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Originally published as JCO Early Release 10.1200/JCO.2005.10.538 on September 19 2005 © 2005 American Society of Clinical Oncology.
End-of-Life Care Preferences of Pediatric Patients With CancerFrom the Division of Nursing Research and Patient Care Services, Department of Hematology-Oncology, Palliative and End-of-Life Care Task Force, and Ethics Committee, St Jude Children's Research Hospital; Baptist Memorial College of Health Sciences, Memphis, TN; and Centre for Children's Cancer and Blood Disorders, Sydney Children's Hospital, Sydney, Australia Address reprint requests to Pamela S. Hinds, RN, PhD, 332 N Lauderdale, Memphis, TN 38105; e-mail: pam.hinds{at}stjude.org
PURPOSE: The viewpoint of the terminally ill child at the time of an end-of-life decision has not been formally investigated. We identified the preferences of children and adolescents with advanced cancer about their end-of-life care and the factors that influenced their decisions. PATIENTS AND METHODS: Pediatric patients 10 or more years of age were interviewed within 7 days of participating in one of the following three end-of-life decisions: enrollment onto a phase I trial (n = 7), adoption of a do not resuscitate order (n = 5), or initiation of terminal care (n = 8). The patient, a parent, and the primary pediatric oncologist were interviewed separately by using open-ended interview questions. RESULTS: Twenty patients, aged 10 to 20 years (mean, 17 years and 4 months), with a refractory solid tumor (n = 12), brain tumor (n = 4), or leukemia (n = 4) participated. Eighteen patients (90%) accurately recalled all of their treatment options and identified their own death as a consequence of their decision. The factors that were most frequently identified included the following: for patients, caring about others (n = 19 patients); for parents, the child's preferences (n = 18 parents); and for physicians, the patient's prognosis and comorbid conditions (n = 14 physicians). CONCLUSION: These children and adolescents with advanced cancer realized that they were involved in an end-of-life decision, understood the consequences of their decision, and were capable of participating in a complex decision process involving risks to themselves and others. The decision factors most frequently reported by patients were relationship based; this finding is contrary to existing developmental theories.
Approximately 2,300 pediatric patients die of cancer each year in the United States,1,2 and approximately 1,815 die each year in Europe.3 Most pediatric patients die of progressive disease, and more than half have a do not resuscitate (DNR) order.4-8 These deaths are usually anticipated, and end-of-life decisions (eg, DNR, withdrawal of life support, aggressive symptom management only, or enrollment onto a phase I study) are not uncommon. Parents report end-of-life decisions to be the most difficult treatment-related decisions they face during their child's cancer experience.9 Clinicians identify end-of-life decision making as a research priority, in part because they perceive the assistance they can offer with these decisions to be inadequate.10-14 To date, research has been limited and has focused on the preferences of the parents and clinicians and not the preferences of children with advanced cancer. Knowledge of patients' preferences about their end-of-life care would enable parents and clinicians to honor those preferences where possible, an approach that could provide comfort to parents after the loss of their child and reassure clinicians about the quality of the care they provide. Inclusion in the decision process may also offer the patient a sense of control during a time when most matters are not within the patient's control. We conducted a descriptive study by interviewing children and adolescents within 7 days of their participation in one of three types of end-of-life decisions to identify the end-of-life care preferences of pediatric patients with advanced cancer and describe the factors that influenced their decisions. We also compared the factors considered by patients, parents, and physicians.
Patients and Interviews The study was conducted at the pediatric oncology centers of St Jude Children's Research Hospital in Memphis, TN, and Sydney Children's Hospital in Sydney, Australia. Eligible patients had parent and physician approval to participate and were English speaking, between age 10 and 20 years, and directly involved in one of three end-of-life decisions (enrollment onto a phase I trial, adoption of DNR status, or aggressive symptom management only [terminal care]). Parent and physician inclusion criteria included the following: English speaking, directly involved in the end-of-life decision, and consent to participate. The patient, parent, and physician were interviewed separately within the same week. The study was approved by the institutional review boards of both centers; written informed consent or assent was obtained from patients and parents, as appropriate, and verbal consent was obtained from physicians. We chose the descriptive decision–theoretic decision analysis model, which focuses on the decision process, including the factors that are considered and the anticipated outcomes,15,16 rather than on predicting the decision or assessing its quality (correctness). We developed and field tested open-ended interview questions about the decision, possible choices, anticipated outcomes of each choice, and influencing factors for use in interviews with patients (Table 1), parents, and physicians.
