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Supportive Care in Lung Cancer
Seminars in Oncology Nursing, Vol 24, No 1 (February), 2008: pp 57-67
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OBJECTIVES: To discuss common lung cancer symptoms including prevalence, assessment, etiology, and recommended interventions.
DATA SOURCES: Research studies and systematic reviews.
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CONCLUSION: A mandate in care of persons with lung cancer is to deliver supportive care concurrently with life-prolonging care or as the main focus of care. Most are diagnosed with advanced disease that impairs health with both physical and psychological symptoms.
IMPLICATIONS FOR NURSING PRACTICE: Early assessment and comprehensive management of symptoms are main components of improving quality of life and functional status for those living with lung cancer.
KEYWORDS: Lung cancer, palliative care, fatigue, dyspnea, cough, pain, cachexia, anorexia, psychosocial distress
Margaret Joyce, PhD(c), RN, AOCNÒ: Nurse Practitioner, Thoracic Oncology, The Cancer Institute of New Jersey, New Brunswick, NJ. Sue Schwartz, MSN, RN, OCNÒ: Nurse Clinician, Thoracic, GU and Breast Studies, The Cancer Institute of New Jersey, New Brunswick, NJ. Maureen Huhmann, MS, RD: Assistant Professor, Department of Primary Care, School Health Related Professions-University of Medicine and Dentistry of New Jersey Clinical Dietitian, The Cancer Institute of New Jersey, New Brunswick, NJ. Address correspondence to Margaret Joyce, PhD(c), RN, AOCNÒ, 104 Wycombe Place, Somerset, NJ 08873; e-mail: joycepe@ umdnj.edu
Ó 2008 Elsevier Inc. All rights reserved. 0749-2081/07/2401-$30.00/0 doi:10.1016/j.soncn.2007.11.013
MARGARET JOYCE, SUE SCHWARTZ, AND MAUREEN HUHMANN
E
ARLY assessment and comprehensive management of both disease and treatment-related symptoms are main components of improving quality of life (QOL) and functional status for those living with lung cancer. Lung cancer, with an estimated 160,390 deaths in 2007, remains the leading cause of cancer death among US men and women.1 This is due in part to the fact that there is no routine screening recommended for lung cancer and, as a result, many tumors are discovered at a late stage of disease. A diagnosis that includes regional or distant spread of disease can produce significant physical and psychological symptoms. Hence, the mandate in the care of persons with lung cancer is to deliver supportive or palliative care concurrently with life-prolonging care or, in some cases, as the main focus of care.2 In addition, the number of symptoms to be managed and therefore the intensity of supportive care required may change as a person moves through the trajectory of their illness. Common symptoms reported by newly diagnosed lung cancer patients include fatigue, pain, anorexia, coughing, and insomnia. However, pain, dyspnea, and anorexia are ranked by patients with advanced lung cancer as the most common and most intense.3 Several researchers have attempted to characterize symptom clusters in lung cancer. Symptom clusters refer to concurrent, related symptoms that may have a synergistic or collective effect on patient outcomes. Depression and fatigue were found in cluster in a group of persons with lung cancer of mixed stages.4 Chan et al5 found a cluster of breathlessness, fatigue, and anxiety in a small sample of advanced lung cancer patients undergoing palliative radiotherapy to various sites. Gift et al6 found, through secondary analysis of a large data set, that nausea, fatigue, weakness, appetite loss, weight loss, altered taste, and vomiting clustered together in a group of newly diagnosed lung cancer patients with both early and late stage disease. A common antecedent related to the cluster was treatment with chemotherapy. This group also reported that the severity of the symptoms in this cluster declined over time, perhaps because of the completion of chemotherapy.7 It is logical to assume that certain symptom clusters may be timed with respect to therapy. Despite the current therapy, or lack thereof, persons with lung cancer experience multiple concurrent symptoms
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that require attention. This discussion is limited to six common symptoms experienced by persons with lung cancer and offers evidence-based practice recommendations.
FATIGUE
O
ne of the most severe and debilitating symptoms for patients undergoing cancer treatment and at the end of life is fatigue.8,9 Seventy-five percent to 100% of patients undergoing chemotherapy report fatigue. Cancer-related fatigue has been found to strongly affect QOL.9,10 In 171 outpatients with advanced lung cancer, Tanaka et al11 found that fatigue affected at least one activity of daily living in more than half the patients (52%). Walking and work were reported as the two physical activities impacted the most. Cancer-related fatigue is a distressing, persistent, and subjective sense of tiredness or exhaustion related to cancer or to treatment for cancer that is not proportional to recent activity and interferes with functioning.12 Regular screening for fatigue is recommended. A simple numerical 0-to10 scale can be used on initial visit and at regular intervals to capture and quantify current fatigue and documentation over time can indicate improvement or decline.12 Patient input is essential when assessing for fatigue. It is crucial to acknowledge fatigue to be as important as other symptoms that affect QOL.13 Clinical assessment for fatigue should include consideration of: 1. Hemoglobin/hematocrit: regular screening of hemoglobin/hematocrit to detect for anemia (hemoglobin # 12 g/dL). 2. Physical appearance: Does the patient look tired? Do they look rested? How is their color? 3. Shortness of breath: Often associated with fatigue. Depending on the level of anemia, patients may be short of breath with activities of daily living. 4. Quality of sleep: Is there a change in sleep habits? Do they nap during the day? Do they go to bed the same time each night and get up the same time each day? Is the quality of sleep the same? Do they wake up feeling refreshed? 5. Pain: A complete pain assessment is needed as fatigue may be a consequence of pain.14 6. Psychosocial issues: Are they experiencing increased stress? Do they have money concerns or concerns about the disease and its treatment?
Two lung cancer-specific assessment tools with demonstrated reliability and validity that assess the impact of fatigue are (1) The Functional Assessment of Cancer Therapy—Lung Cancer (FACT-L) and (2) The Lung Cancer Symptom Scale (LCSS). FACT-L is a 44-item self-report that measures physical and functional well-being with assessment of lung-specific symptoms.15 The LCSS is a site-specific measure of QOL with nine visual analogue scales that evaluate six major symptoms associated with lung cancer and the effect on symptomatic distress, function, and global QOL.16 One general tool to measure the severity of fatigue is The Brief Fatigue Inventory (BFI). The BFI allows rapid assessment with nine questions that evaluate fatigue using a scale of 0 to 10, with 0 being ‘‘No fatigue’’ to 10 being ‘‘As bad as you can imagine.’’ Six of the nine questions ask how much fatigue interferes with various activities of daily living.17 Non-Pharmacologic Interventions Exercise is one intervention to manage fatigue supported by strong evidence from well-designed studies.8 The National Comprehensive Cancer Network (NCCN) guidelines for the management of cancer-related fatigue recommend that all patients, whether actively on treatment or in follow-up, should be encouraged to participate in regular physical activity.12 The type of exercise, frequency, intensity, and duration should be tailored to the patient’s needs. For example, patients with skeletal muscle weakness may need strength training, whereas those who have maintained their lean body mass may benefit from aerobic exercise.18 Energy conservation is defined as the deliberate, planned management of an individual’s personal energy resources so that valued activities and goals can be maintained.19 Energy conservation and activity management as an intervention aims to balance patient activities and rest by prioritizing and planning their day.20 This may include scheduling household chores or using friends or family to assist with activities such as shopping, cooking or cleaning. Sleep hygiene practices that include avoiding long or late-afternoon naps, going to bed only when sleepy, using the bedroom and bed for sleep and sexual activities only, going to bed and getting up at regular times, and avoiding stimulating activity and caffeine, may be helpful to patients. Using
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relaxation techniques at least 1 hour before going to bed has been effective as well.8,21 Although fatigue scores did not decrease simultaneously with various indicators of nutritional status (weight and pre-albumin) in patients with lung cancer receiving radiation therapy in one study,22 a subsequent study contradicts this.23 It seems logical that insufficient provision of nutrients can contribute to fatigue. Data indicate that increases in lean body mass can lead to improvement in reports of fatigue.24 Adequate provision of calories and protein in concert with resistance exercise are essential to increase lean body mass. There is a lack of data to support hydration and nutritional approaches to fatigue management. There is also limited data to support the use of vitamins, minerals, herbs, and nutritional supplements.20 Wells et al25 described the use of complementary and alternative medicine therapies including herbs, tea, acupuncture, massage, meditation, and prayer to control symptoms, including fatigue, in women living with lung cancer. Women used complementary alternative method (CAM) therapies most often for controlling pain, followed by difficulty breathing and fatigue.25 Prayer was the most commonly used CAM for all symptoms. Evaluation of effectiveness of CAM therapies was not reported.
