Comprehensive Patient Assessment

A comprehensive palliative care assessment is essential to the management of cancer patients. Uncontrolled symptoms such as pain and fatigue often result in worsening well-being, psychological symptoms, and ultimately quality of life for patients and their families. Symptom assessment tools are widely available in the field of palliative care to ensure timely screening and diagnosis of symptoms and syndromes, resulting in their timely management. The palliative care domains important to assess are physical symptoms, performance status; psychological/psychiatric symptoms; social and economic needs of the patient, family, caregiver; and religious, spiritual, and existential issues.

One effective tool to screen for palliative care needs is the National Comprehensive Cancer Network (NCCN) distress thermometer which is effective and well validated to evaluate untreated distress in the physical, social, or psychological domains. Patients can rate distress from 0 to 10 and designate particular areas of concern that may merit a palliative care consultation.

The Edmonton Symptom Assessment System (ESAS) and the Memorial Symptom Assessment Scale (MSAS) are reliable, validated tools used to assess physical symptoms in the clinical setting. The ESAS assesses 10 common symptoms (pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, feeling of well-being, and other symptoms) over the past 24 hours. Other less commonly reported symptoms such as pruritus, xerostomia, hiccups, and muscle spasms are also inquired about. Performance status tools used in palliative care include the Karnofsky Performance Status (KPS), Eastern Cooperative Oncology Group (EGOG), and Palliative Performance Scale (PPS). Both the KPS and the ECOG performance status have been validated in patients with cancer and correlate with survival. For example, a KPS of 40 or/and ECOG score of greater than 3 are associated with survival of 3 months or less.

Palliative care clinicians also use a multitude of assessment tools to assess psychological, psychiatric, and cognitive domains; these include ESAS, MDAS (Memorial Delirium Assessment Scale), and PHQ-9. There are also assessment tools used to assess the spiritual domain; these include FICA (faith, importance, community, action), HOPE (sources of hope, organized religion, personal spirituality and practices, effects on medical care, and end-of-life issues), and SPIRIT (spiritual belief system, personal spirituality, integration with a spiritual community, ritualized practices and restrictions, implications for medical care, and terminal event planning). Only FICA has been validated.

Pain Management

Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue injury or damage. The intensity of pain varies with the degree of injury, disease, or emotional impact.” Pain is one of the main symptoms experienced by cancer patients during both curative and palliative therapy. Numerous national and international surveys have found that 30%–50% of cancer patients in active therapy and as many as 60%–90% with advanced disease have pain. Although pain management and the alleviation of suffering are core clinical competencies for all clinicians treating seriously ill patients, in reality pain is frequently undertreated. There are many barriers to pain management which include physicians’ lack of knowledge, lack of availability of opioid medications, governmental regulations, physicians’ fear of regulations, diversion of medications, and fear of addiction.

In 2016 the American Society of Clinical Oncology (ASCO) issued a statement reflecting that cancer patients should be largely exempt from measures taken to halt the epidemic of opioid abuse and addiction, on the grounds that cancer patients are a “special population.” Their statement also reflected that cancer patients should be exempt from regulations that limit their access to appropriate medical opioid therapy given the unique nature of cancer, its treatment, and potentially the lifelong adverse health effects from having had cancer. ASCO also recognized the need to balance public health concerns regarding abuse and misuse of prescription opioids with the need to ensure access to appropriate pain management to cancer patients and survivors. Emphasis should be placed on safe opioid prescribing principles, including appropriate utilization, storage, and disposal of prescription pain medications. Regularly consulting your state’s prescription monitoring program, which enables clinicians to access patients’ controlled substance prescription history, is also highly recommended.

There are multiple etiologies of cancer pain. For example, there is pain associated with direct tumor involvement (infiltration of bone, nerves, and viscera) that occurs in 65%–85% of patients with advanced cancer. Pain can also occur indirectly via tumor release of inflammatory mediators. Treatments aimed at cure or palliation can also cause significant pain in approximately 15%–25% of patients receiving chemotherapy, surgery, or radiation therapy.

Therapeutic choices for pain management are often guided by pathophysiology. Pain syndromes are generally divided into two categories: acute versus chronic. Pain that occurs in the acute setting is mainly related to cancer therapeutic interventions. Chronic pain is subdivided into nociceptive (somatic vs visceral) and neuropathic. Nociceptive pain is associated with ongoing tissue damage. Somatic pain occurs as a result of activation of cutaneous and deep tissue receptors, and it is roughly described as sharp, well localized, throbbing, and gnawing. Visceral pain results when distention, stretching, and inflammation activate nociceptors. It is described as dull, poorly localized, cramping, or pressure. Neuropathic pain is described as tingling, shooting, stabbing, burning, electric like, and numb, and results from damage to nerves.

Breakthrough pain is common in cancer patients and is defined by Yennuranjalingam and Bruera as a “transitory exacerbation of pain that occurs on a background of otherwise stable persistent pain.” Breakthrough pain may be caused by activity or end-of-dose failure (a situation in which a patient experiences pain before their medication therapeutic time is expected to end); it can also occur spontaneously.

A thorough pain history requires eliciting information about anatomic regions and organ systems, temporal characteristics (pattern of occurrence), intensity, time of onset of pain, and etiology. A helpful pneumonic to elicit a pain history is the PQRST mnemonic that stands for provocative factors, quality, region and radiation, severity, and temporal factors. A thorough history should also be followed by a physical exam, review of the medical record, including labs and imaging.