Every 2 to 3 months throughout the 22-month study period, interviewers were retrained in interviewing and in obtaining consent. The same three interviewers (P.S.H., D.D., and L.L.O.) completed all interviews, which were initiated only after the end-of-life treatment decision had been made and documented in the medical record. Patients were screened for eligibility daily during rounds of each clinical team. After the physician confirmed patient eligibility, an interviewer approached the parent and described the study in detail. With the parent's permission, the patient was then invited to participate. All interviews were conducted face to face, tape recorded with the permission of participants, and transcribed by a trained medical transcriptionist.
Data Analysis After the first-level codes were applied to all interviews, team members independently identified codes that consistently occurred together and had overlapping meaning. These codes were grouped into broader categories of response. The frequency of each category of response was calculated. Three to four members of the study team analyzed each interview; and inter-rater reliability was estimated after each of the first 10 interviews and subsequently after every third interview. Reliability estimates for each category ranged from 88% to 100% within and across all interviews.
There were 36 potentially eligible patients. The parents of four patients declined permission because their child had not been involved in the decision (n = 3) or was too ill to participate (n = 1). Of the remaining 32 patients, 20 (62.5%) agreed to participate, and 12 (37.5%) declined (five patients at St Jude and seven patients at Sydney Children's Hospital) for reasons that included "don't want to talk about it" (n = 5), "no time to participate" (n = 4), and "feel good about it and have nothing more to say" (n = 3). Of the 12 patients who declined, seven were male, four were black, and eight were white. A phase I trial was under consideration for three patients who declined, DNR status was adopted for five patients, and terminal care was initiated for four patients. Fourteen participating patients were female, and 17 patients were white. Their diagnoses were solid tumor (n = 12), brain tumor (n = 4), or leukemia (n = 4). Their mean age was 17 years and 4 months (range, 10 years 0 months to 20 years 9 months). Fourteen patients were at St Jude, and six were at Sydney Children's Hospital. Although an eligible parent was present at each patient's consent or assent, one 20-year-old patient requested that her parent not participate in the study, and the parent agreed. Nineteen parents participated (13 mothers and six fathers). Of the 14 participating physicians (two had multiple participating patients), 12 were male. No other demographic data about parents or physicians were collected. The decisions made were terminal care (aggressive symptom management only) versus further disease-directed therapy (eight patients), enrollment versus no enrollment onto a phase I study (defined to parents and patients as a toxicity-finding study involving a new drug for patients whose disease could not be cured; seven patients), and DNR status versus no DNR status (five patients). The decisions that had been made were defined for the study investigators by the attending physician. Six of the eight decisions about terminal care involved a choice between palliative chemotherapy (plus palliative radiation in one patient) and a more limited symptom control effort (ie, oral pain control) that would not require the patient to remain at the cancer center (referred to by four patients as returning home to die). Two of the decisions were a choice of palliative chemotherapy, oral pain control, or alternative therapies (herbs, nutritional supplements, or meditation). Four patients chose aggressive symptom control, two chose alternative therapies, and two chose to return home with oral pain control. The seven phase I trial decisions offered a choice of the phase I trial, palliative chemotherapy, or terminal care. Four patients chose the phase I study, and three chose terminal care. All of the five patients involved in the DNR decision chose DNR status. Responses to the interview questions are described in the following sections. Only question 4 generated responses that could be combined. The number of first-level codes is given to indicate the number of times that a theme was reported; that number is followed by the number of participants who reported the theme (themes/participants).
Interview Question: What Choices Did You Consider?