Pharmacologic Interventions Erythropoietin. Data from systematic reviews suggest that patients receiving erythropoiesis stimulating therapy to correct anemia with hemoglobin less than 10g/dL experience decreased fatigue; however, evidence does not substantiate that erythropoietin improves fatigue when anemia is less severe.8 Recent evidence from a clinical study prompted the US Food and Drug Administration to issue an alert that patients treated with an erythropoiesis-stimulating agent and dosed to a target hemoglobin of 13.5 g/dL are at significant risk for serious and life-threatening cardiovascular complications as compared with use of erythropoiesis stimulating therapy to a target hemoglobin of 11.3g/dL.26 Caution is advised in the use of erythropoiesis-stimulating agents as an intervention for fatigue not associated with severe anemia. Psychostimulants. There have been no placebo-controlled, randomized clinical trials to evaluate the use of psychostimulants, such as methylphenidate or dextroamphetamine, in patients
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with fatigue. Potential side effects include irritability, insomnia, labile mood, and tachycardia.9 The use of steroids is associated with a decrease in fatigue, although the mechanism of action is not known. Most studies have used prednisone 20 to 40 mg/day for 2 to 4 weeks. However, use of steroids should be approached with caution because prolonged use can contribute to myopathy and infection.27 Antidepressants. Depression is common in patients with cancer. However, the use of antidepressants in fatigued patients that are not depressed is not supported by evidence.20,21 Patient education on fatigue and its management is essential to the successful treatment of fatigue. If adequately informed, patients can adjust and adapt to the symptom more realistically. Because fatigue is one of the prominent and pervasive symptoms experienced by persons with lung cancer, teaching and counseling may contribute to fatigue management and overall support.
DYSPNEA
D
yspnea or breathlessness is one of the three most frequently reported symptoms by persons with lung cancer, who also rank it in the top three most severe symptoms.28 The prevalence of dyspnea in the lung cancer population varies from 55% to 87%,29 with most persons reporting it at end of life.30 Lung cancer-related dyspnea varies with an individual’s diagnostic stage, primary tumor location, and therapy.29 Persons with lung cancer describe dyspnea as frightening.31,32 Reduction in functional status and subsequent disability are frequent consequences of dyspnea.33 Furthermore, dyspnea is a difficult problem to manage and, when witnessed, it evokes a response that begs intervention from patients, caregivers, and health professionals. Generally, the term ‘‘dyspnea’’ is applied to sensations experienced by individuals who report unpleasant or difficult respiration. The American Thoracic Society defines dyspnea as ‘‘a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.’’33(p322) Many factors can converge to cause and contribute to the symptom of dyspnea. It is not uncommon for a person with lung cancer to have, in addition to a primary lung tumor, a combination of other factors contributing to dyspnea such as a pleural effusion, anemia, cachexia, and
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underlying chronic obstructive pulmonary disease. Additionally, cognitive variables such as anxiety and depression,34-36 or personality,37 have been shown to modify dyspnea. Hence, the threshold perception of dyspnea varies widely with individuals and is related only moderately to the degree of pulmonary dysfunction.33 Assessment of dyspnea is a challenge because of the symptom’s subjective nature. The most common method of assessment is self-report of the activity level that causes awareness of the symptom. The visual analog scale and numerical rating scale have been shown to be valid and reliable in assessing cancer-related dyspnea.38 Evaluation of dyspnea includes complete history and a focused review surrounding the symptom such as temporal onset, precipitating or relieving events, and response to medication or behavioral approaches. A dyspnea-focused physical exam includes all vital signs and a cardiopulmonary physical assessment. The choice of appropriate diagnostic tests is guided by the stage of disease, usefulness of the information for possible therapeutic intervention, and patient choice. Basic diagnostic testing includes pulse oximetry at rest and with exertion, if feasible, as well as complete blood count. A chest radiograph may be indicated to evaluate acute problems. Considering the complex nature of dyspnea, an important goal of assessment is to differentiate an acute and possibly reversible cause of dyspnea from a condition that requires palliative or supportive interventions. Symptomatic management of dyspnea is based on oxygen therapy, pharmacologic therapy, and general supportive measures. Usually a combination of all three is used to promote comfort, increase exercise tolerance, and support social and emotional well being.39 Oxygen Therapy There is evidence that those patients who are hypoxemic at rest on room air report decreased dyspnea with supplemental oxygen.40 However, the routine use of supplemental oxygen for non-hypoxemic patients did not show a benefit in one study,41 so the recommendation in the absence of hypoxia is less clear. An individual’s response to the effect of oxygen therapy must be assessed. Increased ambient air flow across the face or nasal mucosa, such as generated by oxygen flow or a fan, may alter the perception of dyspnea through poorly understood mechanisms.42
Pharmacologic Therapy Strong evidence from a meta-analysis and smaller studies support the use of short-acting oral and parenteral opioids to treat dyspnea in those with advanced disease.43 Opioids have a respiratory depressive effect that blunts the perception of dyspnea so that for a given stimulus, the intensity of respiratory sensation is reduced.33 Although, morphine was the predominant opioid used in most studies, evidence about a specific dose recommendation is lacking. One exception is a study that showed a supplemental opioid dose equal to 25% of a regular 4-hour opioid dose was as effective as 50%.44 In general, opioid-tolerant patients reported dyspnea relief from supplemental opioid dosing. Further research is needed to find the most beneficial opioid and opioid dose to relieve dyspnea, but conducting research in persons experiencing dyspnea is difficult because of their unstable clinical status. Currently there is no convincing evidence that nebulized opioids are effective in relieving dyspnea, although benefit is reported in some situations.43,45 Individual uncontrolled trials of other nebulized medications such as fentanyl46 and furosemide47 show promise, but need further confirmation before adoption can be recommended. There is a conflicting expert opinion regarding the use of benzodiazepines; some recommend it to treat anxiety associated with dyspnea2,48; others claim the use of an anxiolytic is not supported for relief of cancer-related dyspnea.42,49 In some patients a trial of a benzodiazepine may be reasonable, particularly in those with morbid anxiety or history of panic attacks.33 Because of the common risk factor of tobacco use, persons with lung cancer also present with coexisting pulmonary diagnoses such as obstructive airway disease. Treatment with inhaled beta-2-adrenergic agonists (albuterol), inhaled anticholinergics, and sustained-release theophylline has been shown to improve dyspnea in patients with stable chronic obstructive pulmonary disease.42 General Supportive Measures Persons with dyspnea usually find measures such as positioning, decreasing energy expenditure, and relaxation strategies helpful in minimizing dyspnea. One multicenter randomized trial found that patients with lung cancer who attended weekly sessions to receive specialized nursing
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interventions reported a decrease in breathlessness and improved life quality compared with those who received usual care.50 These interventions included pulmonary assessment, education about breathing control, relaxation and distraction strategies, and emotional support. This rehabilitative approach to cancer-related dyspnea, which is effective in relieving dyspnea from other etiologies, needs confirmation with respect to which intervention or which combination of the interventions are the most significant.
COUGH
C
ough in cancer patients can be a result of direct or indirect tumor effect, treatment, and other unrelated problems.42 Table 1 outlines potential causes of cough in persons with cancer. The initial focus to relieve cough, as with dyspnea, is therapy aimed at the underlying etiology. Central airway obstruction, a common cause of cough and dyspnea in persons with lung cancer, may be palliated with bronchoscopy, which allows visualization of the airway and possible insertion of a stent to open an obstructed airway or laser resection of an obstructing tumor. Malignant pleural effusions are another common cause of cough; symptom relief is possible with thoracentesis drainage of fluid.51 However, therapy is not always effective or cough relief is delayed requiring interim palliative interventions. Typically, the symptomatic management of cough is guided by whether the cough produces sputum. The management goal is to either promote expectoration of sputum or suppress the cough if it is non-productive. Adequate hydration, air humidification, and chest physiotherapy can promote expectoration. Both a pharmacologic expectorant such as guaifenesin or a nebulized mucolytic such as acetylcysteine aim to thin secretions, promote expectoration, and thus decrease cough. Often the cough is unrelenting or non-productive, and cough suppression becomes the management goal. As most patients discover themselves, some relief can be obtained from cough lozenges that promote saliva production; some cough lozenges contain local anesthetics to soothe sensory nerve endings in the pharynx. Table 2 lists common oral antitussives, dose, and frequency.52 Benzonatate is a prescription cough suppressant that may be trialed, but opioid cough suppressants are usually required. One exception
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TABLE 1. Causes of Cough in Cancer Patients Cough directly caused by cancer Pulmonary parenchyma involvement (primary or metastatic) Lymphangitic carcinomatosis Intrinsic or extrinsic airways obstruction by tumor Pleural tumor Pleural effusion Multiple tumor microemboli Pulmonary leukostasis Superior vena cava syndrome Cough caused by cancer treatment Chemotherapy induced pulmonary toxicity Chemotherapy induced cardiomyopathy Radiation pneumonitis Cough indirectly caused by cancer Cachexia Pulmonary aspiration Pulmonary emboli Cough unrelated to cancer Cough caused by chronic obstructive pulmonary disease Asthma Congestive heart failure Interstitial lung disease Pneumothorax Upper respiratory tract infection Bronchiectasis Gastroesophageal reflux Postnasal drip Related other medications From Hematology/Oncology Clinics of North America, 16(3), Dudgeon DJ: Managing Dyspnea and Cough, p. 570. Copyright Ó 2002, reprinted with permission from Elsevier.42
is dextromethorphan, a non-prescription antitussive that acts through non-opioid receptors that may equal codeine as a cough suppressant.42 Codeine is the most widely used opioid for cough suppression. Hydrocodone is a good alternative to codeine. The adverse effects of constipation, nausea, and somnolence are to be expected when opioids are used to suppress cough; practitioners are cautioned to use complementary regimens to prevent anticipated side effects.
