33 Oncological Illnesses

Sarah McCarthy, Kimberly A. Pyke-Grimm, and Angela M. Feraco

Cancer arising in childhood is rare. It encompasses a diverse collection of diseases that can affect every organ system. The most common childhood cancers include leukemias, brain tumors, lymphomas, and extracranial solid tumors arising from the kidney, neuroendocrine tissues, and bone.¹ Over the past 45 years, the overall survival rate for children with cancer has increased dramatically, from approximately 45% in 1975 to more than 80% in recent years.² This substantial increase in survival is driven largely by successes in treating acute lymphoblastic leukemia, the most common cancer of childhood.³ At the end of 2013, approximately 420,000 pediatric cancer survivors were currently living in the United States,⁴ and 1 of every 530 young adults aged 20–39 years had been treated for childhood cancer.⁵ Yet while gains made in pediatric cancer survival over this period are among the most dramatic success stories of modern medicine, pediatric cancer remains a leading cause of death in children living in the United States. More than 15,000 children ages 0–19 are diagnosed with cancer each year, and approximately 1,700 die from their disease.¹ Childhood cancer is a profoundly life-altering experience for the affected child, the child’s family, and the surrounding community.⁶ Children treated for cancer experience immediate and late effects of malignancy and treatment that can affect physical health, cognition, and psychosocial functioning.⁴ Importantly, children, their siblings, and their parents also report substantial psychological growth and resiliency.⁷

Palliative Care as a Standard of Care in Pediatric Oncology

The integration of palliative care into the care of children and adolescents with cancer is supported as best practice by numerous professional organizations.⁸ Palliative care is useful for and intended to be an enhancement to the care of patients with oncological disease at any time during the disease trajectory, from diagnosis to end-of-life^9,10 (Figure 33.1). The role of the interdisciplinary palliative care team may vary with regard to the child with cancer, the child’s family caregivers, and the child’s pediatric oncology team.⁹ For example, the interdisciplinary palliative care team may act as a consultative resource to the interdisciplinary pediatric oncology team, may provide direct care to children and their family caregivers, and, in some circumstances, may assume the role of primary team.^11,12 Patient and family/caregiver distress related to the child’s symptoms, psychosocial distress, and poor communication can occur at any time and can benefit from palliative care therapies provided alongside cancer-directed therapy.^9,11,13 Furthermore, patients and families have reported receptivity to early integration of palliative care principles and personnel.¹⁴

In a landmark paper, Wolfe and colleagues made visible the suffering children with cancer experienced at the end of their lives.¹⁵ At that time, few pediatric oncologists had received formal training in managing symptoms and suffering at the end of life, and few seemed to understand the scope of the problem.¹⁶ Beyond demonstrating the high-intensity care that many children receive at end-of-life, these studies highlighted the need for training in palliative care principles among interdisciplinary clinicians who constitute the pediatric oncology team (“primary” palliative care) as well as the need for specialty pediatric palliative care (PPC) in more complex scenarios. Since that time, the American Academy of Pediatrics has recognized the essential roles that primary and specialty PPC play in the care of seriously ill children.¹⁷ The American Board of Medical Specialties began offering subspecialty certification for Hospice and Palliative Medicine in 2008. The early integration of primary palliative care for all children diagnosed with cancer has been proposed as a standard of care within pediatric oncology.¹⁸ The core tenets of PPC within oncology include systematic symptom assessment and intervention (see Section III), facilitation of family-centered communication (see Chapter 13) including prioritization of the patient’s voice (see Chapters 3 and 9), and developmentally informed advance care planning (see Chapter 14).¹⁸ The provision of psychosocial care for patients and families is a key element of palliative care for pediatric oncology patients; see also Chapter 3, “Children’s Voices” and Chapter 17, “Psychological Symptoms.”¹⁹ PPC teams often include social workers, some of whom have specific training in the field, and may also offer access to assessment and intervention through psychology and psychiatry services. In addition, professionals with expertise in child life, expressive therapies, and chaplaincy can be extremely helpful in promoting coping and augmenting quality of life. Current clinical standards of care^20,21 emphasize the importance of early psychosocial assessment and the development of an individualized psychosocial care plan for the child and the family for all pediatric oncology patients, including those receiving palliative care services.

Research has demonstrated that pediatric oncology patients and their families who receive specialty palliative care experience improvements in psychological and physical symptoms,²² report better quality of life,²³ are more likely to engage in end-of-life discussions and to enroll in hospice,²⁴ and are less likely to die in an intensive care unit (ICU) and/or to receive mechanical ventilation immediately prior to death.²⁵ In addition, specialty palliative care has been associated with improved outcomes for parents before²³ and after their child’s death.²⁶ However, despite the call for early integration of services and the documented positive impact of palliative care involvement, a recent systematic review found that only 54% of children with cancer who subsequently died received any specialty palliative care services prior to their death, and, for the majority, services were not initiated until near the time of death.²⁷ Of note, this literature examines the role of specialty PPC. Primary palliative care efforts are more difficult to identify and study retrospectively.