Interview Question: What Did You Think Would Be the Most Likely Outcome of Your Choice? The outcomes anticipated by the eight parents involved in a terminal care decision included "giving up all hope/go crazy" (n = 13/6 themes/participants), "go home, do what child wants" (n = 10/8 themes/participants), and "child will die/child can't be cured" (n = 9/8 themes/participants). The outcomes anticipated by the six parents considering a phase I study included "might buy a little time" (n = 5/5 themes/participants), "being hospitalized" (n = 5/5 themes/participants), "not too hard on child" (n = 5/4 themes/participants), "prolonging the inevitable" (n = 4/4 themes/participants), "getting sick" (n = 4/4 themes/participants), and "doing what my child wants" (n = 3/3 themes/participants). Outcomes considered by the eight parents considering DNR status included "child will die" (n = 5/5 themes/participants), "being able to go home" (n = 4/4 themes/participants), "extend life a little" (n = 4/4 themes/participants), and "life on a machine is not living" (n = 4/3 themes/participants). The outcomes anticipated by the six physicians involved in a terminal care decision included "patient realizes she/he is dying" (n = 7/6 themes/participants), "not acceptable to patient/family to stop all therapeutic interventions" (n = 4/4 themes/participants), "patient wanting to go home/have fun" (n = 4/4 themes/participants), and "patient would die comfortably"(n = 4/4 themes/participants). Outcomes considered by the four physicians involved in a phase I study decision included "anticipating low toxicity" (n = 6/5 themes/participants), "possible tumor response/delay death" (n = 5/4 themes/participants), "toxicity without cure/being hospitalized" (n = 5/5 themes/participants), "cannot deprive families of hope or jeopardize future options" (n = 2/2 themes/participants), and "difficult to predict responses to a new agent" (n = 2/2 themes/participants). The outcomes reported by the four physicians involved in a DNR decision included "satisfying patient desire to avoid being on a ventilator" (n = 7/4 themes/participants), "patient going to die" (n = 5/4 themes/participants), and "satisfying patient desire to avoid being hospitalized" (n = 5/4 themes/participants).
Interview Question: What Kinds of Things Did You Think About When You Were Trying to Make This Decision?
Nine factors were considered by the 19 parents (Table 3), and six factors were considered by the 14 physicians (Table 4). We compared the definition of each patient factor with the definitions of factors considered by the parents and physicians. The patient factor "thinking about my relationships with others," the parent factor "deciding as my child prefers," and the physician factor "being influenced by patient and family preferences" reflected a common consideration for the preferences (known or believed) of others involved in the decision (94.7% to 100%). Furthermore, this desire to benefit others was reported by 11 (55%) of 20 terminally ill patients, five (26.3%) of 19 parents, and seven (50%) of 14 physicians. The patient factor "avoiding adverse events," the parent factor "avoiding negative outcomes," and the physician factor "wanting to avoid harm" (68.4% to 78.6% of each group) reflected a common desire to prevent or reduce suffering or clinical deterioration. The patient factor "believing treatment now is futile," the parent factor "nothing more to do," and the physician factor "having no other option" showed the common belief that all treatment strategies had been exhausted (30% to 63.2% of each group).
What Kinds of Things Did Your Doctor, Nurse, Social Worker, or Chaplain at the Hospital Do or Say That Helped You With the Decision or That Did Not Help You With the Decision? Phase I trial decisions. Patients reported the following staff behaviors as helpful: "explained everything to me/gave us written information" (n = 16/7 themes/participants), "answered my questions and gave me time to think" (n = 13/6 themes/participants), "told me about how other patients did" (n = 4/4 themes/participants), and "told me they would be there for me" (n = 4/4 themes/participants). Parents reported the following helpful staff behaviors: "didn't try to sway us one way or another/support any decision" (n = 10/7 themes/participants), "gave me information and time to think" (n = 8/6 themes/participants), "did not give up on our child" (n = 5/4 themes/participants), "consulted with other experts" (n = 4/4 themes/participants), and "showed caring about our child's quality of life" (n = 3/3 themes/participants). Physicians did not commonly seek input from other staff members for a phase I trial decision but indicated that "staff agreement on option" (n = 5/4 themes/participants) was helpful. Of the seven patients involved in a phase I trial decision, two reported staff behaviors that were not helpful. They reported that being told of the possible toxicities of the experimental drug made their decision more difficult. All parents but one and all physicians involved in a phase I decision denied that staff actions or words had made the decision more difficult. The one parent reported that not having written information about the drug made the decision more difficult. Terminal care decisions. Patients involved in a terminal care decision reported the following staff behaviors as helpful: "respected my preference/backed me up" (n = 10/8 themes/participants) and "answered my questions" (n = 5/5 themes/participants). Parents reported "gave support to me/my child" (n = 8/8 themes/participants), "helped us or our child identify our preferences" (n = 4/4 themes/participants), "reassured us of continued care for symptoms" (n = 4/3 themes/participants), and "gave us information" (n = 3/3 themes/participants) as helpful. Physicians reported the following two helpful staff behaviors: "validating patient/family preferences" (n = 5/5 themes/participants) and "assuring patient of continued care" (n = 5/5 themes/participants). DNR decisions. Patients reported the following staff behaviors as helpful: "very clear words used to explain to me" (n = 8/5 themes/participants), "told me personal feelings" (n = 4/4 themes/participants), and "there for me" (n = 3/3 themes/participants). Parents reported "gave us the facts" (n = 5/5 themes/participants), "gave us a professional opinion" (n = 5/5 themes/participants), and "asked us to do what we believe is right for our child" (n = 4/4 themes/participants) as helpful. Physicians reported "discussions with team members about appropriateness of the options" (n = 7/6 themes/participants), "receiving moral support from staff" (n = 5/5 themes/participants), and "others on team asking for clarification of patient's status" (n = 4/4 themes/participants) as helpful.
