Scott B. Cantor

The burdens of cancer therapy: Clinical and economic outcomes of chemotherapy-induced mucositis

Mucositis is a common but poorly studied problem among patients with solid tumors. The authors examined the clinical and economic outcomes of oral and gastrointestinal (GI) mucositis among patients receiving myelosuppressive chemotherapy.

Colposcopy For The Diagnosis of Squamous Intraepithelial Lesions: A Meta-Analysis

Objective To quantify by meta-analysis the performance of colposcopy to set a standard against which new technologies can be compared. Data Sources MEDLINE was searched for articles on colposcopy for diagnosis of squamous intraepithelial lesions (SIL). The search selected articles from 1960 to 1996 combining the key word “colposcopy” with key words “diagnosis,” “positive predictive value,” “negative predictive value,” “likelihood ratio,” and “receiver operating characteristic (ROC) curve.” Methods of Study Selection Articles were selected if the authors studied a population of patients with abnormal screening Papanicolaou smears and presented raw data showing for each cervical lesion type the number of patients judged positive and negative by colposcopic impression versus the standard of colposcopic biopsy results. Nine of 86 studies met these criteria. Tabulation, Integration, and Results Biopsies had been categorized as normal, atypia, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, carcinoma in situ, and invasive cancer; we recalculated performance measures using the Bethesda system. Overall sensitivity, specificity, likelihood ratios, ROC curves, and the corresponding areas under the curves were calculated. The average weighted sensitivity of diagnostic colposcopy for the threshold normal compared with all cervix abnormalities (atypia, low-grade SIL, high-grade SIL, cancer) was 96% and the average weighted specificity 48%. For the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer, average weighted sensitivity was 85% and average weighted specificity 69%. Likelihood ratios generated small but important changes in probability for distinguishing normal cervix and low-grade SIL from high-grade SIL and cancer. Areas under the ROC curve were 0.80 for the threshold normal cervix compared with all abnormalities and 0.82 for the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer. Conclusion Colposcopy compares favorably with other medical diagnostic tests in terms of sensitivity, specificity, and area under the ROC curve. New diagnostic methods for the cervix can be compared with colposcopy using these quantified values.

Increasing Disparities in the Age-Related Incidences of Colon and Rectal Cancers in the United States, 1975-2010

IMPORTANCE The overall incidence of colorectal cancer (CRC) has been decreasing since 1998 but there has been an apparent increase in the incidence of CRC in young adults. OBJECTIVE To evaluate age-related disparities in secular trends in CRC incidence in the United States. DESIGN, SETTING, AND PATIENTS A retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) CRC registry. Age at diagnosis was analyzed in 15-year intervals starting at the age of 20 years. SEER*Stat was used to obtain the annual cancer incidence rates, annual percentage change, and corresponding P values for the secular trends. Data were obtained from the National Cancer Institutes SEER registry for all patients diagnosed as having colon or rectal cancer from January 1, 1975, through December 31, 2010 (N = 393 241). MAIN OUTCOME AND MEASURE Difference in CRC incidence by age. RESULTS The overall age-adjusted CRC incidence rate decreased by 0.92% (95% CI, -1.14 to -0.70) between 1975 and 2010. There has been a steady decline in the incidence of CRC in patients age 50 years or older, but the opposite trend has been observed for young adults. For patients 20 to 34 years, the incidence rates of localized, regional, and distant colon and rectal cancers have increased. An increasing incidence rate was also observed for patients with rectal cancer aged 35 to 49 years. Based on current trends, in 2030, the incidence rates for colon and rectal cancers will increase by 90.0% and 124.2%, respectively, for patients 20 to 34 years and by 27.7% and 46.0%, respectively, for patients 35 to 49 years. CONCLUSIONS AND RELEVANCE There has been a significant increase in the incidence of CRC diagnosed in young adults, with a decline in older patients. Further studies are needed to determine the cause for these trends and identify potential preventive and early detection strategies.