The intensity of pain should be measured on a 0 (no pain) to 10 (extreme severe pain) scale, and this intensity should be quantified over time to identify any underlying patterns and to assess treatment efficacy. Mild levels of pain (less than 4/10) are not disabling and allow a more normal function and engagement. Moderate pain levels of 4–6 on a 10-point scale and tend to interfere with normal function and sleep, while severe pain levels of 7/10–10/10 significantly affect the patient’s ability to perform instrumental activities of daily living (IADLs). It is important to remember that psychological, social, spiritual, and financial problems can affect a patient’s perception and tolerance of pain.

Opioids are the basis for the management of cancer-related pain as they are the most effective and fastest acting analgesics to target this condition. The treatment of cancer-related pain should also involve a multidimensional approach that includes the optimization of nonpharmacologic treatments and the expertise of specialists when necessary.

There are no strict rules to follow when choosing between strong opioids (i.e., morphine, hydromorphone, methadone, and fentanyl) to treat cancer-related pain. Generic morphine is a reasonable initial choice because of its efficacy, relatively low cost, familiarity by physicians, wide availability, and variety of formulations. Initial choice of opioid therapy should also be guided by patient factors such as the presence of renal and hepatic insufficiency, and older age.

Renal impairment generally increases a drug’s half-life through a decrease in renal elimination. Since opioids are renally cleared, dose reductions, dose interval increases, or a different drug may be necessary for patients with renal insufficiency. Generally, morphine, codeine, meperidine, and tramadol should be avoided in this setting. Preferred short-acting medications include hydromorphone and oxycodone. Methadone and fentanyl are not dialyzable and therefore should be used with caution in patients on dialysis.

Hepatic impairment may result in decreased metabolism, decreased drug clearance, and increased bioavailability, which may lead to drug accumulation. Fentanyl, hydromorphone, oxycodone, morphine, and methadone can be used with caution. Dosage reductions or increased dosing intervals are warranted in this setting. Codeine and meperidine should be avoided because of the potential for accumulation of metabolites.

Older adults who have reduced renal function need careful choice and dosing of analgesics. However, opioids should not be withheld from older adults in pain. The general approach is to “start low and go slow,” titrating gradually using small increments and monitoring adverse effects, including changes in mental status, excessive sedation, or constipation.

General Guidelines for Pharmacological Pain Management

The goal of pain management from a clinical standpoint is to improve quality of life and improve function. Assessment of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) as well as calculating performance status with ECOG or PPS, should be performed routinely to assess efficacy of therapy.

The first step to pharmacological pain management is to define goals of therapy and setting patients’ expectations. Analgesics should be chosen based on etiology of pain, pathophysiologic mechanism of pain, analgesic responsiveness, potency of analgesic, and side effect profile.

The World Health Organization endorses a three-step ladder approach to analgesic prescribing. For mild pain, acetaminophen and/or nonsteroidal antiinflammatory drugs (NSAIDs) can be initiated with care not to exceed recommended max dose in 24 hours. For moderate-to-severe pain a combination product such as Acetaminophen/Oxycodone (Percocet) may be used, although these products have a ceiling dose for analgesia governed by the nonopioid component. Conversely, one may start a single agent (opioid) and titrate to achieve analgesia prior to adding or switching to another opioid.

The least invasive route should be chosen whenever possible. The oral route is the most convenient and cost-effective. Other available routes include intravenous, subcutaneous, transdermal, per rectum (inconvenient), intramuscular (painful), sublingual, and intrathecal (most invasive).

Clinician should choose a dosing schedule that is simple and individualized, based on temporal patterns. For example, for episodic or breakthrough pain, short-acting opioids every 4 hours as needed may be used. For continuous pain, short-acting opioids dosed every 4 hours around clock (ATC) may be chosen until steady state is reached at approximately 24 hours.

Patients with chronic and severe pain can benefit from long-acting opioids given around the clock because they allow the achievement of more consistent blood levels, reduce pain recurrence, improve adherence to treatment, and reduce dependence. Conversion to a long-acting opioid may start after 24 hours of continuous ATC dosing of immediate release opioid. A short acting opioid (10% of 24 hour total dose) should be added for rescue (for breakthrough pain).

Opioid doses can then be titrated to achieve patient’s preferred goal, only after steady state is reached at 48–72 hours. When a basal dose is increased, the rescue dose should also be increased.

An opioid may be rotated (switched) to a different opioid if there is no response to current regimen, if patient requires a different route of administration (i.e., a patient with dysphagia), or if patient develops intolerable side effects. Rotation should also be considered after nonopioid analgesics have also been tried.

When converting from one opioid to another, it is recommended the equianalgesic dose be reduced by one-third to one-half due to increased sensitivity to a new opioid when switching opioids.

Always treat opioid-related side effects that include nausea with or without vomiting, sedation, myoclonus, delirium, urinary retention, or other intolerable side effects. Usually, the first step in treating adverse effects is to decrease opioid dose or increase dosing frequency. Rapid cessation of opioids may result in opioid withdrawal, which is a syndrome characterized by yawning, sweating, lacrimation, rhinorrhea, anxiety, restlessness, dilated pupils, piloerection, nausea/vomiting, abdominal pain, diarrhea, and muscle aches. The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale administered by a clinician in the inpatient or outpatient setting, to determine the severity of withdrawal and a patient’s dependence on opioids.

