Julie George

Interplay of Race, Socioeconomic Status, and Treatment on Survival of Patients With Prostate Cancer

OBJECTIVES To compare overall and prostate cancer-specific survival, using the Detroit Surveillance, Epidemiology, and End Results registry data, among 8679 Detroit area black and white men with localized or regional stage prostate cancer diagnosed from 1988 to 1992 to determine whether racial disparities in long-term survival remained after adjusting for treatment type and socioeconomic status (SES). METHODS The cases were geocoded to the census block-group, and SES data were obtained from the 1990 U.S. Census. Cox proportional hazards regression analysis was used to estimate the hazard ratio of death from any cause. The median follow-up was 16.5 years. RESULTS Of the 7770 localized stage cases (22% black and 78% white) and 909 regional cases (24% black and 76% white), black men were more likely to receive nonsurgical treatment (P < .001) and to be of low SES (P < .0001). The survival analyses were stratified by stage. For both stages, black men had poorer survival than white men in the unadjusted model. The adjustment for age and tumor grade had little effect on the survival differences, but adjustment for SES and treatment removed the survival differences. CONCLUSIONS Low SES and nonsurgical treatment were associated with a greater risk of death among men with prostate cancer, explaining much of the survival disadvantage for black men with prostate cancer.

Tree-Based Model for Breast Cancer Prognostication

PURPOSE To define prognostic groups for recurrence-free survival in breast cancer, assess relative effects of prognostic factors, and examine the influence of treatment variations on recurrence-free survival in patients with similar prognostic-factor profiles. PATIENTS AND METHODS We analyzed 1,055 patients diagnosed with stage I-III breast cancer between 1990 and 1996. Variables studied included socioeconomic factors, tumor characteristics, concurrent medical conditions, and treatment. The primary end point was recurrence-free survival (RFS). Multivariable analyses were performed using recursive partitioning and Cox proportional hazards regression. RESULTS The most significant difference in prognosis was between patients with fewer than four and those with at least four positive nodes (P <.0001). Four distinct prognostic groups (5-year RFS, 97%, 78%, 58%, and 27%) were developed, defined by the number of positive nodes, tumor size, progesterone receptor (PR) status, differentiation, race, and marital status. Patients with fewer than four positive nodes and tumor < or = 2 cm, PR positive, and well or moderately differentiated had the best prognosis. RFS in this group was unaffected by type of adjuvant therapy (P =.38). Patients with at least four positive nodes and PR-negative tumors had the worst prognosis, and those treated with tamoxifen plus chemotherapy had the best outcome in this group (P =.0001). Among patients in the two intermediate-risk groups, those treated with tamoxifen or a combination of tamoxifen and chemotherapy had the best outcome. CONCLUSION Lymph node status, PR status, tumor size, differentiation, race, and marital status are valuable for prognostication in breast cancer. The prognostic groups derived can provide guidance for clinical trial design, patient management, and future treatment policy.

How reminders given to patients and physicians affected Pap smear use in a health maintenance organization: Results of a randomized controlled trial

Despite its effectiveness as a method of controlling cervical carcinoma, the use of Pap smear testing remains incomplete, and its promotion in the primary care setting provides an important opportunity for intervention.

Disentangling the effects of race on breast cancer treatment.

African Americans (AA) have higher mortality from breast cancer compared with white Americans (WA). Studies using population‐based cancer registries have attributed this to disparities in treatment after normalizing the AA and WA populations for differences in disease stage. However, those studies were hampered by lack of comorbidity data and limited information about systemic treatments. The objective of the current study was to investigate racial disparities in breast cancer treatment by conducting a comprehensive medical records review of women who were diagnosed with breast cancer at the Karmanos Cancer Institute (KCI) in Detroit, Michigan.

