CONTINUING PROGRESS IN treatment effectiveness for

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1 128 ORIGINAL ARTICLE The Impact of Limitations in Physical, Executive, and Emotional Function on Health-Related Quality of Life Among Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study Kirsten K. Ness, PT, PhD, James G. Gurney, PhD, Lonnie K. Zeltzer, MD, Wendy Leisenring, ScD, Daniel A. Mulrooney, MD, MS, Paul C. Nathan, MD, MSc, Leslie L. Robison, PhD, Ann C. Mertens, PhD ABSTRACT. Ness KK, Gurney JG, Zeltzer LK, Leisenring W, Mulrooney DA, Nathan PC, Robison LL, Mertens AC. The impact of limitations in physical, executive, and emotional function on health-related quality of life among adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Arch Phys Med Rehabil 2008;89: From the Department of Epidemiology and Cancer Control, St. Jude Children s Research Hospital, Memphis, TN (Ness, Robison); Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI (Gurney); Departments of Pediatrics, Anesthesiology, and Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA (Zeltzer); Fred Hutchinson Cancer Research Center, Seattle, WA (Leisenring); Department of Pediatrics, University of Minnesota, Minneapolis, MN (Mulrooney); Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada (Nathan); and Aflac Cancer Center & Blood Disorders Service, Emory Children s Center, Atlanta, GA (Mertens). Preliminary data presented at the Psychosocial and Neurocognitive Consequences of Childhood Cancer Conference, September 14, 2006, in Memphis, TN. Supported by the National Cancer Institute (grant no. U24-CA55727), the American Lebanese Syrian Associated Charities, and the Children s Cancer Research Fund. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Reprint requests to Kirsten K. Ness, PT, PhD, St. Jude Children s Research Hospital, Mail Stop 735, 332 N Lauderdale, Memphis, TN 38105, kiri.ness@stjude.org /08/ $34.00/0 doi: /j.apmr Objective: To examine associations between limitations in physical performance, executive function, and emotional health (activity domains) and either social role attainment or healthrelated quality of life (HRQOL) in adult survivors of childhood cancer. Design: Cross-sectional analysis. Setting: Cancer survivors living in the community; previously treated for childhood cancer at one of 26 institutions. Participants: Subjects included 7147 (76.8%) of 9307 eligible adult members of the Childhood Cancer Survivor Study who completed a follow-up questionnaire between 2002 and Interventions: Not applicable. Main Outcome Measures: Demographic information was used to classify social roles and the Medical Outcomes Survey 36-Item Short-Form Health Survey to ascertain HRQOL. Questions from the National Health Interview Survey were used to represent physical performance; from the Brief Symptom Inventory to classify emotional health; and from the Behavioral Rating of Executive Function to describe executive function. Multivariate logistic regression was used to examine the association between limitations in activity domains, role attainment, and HRQOL. Results: In this cohort, 18.1% reported deficits in physical performance, 10.5% in emotional health, and 14.0% in executive function. In adjusted models, when compared with survivors who reported no limitations, those with physical performance, executive function, or emotional health deficits were less likely to be employed, married, or have incomes greater than $20,000 a year. Limitations in executive function or emotional health were associated with no health insurance. Limitations in any activity domain were associated with poor HRQOL. Emotional health limitations had the most impact, with odds ratios from 3.18 (physical performance summary) to (mental health). Conclusions: The results of these analyses show the need for development and testing of interventions to remediate limitations in activity domains, because they negatively impact role attainment and HRQOL. Key Words: Child; Cognition; Emotions; Mobility limitation; Neoplasms; Quality of life; Rehabilitation; Survivors by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation CONTINUING PROGRESS IN treatment effectiveness for children with most types of cancer has stimulated focused research to better understand the long-term consequences of cancer and its treatment effects. Estimates from the National Cancer Institute indicate that there are approximately 1 in 840 adults alive today in the United States between 20 and 44 years of age who had a diagnosis of a cancer during childhood. 1 This increasing population of childhood cancer survivors clearly has public health importance. Understanding that surgery, radiation, and chemotherapy continue to be components of successful treatment of pediatric cancers, 2 modern treatment regimens increasingly incorporate knowledge on long-term adverse effects, and are designed to minimize risk of sequelae to the extent possible. Structural or physiologic impairments of the body s organ systems as a consequence of either the cancer or treatment intervention may alter normal organ system functioning. In turn, impaired functioning may limit the physical performance, executive function, or emotional health of the cancer survivor, and thus interfere with educational attainment, marriage opportunities, employability (social roles), and health-related quality of life (HRQOL). 