PAIN
P
ain is a prevalent symptom in lung cancer. Local tumor invasion of the pleura, ribs, thoracic spinal cord, or brachial plexus are common causes of pain in lung cancer, as well as metastasis to distant sites. In one systematic review of 32
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TABLE 2. Examples of Oral Antitussives Drug
Adults 12 years and older
Codeine Dextromethorphan Benzonate Guaifensen Hydrocodone
10-20 mg orally every 4 to 6 hours (120 mg/24 hours; available in elixir) 10-20 mg orally every 4 to 8 hours or 30 mg every 8 hours (120 mg/24 hours; lozenges or elixir) 100 mg orally 3 times daily; do not chew 5–20 mL orally every 4 hours (or tablets) 5 mL orally every 4 to 6 hours
From Tyson LB, ‘‘Cough’’ (p. 151). In: Camp-Sorrell D, Hawkins RA, Eds. Clinical Manual for the Oncology Advanced Practice Nurse. Ed 2. Pittsburgh, PA: Oncology Nursing Society: Copyright Ó 2006 by the Oncology Nursing Society. Reprinted with permission.52
lung cancer studies, Potter and Higginson53 found that the overall weighted mean prevalence of pain in persons with lung cancer was 47%; multiple sites of pain were noted, but the most common pain sites reported by persons with lung cancer were the chest and lumbar spine. Nociceptive or somatic pain was the major subtype of pain, but neuropathic pain accounted for 30%.53 Silvestri et al54 reported the three main causes of malignancy-related pain in lung cancer are skeletal metastases (34%), Pancoast tumor (31%), and chest wall disease (21%). The primary approach to cancer pain relief is pharmacologic. Basic principles of cancer pain control are recommended by several sources and should be used.2,55 Skeletal metastases usually present with localized pain. The diagnostic evaluation of bone pain includes plain x-rays and either whole-body FFluoro-2-Deoxy-Glucose-Positron Emission Tomography (FDG-PET) scan or whole body bone scan.56 Back or referred pain from vertebral body metastases warrant evaluation with magnetic resonance imaging for spinal cord compression because this is an oncologic emergency with dire consequences if undiagnosed. Palliative radiotherapy is the mainstay of treatment for painful skeletal metastases, complimented with optimal oral, transdermal or parenteral analgesia. Orthopedic evaluation for surgical fixation should be considered for patients with lytic lesions in weight-bearing bones because they are at risk for pathologic fractures.57 The benefit of zoledronic acid for treatment of skeletal metastases in patients with breast and prostate cancers, as well as multiple myeloma, has been established. However, a recent trial involving other solid tumor types, including lung cancer, showed the efficacy of using zoledronic acid compared with placebo to significantly
reduce time to first skeletal-related event, defined as bone pain, pathologic fractures, spinal cord compression, and hypercalcemia.58 Bukowski et al59 recommended zoledronic acid 4 mg infused intravenously over 15 minutes every 3 weeks in patients with NSCLC and bone metastases. Superior pulmonary sulcus tumor, also known as Pancoast tumor, is a primary lung tumor arising in the extreme apex of the lung. The tumor may involve or invade the lower trunk of the brachial plexus, the roots of the eighth cervical and first and second thoracic nerves, adjoining vertebral bodies of the upper thoracic spine, the upper thoracic sympathetic chain, the subclavian vessels, the adjacent ribs, and intercostal muscles. The characteristic clinical syndrome of pain in the shoulder and arm, sensorimotor loss along the ulnar nerve distribution, and Horner’s syndrome was described by Dr. Pancoast in 1932. The pain may be severe and unrelenting, worsened by movement of the affected arm, and often develops months before diagnosis is made.60 Treatment includes vigorous efforts to achieve local control. Radiotherapy alone at a dose of 6,000 cGy is the usual treatment; however, complete surgical excision, when possible, offers the most appreciable pain control.61 Pre- and postoperative radiotherapy is also considered. Pharmacologic management of superior sulcus pain syndrome is very challenging and includes opioids, neuropathic agents, and interventional pain therapy. Chest wall pain also is a common presentation in persons with lung cancer. Often the cause of the chest wall pain can be correlated with thoracic tumor location. Direct chest wall extension of tumor can cause radicular pain. Pleuritic pain can result from pleural invasion with or without effusion. Sternal pain or pressure can result from
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tumor or lymphadenopathy in the mediastinum. Non-specific, non-cardiac pain is noted as a result of tumor compression of surrounding structures.39 Chest wall pain can also be treatment-related, such as post-thoracotomy pain or pain subsequent to pleural drainage and pleurodesis. It is important to correlate the pain symptom with the underlying disease because this often leads to a specific treatment (ie, radiotherapy, tailored pharmacologic agent) and could be of prognostic value concerning pain control.62 Because pain is a prevalent cause of distress in lung cancer, pain control is a high priority in the supportive care of this population. The basics of screening for pain, comprehensive assessment, and methodical use of pain intervention guidelines are recommended. Establishing numerical pain rating levels that indicate pain emergency with proportional response as recommended by NCCN guidelines2 should be a standard approach. Ongoing reassessment of each intervention also is indicated if pain relief is to be achieved and sustained.
ANOREXIA/CACHEXIA
N
utritional decline is often a result of the cancer and its treatment. The prevalence of weight loss in oncology patients depends on tumor site, stage of disease, and treatment, and ranges from 31% to 100%.63-67 Weight loss of as little as 5% is associated with increased mortality and poor prognosis.63 In lung cancer, weight loss is associated with a decrease in survival of 3 to 5 months.68 Cancer Cachexia Syndrome (CCS) refers to the complex metabolic state that leads to depletion of energy and muscle stores in cancer patients.69 Unlike starvation, patients experiencing CCS lose both adipose and skeletal muscle mass, while preserving visceral muscle mass and increasing hepatic mass.70 Also, unlike starvation, the weight loss associated with CCS will continue despite increased administration of nutrients.69,70 Thus, increased caloric intake provides no benefit in terms of weight, survival, or QOL.69 For this reason, appetite stimulants are not an effective treatment for CCS.70 Although there is no universally accepted model that adequately explains the etiology of CCS in all patients,71 it is blamed in part on changes in cytokine and hormone levels. Pro-inflammatory cytokines such as tumor necrosis factor, interferon-g,
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and interleukins 1 and 6 are considered important mediators of CCS. In addition, tumor byproducts such as proteolysis inducing factor, lipid mobilizing factor, and mitochondria uncoupling proteins1, 2, and 3, exhibit specific effects on nutrient metabolism. Loss of body weight by patients with solid tumors is attributed to losses of fat, water, and fatfree mass.72-76 Malnourished cancer patients may experience a 41% decrease in fat-free mass.77 Patients with lung, gastrointestinal, and head and neck tumors can experience weight loss in excess of 10% of their pre-illness weight. Patients with solid tumors can lose as much as 1.34 kg of fatfree mass in 4 weeks.78 A small amount of body fat and the majority of visceral mass are preserved to an extent. Skeletal muscle loss is the primary form of lean body mass loss.79 These changes in body composition affect symptom control and complication rates. Fatigue and psychological symptoms, such as depression and anxiety, can have a multiplicative effect on weight loss.80 The presence of weight loss itself is a constant reminder of disease that interferes with QOL.81 Increased incidence of nutrition related symptoms is also correlated with decreases in QOL.82 A variety of pharmacologic agents have been used to treat or provide symptomatic relief for patients with CCS. Most agents are directed at improving appetite and sense of well-being. The majority of these drugs have failed to show sustained benefit, and long-term use can be associated with unacceptable side effects. The most effective treatment of CCS is the treatment of the underlying disease with the appropriate anticancer therapy while managing symptoms.70 It is important that treatment-related symptoms that may interfere with dietary intake (ie, nausea, diarrhea, constipation) are addressed immediately and in an aggressive manner.83 Routine use of a screening tool, which assesses the presence of dietary interfering symptoms on a regular basis, can be helpful in the early identification of symptoms that may impact nutrition status.82
PSYCHOSOCIAL DISTRESS
I
n one study of a large sample of cancer patients (n ¼ 4496), the prevalence of psychological distress and variations in distress among diagnoses were examined, showing that lung cancer patients surpassed all other patient groups in overall
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prevalence rate for distress (43.4%); however, the mean distress scores of persons with lung cancer were not significantly different than for persons with brain, liver, pancreatic, and head and neck cancer. It was thought that poor prognosis and self-attribution associated with smoking may play a critical role in the actual level of distress in persons with lung cancer.84-86 Depression can be one psychological symptom experienced by patients with lung cancer, including survivors. It is often underdiagnosed, especially by patients that have completed treatment.4 In 142 patients who had survived lung cancer for 5 years or longer, it was found that depressed mood was associated with a lower QOL.87 Assessing for and treating depression is essential to help patients improve QOL during their illness and into survivorship.4 When assessing for depression in persons with cancer, a focus on psychological symptoms such as feelings of helplessness, hopelessness, loss of self-esteem, and anhedonia is recommended. Somatic symptoms such as anorexia, fatigue, insomnia, and weight loss are of less value as diagnostic criteria. Associated and potentially treatable medical, endocrinologic, and neurologic problems are to be included with each assessment. Personal and family history of depression, substance abuse, life stresses, losses secondary to cancer, and social support also should be evaluated.88 Patients may have a depressive syndrome because of the physiological effects of cancer, which is called ‘‘mood disorder due to cancer.’’ This may be because of tumor involvement of the central nervous system or metabolic disturbances (ie, adrenal insufficiency or hypothyroidism).88 A diagnosis of ‘‘substance-induced mood disorder’’ is appropriate when depression is related to drug therapy such as corticosteroids, benzodiazepines, or narcotics. Cytokines, such as interferon for example, can cause depression in 30% to 50% of patients.88 First-line pharmacologic treatment for depression includes agents in the selective serotonin re-
uptake inhibitor (SSRI) drug category because they are better tolerated, have fewer sedative effects, and have a safe cardiac profile. Symptoms start to improve within 2 to 4 weeks. Side effects include nausea, sexual dysfunction, headache, somnolence or insomnia, and a brief period of increased anxiety.88 Psychological treatment or psychotherapy with a goal to reduce emotional distress and to improve coping ability and sense of control has been shown to be effective in treating anxiety and depression in cancer patients. Referral to appropriate disciplines to deliver therapy is indicated at times of crisis in the illness, such as at initial diagnosis, recurrence, or when treatments fail or patients perceive themselves as dying.88
CONCLUSION
P
ersons with lung cancer often experience multiple symptoms associated with disease and therapy. Oncology nurses are in strategic positions to assess and intervene to improve symptom control. Supportive or palliative care can be provided alone as the main focus of care or in combination with life-prolonging therapy. In either situation, an important goal is to improve the patient’s comfort and function. Much can be gained from collaboration with colleagues in other disciplines as they relate to clinical problems reviewed in this article. Using the expertise of colleagues from other specialties can facilitate optimal patient outcomes. Oncology nurses have a responsibility to seek current knowledge in all areas that guide their practice, including symptom management and supportive care. Overall, evidence for supportive care interventions is increasing but gaps in evidence remain. Further research is needed in select areas to show which interventions are effective or most effective and which groups of patients can benefit the most.
