Research on medical and psychological outcomes of pediatric cancer survivors has benefitted from efforts to assemble large cohorts of survivors treated at multiple centers [3–6]. Making use of standardized assessments of outcomes in these large samples, studies of these cohorts have attempted to overcome the limitations common in smaller studies at individual treatment sites (e.g., poor generalizability, lack of power, selection bias) [3]. Because it includes psychological outcome data from a control group of non-treated siblings, findings from the Childhood Cancer Survivors Study (CCSS) [7] have also addressed the lack of controls and questions about the adequacy of normative data that limited many previous studies. Overall, studies from the CCSS and other large survivor cohorts have demonstrated that the majority of survivors of childhood cancers do not experience significant psychological difficulties after treatment. However, as a group, survivors have been found to be at increased risk for psychological distress compared to their peers, and a significant minority of survivors experience symptoms of maladjustment. For example, studies from the CCSS have shown that most survivors do not experience significant impairments in mental health functioning, although 17.2 % do, and survivors are more than twice as likely to have elevated levels of psychological symptoms compared to their siblings [4]. Similarly, results from the Swiss Childhood Cancer Survivors (SCCS) study have shown survivors are at increased risk for high levels of psychological distress. In both the CCSS and the SCCS, survivors were at increased risk for anxiety and depression symptoms [4, 5]. Survivors in the CCSS have also been found to have elevated rates of suicidal ideation [8], and post-traumatic stress symptoms [9]. Taken together, these studies cited above provide some of the strongest evidence that prevalence of psychological distress and adaptive problems is increased in adult survivors of childhood cancers. However, it is important to note that this research focuses almost solely on prevalence of psychological symptoms and not of diagnosable psychiatric disorders. This reflects both the relative difficulty of measuring psychiatric disorders in survey research, and the desire to report on psychological distress rather than exclusively on psychiatric diagnosis. Appreciating this distinction has important implications both for understanding the research on survivors’ psychological late-effects and for planning appropriate assessment and intervention programs. It bears noting that evidence of survivors’ elevated symptoms of distress does not necessarily mean they have a greater prevalence of mental disorders as defined in the psychiatric nosology. Criteria for a psychiatric diagnosis typically include a minimum number of key symptoms that endure for a minimum amount of time, and are associated with at least some amount of impairment. Some survivors with elevated symptoms of distress may not have symptoms of sufficient severity or with sufficient associated impairments to qualify for a particular diagnosis, and others may have severe symptoms that simply do not coincide with the patterns derived from study of mental illness. For a complex diagnostic category like posttraumatic stress disorder (PTSD), the correspondence between symptoms and diagnosis can be particularly difficult to discern since the diagnosis requires not only a particular constellation of symptoms, but also evidence they are all associated with a specific past event and cause current functional impairments. Evidence of higher levels of posttraumatic stress (PTS) symptoms from surveys of childhood cancer survivors may not indicate these survivors have higher rates of posttraumatic stress disorder, and the proportion of survivors who are found to have higher than expected PTS symptoms varies widely depending on how the constellation of PTS symptoms is defined [9–11].

Both investigators and clinicians intentionally adopt a symptom focus rather than mental disorder focus, in part to insure a broad assessment of survivor functioning. Following recommendations from the National Comprehensive Cancer Network (NCCN) [12–14] and others [15, 16], psychological and behavioral symptoms that cause subjective distress are assessed and targeted for intervention, whether or not a psychiatric diagnosis is present. As we discuss in assessment and intervention sections below, clinicians working with long-term survivors should not expect that all of those who report symptoms of psychological distress will have a psychiatric disorder or necessarily require mental health treatments. As we highlight below, understanding factors associated with poor psychological adjustment in survivors can help providers focus on those survivors who are at highest risk.

Studies of quality-of-life (QOL) in cancer survivors generally focus on health-related QOL, a concept that aims to reflect the impact of health on the individual’s functioning in physical, emotional, and social domains [17, 18]. Given their risk for medical late-effects described in previous chapters in this book, and their risks for psychological and social challenges described here, it should not be surprising that childhood cancer survivors also report impairments in their QOL, particularly in physical health domains [3, 19, 20]. Compared to their siblings, survivors in the CCSS have lower average scores for QOL in the physical but not emotional functioning domain [19]. Differences between mean scores for sibling and survivor groups were not large and survivors’ scores were only slightly lower than expected population norms. However, when the proportion of individuals with very low QOL scores was examined, a large proportion of these survivors showed significant impairment in problems related to fatigue (47 % of females and 32 % of males compared to the 16 % that would be expected in the general population [19]). This was similar to findings from the British Childhood Cancer Survivor Study (BCCSS) which also reported a higher than expected proportion of survivors with very poor physical health functioning [20]. Similarly, in a CCSS study examining health problems that interfere significantly with activities of daily living, 12 % of survivors compared to only 2 % of their siblings reported these problems [4]. Survivors were also significantly more likely to report limitations in their physical activities and general health [4, 9, 21], compared to controls [4, 19].

