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Palliative Care^*

^* From the Division of Pulmonary, Critical Care, Allergy, Immunology, and Sleep Disorders Medicine (Drs. Kvale and Simoff), Henry Ford Health System, Detroit, MI; and Division of Thoracic Medicine (Dr. Prakash), Mayo Clinic, Rochester, MN.

Correspondence to: Paul A. Kvale, MD, FCCP, Division of Pulmonary, Critical Care, Allergy, Immunology, and Sleep Disorders Medicine, Henry Ford Health System, 2799 West Grand Blvd, Detroit, MI 48202; e-mail: pkvale1{at}hfhs.org

	Abstract

TOP Abstract Introduction Pain Control Palliative Treatment of Bone... Palliative Treatment of Spinal... Palliative Treatment of Brain... Palliation of Dyspnea and... Pharmacotherapy of Dyspnea Pharmacotherapy of Cough Palliation of Dyspnea Caused... Bronchoscopic Methods to... Palliation of Hemoptysis Palliation of Malignant TEF Palliative Treatment of SVC... Summary of Recommendations References

 
The majority of patients who acquire lung cancer will have troublesome symptoms at some time during the course of their disease. Some of the symptoms are common to many types of cancers, while others are more often encountered with lung cancer than other primary sites. The most common symptoms are pain, dyspnea, and cough. This document will address the management of these symptoms, and it will also address the palliation of specific problems that are commonly seen in lung cancer: metastases to the brain, spinal cord, and bones; hemoptysis; tracheoesophageal fistula; and obstruction of the superior vena cava.

Key Words: bone metastases • brain metastases • dyspnea • hemoptysis • interventional bronchoscopy • pain management • pleural effusions • spinal cord metastases • superior vena cava syndrome • tracheoesophageal fistula

	Introduction

TOP Abstract Introduction Pain Control Palliative Treatment of Bone... Palliative Treatment of Spinal... Palliative Treatment of Brain... Palliation of Dyspnea and... Pharmacotherapy of Dyspnea Pharmacotherapy of Cough Palliation of Dyspnea Caused... Bronchoscopic Methods to... Palliation of Hemoptysis Palliation of Malignant TEF Palliative Treatment of SVC... Summary of Recommendations References

 
Since the vast majority (86%) of patients with lung cancer will die from their disease, it is intuitively obvious that most such patients will have one or more symptoms during the course of their disease. These symptoms produce a clinically significant alteration in quality of life, and—for many of the symptoms and the specific problems that the symptoms represent—a shortening of the quantity of life. Symptoms that may require palliation include those attributable to the primary lung cancer itself (dyspnea, hemoptysis), regional metastases within the thorax (superior vena cava [SVC] syndrome, tracheoesophageal fistula [TEF], pleural effusions), or from metastases to distant sites (brain, spinal cord, bone). Pain is an ever-troublesome symptom for many patients with lung cancer. Clinicians experienced in managing patients with lung cancer must be conversant with the many different ways to palliate the symptoms that may occur with lung cancer.

This section of the evidence-based guidelines is based on an extensive review of the medical literature. The Agency for Health Care Policy and Research (AHCPR) guidelines for the management of cancer pain was used in an abbreviated form for the guidelines regarding management of pain in lung cancer. Randomized controlled trials (RCTs) have generally not been done for most aspects of palliative care in lung cancer specifically, and meta-analyses are not available. Three RCTs were identified that studied surgical resection for brain metastases and whole-brain radiation therapy (WBRT) for brain metastases. One RCT was identified that studied the effect of corticosteroids in bone metastases, spinal cord compression, and brain metastases, respectively. Most reports of the topics considered in this section were case series.

	Pain Control

TOP Abstract Introduction Pain Control Palliative Treatment of Bone... Palliative Treatment of Spinal... Palliative Treatment of Brain... Palliation of Dyspnea and... Pharmacotherapy of Dyspnea Pharmacotherapy of Cough Palliation of Dyspnea Caused... Bronchoscopic Methods to... Palliation of Hemoptysis Palliation of Malignant TEF Palliative Treatment of SVC... Summary of Recommendations References

 
A comprehensive document for the management of cancer pain was developed and published in 1994 as part of a response to Public Law 101–239 (the Omnibus Reconciliation Act of 1989), under the aegis of the AHCPR.¹ The comments in this section are adapted from that resource, which was written by a multidisciplinary panel of private-sector clinicians and other experts convened by the AHCPR. Explicit, science-based methods and expert clinical judgment were used to develop specific statements. The scope of that effort is beyond what can be discussed in detail in this document, and the reader is referred to that resource for additional information.

The causes of cancer pain include tumor progression and related pathology (eg, nerve damage), surgery, and other procedures used for treatment and diagnosis, toxic side effects of chemotherapy and radiation, infection, and muscle aches when patients limit their physical activity. Approximately 75% of patients with advanced cancer have pain. Failure to relieve pain leads to unnecessary suffering. Decreased activity, anorexia, and sleep deprivation caused by pain can further weaken already debilitated patients.

Effective management of pain from cancer can be achieved in approximately 90% of patients. Proper management of a patient’s pain involves more than analgesia, and the program of pain control for any one patient must be individualized. Approaches that may augment analgesia include cognitive/behavioral strategies, physical modalities, palliative radiation and antineoplastic therapies, nerve blocks, and palliative and ablative surgery.

Any analgesic medication program should be kept as simple as possible, both with regard to the frequency and route of administration. Oral medications are preferred, because of convenience and cost-efficacy. If the patient cannot take medications orally, rectal and transdermal routes should be considered because they are relatively noninvasive. IM routes of administration should be avoided because of the associated pain and inconvenience, and also because of unreliable absorption.

A nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen should be used, unless there is a contraindication to their use. If pain persists or becomes worse, an opioid should be added and not substituted. Using opioids and acetaminophen or NSAIDs often provides more analgesia than can be accomplished by either class of drug alone. Further, the use of acetaminophen or NSAIDs may have a dose-sparing effect for opioids, which can provide the benefit of fewer side effects from the opioids. When pain persists despite this approach, the dose of opioids should be increased or a more potent agent chosen. The World Health Organization ladder has been shown to be an effective method to ensure the rational titration of therapy for cancer pain (Fig 1 ).²

View larger version (27K): [in this window] [in a new window] [Download PPT slide]   Figure 1. The World Health Organization three-step analgesic ladder.

