Anne Marie Meyer

Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer

CONTEXT There has been rapid adoption of newer radiation treatments such as intensity-modulated radiation therapy (IMRT) and proton therapy despite greater cost and limited demonstrated benefit compared with previous technologies. OBJECTIVE To determine the comparative morbidity and disease control of IMRT, proton therapy, and conformal radiation therapy for primary prostate cancer treatment. DESIGN, SETTING, AND PATIENTS Population-based study using Surveillance, Epidemiology, and End Results-Medicare-linked data from 2000 through 2009 for patients with nonmetastatic prostate cancer. MAIN OUTCOME MEASURES Rates of gastrointestinal and urinary morbidity, erectile dysfunction, hip fractures, and additional cancer therapy. RESULTS Use of IMRT vs conformal radiation therapy increased from 0.15% in 2000 to 95.9% in 2008. In propensity score-adjusted analyses (N = 12,976), men who received IMRT vs conformal radiation therapy were less likely to receive a diagnosis of gastrointestinal morbidities (absolute risk, 13.4 vs 14.7 per 100 person-years; relative risk [RR], 0.91; 95% CI, 0.86-0.96) and hip fractures (absolute risk, 0.8 vs 1.0 per 100 person-years; RR, 0.78; 95% CI, 0.65-0.93) but more likely to receive a diagnosis of erectile dysfunction (absolute risk, 5.9 vs 5.3 per 100 person-years; RR, 1.12; 95% CI, 1.03-1.20). Intensity-modulated radiation therapy patients were less likely to receive additional cancer therapy (absolute risk, 2.5 vs 3.1 per 100 person-years; RR, 0.81; 95% CI, 0.73-0.89). In a propensity score-matched comparison between IMRT and proton therapy (n = 1368), IMRT patients had a lower rate of gastrointestinal morbidity (absolute risk, 12.2 vs 17.8 per 100 person-years; RR, 0.66; 95% CI, 0.55-0.79). There were no significant differences in rates of other morbidities or additional therapies between IMRT and proton therapy. CONCLUSIONS Among patients with nonmetastatic prostate cancer, the use of IMRT compared with conformal radiation therapy was associated with less gastrointestinal morbidity and fewer hip fractures but more erectile dysfunction; IMRT compared with proton therapy was associated with less gastrointestinal morbidity.

Test-retest reliability of the Women's Health Initiative physical activity questionnaire.

PURPOSE Few physical activity (PA) questionnaires were designed to measure the lifestyles and activities of women. We sought to examine the test-retest reliability of a PA questionnaire used in the Womens Health Initiative (WHI) study. Differences in reliability were also explored by important covariates. METHODS Participants (n = 1092) were postmenopausal women aged 50-79 yr, randomly selected from the baseline sample of participants in the WHI Observational Study. The WHI PA questionnaire collects usual frequency, duration, and pace of recreational walking, frequency, and duration of other recreational activities or exercises (mild, moderate, and strenuous), household, and yard activities. Approximately half of the women (n = 569) repeated questions on recreational PA, the other half (n = 523) repeated questions related to household and yard activities (mean 3 months apart). Test-retest reliability was assessed with kappa and intraclass correlation coefficients (ICC 1,1). RESULTS Overall, questions on recreational walking, moderate recreational PA, and strenuous recreational PA had higher test-retest reliability (weighted kappa range = 0.50-0.60) than questions on mild recreational PA (weighted kappa range = 0.35-0.50). The ICC 1,1 for moderate to strenuous recreational PA was 0.77 (95% confidence interval [CI] = 0.73-0.80), and the total recreational PA was 0.76 (95% CI = 0.71-0.79). Substantial reliability was observed for the summary measures of yard activities (ICC 1,1 = 0.71; 95% CI = 0.66-0.75) and household activities (ICC 1,1 = 0.60, 95% CI = 0.55-0.66). No meaningful differences were observed by race/ethnicity, age, time between test and retest, and amount of reported PA. CONCLUSIONS The WHI PA questionnaire demonstrated moderate to substantial test-retest reliability in a diverse sample of postmenopausal women.

Association Between Choice of Radical Prostatectomy, External Beam Radiotherapy, Brachytherapy, or Active Surveillance and Patient-Reported Quality of Life Among Men With Localized Prostate Cancer.

