age, prostate-specific antigen (PSA) level, and digital rectal examination findings. Results: Men with Type 1 DM (adjusted odds ratio [AOR], 2.05; 95% confidence interval [CI], 1.28-3.27; p = 0.003) or Type 2 DM (AOR, 1.58; 95% CI, 1.26-1.99; p < 0.001) were significantly more likely to be diagnosed with GS 8 to 10 PCa compared with nondiabetic men. However this was not true for GS 7, for which these respective results were AOR, 1.30; 95% CI, 0.93-1.82; p = 0.12 and AOR, 1.13; 95% CI, 0.98-1.32; p = 0.10. Conclusion: Type 1 and 2 DM were associated with a higher odds of being diagnosed with Gleason score 8 to 10 but not 7 PCa. Pending validation, men who are diagnosed with Type I DM with GS 7 or lower should be considered for additional workup to rule out occult high-grade disease. © 2012 Elsevier Inc.


Nanda A.,Md Anderson Cancer Center Orlando | Chen M.-H.,University of Connecticut | Moran B.J.,Prostate Cancer Foundation of Chicago | Braccioforte M.H.,Prostate Cancer Foundation of Chicago | And 5 more authors.
European Urology | Year: 2014

Background Neoadjuvant hormone therapy (NHT) use is associated with an increased risk of all-cause mortality (ACM) in men with a history of coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI). However, its effect in men with no or at least a single risk factor for CAD stratified by prostate cancer (PCa) aggressiveness is unknown. Objective To assess whether NHT use affects the risk of ACM in men with low-, intermediate-, and high-risk PCa treated with brachytherapy who have no or at least a single risk factor for CAD. Design, setting, and participants This retrospective study cohort consisted of 5411 men with low-risk PCa (prostate-specific antigen [PSA] <10 ng/ml, Gleason score 6, and clinical stage T1-T2a); 4365 men with intermediate-risk PCa (PSA 10-20 ng/ml or Gleason score <8 or clinical stage


Hoffman K.E.,Dana-Farber Cancer Institute | Hoffman K.E.,Harvard University | Chen M.-H.,University of Connecticut | Moran B.J.,Prostate Cancer Foundation of Chicago | And 6 more authors.
Cancer | Year: 2010

BACKGROUND: The risk of prostate cancer-specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external-beam radiation to the prostate and seminal vesicles, and androgen-suppression therapy (CMT) in this population. METHODS: The study cohort comprised 764 men aged ≥65 years with high-risk prostate cancer (T3 or T4N0M0, prostate-specific antigen >20 ng/mL, and/or Gleason score 8-10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM. RESULTS: The median patient age was 73 years (interquartile range, 70-77 years). After a median follow-up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017). CONCLUSIONS: Elderly men who had high-risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high-risk prostate cancer. © 2010 American Cancer Society.


D'Amico A.V.,Dana-Farber Cancer Institute | Braccioforte M.H.,Prostate Cancer Foundation of Chicago | Moran B.J.,Prostate Cancer Foundation of Chicago | Chen M.-H.,University of Connecticut
Alzheimer Disease and Associated Disorders | Year: 2010

Purpose: We evaluated the risk of death from Alzheimer disease (AD) in men with prostate cancer undergoing treatment with or without a luteinizing-hormone releasing hormone (LHRH) agonist. Methods: Between 1997 and 2007, 6,647 men were treated with brachytherapy for prostate cancer with (N=1,700) or without (N=4,947) LHRH agonist therapy. Competing risks multivariable regression was performed to assess whether the use of a LHRH agonist was associated with the risk of death from AD adjusting for the presence of mild AD and age at presentation and known prostate cancer prognostic factors. Results: After a median follow-up of 4.1 years, 1.2% (81/6,647) of the study cohort died from AD accounting for 16% (81/506) of all observed mortality. There was a significant reduction in the risk of death from AD in men who were treated with a LHRH agonist for a median of 4.0 months as compared with those who were not [adjusted hazard ratio: 0.45 (95% confidence interval, 0.25-0.83); P=0.01]. Conclusions: LHRH agonist use as compared with no use in men with prostate cancer was associated with a decreased risk of death from AD. © 2010 by Lippincott Williams & Wilkins.


PubMed | Prostate Cancer Foundation of Chicago
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

5154 Background: The purpose of this study was to evaluate causes of death in a large cohort of prostate cancer patients treated with interstitial permanent prostate brachytherapy.8,215 patients underwent prostate brachytherapy at a single institution between October 1997 and October 2007. Mean patient age was 68.9 7.6 years. 48.2% of patients were considered low risk, 39% were intermediate risk and 11.8% were high risk as classified by the DAmico risk groups. Overall, 2,522 patients (30.7%) received androgen deprivation therapy. Median follow-up time was 4.6 years. Specific cause of death was evaluated as well as multiple variables including risk group, smoking status, presence or absence of diabetes, hypercholesterolemia and hypertension.Kaplan-Meier survival analysis demonstrated prostate cancer specific survival was 97.3% (99.8%, 98.0% and 94.1% for Low, Intermediate and High risk patients, respectively). The overall survival for the patient population was 76.9% (83.2%, 80.5% and 67.0% for Low, Intermediate and High risk patients, respectively). 90% of deceased patients were 65 years old. 43% of all deaths were from cancer, however, only 32% of the cancer deaths were due to prostate cancer. Cardiovascular deaths accounted for 25% of all deaths, with myocardial infarction as the leading event. Table 1 provides additional information on the deceased patient cohort.Patients undergoing interstitial permanent prostate brachytherapy have excellent cause-specific and overall survival rates. As techniques in early detection and treatment evolve, these rates will continue to improve. This data is valuable for future patient consultation regarding prostate cancer treatment options and prognosis. [Table: see text] No significant financial relationships to disclose.


PubMed | Brigham and Women's Hospital, Prostate Cancer Foundation of Chicago and University of Connecticut
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

83 Background: Radiation therapy (RT) plus 28-36 months of hormonal therapy (HT) is standard-of-care for men with high-risk prostate cancer (HRPC) based on randomized trials comparing these HT durations to 4-6 months. However, it is unknown whether shorter durations of HT may also decrease mortality. We evaluate the impact of intermediate-course HT on the risk of all-cause mortality (ACM) in men with HRPC treated with RT.The study cohort comprised 554 men with HRPC (PSA > 20; Gleason score 8 or higher; or clinical stage T2c or higher) consecutively treated at the Chicago Prostate Cancer Center between 1997 and 2007. All men received brachytherapy with or without external beam RT and HT of intermediate (> 6 to 24; median 12 months) or short (up to 6; median 4 months) duration. A Cox regression multivariable analysis was performed assessing whether intermediate compared to short-course HT was associated with a decreased risk of ACM, adjusting for age, year and type of RT, treatment propensity score, and known PC prognostic factors.After a median follow up of 4.3 years a total of 64 (11.6%) men died. Intermediate compared to short-course HT was associated with a significantly decreased risk of ACM (adjusted hazard ratio 0.44, 95% confidence interval 0.20 - 0.94, P = 0.03). Other significant covariates are shown in the table. The 5-year estimates of ACM for intermediate versus short-course HT were 7.0% and 15.7%, respectively.In men with HRPC treated with RT, a median HT duration of 12 months was associated with a significantly decreased risk of ACM when compared to a median HT duration of 4 months. This raises the hypothesis that HT durations shorter than 28-36 months may be sufficient to decrease mortality in men with HRPC. The ongoing RADAR trial by the Trans Tasman Radiation Oncology Group comparing 18 to 6 months of HT may provide level I evidence to validate this hypothesis. [Table: see text].

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