Both the cancer patient and family members may shun the use of opioids because of a fear of addiction. Physicians must educate both the patient and the family about pain and how it is to be managed as part of the treatment plan. Effective pain control begins by asking the patient about pain. An easily administered pain rating scale should be used for assessment of pain, both at the time of initial presentation and periodically at regular intervals during the course of the disease. The most common pain scales are numeric (0 to 10 pain intensity), simple descriptive in nature (no pain, mild, moderate, severe), and a visual analog scale.

Analgesic medications should be administered around the clock with extra doses on an as-needed basis, as this approach helps to prevent recurrence of pain. A written pain management plan should be given to the patient with cancer pain. Constipation is a side effect of opioid medications. Constipation should be anticipated, treated prophylactically, and monitored constantly. Mild constipation can be managed by an increase in fiber consumption and a mild laxative such as milk of magnesia. Bulk-forming laxatives such as fiber supplements should be avoided. Unless there are contraindications, cathartic agents should be administered on a regular schedule.

Adjuvant drugs may be used to enhance the efficacy of opioids. Corticosteroids produce effects that include mood elevation, relief of inflammation, and reduction of cerebral or spinal cord edema when there is intracranial metastasis or spinal cord compression. Anticonvulsants such as phenytoin, carbamazepine, and clonazepam are used to manage neuropathic pain. Tricyclic antidepressants are used as an adjuvant to analgesics for the management of neuropathic pain. They augment the effects of opioids and have innate analgesic properties. Their mood-elevating properties may be helpful as an adjuvant to strict analgesics. Other adjunctive pharmacologic approaches include neuroleptics such as the major tranquilizers, hydroxyzine, bisphosphonates, and calcitonin for bone metastases.

There are many different nonpharmacologic methods to manage pain, many of which are very simple, effective, and inexpensive. A list of nonpharmacologic methods to manage pain is outlined in Table 1 . For patients with intractable and persistent pain despite use of all modalities that are known and familiar to the practitioner, referral to a clinic that specializes in the management of pain should be considered. Pain-control specialists can help to select additional methods that may improve the overall palliation of pain.

1. All patients and their families must be reassured that pain can be relieved safely and effectively. Level of evidence: good; net benefit: substantial; grade of recommendation: A
   
2. All patients should be questioned about their pain, and the patient’s self-report of pain should be the primary source of assessment. Simple rating scales for pain should be used to assess pain for all patients, and to document the effectiveness of pain management at regular intervals during treatment. Level of evidence: good; net benefit: moderate; grade of recommendation: B
   
3. For all patients, medications that are used to control pain should be individualized. Level of evidence: fair; net benefit: substantial; grade of recommendation: B
   
4. For all patients, medication administration should be simple and noninvasive, whenever possible. Level of evidence: fair; net benefit: substantial; grade of recommendation: B
   
5. For all patients, mild-to-moderate pain should be managed initially with acetaminophen or an NSAID, assuming there are no contraindications to their use. Opioids should be administered when pain is more severe or when it increases. Level of evidence: good; net benefit: substantial; grade of recommendation: A
   
6. For patients with persisting pain, the dose of opioid or its potency should be increased. Level of evidence: fair; net benefit: substantial; grade of recommendation: B
   
7. For patients with pain not controlled by pure analgesic medications, adjunctive medications such as tricyclic antidepressants, anticonvulsants, and neuroleptic agents will often augment the effects of pure analgesic medications. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
   
8. For patients who require medications to control cancer pain, the medications should be administered around the clock with additional as-needed doses. Level of evidence: fair; net benefit: substantial; grade of recommendation: B
   
9. For any patient, if it is anticipated that there will be a continuous need for opioid medication, meperidine should not be used. It has a short duration of action, and its metabolite, normeperidine, is toxic and causes CNS stimulation with dysphoria, agitation, and seizures. Level of evidence: fair; net benefit: none; grade of recommendation: D
   
10. For all patients, medications should be administered orally because of convenience and cost-effectiveness. If medications cannot be administered orally, rectal and transdermal routes are preferred because they are relatively noninvasive. Level of evidence: fair; net benefit: small; grade of recommendation: C
    
11. For all patients, medications should not be administered IM because of pain and inconvenience, and because IM medications are not reliably absorbed. Level of evidence: fair; net benefit: none; grade of recommendation: D
    
12. For all patients receiving opioids, constipation is common and it should be anticipated, treated prophylactically, and constantly monitored. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
    
13. All patients should be given a written pain management plan. Level of evidence: fair; net benefit: substantial; grade of recommendation: B
    
14. All patients should be encouraged to remain active and to care for themselves whenever possible. Prolonged immobilization should be avoided whenever possible. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
    
15. For patients whose pain is associated with muscle tension and spasm, cutaneous stimulation techniques such as heat and cold applications should be offered for pain relief. Level of evidence: poor; net benefit: small; grade of recommendation: C
    
16. For all patients, psychosocial methods of care should be introduced early in the management plan, but they should not be regarded as a substitute for analgesia. Level of evidence: fair; net benefit: substantial; grade of recommendation: B
    
17. For interested patients and family, pastoral care should be encouraged. Level of Evidence: poor; net benefit: moderate; grade of recommendation: C
    
18. When patients have metastases that have caused pain, palliative radiation therapy should be offered. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
    
19. For all patients with pain, referral to a specialized pain clinic should be considered. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
    

	Palliative Treatment of Bone Metastases

TOP Abstract Introduction Pain Control Palliative Treatment of Bone... Palliative Treatment of Spinal... Palliative Treatment of Brain... Palliation of Dyspnea and... Pharmacotherapy of Dyspnea Pharmacotherapy of Cough Palliation of Dyspnea Caused... Bronchoscopic Methods to... Palliation of Hemoptysis Palliation of Malignant TEF Palliative Treatment of SVC... Summary of Recommendations References

 
Metastatic lung cancer to bone is a manifestation of stage IV disease, and it is an indication that care for the patient will be palliative in nature. Elimination of pain is the primary goal of treatment options. There are no randomized prospective studies that directly compare radiation to pharmacotherapy for the management of pain due to bony metastasis. If a metastasis occurs in a weight-bearing bone, prophylactic surgical stabilization should be considered before a pathologic fracture occurs.