A Comparison of C/B Ratios from Studies Using Receiver Operating Characteristic Curve Analysis ☆

In receiver operating characteristic (ROC) curve analysis, the optimal cutoff value for a diagnostic test can be found on the ROC curve where the slope of the curve is equal to (C/B) x (1-p[D])/p[D], where p[D] is the disease prevalence and C/B is the ratio of net costs of treating nondiseased individuals to net benefits of treating diseased individuals. We conducted a structured review of the medical literature to examine C/B ratios found in ROC curve analysis. Only two studies were found in which a C/B ratio was explicitly calculated; in another 11 studies, a C/B ratio was based on a so-called holistic estimate, an all-encompassing educated estimate of the relative costs and benefits relevant to the clinical situation. The C/B ratios ranged from 0.0025 (tuberculosis screening) to 2.7 (teeth restoration for carious lesions). Clinical scenarios that are directly life threatening but curable had C/B ratios of less than 0.05. This analysis led us to construct a table of ordered C/B ratios that may be used by investigators to approximate C/B ratios for other clinical situations in order to establish cutpoints for new diagnostic tests.

Ethnic and Sex Bias in Primary Care Screening Tests for Alcohol Use Disorders

Alcohol use is the third leading cause of preventable death in the United States [1], and alcohol-related morbidity is substantial [2]. For many persons with alcohol problems, a primary care provider is the first contact with the health care system [3]. Unfortunately, the problem often goes unrecognized until it has had significant consequences for physical health [4]. Many professional organizations recommend questioning patients about alcohol use [5-7]. The routine use of biochemical markers as the primary method for screening for alcohol problems in asymptomatic patients is discouraged by the U.S. Preventive Services Task Force because the accuracy of such tests is poor compared with that of self-report measures [6]. Many self-report screening tests have been developed to help identify patients with alcohol use disorders. Nevertheless, concern is growing over the lack of validation of these tests in patients who are female, elderly, or nonwhite [8]. Concerns about potential ethnic and sex bias in screening accuracy are particularly important because patterns of alcohol use [9, 10], the prevalence of alcohol use disorders [11, 12], and the consequences of alcohol consumption [2, 13] vary in men and women from different ethnic backgrounds in the United States. We tested for bias in the accuracy of three common self-report screening tests across sex and ethnic subgroups of primary care patients. The CAGE questionnaire was selected for evaluation because it is one of the most widely used screening tests for alcoholism. It was developed originally to identify the hidden alcoholic in hospital settings [14] and has also been evaluated in primary care settings [15, 16]. We also selected the Self-Administered Alcoholism Screening Test (SAAST), a self-administered version of the Michigan Alcoholism Screening Test, for evaluation (Appendix Figure 1). The SAAST was developed to screen for alcoholism in general medical patients and is available in a 9-item version with response options in a yes/no format. The final instrument selected for evaluation was the Alcohol Use Disorders Identification Test (AUDIT), developed by the World Health Organization [17] (Appendix Figure 2). The 10-item AUDIT was developed to detect persons with early alcohol use problems who do not necessarily meet the diagnostic criteria for alcohol dependence. In our study, the criterion variable was a current alcohol use disorder, including alcohol abuse and alcohol dependence, as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) [18]. Recommended methodologic standards for evaluating diagnostic tests guided this analysis [19]. Appendix Figure 1. Appendix Figure 2. Methods Patients and Procedures Participants were adult primary care patients presenting to the Family Practice Center at the University of Texas Medical Branch, Galveston, Texas. This family medicine clinic, which is a residency-training site, serves an ethnically diverse community and has an annual patient-visit volume in excess of 30 000; the patients are a mix of privately insured, managed care, Medicaid, Medicare, and uninsured patients. Faculty and resident practices are located at the Center, which has approximately 12 faculty physicians and 20 resident providers. The sampling strategy was designed to ensure adequate representation of minority and female patients. Adult family medicine patients were randomly selected from the Family Practice Center appointment lists. For each clinic session, a patient was selected at random by using a table of random numbers from among those patients who had appointment times within the first 60 minutes of the session. Thereafter, patients were selected according to appointment time at fixed intervals (for example, 45 minutes after the previously selected patient) to allow for a manageable flow of patients through the interview process. Patients were contacted about participating in the study by telephone on the day before their scheduled appointments. Patients who could not be reached by telephone (30%) were approached directly in the clinics waiting area on the day of their appointment. If a patient refused to participate in the study, the next patient on the appointment schedule was approached. Sampling continued until at least 100 men and 250 women in each ethnic group had participated. The sampling strategy is described in more detail elsewhere [20]. Data were collected between October 1993 and December 1994. While waiting to see their physicians, patients completed self-report questionnaires that included questions about sociodemographic indicators and the SAAST. After their office visits, patients participated in an interview that was administered by project interviewers and included the CAGE questionnaire, the AUDIT, and a diagnostic schedule used to determine the presence of an alcohol use disorder. Interviewers were not given the results of the diagnostic interview, which was scored by computer algorithm after the questionnaire and interview had been completed. All study materials were translated into Spanish, and Spanish-speaking interviewers were used with Mexican-American patients (30 patients selected Spanish administration). Patients were reimbursed