Naloxone (Narcan), an opioid antagonist, should only be used in emergencies. It reverses respiratory depression, sedation, as well as analgesia.

Clinicians should remain vigilant in identifying and responding to warning signs of opioid misuse, which include asking for early refills, lost prescriptions, repeated requests for dose escalation, and obtaining prescriptions from multiple sources. If addiction is suspected, it may be helpful to consult an addiction specialist for guidance.

Nonopioid adjuvants have analgesic properties and are frequently used for specific pain syndromes, alongside opioids. Sometimes, they are recommended as first-line agents in cancer pain management. They are recommended at every step of the WHO ladder. The main categories include tricyclic antidepressants, antiepileptic drugs, steroids, bisphosphonates, and selective serotonin and norepinephrine inhibitors. Other adjuvants such as NSAIDs may be added to treat bone pain/metastases, while others such as gabapentin can alleviate neuropathic pain. Dexamethasone is helpful to reduce pain arising from liver capsule distention. Cannabinoids may also be used in pain syndromes (see the section on medical marijuana later in this chapter).

Many patients have also reported improved pain relief from nonpharmacological methods such as massage therapy, distraction, pet therapy, acupuncture, and local heat or cold, although there is little systemic research to guide their use. Nonetheless, these methods are often used alongside pharmacologic methods.

Psychological techniques such as biofeedback, relaxation, hypnosis, and cognitive and operant approaches can enable a patient to accept the responsibility of managing their pain so they can begin to cope and function more effectively.

There may be instances in which an existing pain regimen may fail to provide relief, such as in the setting of cancer progression. A pain crisis is defined as an event in which a patient reports intense, uncontrolled pain that is causing severe personal or family distress. This event represents an acute change in the patient’s condition or it may result from gradually increasing pain that crosses a threshold. Severe pain, usually rated in the range of 7/10–10/10 tends to dominate all other experiences. An acute pain crisis is considered a palliative care emergency. The first step in managing this emergency is to assess the patient. The extent of the workup required to treat it will be guided by the patient’s underlying disease, prognosis, prior functional status, preferences, and past pain experiences and behaviors.

A comprehensive history and physical exam needs to be performed. If the pain results in an abrupt change in clinical status, evaluation may include diagnostic procedures, especially if the results will lead to potentially effective treatments that would improve the patient’s quality of life. While the patient is being evaluated for a specific intervention, an opioid bolus of 10% of the patient’s total daily dose can be given. Efficacy should be assessed every 10–15 minutes. If pain is still present, a higher dose can be administered; for example, rescue dose can be increased by 25% to 50%. Subsequent doses can be administered every 15 minutes until adequate analgesia is obtained. Once the effective dose is found, it can be scheduled to be given every 4 hours. If patient-controlled analgesia (PCA) is required, the hourly basal rate should be calculated after the latest 24 hour total opioid requirement. Rescue doses are typically 50% of the hourly basal rate. These rescue doses may be given in intervals of 15 minutes or up to four rescue doses per hour. A clinician activated dose can also be provided. It is generally 100%–200% of the hourly b; for example, rescue dose can be increased by 25% to 50%.asal rate every 2–4 hours as needed. Expert consultation with an inpatient palliative care service is recommended in an acute pain crisis.

Cancer-related pain management also incorporates procedural methods that can provide pain relief, which may include nerve blocks, spinal infusions, external beam radiation, and radiopharmaceuticals.

Expert pain management is essential to the success of breast and gynecological cancer patients participating in a rehabilitation program, as untreated or poorly controlled pain, could limit rehabilitation potential and could further diminish performance status.

Nausea

Nausea and vomiting (N/V) whether acutely related to chemotherapy, other chronic condition, or cancer complications, often results in significant distress, decreased social interaction, and poor quality of life. The prevalence of N/V is as high as 70% among patients with cancer.

It is also a consequence of metabolic derangements, medication side effects, changes in gastric and bowel motility, and central nervous system disorders. Chemotherapy-induced nausea and vomiting (CINV) is subdivided into three types depending on the onset of symptoms: anticipatory, acute, or delayed. Other causes may be directly related to chemicals (medications, toxins), impaired gastric emptying (opioids, ascites), visceral causes (bowel obstruction, peritoneal carcinomatosis), cortical (intracranial tumor), and vestibular (motion sickness). Nausea and vomiting interferes with patients’ ability to take medications. It also limits oral intake often leading to dehydration, anorexia, weight loss, electrolyte disturbance, and diminished quality of life. These complications also interfere with patients’ ability to receive life-prolonging or palliative chemotherapy, as well as rehabilitative therapy.

The vomiting center is considered the final common pathway in emesis. The vomiting center receives input directly from the cerebral cortex, thalamus, higher brain stem, hypothalamus, sensory organs, and the vestibular apparatus in the inner ear. Indirect stimulation of the vomiting center arrives from the chemoreceptor trigger zone (CTZ) that is located on the floor of the fourth ventricle. Stimulation of the CTZ occurs via noxious stimuli such as chemotherapy, medications, and metabolic disturbances. The CTZ then stimulates the vomiting center via dopamine, serotonin, histamine, vasopressin, and substance P, ultimately resulting in emesis. The most common mechanism implicated in CINV is via direct stimulation of the CTZ within the area postrema.