Pain caused by bone metastases has multiple causes. Periosteal inflammation and elevation is the most common mechanism behind the bone metastasis. Lung cancer metastases to bone are predominately lytic. After controlling pain with pharmacologic methods, treatment should be directed at managing inflammation. External beam radiation should therefore be considered as the initial nonpharmacologic method. This technique uses energy to diminish the local inflammatory response and thereby eliminate the source of the pain. Other nonpharmacologic methods to manage pain from bone metastases include radioactive isotope infusion, supportive measures for pain management, and direct local management (surgery, nerve blocks, etc).

Ninety percent of patients with symptomatic bone metastases obtain some pain relief with a low-dose, brief course of palliative radiation therapy. One half of the responding patients may have complete pain relief.³ For short-term improvement in bone pain, 8 Gy in a single fraction is as effective as higher doses.^{4 5} Although a single dose of radiation may be effective, the duration of pain relief is less than with higher fractionated doses of radiation therapy. Also, if large fields are required, local inflammation and edema may be a problem with a high single dose. A high single dose is more appropriate for small extremity fields, provided internal organs are not included, and for patients whose expected survival is only a few months.

There is a suggestion that different lung cancer cell types that metastasize to the bone may have different responses to radiation therapy. For example, 72% of metastatic adenocarcinoma has been reported to respond as compared to 40% of patients with metastatic squamous cell carcinoma.⁶ Most studies do not delineate between cell types but rather separate only small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC). The reported response to radiation therapy for bony metastases is 75 to 100% for complete to partial relief of pain.^{7 8 9 10 11}

A prospective randomized study compared the addition of methylprednisolone with external beam radiation therapy to radiation therapy alone for bone metastases. The group treated with the combination of methylprednisolone and radiation had more rapid and longer duration relief of pain. Stratification was used based on the hydroxyproline/creatinine ratio of 3.6 mg/g). Patients with a higher ratio had more improvement with the combination of external beam radiation and methylprednisolone.¹²

IV radioisotope infusion can also be used to manage pain from bony metastases. Ethylenediamine tetramethylene phosphonic acid is one such agent. Like many of the studies of different methods to treat bone metastases, only a small number of the patients in the reviewed studies had pain due to metastatic lung cancer; this constrains our interpretation of the results. Pain relief was achieved in 83 to 93% of patients treated in this fashion.^{13 14} Patients with breast cancer responded better than patients with lung cancer, but bone metastases from lung cancer respond better than other primary sites.¹⁵

Other radiopharmaceuticals that have been tried for metastatic cancer to bones include strontium-89 chloride. Response rates vary considerably, with some studies identifying little improvement¹⁶ and others demonstrating a 77% response rate.¹⁷ Re-186 hydroxyethylidene diphosphonate has been studied in patients with bony metastases, and was found not to be effective in patients with lung cancer.¹⁸ Significant data and support are limited for these techniques except in case report format.

Adjunctive therapy with disodium pamidronate has demonstrated good therapeutic response by itself, but more importantly when it is used in combination with radiotherapy for bony metastases. Response rates of 92% were seen in a randomized study with external beam radiation and pamidronate, vs radiation alone (83%), pamidronate alone (85%), or pamidronate in combination with chemotherapy (87%).¹⁹ An evidence-based review of the use of this medication provided similar conclusions.²⁰

Calcitonin, both porcine and salmon, has been studied in patients with bone pain. Porcine calcitonin was used after failure of radiotherapy and analgesics, with reduction in pain demonstrated in 63% of patients.²¹ Salmon calcitonin was studied in different treatment schedules to identify proper dosing regimens for the management of bony pain due to metastatic NSCLC.²²

Other techniques of pain management that have been tried all have limited evidence-based data and are case series with mixed cancer populations. Percutaneous ethanol injection into metastatic lesions under CT guidance was associated with a reduction in analgesic need in 74% of patients.²³ As cancers are highly vascular, 88% of patients who were treated by embolization of the bone tumor vasculature in a small case series had reduced pain.²⁴

Pathologic fractures may occur when lung cancer metastasizes to bones. Fracture of long bones significantly impairs functional status and quality of life. The femur is at special risk because of its role in weight bearing, and surgical intervention may be needed. Other bones that may require palliative surgical intervention include the tibia, hip (proximal femur plus acetabulum), vertebrae, and the humerus.

Prophylactic surgery is recommended for the following situations when long bones are involved: persistent or increasing local pain despite the completion of radiation therapy; a solitary well-defined lytic lesion circumferentially involving > 50% of the cortex; involvement of the proximal femur associated with a fracture of the lesser trochanter; and diffuse involvement of a long bone.²⁵ Contraindications to surgical treatment of metastatic disease to long bones include a survival expectancy < 4 weeks, and a poor general condition that is an obstacle to a safe operation.²⁶

No randomized prospective controlled trials have compared surgery alone, surgery plus radiation therapy, or radiation therapy alone for metastatic long-bone disease. All series that have analyzed operative intervention have included metastatic bone disease from multiple primary organ sites, with breast cancer as the most common. Lung cancer usually is the second most common primary site in reported series. A retrospective study of 60 patients compared adjuvant surgery plus radiation therapy (35 sites) to 29 sites that were treated with surgery alone. Univariate analysis revealed that combined therapy (p = 0.02) and prefracture functional status (p = 0.04) were the only predictors of patients achieving a good functional status after surgery. On multivariate analysis, only postoperative radiation therapy was significantly associated with attaining a good level of function after surgery (p = 0.02).²⁶

Intramedullary nailing is generally regarded as the preferred operative approach to deal with metastatic long bone disease. An ex vivo biomechanical analysis of the forces required to fracture the humerus after fixation of 50% hemicylindrical cortical central third defects showed that intramedullary nailing was significantly better than dynamic compression plating.²⁷ In general, endoprostheses and total arthroplasty are required only for intracapsular or very proximal lesions.²⁸ Operative intervention for metastatic fractures of long bones provides a good functional result in approximately 80 to 85% of patients; a good analgesic effect is accomplished in nearly all patients.