3-5 The spectrum of specific organ system dysfunction and chronic disease in long-term childhood cancer survivors has been well documented. 6-9 In addition, the influence of specific childhood cancers and treatments on activity limitations, social role attainment, and HRQOL 23,26-32 are reported. The prevalence of physical performance limitations ranges from 12% among leukemia survivors to 40% for bone tumor survivors. 16 Less than optimal social role attainment and poor HRQOL are most prevalent among childhood

2 HRQOL IN CHILDHOOD CANCER SURVIVORS, Ness 129 cancer survivors whose cancer or treatment included an insult to the central nervous system (CNS). The literature documenting organ system impairments, activity limitations, role attainment, and HRQOL has not adequately addressed the associations among persistent activity limitations (physical performance, emotional health, executive function) and role attainment or HRQOL. Although some sample sizes have been sufficient, 11,16,20,21 analyses of the effects of treatment on role attainment or HRQOL informative, 11,14,21-25 and reports of the association between a single or even 2 domains of function, and either role attainment or HRQOL mentioned, we could find no comprehensive evaluation of the association between activity limitations in all 3 functional domains and both social role attainment and HRQOL in a large heterogeneous cohort of adult survivors of childhood cancer. Understanding the associations between activity limitations and role attainment and HRQOL is important for members of the rehabilitation community. Irreversible organ system deficits as the result of childhood cancer and its treatment may not be amenable to medical intervention; however, activity limitations can be remediated or ameliorated with compensatory and adaptive strategies provided by rehabilitation professionals. If activity limitations interfere with role attainment and HRQOL, a rehabilitation intervention (physical, occupational, neurocognitive, or psychosocial) designed to address activity limitations may eventually improve HRQOL and provide an avenue for optimal role attainment among those childhood cancer survivors whose disability interferes with performance. The purpose of this analysis was to evaluate the associations among physical performance, executive function, and emotional health and both role performance and HRQOL outcomes among adult survivors of childhood cancer. We hypothesized that cancer survivors with limitations in any of these domains would report deficits in role performance and HRQOL when compared with those who had no limitations. METHODS Study Participants The Childhood Cancer Survivor Study (CCSS) is an ongoing epidemiologic study of long-term survivors of childhood cancer. 33 Persons diagnosed at one of 26 institutions between 1970 and 1986, when younger than age 21, with primary brain cancer, leukemia, Hodgkin s lymphoma, non-hodgkin s lymphoma, kidney tumor, neuroblastoma, soft tissue sarcoma, or malignant bone tumor, who had survived at least 5 years since their original diagnosis, were eligible to participate. Of 20,720 persons originally eligible, 17,703 (85.4%) were located, and 14,372 (81.2%) completed a baseline questionnaire. The human subjects committee at each of the collaborating institutions approved the study protocol and documents prior to participant enrollment. Participants provided informed consent to participate and separate consent for medical record abstraction. Study participants completed the 24-page baseline questionnaire in 1995 and 1996, the first follow-up questionnaire between 2000 and 2002, and the second follow-up questionnaire between 2002 and These analyses include those participants who completed the baseline questionnaire, and the psychosocial component of the second follow-up questionnaire. Variable Definitions Outcomes. The primary outcomes of interest for these analyses were role participation and HRQOL. Role participation, defined as educational attainment, employment, annual household income, and marital status, was taken from participants answers to questions on the second follow-up questionnaire. Variables were dichotomized for analysis and are compared as (1) high school graduate versus non-high school graduate; (2) employed, caring for home/family or student versus unemployed, unable to work or looking for work; (3) household income $20,000 per year versus less than $20,000 per year; and (4) married or living as married versus unmarried. HRQOL was evaluated by having participants complete the Medical Outcomes Survey 36-Item Short-Form Health Survey (SF-36) as part of the second follow-up questionnaire. The SF-36 is a widely used generic health profile with extensive age- and sex-specific norms for the United States. It provides subscale scores for 8 domains of HRQOL: mental health, physical health, emotional role function, physical role function, social health, pain, vitality and energy, health perceptions, and 2 overall summary scores (overall physical [PCS] and overall mental health [MCS]). 