Although many childhood cancer survivors are able to adapt and experience success within the domains of school, work, and interpersonal functioning, there is evidence that childhood cancer survivors can experience a number of medical, neurocognitive, psychological, and/or physical challenges that can impair their ability to attain developmental milestones [22]. There are circumstances in which even relatively minor changes in neurocognitive functioning can have a significant impact on a survivor’s adaptation and can increase their risk of psychosocial issues. Learning difficulties, combined with the symptoms of depression or anxiety, can create even greater barriers to success around social roles and have a negative impact on school performance, employment, and interpersonal relationships. Beyond learning issues, the ongoing medical follow-up needed and the real possibility of additional medical problems are other stressors survivors are managing in the context of trying to maintain “real world” expectations.

The literature has highlighted the neurocognitive issues associated with treatment to the central nervous system (CNS) and readers may refer to the other chapters in this book that address this more throughly. Patients who have received radiation therapy or intrathecal chemotherapy may be at greatest risk for learning difficulties. The CCSS data has indicated that the utilization of special education services has been significantly higher for survivors (23 %) when compared to sibling controls (8 %). Patients with brain tumors, Hodgkin lymphoma, and leukemia, and patients diagnosed before the age of five, were identified at greatest risk for needing special education services [23]. These findings are similar to the results of a Canadian cohort study in which survivors were reported as more likely to be retained, needing special education programs, and having educational/school problems when compared to controls. Patients who had been treated for CNS tumors, leukemia, and neuroblastoma were identified as groups with significant risk factors around educational achievement [24].

Given the issues many cancer survivors experience as a result of learning deficits or ongoing medical concerns, it is not surprising that finding and maintaining employment can be a challenge. While this is addressed in more detail in Chapter 24 of this book, briefly, the issues survivors experience around securing employment can be associated with physical health difficulties [25] or neurocognitive issues. Results from the CCSS indicated that survivors with poor physical health were eight times more likely to be unemployed than healthy survivors, with health related concerns reported as the barrier to employment [26, 27]. The risk for unemployment increases in relation to the chronic medical conditions experienced by survivors post-therapy and this is particularly important given that 73.5 % of the CCSS survivors reported at least one chronic medical condition 30 years after cancer diagnosis [28]. Unemployment also has significant implications for health care access given that in the United States health insurance coverage is typically attained through one’s employer. Data from the CCSS has shown that survivors are more likely than siblings to have difficulty acquiring health care coverage [29] and to have Medicaid or Medicare as their insurance carrier. Lack of insurance can significantly impair a patient’s ability to receive appropriate follow-up care and the additional stress associated with limited access may increase vulnerability to psychological distress.

The multifaceted issues faced by survivors of childhood cancer can also have an impact on interpersonal relationships. It is not unusual for survivors to report difficulties associated with social relationships, dating, and a lack of intimacy. The social challenges can lead to subsequent delays around psychosexual development, independence, and identity. In a study of Dutch survivors, those with slower psychosexual development were more likely not to be married and those with slowed autonomy were less likely to be living independently. As with other studies, brain tumor survivors were identified as a high-risk group and documented as being more likely not to meet developmental milestones according to a typical trajectory (Table 17.2) [22].

A number of large cohort studies have identified childhood cancer survivors as being less likely to be married when compared to the general population [30, 31]. As with other social adjustment data, survivors of CNS tumors are at greatest risk for not becoming married. Late effects of radiation, such as short stature, neurocognitive deficits, and poor physical functioning contributing to marital status [32]. Issues associated with neurocognitive functioning and the ability to live independently clearly impact ability to marry [33] as do physical functioning limitations/restrictions [34]. Interestingly, of those survivors that do marry, divorce rates do not significantly differ from the general population [35].

In social and sexual relationships other than marriage, survivors of childhood cancer can also experience a number of obstacles, frequently based on disease burden [36]. Issues associated with potential sexual dysfunction secondary to cancer and its treatment pose significant barriers to intimate relationships and create a potential vulnerability to anxiety and distress. In addition, for those who are able to develop intimate relationships, the issues associated with possible infertility as a result of cancer treatment create another obstacle. It is not uncommon for young adult survivors to have questions regarding their sexual functioning and fertility, and to need assistance with communicating concerns to their partner. This is an area that can be particularly difficult to broach with a medical provider, but if left unaddressed, can lead to significant psychological distress and the potential loss of a relationship.