Recommendations for Management of Bone Metastases

• For patients with bone metastases, external radiation therapy is indicated to control localized pain. Higher fractionated doses of external radiation therapy provide the most predictable and longer lasting pain relief for bone metastases. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
  
• For most patients with pain from bone metastases, a single large fraction of external radiation will provide pain relief, but this technique is best reserved for patients with survival expectancy < 3 months and for smaller extremity lesions. Level of evidence: fair; net benefit: small; grade of recommendation: C
  
• For patients with bone metastases, systemic corticosteroids (prednisone, 20 to 40 mg/d), when used together with external beam radiation, may augment pain relief. Level of evidence: fair; net benefit: small; grade of recommendation: C
  
• In patients who do not respond to external beam radiation for the relief of pain caused by bony metastases, bisphosphonates can be administered alone or as an adjunct to external radiation therapy for bone metastases. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
  
• For patients with bone metastases for whom external radiation is not effective, calcitonin may provide pain relief. Level of evidence: poor; net benefit: small; grade of recommendation: C
  
• In patients with bone metastases, a variety of radiopharmaceuticals are available to treat pain. They should be considered when analgesics and external radiation therapy fail to control pain. Level of evidence: poor; net benefit: small; grade of recommendation: C
  
• In patients with bone metastases, if survival is expected for > 4 weeks and general health status is satisfactory, surgical fixation of a symptomatic or an asymptomatic metastasis to long and/or weight-bearing bones is indicated to minimize the potential for a fracture. Intramedullary nailing is the preferred approach, especially for the femur or the humerus. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
  

	Palliative Treatment of Spinal Cord Compression

TOP Abstract Introduction Pain Control Palliative Treatment of Bone... Palliative Treatment of Spinal... Palliative Treatment of Brain... Palliation of Dyspnea and... Pharmacotherapy of Dyspnea Pharmacotherapy of Cough Palliation of Dyspnea Caused... Bronchoscopic Methods to... Palliation of Hemoptysis Palliation of Malignant TEF Palliative Treatment of SVC... Summary of Recommendations References

 
Spinal cord compression by epidural tumor is an important complication for many patients with lung cancer, with an estimated frequency of 5% based on autopsy data.²⁹ Spinal cord compression can be classified anatomically as intramedullary, leptomeningeal, and extradural. No studies focus on functional results of treating intramedullary or leptomeningeal compression of the spinal cord; paraplegia and death occur rapidly in almost all such cases, and treatment is merely supportive. Early detection of epidural metastases with compression of the spinal cord and prompt treatment appear to favorably affect outcome. Epidural spinal cord compression is defined as compression of the dural sac and its contents (spinal cord and/or cauda equina) by an extradural tumor mass. The minimum radiologic evidence for cord compression is indentation of the theca at the level of clinical features, which include any or all of the following: pain (local or radicular), weakness, sensory disturbance, and/or evidence of sphincter dysfunction.

There is good evidence to support the use of high-dose dexamethasone (64 mg/d). One well-designed RCT compared high-dose dexamethasone to no dexamethasone in malignant spinal cord compression treated with radiation therapy alone.³⁰ Eighty-one percent of patients in the high-dose dexamethasone treatment arm who were ambulatory before treatment remained ambulatory after treatment, compared with 63% in the control arm. In patients who are paretic or paraplegic before treatment, there is a lesser likelihood that gait function will be regained, but the addition of dexamethasone appears to improve the probability of regaining the ability to ambulate. Significant side effects occur in 11% of those who receive high-dose dexamethasone. High-dose dexamethasone is therefore recommended as an adjunct to radiation therapy in retaining or restoring ambulation after treatment, but with a relatively high incidence of serious side effects that must be accepted. There is inconclusive evidence to support the use of moderate-dose dexamethasone (16 mg/d) plus radiation therapy for malignant epidural spinal cord compression.³¹ Methylprednisolone has not been compared to dexamethasone in head-to-head studies.

The evidence for radiation therapy with subclinical epidural spinal cord compression is fair, and a combination of high-dose steroids plus radiation should be administered to patients who are not paretic and ambulatory.³² The dose prescription should be left to the discretion of the prescribing radiation oncologist, as no study has stratified the results by dosing protocol. Most lesions can be managed with nonoperative aggressive treatment aimed at shrinking tumor size and halting growth of the tumor. There is reasonable evidence that there is a difference in relapse rates between those who receive prophylactic radiation and those who do not for patients with asymptomatic epidural spinal cord compression, but the optimal screening process has not been elucidated.³¹

Surgical intervention is limited to specific indications, including spinal instability, progressive neurologic deterioration from bony collapse and compression, intractable pain, and failure of conservative treatment.³² Laminectomy alone was once the intervention of choice, but it was associated with a high rate of spinal instability and inferior ambulatory outcomes compared with radiation therapy alone. Vertebral body resection with stabilization has the advantage of maintaining the structural integrity of the spine and removing the bulk of bony disease. There is, however, a higher complication rate and perioperative mortality. No study has evaluated these techniques against each other.

Radiation therapy alone should be the first line of treatment for patients who are ambulatory. When there is spinal instability, bony compression, or paraplegia at the time of presentation, surgery should be performed first. In a retrospective analysis of 123 patients treated at a single institution between 1970 and 1996, the major wound complication rate for patients who had radiation before surgical decompression and stabilization was 32%, as compared with 12% for patients whose surgery was done first (p < 0.05). Patients treated initially with surgery had better functional outcomes, with 75% of ambulatory patients remaining ambulatory and continent 30 days after treatment, compared to 50% for those whose surgery followed radiation.³³ The type of surgical decompression depends on the topography of the metastasis: when the anterior or middle column are involved, an anterior decompression should be performed. When the posterior column is involved, a posterior approach may be preferred. A combined approach may be needed when circumferential involvement is present. Reconstruction (cement or prosthesis) is often needed.^{34 35} Both surgical and radiation therapy specialties recommend the routine use of surgery for patients with bony compression and for surgical salvage after progression on radiation therapy.²⁷

Recommendations for the Palliation of Epidural Spinal Cord Metastases

• For patients with epidural spinal cord metastases, prompt treatment favorably affects outcome and should be given to all such patients. Level of evidence: fair; net benefit: substantial; grade of recommendation: B
  
• For patients who are not paretic and ambulatory, a combination of high-dose steroids plus radiation should be administered. High-dose dexamethasone (64 mg/d) is recommended as an adjunct to radiation therapy in retaining or restoring ambulation after treatment, but with a relatively high incidence of serious side effects that must be accepted. Level of evidence: fair; net benefit: substantial; grade of recommendation: B
  