34 The internal consistency, validity of the instrument among different groups reporting ill health, and the test-retest reliability of the SF-36 are excellent Raw scores from the SF-36 were converted to T scores (range, 0 100) and dichotomized so that a score at or below 40 (1 standard deviation [SD] below the population mean) on a particular summary or subscale was classified as a poor HRQOL outcome. Predictor variables. We abstracted diagnosis and treatment data from medical records at baseline, and, although reported in a previous analysis of quality of life (QOL) in this cohort, they are included as predictors of the HRQOL summary outcomes for completeness. Activity limitations, defined as physical, executive, and/or emotional function, were considered as the primary risk factors for the role participation and for both the domain specific and summary HRQOL outcomes. As in our previous evaluation of physical function in this cohort, 16 we scored physical performance by adding the participants answers to 6 questions derived from the National Health Interview Survey 38 that were part of the baseline questionnaire. Although these questions are similar in content to the physical function questions on the SF-36, they ask how long a limitation has been present rather than how much a limitation is affected by health. The initial, unadjusted, correlation between the physical performance scores and the physical function scale norm scores on the SF-36 was.46 (P.05), reflecting a potential association rather than convergent variables. These questions reflect the presence of persistent physical disability and ask the following: Over the past 2 years, how long, if at all, has your health limited you in each of the following activities: (1) vigorous activities like lifting heavy objects, running, or participating in strenuous sports; (2) moderate activities like moving a table, carrying groceries, or bowling; (3) walking uphill or climbing a few flights of stairs; (4) bending, lifting, or stooping; (5) walking 1 block; and (6) eating, dressing, bathing, or using the toilet? Individual questions were scored as 1 if activity was limited for more than 3 months, 2 if the activity was limited for 3 months or less, and 3 if the activity was not limited at all. Scores ranged from 6 (most physical limitation) to 18 (no physical limitation). Graphical examination of the distribution resulted in a dichotomy, such that survivors with a score at or below the score representing the lowest 10th percentile of a sibling comparison group were classified as having limited physical performance.

3 130 HRQOL IN CHILDHOOD CANCER SURVIVORS, Ness We classified executive function by summing participants answers to 15 questions from the Behavioral Rating Inventory of Executive Function Adult Version (BRIEF-A), 39 representing meta-cognition and behavioral regulation over the previous 6 months. The questions are listed in appendix 1. Individual questions were scored on a scale of 1 to 3, where 1 indicated that the item was never a problem, 2 indicated that the item was sometimes a problem, and 3 indicated that the item was often a problem. Questions were summed and converted to T scores using values calculated from the population used to create the BRIEF-A. 39 The scale was dichotomized so that participants with T scores of 63 or greater were classified as having limited executive function. This corresponded to the 90th percentile of the normative population used to develop the scale. Emotional health was classified by having participants complete the Brief Symptom Inventory 18 (BSI-18). The BSI-18 is a measure of global mental health, and of depression, somatization, and anxiety. The BSI-18 has been validated in cancer survivors and population controls. 40 It is highly correlated with the Symptom Checklist-90 Revised (r.93) and the clinical scales, the Wiggins content scales and the Tryon cluster scales of the Minnesota Multiphasic Personality Inventory (r.60). As in previous reports, 20,41 participants with T scores of 63 or more on the global status index were classified as having poor emotional health. Sex, age at the second follow-up, and survival time were considered as potential confounders or effect modifiers of the association among the function domains and the outcomes of interest in our multivariate models. Data Analysis We calculated descriptive statistics, including frequencies and percentages, for the demographic and treatment characteristics of the eligible participants and compared between participants and nonparticipants with 2 sample t tests and chisquare statistics. Participants who reported poor outcomes on the summary and subscales of the SF-36 were compared by diagnostic and treatment groups in age- and sex-adjusted logistic regression models. The prevalence of high school graduates, survivors currently employed or full-time students, households with incomes more than $20,000 a year, persons currently married, and those reporting poor HRQOL on the summary or subscales of the SF-36 were compared between survivors with limitations in physical, executive, and emotional function and those without, using multivariate logistic regression. 