The assessment of nausea and vomiting requires a careful history and a focused physical examination to identify specific physical and psychological contributors. In the palliative care setting, the causes are almost always multifactorial.

Diagnostic workup will depend in part on the stage of the patient’s illness and the patient’s goals of care. Workup may include blood draws to check electrolytes and drug levels. Radiologic imaging may be necessary to rule out potential medical complications including increased intracranial pressure, gastroparesis, ileus, gastric outlet obstruction, and bowel obstruction. Intraabdominal sources are common in gynecological and gastrointestinal cancer patients and often present with an obstructive component. The goal is to rapidly identify and treat underlying reversible causes. Empiric pharmacologic treatment is usually needed to control symptoms. A strategic approach in the management of nausea and vomiting is to target several implicated receptors simultaneously for a synergistic effect in order to achieve optimal control of symptoms.

Presently, the management of acute chemotherapy-induced nausea and vomiting (CINV) due to chemotherapy with high emetogenic potential includes a combination of a 5-HT3 (5-hydroxytryptamine) receptor antagonist, corticosteroids, a neurokinin-1-receptor antagonist, and olanzapine. Olanzapine is excluded if CINV is due to chemotherapy with moderate emetogenic potential.

The treatment of delayed CINV due to chemotherapy with high emetogenic potential is dexamethasone on days 2–4, plus Aprepitant. For moderate emetogenic chemotherapy, the treatment for delayed CINV is Aprepitant on days 2 and 3.

Treatment for anticipatory CINV includes an effective antiemetic regimen prior to chemotherapy. Short-acting benzodiazepines (alprazolam, lorazepam) are also useful. Nonpharmacologic strategies include relaxation, music therapy, and acupuncture.

For breakthrough CINV, antipsychotics such as metoclopramide can substitute 5-HT3 antagonists. For refractory symptoms or failure to respond to conventional antiemetics, cannabinoids such as dronabinol and nabilone may be added. The atypical antipsychotic Olanzapine has potential antiemetic properties because of its effects on multiple receptor sites implicated in the nausea and vomiting pathway.

When treating nausea and vomiting from other causes, a nonpharmacological approach can be helpful. For example, environmental factors should be identified and eliminated (i.e., fragrances, strong cooking smells) prior to initiating a pharmacological regimen. The treatments for other conditions contributing to nausea and vomiting should also be implemented.

Antiemetics can be started using a case-based or empirical approach. Antiemetics should be taken when best tolerated, either spread throughout the day or after meals. They can also be taken prophylactically or on a regular basis. Treating nausea and vomiting effectively and aggressively is vital to optimizing a patient’s rehabilitation potential.

Constipation

Constipation is prevalent in the palliative care population and in end-of-life care. It involves a complex interaction of anatomic, neurologic, and iatrogenic factors. Constipation may be caused by low intake of food, fluid and fiber, immobility, and drugs used to treat other conditions that impair gut motility such as opioids, antiemetics, anticholinergics, and NSAIDs. Cancer-related complications such as bowel obstruction, hypercalcemia, intraabdominal, and pelvic disease; cord compression; and cauda equina syndrome are other contributing factors. Constipation is defined as infrequent or absent bowel movements; decrease of BM volume; difficulty or pain with defecation; incomplete defecation, abdominal distention, oozing liquid stool; or hard stool. It should be treated quickly and aggressively.

Assessment includes taking a careful history about bowel habits, stool frequency and consistency, laxative use, and associated environmental factors such as lack of privacy or a long distance to the toilet and performing a physical exam (including a digital rectal exam). Bowel obstruction must be ruled out prior to any further investigation.

The treatment of constipation in the palliative care setting is based on limited research evidence. Most patients will need both a scheduled medication regimen and the use of rescue medications for episodes of constipation. Patients on regular doses of opioid therapy should receive a regularly scheduled laxative, and most will benefit from a stimulant or osmotic laxative administered as needed (PRN).

Bulk-forming fiver agents (e.g., psyllium and methylcellulose) should be avoided because of their tendency to form impactions when patients stop taking adequate amounts of fluids. Approach to management of constipation is mainly pharmacological, but nonpharmacological options should also be considered. Drug choice should be individualized.

Drug classes frequently used to treat constipation include stool softeners, stimulants, osmotic agents, enemas, antipsychotics, and opioid antagonists. One senna tablet daily is a common starting point, although it may require titration to a maximum of four tabs twice a day. Additional medications can be added in a stepwise fashion.

Polyethylene glycol a commonly used osmotic laxative that is tasteless, odorless, and generally well tolerated by patients. It has been found to be effective for opioid-induced constipation, and there is evidence that it may be more effective than lactulose for chronic constipation.

Rectal suppositories and enemas may be used when constipation is severe. Oral medications should limit the need for their use if the bowel regimen if used efficiently. Common side effects include bloating, flatulence, disliked taste, and diarrhea. Tolerance to stimulant laxatives is uncommon. Bowel obstruction may be a contraindication to stimulant laxatives, as laxatives may increase colic. Increased activity, ambulation, and exercise can also improve constipation.