Pain and Quality of Life After Treatment in Patients With Locally Recurrent Rectal Cancer

10 for their time. Written informed consent was obtained from each patient, and the project was approved by our institutional review board. Instruments CAGE The acronym CAGE represents four brief questions: Have you ever felt you should Cut down on your drinking? Have people Annoyed you by criticizing your drinking? Have you ever felt bad or Guilty about your drinking? Have you ever had a drink first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover? The CAGE was developed as a device to screen for alcoholism in hospital settings, where high rates of alcohol abuse are often seen [14]. It is also widely used in clinical settings and community-based studies and is considered an indirect measure of alcoholism because it addresses the consequences of drinking (with the exception of the eye-opener question) rather than alcohol consumption per se [21]. The CAGE can be used during the clinical interview (self-administered) or as part of a broader assessment of alcohol use (as was done in this study). A yes answer to two or more questions is generally considered a positive result [21], although an approach that uses likelihood ratios has also been proposed [15]. The time frame for the CAGE is lifetime. Self-Administered Alcoholism Screening Test The SAAST [22-24] is a modified, self-administered version of the Michigan Alcoholism Screening Test. In our study, we used the 9-item version of the SAAST (completed by patients before the diagnostic interview) because its reduced length is more amenable to primary care settings [25]. The Michigan Alcoholism Screening Test is a structured, 25-item questionnaire that has been used to detect alcoholism in many groups, including persons suspected of driving while under the influence of alcohol [26]. The 9-item version of the SAAST was developed for use in medical settings and has shown consistency in U.S. and Mexican samples [27]. Three items are similar to the annoyed, eye-opener, and cut down questions from the CAGE; the rest address the consequences of drinking and indicators of dependence. The instrument is scored by summing responses to the questions (the annoyed and cut-down questions each receive a weight of 2, and all others receive a weight of 1), and a score of 3 or more is considered a positive result [25]. The time frame for the SAAST is lifetime. Alcohol Use Disorders Identification Test The AUDIT is a 10-item, self-report screening test that identifies patients at risk for alcohol use disorders by using procedures appropriate for the variety of health care facilities in developed and developing counties [17, 28, 29]. The AUDIT was developed by the World Health Organization (WHO) for the express purpose of avoiding ethnic and cultural bias. An extensive, multinational instrument development study of primary health care patients was coordinated by WHO (the WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption) to eliminate such bias [17]. The AUDIT has three important advantages over other screening tests: It 1) identifies at-risk alcohol users who do not meet criteria for alcohol dependence, 2) includes both consumption-based indicators of alcohol problems and indicators of harmful use and dependence, and 3) uses both current (defined as within the past month) and lifetime time frames. Response options range from 0 to 4, and a positive result is a score of 8 or more [28] (alternative cut-points and approaches using likelihood ratios have been suggested [20, 30, 31]). The instrument can be self-administered or given orally (as was done in our study). Alcohol Use Disorders Diagnostic Schedule The patient interview included the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS), a structured diagnostic schedule developed for use in the National Longitudinal Alcohol Epidemiologic Survey, which was started in 1992 by the National Institute on Alcohol Abuse and Alcoholism [32]. The AUDADIS has shown reliability in clinical and general population studies, applicability for cross-cultural research, and concordance with other diagnostic instruments [33-36]. It was designed to be administered by trained lay interviewers, as was done in our study. We used the AUDADIS Alcohol Experiences module to determine the presence of alcohol abuse or dependence according to the DSM-IV criteria [18]. Alcohol dependence, as defined by DSM-IV, is a maladaptive pattern of alcohol use leading to clinically significant impairment or distress as manifested by three or more of the following criteria: increased tolerance, withdrawal, impaired control, neglect of activities, increased time spent drinking, and drinking despite problems.