42 All models were adjusted for sex, age at questionnaire, and length of follow-up after diagnosis. Colinearity among the physical performance, emotional health, and executive function variables were evaluated both by examining correlations and with linear regression diagnostics. The correlations among the 3 variables ranged from.08 to.37; however, all of the variance inflation factors were less than 1.2 and tolerance levels over.85, so all 3 variables were retained in the models. 42 Results are reported as frequencies and percentages, with odds ratios (ORs), 95% confidence intervals (CIs), and P values. RESULTS There were 9307 childhood cancer survivors who completed the second follow-up questionnaire. Among this group, 7147 (76.8%) also filled out the psychosocial component of the questionnaire and provided all responses necessary for evaluating predictor and outcome variable scores. The demographic and treatment characteristics of the eligible participants and nonparticipant survivors are shown in table 1. Participants were more likely than nonparticipants to be women (51.3% vs 42.7%), white (90.9% vs 82.6%), to be older than age 35 years at the second follow-up questionnaire (34.9% vs 28.5%), and to be older than age 10 years when diagnosed with their malignancy (38.7% vs 29.9%). Nonparticipants were somewhat less likely to have given permission for medical record abstraction at the time of initial enrollment in the CCSS cohort (82.4% vs 94.3%) but were equally likely to report a post-treatment major medical condition, defined previously by Hudson et al 41 as complete deafness, kidney dialysis, congestive heart failure, myocardial infarction, angioplasty, bypass surgery, stroke, liver cirrhosis, a heart, lung, or kidney transplant, amputation, joint replacement or second cancer, and/or current use of seizure medications, medications for heart problems or high blood pressure, chemotherapy, immune suppressants, or oxygen (18.8% vs 17.5%). The proportions of survivors reporting poor HRQOL outcomes on the PCS and MCS scales of the SF-36 are shown in table 2 by diagnosis and treatment groups. In an adjusted model, when compared with leukemia survivors, a higher percentage of participants with CNS malignancies, Hodgkin s lymphoma, neuroblastoma, and bone tumors reported poor HRQOL outcomes on the PCS of the SF-36. After adjusting for sex, age, time since diagnosis, and the other treatment interventions, survivors who were treated with surgery or cranial radiation were more likely than those without to report poor HRQOL outcomes on the PCS. The frequency of scoring in the limited range of performance in the physical, executive, and emotional function domains are shown in table 1. Physical performance limitations were most prevalent, with 18.1% of survivors scoring at or below the 10th percentile of the sibling comparison groups scores. The prevalence of limitations in executive function was 14.0%, and in emotional health was 10.5%. Table 3 shows the frequency and percentage of cancer survivors who reported high school graduation, current employment, household income more than $20,000 annually, and current status of married or living as married, by each of the 3 limitation categories: physical performance, executive function, and emotional health. ORs and 95% CIs from multivariate unconditional logistic regression are also shown. Models were adjusted concurrently for age at the second follow-up, time since diagnosis, sex, and each limitation category. Cancer survivors with limitations in physical performance were slightly less likely to graduate from high school, less likely to be employed, and less likely to have an annual household income of $20,000 or more than were those with no physical performance limitations. Cancer survivors with limited executive function were also less likely to graduate from high school or be employed than were those without limits on executive function. Participants with limited executive function were also less likely to report being married or living as married, and less likely to report an annual household income of $20,000 or more when compared with those who had intact executive function. Poor emotional health was associated with a lower likelihood of current employment, and being married or living as married. Participants who reported poor emotional health were less likely to have household incomes of $20,000 per year or more than those who did not report poor emotional health. The associations between limitations in physical performance, executive function, emotional health and scoring 1 or more SDs below the population norms of the summary and subscales of the SF-36 are shown in table 4. After adjusting for age at interview, years since diagnosis, and sex, as well as for executive function and emotional health, participants with limitations in physical function were 4 times more likely to report

