Kathleen J. Yost

The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System: properties, applications, and interpretation.

The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System is a collection of health-related quality of life (HRQOL) questionnaires targeted to the management of chronic illness. The measurement system, under development since 1987, began with the creation of a generic CORE questionnaire called the F unctional A ssessment of C ancer T herapy-G eneral (FACT-G). The FACT-G (now in Version 4) is a 27-item compilation of general questions divided into four primary QOL domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. It is appropriate for use with patients with any form of cancer, and extensions of it have been used and validated in other chronic illness condition (e.g., HIV/AIDS; multiple sclerosis; Parkinsons disease; rheumatoid arthritis), and in the general population. The FACIT Measurement System now includes over 400 questions, some of which have been translated into more than 45 languages. Assessment of any one patient is tailored so that the most-relevant questions are asked and administration time for any one assessment is usually less than 15 minutes. This is accomplished both by the use of specific subscales for relevant domains of HRQOL, or computerized adaptive testing (CAT) of selected symptoms and functional areas. FACIT questionnaires can be administered by self-report (paper or computer) or interview (face-to-face or telephone). Available scoring, normative data and information on meaningful change now allow one to interpret results in the context of a growing literature base.

Socioeconomic status and breast cancer incidence in California for different race/ethnic groups

AbstractObjective: The majority of research on breast cancer risk and socioeconomic status (SES) has been conducted for blacks and whites. This study evaluates the relationship between SES and breast cancer incidence in California for four race/ethnic groups. Methods: Principal component analysis was used to create an SES index using 1990 Census data. Untracted cases were randomly allocated to census block groups within their county of residence. A total of 97,227 female breast cancer cases diagnosed in California between 1988 and 1992 were evaluated. Incidence rates and rate ratios (RRs) were estimated and a χ2 test for trend across SES levels was performed. Results: SES was positively related to breast cancer incidence, and this effect was stronger for Hispanics and Asian/others than for whites and blacks. Adjusting by SES did not eliminate the differences in breast cancer rates among race/ethnic groups. RR differences between the race/ethnic groups were greatest in the lowest SES category and attenuated with increasing SES. An increasing trend over SES was statistically significant for all race/ethnic groups. Including randomly allocated cases affected RR estimates for white women only. Conclusions: Our results are consistent with similar findings for the Los Angeles area but differ from previous results for the San Francisco Bay area.

General Population and Cancer Patient Norms for the Functional Assessment of Cancer Therapy-General (FACT-G)

Given the number of new cancer cases diagnosed each year and the increases in survival rates, the importance of having a clinically useful health-related quality of life (HRQOL) instrument has increased. The Functional Assessment of Cancer Therapy-General (FACT-G) is one such instrument that has been used worldwide to assess HRQOL. Previously, the use of the FACT-G had been limited because of a lack of published normative data. Normative data are useful for consumers to place their results in an appropriate context by comparing their scores of individuals or group of individuals to a reference group. Here, we present normative data for the FACT-G for two reference groups: (a) a sample of the general U.S. adult population and (b) a large, heterogeneous sample of adult patients with cancer. In addition, we demonstrate various uses of the normative data.

Combining Distribution- and Anchor-Based Approaches to Determine Minimally Important Differences The FACIT Experience

Health-related quality of life (HRQOL) is an important endpoint in cancer clinical trials and in cancer treatment in general; however, the meaningfulness of HRQOL scores may not be apparent to clinicians or researchers. Minimally important differences (MIDs) can enhance the interpretability of HRQOL scores by identifying differences likely to be meaningful to patients and clinicians. This article’s objective is to describe and provide examples of approaches we have used to identify MIDs for instruments in the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system. Distribution- and anchor-based approaches are described and illustrated. We also discuss the importance of assessing the appropriateness of anchors, and we provide suggestions for combining results into a single range of plausible MIDs. MIDs for FACIT instruments established to date are summarized, and general guidelines that can be used to estimate MIDs for other FACIT instruments are provided. Applications of MIDs in research are illustrated.

Development and Validation of a Symptom-Based Activity Index for Adults With Eosinophilic Esophagitis

BACKGROUND & AIMS Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE) and to provide end points for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patient assessments of disease severity. We also evaluated relationships between patient assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS We collected information from 186 patients with EoE in Switzerland and the United States (69.4% male; median age, 43 y) via surveys (n = 135), focus groups (n = 27), and semistructured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patient assessment of EoE severity. The PRO instrument was used prospectively in 153 adult patients with EoE (72.5% male; median age, 38 y), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 y). RESULTS Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patient assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity (range, 0-10) and PRO score (range, 0-8.52) was 0.15. CONCLUSIONS We developed and validated an EoE scoring system based on 7 PRO items that assess symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263.

Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis

BACKGROUND & AIMS It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.

Lymphedema after surgery for endometrial cancer: Prevalence, risk factors, and quality of life

OBJECTIVE: To estimate lower extremity lymphedema prevalence in patients surgically treated for endometrial cancer, identify predictors of lymphedema, and evaluate the effects of lymphedema on quality of life. METHODS: One thousand forty-eight consecutive patients who were operated on between 1999 and 2008 at the Mayo Clinic were mailed a survey, which included our validated 13-item lymphedema screening questionnaire and two validated quality-of-life measures. Logistic regression models were fit to identify factors associated with prevalent lymphedema; a multivariable model was obtained using stepwise and backward variable selection methods. The relationship between lymphedema and obesity with each quality-of-life score was evaluated separate multivariable linear models. RESULTS: There were 591 responders (56%) after exclusions. Our questionnaire revealed a previous self-reported lymphedema diagnosis in 103 (17%) patients and identified undiagnosed lymphedema in 175 (30%) (overall prevalence 47.0%, median 6.2 years follow-up). Lymphedema prevalence in patients treated with hysterectomy alone compared with lymphadenectomy was 36.1% and 52.3%, respectively (attributable risk 23%). Lymphedema risk was not associated with the number of nodes removed or the extent of lymphadenectomy after adjusting for other factors. On multivariable analysis, higher body mass index, congestive heart failure, performance of lymphadenectomy, and radiation therapy were associated with prevalent lymphedema. Multiple quality-of-life scores were worse in women with lymphedema. CONCLUSION: The attributable risk of developing lower extremity lymphedema was 23% for patients with endometrial cancer who underwent lymphadenectomy compared with hysterectomy alone with an overall prevalence of 47%. Lymphedema was associated with reductions in multiple quality-of-life domains. LEVEL OF EVIDENCE: II

Fertility Preservation and Adolescent Cancer Patients: Lessons from Adult Survivors of Childhood Cancer and Their Parents

Building on 40 years of progress in cancer detection and treatment, survival rates for childhood cancers have risen from 20 % to almost 80 % [1,2]. Approximately 270,000 Americans are childhood cancer survivors and, by 2010, an estimated 1 in every 250 adults will be living with a history of childhood cancer [2,3]. The early and late effects of treatment are beginning to take on greater importance for survivors, their families and providers [4]. Increasing numbers of childhood cancer survivors are beginning to face a new challenge in returning to normalcy after cancer. Infertility is one of the most common chronic medical problems reported by childhood cancer survivors [5] and can be a primary concern particularly among female survivors [6]. Female infertility has biological and psychosocial implications that cannot be easily addressed given the ethical and legal questions surrounding fertility preservation [7–9]. Recent advances in fertility preservation may soon offer potential methods for females of all ages to protect their reproductive capacity from damaging radiation and/or chemotherapy [10]. Current literature focuses on the further development of preservation techniques and the numerous ethical and legal questions, but little knowledge is available on the attitudes and opinions of childhood cancer patients and their parents regarding fertility preservation. Progress is being made in understanding the fertility issues that women may face after treatment. Infertility as an isolated health problem can be emotionally devastating for a woman [11] and is often viewed as a loss of one’s sense of femininity [12]. The risk of infertility touches on the most intimate aspects of a woman’s life after cancer, particularly her relationships, future plans for a family, and concerns about pregnancy and birth [4,12–16]. For cancer survivors who may be dealing with additional physical and emotional concerns, infertility may add yet another concern to an already lengthy list of fears and worries [17]. Some survivors describe that the loss of fertility can be as painful as facing cancer itself [15,18]. The situation is further complicated by the fact that female cancer survivors, particularly pediatric cancer patients, lack clear-cut options to address their fertility that are available to their male counterparts. Advancements in semen cryopreservation and intracytoplasmic sperm injection (ICSI) have revolutionized the reproductive outlook of male patients who have reached puberty [19]. Recent advances in reproductive science are beginning to change what is possible for female survivors as well. Traditionally, few options existed for female cancer patients who may want to have their own biological children in the future. The only two established techniques women have for fertility preservation are protecting the ovaries from radiation and emergency in vitro fertilization (IVF) [20,21]. While protecting a patient’s ovaries has become common practice, emergency IVF cannot be offered to patients diagnosed with cancer before puberty because mature oocytes cannot be collected [22]. The promise for female patients with childhood cancer lies in the strides made toward ovarian transplantation and in vitro follicle maturation. Ovarian transplantation involves the removal and cryopreservation of ovarian tissue before treatment and the reintroduction of tissue after treatment, either orthotopically or heterotopically, such as in muscle or subcutaneously [23]. Researchers have demonstrated that transplantation of cryopreserved ovarian tissue has led to human embryonic development when accomplished heterotopically [24] and to a live birth after orthotopic transplantation [25]. Another promising method of fertility preservation is in vitro maturation of immature oocytes. Similar to ovarian transplantation, ovarian tissue is removed and cryopreserved before fertility-threatening treatment. Once a woman is prepared to have a child, follicles can be isolated from the thawed tissue, matured in vitro in a three-dimensional culture system, and the mature oocyte can be fertilized through IVF. Murine oocytes have been collected from in vitro grown follicles, matured, and fertilized in vitro, which has resulted in live births [26]. Human trials, where one ovary is laparoscopically removed before treatment, are being conducted on adult patients in order to begin the experimental process of perhaps one day delivering this option to female cancer patients. As research begins to enter the clinical arena, a large number of unanswered questions remain regarding the application of the procedures, the legal and ethical considerations involved, and the receptiveness of patients and their families to fertility preservation. Thus far, very few studies have considered the viewpoints of childhood cancer patients and their parents [27]. Since decisions regarding fertility preservation must be made before treatment begins, parents, physicians, and patients are required to make a complex decision in a short amount of time during an extremely stressful situation, similar to the anxiety involved in the informed consent process of clinical cancer research trials [28]. In order for fertility preservation to become a realistic and valued addition to the treatment of childhood cancer patients, a better understanding of the decision-making process that parents and their children go through at the time of diagnosis and their interest in fertility preservation is needed. Further, a more thorough exploration of the patients’ and parents’ thoughts regarding the child’s fertility at the time of diagnosis as well as later in the patient’s life will be valuable in the continued advancement and eventual application of fertility preservation.