Malignant Bowel Obstruction

Malignant bowel obstruction is a common complication of gastrointestinal and ovarian cancers. It usually occurs in the advanced stages of illness. The average life expectancy is about 80 days at the time of presentation, as evidenced by a recent prospective study. The pathogenesis of bowel obstruction may be directly related to cancer lesions. There are several types observed clinically. One type is the intraluminal obstruction that leads to impaired peristalsis and occlusion of the lumen. Extramural obstructions are generally caused by mesenteric lesions, omental masses, and adhesions. Complications of cancer treatments such as surgical adhesions and intraperitoneal chemotherapy are also causes of obstruction. Obstructions can be partial or complete. The absence of feces or flatus suggests a complete obstruction while incomplete obstruction may present with overflow incontinence. Common symptomatology includes nausea with or without vomiting and periumbilical, colicky abdominal pain that travels in waves. The pathophysiology is described next.

At the onset of obstruction, there is significant damage that occurs to the gut epithelium. This damage triggers an inflammatory response marked by release of inflammatory mediators such as prostaglandins, vasoactive peptide, and other secretagogues. This inflammatory cascade ultimately stimulates a large influx of fluid into the gut lumen with concomitant decreased reabsorption of water and electrolytes. Eventually, bowel dilation and edema ensue, leading to colicky pain, nausea, and vomiting. This cycle is viciously repeated as the gut continues to contract. Complications of malignant bowel obstruction include dehydration, electrolyte disturbances, and ultimately perforation. Diagnosis is confirmed via imaging (i.e., abdominal XR revealing air-fluid levels and distended loops of bowel).

Although most bowel obstructions are partial obstructions and can be managed effectively with medications, surgical intervention, venting gastrostomy, or metallic stenting should also be considered as part of palliative care management plans. Venting gastrostomy may be helpful for high-grade proximal obstructions, eliminating the necessity of nasogastric (NG) tube suctioning and IV fluids for symptom control. In addition, self-expanding metallic stents (SEMS) are possible alternatives for individuals with esophageal gastric outlet, proximal bowel, and large bowel obstructions. Late complications of SEMS placement can be as high as 50% and include migration, obstruction, perforation, and tenesmus.

Surgical interventions may or may not be practical, especially if there are multiple sites of obstruction present. Patient selection is critical, as patients with advanced disease carry significant perioperative morbidity and mortality. Generally, patients with a life expectancy of 2 months or less and patients with poor performance status should forgo surgery.

Successful symptom control can also be achieved with a combination of analgesic, anticholinergic, and antiemetic drugs, thought to reduce intestinal secretions and intraluminal hypertension, working synergistically.

For intractable symptoms and in the setting of partial obstruction, combinations of opioids, dexamethasone, haloperidol, and metoclopramide may be needed. Octreotide has been used to reduce gastrointestinal secretions in malignant obstructions, although a recent systematic review suggested that its efficacy on key clinical outcomes may be limited. Timely treatment increases the possibility of return to normal bowel function, which is instrumental in allowing eating, improved quality of life, and possibly survival.

Anorexia Cachexia Syndrome

Anorexia, or loss of appetite, is frequently encountered in the cancer-palliative care setting. Cachexia, which frequently accompanies anorexia, is among the most debilitating and life-threatening aspects of cancer progression, occurring in about 80%–90% of patients with advanced cancer. Cachexia is usually associated with significant patient and family distress. It is associated with poor prognosis and occurs in a spectrum (precachexia, cachexia, refractory cachexia).

This is a multifactorial syndrome characterized by ongoing loss of skeletal muscle mass (with or without the loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment.

Nutritional impact symptoms and a proinflammatory response are two of several interrelated mechanisms responsible for the anorexia cachexia syndrome. The role of nutritional impact symptoms, such as dental problems, severe pain, mouth sores, altered taste, dry mouth, fatigue, early satiety, constipation, and nausea and vomiting, are well established. These ultimately lead to decreased oral intake and malnutrition. A proinflammatory response mainly involving IL-6 (interleukin 6), IFN (interferon), and TNF (tumor necrosis factor) ultimately result in muscle wasting. Proinflammatory cytokines are thought to induce catabolism; this may explain the inability of artificial feeding techniques to improve the cachexia associated with terminal illness.

In the evaluation of anorexia–cachexia, it is important to take a careful history, including a nutritional history and a medication history. It is also important to assess for other contributing symptoms via the ESAS tool and to screen for nutritional impact symptoms leading to poor oral intake.

The objective assessment includes documenting weight loss of ≥5% in 6 months or weight loss of >2% in patients showing decreasing BMI or decrease in muscle mass within 6 months, physical exam and body composition, serial measurement of body weight and oral intake, and imaging and labs.

Generally, the management of anorexia–cachexia is challenging (even with involvement of palliative care specialists) due to current lack of effective treatments. If cachexia does not respond to treatments aimed at reversing treatable causes, the treatment approach becomes a multidisciplinary one. The goals of therapy may include decreasing family distress, improving appetite, increasing social interaction, and improving physical function as recovery of muscle is less likely. The treatment approach may include best supportive care/palliative care, psychosocial support, incorporating an exercise program, incorporating nutritional support/dietary counseling, managing nutritional impact symptoms, and incorporating pharmacological management to increase appetite.