• For patients with asymptomatic epidural spinal cord compression, prophylactic radiation should be prescribed. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
  
• For patients with epidural spinal cord compression and spinal instability, progressive neurologic deterioration from bony collapse and compression, intractable pain, and failure of conservative treatment, surgical intervention is indicated. Progression of neurologic deficit while patients are receiving radiation is also an indication for surgical stabilization. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
  
• When there is spinal instability, bony compression, or paraplegia at the time of presentation, surgery should be performed first and should then be followed by radiation. Level of evidence: poor; net benefit: moderate; grade of recommendation: C
  

	Palliative Treatment of Brain Metastases

TOP Abstract Introduction Pain Control Palliative Treatment of Bone... Palliative Treatment of Spinal... Palliative Treatment of Brain... Palliation of Dyspnea and... Pharmacotherapy of Dyspnea Pharmacotherapy of Cough Palliation of Dyspnea Caused... Bronchoscopic Methods to... Palliation of Hemoptysis Palliation of Malignant TEF Palliative Treatment of SVC... Summary of Recommendations References

 
Brain metastases are more common from lung cancer than from any other primary site. Brain metastases from NSCLC occur in approximately one third of patients, and brain metastases occur in 40% of patients with SCLC.^{36 37} If patients with brain metastases are not treated, neurologic deterioration occurs quickly.^{38 39} There are four methods currently available to treat patients with metastatic lung cancer to the brain: (1) systemic corticosteroids, used to ameliorate the brain edema that typically accompanies intracranial metastases; (2) WBRT; (3) surgical resection of the metastasis; and (4) stereotactic radiosurgery.

Treatment with systemic glucocorticoids is known to improve neurologic function only for a short time (maximum 1 month).⁴⁰ Two thirds of patients will have improvement in their neurologic signs and symptoms with the use of steroids.⁴¹ Dexamethasone is the most commonly used glucocorticoid, because it has minimal mineralocorticoid activity as compared with other steroids. Conventional dosing with dexamethasone for brain tumor edema is 16 mg/d.^{42 43 44} When dexamethasone is administered in these doses for > 1 month, serious side effects are common.⁴⁵ Two consecutive, randomized, double-blind, prospective controlled trials of patients with brain metastases and Karnofsky scores 80 compared dexamethasone, 8 mg/d, or dexamethasone, 4 mg/d, to dexamethasone, 16 mg/d.⁴⁶ Lower doses of dexamethasone were equally effective for improvement in quality of life as compared with patients treated with 16 mg/d, with significantly fewer toxic side effects (cushingoid facies, peripheral edema, steroid-induced myopathy) than in the group receiving 16 mg/d (p < 0.03). One other study (nonrandomized and nonblinded) also reported on the effect of lower doses of dexamethasone; there were similar benefits from lower doses and fewer toxic side effects.⁴⁷ In a small pilot study, 12 patients with intracranial metastases were initially administered 24 mg of dexamethasone IV q6h for 48 h, and then randomized to receive either 4 mg of dexamethasone po q6h for approximately 2 weeks during brain irradiation or no further dexamethasone during the radiotherapy.⁴⁸ Withholding steroids during the radiotherapy did not result in pronounced deterioration of general performance status or neurologic function at the conclusion of treatment or in reduction in overall survival. A multi-institutional prospective trial is needed to perform adequate statistical evaluation of patients regarding the role of steroid therapy in managing intracranial metastases. Until such a study is done, the consensus of opinion holds that dexamethasone, 16 mg/d, should be administered for 4 weeks, during the time of WBRT, and that it should then be rapidly tapered and discontinued.

Because of the frequency with which brain metastases occur in patients with SCLC, prophylactic WBRT is routinely indicated in patients with limited stage disease who achieve either a complete or a near complete response in the thorax following combined radiation and chemotherapy. When intracranial metastases are known to be present with SCLC, WBRT is again the primary method for palliating symptoms.

Patients with more than one intracranial metastasis from NSCLC are generally treated with WBRT. Median survival with this approach is 3 to 7 months, depending on prognostic factors.⁴⁹

Currently, there are three treatment options available for patients with a known NSCLC and a solitary intracranial metastasis: surgical resection, external beam WBRT, and stereotactic radiosurgery⁵⁰ (see also chapter on special treatment issues in this guideline). Most often, some combination of these methods of treatment is preferable. Almost all studies of patients with solitary intracranial metastases that have compared two or more methods of treatment have included patients with tumors from a variety of primary sites, not solely lung cancer. Lung cancer is almost always the most common primary site in these studies; SCLC is usually an exclusion criterion. Whereas data analyses are done on the group as a whole, it is reasonable to apply the conclusions to the subset of NSCLC patients with solitary intracranial metastases.

Two randomized, prospective, controlled trials have demonstrated a better outcome for a combination of WBRT plus surgical resection over WBRT alone.^{51 52} Surgery is appropriate for a solitary metastasis in patients with good functional status and a surgically accessible lesion. Median survival for the patients treated with combination therapy was significantly better in both studies as compared with WBRT alone (a third randomized trial failed to show a benefit from surgery, but more patients with active systemic disease were included in this study⁵³ ). In one of the two studies that showed a significant difference in median survival for the combined approach, the differences were most pronounced for patients with stable extracranial disease.⁵²

The rationale for adding WBRT to surgical resection in the setting of a solitary brain metastasis is based on the notion that micrometastases cannot reliably be detected with current technology. A randomized, prospective, controlled trial that compared postoperative WBRT plus surgical resection to surgery alone demonstrated that recurrence of tumor anywhere in the brain was less frequent in the WBRT group than in the observation group (18% vs 70%, p < 0.001).⁵⁴ The time to any brain recurrence was also significantly longer in the WBRT group. Overall survival was not different between the two groups; thus, postoperative radiotherapy prevented death due to neurologic causes but death due to systemic cancer was more frequent.

There are no significant differences among various conventional radiation therapy fractionation schemes (20 Gy in 5 fractions, 30 Gy in 10 fractions, 40 Gy in 20 fractions). A common dose of radiation therapy administered is 30 Gy given at 3 Gy per fraction in 10 fractions. A more protracted schedule is used for patients who have limited or no evidence of systemic disease or those who have undergone resection of a single brain metastasis, since these patients have the potential for long-term survival or even cure.^{55 56} Side effects of WBRT may include measurable deterioration of neuropsychological function.

