43 Integration of Therapeutic and Palliative Care in Pediatric Oncology

Deborah A. Lafond, Brian R. Rood, Shana S. Jacobs, Gregory H. Reaman

If we listen closely, children who are dying, and their families, will tell us everything we need to know to care for them: they want to be loved, to be cared for and cared about, to know that their lives have meaning and purpose, to be remembered as the special people they are. Most of all, they want the people caring for them to appreciate and celebrate their lives.

The improved outcome for children with cancer is a success story of modern medicine and one of several examples from the past century of previously untreatable diseases for which effective treatments have now been identified. These treatments have been identified through successive series of randomized controlled trials resulting in a strong evidence base, which has translated into progressively improving standards of care. This success has been accomplished through the integration of clinical research and clinical care of pediatric cancer patients primarily in academic settings, which has been linked tightly within a national clinical trials infrastructure.

The overall five-year survival rates for children younger than 15 years with cancer have increased from less than 60% from 1975 to 1978 to more than 80% from 1999 to 2002.¹ Most notable have been improvements in 5-year survival rates for children with acute lymphoblastic leukemia (ALL) now approaching 90%; non-Hodgkin lymphoma similarly approaching 90%; and Wilm tumor, exceeding 90% since the late 1980s. Overall 5-year survival rates most recently reported by the Surveillance Epidemiology and End Results (SEER) Program of the National Cancer Institute approximate 70% overall for primary central nervous system (CNS) tumors and approach 65% to 75% for sarcomas of soft tissue and bone.

Given the profound heterogeneity in diagnosis, clinical presentation, biologic behavior and outcome in primary tumors of the CNS, survival rates for individual tumor types vary considerably. Similarly, for soft-tissue and bone sarcomas, the likelihood of prolonged survival is highly linked to the initial extent of disease. Therefore, reported overall 5-year survival rates should not be considered predictive of cure for all patients with these diseases.² For example, whereas 5-year survival rates for infants with neuroblastoma are extremely favorable and have been relatively stable at 90% to 95% since the early 1980s, until very recently, improvements in older patients with unfavorable biologic features have not shown the same improvement with current five-year survival rates now approaching only 50%.³

As survival rates differ depending upon the cancer diagnosis, trajectories of illness and patterns of death also differ. For most pediatric oncology diseases, the trajectory from diagnosis to long-term survival or death is characterized by periods of relative stability interspersed with periods of decline or crisis. Symptoms and the trajectory of illness are dependent upon the underlying malignancy.⁴ Leukemias are the most common type of childhood cancer and tumors of the central nervous system are the most frequent type of solid tumor in children.¹ However, specific types of these common childhood malignancies have unique trajectories of illness. For example, a child diagnosed with a brain stem glioma has a poor chance of long-term survival and often presents with multiple neurological deficits, however, a period of symptom improvement may occur with treatment. Unfortunately this period of improvement may be short-lived and is likely followed by exacerbation of symptoms and ultimately death from progressive disease. The timeline from diagnosis to death may be as short as a few months to a couple of years. In contrast, a child with leukemia may initially respond well to treatment and remain in remission. However, if the leukemia returns then the course of illness may be characterized by multiple treatment protocols followed by periods of remission, but may still ultimately end in death due to progressive disease over a period of years. As a further contrast, children undergoing stem cell transplant for a variety of childhood malignancies may die relatively quickly in the trajectory of illness because of sepsis or other side effects of treatment. The palliative care practitioner should be familiar with the symptoms and disease trajectory of the underlying malignancy in order to provide recommendations for effective symptom management.

Despite the impressive record of success in improving survival outcomes, cancer remains the leading cause of death from disease in the pediatric age group. Even cancers such as ALL with high cure rates still account for a significant number of deaths from cancer. Because ALL is the most common cancer of childhood, death related to treatment failure and treatment-related complications in acute leukemia contribute the most to cancer-related mortality statistics in children.¹

For decades the focus of clinical investigation, translating to standards of clinical care for childhood cancer, has centered on cure. Significant sequelae and late effects associated with the various diagnoses and successful anti-cancer treatments are now well recognized and have become a major area of research. More recently, while not diminishing the importance of cure and quality of survivorship, appropriate attention and clinical research focus on the quality of life during the entirety of the cancer experience has begun to assume a more prominent position, with corresponding attention paid to symptom management using pharmacologic as well as behavioral approaches for children with cancer.