The established therapies in the cancer population include megestrol acetate (160 mg/day titrated to 800 mg/day), glucocorticoids (prednisone 20–40 mg/day) or equivalent doses of dexamethasone (3–4 mg/day in divided doses). Cannabinoids have not demonstrated any activity against anorexia and cachexia in patients with advanced cancer. Cyproheptadine (serotonin and histamine antagonist) 8 mg three times daily is a good option for patients with carcinoid syndrome who have anorexia/cachexia. Miscellaneous treatments include mirtazapine and olanzapine. Mirtazapine is a tetracyclic antidepressant–inducing weight gain and food intake. Definitive proof of benefit requires randomized, placebo-controlled trial.

Data suggests that olanzapine adds to the already established benefits of megestrol acetate in reducing the severity of cancer-associated anorexia and increasing nonfluid weight gain, but results were not considered definitive due to single-institution study.

Artificial nutrition is generally not recommended for cancer cachexia–anorexia syndrome, as systematic reviews suggest that parenteral nutrition is harmful when provided to patients undergoing radiation or chemotherapy for cancer. Artificial nutrition and hydration has not been shown to prolong life.

It is important to educate and counsel patients and families in distress. It is helpful to explain that anorexia is part of the advanced disease process and a natural part of life coming to an end. It is important to note that patients are not starving and can live comfortably for long periods on minimal food or water. On the contrary, force-feeding causes patient discomfort, nausea, aspiration, and potentially respiratory distress.

Control should be placed back on the patients, and they should be encouraged to choose their favorite foods, quantities, and eating schedules. Dietary restrictions should be liberalized.

Depression and Anxiety

Psychological distress is a significant cause of suffering among patients with advanced cancer and is highly associated with decreased quality of life. More than 60% of patients with cancer report experiencing distress. Differentiating these causes of normative distress associated with illness from other psychiatric disorders is essential to the implementation of appropriate treatment plans and to prevent any further threats to patients’ physical, psychological, social, and spiritual well-being.

Depression is a significant distressing emotional experience for patients and their families. In the context of a serious illness such as cancer, it can be amplified by physical symptoms, fear of dying, family distress, and as death approaches. It also decreases patient’s ability to feel pleasure and connectedness. Depression is also associated with decreased adherence to treatments, prolonged hospital stays, and reduced quality of life. It is also an independent risk factor for suicide and requests for hastened death. Depression has been increasingly recognized to affect survival in several cancers. Symptoms of depression have been reported in up to 58% of the patients with cancer. Rates of major depression range as high as 38% among these patients.

Anxiety is an expected, normal, transient response to stress. An excessive response to an unidentified internal stressor is considered pathological. Anxiety symptoms are often physical (diaphoresis, dizziness), emotional (feeling of impending doom), behavioral (psychomotor agitation), and cognitive (worry, fear). Anxiety symptoms are thought to occur in more than 70% of medically ill patients, especially those with cancer or those approaching the end of life. Anxiety often cooccurs with adjustment disorders. An adjustment disorder is a psychological response to an identifiable stressor that results in the development of clinically significant emotional or behavioral symptoms but does not qualify for a diagnosis of anxiety disorder. Many people with serious medical illnesses may have trouble adjusting psychologically to their diagnosis, prognosis, or treatment regimens.

The following two questions have been found to have good sensitivity to screen for depression. A more formal exploration is indicated if the patient has a positive answer to either of these questions: Are you depressed? Do you have much interest or pleasure in doing things?

Clinical depression is associated with hopelessness, helplessness, worthlessness, and guilt. Clinically depressed terminally ill patients are at higher risk of suicide and suicidal ideation, and they may have increased desires and requests for hastened death. Because many of the symptoms of severe illness overlap with symptoms of depression (fatigue, anorexia, sleep disturbance, poor concentration, social withdrawal, hopelessness), consultation with an experienced psychiatrist and/or psychologist may be helpful in complex situations.

Performing a history and physical exam in addition to identifying treatable and reversible medical complications are essential first steps. Special attention should be placed on concomitant symptoms such as physical, psychological, social, and spiritual pain.

Anxiety symptoms may be triggered by a range of medical transitions such as the initial diagnosis of a serious illness, a recurrence, treatment side effects or failure, or discussion of hospice. Other fears or anxiety triggers less often brought to the attention of the clinician include uncontrolled pain, isolation, abandonment, loss of control, worrying about a spouse or child, being a burden, death, and dying. Anxiety disorder is very treatable when recognized.

The need to medically treat depression and anxiety depends on their intensity, persistence, and disruption of basic life functioning. Treatment should be considered when these effects dominate other emotions and interfere with the ability to enjoy other aspects of life.

The treatment of anxiety and depression in cancer patients incorporates antidepressant medications, supportive psychotherapy, and patient and family education. Drugs classes include psychostimulants such as methylphenidate, selective serotonin receptor inhibitors (SSRIs), selective serotonin–norepinephrine receptor inhibitors (SSNRIs), tricyclic antidepressants (TCAs), and bupropion. Pharmacological therapy for anxiety also includes benzodiazepines, buspirone, and atypical antipsychotics. Potential nonpharmacological interventions include psychotherapy, meaning-centered therapy, mindfulness meditation, and relaxation. Palliative care specialists work hand-in-hand with mental health professionals such as psychiatrists, psychologists, and licensed clinical social workers to comanage mood disorders.

