Lois Lamerato

Effect of Screening on Ovarian Cancer Mortality: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial

CONTEXT Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality. OBJECTIVE To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at 10 screening centers across the United States between November 1993 and July 2001. Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010. MAIN OUTCOME MEASURES Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. RESULTS Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person-years) in the intervention group and 2914 deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06). CONCLUSIONS Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. Trial Registration clinicaltrials.gov Identifier: NCT00002540.

Racial Disparities in Treatment and Survival Among Women With Early-Stage Breast Cancer

PURPOSE Black women with breast cancer are known to have poorer survival than white women. Suboptimal treatment may compromise the survival benefits of adjuvant chemotherapy. We analyzed the association of race and survival with duration of treatment and number of treatment cycles among women receiving chemotherapy for early-stage breast cancer. PATIENTS AND METHODS Patients were women in the Henry Ford Health System tumor registry who were diagnosed with stage I/II breast cancer between January 1, 1996, and December 31, 2001, who received adjuvant chemotherapy. We calculated an observed/expected ratio of treatment duration and of completed chemotherapy cycles for each patient. Using Cox proportional hazards models, we analyzed the association of early treatment termination and treatment duration with all-cause mortality, controlling for age, race, stage, hormone receptor status, grade, comorbidity score, and doxorubicin use. RESULTS Of 472 eligible patients, 28% (31% black, 23% white; P = .03) received fewer cycles of treatment than expected. Black race, receipt of < or = 75% of the expected number of cycles, increasing age, hormone receptor negativity, and a comorbidity score of more than 1 were associated with poorer survival. Among the 344 patients receiving the expected number of cycles, 60% experienced delays. These delays did not reduce survival. CONCLUSION This study is the first to find that a substantial fraction of women with early-stage breast cancer terminated their chemotherapy prematurely and that early termination was associated with both black race and poorer survival. A better understanding of the determinants of suboptimal treatment may lead to interventions that can reduce racial disparities and improve breast cancer outcomes for all women.

Race and Colorectal Cancer Disparities: Health-Care Utilization vs Different Cancer Susceptibilities

BACKGROUND It is unclear whether the disproportionately higher incidence and mortality from colorectal cancer among blacks compared with whites reflect differences in health-care utilization or colorectal cancer susceptibility. METHODS A total of 60, 572 non-Hispanic white and black participants in the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial underwent trial-sponsored screening flexible sigmoidoscopy (FSG) without biopsy at baseline in 10 geographically dispersed centers from November 1993 to July 2001. Subjects with polyps or mass lesions detected by FSG were referred to their physicians for diagnostic workup, the cost of which was not covered by PLCO. The records of follow-up evaluations were collected and reviewed. We used log binomial modeling with adjustment for age, education, sex, body mass index, smoking, family history of colorectal cancer, colon examination within previous 3 years, personal history of polyps, and screening center to examine whether utilization of diagnostic colonoscopy and yield of neoplasia differed by race. RESULTS Among 57 561 whites and 3011 blacks who underwent FSG, 13,743 (23.9%) and 767 (25.5%) had abnormal examinations, respectively. A total of 9944 (72.4%) whites and 480 (62.6%) blacks had diagnostic colonoscopy within 1 year following the abnormal FSG screening. When compared with whites, blacks were less likely to undergo diagnostic evaluation (adjusted risk ratio = 0.88, 95% confidence interval = 0.83 to 0.93). Overall, among subjects with diagnostic colonoscopy (n = 10 424), there was no statistically significant difference by race in the prevalence of adenoma, advanced adenoma, advanced pathology in small adenomas (high-grade dysplasia or villous histology in adenomas <10 mm), or colorectal cancer. CONCLUSIONS We observed a lower follow-up for screen-detected abnormalities among blacks when compared with whites but little difference in the yield of colorectal neoplasia. Health-care utilization may be playing more of a role in colorectal cancer racial disparity than biology.

Racial differences in tumor stage and survival for colorectal cancer in an insured population

Despite declining death rates from colorectal cancer (CRC), racial disparities have continued to increase. In this study, the authors examined disparities in a racially diverse group of insured patients.