4 HRQOL IN CHILDHOOD CANCER SURVIVORS, Ness 131 Table 1: Characteristics of the Study Population Participants (N 7147) Nonparticipants (n 2160) Characteristics n % n % Sex Male Female Race and ethnicity White Black Hispanic Other Not indicated Age at second follow-up (y) Age at diagnosis (y) Survival time (y) Diagnosis Acute lymphoblastic leukemia Acute myeloid leukemia Other leukemia Astrocytoma Medulloblastoma/PNET Other CNS tumor Hodgkin s disease Non-Hodgkin s lymphoma Wilms tumor Neuroblastoma Soft tissue sarcoma Ewing s sarcoma Osteosarcoma Other bone tumors Surgery No Yes Medical records not available Chemotherapy Alkylating agent Anthracycline Both alkylating agent and anthracycline Other chemotherapy agent No chemotherapy Medical records not available Radiation None Radiation, not cranial Cranial radiation Medical records not available Major medical condition.33 No Yes Limited physical function No NA NA Yes NA NA P

5 132 HRQOL IN CHILDHOOD CANCER SURVIVORS, Ness Table 1: Characteristics of the Study Population (Cont d) Participants (N 7147) Nonparticipants (n 2160) Characteristics n % n % No NA NA Yes NA NA Limited emotional function No NA NA Yes NA NA P Abbreviations: NA, not applicable; PNET, primitive neuroectodermal tumor. poor overall physical health and 28% more likely to report poor overall mental health than those without physical performance limitations. These associations were apparent for each subscale of the SF-36, except for the mental health subscale. Similarly, limitations in executive function and emotional health were associated with reports of poor HRQOL on both the PCS and MCS scales of the SF-36. The increased odds of reporting a poor HRQOL outcome ranged from 1.81 for the bodily pain subscale to 3.06 for the role emotional subscale between those with limitations in executive function and those without limitations. Emotional health limitations had an even greater impact on reporting poor HRQOL with the increased odds of a poor outcome ranging from 3.18 for the PCS to for the SF-36 mental health subscale for those with poor emotional health compared with those who had no emotional health limitations. DISCUSSION This analysis showed that limitations in physical performance, executive function, and emotional health are negatively associated with both role performance and self-reported HRQOL among adult survivors of childhood cancer. We confirmed findings from a previous analysis showing the highest percentage of poor physical HRQOL outcomes among survivors of CNS malignancies, Hodgkin s lymphoma, neuroblastoma, and bone tumors. Previous treatment with either surgery or cranial radiation also predicted poor physical HRQOL outcomes. Other reports from the CCSS cohort have indicated that physical performance and emotional health problems are most prevalent among survivors of CNS malignancies or bone tumors, among those treated with CNS radiation at an early age, and among those whose organ system late effects include cardiac abnormalities, neurologic impairment, or musculoskeletal deficits. 16,20,41 Poor outcomes in social role attainment and HRQOL are also present in a small group of survivors and are associated with CNS malignancies or bone tumors, treatment with cranial radiation, and younger age at diagnosis. 22,43 The results of these analyses extend the results of our previous study on physical performance limitations among adult survivors of childhood cancer, 16 which did not include assessments of emotional health, executive function, or measures of HRQOL. In the current analysis, we show that activity limitations in the physical performance, emotional health, and exec- Table 2: Number and Percent of Participants Scoring More Than 1 SD Below the Population Mean on the Summary Scales of the SF-36 by Diagnosis and Treatment Group PCS MCS Group n % P* n % P* Diagnosis group Leukemia Referent Referent CNS malignancy Hodgkin s lymphoma Non-Hodgkin s lymphoma Wilms tumor Neuroblastoma Soft tissue sarcoma Bone cancer Treatment group Surgery No Referent Referent Yes Chemotherapy No Referent Referent Yes Radiation None Referent Referent Cranial Other than cranial *Adjusted for sex, age, and time since diagnosis.