What Helps You Now to Feel Okay About That Decision? Parents. All parents reported feeling positive about the decision. The most frequently reported reasons in a phase I trial decision were "didn't have to just do ‘nothing’ " (n = 10/5 themes/participants), "my faith carries me" (n = 6/5 themes/participants), "the drug is not making my child sick" (n = 5/3 themes/participants), "we know we tried" (n = 4/4 themes/participants), and "seeing others benefit" (n = 3/3 themes/participants). The most frequently reported reasons in a terminal care decision were "child is happier" (n = 5/4 themes/participants) and "this is right for us" (n = 4/4 themes/participants). In a DNR decision, reasons for feeling okay included "my faith carries me" (n = 5/5 themes/participants), "child will not suffer" (n = 4/4 themes/participants), and "machine will not help" (n = 3/2 themes/participants). Physicians. Physicians reported the following reasons for feeling okay about their part in a phase I decision: "tolerated the drug well" (n = 6/4 themes/participants), "best cost/benefit ratio for the child" (n = 5/4 themes/participants), and "consistent with my ethical standards" (n = 5/5 themes/participants). The most frequently reported reasons in a terminal care decision were "did as patient prefers" (n = 13/7 themes/participants), "consistent with my ethical standards" (n = 4/3 themes/participants), and "seeing patient happy with decision" (n = 4/3 themes/participants). For a DNR decision, physicians reported the following reasons: "easier death for my patient" (n = 6/4 themes/participants), "consistent with my ethical standards" (n = 5/4 themes/participants), and "seeing patient happy with decision" (n = 3/3 themes/participants).
How end-of-life decisions are made and what factors influence those decisions,22 particularly from the perspectives of children, adolescents, and their parents, is not well understood.23 Almost all patients (18 of 20 patients) in this study accurately recalled their treatment options and were able to identify the likely outcome of each. They identified their death as an outcome of their decision and, therefore, understood that they were participating in a decision about the end of their own life and recognized the consequences of their decision. Additional responses indicated that they understood what would happen as a result of their decision in the short term (eg, get sick from an experimental drug), the intermediate term (eg, delay the inevitable of dying), and the longer term (eg, dying). The patients considered these outcomes and the impact of their decision on others (loved ones, staff, and future patients unknown to them). These patients were able to negotiate a complex decision process during which they considered more than one element at a time and were able to integrate these diverse elements into a decision. These abilities are the characteristics of competent decision making when risk is involved.15,16,24 Taken together, our findings support the ability of children and adolescents between 10 and 20 years old with advanced cancer to participate in end-of-life decision making. Decision making at the end of a child's life is a multistep, involved process that is further complicated by individual values and patient and parent understanding of the clinical situation and of the available options.25,26 Although our study design did not allow us to assess the sequence in which specific factors were considered, the factors typically mentioned first by patients were avoiding adverse effects (n = 9) and information from health care professionals (n = 6). The factors most frequently mentioned first by parents were continuing to try for cure or longer life (n = 5), trusting staff and being supported by them (n = 4), and deciding as my child prefers (n = 4). The factors most frequently mentioned first by the physicians were the patient's prognosis and comorbid conditions (n = 8) and patient and family preferences (n = 6). It is likely that these factors were considered first or were most compelling for each of the three groups of participants. Similar future studies would benefit from asking the patients to identify the sequence in which they considered factors and the weight they gave to each one. A striking finding is the wish of patients and parents to benefit others as a factor in their decisions. This concern for others, particularly for unknown others