Noninvasive Serum Fibrosis Markers for Screening and Staging Chronic Hepatitis C Virus Patients in a Large US Cohort

BACKGROUND Liver biopsy remains critical for staging liver disease in hepatitis C virus (HCV)-infected persons, but is a bottleneck to evaluation, follow-up, and treatment of HCV. Our analysis sought to validate APRI (aspartate aminotransferase [AST]-to-platelet ratio index) and FIB-4, an index from serum fibrosis markers (alanine aminotransferase [ALT], AST, and platelets plus patient age) to stage liver disease. METHODS Biopsy results from HCV patients in the Chronic Hepatitis Cohort Study were mapped to an F0-F4 equivalent scale; APRI and FIB-4 scores at the time of biopsy were then mapped to the same scale. RESULTS We identified 2372 liver biopsies from HCV-infected patients with contemporaneous laboratory values for imputing APRI and FIB-4. Fibrosis stage distributions by the equivalent biopsy scale were 267 (11%) F0; 555 (23%) F1; 648 (27%) F2; 394 (17%) F3; and 508 (21%) F4. Mean APRI and FIB-4 values significantly increased with successive fibrosis levels (P < .05). The areas under the receiver operating characteristic curve (AUROC) analysis distinguishing severe (F3-F4) from mild-to-moderate fibrosis (F0-F2) were 0.80 (95% confidence interval [CI], .78-.82) for APRI and 0.83 (95% CI, .81-.85) for FIB-4. There was a significant difference between the AUROCs of FIB-4 and APRI (P < .001); 88% of persons who had a FIB-4 score ≥2.0 were at stage F2 or higher. CONCLUSIONS In a large observational cohort, FIB-4 was good at differentiating 5 stages of chronic HCV infection. It can be useful in screening patients who need biopsy and therapy, for monitoring patients with less advanced disease, and for longitudinal studies.

Cumulative incidence of false-positive results in repeated, multimodal cancer screening

PURPOSE Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program. METHODS Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and flexible sigmoidoscopies. Men received serial chest radiographs, flexible sigmoidoscopies, digital rectal examinations, and serum prostate-specific antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period. RESULTS After 14 tests, the cumulative risk of having at least 1 false-positive screening test is 60.4% (95% CI, 59.8%–61.0%) for men, and 48.8% (95% CI, 48.1%–49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (CI, 27.8%–29.3%) for men and 22.1% (95% CI, 21.4%–22.7%) for women. CONCLUSIONS For an individual in a multimodal cancer screening trial, the risk of a false-positive finding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening.

Antiviral Therapy for Chronic Hepatitis B Virus Infection and Development of Hepatocellular Carcinoma in a US Population

BACKGROUND & AIMS Antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) among persons with chronic hepatitis B virus (HBV) infection. We evaluated the relationship between therapy for chronic HBV infection and HCC incidence using data from a longitudinal study of patients at 4 US healthcare centers. METHODS We analyzed electronic health records of 2671 adult participants in the Chronic Hepatitis Cohort Study who were diagnosed with chronic HBV infection from 1992 through 2011 (49% Asian). Data analyzed were collected for a median of 5.2 years. Propensity-score adjustment was used to reduce bias, and Cox regression was used to estimate the relationship between antiviral treatment and HCC. The primary outcome was time to event of HCC incidence. RESULTS Of study subjects, 3% developed HCC during follow-up period: 20 cases among the 820 patients with a history of antiviral HBV therapy and 47 cases among the 1851 untreated patients. In propensity-adjusted Cox regression, patients who received antiviral therapy had a lower risk of HCC than those who did not receive antiviral therapy (adjusted hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .001), after adjusting for abnormal level of alanine aminotransferase. In a subgroup analysis, antiviral treatment was associated with a lower risk of HCC after adjusting for serum markers of cirrhosis (adjusted hazard ratio, 0.24; 95% confidence interval, 0.15-0.39; P < .001). In a separate subgroup analysis of patients with available data on HBV DNA viral load, treated patients with viral loads >20,000 IU/mL had a significantly lower risk of HCC than untreated patients with viral loads >20,000 IU/mL. CONCLUSIONS In a large geographically, clinically, and racially diverse US cohort, antiviral therapy for chronic HBV infection was associated with a reduced risk for HCC.