6 HRQOL IN CHILDHOOD CANCER SURVIVORS, Ness 133 Table 3: Frequency and Percentage of Role Participation Outcomes by Functional Status, ORs, and 95% CIs Comparing Those With and Without a Functional Loss High School Graduate (n 6803) vs Nongraduate (n 344) Currently Employed (n 6194) vs Not Employed (n 953) Functional Status n % OR* 95% CI P n % OR* 95% CI P No (n 5856) Yes (n 1291) No (n 6148) Yes (n 999) No (n 6395) Yes (n 752) Married (n 3432) vs Not Married (n 3715) Income $20,000 /y (n 6367) vs Income $20,000 /y (n 780) n % OR* 95% CI P n % OR* 95% CI P No (n 5856) Yes (n 1291) No (n 6148) Yes (n 999) No (n 6395) Yes (n 752) *Relative odds of achieving the positive role participation (high school graduate, married, employed, and income $20,000 /year) compared with the less positive outcome, adjusted for current age, time since diagnosis, sex, and the other function domains in the model. ORs less than one indicate lower likelihood of achieving the positive outcome. utive function domains are associated with HRQOL deficits in this population. The findings of this study are the first that we know of to specifically examine the associations between activity domains, role performance, and HRQOL among adult survivors of childhood cancer. However, our results are similar to several recent studies that have evaluated the association between specific medical late effects, psychosocial outcomes, cognitive coping abilities, and HRQOL among other long-term survivors of childhood cancer. Blaauwbroek et al 26 evaluated the impact of organ system late effects on HRQOL among a group of 313 Dutch adult long-term survivors of childhood cancer. They found lower mean scores on the physical functioning subscale of the SF-36 among survivors who reported orthopedic, neurologic, and psychosocial late effects when compared with those who did not report these late effects. They also found associations between psychosocial late effects and poor outcomes on the mental health, vitality, and bodily pain subscales of the SF-36. Another study examined the association between post-traumatic stress disorder (PTSD), defined as debilitating cognitive, behavioral, and physiologic reactions when a memory of the cancer event was activated, and HRQOL. These authors found that survivors with PTSD reported lower HRQOL on both the physical and mental health component scales of the SF-36 when compared with those who did not report PTSD. 44 Finally, Stam et al 32 reported an association between health status (medical and psychosocial late effects) and the PCS score and between health status, cognitive coping skills, and the MCS score of the SF-36 in a cohort of 353 young adult cancer survivors. Study Limitations The findings of these analyses should be considered in the context of several study limitations. First, our study instrument was a self-report questionnaire, thus reflecting the cancer survivors perceptions; their answers, however, were not verified with objective physical, neurocognitive, or psychologic testing. We were not able to specifically differentiate between functional loss as a result of poor coping ability and functional loss as a result of a direct insult to the organ structure (brain, bone). Second, although we used validated instruments for each activity domain, it is possible that participants who perceived their limitations in physical performance, executive function, and/or emotional health as important to life quality were more likely than those who do not report poor HRQOL even with similar levels of functional loss. 45,46 In addition, our study has the potential for selection bias. The survivor participants in our study were more likely than were nonparticipants to be women, white, older than age 35 at the time of the questionnaire, and older than age 10 when diagnosed with their malignancy. It is possible that these survivors were motivated by positive, or more concerned with negative, activity limitations than those who did not participate, and thus they may be either more or less likely to express dissatisfaction with their HRQOL outcomes. Finally, although our results are important as they relate to adult survivors of childhood cancer, differences in modern treatment modalities limit our ability to apply these findings to children treated more recently than our study population. CONCLUSIONS This study provides novel information to the literature about the negative impact of persistent limitations in physical perfor-

7 134 HRQOL IN CHILDHOOD CANCER SURVIVORS, Ness Table 4: Frequency and Percentage of Those Scoring 40 or Less on the Summary and Subscales of the SF-36 by Functional Status With OR and 95% CI Comparing Those With and Without a Functional Loss PCS (n 1137) MCS (n 1439) Functional Status n % OR* 95% CI P n % OR* 95% CI P No (n 5856) Yes (n 1291) No (n 6148) Yes (n 999) No (n 6395) Yes (n 752) Physical Function Subscale (n 794) Role Physical Subscale (n 1423) n % OR* 95% CI P n % OR* 95% CI P No (n 5856) Yes (n 1291) No (n 6148) Yes (n 999) No (n 6395) Yes (n 752) Bodily Pain Subscale (n 950) General Health Subscale (n 1392) n % OR* 95% CI P n % OR* 95% CI P No (n 5856) Yes (n 1291) No (n 6148) Yes (n 999) No (n 6395) Yes (n 752) Vitality Subscale (n 2850) Social Function Subscale (n 1073) n % OR* 95% CI P n % OR* 95% CI P No (n 5856) Yes (n 1291) No (n 6148) Yes (n 999) No (n 6395) Yes (n 752) Role Emotional Subscale (n 1342) Mental Health Subscale (n 647) N % OR* 95% CI P N % OR* 95% CI P No (n 5856) Yes (n 1291) No (n 6148) Yes (n 999) No (n 6395) Yes (n 752) *Relative odds of reporting a poor HRQOL outcome compared with a more positive outcome, adjusted for current age, time since diagnosis, sex, and the other function domains in the model. ORs greater than 1 indicate a higher likelihood of achieving the poor outcome.