Stereotactic radiosurgery utilizes a stereotactic fixation system and noncoplanar convergent beams that create a very sharp peripheral dose fall-off along the edge of the target. Thus, the surrounding normal tissues are spared while the radiation kills the tumor cells; accordingly, a single large fraction of ionizing radiation can be administered, making this method of treatment an attractive alternative to treat lesions whether surgically accessible or not. Stereotactic radiosurgery is usually restricted to lesions < 3 cm in diameter.

No randomized prospective trials have compared stereotactic radiosurgery to surgery. Many studies of stereotactic radiosurgery for patients with intracranial metastases have reported similar median survival times to surgery as reported by others.^{57 58 59 60 61} A retrospective study has demonstrated equal local tumor control rates and equal neurologic death rates between surgery and stereotactic radiosurgery.⁶² A prospective but nonrandomized study of patients with lung cancer (both SCLC and NSCLC) demonstrated significantly longer median survival for stereotactic radiosurgery with or without WBRT over WBRT alone (10.6 months and 9.3 months vs 5.7 months, p < 0.0001).⁶³ A randomized study of WBRT alone vs WBRT plus stereotactic radiosurgery in patients with two to four intracranial metastases showed significantly improved local control with a trend toward increased survival for WBRT plus stereotactic radiosurgery.⁶⁴ Stereotactic radiosurgery can be performed after brain recurrence in patients who previously have had WBRT, surgical excision of a metastasis, or both. Median survival in a case series of patients with lung cancer whose brain metastases were treated with stereotactic radiosurgery alone was 13.9 months, 14.5 months for stereotactic radiosurgery plus WBRT, and 10 months for patients treated with stereotactic radiosurgery for recurrent brain metastases.⁶⁵

Recommendations for Palliative Treatment of Brain Metastases From Lung Cancer

• Patients with symptomatic brain metastases should be treated with dexamethasone, 16 mg/d, for 4 weeks, during the course of WBRT; dexamethasone should then be rapidly tapered and discontinued. Level of evidence: good; net benefit: moderate; grade of recommendation: B
  
• Patients with multiple brain metastases from lung cancer should be treated with WBRT. Level of evidence: fair; net benefit: moderate; grade of recommendation: B
  
• For patients with intracranial metastases that are not surgically accessible, or when two to four intracranial metastases are present, or for intracranial recurrence after surgery, stereotactic radiosurgery, accompanied by WBRT, can also be offered. Level of evidence: poor; net benefit: moderate; grade of recommendation: C
  

	Palliation of Dyspnea and Cough

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Dyspnea is a subjective experience of difficult, labored, and uncomfortable breathing. Dyspnea is a common symptom of lung cancer, is most prevalent in advanced disease, and may present as "air hunger." Dyspnea and cough are the most commonly reported symptoms in lung cancer, with 15% of patients having dyspnea at diagnosis and 65% at some point during their illness.^{66 67} One major cancer center in the United States reported that dyspnea was the fourth most common symptom among patients with cancer who presented to the emergency department.⁶⁸ A prospective cohort study of seriously ill, hospitalized adults in five teaching hospitals in the United States reported that among 939 patients with stage III or IV NSCLC, severe dyspnea was recorded in 32%.⁶⁹ Patients with lung cancer presenting to emergency departments with dyspnea have a much shorter survival than patients with other malignancies.⁶⁸ One study of 120 patients with stage I through IV lung cancer used a questionnaire to evaluate the importance of dyspnea and observed that 87% had dyspnea, and patients with high dyspnea scores had lower quality of life.⁷⁰

The causes of dyspnea in patients with lung cancer can be classified into five broad groups: (1) the result of direct involvement of the respiratory system by lung cancer, (2) the result of indirect respiratory complications caused by lung cancer (postobstructive pneumonia, pleural effusion, etc), (3) the result of specific therapies to treat lung cancer (radiation-induced and chemotherapy-induced lung toxicity, anemia, etc, (4) the result of respiratory complications that occur more frequently in these patients (pulmonary embolism, lung infections, etc), and (5) comorbid conditions (COPD, heart failure, prior lung resection, malnutrition, etc).

Irrespective of the stage of lung cancer, dyspnea usually impacts the patient’s physical, social, and psychological well-being. Anxiety, fear of impending death, and pain caused by lung cancer are among the factors that contribute to the subjective symptoms of dyspnea. A prospective study of 100 terminally ill cancer patients (49 patients with lung cancer) observed that dyspnea, measured on visual analog scale, was significantly associated with anxiety (p = 0.001).⁷¹ From the perspectives of the patient and health-care providers, dyspnea can be perceived as panic, chest congestion and tightness, and suffocation. One study of 52 patients with lung cancer noted that both physical and emotional sensations were associated with descriptions of breathlessness, such as the feeling of being unable to get enough breath, or of panic or impending death.^{70 72} Increased anxiety has been connected with worse dyspnea in patients with obstructive lung disease, chronic pulmonary disease, and/or cancer.^{73 74 75} One study of 120 patients with stage I through IV lung cancer observed no difference in dyspnea based on cancer stage, cell type, or performance status. However, pain and anxiety scores were higher in patients with high dyspnea scores.⁷⁰

Fatigue is a common symptom among patients with lung cancer, particularly those with advanced disease. One study of 227 cancer patients and 98 control subjects reported that the prevalence of severe fatigue was 15% among patients with recently diagnosed breast cancer, 16% among patients with recently diagnosed prostate cancer, 50% among patients with inoperable NSCLC, and 78% among patients receiving specialist inpatient palliative care. Fatigue was significantly associated with the severity of psychological symptoms (anxiety and depression) and with the severity of pain and dyspnea.⁷⁶

	Pharmacotherapy of Dyspnea

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Pharmacologic treatments for dyspnea caused by lung cancer have included oxygen, bronchodilators, corticosteroids, antibiotics, and opioids. One retrospective study at a medical center specializing in cancer assessed the resource utilization associated with the management of dyspnea caused by lung cancer in 45 patients. The most common therapies administered in the emergency department were oxygen (31%), ß₂-agonists (14%), antibiotics (12%), and opioids (11%).⁶⁸

Bronchodilators
Standard bronchodilators such as ß₂-agonists, anticholinergics, and aerosolized corticosteroids are commonly prescribed to patients with lung cancer who have underlying COPD or asthma. There is no evidence that the presence of lung cancer induces bronchospastic disease. However, the onset of lung cancer in patients with underlying obstructive lung diseases usually aggravates symptoms of preexisting obstructive lung disease. There are not many studies to prove a beneficial effect of bronchodilators in patients with lung cancer. However, a prospective study of 100 terminally ill cancer patients (49 patients with lung cancer) observed that the potentially correctable causes of dyspnea included bronchospasm (in 52%) and hypoxia (in 40%).⁷¹ It is important to ensure that bronchodilator therapy is optimized if the patient has obstructive airways disease.