Medical Cannabis

Medical cannabis is a novel modality used in palliative care for a multitude of physical and psychological symptoms. Cannabis is an investigational new drug in the United States. Although it is classified as a schedule I controlled substance in the United States, in recent decades an increasing number of states have legalized cannabis for medical purposes via state medical cannabis programs.

For cancer pain a multicenter randomized controlled trial (RCT) involving 360 patients investigated oral cannabis to treat breakthrough cancer pain in subjects who were started on long-acting opioids. It showed analgesic efficacy in the low- and medium-dose ranges that were also well tolerated. Three additional RCTs, including 100 subjects in total of inhaled cannabis for chronic intractable neuropathic pain due to multiple etiologies, showed efficacy for smoked and vaporized cannabis.

The cannabis plant, which comes in different strains, produces resins with varying ratios of pharmacologically active cannabinoids, principally tetrahydrocannabinol (THC) and cannabidiol (CBD), along with terpenoids, flavonoids, and other molecules. The majority of the effects of THC from cannabis are mediated through partial agonism of central and peripheral cannabinoid receptors CB1 and CB2. THC is excreted via hepatic and renal mechanisms. In setting of hepatic and renal impairment, it is expected to cause side effects that are more exaggerated or prolonged. Cannabinoids are highly protein bound in the blood and are not expected to be removed by hemodialysis.

Dosing depends on individual patient needs and tolerance of side effects. A general principal of dosing is to start low and go slow. Routes of delivery include oral route, mucosal, topical, rectal, and inhalation. Vaporization has the advantage of rapid onset of effects and easy titration. Oral ingestion of cannabis has a delayed onset of action, compared to other routes, so titration is more difficult. In the palliative care setting, cannabinoids are generally used to treat pain, nausea/vomiting, anorexia, insomnia, fatigue, and neuropathy. Common side effects include xerostomia, drowsiness, dizziness, nausea, confusion, dysphoria, anxiety, and acute psychosis. Cannabis ingestion increases the risk of motor vehicle accidents (MVAs).

It is important to screen patients for marijuana use in a nonjudgmental manner. Whether patients are using it recreationally or medically, it is a potent drug and has clinical side effects, in addition to drug–drug interactions. More research studies are required in order to expand and standardize its therapeutic use.

Spiritual Issues and Existential Distress

Periyajoil et al. define spirituality as “a dynamic and intrinsic aspect of humanity through which persons seek ultimate meaning, purpose, and transcendence in relationship to self, family, community, society, nature, and the significant, or sacred, expressed via beliefs, values, traditions, and practices.” In contrast, religions are belief systems that provide a framework for making sense of life, death, and suffering cannabinoids. They involve beliefs and rituals shared by a community in the context of a relationship with the transcendent. During the course of an illness, both spiritual and religious rituals may be a source of support for patients.

Spiritual or existential distress has been defined as the distress brought about by the actual or perceived threat to the integrity or continued existence of the whole person. Spiritual and existential distress are common in the cancer population. Spiritual distress is reported in more than one-half of patients with advanced cancer receiving palliative care. Although patients place high value on these issues and often want to discuss it with health-care professionals, it is often unrecognized by clinicians and is generally a neglected area of cancer care.

Sources of spiritual and existential distress may include hopelessness, lack of purpose or meaning, grief, loss, guilt, anger, and abandonment by God or others. It is the duty of all health-care providers to address every aspect of suffering—psychosocial, spiritual, and physical— as spiritual and existential well-being. The World Health Organization has emphasized the importance of palliative care and the integration of psychological and spiritual care in order to help patients live as meaningfully as possible until death.

The following two questions are useful to screen for spiritual issues: (1) Is spirituality or religion important for you? and (2) Are your spiritual or religious beliefs helping you right now? A yes/no combination answer to these questions triggers a referral to a board-certified chaplain.

There are several tools available to elicit a spiritual history: (1) FICA (faith, importance, community, action), (2) HOPE (sources of hope, organized religion, personal spirituality and practices, effects on medical care and end-of-life issues), and (3) SPIRIT (spiritual belief system, personal spirituality, integration with a spiritual community, ritualized practices and restrictions, implications for medical care and terminal event planning). Only FICA has been validated.

Board-certified chaplains integrate spirituality into the treatment care plan. Spiritual care interventions can vary from communication techniques, to therapy, or self-care. Communication techniques such as life review are helpful to gain insight about a patient’s life and his/her story.

Some specific approaches include meaning-centered therapy, which helps a patient address the unique meaning of his or her life, and dignity therapy, which addresses what a patient finds most meaningful and helps them to identify a personal history they want to be remembered by.

Advance Care Planning and End-of-Life

Understanding patients’ goals in the context of their cancer diagnosis enhances the clinician’s ability to align the care that is delivered to patients with what is most important to them. Frequent discussions about patients’ goals, values, and what matters to them, also promote good decision-making, patient-centered are, and earlier end-of-life planning. These high quality discussions are often missing in the process of completing an advance directive (AD)—a document a patient completes while still in possession of decisional capacity, and reflects how treatment decisions should be made on her or his behalf in the event she or he loses the capacity to make such decisions.

Prior to completing an advance directive, a clear understanding of an evolving medical problem is needed, frequent conversations about patients’ goals of care in the context of their illness are also required, as well as patients and providers willingness to discuss patients’ care preferences. For these reasons ADs are less frequently completed, even less frequently executed.