Mechanism for maintenance of high breast tumor estradiol concentrations in the absence of ovarian function : Role of very high affinity tissue uptake

Breast tumors from postmenopausal women contain levels of estradiol similar to those in premenopausal patients even though serum estradiol levels fall by an order of magnitude upon cessation of ovarian function. The present study sought to examine enhanced uptake from plasma as one potential mechanism for maintenance of high tissue estradiol levels in postmenopausal patients. Accordingly, we used osmotic minipumps to continuously infuse estradiol (E2) at rates producing serum concentrations ranging from pre- to postmenopausal levels for two weeks to oophorectomized Sprague-Dawley rats bearing nitrosomethylurea-induced mammary tumors. We then measured E2 concentrations in various tissues and sera and reasoned that tissue affinities for estradiol could be directly calculated from in vivo measurements by adapting Scatchard analysis to steroid infusion data. Using this method, we demonstrated a very high affinity estradiol binding component with a Kd two orders of magnitude higher (i.e., 0.35 × 10-12 M) than determined with standard in vitro techniques. A second estradiol binding component with the expected Kdd of 1 × 10-10 M was also present. Estradiol bound to both classes of binding sites could be 98% displaced with diethylstilbestrol within a 6-hr period. In vivo steroid binding off-times calculated from log-linear slopes averaged approximately 60 min. These data demonstrated that the actual E2 binding affinity in target tissues in vivo, especially at low estrogen concentrations, is much higher than usually estimated from standard, in vitro estrogen receptor assays. These observations provide one mechanism to explain why estradiol concentrations remain high in breast cancer tissue from postmenopausal women and consequently can stimulate tumor proliferation.

Mammography use among women as a function of age and patient involvement in decision-making.

OBJECTIVE: To assess the extent to which self‐reported patient involvement in decision‐making for initiation of mammography differs with age.

Telephone reminders increase re-screening in a county breast screening program

Introduction. Mammography can reduce breast cancer mortality through routine screening. We tested an intervention to increase re-screening in a county program. Methods. The program requires enrollment before screening. We randomized women who had previously been screened by the program to a telephone call reminder for re-enrollment or usual care (postcard reminder). We followed re-enrollment and re-screening rates for both groups. Results. Compared with the control group (n=610), women in the intervention group (n=599) had higher rates of initial re-enrollment at one month (10% vs. 24%, p<.001) and re-screening at two months (11% vs. 19%, p<.001). These effects persisted over time (five-month re-enrollment: 24% vs. 35%, p<.001; six-month re-screening: 23% vs. 31%, p=.004). The intervention did not alter the odds of a womans being re-screened once re-enrolled. Conclusion. The increase in our re-screening rate after this simple intervention was as great or greater than the rates reported in other studies. A telephone reminder for women previously enrolled in a county breast screening program can increase re-enrollment and subsequent re-screening rates.

A randomized design for repeated binary outcomes used to evaluate continued effectiveness of a breast cancer control intervention strategy

The literature has not discussed in detail design and evaluation strategies for the assessment of continued effectiveness of intervention strategies. In this article we present an approach to evaluating continued effectiveness with two repeated binary outcomes that are related to the use of preventive services. We present a two-stage design with independent randomization procedures for each of two successive controlled trials and discuss the implications of the randomization plan for the statistical evaluation. Intervention effectiveness for each year is determined by an adjusted odds ratio that compares the odds of procedure use for those who received the intervention to those who did not. Changes in the two adjusted odds ratios between successive years are assessed within the context of a regressive logistic model. We demonstrate these methods by applying them to the Metropolitan Detroit Project to Reduce Avoidable Mortality from Breast Cancer. In this project, computer-generated physician mammography reminders placed prominently in medical records were used to promote mammography referrals among women visiting primary care clinics during a 2-year intervention period. An assessment of the change in intervention effectiveness as well as an adjusted estimate of the overall intervention effectiveness for the 2 years were obtained from a multivariate regressive logistic model. The advantage of this approach was its potential for reducing bias and producing a balanced comparison between intervention groups during the second year of intervention. This issue was important because previous work indicated that having had a mammogram had a significant impact on subsequent mammography use. An important component in the implementation of this design was an information management system that facilitated doing two randomization procedures efficiently. As information and computer technology advance, and as more sophisticated information systems are used for data management, designs such as these become reasonable alternatives to consider.

