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Improvements in survival for all childhood cancers combined have increased between the mid-1970s and today, with overall survival approximating 83% and some children with certain diseases approaching or exceeding 90% long-term survival. With these improved outcomes, the focus of research and expectations of patients, parents, and health care providers has increasingly emphasized reducing the burden of cancer and its treatment for these children during treatment, after the completion of treatment, and as adult survivors.
Cancer treatment for children differs in many ways from treatment for adults. Some of the principal differences include the following:
Fundamental to these differences is the clear recognition that children are not small adults and that even the term children is not all-encompassing. Treatment and supportive care require different approaches across the spectrum from newborn through young adult age groups, and the outcomes of both cancer survivorship (control of disease) and quality of survivorship (impact of toxicities) differ with the age of a child at the time of treatment.
Equally important is the recognition that treatment of childhood cancer inevitably occurs in the context of a family. Frequently, the impact of an adult's cancer treatment focuses on one or two key adults in the cancer patient's life. In childhood cancer, the effects are often felt by more individuals, including one or both parents, one or more siblings who are themselves children or adolescents, grandparents, aunts and uncles, teachers, friends, and other individuals who may be directly involved in the care or life experience of the child. Furthermore, because children are not considered legally competent exclusively on the basis of age, most decisions about cancer treatment are made by proxy. Instead of children making decisions about their own care, their parents or guardians make these decisions for them. The large number of people involved, legal issues related to decision making about minors by others, and ethical concerns about informed consent and assent involving children add extra layers to the complexity of treatment for children.
In this pediatric supportive care summary, issues specifically related to children and adolescents will be reviewed. Evidence and recommendations may differ significantly from information provided about supportive care for adults.
Topics addressed include the following:
The following information will be added to the summary as it is completed:
Treatment of childhood cancer is a highly stressful experience, challenging and disruptive to children and their family members. It is therefore assumed that children undergoing cancer treatment are at significantly higher risk for depression, anxiety, and other indicators of psychological distress. However, the empirical evidence to support this assumption is weak. Overall, studies suggest that children treated for cancer and children who are long-term survivors of cancer experience few significant psychological adjustment problems.[1,2,3]
There is evidence that children experience distress during the cancer treatment process. Distress appears to be most significant early in therapy, typically when frequent hospitalizations are necessary, with a pattern of less distress occurring over time.[4,5] One group of 39 families of children newly diagnosed with leukemia was compared with a group of 49 families of healthy children. While parents and the children treated for cancer reported higher levels of distress immediately following diagnosis, these levels of distress decreased over 4 years of follow-up, and there were no significant differences in psychological distress compared with the healthy comparison cohort. Similar findings have been reported across cultures.
The validity of obtaining accurate reports of psychologic distress in this population has been questioned. One investigation of whether psychological defensiveness might mask the reporting of depression and other symptoms of psychological distress studied 107 children treated for cancer and 422 healthy controls who completed a series of measures of depression and anxiety.[Level of evidence: II] Children treated for cancer reported significantly fewer depressive symptoms than did healthy children, and defensive style was not related to report of depression. Another study of 205 children and 321 parents of children with either cancer, asthma, or no significant health problem also found no significant levels of depression in children treated for cancer. However, parents of children with cancer attributed more cheerful characteristics to their children than did the parents of children in the other groups.[Level of evidence: II]
Studies have reported no differences from controls on the following measures:
One group of investigators  found that teachers perceived children with cancer as more social and less aggressive, and peers rated them as less aggressive and having greater social acceptance than other peers. It may make a difference who is reporting: parents of children report more limitations in their children than the children themselves report, although children do report lower satisfaction with athletic competence than do their peers.
Differences in Adjustment
Diagnosis and type of treatment appear to make a difference in adjustment in specific subgroups of children with cancer.
Children treated for solid tumors not involving the central nervous system (CNS) appear to have minimal psychological distress, and this is maintained after treatment.
Acute lymphoblastic leukemia or lymphoma
Children treated for acute lymphoblastic leukemia (ALL) or lymphoma report poorer emotional functioning, cognitive skills, autonomy, and family interaction than do children treated for non-CNS solid tumors.
For children whose disease or treatment directly involves the CNS, the risk of developing social and emotional problems appears much greater. Children with brain tumors are seen by their peers as being sick, fatigued, absent from school, and socially isolated and are less likely to be endorsed as friends by their peers.
Stem cell transplantation
Children receiving hematopoietic stem cell transplantation (HSCT) are likely to experience declines in both social competence and self-concept over time.
Ethnicity can also play a role in quality of life.