as identified by 11 of the 20 patients, was not anticipated and is not reflected in existing theories of child development.27 Altruism or the intention to benefit another is incorporated into some child developmental theories but tends to reflect a child's expectation of personal benefit along with the help given another.28 In contrast, the patients in our study reported considering participation in a phase I study because it could benefit another, although it might harm self. This concern for others may reflect what has been referred to as the maturational effect of a life-ending illness on a child or adolescent.29 Parent altruism has also been reported. A survey of pediatric oncologists in the United Kingdom (n = 53) and North America (n = 78) concluded that parents generally enroll their child onto phase I trials for reasons of medical benefit, hope, and altruism.23 Adult oncology patients do not report altruism as a major factor in their decisions about a phase I study.30 Consideration of others' preferences was the factor most frequently reported by patients, parents, and physicians, indicating that human relationships strongly influence end-of-life decisions in pediatric oncology. Children, even older adolescents, do not have legal decisional authority in the United States or Australia unless they are emancipated minors, and patient preferences do not have legal standing. However, as shown here and reported elsewhere,31 some families and health care professionals involve pediatric patients with advanced cancer in decisions. One report described the inclusion of patients as young as 6 years old in end-of-life decisions and described the children as directing the decision in most cases.32 That report and our own findings show that the patient's perspective is important to the parents and physicians and that it influences the decision. The patient's influence on end-of-life decisions is at odds with the reported inability of pediatric patients and their parents to influence treatment decisions during hospitalization for non–life-threatening procedures.33 The source of this difference in end-of-life care versus active treatment should be scrutinized. Although the study was conducted at only two sites and involved a small sample, the nearly universal report of the patients that their decision making was relationship-based is a particularly striking finding. Although patients absorbed the factual information about their treatment options, concern and care about family, friends, health care providers, and even unknown others influenced the patients' decision making. Several adolescents in our study sample referred to their decision as their chance to do something good for someone else; one referred to his decision as his final gift to his parent. It is important that the relationship-based decision making be anticipated by pediatric oncology professionals when facilitating end-of-life care preferences and that more research be completed on this type of decision making. Kane et al34 have noted that the end-of-life illness experience is a relational process and that the suffering inherent in this experience can be endured because of the presence of meaningful relationships. In conclusion, pediatric oncology patients are involved in making decisions about their own end-of-life care. Patients in this study were able to accurately identify their treatment options and understood that their death would be one of the outcomes of their decision. Their decision making was relationship based, and concern and caring about others was the most frequently reported factor influencing their decision making. Patient, parent, and physician decision making had important similarities, including sensitivity to the others preferences. Although key aspects of pediatric end-of-life decision making remain unexplored, our findings support the ability of some pediatric oncology patients to participate in end-of-life decisions on their own behalf.
The authors indicated no potential conflicts of interest.
We thank Sharon Naron, MPA, ELS, for her editorial assistance.
Supported by Grants from Project on Death in America (the Soros Foundation) and the Oncology Nursing Foundation; by Grant No. P30 CA-21765 from the National Cancer Institute; and by the American Lebanese Syrian Associated Charities. Authors' disclosures of potential conflicts of interest are found at the end of this article.