A systematic review of patient-reported measures of burden of treatment in three chronic diseases

Background Burden of treatment refers to the workload of health care and its impact on patient functioning and well-being. There are a number of patient-reported measures that assess burden of treatment in single diseases or in specific treatment contexts. A review of such measures could help identify content for a general measure of treatment burden that could be used with patients dealing with multiple chronic conditions. We reviewed the content and psychometric properties of patient-reported measures that assess aspects of treatment burden in three chronic diseases, ie, diabetes, chronic kidney disease, and heart failure. Methods We searched Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, and EBSCO CINAHL through November 2011. Abstracts were independently reviewed by two people, with disagreements adjudicated by a third person. Retrieved articles were reviewed to confirm relevance, with patient-reported measures scrutinized to determine consistency with the definition of burden of treatment. Descriptive information and psychometric properties were extracted. Results A total of 5686 abstracts were identified from the database searches. After abstract review, 359 full-text articles were retrieved, of which 76 met our inclusion criteria. An additional 22 articles were identified from the references of included articles. From the 98 studies, 57 patient-reported measures of treatment burden (full measures or components within measures) were identified. Most were multi-item scales (89%) and assessed treatment burden in diabetes (82%). Only 15 measures were developed using direct patient input and had demonstrable evidence of reliability, scale structure, and multiple forms of validity; six of these demonstrated evidence of sensitivity to change. We identified 12 content domains common across measures and disease types. Conclusion Available measures of treatment burden in single diseases can inform derivation of a patient-centered measure of the construct in patients with multiple chronic conditions. Patients should take part in developing the measure to ensure salience and relevance.

Comparing SF-36 scores across three groups of women with different health profiles

Background: The widespread use of the Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) facilitates the comparison of health-related quality of life (HRQL) across independent studies. Objectives: To compare the scores of eight scales and two summary scales of the SF-36 across participants in the Women’s Healthy Eating and Living (WHEL) trial, the Women’s Health Initiative-Dietary Modification trial (WHI-DM), and the MOS, and to illustrate the use of effect sizes for interpreting the importance of group differences. Methods: WHEL and WHI-DM are both multi-center dietary interventions; only data from the UC Davis sites were used in our study. WHEL participants had a recent history of breast cancer, WHI-DM participants were healthy, postmenopausal women, and women in the MOS had a history of hypertension, diabetes, heart disease, or depression. General linear models were used to identify statistically significant differences in scale scores. Meaningful differences were determined by effect sizes computed using a common within-group standard deviation (SD) and SDs from normative data. Results: After adjusting for age and marital status, SF-36 scores for the WHI-DM and WHEL samples were similar and both had statistically significantly higher scores than the MOS sample. Relative to the WHEL or WHI-DM studies, MOS scores for scales related to the physical domain were clearly meaningfully lower whereas scale scores related to the mental health domain were potentially meaningfully lower. Conclusions: The HRQL of breast cancer survivors is comparable to that of healthy women and better than that of women with chronic health conditions, particularly with respect to physical health. This study illustrated the use of ranges of effects sizes for aiding the interpretation of SF-36 scores differences across independent studies.