Corticosteroids
The role for systemic corticosteroids is limited for relieving dyspnea from lung cancer. As is the case with bronchodilator therapy, patients with obstructive airways disease may benefit from treatment with systemic corticosteroids to decrease mucus production and inflammatory changes in the airway mucosa. It is also important to recognize that patients with lung cancer who are actively receiving specific therapy, such as radiotherapy and/or chemotherapy, may have varying degrees of dyspnea.⁷⁷ This may reflect pulmonary toxicity to such therapies. Pulmonary parenchymal toxicity leading to dyspnea may require discontinuation of tumor-specific therapies and administration of systemic corticosteroids.

Oxygen
Supplemental oxygen is perhaps the most commonly prescribed therapy to relieve dyspnea in patients with lung cancer.⁶⁸ Significant involvement of the respiratory system by lung cancer or underlying obstructive airways disease usually produces or aggravates dyspnea and hypoxemia. A limited number of studies have shown the beneficial effects of supplemental oxygen therapy. A prospective, double-blind, crossover trial assessed the effects of supplemental oxygen on the intensity of dyspnea in 14 patients with advanced cancer. Patients were randomized to receive either oxygen or air delivered at 5 L/min by mask. Dyspnea was evaluated with a visual analog scale. The results showed that 12 patients consistently preferred oxygen to air, and patients reported little or no benefit from air compared with moderate to much benefit from oxygen.⁷⁸

Irrespective of the oxygenation status, supplemental oxygen therapy should be considered if patients with lung cancer have dyspnea. Multiple blood gas analyses should be avoided to justify oxygen therapy. Percutaneous oximetry should suffice to assess adequate oxygenation.

Analgesics
Dyspnea has been shown to be more severe in patients with severe pain.^{70 73} Dyspneic sensation caused or aggravated by cancer-induced pain may respond to nonnarcotic analgesic therapy. However, dyspnea due to pain caused by bony metastases, malignant pleural effusions, or fatigue is unlikely to respond to conventional analgesic therapy. Such circumstances require more aggressive pain control, including palliative radiotherapy for skeletal metastasis. In patients with dyspnea caused by milder pain and discomfort, nonnarcotic analgesics should be tried for a brief period.

Opioid Analgesics
Opioids are frequently used to alleviate dyspnea in patients with advanced lung cancer, advanced obstructive airway disease, and cardiac failure.⁷⁹ A wide variety of opioid analgesics have been used to control both dyspnea and pain in patients with cancer of lung and other organs. They include morphine, oxycodone, hydromorphone, and others. Opioids have been used orally, parenterally, and by aerosol. It is unclear if all opioids are equally efficacious in decreasing dyspnea perception in patients with lung cancer. In a study of 104 patients with lung cancer, opioids administered to treat pain did not decrease dyspnea.⁷⁰

An open, uncontrolled study evaluated the role of oral morphine to relieve dyspnea in 15 patients with advanced malignancy receiving standard care and noted that regular, titrated oral morphine may improve dyspnea but can cause significant short-term adverse effects.⁷⁹ The relief of dyspnea is usually noted within 24 h and the relief stays at a plateau with continued opioid therapy.⁸⁰

Continuous IV infusion of morphine has been used in patients with terminal lung cancer with severe dyspnea, unrelieved by oxygen, nonnarcotic drugs, or intermittent bolus narcotics.⁸¹ Even when patients achieve good dyspnea relief, the major side effect is sedation. Health-care providers, patients, and family members should be cognizant of the possibility of severe hypoventilation and hypercarbic respiratory failure and death. This side effect also has been described with inhaled morphine.⁸²

Other Methods
Nonpharmacologic, noninterventional methods for the control of dyspnea include patient education and intervention by allied health personnel. A multicenter RCT of 119 patients with SCLC or NSCLC or with mesothelioma, who had completed first-line treatment and reported dyspnea, used various strategies. These included breathing control, activity pacing, relaxation techniques, and psychosocial support, in addition to standard management and treatment available for dyspnea. The group assigned to intervention by nurses improved significantly at 8 weeks in breathlessness, performance status, and physical and emotional status compared to the control group.^{83 84}

	Pharmacotherapy of Cough

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Cough is a frequent and distressing symptom in patients with lung cancer. Cough can be dry or associated with sputum production. Involvement of any part of the respiratory system can lead to cough. Among the initial symptoms of lung cancer, cough is present in > 65% and productive cough in > 25% of patients.⁸⁵ Cough can be the presenting or leading symptom of lung cancer. It is more likely among patients with lung cancer originating in the airways.

All pharmacologic therapies aimed at controlling cough caused by lung cancer are symptomatic. Even if complete cessation of cough is not possible, a significant control of cough may help patients enjoy cough-free periods. In late-stage cancer when no specific therapy can address the cancer itself, control of bothersome cough becomes a problem. The pharmacologic agents available include the following.

Cough Suppressants
Nonopioid cough suppressants may work in a small group of patients with advanced lung cancer. Occasionally, even opioid-resistant cough may respond to agents such as the peripherally acting nonopioid drug benzonatate.⁸⁶

Bronchodilators
Bronchospasm can cause or contribute to cough. If the patient with lung cancer also has underlying bronchospastic obstructive airways disease, then standard bronchodilator therapy may help alleviate the cough.

One study tested the role of inhaled sodium cromoglycate in 20 patients with NSCLC and cough resistant to conventional treatment. The patients were randomized to receive, in a double-blind trial, either inhaled sodium cromoglycate or placebo. The results showed that inhaled sodium cromoglycate reduced cough in all patients with NSCLC.⁸⁷

Opioids
Opioids are the best cough suppressants in patients with lung cancer. Codeine is the most widely used opioid. In advanced stages of lung cancer, standard nonopioid cough suppressants may not control the cough. Intractable or troublesome cough should be treated with opioid agents. Caution should be exercised in prescribing graduated doses of these drugs because of the risk of respiratory suppression and hypoventilation.