Family factors appear to play a large role in child adjustment, with family cohesion and expressiveness associated with better outcomes and family conflict associated with poorer outcomes, particularly for children experiencing more-intensive treatment. Younger (pre-school) children are more likely to experience higher levels of externalizing behavior problems (e.g., aggression, impulsivity, or disruptive behavior) during treatment than do adolescents, but overall health-related quality of life (HRQL) reported by parents is better for younger children than for adolescents. Age may also serve as a mediator in the approach to coping and perceived level of control experienced by children being treated for cancer. While one group of researchers found that children with cancer reported significantly more use of avoidant coping strategies than did healthy children, regardless of age, another group found that the relationship between perceived control and problem-focused or emotion-focused coping (problem-focused coping related to higher appraisals of control) was mediated by age. A limited number of studies has been conducted in this area, and there are likely a number of additional mediators of adjustment-coping relationships that have not yet been examined.
Childhood Cancer Survivor Study
The Childhood Cancer Survivor Study (CCSS) is a large, ongoing, multicenter study of more than 10,000 long-term survivors of childhood cancer and a comparison sibling control population. Using extensive survey methodology that links reports of current functioning to diagnosis, types of treatment, and other health factors associated with cancer and its treatment, the CCSS has selectively looked at long-term adjustment in large samples of young adults treated for similar childhood cancers. In one CCSS report, 2,778 survivors of solid tumors diagnosed in childhood and 2,925 siblings were surveyed using a standardized long-term follow-up questionnaire. Symptoms associated with depression, somatization, and anxiety were reported, along with demographic, health, and medical information. Few, if any, symptoms of psychological distress were reported by the cancer survivors, although survivors of solid-tumor cancers reported higher levels of global distress than did their siblings. There were no differences on these measures from population norms. For both cancer survivors and their siblings, female gender, lower education and income attainment, perceived poor health status, and reports of current health problems were all associated with higher levels of psychological distress symptoms.[Level of evidence: II]
Positive findings also have been reported by the CCSS for young adults who are survivors of leukemias and lymphomas. Follow-up questionnaires about psychological adjustment were administered to 5,736 young adult survivors of leukemia, non-Hodgkin lymphoma, and Hodgkin disease and to 2,565 adult siblings. Survivors reported higher levels of depressive symptoms and somatic distress than did siblings, but scores for neither group fell within the clinically significant range for the general population. Sociodemographic factors such as gender and socioeconomic status were associated with reports of depressive symptoms, regardless of treatment status. The only disease-related factor associated with psychological distress was intensive chemotherapy, which was associated with an increase in somatic complaints.[Level of evidence: II] Similar outcomes were reported for survivors of brain cancers. Brain tumor survivors reported higher levels of depressive symptomatology than did siblings, but the rates for both groups were similar to rates for the general population.[Level of evidence: II] A summary of the main psychosocial outcomes reported by the CCSS is available.[Level of evidence: II] Other reports from the CCSS address alcohol consumption, the role of physical limitations on HRQL,[Level of evidence: II] fatigue, and sleep.
Depression and Suicide
Young adult survivors of childhood cancer may have an elevated risk for suicidality. A report from Eastern Europe compared the responses of 228 long-term survivors of childhood cancer with those of 127 controls to the Center for Epidemiologic Studies Depression Scale (CES-D) and the Suicidal Ideation and Behaviour Questionnaire. The rates of depressive symptoms reported by the childhood cancer survivors were three times the rates reported by the controls, with 13% indicating some level of suicidal ideation. Similarly, 226 adult survivors of childhood cancer seen in a survivor clinic completed the Short Form-36 (SF-36), the Beck Depression Inventory (BDI), and suicide items from the Symptom Checklist-90-Revised (SCL-90-R) and the Beck Scale for Suicide Ideation (BSS). The measures assessed whether the survivors had ever attempted suicide or whether they had experienced significant suicidal ideation within the past week; 29 participants (12.83%) reported suicidality. Suicidality was associated with younger age at diagnosis, longer time since diagnosis, cranial radiation therapy, a diagnosis of leukemia, pain, and concerns about physical appearance. Current physical condition, including pain, was associated with suicidality.[Level of evidence: II] These studies represent relatively small samples with small comparison groups and may reflect a reporting bias represented in individuals who actively attend follow-up clinics. Nonetheless, while these results are inconsistent with other findings related to psychological distress, they do suggest the need for ongoing monitoring and surveillance of adults who are survivors of childhood cancer.