8 HRQOL IN CHILDHOOD CANCER SURVIVORS, Ness 135 mance, executive function, and emotional health on role attainment and HRQOL among childhood cancer survivors. Longterm disability may be associated with poor health, and may reduce overall QOL Persons with physical performance limitations, constrained executive function, and deficits in emotional health are less likely to live independently or participate fully in life roles. 47 Executive function limitations, like poor organizational skills, difficulty initiating a new task, or persistent memory problems, interfere with educational and job opportunities. Emotional health limitations dampen peer interactions and leisure choices, and limitations in physical performance prevent easy participation in many aspects of daily life. Interventions designed to remediate limitations in the physical performance, executive function, and emotional health domains should be studied to see if they improve social role attainment and HRQOL among those survivors who traditionally report poor outcomes, and thus reduce the consequences of the cancer experience. APPENDIX 1: QUESTIONS FROM THE BRIEF-A USED IN THE SECOND FOLLOW-UP SURVEY Below is a list of statements that describe problems that people can have. We would like to know if you have had any of these problems over the past six months 1. I get upset easily 2. I don t think of consequences before acting 3. I am disorganized 4. I forget instructions easily 5. I have problems completing my work 6. My mood changes frequently 7. I am impulsive 8. I have trouble finding things in my bedroom, closet or desk 9. I forget what I am doing in the middle of things 10. I have problems getting started on my own 11. I am easily overwhelmed 12. I have trouble doing more than one thing at a time 13. My desk/workspace is a mess 14. I have trouble remembering things, even for a few minutes (such as directions, phone numbers, etc.) 15. I have trouble prioritizing my activities References 1. National Cancer Institute. US estimated 29-year L-D prevalence (including counts) by duration Available at: URL: srab.cancer.gov/prevalence/canques.html. Accessed May 15, Alcoser PW, Rodgers C. Treatment strategies in childhood cancer. J Pediatr Nurs 2003;18: American Physical Therapy Association. Guide to physical therapist practice. 2nd ed. Phys Ther 2001;81: Nagi SZ. An epidemiology of disability among adults in the United States. Milbank Mem Fund Q Health Soc 1976;54: World Health Organization. International classification of functioning, disability and health (ICF). Geneva: WHO; Bhatia S. Late effects among survivors of leukemia during childhood and adolescence. Blood Cells Mol Dis 2003;31: Oeffinger KC, Hudson MM. Long-term complications following childhood and adolescent cancer: foundations for providing riskbased health care for survivors. CA Cancer J Clin 2004;54: Oeffinger KC, Mertens AC, Sklar CA, et al; Childhood Cancer Survivor Study. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 2006;355: Bottomley SJ, Kassner E. Late effects of childhood cancer therapy. J Pediatr Nurs 2003;18: Dimeo F, Schmittel A, Fietz T, et al. Physical performance, depression, immune status and fatigue in patients with hematological malignancies after treatment. Ann Oncol 2004;15: Duell T, van Lint MT, Ljungman P, et al. Health and functional status of long-term survivors of bone marrow transplantation. EBMT Working Party on Late Effects and EULEP Study Group on Late Effects. European Group for Blood and Marrow Transplantation. Ann Intern Med 1997;126: Gocha Marchese V, Chiarello LA, Lange BJ. Strength and functional mobility in children with acute lymphoblastic leukemia. Med Pediatr Oncol 2003;40: Hovi L, Era P, Rautonen J, Siimes MA. Impaired muscle strength in female adolescents and young adults surviving leukemia in childhood. Cancer 1993;72: Macedoni-Luksic M, Jereb B, Todorovski L. Long-term sequelae in children treated for brain tumors: impairments, disability, and handicap. Pediatr Hematol Oncol 2003;20: Mulhern RK, Merchant TE, Gajjar A, Reddick WE, Kun LE. Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol 2004;5: Ness KK, Mertens AC, Hudson MM, et al. Limitations on physical performance and daily activities among long-term survivors of childhood cancer. Ann Intern Med 2005;143: Robison LL, Bhatia S. Late-effects among survivors of leukaemia and lymphoma during childhood and adolescence. Br J Haematol 2003;122: Schwartz CL. Health status of childhood cancer survivors: cure is more than the eradication of cancer. JAMA 2003;290: Schwartz L, Drotar D. Posttraumatic stress and related impairment in survivors of childhood cancer in early adulthood compared to healthy peers. J Pediatr Psychol 2006;31: Zebrack BJ, Gurney JG, Oeffinger K, et al. Psychological outcomes in long-term survivors of childhood brain cancer: a report from the childhood cancer survivor study. J Clin Oncol 2004;22: Haupt R, Fears TR, Robison LL, et al. Educational attainment in long-term survivors of childhood