Language, Communication, and Uncertainty in Childhood Cancer

Communication is fundamental to PPC. This includes communication with the child and family as well as among all members of the interdisciplinary team.²⁸ As highlighted in Chapter 13 and throughout this book, effective patient- and family-centered communication stems from foundational knowledge and attitudes and requires deliberate practice.^29,30,31,32 Within pediatric oncology, the practice of compassionate and honest communication throughout the disease trajectory has been shown to enhance patient, parent, and provider outcomes.^12,33 Because pediatric cancer occurs throughout childhood and adolescence, each child’s developmental context shapes the care that is needed.³⁴

As noted in the first chapter, language is powerful, and language and narrative are important drivers of how children and their families experience childhood cancer.³⁵ Clinicians frequently use the term “cure” when discussing the goal of treatment for cancer arising in childhood.^3,36 The word “cure” is meant to imply lifelong disease eradication. Despite the incredible progress made in treating childhood cancers, many children face lifelong changes in health due to consequences of their underlying cancer or the treatment they receive.^37,38,39,40 The life-threatening nature of cancer, the possibility of cancer progression or recurrence, and the possibility of future health conditions resulting from cancer treatment all contribute to a future that may feel profoundly uncertain.⁴¹ Likewise, clinicians who care for children with cancer over the course of a career see that illness trajectories are frequently uncertain. Children expected to live a long life after completing treatment sometimes die suddenly from infection or from unintended effects of that very treatment, while children with advanced cancer may live far longer than anticipated. This should not discourage clinicians from sharing their best understanding of what a child and family are likely to experience immediately and in the long-term.^42,43 We encourage clinicians to describe the goal of proposed cancer treatments, whether that goal is to live a long life with disease eradication, life extension without expectation that the cancer can be eradicated, or to reduce symptoms arising from active cancer, perhaps without an expectation that this will extend life.

Parents of children with cancer have reported wanting detailed prognostic information, opportunities to revisit initial discussions, and time to consider treatment decisions.^44,45 The time around diagnosis has also been identified to be important for influencing patterns of communication.⁴⁶ Open communication between the team and the patient/family all along the illness trajectory can enhance the therapeutic relationship, improve quality of life, and facilitate shared decision-making (Figure 33.2).⁴⁷ Other benefits include reducing decisional regret,⁴⁸ optimizing medical treatment, and ensuring that treatment is aligned with the goals of care desired by the patient and family. High-quality communication ideally begins with the initial visits⁴⁹ and continues throughout the relationship with the interdisciplinary team.^20,50,51,52 Importantly, communication takes place between the patient/family and multiple individuals from different disciplines who may bring complementary perspectives. These interactions may focus on different aspects of care reflecting the expertise of each discipline (e.g., medicine, nursing, social work, psychology, chaplaincy, child life, rehabilitative therapists). To ensure a clear message and that everyone is “working in the same direction” it is critical that there is also clear communication and mutual exchange among these professionals.⁵¹

A developmentally sensitive approach to communicating with children is critical in establishing a relationship with them. Table 33.1 highlights the typical cognitive development of children and recommendations for communication matched to developmental level. Increasingly, children who survived cancer and their families believe that the diagnosis and management should be discussed with the child starting early at diagnosis if possible.^34,53,54,55 Learning how the parents have approached scary or difficult situations with their child prior to the child’s diagnosis can begin a conversation about how to involve the child or adolescent in discussions of the child’s health. Attending to families’ approaches to communication and decision-making and eliciting the cultural, ethnic, or religious basis of these preferences demonstrates respect for the family’s norms, rules, and cohesiveness.⁵⁶ When there is news to share with the child, such as a diagnosis of cancer, questions to consider discussing with the parents might include: Do they want or need additional time before involving the child? And Do they want to talk with the child privately or with a professional present for support? Eliciting and respecting parents’ preferences for how and when to share news with children reinforces the parental role and shows the healthcare team’s commitment to aligning with the family.^57,58 Once parents have indicated their readiness, involvement of the child in these conversations should be with the participation of the parents and carefully orchestrated to address concerns and issues in an age-appropriate manner.³⁴ For many children and most adolescents, the question isn’t if they should participate but how, when, and to what extent.^34,59,60 For adolescents, there is also the consideration of their evolving sense of themselves apart from their parents, siblings, and extended family members. Adolescents might want to meet privately with the team. Participation in these conversations serves not only to impart information but also to enhance feelings of control and to establish trust with clinicians.¹⁸

Communicating with siblings and extended family members^57,61 is very important. Prior to meeting with extended family, it is important to discuss with the parents and, if developmentally appropriate, the child, to determine what and with whom the team can communicate. Direct communication by the healthcare team with siblings and other family members can improve family adjustment, enhance sibling understanding, and help siblings adjust to new life circumstances.⁵⁷ When desired by parents, communicating directly with key extended family members may reduce the burden on them to remember to inform and interpret complicated concepts and issues. Developing relationships between members of the healthcare team, siblings, and other family members may contribute to the overall coping of the family.

Quality of life encompasses all facets of life, including physical, emotional, social, and spiritual domains.⁶² Children with cancer are at high risk for poor quality of life,⁶³ and efforts to promote well-being should include all these domains. Important symptoms that result from cancer and its treatment (e.g., pain, nausea/vomiting, insomnia, bodily changes, cognitive dysfunction, and psychological symptoms) all impact quality of life. Changes in daily life that may contribute to social isolation also have enormous implications. Much of the empiric evidence and available interventions focus on the role of physical symptoms. Efforts to promote standardization of symptom detection and management include patient-report symptom tools⁶⁴ and consensus- and evidence-based guidelines.^65,66 Interdisciplinary palliative care teams facilitate detection and amelioration of poor quality of life related to physical and psychological suffering, social isolation, or spiritual suffering.⁶⁷ Supportive discussion characterized by deeply attentive listening and sensitive questioning may at times be the most powerful intervention for children and families experiencing sudden, progressive, or severe changes to the quality of their lives.