REFERENCES 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43-66. 2. National Comprehensive Cancer Network. NCCN Clinical practice guidelines in oncology. v.1.2007. Palliative care. Available at: http://www.nccn.org/professionals/physician_gls/PDF/ palliative.pdf (accessed Dec 18, 2007).
3. Cooley ME. Symptoms in adults with lung cancer. A systematic research review. J Pain Symptom Manage 2000; 19:137-153. 4. Fox SW, Lyon DE. Symptom clusters and quality of life in survivors of lung cancer. Oncol Nurs Forum 2006;33:931936.
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5. Chan CW, Richardson A, Richardson J. A study to assess the existence of the symptom cluster of breathlessness, fatigue and anxiety in patients with advanced lung cancer. Eur J Oncol Nurs 2005;9:325-333. 6. Gift AG, Stommel M, Jablonski A, Given W. A cluster of symptoms over time in patients with lung cancer. Nurs Res 2003;52:393-400. 7. Gift AG, Jablonski A, Stommel M, et al. Symptom clusters in elderly patients with lung cancer. Oncol Nurs Forum 2004;31:202-212. 8. Mitchell SA, Beck SL, Hood LE, et al. Putting evidence into practice: evidence-based interventions for fatigue during and following cancer and its treatment. Clin J Oncol Nurs 2007; 11:99-113. 9. Kim Y, Hickok JT, Morrow G. Fatigue and depression in cancer patients undergoing chemotherapy: an emotion approach. J Pain Symptom Manage 2006;32:311-321. 10. Munch TN, Stromgren AS, Pedersen L, et al. Multidimensional measurement of fatigue in advanced cancer patients in palliative care: an application of the multidimensional fatigue inventory. J Pain Symptom Manage 2006;31:533-541. 11. Tanaka K, Akechi T, Okuyama T, et al. Impact of dyspnea, pain, and fatigue on daily life activities in ambulatory patients with advanced lung cancer. J Pain Symptom Manage 2002;23:417-423. 12. National Comprehensive Cancer Network. NCCN Clinical practice guidelines in oncology. v.4.2007. Cancer-related fatigue. Available at: www.nccn.org/professionals/physician_gls/ PDF/fatigue.pdf (accessed Dec 18, 2007). 13. Johnston MP, Coward DD. Cancer-related fatigue: nursing assessment and management: increasing awareness of the effect of cancer-related fatigue. Am J Nurs 2001;101(suppl):19-22. 14. Kaasa S, Loge JH, Knobel H, et al. Fatigue. Measures and relation to pain. Acta Anaesthesiol Scand 1999;43:939-947. 15. Cella DF, Bonomi AE, Lloyd SR, et al. Reliability and validity of the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Lung Cancer 1995;12: 199-220. 16. Hollen PJ, Gralla RJ, Kris MG, et al. Quality of life assessment in individuals with lung cancer: testing the Lung Cancer Symptom Scale (LCSS). Eur J Cancer 1993;29A(suppl 1):S51-S58. 17. Mendoza T, Wang X, Cleeland C, et al. The rapid assessment of fatigue severity in cancer patients. Cancer 1999; 85:1186-1196. 18. Stricker CT, Drake D, Hoyer KA, et al. Evidence-based practice for fatigue management in adults with cancer: exercise as an intervention. Oncol Nurs Forum 2004;31:963-976. 19. Barsevick AM, Dudley W, Beck S, et al. A randomized clinical trial of energy conservation for patients with cancerrelated fatigue. Cancer 2004;100:1302-1310. 20. Nail LM. Fatigue in patients with cancer. Oncol Nurs Forum 2002;29:537-546. 21. Morrow GR, Shelke AR, Roscoe JA, et al. Management of cancer-related fatigue. Cancer Invest 2005;23:229-239. 22. Beach P, Siebeneck B, Buderer NF, et al. Relationship between fatigue and nutritional status in patients receiving radiation therapy to treat lung cancer. Oncol Nurs Forum 2001;28:1027-1031. 23. Yang YH. Relationship between fatigue and nutritional status in patients with cancer undergoing radiotherapy. Taehan Kanho Hakhoe Chi 2003;33:478-487. 24. Gramignano G, Lusso MR, Madeddu C, et al. Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative
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stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy. Nutrition 2006;22:136-145. 25. Wells M, Sarna L, Cooley ME, et al. Use of complementary and alternative medicine therapies to control symptoms in women living with lung cancer. Cancer Nurs 2007;30:45-55. 26. Administration USFaD. Information on erythropoiesis stimulating agents (ESA). Available at: http://fda.gov/cder/drug/ infopage?RHE/default.htm. (accessed Dec 18, 2007). 27. Barnes EA, Bruera E. Fatigue in patients with advanced cancer: a review. Int J Gynecol Cancer 2002;12:424-428. 28. Hopwood P, Stephens RJ. Symptoms at presentation for treatment in patients with lung cancer: implications for the evaluation of palliative treatment. The Medical Research Council (MRC) Lung Cancer Working Party. Br J Cancer 1995;71:633-636. 29. Dudgeon DJ, Kristjanson L, Sloan JA, et al. Dyspnea in cancer patients: Prevalence and associated factors. J Pain Symptom Manage 2001:2195–2102. 30. Ripimonti C, Fusco F. Respiratory problems in supportive care. Cancer 2002;10:204-216. 31. Brown ML, Carrieri V, Janson B, et al. Lung cancer and dyspnea: the patient’s perception. Oncol Nurs Forum 1986;13:19-24. 32. O’Driscoll M, Corner J, Bailey C. The experience of breathlessness in lung cancer. Eur J Cancer Care (Engl) 1999;8:37-43. 33. American Thoracic Society. Dyspnea. Mechanisms, assessment, and management: a consensus statement. Am J Respir Crit Care Med 1999;159:321-340. 34. Dudley DL, Martin CJ, Holmes TH. Psychophysiologic studies of pulmonary ventilation. Psychosom Med 1964;26: 645-660. 35. Gift AG. Psychologic and physiologic aspects of acute dyspnea in asthmatics. Nurs Res 1991;40:196-199. 36. Smith EL, Hann DM, Ahles TA, et al. Dyspnea, anxiety, body consciousness, and quality of life in patients with lung cancer. J Pain Symptom Manage 2001;21:323-329. 37. Chetta A, Gerra G, Foresi A, et al. Personality profiles and breathlessness perception in outpatients with different gradings of asthma. Am J Respir Crit Care Med 1998;157:116-122. 38. Joyce M, Beck SL. Measuring oncology nursing-sensitive patient outcomes: evidence based summary. Available at: http://onsopcontent.ons.org/toolkits/evidence/Clinical/pdf/ DyspneaTools.pdf (accessed July 24, 2005). 39. Houlihan NG, Inzeo D, Joyce M, et al. Symptom management of lung cancer. Clin J Oncol Nurs 2004;8:645-652. 40. Bruera E, de Stoutz N, Velasco-Leiva A, et al. Effects of oxygen on dyspnoea in hypoxaemic terminal-cancer patients. Lancet 1993;342:13-14. 41. Bruera E, Sweeney C, Willey J, et al. A randomized controlled trial of supplemental oxygen versus air in cancer patients with dyspnea. Palliat Med 2003;17:659-663. 42. Dudgeon DJ. Managing dyspnea and cough. Hematol Oncol Clin North Am 2002;16:557-577. 43. Jennings AL, Davies AN, Higgins JP, et al. A systematic review of the use of opioids in the management of dyspnoea. Thorax 2002;57:939-944. 44. Allard P, Lamontagne C, Bernard P, et al. How effective are supplementary doses of opioids for dyspnea in terminally ill cancer patients? A randomized continuous sequential clinical trial. J Pain Symptom Manage 1999;17:256-265. 45. Joyce M, McSweeney M, Carrieri-Kohlman VL, et al. The use of nebulized opioids in the management of dyspnea: evidence synthesis. Oncol Nurs Forum 2004;31:551-561.