Significant concern about the potential for suicide as a side effect of selective serotonin reuptake inhibitors (SSRIs) has led the U.S. Food and Drug Administration (FDA) to issue a caution about their use that includes the importance of careful monitoring of potential risks. Before this FDA Health Advisory was issued, clinical experience and the results of small clinical trials suggested that antidepressants can be safely administered to adult cancer patients, although there are no controlled clinical trials to support this position. The risk/benefit ratio for use of SSRIs may not be as favorable for children and adolescents. Several multicenter, double-blind, randomized, placebo-controlled clinical trials using SSRIs with children and adolescents with major depressive disorder but not cancer found modest improvements for fluoxetine,[28,29] paroxetine, and sertraline.[Level of evidence: I] Balancing these improvements were reports of serious adverse events that included worsening of psychiatric symptoms, increased suicidal ideation and gestures, increased conduct problems or hostility with paroxetine, and suicide and suicide attempts with sertraline.[Level of evidence: I]
None of these clinical trials have included or focused on children and adolescents being treated for cancer. Risk/benefit concerns have reached the level of international regulatory concern. The Medicines and Healthcare Products Regulatory Agency of Great Britain has recommended that most of the drugs in the SSRI category not be used with children and adolescents, and the FDA raised similar concerns in a Talk Paper and subsequently issued a "black box" warning. A major meta-analysis published in the Journal of the American Medical Association reanalyzed the data from the child and adolescent studies [Level of evidence: I] (including seven studies not included in the initial meta-analysis [Level of evidence: I]) using a random-effects model. While this reanalysis found an overall increased risk of suicidal ideation/suicide attempt consistent with the initial meta-analysis, the pooled risk differences were found to be smaller and statistically insignificant. Furthermore, another study examining the U.S. and Dutch data suggests a drop in SSRI prescriptions for children and adolescents and a simultaneous increase in suicide rates in this patient population since the FDA Health Advisory was issued.
In summary, the risk/benefit equation favors appropriate use of antidepressants with careful monitoring for suicidality. The British Committee on Safety of Medicines considered only one of the SSRIs (fluoxetine) to have a favorable balance of risks and benefits, but it is only considered beneficial in approximately one in ten patients. Consistent with this finding, age-stratified analyses of the child and adolescent studies found that for children younger than 12 years who have major depression, only fluoxetine showed benefit over placebo.
As noted, none of the children or adolescents in these studies had cancer, so there are no reports available that address whether there are additional increased risks of adverse events associated with the use of SSRIs following exposure to different chemotherapeutic agents and/or CNS radiation treatment. Frontline, alternative, effective, behavioral, and pharmacologic treatments for depression should be used for children and adolescents being treated for cancer. However, if the risks of depression are significant and SSRIs are considered, consultation with a child psychiatrist or neurologist is essential, and close monitoring of potential adverse events is crucial.
Post-traumatic Stress Disorder and Post-traumatic Stress Symptoms
The cancer treatment experience may be considered a significant traumatic event, given the nature of diagnosis, the number of invasive and painful procedures, and the often long hospitalizations that children and their families must experience. On the basis of this exposure model, a number of studies have examined whether children treated for cancer are at a significantly higher risk for the development of symptoms of post-traumatic stress disorder (PTSD). The results of these studies have been mixed. One study reported that children and adolescents who were undergoing treatment reported some symptoms of post-traumatic stress; however, for most children these symptoms did not meet the criteria for a diagnosis of PTSD, and the symptoms diminished over time.[Level of evidence: II]
Other studies suggest that survivors of childhood cancer have an increased risk for post-traumatic stress symptoms and PTSD after treatment is finished. In a study of 78 adults aged 18 to 41 years who had been treated for childhood cancer, 20.5% met the criteria for a diagnosis of PTSD at some time since the end of their treatment. Clinically significant events of intrusive symptoms (9%) and avoidant symptoms (16.7%) were reported in the sample, and the symptoms were associated with elevated reports of anxiety and other measures of psychologic distress.[Level of evidence: II] Survivors who report higher levels of uncertainty about their disease and future appear to be more likely to have elevated reports of post-traumatic stress symptoms.[Level of evidence: II] A study of 182 adolescent and young adult cancer survivors who were more than 5 years from diagnosis and more than 2 years from completion of cancer treatment also found that 16% met the criteria for PTSD. A relationship between PTSD and higher levels of other psychological problems was also reported. When survivors meet the criteria for PTSD, they are more likely to experience depression and negative affect, lower satisfaction with life, and poorer reported HRQL, as well as difficulty performing developmental tasks.[Level of evidence: II]
A commonly repeated idea in the cancer community is that cancer is a family disease; this concept is clearly supported by parents and siblings of children who are being treated for cancer. However, the effects of having a child or sibling with cancer are not uniform, either for all family members or at all points in the treatment process, and the literature reflects the variability of each family member's experience.
