Palliative care

Core elements of palliative care should be provided by all clinicians across all specialties and levels of training. In the U.S., the National Coalition for Hospice and Palliative Care led the National Consensus Project for Quality Palliative Care, which created Clinical Practice Guidelines for Quality Palliative Care, currently in its fourth edition (20). Within their blueprint are eight domains, each citing their recommendations for essential palliative care skills needed by all clinicians (Table 1).

Table 1. National Consensus Project for Quality Palliative Care and National Coalition for Hospice and Palliative Care: Essential Palliative Care Skills Needed by All Clinicians

Domain 1: Structure and processes of care
	Clinicians and staff working in all care settings benefit from an understanding of the value of palliative care, as well as an overview of palliative care principles and practices. Clinicians caring for the seriously ill have sufficient training and experience to complete palliative assessments and address common sources of suffering. The palliative assessment addresses the essential elements of the domains of palliative care but may not be as in-depth as the assessment a palliative care team would provide.
Domain 2: Physical aspects of care
	All clinicians need expertise in the assessment of patient symptom burden, functional status, and quality of life and in the development of a palliative treatment plan that is consistent with patient and family needs and preferences. Clinicians need the skills to identify and treat symptoms associated with serious illness and related treatments, including pain, nausea, constipation, dyspnea, fatigue, and agitation.
Domain 3: Psychological and psychiatric aspects of care
	Clinicians in all care settings can help ease the burden of a serious illness by screening for, assessing, and managing psychological or psychiatric concerns that may occur. Specific knowledge and skills needed include the identification and treatment of basic psychological conditions, such as depression; an understanding of both pharmacological and nonpharmacological interventions; and effective patient and family education strategies specific to the mental health diagnosis in the context of serious illness. In addition, clinicians benefit from an understanding of the psychological reactions to serious illness, grief, and loss.
Domain 4: Social aspects of care
	All clinicians can learn how to perform and integrate social assessments into the care of seriously ill patients to identify patient strengths; availability of caregiving and social support; access to reliable food, housing, and transportation; the need for adaptive equipment; and other social or environmental issues. Understanding the social consequences of a serious illness enables the clinician to support the ongoing practical and social needs, including the identification of patient and family coping strategies. In addition, identifying and addressing indicators of caregiver isolation and burnout are critically important in achieving patient and family goals.
Domain 5: Spiritual, religious, and existential aspects of care
	The process and tools needed to conduct a spiritual screening and assessment for spiritual distress and spiritual needs can be learned by all clinicians. In addition, clinicians can learn to identify and utilize resources available in the team, within the patient and family, or in the community or care setting to ensure that spiritual needs are promptly addressed.
Domain 6: Cultural aspects of care
	Clinicians can acquire knowledge and skills to recognize how culture (values; beliefs; gender identity and expression; physical appearance; abilities; social class; religion; race; ethnicity; traditions related to health, illness, caregiver roles, decision-making) influences patient and family decision-making and their approach to illness; pain; psychological, social, and spiritual factors; and grief, dying, death, and bereavement. Clinicians incorporate palliative care specialists and cultural representatives into the care plan to navigate cultural nuances, as needed.
Domain 7: Care of the patient nearing the end of life
	Clinicians in all care settings who learn the hospice eligibility criteria can make timely referrals to hospice. In addition, clinicians can improve patient care by learning how to assess and manage physical symptoms common among patients nearing the end of life. All clinicians must have the knowledge and skills to talk to patients and families about dying.
Domain 8: Ethical and legal aspects of care
	Many clinicians have studied medical ethics and understand the ethical principles most applicable at the end of life. All clinicians working with seriously ill patients benefit from learning about advance care planning and common scenarios that cause ethical and legal conflicts. In addition, all clinicians know how to access legal experts, ethicists, or ethics committees, as well as specialist-level palliative care teams, to ensure the provision of high-quality care in alignment with patient goals.

Primary palliative care

Overview. Primary palliative care simply refers to the delivery of essential palliative care to any patient with a serious illness by clinicians without subspecialty training in palliative medicine. The American Society for Clinical Oncology (ASCO) Practice Guideline Update on the Integration of Palliative Care into Standard Oncology Care, based on an expert panel using evidence from nine randomized controlled trials, one quasi-experimental trial, and secondary analyses of five randomized controlled trials, cites its recommendation for the essential components of palliative care for people with advanced cancer (Table 2).