A double-blind, RCT regarding the treatment of nonproductive cough was performed in 140 adults with primary lung cancer or metastatic cancer of the lungs. The therapeutic efficacy and the tolerability of a 7-day treatment with levodropropizine drops (75 mg tid) were evaluated in comparison with dihydrocodeine drops (10 mg tid). Efficacy was assessed on the basis of cough severity scores, the number of night awakenings due to cough, and overall estimate of antitussive efficacy. Tolerability was evaluated by laboratory results, vital signs, and any adverse event occurring during the clinical trial, including the presence or absence of somnolence. Subjective cough severity was significantly reduced during treatment with levodropropizine and dihydrocodeine, the antitussive effect and its time profile being similar for both drugs. Also, according to the investigator’s evaluation, both levodropropizine and dihydrocodeine treatment produced a significant decrease in cough severity. Concurrently with the relief of cough, the number of night awakenings was decreased significantly by both drugs, with no difference between the two treatments. No change in laboratory test values was considered clinically relevant, and vital signs were not clinically affected. The number of patients reporting adverse events was similar in the levodropropizine group (n = 6) and dihydrocodeine group (n = 4). However, the percentage of patients experiencing somnolence in the group receiving levodropropizine (8%) was significantly lower as compared with that of the dihydrocodeine group (22%). These results confirm the antitussive effectiveness of levodropropizine and suggest a more favorable benefit/risk profile when compared to dihydrocodeine.⁸⁸ However, levodropropizine is not available for use in the United States.

Corticosteroids
There are no studies on steroids specifically for cough in lung cancer. If cough is caused by radiation-induced lung problems, then high-dose corticosteroid therapy may relieve a significant degree of cough.

Lidocaine
There are no studies on the role of inhaled lidocaine on cough in patients with lung cancer.

	Palliation of Dyspnea Caused by Pleural Effusions

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Malignant pleural effusions occur in 7 to 15% of patients with lung cancer,^{89 90 91} more than half of whom acquire dyspnea.⁹² The mechanism of dyspnea with pleural effusions is unclear. Mechanical factors influencing the chest wall, mediastinum, pleural space, and the lung itself all may contribute to the sensation of dyspnea in the patient with a pleural effusion. Several studies have evaluated various aspects of compliance, lung volume, muscle strength, and gas exchange in patients before and after therapeutic aspiration of pleural effusions.^{93 94 95 96 97 98}

When a pleural effusion is identified and suspected as the etiology of dyspnea in a patient with lung cancer, the first requisite is to determine if the effusion is malignant or due to some other cause. The methods for this differentiation have been discussed in another section (see chapter on diagnosis in this guideline).

The major indication for treating a malignant pleural effusion is to relieve dyspnea. Often there are multiple causes of dyspnea in patients with lung cancer, so removal of the pleural fluid may or may not provide adequate relief of dyspnea. Chest radiographs, often including decubitus views, should be assessed to determine if the pleural fluid is free flowing or loculated. Contralateral shift of the mediastinum with large effusions suggests that evacuation of the effusion should provide relief of dyspnea for the patient. The next step is to perform a therapeutic thoracentesis to assess the effects on breathlessness after fluid removal, as well as the rate and degree of reaccumulation of pleural fluid. If the lung is trapped because of parenchymal or pleural disease, there will be minimal relief of dyspnea and the lung will not re-expand. The volume of fluid removed with the initial thoracentesis should be no more than 1 to 1.5 L, stopping earlier should the patient have dyspnea, chest pain, or cough. Removal of larger amounts of pleural fluid may be associated with re-expansion pulmonary edema, particularly if there is coexisting endobronchial obstruction.⁹⁹ Although complicated, this technique may minimize the risk of re-expansion pulmonary edema and help assess for the presence of a trapped lung at the time of the diagnostic or therapeutic thoracentesis.^{100 101} Pleural pressure monitoring may be a more objective assessment for trapped lung than chest radiograph assessment.

If the initial thoracentesis provides relief of dyspnea and lung re-expansion is seen on postprocedure chest radiography, reaccumulation of fluid can be managed in two basic ways: intermittent therapeutic thoracentesis, or insertion of a chest tube to completely evacuate the pleural fluid, followed by pleurodesis.⁹⁹

Repeated therapeutic thoracentesis is a viable option for patients with poor performance status or with advanced disease. There are no studies that compare repeated thoracentesis to other management approaches. If the malignant pleural effusion continues to accumulate, a more definitive procedure can be considered. Chemical pleurodesis via chest tube or medical thoracoscopy is the most common and effective approach, but pleuroperitoneal shunting, pleural drainage catheters, and systemic therapy are other options.

The overall complete response rate to chemical pleurodesis is 64%.¹⁰² Further analysis according to the type of agent used reveals that fibrosing agents as a group are associated with a 75% complete response rate and that talc, specifically, is associated with a 91% complete response rate. Antineoplastic agents are less often successful, with a reported complete response of 44%.¹⁰² Reported complete response rates to various sclerosing agents are listed in Table 2 .

Pleuroperitoneal shunting is another technique to manage malignant and other intractable pleural effusions. All studies of pleuroperitoneal shunting are case series. Many patients with malignant pleural effusions lack the ability to actively utilize the pumping device, which must be pushed at least 100 times or so daily to overcome the positive peritoneal pressure.^{126 127 128 129 130}

Another technique for managing malignant pleural effusions is tunneled long-term catheter drainage of the pleural space. Case series suggest good results for the relief of dyspnea over an extended time in patients with malignant effusions. Although encouraging, many of these studies are retrospective and there has been no comparison to other treatment modalities.^{131 132 133}

The treatment of choice for malignant effusions due to SCLC is systemic chemotherapy. Many patients will respond with resolution of pleural effusions and the associated dyspnea.¹³⁴

	Bronchoscopic Methods to Palliate Dyspnea and Cough

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Introduction
Central airway obstruction refers to significant obstruction of the trachea and main bronchi. Obstruction of lobar bronchi in a patient with limited pulmonary