The diagnosis of childhood cancer represents the start of a period of substantial distress for parents, who report shock, emotional pain, difficulty coping with the necessary procedures performed on their child, rumination, and high levels of information seeking accompanied by a sense of lack of control.[1,2,3] One study found that all but one participant in a sample of 119 mothers and 52 fathers of children undergoing cancer treatment reported traumatic stress symptoms such as intrusive thoughts, physiologic arousal, and avoidance. When parents of children undergoing treatment (n = 175) were compared with parents of children who had completed treatment (n = 238), symptoms of traumatic stress (intrusion, arousal) were reported more frequently by the parents during the acute phase of treatment than by the parents after treatment, though some parents reported these symptoms after treatment. Some demographic factors may play a role in the degree to which parents experienced significant stress that impairs function. Mothers were more likely to report higher levels of stress than were fathers, and parents with fewer years of formal education and lower socioeconomic status were more likely to experience traumatic stress at any time.
Patterns of parental stress in families of children treated for cancer differ from those in families of children treated for other diseases. In one large study of 675 parents of children who were treated for cancer or diabetes or who were healthy, parents of children with cancer reported significantly higher levels of distress—as indicated in the specific areas of anxiety, physical and psychological distress, depression, and loneliness—than did parents of children with diabetes. Distress levels of parents of patients with cancer matched those in parents of patients with diabetes in measures of uncertainty, loss of control, self-esteem, disease-related fear, and sleep disturbances. Distress levels for parents of children with cancer decreased in intensity with longer time since diagnosis.
At the same time that they are dealing with increased distress, parents of children with cancer report wanting to remain strong and optimistic for their children. One study found no differences in multiple measures of family distress and psychological functioning between families of children with cancer and families with healthy children.
Several factors appear to be predictive of long-term parental adjustment. Better short- and long-term adjustment is experienced by parents who:[9,10,11]
Factors associated with poorer parental adjustment include the following:[12,13]
Race  and parent gender  may affect the intensity of the effect of these factors on parental functioning. In rare circumstances, the stress of coping with pain, adverse side effects, lack of control or understanding of information or outcomes, and conflicts with health care professionals may lead parents to drop out of cancer treatment for their children.
Most studies suggest that over time, maternal affective distress and perceived stress have been shown to decline, but the perceived burden of caring for a child with cancer remains stable, as do positive characteristics such as parental control, nurturance, and responsiveness. This pattern may be related to the high levels of social support provided at the time of diagnosis, with a gradual decrease in the quantity of support but stable perceived quality of support across all phases of cancer treatment. In general, parents are seen as resilient,[Level of evidence: II] but parental loneliness and continued uncertainty may last far beyond the treatment phase if there are ongoing late effects of treatment for the child.[Level of evidence: II] A few studies have found that a substantial number of parents (30%–36%) of long-term cancer survivors may experience intense long-term stress-related symptoms that fall below the threshold for a diagnosis of post-traumatic stress disorder (PTSD) but that are nevertheless a significant problem for these parents.[18,19][Level of evidence: II] Symptoms were severe enough that in 20% of families, at least one parent met the criteria for a diagnosis of PTSD.
The challenges of dealing with the diagnosis and treatment of childhood cancer also has implications for the coping and adjustment of siblings. During treatment, siblings of children with cancer may report:
Siblings of children with cancer also report becoming more compassionate and perceiving that their families are drawn closer together through the experience.
The risk to families increases with the following conditions:
For siblings of children who undergo allogeneic hematopoietic stem cell transplantation, the risk for anxiety and lower self-esteem is higher for siblings who serve as hematopoietic stem cell donors, while non-donors are at higher risk of developing school problems. Social support programs such as sibling groups  or summer camp experiences  appear to result in reductions in reported anxiety and improved self-esteem in siblings of children treated for cancer.
Despite significant improvements in long-term, disease-free survival in children treated for cancer, cancer is the leading disease-related cause of death for children in the United States. For more than half of children for whom frontline treatment fails, treatment using relapse and disease recurrence clinical trials (phase I and phase II) and unrelated hematopoietic stem cell transplantation is common. For children, this strategy is sometimes effective in providing prolonged remissions with patient-valued quality of life. For these reasons, many children treated for cancer in the United States and around the world die in inpatient settings while receiving active cancer treatment. Clinical practice and experience is the driving force in this field; unfortunately, very few empirical studies have been published to guide practice.