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Wolfe J, Grier EH, Klar N, et al: Symptoms and suffering at the end of life in children with cancer. N Engl J Med 342:326-333, 2000 8. Bradshaw G, Hinds PS, Lensing S, et al.: Characteristics of children and adolescents dying cancer-related deaths. J Palliat Med 8:86-95, 2005[CrossRef][Medline] 9. Hinds PS, Oakes L, Furman W, et al: Decision making by parents and healthcare professionals when considering continued care for pediatric patients with cancer. Oncol Nurs Forum 24:1523-1528, 1997[Medline] 10. Hilden JM, Emanuel EJ, Fairclough DL, et al: Attitudes and practices among pediatric oncologists regarding end-of-life care: Results of the 1998 American Society of Clinical Oncology survey. J Clin Oncol 19:205-211, 2001 11. Hinds PS, Quargnenti A, Olson MS, et al: The 1992 APON Delphi study to establish research priorities for pediatric oncology nursing. J Pediatr Oncol Nurs 11:20-27, 1994 12. Hinds PS, Kelly KP: Studying clinical decision making by patients, parents, and healthcare providers in pediatric oncology. J Pediatr Oncol Nurs 15:1-2, 1998 13. Kane JR, Primomo MP: Alleviating the suffering of seriously ill children. Am J Hosp Palliat Care 18:161-169, 2001 14. Lindquist R, Banasik J, Barnsteiner J, et al: Determining AACN's research priorities for the 90s. Am J Crit Care 2:110-117, 1993[Abstract] 15. Eraker S, Politser P: How decisions are reached: Physician and patient. Ann Intern Med 97:262-268, 1982 16. Winterfeldt D, Edwards W: Decision Analysis and Behavioral Research. London, United Kingdom, Cambridge University Press, 1986 17. Seidel J: The ETHNOGRAPH, Version 4.0 Computer Software. Littlejohn, CO, Qualis Research Associates, 1995 18. Krippendorff K: Content Analysis: An Introduction to Its Methodology. Newbury Park, CA, SAGE Publications, 1980 19. Hinds PS, Oakes L, Furman WL, et al: End-of-life decision making by adolescents, parents, and health care providers in pediatric oncology: Research to evidence-based practice guidelines. Cancer Nurs 24:122-134, 2001[CrossRef][Medline] 20. Hinds PS, Oakes L, Quargnenti A, et al: An international feasibility study of parental decision making in pediatric oncology. Oncol Nurs Forum 27:1233-1243, 2000[Medline] 21. Hinds PS, Gattuso JS, Fletcher A, et al: Quality of life as conveyed by pediatric patients with cancer. Qual Life Res 13:761-772, 2004[CrossRef][Medline] 22. Hoehn SK, Nelson RM: Parents should not be excluded from decisions to forgo life-sustaining treatments. Crit Care Med 29:1480-1481, 2001[CrossRef][Medline] 23. Estlin EJ, Cotterill S, Pratt CB, et al: Phase I trials in pediatric oncology: Perceptions of pediatricians from the United Kingdom Children's Cancer Study Group and the Pediatric Oncology Group. J Clin Oncol 18:1900-1905, 2000 24. Beyth-Marom R, Fischhoff B: Adolescents' decisions about risks: A cognitive perspective, in Schulenberg J, Maggs J, Hurrelmann K (eds): Health Risks and Developmental Transitions During Adolescence. New York, NY, Cambridge University Press, 1997, pp 110-135 25. Himelstein BP, Hilden JM, Boldt AM, et al: Pediatric palliative care. N Engl J Med 350:1752-1762, 2004 26. Hinds P, Oakes L, Furman W: End-of-life decision making in pediatric oncology, in Ferrell B, Coyle N (eds): Textbook of Palliative Nursing (ed 2). New York, NY, Oxford University Press, in press 27. Shaffer DR: Social and Personality Development (ed 4). Belmont, CA, Wadsworth/Thomas Learning, 2000, pp 305-354 28. Eisenberg N, Fabes RA: Prosocial development, in Damon W, Eisenberg N (eds): Handbook of Child Psychology: Volume 3—Social, Emotional, and Personality Development (ed 5). New York, NY, Wiley, 1998, pp 701-778 29. Neville KL: Mature Beyond Their Years: The Impact of Cancer on Adolescent Development. Pittsburgh, PA, Oncology Nursing Press, 2000 30. Daugherty C, Ratain MJ, Grochowski E, et al: Perceptions of cancer patients and their physicians involved in phase I trials. J Clin Oncol 13:1062-1072, 1995[Abstract] 31. Freyer DR: Care of the dying adolescent: Special considerations. Pediatrics 113:381-388, 2004 32. Nitschke R, Humphrey G, Sexauer C, et al: Therapeutic choices made by patients with end-stage cancer. J Pediatr 101:471-476, 1982[CrossRef][Medline] 33. Hallstrom I, Elander G: Decision-making during hospitalization: Parents' and children's involvement. J Clin Nurs 13:367-375, 2004[CrossRef][Medline] 34. Kane JR, Hellsten MB, Coldsmith A: Human suffering: The need for relationship-based research in pediatric end-of-life care. J Pediatr Oncol Nurs 21:180-185, 2004 Submitted December 29, 2004; accepted May 1, 2005.
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