Patterns of Treatment and Outcomes for Definitive Therapy of Early Stage Non-Small Cell Lung Cancer

BACKGROUND Definitive surgical and radiation therapy (RT) treatments are evolving rapidly for stage I non-small cell lung cancer (NSCLC). We hypothesized that utilization of definitive therapies increased between 2000 and 2010 and that survival improved for stage I NSCLC patients over the same time period. Secondary objectives were determining trends in patterns of care and predictors of utilization. METHODS Population-based, observational, comparative effectiveness study used Surveillance, Epidemiology, and End Results-18 data from 2000 to 2010. The main outcome measure was 2-year risk of death for stage I NSCLC. RESULTS Between 2000 and 2010, 40,589 patients (62%) underwent surgery, 10,048 (15%) received RT, 2,130 (3%) received both surgery and RT, and 11,537 (18%) received neither surgery nor RT. Annually, the odds of receiving either definitive RT or undergoing surgery increased relative to the odds of receiving no treatment (odds ratio [OR] radiation 1.04, 95% confidence interval [CI]: 1.03 to 1.05; OR surgery 1.05, 95% CI: 1.04 to 1.05). Among surgical patients, the proportion of sublobar resections steadily increased from 12.9% to 17.9%. For all patients, the 2-year risk of death decreased by 3.5% each year (hazard ratio [HR] 0.965, 95% CI: 0.962 to 0.969), driven primarily by improved survival for surgical (annualized HR 0.959, 95% CI: 0.954 to 0.964) and RT (annualized HR 0.942, 95% CI: 0.935 to 0.949) patients. CONCLUSIONS Between 2000 and 2010, stage I NSCLC patients were more likely to receive definitive treatment with either surgery or RT, leading to a decline in the number of untreated patients. Survival also improved substantially for stage I NSCLC patients, with the largest survival improvements observed in patients undergoing definitive RT.

Comparing Treatment Strategies for Stage I Small-cell lung Cancer

Micro‐Abstract: Stage I small‐cell lung cancer is increasing in incidence and there are limited clinical data upon which to make treatment recommendations for this population. In this study we compared outcomes for patients receiving surgery, stereotactic body radiation therapy (SBRT), and conventional radiation therapy. Patients who underwent surgery had the best survival outcomes. For those who did not have surgery, SBRT resulted in better outcomes that standard radiotherapy. Introduction: The diagnosis of stage I small‐cell lung cancer (SCLC) is increasing in incidence with the advent of low‐dose screening computed tomography. Surgery is considered the standard of care but there are very few data to guide clinical decision‐making. The purpose of this study was to compare outcomes for patients receiving definitive surgery, stereotactic body radiation therapy (SBRT), or external beam radiation therapy (EBRT) for stage I SCLC. Patients and Methods: Patients with a primary diagnosis of stage I SCLC were identified in the National Cancer Database. Patients were defined as having a first course of treatment of either surgery, EBRT, or SBRT. Overall survival (OS) was determined using the Kaplan–Meier method and Cox proportional hazards regression methods were used to estimate risk of overall mortality. Results: A total of 2678 patients were included in the analysis. The 2‐ and 3‐year OS for the whole cohort was 62% and 50%. Comparing treatment strategies in a multivariate model, surgical resection showed improved OS over EBRT (P < .001) and SBRT (P < .001), however, the OS benefit over SBRT did not persist for patients who underwent limited resection. When excluding patients who underwent surgery, SBRT showed improved OS compared with EBRT (P = .04). Additional use of chemotherapy with any treatment modality resulted in improved OS (P < .001). Conclusion: In this hospital‐based registry study, definitive surgical resection and use of chemotherapy resulted in improved survival for patients with early stage SCLC. For patients who are not candidates for surgery, SBRT may offer a survival benefit compared with standard EBRT.