Impact of Childhood Cancer on the Child’s Family

The diagnosis and treatment of pediatric cancer stresses the psychosocial functioning of the family, including health-related quality of life and marital adjustment.^68,69,70 Milestones in the cancer trajectory, including initial diagnosis, relapses, and even the positive step of moving to “off-treatment” status place additional stress on caregivers and family relationships.^70,71

Intensive treatment schedules frequently remove the child from the rhythms of daily family life⁷² because of prolonged hospitalizations or long-distance travel to receive cancer care. In two-parent families, frequently one parent will accompany the child to outpatient appointments or stay with the child in the hospital, while the other parent cares for the siblings, while continuing to work and maintain the household. Posttraumatic stress symptoms have been reported in siblings; fortunately, there is some awareness of these problems among parents and growing awareness among professionals.⁷³ Interventions such as dedicated programs for siblings may be a useful preventive approach, while group interventions can be useful⁷⁴ to treat symptoms of depression in siblings.

Grandparents may become important caregivers for the child with cancer and siblings and provide support to the parents.^75,76,77 Families frequently experience financial disruption, including high out-of-pocket medical expenses and loss of income due to missed work and job loss.^78,79,80 There is profound economic loss and material hardship among families of children with cancer, which is associated with psychological distress^78,81 and reduced marital adjustment. Those with preexisting stressors, such as underemployment, poverty, inadequate transportation, lack of legal protections, caregiver mental illness, or poor family functioning, are in particular need of support.⁶⁸ This may take the form of concrete resources, legal advocacy, caregiver or family counseling, and spiritual support. Interdisciplinary palliative care teams may be particularly helpful in eliciting sources of stress and identifying supports within the healthcare system or in the surrounding community.¹² When there are psychologists and psychiatrists with expertise in pediatric psycho-oncology, collaboration between interdisciplinary palliative care teams and these clinicians will ensure optimal comprehensive care.^51,82 Spiritual assessment and support from hospital chaplaincy or their own clergy may be particularly important for some families as the experience of receiving a life-threatening diagnosis may change individuals’ sense of the world and how it is ordered.^67,83 If a chaplain is not available, another clinician on the interdisciplinary team may at least open the conversation.

Participating in the Care of Children with Cancer: Impact on Clinicians

Pediatric oncology, especially, attracts clinicians who wish to help children and families who are at special risk. Caring for children with cancer and their families can be fulfilling and inspiring. Yet this setting can be both personally and professionally demanding (see also Chapter 12).^84,85,86 Participating in the care of children with cancer can lead to burnout.^84,87,88 Long-term relationships, incurable diseases, unanticipated complications, suffering, loss, grief, and ethical dilemmas—each characteristic of pediatric oncology practice—increase the risk of clinicians developing burnout.⁸⁵ Manifestations of burnout can include disengagement from or depersonalization of needy patients and families, poor communication with patients, increased medical errors, physician job dissatisfaction, guilt, and reduced feelings of accomplishment and work effort.^89,90,91

Clinicians caring for children with cancer and their families are also at risk for compassion fatigue, moral distress, and moral injury.⁹² These forms of work-associated distress may arise when clinicians feel unable to meet the needs of a child or their family due to barriers that may stem from personal, financial, cultural, institutional, ethical, or other sources. When this perception is repeated or prolonged, the clinician’s resources are ultimately depleted, and they may retreat to harmful (or at least unhelpful) coping strategies. Use of education and self-care activities reduces compassion fatigue in inpatient pediatric oncology nurses.

All clinical care providers are at risk including nurses, physicians, social workers, psychologists and other clinicians. Rates of burnout among oncology healthcare professionals are reported to be elevated.⁹³ Burnout among female physicians has been reported to be higher compared to males in various healthcare settings.^88,94

Barriers to providing optimal care for families might include suboptimal clinical team dynamics⁹⁴ and structural barriers such as excessive workload or work hours.^94,95,96 Institution level barriers include demands for excessive documentation and order entry requirements caused by the electronic health record which might lead to a higher risk for burnout⁹⁷ and lack of institutional support.^87,96

When clinicians experience these barriers infrequently, their ability to cope is likely to remain intact. However continuous exposure can deplete coping reserves and lead to problematic coping mechanisms. Efforts to reduce these barriers, such as increasing work hour flexibility, lightening the schedule, organizational support, improved team communication, and self-care interventions, all may help to mitigate the risk of burnout.⁹⁸ Interdisciplinary palliative care teams frequently possess expertise in facilitating reflection and meaning-making. This expertise can be a support to professionals at risk for burnout due to the stresses associated with caring for children with cancer and their families.⁹⁹

Palliative Care Throughout the Continuum of Childhood Cancer Care Palliative care should be offered throughout the continuum of the child’s care beginning at diagnosis through to survivorship care or bereavement care if the child does not survive. Palliative care may be delivered by cancer care teams (primary palliative care) or by specialty palliative care teams. Ideally, all children with cancer would receive primary palliative care from skilled clinicians and some children would receive specialty palliative care. Specialty palliative consultation is particularly appropriate when advanced expertise would enhance the child’s quality of life and/or family’s experience of their child’s interest.