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46. Coyne PJ, Viswanathan R, Smith TJ. Nebulized fentanyl citrate improves patients’ perception of breathing, respiratory rate, and oxygen saturation in dyspnea. J Pain Symptom Manage 2002;23:157-160. 47. Kohara H, Ueoka H, Aoe K, et al. Effect of nebulized furosemide in terminally ill cancer patients with dyspnea. J Pain Symptom Manage 2003;26:962-967. 48. Campbell ML. Terminal dyspnea and respiratory distress. Crit Care Clin 2004;20:403-417. 49. Ripamonti C. Management of dyspnea in advanced cancer patient. Support Care Cancer 1999;7:233-243. 50. Bredin M, Corner J, Krishnasamy M, et al. Multicentre randomised controlled trial of nursing intervention for breathlessness in patients with lung cancer. BMJ 1999;318:901-904. 51. Kvale PA, Simoff M, Prakash UB. Palliative care. Chest 2003;123:284S-311S. 52. Tyson LB. Cough. In: Camp-Sorrell D, Hawkins R, eds. Clinical manual for the oncology advanced practice nurse. Ed 2. Pittsburgh, PA: Oncology Nursing Society; 2006, pp 147-151. 53. Potter J, Higginson IJ. Pain experienced by lung cancer patients: a review of prevalence, causes and pathophysiology. Lung Cancer 2004;43:247-257. 54. Silvestri GA, Sherman C, Williams T, et al. Caring for the dying patient with lung cancer. Chest 2002;122:1028-1036. 55. Miaskowski C, Cleary J, Burney R, et al. Guideline for the management of cancer pain in adults and children Glenview, IL: American Pain Society; 2004. 56. Cheran SK, Herndon JE II, Patz EF Jr. Comparison of whole-body FDG-PET to bone scan for detection of bone metastases in patients with a new diagnosis of lung cancer. Lung Cancer 2004;44:317-325. 57. Pinover W, Coia L. Palliative radiation therapy. In: Berger AM, Portenoy R, Weissman D, eds. Principles and practice of supportive oncology. Philadelphia, PA: Lippincott-Raven; 1998, pp 603-626. 58. Rosen LS, Gordon D, Tchekmedyian S, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial–the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 2003;21:3150-3157. 59. Bukowski R, Rosen L, Gordon D, et al. Long-term therapy with zoledronic acid is effective and safe in reducing the risk of skeletal complications in patients with bone metastases from non-small cell lung cancer. Lung Cancer 2003;41(suppl 2): S262-S263. 60. Ginsberg R, Payne D, Shamji F. Superior sulcus tumors. In: Aisner J, Arriagada R, Green M, Martini N, Perry M, eds. Comprehensive textbook of thoracic oncology. Baltimore, MD: Williams &Wilkins; 1996, pp 375-387. 61. Guerrero M, Williams S. Pancoast tumor. E-Medicine. Available at: http://www.emedicine.com/radio/topic515.htm 2004 (accessed March 23, 2007). 62. Klastersky J. Supportive care in cancer patients. In: Aisner J, Arriagada R, Green M, Martini N, Perry M, eds. Comprehensive textbook of thoracic oncology. Baltimore, MD: Williams & Wilkins; 1996, pp 980-1001. 63. Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 1980;69:491-497. 64. Bozzetti F. Rationale and indications for preoperative feeding of malnourished surgical cancer patients. Nutrition 2002;18:953-959.
65. Linn BS, Robinson DS, Klimas NG. Effects of age and nutritional status on surgical outcomes in head and neck cancer. Ann Surg 1988;207:267-273. 66. Nguyen TV, Yueh B. Weight loss predicts mortality after recurrent oral cavity and oropharyngeal carcinomas. Cancer 2002;95:553-562. 67. Haugstvedt TK, Viste A, Eide GE, et al. Factors related to and consequences of weight loss in patients with stomach cancer. The Norwegian Multicenter experience. Norwegian Stomach Cancer Trial. Cancer 1991;67:722-729. 68. Milstein D, Sapir D, Cohen Y, et al. Prognostic factors in patients with lung cancer. Isr J Med Sci 1988;24:588592. 69. Barber M. The pathophysiology and treatment of cancer cachexia. Nutr Clin Pract 2002;17:203-209. 70. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer 2002;2:862-871. 71. Lind D, Souba W, Copeland E. Weight loss and cachexia. In: Abeloff M, Armitage J, Lichter A, Niederhuber J, eds. Clinical oncology. New York, NY: Churchill Livingstone; 1995, pp 393407. 72. Cohn S, Sawitsky A, Vartsky D. In vivo quantification of body nitrogen and body composition in cancer patients and cancer nutrition studies. Nutr Cancer 1980;2:67-71. 73. Cohn S, Ellis K, Vartsky D. Comparison of methods of estimating body fat in normal subjects and cancer patients. Am J Clin Nutr 1981;34:2839-2847. 74. Cohn S, Gartenhaus W, Sawitsky A. Compartmental body composition of cancer patients by measurement of total body nitrogen, potassium, and water. Metabolism 1981;30: 222-229. 75. Cohn S, Gartenhaus W, Vartsky D. Body composition and dietary intake in neoplastic disease. Am J Clin Nutr 1981; 34:1997-2004. 76. Cohn S, Vaswani A, Vartsky D. In vivo quantification of body nitrogen for nutritional assessment. Am J Clin Nutri 1982;35:1186-1191. 77. Shizgal HM. Body composition of patients with malnutrition and cancer. Summary of methods of assessment. Cancer 1985;55(suppl):250-253. 78. May P, Barber A, D’Olimpio J, et al. Reversal of cancer related wasting using oral supplementation with a combination of B-hydroxy-B-methylbutyrate, arginine, adn glutamine. Am J Surg 2002;183:471-479. 79. Marian M. Cancer cachexia: prevalence, mechanisms, and interventions. Support Line 1998;20:3-12. 80. Capra S, Ferguson M, Ried K. Cancer: impact of nutrition intervention outcome–nutrition issues for patients. Nutrition 2001;17:769-772. 81. Ovesen L, Allingstrup L, Hannibal J, et al. Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study. J Clin Oncol 1993;11:2043-2049. 82. McCallum PD, Elliott L, Molseed L, Grant B, eds. The clinical guide to oncology nutrition. Chicago, IL: American Dietetic Association: 2006. 83. Brown JK. A systematic review of the evidence on symptom management of cancer-related anorexia and cachexia. Oncol Nurs Forum 2002;29:517-532. 84. Zabora J, Brintzenhofeszoc K, Curbow B, et al. The prevalence of psychological distress by cancer site. Psychooncology 2001;10:19-28.
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85. Faller H, Schilling S, Lang H. Causal attribution and adaptation among lung cancer patients. J Psychosomatic Res 1995; 39:619-627. 86. Walker MS, Zona DM, Fisher EB. Depressive symptoms after lung cancer surgery: Their relation to coping style and social support. Psychooncology 2006;15:684-693.
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87. Sarna L, Evangelista L, Tashkin D, et al. Impact of respiratory symptoms and pulmonary function on quality of life of long-term survivors of non-small cell lung cancer. Chest 2004;125:439-445. 88. Miller K, Massie MJ. Depression and anxiety. Cancer J 2006;12:388-397.
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OBJECTIVES: To discuss common lung cancer symptoms including prevalence, assessment, etiology, and recommended interventions.
DATA SOURCES: Research studies and systematic reviews.
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CONCLUSION: A mandate in care of persons with lung cancer is to deliver supportive care concurrently with life-prolonging care or as the main focus of care. Most are diagnosed with advanced disease that impairs health with both physical and psychological symptoms.
IMPLICATIONS FOR NURSING PRACTICE: Early assessment and comprehensive management of symptoms are main components of improving quality of life and functional status for those living with lung cancer.