Table 2. Essential Components of Palliative Care

	• Rapport and relationship building with the patient and family caregivers
	• Symptom, distress, and functional status management (eg, pain, dyspnea, fatigue, sleep disturbance, mood, nausea, constipation)
	• Exploration of understanding and education about illness and prognosis
	• Clarification of treatment goals
	• Assessment and support of coping needs
	• Assistance with medical decision-making
	• Coordination with other care providers
	• Provision of referrals to other care providers, as indicated

All clinicians should be experts in the assessment and management of common physical symptoms, such as pain, nausea, fatigue, anxiety, and depression, and should have excellent communication skills requisite to initiating and guiding patients and their caregivers through iterative discussions about illness understanding, prognosis, goals of care, and adjusting care plans accordingly. All clinicians should be highly competent in providing palliative care, not only because the demand for specialty palliative care clinicians far exceeds their availability, but because patients significantly benefit from receiving such care and guidance from their treating clinicians with whom they already have formed a strong relationship. This is particularly true for people with CNS cancer who receive care from multiple specialists and rely on their guidance about symptom management, psychosocial needs, and addressing advanced care planning and goals of care, especially as their disease progresses. Of note, supportive care largely arose out of the need to provide adults receiving cancer treatment with management of treatment- and disease-related toxicities and symptoms. Although known to be used in lieu of palliative care due to the concerns of clinicians, patients, and their families conflating specialty palliative care with hospice care, supportive care programs may focus largely on symptom and toxicity management without specialty training or certification in palliative medicine, or they may practice within an interdisciplinary team approach and, therefore, are not equivalent to specialty palliative care.

Symptom management. Neuro-oncology clinicians should regularly monitor their patients for new and worsening symptoms and refer patients with refractory or complex symptoms to specialty palliative care. Symptom management is imperative as uncontrolled symptoms worsen quality of life and survival. Instruments have been developed to enable patients to self-report their symptoms and merit wider use. Although clinical factors, such as tumor location, stage, age, functional status, and comorbidities, impact individual symptom burden and neurologic dysfunction, the following addresses common physical symptoms in the adult CNS cancer population and their management.

Fatigue is the most common symptom among all people with cancer, including those with CNS cancer. Its etiology has been attributed to multiple factors: cancer itself, the associated inflammatory cytokines, chemotherapy, radiation therapy, acute and chronic stress, psychological and social distress, medication side effects, sleep disturbance, and changes in activity level, among others (01). The fatigue people experience can be unlike anything they have ever felt. It can be quite debilitating and severely limit their daily functioning. The first step in its management is to assess and address as many of these contributing factors as possible as no medications to date have been found to effectively alleviate fatigue. As in the general cancer patient population, the most efficacious interventions may be energy conservation during intensive treatment, then adding back exercise through increasing daily activity and integrating an exercise regimen, such as was prescribed during physical therapy. However, this may be challenging for those who have neurocognitive dysfunction or significant paresis. Identifying and addressing distress using supportive and psychosocial care resources are key. Optimizing the timing and dosing of supportive medications based on their side effect profiles, such as taking dexamethasone before 3 PM and taking sedating antiemetics in the evening or at bedtime, can help achieve restorative sleep.

Headaches are highly prevalent among people with CNS cancer. Headaches may be worse at initial diagnosis, during radiotherapy, at disease recurrence or progression, and at the end of life, though they may start or worsen at any time through the illness trajectory. A cardinal sign of increased intracranial pressure, hemorrhage, or leptomeningeal disease, headaches can have various other etiologies, such as post-craniotomy muscle spasms or neuralgia, temporomandibular joint dysfunction, muscle tension, referred pain from the skull base, migraine, medication side effects, dehydration, sleep disturbances, carbon dioxide retention, and NSAID or caffeine overuse. Chronic headache management in neuro-oncology does not significantly differ from general neurology practice other than more frequently prescribing dexamethasone to manage vasogenic edema as the tumor burden increases (21). Migraine prophylaxis with gabapentin, pregabalin, duloxetine, or a tricyclic antidepressant is advised with a reasonable abortive regimen (NSAIDs, antiemetic, hydration, etc.). When choosing a prophylactic medication, it is particularly important to consider its entire effect profile to leverage the use of those advantageous to the patient (choosing valproic acid if seizures and mood lability are comorbid symptoms) and to defer on those likely to cause cognitive dysfunction or sedation. Judicious use of dexamethasone is recommended given its myriad of untoward side effects (07).