Palliative Care Needs of Children and Families at the Time of Diagnosis

Children and families experience high degrees of distress at the time of diagnosis, particularly around symptoms related to the underlying disease, learning the diagnosis, hearing about cancer treatments and participating in treatment decisions, and trying to make sense of how the diagnosis will affect their lives immediately and in the future.^100,101

How a family learns that their child has cancer has implications for their subsequent expectations and experiences of their child’s care. For many, the period of time between suspecting that their child is very ill and learning that their child has cancer is characterized by repeated medical visits in which the suspicion for cancer slowly increases.⁴⁶ In most situations, the patient is referred to the oncology team once cancer is thought to be highly likely. Initial visits, which may include diagnostic disclosure and discussions of treatment recommendations, sometimes referred to as the “Day One talk,”⁴⁹ may set the tone for many aspects of the long-term relationship between oncology team members and the patient and their family. However, parents and children may be highly distressed during these conversations.¹⁰⁰ As such, there has been recent focus on the importance of deepening these initial discussions to ensure that each family’s hopes, worries, and unique context are elicited to enable family-centered care.^100,102

Patients and families bring with them as many backgrounds as there are human beings when they come to the “Day One Talk.”⁴⁹ They may have suspected cancer and feel that they are finally receiving the answers they sought, or the possibility of cancer may be completely unexpected and learning the diagnosis will be akin to “shell shock.” They may have experience with friends or family members that may influence their perceptions of cancer.¹⁰³ Family members may have backgrounds in the health sciences or hospital services and may have encountered people with cancer in their workplace, as a volunteer, or in their faith communities. In preparation for the “Day One talk,” team members may seek advice or insight from the medical record or from clinicians who have already interacted with the family. However, much of this information may not be available. It is important that team members be sensitive and flexible in their approach. During this talk, they must continually assess the family for their understanding of the material, ability to hear and entertain new material, emotional responses, and priorities. Rarely can the team share all the information and provide anticipatory guidance in a single visit—nor is it a realistic goal. “Telling” is never a one-time occurrence: it is a process over time. Clinicians may have to modify their approaches based on the family’s cultural, scientific, and cognitive background and abilities. Interdisciplinary participation in discussions during the early treatment period, such as the “Day Two Talk”¹⁰² and the “Day 100 Talk,”¹⁰⁴ amplifies the family’s voice in the child’s care. Engaging in ongoing assessment and taking a flexible approach are critical to developing successful long-term relationships with the child and family and facilitate their eventual participation in truly shared decision-making.

Prognosis and Hope

In disclosing the diagnosis and prognosis, the clinician must begin by learning what the family already knows and then seek permission to proceed.¹⁰⁵ By continually assessing the patient and family’s reaction and ability to continue the conversation, the clinician will maximize the likelihood of matching the pace and content of the discussion to the family’s needs. Techniques such as assessing understanding, providing succinct information, and then reassessing (“ask-tell-ask”) can be very useful.³² Assessing what information is desired and matching this with what is told can prevent families from becoming overwhelmed by information and demonstrates sensitivity and respect.

With the diagnosis of cancer, families—including some children—may wonder (either silently or aloud) “What does this mean for me/us?” or even more explicitly, “How long does he/she/I have?” Disclosing prognosis may be anxiety-provoking for clinicians because they are concerned that families may become overwhelmed and excessively distressed⁴² and lose hope. Multiple studies show that patients and families want to hear prognostic information even if the prognosis is poor.^42,106 Most want as much detail as possible.¹⁰⁷ In the face of the unknown, some people prefer to receive even negative information as a way to reduce uncertainty and anxiety.¹⁰⁸

There is evidence that receiving more information about prognosis (even when poor) is associated with increased hope.¹⁰⁹ The commitment of the healthcare team to provide information is beneficial and may reduce decisional regret.⁴⁸ In a study of parental hope for children with advanced cancer, Kamihara and colleagues found that while the vast majority (88%) of parents recognized their child’s poor condition, they still maintained hope for a cure and most (66%) continue to hope for a long life.¹¹⁰ Prognostic knowledge allows parents to adjust their goals and expectations¹¹¹ and may result in prioritizing quality time with their children.¹¹² For some parents of children with advanced cancer, the act of seeking cancer-directed therapy may become part of the parental role.¹¹³

Overview of Cancer-Directed Treatments

Childhood cancers are treated with chemotherapy, radiation, surgery, immune-based therapies, and/or cellular therapies. The following sections provide an overview of these treatment strategies, as well as of the child and family experiences engendered by them. The child’s developmental stage, the body systems affected by the cancer and treatment, the family’s previous experiences of cancer, cultural depictions of cancer,¹¹⁴ and significant stressors¹¹⁵ all contribute to the patient’s and family’s experience.

Leukemias and Lymphomas

These entities are treated mainly with chemotherapy and sometimes radiation therapy. Treatment durations range from a few months for low-stage Hodgkin lymphoma¹¹⁶ to 2–3 years for acute lymphoblastic leukemia.¹¹⁷ Children with leukemia frequently require blood and platelet transfusions throughout the initial months of treatment due to replacement of the healthy blood-forming elements by leukemic cells as well as the myelosuppressive effects of leukemia treatment.⁶⁶ Though once universally employed in the treatment of acute lymphoblastic leukemia, radiation therapy is now typically reserved only for patients who have frank central nervous system (CNS) involvement by leukemia at diagnosis. Radiation therapy is still commonly employed in the treatment of pediatric Hodgkin lymphoma. Leukemias with certain high-risk features and relapsed leukemias and lymphomas may be treated with immunotherapies or cellular therapies, such as stem cell transplant and chimeric antigen receptor (CAR) T cells, bispecific antibodies, tumor-specific antibodies, or immune checkpoint inhibitors.^118,119 Treatment of select leukemias, such as chronic myelogenous leukemia and Philadelphia-positive acute lymphoblastic leukemias, utilizes tyrosine kinase inhibitors, which have distinct side-effect profiles.¹²⁰ Children with high-risk acute myeloid leukemia, relapsed acute lymphoblastic or myeloid leukemia, or relapsed Hodgkin lymphoma cancer may receive infusions of stem cells as a component of cancer-directed treatment. Stem cell transplantation is a particularly intensive treatment as children typically must undergo “conditioning” with high doses of myeloablative chemotherapy and/or immunosuppressive medications prior to infusion of the cellular product. Whole-body irradiation may be a component of some conditioning regimens.