Importance Patients diagnosed with localized prostate cancer have to decide among treatment strategies that may differ in their likelihood of adverse effects. Objective To compare quality of life (QOL) after radical prostatectomy, external beam radiotherapy, and brachytherapy vs active surveillance. Design, Setting, and Participants Population-based prospective cohort of 1141 men (57% participation among eligible men) with newly diagnosed prostate cancer were enrolled from January 2011 through June 2013 in collaboration with the North Carolina Central Cancer Registry. Median time from diagnosis to enrollment was 5 weeks, and all men were enrolled with written informed consent prior to treatment. Final follow-up date for current analysis was September 9, 2015. Exposures Treatment with radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance. Main Outcomes and Measures Quality of life using the validated instrument Prostate Cancer Symptom Indices was assessed at baseline (pretreatment) and 3, 12, and 24 months after treatment. The instrument contains 4 domains—sexual dysfunction, urinary obstruction and irritation, urinary incontinence, and bowel problems—each scored from 0 (no dysfunction) to 100 (maximum dysfunction). Propensity-weighted mean domain scores were compared between each treatment group vs active surveillance at each time point. Results Of 1141 enrolled men, 314 pursued active surveillance (27.5%), 469 radical prostatectomy (41.1%), 249 external beam radiotherapy (21.8%), and 109 brachytherapy (9.6%). After propensity weighting, median age was 66 to 67 years across groups, and 77% to 80% of participants were white. Across groups, propensity-weighted mean baseline scores were 41.8 to 46.4 for sexual dysfunction, 20.8 to 22.8 for urinary obstruction and irritation, 9.7 to 10.5 for urinary incontinence, and 5.7 to 6.1 for bowel problems. Compared with active surveillance, mean sexual dysfunction scores worsened by 3 months for patients who received radical prostatectomy (36.2 [95% CI, 30.4-42.0]), external beam radiotherapy (13.9 [95% CI, 6.7-21.2]), and brachytherapy (17.1 [95% CI, 7.8-26.6]). Compared with active surveillance at 3 months, worsened urinary incontinence was associated with radical prostatectomy (33.6 [95% CI, 27.8-39.2]); acute worsening of urinary obstruction and irritation with external beam radiotherapy (11.7 [95% CI, 8.7-14.8]) and brachytherapy (20.5 [95% CI, 15.1-25.9]); and worsened bowel symptoms with external beam radiotherapy (4.9 [95% CI, 2.4-7.4]). By 24 months, mean scores between treatment groups vs active surveillance were not significantly different in most domains. Conclusions and Relevance In this cohort of men with localized prostate cancer, each treatment strategy was associated with distinct patterns of adverse effects over 2 years. These findings can be used to promote treatment decisions that incorporate individual preferences.

Trends in stage‐specific incidence rates for urothelial carcinoma of the bladder in the United States: 1988 to 2006

Bladder cancer is notable for a striking heterogeneity of disease‐specific risks. Among the approximately 75% of incident cases found to be superficial to the muscularis propria at the time of presentation (non–muscle‐invasive bladder cancer), the risk of progression to the lethal phenotype of muscle‐invasive disease is strongly associated with stage and grade of disease. Given the suggestion of an increasing percentage of low‐risk cases in hospital‐based registry data in recent years, the authors hypothesized that population‐based data may reveal changes in the stage distribution of early‐stage cases.

Preoperatively Misclassified, Surgically Removed Benign Renal Masses: A Systematic Review of Surgical Series and United States Population Level Burden Estimate

PURPOSE A significant proportion of renal masses removed for suspected malignancy are histologically benign with the probability inversely proportional to lesion size. To our knowledge the number of preoperatively misclassified benign renal masses treated with nephrectomy is currently unknown. Given the increasing incidence and decreasing average size of renal cell carcinoma, this burden is likely increasing. We estimated the population level burden of surgically removed, preoperatively misclassified benign renal masses in the United States. MATERIALS AND METHODS We systematically reviewed the literature for studies of pathological findings of renal masses removed for suspected renal cell carcinoma based on preoperative imaging through July 1, 2014. We excluded studies that did not describe benign pathology and with masses not stratified by size, and in which pathology results were based on biopsy. SEER data were queried for the incidence of surgically removed renal cell carcinomas in 2000 to 2009. RESULTS A total of 19 studies of tumor pathology based on size met criteria for review. Pooled estimates of the proportion of benign histology in our primary analysis (American studies only and 1 cm increments) were 40.4%, 20.9%, 19.6%, 17.2%, 9.2% and 6.4% for tumors less than 1, 1 to less than 2, 2 to less than 3, 3 to less than 4, 4 to 7 and greater than 7, respectively. The estimated number of surgically resected benign renal masses in the United States from 2000 to 2009 increased by 82% from 3,098 to 5,624. CONCLUSIONS These estimates suggest that the population level burden of preoperatively misclassified benign renal masses is substantial and increasing rapidly, paralleling increases in surgically resected small renal cell carcinoma. This study illustrates an important and to our knowledge previously unstudied dimension of overtreatment that is not directly quantified in contemporary surveillance data.