Nausea may be related to the disease process, especially if advanced, but it is more commonly a side effect of tumor-directed treatment or medications. One of the most feared and common adverse effects of cancer treatment, chemotherapy-induced nausea and vomiting (CINV), can cause significant worsening of patients’ quality of life. The American Society for Clinical Oncology’s antiemetic guideline provides recommendations on anticancer agent and radiotherapy emetogenicity and respective antiemetic regimens as well as adjunctive drugs, cannabinoids, complementary and alternative therapies, and breakthrough and anticipatory nausea and vomiting (14). Of note, temozolomide’s emetogenic potential is dose dependent; doses up to 75 mg/m2 have low, and doses more than 75 mg/m2 have moderate, emetogenic potential (22). Constipation is a well-recognized side effect of both 5-HT3 antagonists and temozolomide; severe constipation may warrant using an antiemetic other than a 5-HT3 antagonist, such as dopamine antagonists and NK1 receptor antagonists. Olanzapine has randomized controlled trial data supporting its use in preventing CINV in the general cancer population (13). However, its use within neuro-oncology is constrained by its potential to exacerbate confusion and sedation.

Psychological distress management. Receiving a diagnosis of CNS cancer is a major life event. People have valid fears about treatment and their prognosis as well as the implications of their illness on nearly every aspect of their life and that of their family members. Anxiety, depressive symptoms, grief reaction, adjustment disorder, major depression, and posttraumatic stress disorders are highly prevalent among people with CNS cancer. In addition, neuropsychiatric effects secondary to direct CNS involvement by cancer and its treatment are common. These cumulative neuropsychological factors have notable detrimental effects on functional status, symptom burden, symptom interference with daily activities, and health-related quality of life for those living with CNS cancer. Patients should be regularly screened for distress along with physical symptoms, and distress should be appropriately assessed and managed when present.

No high-level evidence demonstrating benefit of any specific psychiatric medication for depression or anxiety in the CNS tumor patient population exists; therefore, treatment should follow standard clinical guidelines. Notable specific drug-drug and drug-cancer interactions and contraindications have been thoroughly reviewed elsewhere (18; 24; Yap et al 2011; 06; 12; 23). A selective serotonin or norepinephrine reuptake inhibitor, such as citalopram, escitalopram, or sertraline, may be considered in addition to facilitating the receipt of mental health services, stopping medications with untoward mood effects, optimizing sleep, and encouraging exercise, as feasible. People with CNS cancer and their close others should be encouraged early after diagnosis to establish care with therapists or counselors who are specifically trained in serious illness and grief. Support groups available locally, in-person, or virtually through national patient advocacy organizations, such as the American Brain Tumor Association, may also be very helpful for patients and caregivers. For those with high psychological distress or high or complex symptom burdens, early referral to specialty palliative care for consultation is recommended.

Advanced care planning and discussing prognosis and goals of care. Strong communication skills are crucial for all clinicians caring for people with CNS cancer given the many sensitive and difficult conversations that need to be held throughout the course of the illness. There are multiple discussions that must be conducted with great transparency, directness, and compassion, such as breaking the news of the diagnosis, deciding on treatment options, designating a durable healthcare power of attorney, and iterative discussions about prognosis and goals of care, especially when the disease has progressed. Although the involvement and assistance of specialist palliative care may be helpful or needed at certain junctures, it is critically important that primary teams have high-quality communication with patients and their caregivers. Primary teams have the advantage of a strong relationship built over time with the patient, which also allows for gaining a sense of patients’ values, hopes, and priorities, in addition to knowing their disease trajectory and the anticipated course. Learning how to empathetically respond to emotion, deliver serious news, and discuss transitions in goals of care are requisite skills for all clinicians.