Considering End-of-Life Issues
Planning for a child's death is often a very uncomfortable topic for parents, other family members, and members of the health care team. Children are not supposed to die. Although there has been a significant emphasis on better understanding the decision-making process and the care provided for children at the end of life, many parents choose to continue active cancer treatment until death.
One hundred forty-one parents who had lost a child to cancer were asked whether their children benefited or suffered from treatment with no realistic expectation of success. Thirty-eight percent of the parents indicated that their children continued to receive cancer-directed therapy, even after the parents recognized that there was no realistic chance of success. Sixty-one percent of these reported that their child experienced some suffering, and 57% reported little or no benefit from the continued treatment. Despite these experiences, 57% reported that they would recommend standard chemotherapy during the end-of-life phase, and 33% would recommend experimental (phase I and phase II) treatment. Parents who felt that their child suffered at the end of life were less likely to recommend additional chemotherapy. However, even those who did not personally support using standard chemotherapy at the end of life (91%) felt that physicians should offer this as an option.
Parent and physician perspectives on quality of care at the end of life do not always match. Parents of children who died from cancer reported focusing primarily on relationship issues, with higher ratings for physician care when oncologists:
Oncologists based care ratings on biomedical measures such as lower ratings of pain by parents and fewer days of hospitalization.
Support for End-of-Life Care
Resources to support palliative care and end-of-life care for children treated for cancer are often quite limited. A survey of member institutions of the Children's Oncology Group (81% response rate) found that only 58% had a pediatric palliative care team available to families, although the following related services were available:
Complementary and alternative medicine services were available in 39% of institutions and in 95% of communities served by the institutions. Support for other family members, particularly siblings, is often missing from these programs.
Referrals to hospice care are often limited by hospice policies that do not accept patients still receiving active chemotherapy. Twelve hundred pediatric oncologists in the Children's Oncology Group were surveyed about hospice referral practices (67% response rate). Hospice referrals were limited by lack of access to inpatient hospice programs. However, pediatric oncologists indicated that if the hospice program accepted children still receiving chemotherapy, referrals were more likely and the children were also more likely to die at home than in hospitals.
Complementary and alternative therapies
Despite broad popular interest in complementary and alternative therapies, few children are offered access to this treatment. A study of Children's Oncology Group institutions in Canada found that complementary and alternative therapies were offered at only 18% of treating institutions, although these were available in 94% of communities. Direct referrals were only provided to 6% of families, and only 20% of institutions had developed any guidelines for the use of complementary and alternative therapies. To address this issue, studies are in progress to examine the integration of complementary and alternative therapies with conventional treatment in the Children's Oncology Group.
Despite the relative absence of structured palliative care and end-of-life care for children treated for cancer, personal discussions about palliation and end-of-life care between oncologists and parents nevertheless take place. A study of 140 parents whose children died of cancer found that if the primary oncologist discussed options and if home health support were available, 88% of parents planned how they wanted their child's end-of-life care to be provided, and 97% accomplished their plan. This was associated with more home deaths (72% vs. 8% who did not plan); fewer hospital admissions (54% vs. 98%); parents feeling more prepared (37% vs. 12%) and comfortable with the process (84% vs. 40%); and, for those who died in the hospital, fewer deaths in the intensive care unit (92% vs. 33%) and with intubation (21% vs. 48%).
Strategies for Improving End-of-Life Care
Care of children at the end of their lives is complex. A comprehensive summary of pediatric palliative care has highlighted the following general issues that need to be considered:
Many aspects of end-of-life care for adults and children with cancer overlap. At the same time, specific developmental, family, and even legal issues are unique to children and require careful consideration. State laws related to withdrawal or withholding of care vary, and end-of-life care may be affected by whether a child is in the custody of biologic parents or legal guardians or is a ward of the state. Some states do not permit DNR decisions to be made for children in their care. Health care teams have a responsibility to be aware of state laws, hospital policies, and ethical standards in their community and integrate this information into end-of-life care. Ultimately, the challenge is to balance available intervention and support with unique family, child, and physician concerns in a way that optimizes quality of life for the child and family. (Refer to the PDQ summary on Last Days of Life for more information.)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
End of Life
Revised text to state that despite significant improvements in long-term, disease-free survival in children treated for cancer, cancer is the leading disease-related cause of death for children in the United States (cited Kochanek et al. as reference 2).
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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about supportive care issues related to treatment in children and adolescents. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
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