Central Nervous System Tumors

The concept of “local control” stipulates that the primary mass of cancer cells in the brain and/or spinal cord must be surgically removed and/or irradiated in order to prevent additional growth or, for some CNS tumors, metastatic spread. For some children with brain tumors, an operation may completely remove the cancer and may be the definitive treatment. Radiation therapy is a mainstay of treatment for many CNS tumors. Radiation treatment doses for most common childhood CNS cancers range from 18 Gy to 55 Gy. Radiation therapy is typically delivered in daily fractions of approximately 150–180 cGy. Thus, treatment may require daily visits for a period of a few days up to 6 weeks for the highest total doses. Increasingly, adjuvant (postsurgical or post-radiation) chemotherapy, including high-dose chemotherapy with autologous stem cell rescue or targeted therapies, are also employed in the initial treatment of CNS tumors. Tumors such as medulloblastoma in children younger than 3 years are treated exclusively with high-dose chemotherapy with autologous stem cell rescue due to the devastating neurologic consequences of high doses of radiation to the developing brain and spinal cord.¹²¹ Even among older children, tradeoffs between neurologic function (including long-term cognitive outcomes) and disease control may require complex decision-making on the part of the families and treating clinicians. Thus, expert interprofessional support, such as that available from an interdisciplinary palliative care team, may be particularly helpful to families of children with CNS tumors. Finally, targeted therapies are increasingly important in the treatment of cancers of the brain and spinal cord. Identification of BRAF mutations in low-grade gliomas, which were previously treated with months or years of cytotoxic chemotherapy, is altering the treatment paradigm for this disease, enabling some children to receive oral medications and avoid chemotherapy.

Extracranial Solid Tumors

As for CNS tumors, treatment for extracranial solid tumors emphasizes “local control” through surgical resection and/or radiation therapy.¹²² For some children with extracranial solid tumors, an operation may completely remove the cancer and may be the definitive treatment. Neoadjuvant (pr-surgical or pre-radiation) and/or adjuvant (postsurgical or post-radiation) chemotherapy is also used for many of the most common extracranial solid tumors, even if the cancer is confined to a single location or organ at the time of diagnosis. Osteosarcoma, a malignant tumor of bone, is treated with both neoadjuvant and adjuvant chemotherapy in addition to surgical removal of the tumor.¹²³ For children and adolescents with bone tumors, local control decisions may involve tradeoffs between the appearance of an intact limb and limb function. These decisions require complex decision-making by families and treating clinicians, and patients and families may particularly benefit from skilled communication that can elicit goals and values to enable the best possible treatment decision. In addition to chemotherapy, surgical resection, radiation, and immunotherapy, children with high-risk neuroblastoma receive high-dose chemotherapy and infusions of autologous stem cells. At the time of this writing, treatment for high-risk neuroblastoma is among the most intensive due to the prolonged nature of treatment (~18 months) and the use of multiple modalities, each with the potential for severe side effects during and after treatment.¹²⁴ Finally, as is true for leukemia, lymphomas, and brain and spinal cord tumors, treatment of extracranial solid tumors increasingly includes so-called targeted therapies that act on a biochemical pathway important to the growth or survival of the cancerous cells.

Genomics, Precision Medicine, and Tumor Profiling

Profiling the genome and mutations of the tumor is a relatively new field of precision cancer treatment that allows the oncologist to select therapies based on the individual patient’s tumor biology.¹²⁵ In this way, it is hoped to improve the success of therapy and decrease toxicity by avoiding medications that are unlikely to be successful.¹²⁶

Increasingly, the fields of cancer genomics and so-called precision medicine are being incorporated into clinical research studies of children with cancer. The Children’s Oncology Group, St. Jude Children’s Research Hospital, and other national and international childhood cancer research consortia are studying whether gathering information about the specific genomes and epigenomes of advanced childhood cancers can enable “rationally targeted” treatments.¹²⁷ Gathering information about the biology of a cancer arising in individual persons is sometimes referred to as “tumor profiling.” This strategy has significantly altered the landscape of adult oncology, where the approach to advanced lung cancer, colon cancer, and breast cancers now incorporates genomic information to help determine recommended treatments.^128,129,130 In childhood cancer, tumor profiling is contributing to changes in recommended treatments, particularly among cancers viewed as “high risk” or “advanced.”^131,132 “Advanced cancer” is a term used to describe cancer that is either metastatic at the time of diagnosis, relapsed, or that progresses during treatment.¹³³

In pediatric cancer, leukemia has been the area of the most rapid progression in this field. The Children’s Oncology Group (COG)/National Cancer Institute Pediatric Molecular Analysis for Therapy Choice (MATCH) trial opened in 2017 and is still under way. Other, disease-specific trials taking place include profiling mutations in leukemia and lymphoma and newly diagnosed medulloblastoma patients.¹²⁶ Other areas of rapid progress are in immune modulation (checkpoint inhibition) and genetically engineered CAR-T cells. This field is rapidly developing and the value and limitations of this technology are still emerging.

Experiences of Receiving Cancer Therapeutics

Individual experiences of receiving cancer therapeutics will vary widely and will be influenced by the child’s developmental stage, underlying health, comorbidities, the family’s history of experiences with illness and healthcare systems, and the child’s and family’s additional stressors, supports, and strengths. Knowledge of common experiences and side effects will enable the clinician to be most helpful to a child or family experiencing symptom distress or poor quality of life. The following sections provide an introduction to facets of cancer care most likely to have a significant impact on quality of life.