Receiving a CNS cancer diagnosis is overwhelming and extremely distressing for people and their loved ones. Initial visits with the primary team often focus on delivering important medical information about the tumor, discussing treatment options, and deciding on a treatment plan. In this time of distress and anxiety, people and their caregivers seek information on prognosis and what to expect across the disease trajectory. Conversations about these topics should start by first asking how much information the patient and their family members prefer to receive; some may be detail-oriented and want to know lots of information, and others might prefer to only receive specific information. Further, caregivers often have different informational needs than patients. For those who want to discuss prognosis in detail, providing prognosis in time ranges (eg, years, months to years, weeks to months, days to weeks, hours to days) and setting the expectation that discussions about prognosis are an ongoing dialogue that will be readdressed as events necessitate are recommended. People and their caregivers should anticipate revisiting this topic during future visits, and clinicians should feel comfortable openly addressing the re-evaluation of prognosis when there is radiographic disease reoccurrence or progression, clinical progression (worsening neurologic or functional status), or significant disease or treatment complications.

When discussing advanced care plans and goals of care, it is important to first elicit concerns and respond empathetically to foster emotional processing and then to address concerns with appropriate information. Next, elicit goals, such as attending a wedding or reconciling an important relationship, and values by asking open-ended questions about what their biggest goals are and what in their life is most valuable to them right now. Next, clinicians can maintain hope in balance with reality by inquiring about what they are hoping for and providing honest yet kind and compassionate responses by acknowledging any unachievable hopes and hopes that could be fulfilled, such as relieving a symptom or spending time with someone, and what care is available to provide emotional and practical support, symptom control, preservation of autonomy, and dignity. Encourage people to state their wishes for their care, and use this opportunity to explain that there is care available no matter what happens. This avoids the false dichotomy that unless cancer-directed treatment is given, there is no care available and that they face abandonment and have no healthcare options if they do not receive cancer treatment, which is untrue. Furthermore, this is an optimal time to address the potential to refer to specialty palliative care in the case of any significant quality-of-life concerns, high or complex symptom burden, or high support needs and to explain that hospice care is end of life care that focuses on quality of life and that maximizing symptom management is available when tumor-directed care is no longer desired or feasible. In the context of this discussion, clinicians should then ask what the person would find acceptable or unacceptable in terms of their quality of life by asking whether there is a degree of disability they believe they could not cope with? Are there symptoms that they would find tolerable (eg, severe pain, unrelenting nausea)? How do they feel about prolonged hospitalization, or a nursing facility stay? Would they accept artificial feeding for a short period of time, or indefinitely? What is their understanding of resuscitation if they die in the hospital?

The modern conceptualizing of advanced care planning includes caregivers hearing the patients’ responses as it is likely the patient will lack decision-making capacity late in their disease trajectory, and the caregiver will be asked to relay their understanding of the patient’s wishes. Also, patients should designate a medical/healthcare durable power of attorney (DPOA) early in the course of the disease; the DPOA may not be the caregiver. If no DPOA is designated, the state law indicates who the legal next of kin is, usually starting with a legal spouse or parent. Several toolkits and guides exist that can guide people and their medical DPOA to have advanced care planning conversations, including The Conversation Project, Five Wishes, etc.

In summary, the basic tenets of communication in delivering primary palliative care in neuro-oncology practice include the following:

A. Eliciting patients’ preferences around receiving information.

B. Transparent, compassionate, high-quality communication about prognosis that provides the needed guidance patients and their caregivers seek.

C. Iteratively eliciting patients’ values, hopes, and goals as well as acceptable limits for medical interventions.

D. Ensuring the patient has identified and legally established a durable medical power of attorney early in the course of the disease who knows them well and can be part of the conversations about what they would want and not want in advanced stages of illness and at the end of life.

Specialty palliative care

Overview. Specialty palliative care is defined as such by the fact that it is delivered by board-certified or subspecialty-trained clinicians, or those with significant clinical experience and expertise. Specialty palliative care employs an interdisciplinary practice model, and its team may consist of certified physicians, advanced practice providers, pharmacists, nurses, social workers, chaplains, counselors, massage therapists, physical therapists, and/or nutritionists. Specialty palliative care utilizes the “total care” concept for individuals and their family members; the total care concept refers to comprehensive and ongoing assessments and interventions addressing not only the physical domain, but also psychological, social-cultural, and spiritual-existential domains. To achieve this, the interdisciplinary team conducts a comprehensive assessment of the patient and family to develop an individualized care plan. Included is the patient’s and family’s understanding of the illness; their goals of care; communication and treatment preferences; a review of any advance directives; determination of the patient’s decision-making capacity and identification of who is the durable healthcare power of attorney or surrogate decision-maker; patient and family emotional and spiritual concerns; and needs related to grief, loss, and bereavement. Specialty palliative care providers are most effective when they can collaborate and coordinate care with the primary team and any consultants. There are multiple models of specialty palliative care delivery that are beyond the scope of this article (15). Specialty palliative care is typically delivered within the inpatient setting or in outpatient clinics and less frequently in private residences, assisted living facilities, or long-term care hospitals, among other settings.