KEYWORDS: Lung cancer, palliative care, fatigue, dyspnea, cough, pain, cachexia, anorexia, psychosocial distress
Margaret Joyce, PhD(c), RN, AOCNÒ: Nurse Practitioner, Thoracic Oncology, The Cancer Institute of New Jersey, New Brunswick, NJ. Sue Schwartz, MSN, RN, OCNÒ: Nurse Clinician, Thoracic, GU and Breast Studies, The Cancer Institute of New Jersey, New Brunswick, NJ. Maureen Huhmann, MS, RD: Assistant Professor, Department of Primary Care, School Health Related Professions-University of Medicine and Dentistry of New Jersey Clinical Dietitian, The Cancer Institute of New Jersey, New Brunswick, NJ. Address correspondence to Margaret Joyce, PhD(c), RN, AOCNÒ, 104 Wycombe Place, Somerset, NJ 08873; e-mail: joycepe@ umdnj.edu
Ó 2008 Elsevier Inc. All rights reserved. 0749-2081/07/2401-$30.00/0 doi:10.1016/j.soncn.2007.11.013
MARGARET JOYCE, SUE SCHWARTZ, AND MAUREEN HUHMANN
E
ARLY assessment and comprehensive management of both disease and treatment-related symptoms are main components of improving quality of life (QOL) and functional status for those living with lung cancer. Lung cancer, with an estimated 160,390 deaths in 2007, remains the leading cause of cancer death among US men and women.1 This is due in part to the fact that there is no routine screening recommended for lung cancer and, as a result, many tumors are discovered at a late stage of disease. A diagnosis that includes regional or distant spread of disease can produce significant physical and psychological symptoms. Hence, the mandate in the care of persons with lung cancer is to deliver supportive or palliative care concurrently with life-prolonging care or, in some cases, as the main focus of care.2 In addition, the number of symptoms to be managed and therefore the intensity of supportive care required may change as a person moves through the trajectory of their illness. Common symptoms reported by newly diagnosed lung cancer patients include fatigue, pain, anorexia, coughing, and insomnia. However, pain, dyspnea, and anorexia are ranked by patients with advanced lung cancer as the most common and most intense.3 Several researchers have attempted to characterize symptom clusters in lung cancer. Symptom clusters refer to concurrent, related symptoms that may have a synergistic or collective effect on patient outcomes. Depression and fatigue were found in cluster in a group of persons with lung cancer of mixed stages.4 Chan et al5 found a cluster of breathlessness, fatigue, and anxiety in a small sample of advanced lung cancer patients undergoing palliative radiotherapy to various sites. Gift et al6 found, through secondary analysis of a large data set, that nausea, fatigue, weakness, appetite loss, weight loss, altered taste, and vomiting clustered together in a group of newly diagnosed lung cancer patients with both early and late stage disease. A common antecedent related to the cluster was treatment with chemotherapy. This group also reported that the severity of the symptoms in this cluster declined over time, perhaps because of the completion of chemotherapy.7 It is logical to assume that certain symptom clusters may be timed with respect to therapy. Despite the current therapy, or lack thereof, persons with lung cancer experience multiple concurrent symptoms
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that require attention. This discussion is limited to six common symptoms experienced by persons with lung cancer and offers evidence-based practice recommendations.
FATIGUE
O
ne of the most severe and debilitating symptoms for patients undergoing cancer treatment and at the end of life is fatigue.8,9 Seventy-five percent to 100% of patients undergoing chemotherapy report fatigue. Cancer-related fatigue has been found to strongly affect QOL.9,10 In 171 outpatients with advanced lung cancer, Tanaka et al11 found that fatigue affected at least one activity of daily living in more than half the patients (52%). Walking and work were reported as the two physical activities impacted the most. Cancer-related fatigue is a distressing, persistent, and subjective sense of tiredness or exhaustion related to cancer or to treatment for cancer that is not proportional to recent activity and interferes with functioning.12 Regular screening for fatigue is recommended. A simple numerical 0-to10 scale can be used on initial visit and at regular intervals to capture and quantify current fatigue and documentation over time can indicate improvement or decline.12 Patient input is essential when assessing for fatigue. It is crucial to acknowledge fatigue to be as important as other symptoms that affect QOL.13 Clinical assessment for fatigue should include consideration of: 1. Hemoglobin/hematocrit: regular screening of hemoglobin/hematocrit to detect for anemia (hemoglobin # 12 g/dL). 2. Physical appearance: Does the patient look tired? Do they look rested? How is their color? 3. Shortness of breath: Often associated with fatigue. Depending on the level of anemia, patients may be short of breath with activities of daily living. 4. Quality of sleep: Is there a change in sleep habits? Do they nap during the day? Do they go to bed the same time each night and get up the same time each day? Is the quality of sleep the same? Do they wake up feeling refreshed? 5. Pain: A complete pain assessment is needed as fatigue may be a consequence of pain.14 6. Psychosocial issues: Are they experiencing increased stress? Do they have money concerns or concerns about the disease and its treatment?
Two lung cancer-specific assessment tools with demonstrated reliability and validity that assess the impact of fatigue are (1) The Functional Assessment of Cancer Therapy—Lung Cancer (FACT-L) and (2) The Lung Cancer Symptom Scale (LCSS). FACT-L is a 44-item self-report that measures physical and functional well-being with assessment of lung-specific symptoms.15 The LCSS is a site-specific measure of QOL with nine visual analogue scales that evaluate six major symptoms associated with lung cancer and the effect on symptomatic distress, function, and global QOL.16 One general tool to measure the severity of fatigue is The Brief Fatigue Inventory (BFI). The BFI allows rapid assessment with nine questions that evaluate fatigue using a scale of 0 to 10, with 0 being ‘‘No fatigue’’ to 10 being ‘‘As bad as you can imagine.’’ Six of the nine questions ask how much fatigue interferes with various activities of daily living.17 Non-Pharmacologic Interventions Exercise is one intervention to manage fatigue supported by strong evidence from well-designed studies.8 The National Comprehensive Cancer Network (NCCN) guidelines for the management of cancer-related fatigue recommend that all patients, whether actively on treatment or in follow-up, should be encouraged to participate in regular physical activity.12 The type of exercise, frequency, intensity, and duration should be tailored to the patient’s needs. For example, patients with skeletal muscle weakness may need strength training, whereas those who have maintained their lean body mass may benefit from aerobic exercise.18 Energy conservation is defined as the deliberate, planned management of an individual’s personal energy resources so that valued activities and goals can be maintained.19 Energy conservation and activity management as an intervention aims to balance patient activities and rest by prioritizing and planning their day.20 This may include scheduling household chores or using friends or family to assist with activities such as shopping, cooking or cleaning. Sleep hygiene practices that include avoiding long or late-afternoon naps, going to bed only when sleepy, using the bedroom and bed for sleep and sexual activities only, going to bed and getting up at regular times, and avoiding stimulating activity and caffeine, may be helpful to patients. Using
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relaxation techniques at least 1 hour before going to bed has been effective as well.8,21 Although fatigue scores did not decrease simultaneously with various indicators of nutritional status (weight and pre-albumin) in patients with lung cancer receiving radiation therapy in one study,22 a subsequent study contradicts this.23 It seems logical that insufficient provision of nutrients can contribute to fatigue. Data indicate that increases in lean body mass can lead to improvement in reports of fatigue.24 Adequate provision of calories and protein in concert with resistance exercise are essential to increase lean body mass. There is a lack of data to support hydration and nutritional approaches to fatigue management. There is also limited data to support the use of vitamins, minerals, herbs, and nutritional supplements.20 Wells et al25 described the use of complementary and alternative medicine therapies including herbs, tea, acupuncture, massage, meditation, and prayer to control symptoms, including fatigue, in women living with lung cancer. Women used complementary alternative method (CAM) therapies most often for controlling pain, followed by difficulty breathing and fatigue.25 Prayer was the most commonly used CAM for all symptoms. Evaluation of effectiveness of CAM therapies was not reported.
Pharmacologic Interventions Erythropoietin. Data from systematic reviews suggest that patients receiving erythropoiesis stimulating therapy to correct anemia with hemoglobin less than 10g/dL experience decreased fatigue; however, evidence does not substantiate that erythropoietin improves fatigue when anemia is less severe.8 Recent evidence from a clinical study prompted the US Food and Drug Administration to issue an alert that patients treated with an erythropoiesis-stimulating agent and dosed to a target hemoglobin of 13.5 g/dL are at significant risk for serious and life-threatening cardiovascular complications as compared with use of erythropoiesis stimulating therapy to a target hemoglobin of 11.3g/dL.26 Caution is advised in the use of erythropoiesis-stimulating agents as an intervention for fatigue not associated with severe anemia. Psychostimulants. There have been no placebo-controlled, randomized clinical trials to evaluate the use of psychostimulants, such as methylphenidate or dextroamphetamine, in patients
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with fatigue. Potential side effects include irritability, insomnia, labile mood, and tachycardia.9 The use of steroids is associated with a decrease in fatigue, although the mechanism of action is not known. Most studies have used prednisone 20 to 40 mg/day for 2 to 4 weeks. However, use of steroids should be approached with caution because prolonged use can contribute to myopathy and infection.27 Antidepressants. Depression is common in patients with cancer. However, the use of antidepressants in fatigued patients that are not depressed is not supported by evidence.20,21 Patient education on fatigue and its management is essential to the successful treatment of fatigue. If adequately informed, patients can adjust and adapt to the symptom more realistically. Because fatigue is one of the prominent and pervasive symptoms experienced by persons with lung cancer, teaching and counseling may contribute to fatigue management and overall support.