Risk of Impaired Renal Function After Colonoscopy : A Cohort Study in Patients Receiving Either Oral Sodium Phosphate or Polyethylene Glycol

OBJECTIVES: We aimed to evaluate frequency, predictors, and monitoring of renal dysfunction related to the use of oral sodium phosphates for colonoscopy in clinical practice.METHODS: Cohort study using clinical records and electronic patient information from the Henry Ford Health System, Detroit, MI. We identified patients undergoing colonoscopy using sodium phosphate or polyethylene glycol (PEG), and estimated the risk of renal impairment associated with bowel preparation and other risk factors.RESULTS: Out of 7,897 patients, 6,833 had used sodium phosphate; 1,617 patients had renal dysfunction within 12 months prior to colonoscopy and 3,928 patients had no creatinine measurement within 12 months prior to or 6 months postcolonoscopy. Among the remaining 2,352 patients, 88 had incident renal dysfunction (glomerular filtration rate [GFR] <60 mL/min) after colonoscopy. The relative risk (RR) estimate for renal dysfunction comparing sodium phosphate with PEG was 1.13 (95% CI 0.58–2.23) without adjustment, and 1.14 (95% CI 0.55–2.39) after multivariate adjustment. Significant univariate risk factors were age ≥65 yr, African-American race, low baseline GFR, hypertension, and use of angiotensin-converting enzyme inhibitors (ACE inhbitors), angiotensin-renin blockers, or thiazide diuretics.CONCLUSIONS: In patients without preexisting renal disease, the risk of renal impairment after colonoscopy appears to be similar between sodium phosphate and PEG users. Sodium phosphate use in patients with preexisting renal disease is not recommended, but common in clinical practice. Sodium phosphate should not be used in patients with preexisting serious renal disease, adequate hydration should be assured in all patients, and renal function should be monitored before and after colonoscopy in those at risk of renal dysfunction.

Routine surveillance care after cancer treatment with curative intent.

Background:Many consensus guidelines recommend routine surveillance to detect recurrent disease among cancer survivors. We compare surveillance care receipt to guideline recommendations. Methods:Cohorts of patients aged 30 years or older diagnosed with breast, colorectal, endometrial, lung, or prostate cancer between 1990 and 1995 and treated with curative intent were identified (n = 100 per site). Receipt and indications for examinations and procedures were abstracted from medical records for as long as 5 years after treatment. Kaplan-Meier product estimates were used to estimate time to initial and subsequent service receipt. Results:Most cancer patients received the recommended minimum number of physical examinations after treatment. In fact, a sizable number of cancer survivors received physical examinations at a frequency in excess of what is currently recommended. Similarly, most of these cancer survivors received recommended testing for local recurrence. Yet, less than two thirds of colorectal cancer patients received recommended colon examinations in the initial year after treatment. Among colorectal, lung, and prostate cancer patients who received recommended initial local recurrence testing, repeat testing tended to occur more frequently than what is currently recommended. The use of testing for metastatic disease that is not recommended in guidelines is also commonplace among these cancer survivors. Conclusions:Among cohorts of cancer patients, we found wide variation in the use of surveillance care, including patterns of care receipt reflective of both underuse and overuse relative to guideline recommendations. Clinical reasons for these variations and the cost and health implications deserve further study.

Mortality Among Persons in Care With Hepatitis C Virus Infection: The Chronic Hepatitis Cohort Study (CHeCS), 2006–2010

BACKGROUND The number of deaths in hepatitis C virus (HCV)-infected persons recorded on US death certificates has been increasing, but actual rates and causes of death in these individuals have not been well elucidated. METHODS Disease-specific, liver-related, and non-liver-related mortality data for HCV-infected patients in an observational cohort study, the Chronic Hepatitis Cohort Study (CHeCS) at 4 US healthcare systems, were compared with multiple cause of death (MCOD) data in 12 million death certificates in 2006-2010. Premortem diagnoses, liver biopsies, and FIB-4 scores (a noninvasive measure of liver damage) were examined. RESULTS Of 2 143 369 adult patients seen at CHeCS sites in 2006-2010, 11 703 (0.5%) had diagnosed chronic HCV infection, and 1590 (14%) died. The majority of CHeCS decedents were born from 1945 to 1965 (75%), white (50%), and male (68%); mean age of death was 59 years, 15 years younger than MCOD deaths. The age-adjusted mortality rate for liver disease in CHeCS was 12 times higher than the MCOD rate. Before death, 63% of decedents had medical record evidence of chronic liver disease, 76% had elevated FIB-4 scores, and, among those biopsied, 70% had moderate or worse liver fibrosis. However, only 19% of all CHeCS decedents and only 30% of those with recorded liver disease had HCV listed on their death certificates. CONCLUSIONS HCV infection is greatly underdocumented on death certificates. The 16 622 persons with HCV listed in 2010 may represent only one-fifth of about 80 000 HCV-infected persons dying that year, at least two-thirds of whom (53 000 patients) would have had premortem indications of chronic liver disease.