Television, physical activity, diet, and body weight status: the ARIC cohort.

BackgroundTelevision (TV) watching is the most common leisure activity in the United States. Few studies of adults have described the relationship between TV and health behaviors such as physical activity, diet, and body weight status.MethodsExtant data from the Atherosclerosis Risk in Communities (ARIC) Study were analyzed to assess the association of TV with physical activity, diet, and body mass index (BMI) among 15,574 adults at baseline (1986–89) and 12,678 adults six years later. Television, physical activity, and diet were collected with questionnaires and BMI was measured at both time points. Based on baseline TV exposure, adults were categorized into high, medium, and low TV exposure. Linear and logistic regression models were adjusted for gender, age, race-center, smoking, education, and general health.ResultsRelative to participants who had low TV exposure, those with high TV exposure were more likely to be less physically active and have a poorer dietary profile at baseline and six-years later. Participants with high TV exposure at baseline had a 40% and 31% greater odds of being considered insufficiently active at baseline (1.40, 95% CI 1.26, 1.55), and six years later (1.31, 95% CI 1.18, 1.46). At baseline, high TV exposure was also associated with a 20% to 30% greater odds of being above the median for servings of salty snacks (1.37, 95% CI 1.24, 1.51), sweets (1.26, 95% CI 1.15, 1.38), and sweetened drinks (1.29, 95% CI 1.17, 1.42), and below the median for fruit and vegetable servings (1.36, 95% CI 1.24, 1.50). Higher TV exposure was also cross-sectionally associated with a greater odds for being overweight or obese (1.43, 95% CI 1.29, 1.58). Similar associations were observed between baseline TV exposure and six-year physical activity and diet, but were not observed with BMI after six years follow-up.ConclusionThese results support the hypothesis that time spent watching TV is associated with deleterious effects on physical activity, diet, and BMI.

Impact of Distance to a Urologist on Early Diagnosis of Prostate Cancer Among Black and White Patients

PURPOSE We examined whether an increased distance to a urologist is associated with a delayed diagnosis of prostate cancer among black and white patients, as manifested by higher risk disease at diagnosis. MATERIALS AND METHODS North Carolina Central Cancer Registry data were linked to Medicare claims for patients with incident prostate cancer diagnosed in 2004 to 2005. Straight-line distances were calculated from the patient home to the nearest urologist. Race stratified multivariate ordinal logistic regression was used to examine the association between distance to a urologist and prostate cancer risk group (low, intermediate, high or very high/metastasis) at diagnosis for black and white patients while accounting for age, comorbidity, marital status and diagnosis year. An overall model was then used to examine the distance × race interaction effect. RESULTS Included in analysis were 1,720 white and 531 black men. In the overall cohort the high risk cancer rate increased monotonically with distance to a urologist, including 40% for 0 to 10, 45% for 11 to 20 and 57% for greater than 20 miles. Correspondingly the low risk cancer rate decreased with longer distance. On race stratified multivariate analysis longer distance was associated with higher risk prostate cancer for white and black patients (p = 0.04 and <0.01, respectively) but the effect was larger in the latter group. The distance × race interaction term was significant in the overall model (p = 0.03). CONCLUSIONS Longer distance to a urologist may disproportionally impact black patients. Decreasing modifiable barriers to health care access, such as distance to care, may decrease racial disparities in prostate cancer.

The role of organizational affiliations and research networks in the diffusion of breast cancer treatment innovation.