Central Venous Access Devices

Children receiving treatment for cancer typically require central venous access, either an implanted port or a central venous catheter that communicates with the external environment.⁶⁶ For children with implanted ports, the port is accessed via a Huber needle that penetrates the skin and enters the subcutaneous reservoir that connects to the internal central venous catheter. For many families, particularly those whose children are toddlers, acclimating to Huber needle placement can be challenging. Children frequently develop procedural anxiety around placement of the Huber needle. Integrative strategies such as preparatory medical play distraction and self-hypnosis may reduce distress around Huber needle placement.¹³⁴ Topical anesthetics may reduce the physical discomfort associated with the Huber needle penetrating the skin.

Children who require more than one lumen of central venous access may have a Hickman or Broviac central venous line (CVL) placed surgically. Others may have a nonsurgical peripherally inserted central catheter (PICC). Both CVLs and PICCs require instillation of anticoagulants at regular intervals to maintain patency of the lumens. Families are frequently expected to learn to perform this “line care,” as well as learn how to prevent microbial contamination of the CVL/PICC. Line care contributes to the burden of medical caregiving families face during the period of active treatment for childhood cancer.¹³⁵

Cytotoxic Chemotherapy

Chemotherapy-Induced Nausea and Vomiting

Children who receive cytotoxic chemotherapy are at risk for experiencing chemotherapy-induced nausea and vomiting (CINV). Emetogenicity of chemotherapeutics and chemotherapeutic combinations vary widely. The chemoreceptor trigger zone, an area of the medulla characterized by serotonergic (5HT₃), dopaminergic (DA₂), and neurokinin (NK₁) receptors, receives afferent input from the gut and communicates with the vomiting center. See Chapter 25 for a more in-depth discussion of the neurophysiology of vomiting. The Children’s Oncology Group, a consortium of pediatric cancer centers largely based in North America, has published evidence-based guidelines for use of pharmacologic antiemetics and integrative strategies to reduce acute, delayed, refractory, and anticipatory CINV.^65,66 In the current era, the 5HT₃ class of antiemetics, of which ondansetron is a prototypical agent, is a mainstay of pharmacologic treatment for acute CINV. Dexamethasone is also highly effective, particularly in regimens that contain anthracyclines and for prevention of delayed CINV such as that classically associated with platinum compounds.⁶⁶ Dexamethasone may be contraindicated in certain populations, such as those with lymphoid malignancies and those where CNS penetration of chemotherapy is of particular concern.⁶⁶ Aprepitant, an agent that prevents signaling through NK₁ receptors, is increasingly utilized in children receiving highly emetogenic chemotherapy but alters blood concentrations of common chemotherapeutic agents due to its interaction with the cytochrome p450 isoforms 3A4 and 2C9.^136,137 Olanzapine is also increasingly used for enhanced control of acute CINV in children, though sedative effects may be dose-limiting.^138,139 Multiagent antiemetic regimens that incorporate multiple mechanisms of action are associated with enhanced prevention of CINV, and prevention of acute CINV is associated with prevention of delayed CINV.¹⁴⁰ Thus, pharmacologic antiemetic regimens should be constructed with attention to the child’s overall treatment plan, active symptoms, and with the goal of minimizing bothersome side effects. Integrative therapies such as aromatherapy and acupressure may be helpful for preventing and treating CINV, and specialty palliative care teams are encouraged to master these strategies and/or to serve as liaisons to hospital- or community-based practitioners.¹³⁴

Alopecia

Alopecia is a common, highly visible, and distressing side-effect of many cytotoxic chemotherapies and cranial radiation.^141,142 Alopecia is the sign that is perhaps most culturally symbolic of cancer and cancer treatment. Prevention of alopecia has been explored through cooling the skin during chemotherapy administration.¹⁴³ This strategy is not commonly integrated into current pediatric oncology practice but may be considered for patients for whom alopecia is particularly distressing. Promotion of a positive self-image among children, adolescents, and young adults experiencing alopecia may take the form of adornment through use of wigs, hats, headscarves, makeup, and/or jewelry. Family caregivers of children with cancer and children themselves may benefit from supportive listening to enable them to voice feelings of overall loss and fear related to hair loss.

Myelosuppression

Consequences of myelosuppression include fatigue and pallor from anemia, easy bruising and abnormal bleeding from thrombocytopenia, and mucosal ulceration and risk from infection from granulocytopenia. Although anemia and abnormal bleeding are typically managed with transfusions of erythrocytes and platelets, mucosal ulceration and infection present much greater challenges. Strategies under study to prevent mucosal ulceration include light therapy. Treatment of the pain associated with mucosal ulceration (mucositis) may include use of topical anesthetics and systemic analgesics including acetaminophen and opioid medications. If mucosal ulceration interferes with the provision of oral medications, the intravenous route is preferred. Integrative strategies such as self-hypnosis, guided imagery, and Reiki may all be useful in mitigating the pain of mucositis and may have the added benefit of promoting a sense of empowerment among children and families since some of these strategies can be learned and subsequently used without requiring the input of a healthcare professional.¹⁴⁴ The risk of infection is mitigated in part through cleansing the body and teeth regularly, sterilizing the point of entry of CVLs and implanted ports prior to use, prophylactic antibiotics, and, in some cases, use of granulocyte colony-stimulating factors to reduce the duration of neutropenia. Of note, lifestyle and behavioral recommendations for individuals with myelosuppression vary widely, and patients and families may receive conflicting information about what to eat, how to dress (e.g., whether to don a mask), whether school attendance is permitted, and whether intimate contact such as sexual intercourse should be avoided. These recommendations may have profound impacts on patients’ and families’ experience of the illness and quality of life. Interdisciplinary palliative care teams may be ideally positioned to elicit what is most important to the patient and family, identify the rationale for the recommendation or restriction, and facilitate negotiation toward shared understanding on how to proceed.