These shortcomings of the advance directive pushed for a more comprehensive approach that focuses on communication, rather than merely completing a form. The advance care planning (ACP) process extends beyond completing an advance directive because it stresses ongoing conversations among patients, their families, caregivers, and healthcare providers. It reflects on the exploration of goals, values, beliefs, illness understanding, medical care/treatment options, and plans for the future. It also promotes the documentation of these conversations in the electronic medical record. Ideally these conversations are integrated into routine care, are often revisited throughout the disease trajectory or natural course of the illness. ACP should also be held during important transition points such as prior to embarking on a potentially life threatening or risky treatment or procedure (i.e. a new chemotherapy regimen, high-risk surgery, or hematopoietic cell transplantation) and in the presence of evidence-based indicators for limited life expectancy (Stage IV status at cancer diagnosis, cancer progression). A patient’s primary care physician or a specialist such as an oncologist who has been following a patient longitudinally for their cancer treatment, are the most appropriate persons to initiate goals of care discussions. Specialty Palliative Care consultations should be requested for complex goals of care and/or in depth advance care planning.

When ACP discussions are held, patients and families report a higher satisfaction with care, as well as lower risks of stress, anxiety, and depression. ACP is also associated with better patient outcomes. When these discussions occur routinely, providers also benefit by enhanced trust between patient and providers and lessening of conflict among family members and the health care team.

Given that one of the identified barriers to ongoing ACP among providers includes lack of training or experience in having these conversations, strategies and tools have been developed to assist clinicians with these tasks. At VitalTalk.org , a stepwise approach to goals of care discussions, such as REMAP—Reframe, Expect emotion and Empathize, Map the future, Align with the patient’s values, Plan medical treatments that match patient’s values—is available. The 2017 guideline from the American Society of Clinical Oncology also provides some recommendations about how to optimize communication about goals of care, treatment options, and prognosis.

The Role of Rehabilitation in the Palliative Care Setting

Palliative care specialists work hand-in-hand with rehabilitation specialists synergistically with overall goals to alleviate suffering and promote the best quality of life for patients and their families. Rehabilitation has a definitive role in the management of cancer patients receiving palliative care. Rehabilitation services play an indisputable role in pain management, in maximizing function, independence, and well-being and improving quality of life. Physiatrists may be able to identify other drivers of pain that could intensify a patient’s pain experience in the setting of newer acute or chronic cancer-related pain.

Synergistically, expert symptom assessment and management by palliative care specialists are critical to optimize a patient for a rehabilitation program.

Conclusion

Palliative care is specialized, whole-person care, delivered in an interdisciplinary fashion, and aimed at relieving suffering due to a serious illness. Palliative care is appropriate at any age or stage of a serious illness such as cancer, as evidence suggests that while provided concurrently with active cancer treatment, it can improve quality of life and potentially have a measurable mortality benefit. Integration of palliative care is becoming the new standard of care in oncology care. The early provision of palliative care minimizes suffering, improves quality of life, and helps elucidate patient preferences and goals of care. Palliative care teams can also assist patients, families, and caregivers in the transition from receiving aggressive medical therapies to a more comfort based approach when appropriate.

Patient Resources

• 1.
  

  Getpalliativecare.org

  
  
• 2.
  

  Caregiver.org —Understanding Palliative/Supportive Care: What Every Caregiver Should Know

  
  
• 3.
  

  Fivewishes.org

Analgesics used in cancer pain management

Medication/Drug Class	Advantages	Disadvantages/Adverse Effects
Acetaminophen	Available OTC Rapid onset	Hepatotoxic at high doses. Max dose 3000 mg/day Monitor liver function/disease Ceiling effect for analgesia
NSAIDs (i.e. ibuprofen, celecoxib)	Rapid onset Effective for bone pain	Ceiling effect for analgesia GI/renal/cardiac toxicity Avoid in older adults
Corticosteroids	Rapid onset Effective for bone pain Benefit for other symptoms (n/v, anorexia, etc.)	Discouraged with immunotherapy Short-term AE: thrush, impaired glucose control, insomnia, delirium Long-term AE: myopathy, aseptic necrosis
Opioids (i.e. morphine, hydromorphone, methadone)	Rapid onset No ceiling effect Helpful for somatic, visceral, and neuropathic pain	Constipation Sedation, confusion, delirium Cognitive side effects Nausea/vomiting Tolerance Addiction
Antiepileptic drugs (i.e. gabapentin, pregabalin)	Minimal drug–drug Interactions Well tolerated Helpful for neuropathic pain and mucositis	Slow acting. May take weeks to reach analgesia Dose adjustment needed for renal dysfunction sedation, dizziness, ataxia
Tricyclic antidepressants	Helpful for neuropathic pain	Slow acting. May take weeks to reach analgesia Sedation, anticholinergic AE, cardiac arrhythmia
SSNRIs (i.e. duloxetine, venlafaxine)	Helpful for neuropathic pain	Slow acting. May take weeks to reach analgesia Drug–drug interactions SSNRIs may decrease effect of tamoxifen Fentanyl and SSNRI, increase risk of serotonin syndrome avoid if renal impairment
Topical analgesics (i.e lidocaine, capsaicin)	Helpful for neuropathic pain	Localized skin reaction, not practical for diffuse pains

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