When to refer to specialty palliative care. Evidence from randomized controlled trials support early referrals to specialty palliative care for people with advanced stage malignancies, such as those with CNS metastasis or life-limiting cancer types with life expectancies of 6 to 24 months. Additionally, given the acuity of the illness course and the high risk for specialty palliative care needs, their caregivers benefit from the early establishment of a relationship with the specialty palliative care team. These specialty care needs include but are not limited to the management of refractory physical symptoms or high, complex symptom burdens; severe psychosocial distress; or complicated family dynamics. The Center to Advance Palliative Care (CAPC) recommends the presence of any of the following clinical features as palliative care referral criteria for people with cancer: (1) metastatic or locally advanced cancer that progresses despite treatment; (2) brain metastasis, spinal cord compression, or neoplastic meningitis; (3) any recurrent brain neoplasm; (4) Karnofsky Performance Scale (KPS) score of less than 50 or ECOG scale score of greater than 30 (indicating very poor functional status and ambulatory ≤ 50%); (5) malignant hypercalcemia; (6) progressive pleural, peritoneal, or pericardial effusions (03). Moreover, international consensus guidelines (17) and National Comprehensive Cancer Network criteria (19), as applicable to patients with brain or cerebrospinal fluid metastasis, also recommend outpatient referral to specialty palliative care at any time after diagnosis. Additionally, using criteria from CAPC, patients with malignant brain tumors (ie, metastatic or locally advanced incurable cancer) may meet criteria for at least an initial specialty palliative care assessment during their hospitalization, but they may not necessarily require daily rounding (27).

Specialty palliative care is not ubiquitously available and remains a finite resource. The concept of “timely” versus “early” specialty palliative care has been introduced. “Timely” specialty palliative care is a way to apply a systematic process to identify patients with more palliative care needs and refer them to specialty palliative care based on standardized criteria (16). This approach may allow for a more dynamic person-centered approach to specialty palliative care referral and hopefully maximize the available resources.

Hospice care

Hospice is the best approach for the management of end of life needs and is an important care option for people with CNS cancer given the poor prognosis of many. However, up to a quarter of Medicare beneficiaries with primary malignant brain tumors and a third of Medicare beneficiaries with secondary malignant brain tumors never enrolled in hospice or enrolled late (within 1 to 3 days of death) (11). Neuro-oncologists, as referring physicians to hospice, should have a general understanding of the provision of hospice care and its benefits. Although hospice is essentially highly specialized palliative care, it is an entirely different healthcare entity from palliative care with respect to eligibility and service delivery. Understanding these differences is important for optimal timing of referral and for counseling patients and their family members.

In the U.S., the Medicare hospice model sets the standard followed by most insurance companies in their reimbursement for hospice care and, thus, will be discussed here (04). The provision of hospice care provides specialized, interdisciplinary care focused on symptom management and optimizing quality of life. Although hospice and palliative medicine both leverage interdisciplinary care to relieve suffering and promote quality of life, hospice is exclusively for people with a prognosis of 6 months or less, whereas palliative care involvement is appropriate at any stage of serious illness and concurrent with curative or life-prolonging treatment. Hospice eligibility based on Medicare insurance coverage depends on two physicians’ certifications that the individual has a terminal illness and a life expectancy of 6 months or less if the illness runs its normal course. Additionally, the individual must be willing to forego receiving disease-directed treatment. Medicare stipulates that individuals with cancer are hospice eligible if they have impaired functional status (Karnofsky Performance Scale score < 70 or Palliative Performance Score of < 70%, meaning that they are unable to carry out normal work or activity) and require assistance with at least two activities of daily living, in addition to having either distant metastases or progression despite therapy (05). However, as noted under the cancer diagnoses section of determining terminal status, CMS often extends hospice eligibility to people diagnosed with brain cancer and other certain cancers with poor prognoses based on the diagnosis alone, without fulfilling other criteria.