Unique Symptoms and Side-Effects Associated with Individual Chemotherapeutic Agents

Several commonly used chemotherapeutic medications have distinct side effects that require preventive medication administration and familiarity with the phenomenon. Examples of these include irinotecan-associated diarrhea, cutaneous reactions to tyrosine kinase inhibitors (e.g., sorafenib), and hemorrhagic cystitis associated with cyclophosphamide administration.⁶⁶ While pediatric oncologists and pediatric oncology nurses are typically highly knowledgeable about these side effects and their prevention, identification, and treatment, interdisciplinary palliative care teams should also develop familiarity with these symptoms and side effects to enable collaborative symptom management efforts.

Radiation Therapy

Though treatment sessions are typically brief, radiation therapy requires precise positioning to ensure that the dose is delivered to the intended body tissues. For young children, this may require sedation, which carries with it the burden of refraining from eating and drinking in the hours before radiation. In addition to the experience of traveling to and from the treatment center and remaining still for treatments, children receiving radiation frequently experience fatigue and may experience acute symptoms resulting from damage to healthy tissue in the radiation field, such as radiation-induced dermatitis, esophagitis, pneumonitis, or colitis. If hematopoietic marrow is in the radiation field, children may experience myelosuppression requiring transfusions. Children who receive chemotherapy after receiving radiation therapy may experience an inflammatory phenomenon known as “radiation recall,” which frequently manifests as dermatitis in the skin overlying previously irradiated areas. Radiation recall reactions can present in other tissues as well, including the lungs, gastrointestinal tract, and muscles.

The experience of stem cell transplantation is marked by prolonged hospitalization and relative isolation as well as high symptom burdens from mucositis, fevers, and other cutaneous and gastrointestinal symptoms.⁶⁶ Interprofessional palliative care consultation may be particularly helpful for patients who are undergoing stem cell transplantation.

Complications of immune-based therapies include cytokine release syndrome, which has been well-characterized in recipients of CAR-T cell therapy and can produce severe neurologic symptoms.¹⁴⁵ Aberrant inflammation such as pneumonitis, hepatitis, and hypophysitis has been characterized in patients receiving immune checkpoint inhibitors such as the anti-programmed death-1 agents nivolumab and pembrolizumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA 4) agent ipilimumab. As these and other novel, immune-based treatments become more common in the treatment of pediatric cancers, knowledge of immune-related complications will be important for members of interdisciplinary palliative care teams.

Targeted Therapies

Use of targeted therapies is likely to increase substantially over the next 5–10 years, especially as tumor profiling becomes more common.¹²⁶ Knowledge of the unique symptom profiles associated with each of these agents will become increasingly important to promote quality of life among children receiving these treatments. Rash is a particularly common side effect of many tyrosine kinase inhibitors, the most common class of targeted therapies used today in treating childhood cancers.¹⁴⁶

Surgery

Undergoing surgery for cancer may lead to marked, permanent body changes. For example, treatment of bone tumors may require either amputation of a limb or replacement of the limb with an internal prosthesis or allograft that renders the limb less functional.¹⁴⁷ Treatment of Wilms tumor typically requires complete removal of a kidney.^131,148 As noted earlier, operative management of CNS tumors may lead to compromised neurologic function. In the immediate postoperative period, acute pain is common and may require systemic and regional analgesic strategies. Amputation may lead to phantom limb pain, which may require multiple treatment modalities, such as pharmacologic treatments for neuropathic pain and integrative strategies such as mirror therapy.^{149,150,151,152} Diagnosing and managing phantom limb pain may be particularly challenging in younger children, who may not be able to express their symptoms verbally. All children who undergo operations to treat cancer may be at risk for dysesthesia at the site of surgical incision. Careful assessment and provision of multimodal strategies, including medical play, Reiki, and healing touch or massage may be helpful to alleviate distress associated with undergoing a surgical operation.^153,154,155

Special Considerations for Children with Advanced Cancer and Rare Cancers

While cancers are inherently life-threatening entities, advanced cancer tends to be associated with much higher risks of death.¹⁵⁶ An important role for interdisciplinary PPC teams is to facilitate communication that enables true understanding among the child with advanced cancer, the parent(s) or other important family figures in the child’s life, and the treating clinicians.¹² How families approach their child’s medical care in these circumstances will be shaped in part by what is communicated to them and in part by their own appraisal of the possibilities and tradeoffs.¹¹³ Importantly, parents and children may hold many hopes and expectations that may reflect complicated prognostic understanding: a hope for a long life and yet an expectation that death from progressive cancer is near.¹⁵⁷ Increasingly, the fields of pediatric oncology and PPC recognize that hopes for a long, healthy life and expectations for death from progressive cancer may coexist. Engaging in shared decision-making requires eliciting these frames of reference and making recommendations that reflect what is most important to the child and family.^110,157