Given that only a minority of childhood cancer survivors will be expected to have significant psychological late effects, many studies have attempted to identify important risk factors for psychological distress in this population. Since the relevance of specific risk factors can vary across types of cancer, age groups, and even social and cultural contexts, an exhaustive treatment of risk factors is beyond the score of this chapter. Instead, we present an overview of the risk factors most important for understanding and assessing childhood cancer stress along with our interpretation of the ways in which these factors may influence development and adaptation in individual survivors. Risk factors can be an important guide to assessing and monitoring survivors, however, it is important to appreciate that the course of cancer survivorship is dynamic and individuals who may initially present with no risk factors require ongoing monitoring and evaluation as their risk status and emotional outcomes can change significantly over time (Table 17.3).

In terms of demographic factors associated with psychological adjustment, female survivors have been found to be more likely to report psychological problems [3, 4], a finding consistent with studies in normal populations [37, 38], suggesting that females may be more vulnerable to distress or more willing to report psychological problems when they occur. Other demographic variables such as lower income, lower education, disability status, and unmarried status, have been associated with poor psychological and QOL outcomes in a number of studies [4, 19], but it is important to note that these factors may be both the result of poor psychological adaptation, as well as contributors to it. For example, depression would be expected to impair functioning in a way that makes it difficult for survivors to function in work and school environments, while problems with work and the stress of low income would also be expected to contribute to depression [39]. Although the precise relationship of these sociodemographic variables with psychological adaptation may not be known, their relationship with adaptation problems makes them important indicators of groups of survivors who should be considered at higher risk. Background factors or pre-existing conditions such as psychiatric history and pre-morbid functioning are important to consider, as these are known or suspected to be associated with poor outcomes after cancer. Similarly, extreme emotional or behavioral reactions that occurred during treatment suggest increased vulnerability to future psychological distress and should be considered risk factors for future adjustment problems.

Specific aspects of a child’s cancer and cancer treatments are also thought to increase risk for long-term psychological adjustment problems. Conceptually, we would expect intensive treatments to result in later adjustment problems if these treatments increase distress or developmental disruption during treatment, disrupt the ability to learn or acquire certain skills, or increase the risk for medical late-effects including cognitive limitations, physical limitations, physical disfigurement, secondary cancers or chronic conditions—and there is data to support this expectation. Within cancer-related factors, a brain tumor diagnosis is one factor consistently found to be associated with psychological symptoms, poor functional outcomes, and poor QOL [3, 8]. This association is likely due in large part to the negative impact that CNS tumors and associated treatments can have on learning, educational, and social skills later in life (described below). Survivors of bone tumors have also been found to be at higher risk for psychosocial problems in some studies, which may reflect the impact of physical mobility problems and pain on both physical and emotional quality of life [40]. Radiation therapy which can disrupt normal development of treated areas in later life has been associated with psychological problems, poor functional outcomes, and reduced QOL, though the effects will be different across types of radiation and types of cancers [3]. Cranial radiation, for example, can cause neurocognitive late-effects and growth deficiency, while pelvic radiation can also cause problems with growth, as well as mobility and fertility; radiation to each of these fields have been found to increase risk of adaptation problems later in life [3, 41]. Similarly, chemotherapy generally, especially in intensive chemotherapy regimens, has also been associate with greater likelihood of impaired QOL and psychological functioning [4, 42, 43]. Age at diagnosis might be expected to affect risk of long-term psychosocial complication since it could affect both the child’s experience of treatment, disruptions to their developmental course, and their sensitivity to the effects of specific treatments. Several studies have not supported relationship between age of diagnosis and later adjustment [8, 19], indicating no particular age group should be considered to be at increased risk. Nonetheless, clinicians working with individual survivors should consider how age at time of treatment may affect survivors differently. For example, those diagnosed at younger ages may be less likely to recall their treatment and less likely to identify as “survivors” than those diagnosed in their teenage years [44].