acute lymphoblastic leukemia. JAMA 1994;272: Nagarajan R, Neglia JP, Clohisy DR, et al. Education, employment, insurance, and marital status among 694 survivors of pediatric lower extremity bone tumors: a report from the childhood cancer survivor study. Cancer 2003;97: Pastore G, Mosso ML, Magnani C, Luzzatto L, Bianchi M, Terracini B. Physical impairment and social life goals among adult long-term survivors of childhood cancer: a population-based study from the childhood cancer registry of Piedmont, Italy. Tumori 2001;87: Punyko JA, Gurney JG, Scott Baker K, et al. Physical impairment and social adaptation in adult survivors of childhood and adolescent rhabdomyosarcoma: a report from the Childhood Cancer Survivors Study. Psychooncology 2007;16: Stam H, Grootenhuis MA, Last BF. The course of life of survivors of childhood cancer. Psychooncology 2005;14: Blaauwbroek R, Stant AD, Groenier KH, Kamps WA, Meyboom B, Postma A. Health-related quality of life and adverse late effects in adult (very) long-term childhood cancer survivors. Eur J Cancer 2007;43: Crom DB, Chathaway DK, Tolley EA, Mulhern RK, Hudson MM. Health status and health-related quality of life in long-term adult survivors of pediatric solid tumors. Int J Cancer Suppl 1999;12: Langeveld NE, Grootenhuis MA, Voute PA, de Haan RJ. Posttraumatic stress symptoms in adult survivors of childhood cancer. Pediatr Blood Cancer 2004;42:

9 136 HRQOL IN CHILDHOOD CANCER SURVIVORS, Ness 29. Langeveld NE, Grootenhuis MA, Voute PA, de Haan RJ, van den Bos C. Quality of life, self-esteem and worries in young adult survivors of childhood cancer. Psychooncology 2004;13: Meeske KA, Ruccione K, Globe DR, Stuber ML. Posttraumatic stress, quality of life, and psychological distress in young adult survivors of childhood cancer. Oncol Nurs Forum 2001;28: Nathan PC, Ness KK, Greenberg ML, et al. Health-related quality of life in adult survivors of childhood Wilms tumor or neuroblastoma: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 2007;49: Stam H, Grootenhuis MA, Caron HN, Last BF. Quality of life and current coping in young adult survivors of childhood cancer: positive expectations about the further course of the disease were correlated with better quality of life. Psychooncology 2006;15: Robison LL, Mertens AC, Boice JD, et al. Study design and cohort characteristics of the Childhood Cancer Survivor Study: a multiinstitutional collaborative project. Med Pediatr Oncol 2002;38: Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30: McHorney CA, Kosinski M, Ware JE Jr. Comparisons of the costs and quality of norms for the SF-36 health survey collected by mail versus telephone interview: results from a national survey. Med Care 1994;32: McHorney CA, Ware JE Jr, Raczek AE. The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 1993;31: Sutherland HJ, Fyles GM, Adams G, et al. Quality of life following bone marrow transplantation: a comparison of patient reports with population norms. Bone Marrow Transplant 1997;19: Benson V, Marano MA. Current estimates from the National Health Interview Survey, Vital Health Stats ;(199): Roth RM, Isquith PK, Gioia GA. BRIEF-A. Behavior Rating Inventory of Executive Function-Adult version professional manual. Lutz: Psychological Assessment Resources; Derogatis LR. Brief Symptom Inventory (BSI) 18, administration, scoring, and procedures manual. Minneapolis: NCS Pearson; Hudson MM, Mertens AC, Yasui Y, et al. Childhood Cancer Survivor Study Investigators. Health status of adult long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. JAMA 2003;290: Allison PD. Logistic regression using the SAS system. Cary: SAS Institute; Mitby PA, Robison LL, Whitton JA, et al. Childhood Cancer Survivor Study Steering Committee. Utilization of special education services and educational attainment among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 2003;97: Schwartz L, Drotar D. Posttraumatic stress and related impairment in survivors of childhood cancer in early adulthood compared to healthy peers. J Pediatr Psychol 2006;31: Llewellyn Thomas HA, Naylor CD, Cohen MM, Basinski SH, Ferris LE, Williams JI. Studying patients preferences in health care decision making. Can Med Assoc J 1992;147: Torrance GW. Preferences for health states: a review of measurement methods. Mead Johnson Symp Perinat Dev Med 1982;20: Centers for Disease Control. Healthy people with disabilities throughout HP Available at: ncbddd/factsheets/dh_hp2010.pdf. Accessed May 15, Nosek MA, Hughes RB, Petersen NJ, et al. Secondary conditions in a community-based sample of women with physical disabilities over a 1-year period. Arch Phys Med Rehabil 2006;87: Havercamp SM, Scandlin D, Roth M. Health disparities among adults with developmental disabilities, adults with other disabilities, and adults not reporting disability in North Carolina. Public Health Rep 2004;119: Kinne S, Patrick DL, Doyle DL. Prevalence of secondary conditions among people with disabilities. Am J Public Health 2004; 94:443-5.