For children facing advanced cancer and those with rare cancers, there may be no agreed upon standard treatment. In this setting, it is increasingly common for families to consider traveling to receive treatment at a highly specialized center that offers experimental treatments.¹¹³ Experimental treatments are sometimes referred to as “Phase I” or “Phase II” clinical trials.¹¹⁸ Phase I clinical trials are typically dose-finding studies in small numbers of individuals. The safety of the treatment under study may not be known, or there may be preliminary information about the safety of the treatment in adults.¹⁵⁸ Phase II clinical trials are slightly larger studies that are typically studying the apparent effect of the treatment as well as evaluating side effects of the treatment. Several groups have studied decision-making around participation in Phase I trials^159,160,161 and tumor profiling studies.^162,163 Among children enrolling in Phase I oncology clinical trials, median life expectancy is frequently 6 months or fewer.^164,165,166 As such, children enrolled on early-phase clinical trials are likely to be at particular risk for symptom distress related to progressive cancer and may benefit from discussions that allow for sharing of illness understanding, goals, and values. Collaboration between early therapeutics programs and interdisciplinary PPC teams can increase the likelihood of providing “total care” for children, particularly if trial participation requires travel away from the child’s home and community. Interdisciplinary PPC teams may be able to engage the child and family in discussions of what may lie ahead and provide anticipatory guidance based on discussions of the family’s goals and values.¹⁶⁷ Involvement in a Phase I trial should not preclude involvement with and care by palliative care clinicians. Palliative care clinicians/teams can manage symptoms and address distress felt by the child and the family.^113,168,169 There is evolving evidence that involvement in Phase I trials may be associated with delayed utilization of palliative care.¹⁷⁰ At the same time, interdisciplinary PPC teams may enhance the care of children with advanced cancer through collaboration with experimental therapeutics programs.^9,12,168 As such palliative care professionals should redouble their efforts to be involved at this stage in the disease care continuum.

Palliative Care at End of Life

Palliative care at end of life should be available to all children with cancer, but this goal has not yet been achieved in the United States. Certain areas of the United States and larger hospitals are more likely to provide palliative care.^171,172 Multiple professional organizations support an interdisciplinary approach to care for children at end of life that ensures attention to physical, psychosocial, and spiritual distress.^17,173

Acknowledging that a child is nearing the end of his or her life may be very difficult for parents, clinicians who may have cared for the child for prolonged periods, and for the children themselves.^167,174 If an interdisciplinary PPC team and/or primary palliative care delivered by an interdisciplinary pediatric oncology team has been a routine part of the care of the patient from diagnosis, with careful attention to symptom management and communication through all phases of the illness, then there is less likely to be a sense that palliative care stands in conflict with disease-directed care.^14,102 However, lack of provision of primary or specialty palliative care in early stages of cancer care means there are many patients for whom palliative care is introduced only near end of life.^175,176 Concurrent palliative care and disease-directed care is sometimes conceptualized as “blended” care. The role of palliative care may become more prominent as issues such as pain, existential distress, and consideration of the child’s legacy emerge more near the end of life. Ideally, open communication enables recognition that goals and values may evolve in step with changes in the child’s health.^{167,177,178,179}

In the United States, “hospice” typically refers to an insurance benefit, and hospice services are typically delivered in the home of the seriously ill individual, whether that individual is an adult or a child. Hospice houses do exist in North America, though the number of free-standing children’s hospice houses is small.¹⁸⁰ For children and young adults with serious illness, laws vary at the state level with regard to whether concurrent disease-directed care and hospice benefits can be received.¹⁸¹ Many children may live in communities where access to hospice services with pediatric expertise is limited.¹⁸² Hospice benefits also typically exclude certain treatments, such as the transfusion of blood products.¹⁸³ This may have implications for children with advanced cancer, and decision-making around the location of end-of-life care and whether to involve hospice services should be individualized to promote the child’s comfort and the family’s peace of mind and to enable care provision by clinicians with the skills to meet the child’s and family’s needs.¹⁸⁰

Addressing Symptoms Among Children with Cancer at End of Life

Children with cancer at end of life are at risk for distress from symptoms related to progressive cancer, such as bone pain, bowel obstruction, paralysis, dyspnea, and hemoptysis from metastatic lesions to the skeleton, abdomen, spinal cord, and chest.¹⁸⁴ Poly-symptomatology is common.^15,184 Bone pain is frequently encountered in children with metastatic cancer. Treatments for bone pain from metastatic disease include dexamethasone, hypofractionated radiation therapy, systemic opioids, nonsteroidal anti-inflammatory drugs, regional analgesia, and intravenous bisphosphonates.^185,186 Observable and predictably distressing end-of-life symptoms include altered breathing and handling of secretions, loss of neurologic function, and bleeding.^{15,184,187,188} Ideally, the approach to assessing and treating symptom distress in children at the end of their lives is holistic, incorporating both the best evidence for what helps as well as child and family preferences. Relevant preferences might include the location of care, the route by which a medication is administered, or the ability to engage in a treasured activity. For example, a celiac plexus block for pain arising from tumor infiltration into the liver or other upper abdominal viscera may enable a child to be relatively comfortable while reducing the need for systemic opioids that may be contributing to unwanted fatigue.¹⁸⁶ However, this may not be the optimal approach for a child whose family prefers not to travel to a tertiary care center that offers regional analgesia/anesthesia. Integrative treatments and attention to the child’s and family’s environment may be particularly helpful at end of life. Beyond treating symptom distress as it arises, anticipatory guidance to the child and family about the end-of-life period¹⁸⁹ and efforts to honor the child’s life and role in the family and community¹¹ are key components of palliative care. See Table 33.2 for descriptions of end-of-life symptoms and multimodal approaches to addressing symptom distress.

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Quality in Pediatric Palliative Care Program Development The Language of Pediatric Palliative Care Relationships with Children and Ensuring Their Voices in Decision-Making Advanced Heart Disease Children’s Voices: The Experience of Patients and Their Siblings

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