Hospice core services include physician, nursing, medical, social, and counseling (bereavement for up to 12 or 13 months, spiritual, and dietary) services. The interdisciplinary team includes a hospice medical director, hospice nurse(s), social worker(s), and chaplain(s)/spiritual counselor(s) as well as any non-core service providers, such as hospice aides and physical, occupational, and speech therapists, as indicated for symptom management. Hospice does not provide 24-hour in-person nursing care as is commonly assumed, but it does provide nursing support by phone 24/7, with physician support available to the nurse 24/7. Therefore, caregiver involvement in the provision of hospice care delivered in a private residence or an assisted living facility is a prerequisite unless a continuous or inpatient care need arises that meets specific criteria warranting constant nursing care. Although the majority of hospice enrollees receive hospice services in a private residence, dying at home is one of the key aspects of hospice that may be desired by individuals and their family members. Hospice services can also be delivered in a nursing home or assisted living facility, among other settings. Also, hospice provides 100% medical supplies and durable medical equipment coverage and assumes all medication prescribing, which is focused on symptom management.

Benefits of hospice for patients include spending more time at home and with family and friends, improved symptom control, and receiving much needed psychosocial and spiritual support (10). Benefits for caregivers include better fulfillment of informational needs and improved bereavement and coping (10). Timely referral when appropriate is necessary for these benefits to be actualized. Above and beyond hospice eligibility criteria, the most important factor is whether the individual’s goals align with comfort-focused care and not receiving cancer-directed treatment. A potential explanation for the infrequent and late hospice enrollment is that primary teams do not discuss care options outside of cancer-directed treatment with their patients until very late in the disease course. For some patients, they may prefer to forego (further) tumor-directed treatment if the options are frankly discussed. Table 3 provides guidance on how to structure conversations around shifting the focus from managing the disease to focusing on quality of life with hospice support (08). Clinicians should be prepared to address feelings of abandonment, avoid phrases like “There is nothing more we can do,” and, if possible, provide a mechanism for ongoing contact with the patient and their caregiver following hospice referral (02). Emphasizing alignment regardless of their goals and wishes is also important. When needed, early referral to specialty palliative care may also help to facilitate these conversations in a more timely manner.

Table 3. How To Structure a Goals of Care Conversation That May Include Discussion of Hospice Using The “Reframe, Explore, Map (Out Goals), Align, Plan (REMAP)” Tool

The steps of REMAP are to:
	(1) Reframe: provide information, such as progression of disease, to couch the conversation;
	(2) Explore: explore the patient’s and/or family’s emotions about the information;
	(3) Map: without addressing specific choices such as hospice enrollment, inquire about the patient’s and/or family’s broad goals in light of the new information;
	(4) Align: reflect back what the clinician has understood about the patient’s goals; and
	(5) Plan: recommend a care plan(s) aligned with the stated goals.

Future directions

As the field of specialty palliative care continues to grow and evolve, palliative medicine clinicians with primary training in diverse fields of medicine are becoming certified and are expanding their practice into more medical specialties, bringing their clinical expertise to a wider scope of people living with disease. Among this trend are neurology-trained palliative and hospice medicine clinicians creating the emerging specialty of neuropalliative care (26). The American Academy of Neurology (AAN) has published a position statement that specifically highlights the role of neuropalliative care in the subspecialty of neuro-oncology (25). The position statement stresses the following (25):

[P]atients diagnosed with low-grade and malignant brain tumors want prognostic information even though this can be difficult and unreliable with molecular markers changing histologic diagnoses and new therapies becoming available. Caregiver and psychosocial support are essential given the high rates of distress and burnout in caregivers of patients with primary CNS malignancies, compounded by frequent loss of language and cognitive abilities on the part of the patient, coupled with common cortical neglect syndromes that can lead to significant family conflict. Communication challenges include when to begin goals of care discussions, how to support patients and caregivers during decision making, and how to increase familiarity with potential behavioral and communication problems in the future.

Curricula to educate neurologists across all subspecialties and levels of training about palliative and hospice care, as well as to teach the requisite communication skills, are being designed and implemented to meet these needs (09).