Incidence, Cost, and Outcomes of Bleeding and Chemotherapy Dose Modification Among Solid Tumor Patients With Chemotherapy-Induced Thrombocytopenia

PURPOSE Because survival in patients with locally recurrent rectal cancer (LRRC) is limited, pain control and quality of life (QOL) are important parameters. The purpose of this study was to assess the prevalence of posttreatment pain and QOL of patients with LRRC treated with nonsurgical palliation or resection and identify predictors of poor outcome. PATIENTS AND METHODS Posttreatment pain severity and QOL were prospectively assessed in 45 patients with LRRC using the Brief Pain Inventory and Functional Assessment of Cancer Therapy-Colorectal questionnaire. RESULTS Fifteen patients received nonsurgical palliation, and 30 patients underwent resection of their pelvic tumors. There was a significant association between higher posttreatment pain scores and worse QOL (P <.001). Patients treated with nonsurgical palliation reported moderate to severe pain beyond the third month of treatment. Resected patients reported comparable levels of pain during the first 3 postoperative years, particularly after bony resections; long-term survivors (beyond 3 years), however, reported minimal pain and good QOL. Female sex, pelvic/sciatic pain at presentation, total pelvic exenteration, and bony resection were associated with higher rates of moderate to severe posttreatment pain (P =.04, P <.001, P =.04, and P =.02, respectively). Pain at presentation was an independent predictor of posttreatment pain (odds ratio, 7.4 [95% confidence interval, 1.8 to 30.3]; P =.006). CONCLUSION Patients with LRRC treated with nonsurgical palliation or resection experience significant levels of pain after treatment. Close posttreatment pain monitoring is warranted in patients presenting with pelvic pain, and more aggressive pain management strategies may improve posttreatment QOL.

Dyspnea in cancer patients: Etiology, resource utilization, and survival-Implications in a managed care world

PURPOSE To describe the incidence and outcomes of bleeding and chemotherapy dose modifications associated with chemotherapy-induced thrombocytopenia (platelets < 50,000/microL). PATIENTS AND METHODS Six hundred nine patients with solid tumors or lymphoma were followed-up during 1,262 chemotherapy cycles complicated by thrombocytopenia for development of bleeding, delay or dose reduction of the subsequent cycle, survival, and resource utilization. The association between survival and bleeding or dose modification was examined using the Cox proportional hazards model. Predisposing factors were identified by logistic regression. RESULTS Bleeding occurred during 9% of cycles among patients with previous bleeding episodes (P <.0001), baseline platelets less than 75,000/microL (P <.0001), bone marrow metastases (P =.001), poor performance status (P =.03), and cisplatin, carboplatin, carmustine or lomustine administration (P =.0002). Major bleeding episodes resulted in shorter survival and higher resource utilization (P <.0001). Chemotherapy delays occurred during 6% of cycles among patients with more than five previous cycles (P =.003), radiotherapy (P =.03), and disseminated disease (P =.04). They experienced similar clinical outcomes but used significantly more resources. Dose reductions occurred during 15% of cycles but were not associated with poor clinical outcomes or excess resource utilization. Significantly shorter survival and higher resource utilization were observed among the 20% of patients who failed to achieve an adequate response to platelet transfusion. CONCLUSION The incidence of bleeding is low among solid tumor patients overall but exceeds 20% in some subgroups. These subgroups are easily identifiable using routinely available clinical information. A clinical prediction rule is being developed. Poor response to platelet transfusion is a clinically and financially significant downstream effect of thrombocytopenia and warrants further investigation.

Determining the area under the ROC curve for a binary diagnostic test

Dyspnea is the fourth most common symptom of patients who present to the emergency department (ED) at The University of Texas M. D. Anderson Cancer Center and may, in some patients with advanced cancer, represent a clinical marker for the terminal phase of their disease. This retrospective study describes the clinical characteristics of these patients, the resource utilization associated with the management of dyspnea, and the survival of patients with this symptom.

Long-term quality of life after radiotherapy for the treatment of anal cancer

The authors provide a simple calculation for the unbiased estimation of the area under the ROC curve for a binary diagnostic test or a continuously valued test result that is effectively used in a binary way. The formula described can be used to interpret the discriminative ability of a diagnostic test. Key words: ROC curve analysis, binary diagnostic test; discriminative ability. (Med Decis Making 2000;20:468-470)