Introduction:The National Institutes of Health (NIH) sees provider-based research networks and other organizational linkages between academic researchers and community practitioners as promising vehicles for accelerating the translation of research into practice. This study examines whether organizational research affiliations and teaching affiliations are associated with accelerated diffusion of sentinel lymph node biopsy (SLNB), an innovation in the treatment of early-stage breast cancer. Methods:Surveillance Epidemiology and End Results-Medicare data were used to examine the diffusion of SLNB for treatment of early-stage breast cancer among women aged 65 years and older diagnosed between 2000 and 2002, shortly after Medicare approved and began reimbursing for the procedure. Results:In this population, patients treated at an organization affiliated with a research network—-the American College of Surgeons Oncology Group (ACOSOG) or other National Cancer Institute (NCI) cooperative groups—-were more likely to receive the innovative treatment (SLNB) than patients treated at unaffiliated organizations (odds ratio: 2.70, 95% confidence interval: 1.77–4.12; odds ratio: 1.84, 95% confidence interval: 1.26–2.69, respectively). Neither hospital teaching status nor surgical volume was significantly associated with differences in SLNB use. Discussion:Patients who receive cancer treatment at organizations affiliated with cancer research networks have an enhanced probability of receiving SLNB, an innovative procedure that offers the promise of improved patient outcomes. Study findings support the NIH Roadmap and programs such as the NCIs Community Clinical Oncology Program, as they seek to accelerate the translation of research into practice by simultaneously accelerating and broadening cancer research in the community.

Comparative effectiveness of intensity-modulated radiotherapy and conventional conformal radiotherapy in the treatment of prostate cancer after radical prostatectomy.

IMPORTANCE Comparative effectiveness research of prostate cancer therapies is needed because of the development and rapid clinical adoption of newer and costlier treatments without proven clinical benefit. Radiotherapy is indicated after prostatectomy in select patients who have adverse pathologic features and in those with recurrent disease. OBJECTIVES To examine the patterns of use of intensity-modulated radiotherapy (IMRT), a newer, more expensive technology that may reduce radiation dose to adjacent organs compared with the older conformal radiotherapy (CRT) in the postprostatectomy setting, and to compare disease control and morbidity outcomes of these treatments. DESIGN AND SETTING Data from the Surveillance, Epidemiology, and End Results-Medicare-linked database were used to identify patients with a diagnosis of prostate cancer who had received radiotherapy within 3 years after prostatectomy. PARTICIPANTS Patients who received IMRT or CRT. MAIN OUTCOMES AND MEASURES The outcomes of 457 IMRT and 557 CRT patients who received radiotherapy between 2002 and 2007 were compared using their claims through 2009. We used propensity score methods to balance baseline characteristics and estimate adjusted incidence rate ratios (RRs) and their 95% CIs for measured outcomes. RESULTS Use of IMRT increased from zero in 2000 to 82.1% in 2009. Men who received IMRT vs CRT showed no significant difference in rates of long-term gastrointestinal morbidity (RR, 0.95; 95% CI, 0.66-1.37), urinary nonincontinent morbidity (0.93; 0.66-1.33), urinary incontinence (0.98; 0.71-1.35), or erectile dysfunction (0.85; 0.61-1.19). There was no significant difference in subsequent treatment for recurrent disease (RR, 1.31; 95% CI, 0.90-1.92). CONCLUSIONS AND RELEVANCE Postprostatectomy IMRT and CRT achieved similar morbidity and cancer control outcomes. The potential clinical benefit of IMRT in this setting is unclear. Given that IMRT is more expensive, its use for postprostatectomy radiotherapy may not be cost-effective compared with CRT, although formal analysis is needed.

Racial difference in histologic subtype of renal cell carcinoma.

In the United States, renal cell carcinoma (RCC) has rapidly increased in incidence for over two decades. The most common histologic subtypes of RCC, clear cell, papillary, and chromophobe have distinct genetic and clinical characteristics; however, epidemiologic features of these subtypes have not been well characterized, particularly regarding any associations between race, disease subtypes, and recent incidence trends. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we examined differences in the age‐adjusted incidence rates and trends of RCC subtypes, including analysis focusing on racial differences. Incidence rates increased over time (2001–2009) for all three subtypes. However, the proportion of white cases with clear cell histology was higher than among blacks (50% vs. 31%, respectively), whereas black cases were more likely than white cases to have papillary RCC (23% vs. 9%, respectively). Moreover, papillary RCC incidence increased more rapidly for blacks than whites (P < 0.01) over this period. We also observed that increased incidence of papillary histology among blacks is not limited to the smallest size strata. We observed racial differences in proportionate incidence of RCC subtypes, which appear to be increasing over time; this novel finding motivates further etiologic, clinical, molecular, and genetic studies.