DYSPNEA
D
yspnea or breathlessness is one of the three most frequently reported symptoms by persons with lung cancer, who also rank it in the top three most severe symptoms.28 The prevalence of dyspnea in the lung cancer population varies from 55% to 87%,29 with most persons reporting it at end of life.30 Lung cancer-related dyspnea varies with an individual’s diagnostic stage, primary tumor location, and therapy.29 Persons with lung cancer describe dyspnea as frightening.31,32 Reduction in functional status and subsequent disability are frequent consequences of dyspnea.33 Furthermore, dyspnea is a difficult problem to manage and, when witnessed, it evokes a response that begs intervention from patients, caregivers, and health professionals. Generally, the term ‘‘dyspnea’’ is applied to sensations experienced by individuals who report unpleasant or difficult respiration. The American Thoracic Society defines dyspnea as ‘‘a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.’’33(p322) Many factors can converge to cause and contribute to the symptom of dyspnea. It is not uncommon for a person with lung cancer to have, in addition to a primary lung tumor, a combination of other factors contributing to dyspnea such as a pleural effusion, anemia, cachexia, and
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underlying chronic obstructive pulmonary disease. Additionally, cognitive variables such as anxiety and depression,34-36 or personality,37 have been shown to modify dyspnea. Hence, the threshold perception of dyspnea varies widely with individuals and is related only moderately to the degree of pulmonary dysfunction.33 Assessment of dyspnea is a challenge because of the symptom’s subjective nature. The most common method of assessment is self-report of the activity level that causes awareness of the symptom. The visual analog scale and numerical rating scale have been shown to be valid and reliable in assessing cancer-related dyspnea.38 Evaluation of dyspnea includes complete history and a focused review surrounding the symptom such as temporal onset, precipitating or relieving events, and response to medication or behavioral approaches. A dyspnea-focused physical exam includes all vital signs and a cardiopulmonary physical assessment. The choice of appropriate diagnostic tests is guided by the stage of disease, usefulness of the information for possible therapeutic intervention, and patient choice. Basic diagnostic testing includes pulse oximetry at rest and with exertion, if feasible, as well as complete blood count. A chest radiograph may be indicated to evaluate acute problems. Considering the complex nature of dyspnea, an important goal of assessment is to differentiate an acute and possibly reversible cause of dyspnea from a condition that requires palliative or supportive interventions. Symptomatic management of dyspnea is based on oxygen therapy, pharmacologic therapy, and general supportive measures. Usually a combination of all three is used to promote comfort, increase exercise tolerance, and support social and emotional well being.39 Oxygen Therapy There is evidence that those patients who are hypoxemic at rest on room air report decreased dyspnea with supplemental oxygen.40 However, the routine use of supplemental oxygen for non-hypoxemic patients did not show a benefit in one study,41 so the recommendation in the absence of hypoxia is less clear. An individual’s response to the effect of oxygen therapy must be assessed. Increased ambient air flow across the face or nasal mucosa, such as generated by oxygen flow or a fan, may alter the perception of dyspnea through poorly understood mechanisms.42
Pharmacologic Therapy Strong evidence from a meta-analysis and smaller studies support the use of short-acting oral and parenteral opioids to treat dyspnea in those with advanced disease.43 Opioids have a respiratory depressive effect that blunts the perception of dyspnea so that for a given stimulus, the intensity of respiratory sensation is reduced.33 Although, morphine was the predominant opioid used in most studies, evidence about a specific dose recommendation is lacking. One exception is a study that showed a supplemental opioid dose equal to 25% of a regular 4-hour opioid dose was as effective as 50%.44 In general, opioid-tolerant patients reported dyspnea relief from supplemental opioid dosing. Further research is needed to find the most beneficial opioid and opioid dose to relieve dyspnea, but conducting research in persons experiencing dyspnea is difficult because of their unstable clinical status. Currently there is no convincing evidence that nebulized opioids are effective in relieving dyspnea, although benefit is reported in some situations.43,45 Individual uncontrolled trials of other nebulized medications such as fentanyl46 and furosemide47 show promise, but need further confirmation before adoption can be recommended. There is a conflicting expert opinion regarding the use of benzodiazepines; some recommend it to treat anxiety associated with dyspnea2,48; others claim the use of an anxiolytic is not supported for relief of cancer-related dyspnea.42,49 In some patients a trial of a benzodiazepine may be reasonable, particularly in those with morbid anxiety or history of panic attacks.33 Because of the common risk factor of tobacco use, persons with lung cancer also present with coexisting pulmonary diagnoses such as obstructive airway disease. Treatment with inhaled beta-2-adrenergic agonists (albuterol), inhaled anticholinergics, and sustained-release theophylline has been shown to improve dyspnea in patients with stable chronic obstructive pulmonary disease.42 General Supportive Measures Persons with dyspnea usually find measures such as positioning, decreasing energy expenditure, and relaxation strategies helpful in minimizing dyspnea. One multicenter randomized trial found that patients with lung cancer who attended weekly sessions to receive specialized nursing
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interventions reported a decrease in breathlessness and improved life quality compared with those who received usual care.50 These interventions included pulmonary assessment, education about breathing control, relaxation and distraction strategies, and emotional support. This rehabilitative approach to cancer-related dyspnea, which is effective in relieving dyspnea from other etiologies, needs confirmation with respect to which intervention or which combination of the interventions are the most significant.
COUGH
C
ough in cancer patients can be a result of direct or indirect tumor effect, treatment, and other unrelated problems.42 Table 1 outlines potential causes of cough in persons with cancer. The initial focus to relieve cough, as with dyspnea, is therapy aimed at the underlying etiology. Central airway obstruction, a common cause of cough and dyspnea in persons with lung cancer, may be palliated with bronchoscopy, which allows visualization of the airway and possible insertion of a stent to open an obstructed airway or laser resection of an obstructing tumor. Malignant pleural effusions are another common cause of cough; symptom relief is possible with thoracentesis drainage of fluid.51 However, therapy is not always effective or cough relief is delayed requiring interim palliative interventions. Typically, the symptomatic management of cough is guided by whether the cough produces sputum. The management goal is to either promote expectoration of sputum or suppress the cough if it is non-productive. Adequate hydration, air humidification, and chest physiotherapy can promote expectoration. Both a pharmacologic expectorant such as guaifenesin or a nebulized mucolytic such as acetylcysteine aim to thin secretions, promote expectoration, and thus decrease cough. Often the cough is unrelenting or non-productive, and cough suppression becomes the management goal. As most patients discover themselves, some relief can be obtained from cough lozenges that promote saliva production; some cough lozenges contain local anesthetics to soothe sensory nerve endings in the pharynx. Table 2 lists common oral antitussives, dose, and frequency.52 Benzonatate is a prescription cough suppressant that may be trialed, but opioid cough suppressants are usually required. One exception
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TABLE 1. Causes of Cough in Cancer Patients Cough directly caused by cancer Pulmonary parenchyma involvement (primary or metastatic) Lymphangitic carcinomatosis Intrinsic or extrinsic airways obstruction by tumor Pleural tumor Pleural effusion Multiple tumor microemboli Pulmonary leukostasis Superior vena cava syndrome Cough caused by cancer treatment Chemotherapy induced pulmonary toxicity Chemotherapy induced cardiomyopathy Radiation pneumonitis Cough indirectly caused by cancer Cachexia Pulmonary aspiration Pulmonary emboli Cough unrelated to cancer Cough caused by chronic obstructive pulmonary disease Asthma Congestive heart failure Interstitial lung disease Pneumothorax Upper respiratory tract infection Bronchiectasis Gastroesophageal reflux Postnasal drip Related other medications From Hematology/Oncology Clinics of North America, 16(3), Dudgeon DJ: Managing Dyspnea and Cough, p. 570. Copyright Ó 2002, reprinted with permission from Elsevier.42
is dextromethorphan, a non-prescription antitussive that acts through non-opioid receptors that may equal codeine as a cough suppressant.42 Codeine is the most widely used opioid for cough suppression. Hydrocodone is a good alternative to codeine. The adverse effects of constipation, nausea, and somnolence are to be expected when opioids are used to suppress cough; practitioners are cautioned to use complementary regimens to prevent anticipated side effects.