Whereas the concepts of cure and palliation have historically been somewhat competing objectives, recognition that palliation should not be considered exclusively applicable to end of life is paramount to the childhood cancer journey. Understanding and evaluating interventions to address physical, psychological, social, educational, and spiritual needs in children with cancer from the time of diagnosis onward must be considered.⁵

This chapter will address the needs of pediatric cancer patients and their families as well as the requirement for an interdisciplinary approach to providing appropriate palliative care. In addition, we will discuss opportunities for and challenges to the effective integration of appropriate palliative care with both curative disease management and investigational therapies where the potential for clinical benefit may be considerably smaller. A particular emphasis will be on the integration of palliation and symptom management with curative therapy that would appear warranted in patients with specific diagnoses where the prognosis for favorable outcome with current therapy approaches is less optimal. However, approaching every patient and family faced with a potentially life-threatening illness with a recognition of the need to address palliative elements would benefit patients, families, and providers in guiding those important considerations and decisions involving cancer-directed care, quality of life, symptom management, and, if necessary, end of life care and bereavement.

The Need for Palliative Care Services in Pediatric Oncology

Approximately 2300 pediatric patients die of cancer in the United States each year.^6,⁷ Most of these patients die of recurrent or progressive disease, and most have been battling their cancers for months to years. For pediatric patients with cancer, cure-directed therapy and palliative care needs go hand in hand from the moment of diagnosis throughout therapy. All patients, even patients with a high likelihood of cure, are likely to suffer multiple symptoms from the point of diagnosis onward. These symptoms include physical side effects from chemotherapy, such as nausea and vomiting, mouth sores and pain, and fevers and hospitalizations, as well as spiritual and psychological malaise. On the other side of the spectrum, many patients who reach the point where there are no known cures for their cancers may continue chemotherapy either as part of an experimental protocol or for palliative purposes.⁸ Therefore, unlike many other disciplines, pediatric oncology patients are often in need of simultaneous cure-directed and palliative therapies. Effective palliative care services can ease suffering in children with cancer, allowing more hospice referrals and home death, less pain and dyspnea, and better preparation for death compared to families who did not receive palliative care services.⁹

Despite the clear relationship between palliative care and cancer care for children, many pediatric cancer patients do not receive palliative care services. A survey of institutions that are members of the Children’s Oncology Group revealed that only 58% have palliative care services available for their patients.¹⁰ Children with cancer are often receiving intense therapies for extended periods, sometimes years. As a result, they form strong relationships with their oncology team. These relationships can be a great asset as patients and families feel supported by members of the healthcare team who care a great deal about them. However, at times the intensity of the relationship may interfere with a patient’s ability to get appropriate palliative or end of life care. The healthcare team’s members may feel they have failed the patient if cure cannot be offered and may therefore push for cure-directed therapy over comfort care even when the chance of cure is very small.¹¹ In addition, the healthcare team may overestimate the patients’ prognosis in an effort to keep the patient and family hopeful, which affects the families’ ability to make informed decisions about care.⁶ One study showed that physicians understand that patients have no realistic chance of cure a mean of 101 days before the parents’ recognition.¹² Despite the clinicians’ worry, an accurate portrayal of prognosis, even bad, makes families more hopeful, not less.¹³ Even when parents find the news upsetting, they still derive benefit from hearing the prognosis.¹⁴ Additionally, families who know that a child is dying are more likely to spend their end of life period pain-free at home.¹⁵

Common symptoms of children with advanced cancers

Effective pain and symptom management for children with advanced cancers is dependent upon a sound knowledge of these symptoms.¹⁶ Cancer is not unique in the palliative care spectrum in that children often experience multiple symptoms of varying intensities throughout the trajectory of illness. Few studies to date have addressed symptoms or the quality of life experienced by children with advanced cancer or who are dying of cancer.¹⁷ Of particular interest are CNS tumors, which are a life-threatening illness with high morbidity and the second-leading cause of cancer deaths in children.¹⁸ Children with brain tumors experience more severe symptom distress and treatment-related distress than children with other cancers.¹⁹ A variety of symptoms are reported in pediatric patients with advanced cancer. The underlying malignancy impacts the type and severity of symptom distress, however the most common symptoms include pain, fatigue, dyspnea, nausea and vomiting, anxiety, and weight loss and/or cachexia.^16,²⁰^–²³ In addition to these commonly experienced symptoms, children with hematologic malignancies may experience increased bleeding and coagulopathies and children with solid tumors may experience other symptoms related to compression of vital structures by tumor, such as spinal cord compression. An analysis of 164 children with advanced cancers in the last month of life noted that many symptoms are under-recognized and symptoms vary significantly based on the underlying malignancy⁴ (Table 43-1). Palliative care practitioners must have knowledge of the symptoms associated with the specific pediatric malignancies in order to adequately address symptom distress. Symptom distress is significant for children with advanced cancers and affects their quality of life. Healthcare must not merely be vested in tumor outcomes but must instead address quality of life and functional status outcomes.