As noted, the effects of childhood cancer treatments on later psychological functioning may be due, in part, to their effects on long-term physical health, and poor physical health functioning has been noted to be strongly associated with poor psychological functioning in this population. Survivors with multiple medical problems have been found to report more psychological distress [19, 45], and a study of suicidal ideation among survivors [8] showed that poor health outcomes, including pain, are associated with greater likelihood of reporting suicidal ideation even after adjusting for depression. Survivors with poor physical health were also noted to be less likely to be employed, married, or have medical insurance, and more likely to have low educational attainment, and at least one major medical condition [19]. This, too, is consistent with previous research showing that medical problems, especially chronic conditions that are likely to interfere with routine functioning, are associated with significant psychological morbidity. Childhood cancer survivors are vulnerable to a number of medical late-effects (described in previous chapters) which would be expected to carry this kind of psychological burden as seen in other groups. In particular, physical symptoms that lead to loss of important aspects of individual identity—sexual dysfunction, problems with bladder or bowel control, as well as disfigurement, fatigue, and cognitive changes—can be particularly burdensome and lead to increased psychological distress. Similarly, the loss of independence associated with not being able to participate in age appropriate activities or work, or any condition that limits independence should be considered a likely risk factor. Because survivors are likely to be diagnosed with chronic conditions at a much younger age than their peers [28], they may have fewer coping resources and their educational, career, and relationship plans may be more vulnerable. Developing a chronic condition while still young, many survivors feel unfairly burdened, a sentiment sometimes expressed as “I am too young for this!” Some survivors find the diagnosis of a treatment-related condition extremely anxiety provoking, raising fears that they may be never feel at ease with their health again, especially if the new condition is chronic and unlikely to be cured. “It’s not over when it’s over,” is a phrase commonly heard from survivors expressing a feeling of resignation that they are still not free from the negative impact of cancer despite having been cured of their disease.

The literature has focused on identifying survivors of childhood cancer who are at greatest risk for psychological distress, and though findings can be inconsistent, survivors of pediatric brain tumors are consistently noted as a high-risk cohort for psychological morbidity. The significant burden of disease location, treatment intensity, and treatment toxicity all contribute to this finding. The neurocognitive, physical functioning, and medical issues that can arise from having a brain tumor can be significant and the types of issues experienced relate to diagnosis and tumor location. Surgery is the most optimal choice of up-front therapy for children with brain tumors and the extent of resection attained has been related to cure of disease [46]. While many surgeries are successful and patients experience minimal to no post-operative complications deficits, there are a subset of patients who have neurological impairments either as a result of the tumor pressing on important areas of the brain pre-diagnosis, due to the surgical resection itself, or complications from surgery. Although we have mentioned throughout the chapter that those survivors treated with more intensive treatments are at greatest risk for the development of medical, physical, and emotional difficulties, research has demonstrated that even patients who are treated for brain tumors with surgery as their sole form of treatment have been identified as having impaired IQ, academic achievement, and adaptive behavior as compared to the normative population [47] and have high utilization rates of special education services (Table 17.4) [48].

In addition to the challenges posed to patients as a result of surgical intervention, the actual location of the tumor and the tumor diagnosis are of great significance in terms of survival and quality of life. For instance, craniopharyngioma is a tumor with a high cure rate and these patients tend to be treated with surgery and/or radiation therapy. While a curable disease, the location of this tumor comes with significant morbidity [49]. Survivors must cope with memory issues, sleep disturbance (narcolepsy), mood issues, and certain endocrinopathies, such as hypothalamic obesity that can severely impact physical appearance. These are patients who are seen in the clinic setting for whom it may be difficult to find an appropriate school placement due to the complex learning, medical, and behavioral issues experienced. It is not uncommon for families to report to clinicians the need to lock kitchen cabinets due to insatiability associated with the disease. The psychosocial challenges facing these survivors such as significant academic needs, physical appearance changes, behavioral issues that impact social functioning, and fatigue that can negatively impact employment, leaves this subset of patients at a particularly high risk for developing depression and/or other psychological adjustment issues.

In addition to tumor location and diagnosis, the treatment utilized for CNS tumors such as cranial radiation, intrathecal chemotherapy, and high-dose chemotherapy with stem cell rescue, increase the number of learning, physical, and medical problems [23, 24, 50] and leave survivors vulnerable to psychological distress. The effect of multiple medical issues is dynamic and can have a negative cumulative impact on psychological adaptation over time. For instance, school-aged survivors who struggle academically despite receiving special education services are at-risk for depression and anxiety. It is not unusual to hear of patients spending 4–5 hours on homework a night as a result of slowed processing speed. The time spent on homework and the stress associated with academic success can leave survivors with anxiety and significant social isolation. These students are then ill-prepared to manage the social demands at the higher education level and tend to experience failure when they transition to college. Such failure can lead to disappointment, feelings of helplessness and hopelessness, withdrawal, and subsequent depression. There are other situations in which patients have difficulty accepting the help that they need and continue to struggle with their academics and psychological adjustment, despite schools and teachers being willing to accommodate their learning needs. The “rejection of help” can have a cumulative impact on mood and self-esteem over time and set survivors up for failure as the academic demands increase in later grades. For instance, one pre-teen survivor felt so strongly that she did not want to be different from peers that she insisted on completing all the homework that was assigned to the class. She presented with significant anxiety, stress, and low self-esteem, and due to the hours she was spending on homework, she was also socially isolated. This situation occurred despite the fact that she had a special education plan that provided homework modifications, supportive teachers, and strong parental advocacy. Her unwillingness to accept help was the barrier to success.