PAIN
P
ain is a prevalent symptom in lung cancer. Local tumor invasion of the pleura, ribs, thoracic spinal cord, or brachial plexus are common causes of pain in lung cancer, as well as metastasis to distant sites. In one systematic review of 32
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TABLE 2. Examples of Oral Antitussives Drug
Adults 12 years and older
Codeine Dextromethorphan Benzonate Guaifensen Hydrocodone
10-20 mg orally every 4 to 6 hours (120 mg/24 hours; available in elixir) 10-20 mg orally every 4 to 8 hours or 30 mg every 8 hours (120 mg/24 hours; lozenges or elixir) 100 mg orally 3 times daily; do not chew 5–20 mL orally every 4 hours (or tablets) 5 mL orally every 4 to 6 hours
From Tyson LB, ‘‘Cough’’ (p. 151). In: Camp-Sorrell D, Hawkins RA, Eds. Clinical Manual for the Oncology Advanced Practice Nurse. Ed 2. Pittsburgh, PA: Oncology Nursing Society: Copyright Ó 2006 by the Oncology Nursing Society. Reprinted with permission.52
lung cancer studies, Potter and Higginson53 found that the overall weighted mean prevalence of pain in persons with lung cancer was 47%; multiple sites of pain were noted, but the most common pain sites reported by persons with lung cancer were the chest and lumbar spine. Nociceptive or somatic pain was the major subtype of pain, but neuropathic pain accounted for 30%.53 Silvestri et al54 reported the three main causes of malignancy-related pain in lung cancer are skeletal metastases (34%), Pancoast tumor (31%), and chest wall disease (21%). The primary approach to cancer pain relief is pharmacologic. Basic principles of cancer pain control are recommended by several sources and should be used.2,55 Skeletal metastases usually present with localized pain. The diagnostic evaluation of bone pain includes plain x-rays and either whole-body FFluoro-2-Deoxy-Glucose-Positron Emission Tomography (FDG-PET) scan or whole body bone scan.56 Back or referred pain from vertebral body metastases warrant evaluation with magnetic resonance imaging for spinal cord compression because this is an oncologic emergency with dire consequences if undiagnosed. Palliative radiotherapy is the mainstay of treatment for painful skeletal metastases, complimented with optimal oral, transdermal or parenteral analgesia. Orthopedic evaluation for surgical fixation should be considered for patients with lytic lesions in weight-bearing bones because they are at risk for pathologic fractures.57 The benefit of zoledronic acid for treatment of skeletal metastases in patients with breast and prostate cancers, as well as multiple myeloma, has been established. However, a recent trial involving other solid tumor types, including lung cancer, showed the efficacy of using zoledronic acid compared with placebo to significantly
reduce time to first skeletal-related event, defined as bone pain, pathologic fractures, spinal cord compression, and hypercalcemia.58 Bukowski et al59 recommended zoledronic acid 4 mg infused intravenously over 15 minutes every 3 weeks in patients with NSCLC and bone metastases. Superior pulmonary sulcus tumor, also known as Pancoast tumor, is a primary lung tumor arising in the extreme apex of the lung. The tumor may involve or invade the lower trunk of the brachial plexus, the roots of the eighth cervical and first and second thoracic nerves, adjoining vertebral bodies of the upper thoracic spine, the upper thoracic sympathetic chain, the subclavian vessels, the adjacent ribs, and intercostal muscles. The characteristic clinical syndrome of pain in the shoulder and arm, sensorimotor loss along the ulnar nerve distribution, and Horner’s syndrome was described by Dr. Pancoast in 1932. The pain may be severe and unrelenting, worsened by movement of the affected arm, and often develops months before diagnosis is made.60 Treatment includes vigorous efforts to achieve local control. Radiotherapy alone at a dose of 6,000 cGy is the usual treatment; however, complete surgical excision, when possible, offers the most appreciable pain control.61 Pre- and postoperative radiotherapy is also considered. Pharmacologic management of superior sulcus pain syndrome is very challenging and includes opioids, neuropathic agents, and interventional pain therapy. Chest wall pain also is a common presentation in persons with lung cancer. Often the cause of the chest wall pain can be correlated with thoracic tumor location. Direct chest wall extension of tumor can cause radicular pain. Pleuritic pain can result from pleural invasion with or without effusion. Sternal pain or pressure can result from
SUPPORTIVE CARE IN LUNG CANCER
tumor or lymphadenopathy in the mediastinum. Non-specific, non-cardiac pain is noted as a result of tumor compression of surrounding structures.39 Chest wall pain can also be treatment-related, such as post-thoracotomy pain or pain subsequent to pleural drainage and pleurodesis. It is important to correlate the pain symptom with the underlying disease because this often leads to a specific treatment (ie, radiotherapy, tailored pharmacologic agent) and could be of prognostic value concerning pain control.62 Because pain is a prevalent cause of distress in lung cancer, pain control is a high priority in the supportive care of this population. The basics of screening for pain, comprehensive assessment, and methodical use of pain intervention guidelines are recommended. Establishing numerical pain rating levels that indicate pain emergency with proportional response as recommended by NCCN guidelines2 should be a standard approach. Ongoing reassessment of each intervention also is indicated if pain relief is to be achieved and sustained.
ANOREXIA/CACHEXIA
N
utritional decline is often a result of the cancer and its treatment. The prevalence of weight loss in oncology patients depends on tumor site, stage of disease, and treatment, and ranges from 31% to 100%.63-67 Weight loss of as little as 5% is associated with increased mortality and poor prognosis.63 In lung cancer, weight loss is associated with a decrease in survival of 3 to 5 months.68 Cancer Cachexia Syndrome (CCS) refers to the complex metabolic state that leads to depletion of energy and muscle stores in cancer patients.69 Unlike starvation, patients experiencing CCS lose both adipose and skeletal muscle mass, while preserving visceral muscle mass and increasing hepatic mass.70 Also, unlike starvation, the weight loss associated with CCS will continue despite increased administration of nutrients.69,70 Thus, increased caloric intake provides no benefit in terms of weight, survival, or QOL.69 For this reason, appetite stimulants are not an effective treatment for CCS.70 Although there is no universally accepted model that adequately explains the etiology of CCS in all patients,71 it is blamed in part on changes in cytokine and hormone levels. Pro-inflammatory cytokines such as tumor necrosis factor, interferon-g,
63
and interleukins 1 and 6 are considered important mediators of CCS. In addition, tumor byproducts such as proteolysis inducing factor, lipid mobilizing factor, and mitochondria uncoupling proteins1, 2, and 3, exhibit specific effects on nutrient metabolism. Loss of body weight by patients with solid tumors is attributed to losses of fat, water, and fatfree mass.72-76 Malnourished cancer patients may experience a 41% decrease in fat-free mass.77 Patients with lung, gastrointestinal, and head and neck tumors can experience weight loss in excess of 10% of their pre-illness weight. Patients with solid tumors can lose as much as 1.34 kg of fatfree mass in 4 weeks.78 A small amount of body fat and the majority of visceral mass are preserved to an extent. Skeletal muscle loss is the primary form of lean body mass loss.79 These changes in body composition affect symptom control and complication rates. Fatigue and psychological symptoms, such as depression and anxiety, can have a multiplicative effect on weight loss.80 The presence of weight loss itself is a constant reminder of disease that interferes with QOL.81 Increased incidence of nutrition related symptoms is also correlated with decreases in QOL.82 A variety of pharmacologic agents have been used to treat or provide symptomatic relief for patients with CCS. Most agents are directed at improving appetite and sense of well-being. The majority of these drugs have failed to show sustained benefit, and long-term use can be associated with unacceptable side effects. The most effective treatment of CCS is the treatment of the underlying disease with the appropriate anticancer therapy while managing symptoms.70 It is important that treatment-related symptoms that may interfere with dietary intake (ie, nausea, diarrhea, constipation) are addressed immediately and in an aggressive manner.83 Routine use of a screening tool, which assesses the presence of dietary interfering symptoms on a regular basis, can be helpful in the early identification of symptoms that may impact nutrition status.82
PSYCHOSOCIAL DISTRESS
I
n one study of a large sample of cancer patients (n ¼ 4496), the prevalence of psychological distress and variations in distress among diagnoses were examined, showing that lung cancer patients surpassed all other patient groups in overall
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prevalence rate for distress (43.4%); however, the mean distress scores of persons with lung cancer were not significantly different than for persons with brain, liver, pancreatic, and head and neck cancer. It was thought that poor prognosis and self-attribution associated with smoking may play a critical role in the actual level of distress in persons with lung cancer.84-86 Depression can be one psychological symptom experienced by patients with lung cancer, including survivors. It is often underdiagnosed, especially by patients that have completed treatment.4 In 142 patients who had survived lung cancer for 5 years or longer, it was found that depressed mood was associated with a lower QOL.87 Assessing for and treating depression is essential to help patients improve QOL during their illness and into survivorship.4 When assessing for depression in persons with cancer, a focus on psychological symptoms such as feelings of helplessness, hopelessness, loss of self-esteem, and anhedonia is recommended. Somatic symptoms such as anorexia, fatigue, insomnia, and weight loss are of less value as diagnostic criteria. Associated and potentially treatable medical, endocrinologic, and neurologic problems are to be included with each assessment. Personal and family history of depression, substance abuse, life stresses, losses secondary to cancer, and social support also should be evaluated.88 Patients may have a depressive syndrome because of the physiological effects of cancer, which is called ‘‘mood disorder due to cancer.’’ This may be because of tumor involvement of the central nervous system or metabolic disturbances (ie, adrenal insufficiency or hypothyroidism).88 A diagnosis of ‘‘substance-induced mood disorder’’ is appropriate when depression is related to drug therapy such as corticosteroids, benzodiazepines, or narcotics. Cytokines, such as interferon for example, can cause depression in 30% to 50% of patients.88 First-line pharmacologic treatment for depression includes agents in the selective serotonin re-
uptake inhibitor (SSRI) drug category because they are better tolerated, have fewer sedative effects, and have a safe cardiac profile. Symptoms start to improve within 2 to 4 weeks. Side effects include nausea, sexual dysfunction, headache, somnolence or insomnia, and a brief period of increased anxiety.88 Psychological treatment or psychotherapy with a goal to reduce emotional distress and to improve coping ability and sense of control has been shown to be effective in treating anxiety and depression in cancer patients. Referral to appropriate disciplines to deliver therapy is indicated at times of crisis in the illness, such as at initial diagnosis, recurrence, or when treatments fail or patients perceive themselves as dying.88
CONCLUSION
P
ersons with lung cancer often experience multiple symptoms associated with disease and therapy. Oncology nurses are in strategic positions to assess and intervene to improve symptom control. Supportive or palliative care can be provided alone as the main focus of care or in combination with life-prolonging therapy. In either situation, an important goal is to improve the patient’s comfort and function. Much can be gained from collaboration with colleagues in other disciplines as they relate to clinical problems reviewed in this article. Using the expertise of colleagues from other specialties can facilitate optimal patient outcomes. Oncology nurses have a responsibility to seek current knowledge in all areas that guide their practice, including symptom management and supportive care. Overall, evidence for supportive care interventions is increasing but gaps in evidence remain. Further research is needed in select areas to show which interventions are effective or most effective and which groups of patients can benefit the most.
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