1. A Slide Presentation for Oncology Nurses
Lung Cancer Overview
A Slide Presentation for
Oncology Nurses
Lung cancer is a common, yet challenging type of cancer to screen and manage. This program focuses on the basic epidemiology, screening tools, and treatment methods of both non-small cell and small cell lung cancer.

2. Lung Cancer: What is it?
Uncontrolled growth of malignant cells in one or both lungs and tracheo-bronchial tree
Arises from protective or ciliated cells in the bronchial epithelium
Begins as a result of repeated carcinogenic irritation causing increased rates of cell replication
Proliferation of abnormal cells leads to hyperplasia, dysplasia or carcinoma in situ
Lung cancer is thought to arise from a single stem cell that is capable of expressing a variety of phenotypes. Normally, this stem cell differentiates to form those cells found in the tracheobronchial tree, including pseudostratified reserved cells, ciliated goblet columnar cells, neuroendocrine cells, and type I and II pneumocytes. However, as with any cell capable of division, hyperplastic, metaplastic, or neoplastic changes are possible. These may be caused by repeated exposure to a carcinogen, such as tobacco smoke, leading to an increased rate of cell replication and uncontrolled growth of malignant cells.
There is strong evidence for a genetic predisposition to lung cancer as various chromosomal abnormalities have been demonstrated. In almost all cases of primary lung cancer as well as metastatic tumors, lesions occur in chromosome region 3p (14-23). Another abnormality is the mutation of the p53 gene. These and numerous other rearrangement and deletion types of chromosomal abnormalities are thought to result from the effects of carcinogens or the genetic instability observed in malignant transformation.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

3. Lung Cancer: Incidence in US
173,770 new cases yearly (2004 statistics)
160,440 deaths yearly (2004 statistics)
More deaths from lung cancer than prostate, breast and colorectal cancers combined
Closely correlated with smoking patterns
Decreasing incidence and deaths in men; continued increase in women
Incidence and mortality rates higher for African Americans than white Americans
It is estimated that approximately 173,770 new cases of lung cancer will be diagnosed in the United States in It is also estimated that 160,440 persons will die as a result of lung cancer in 2004, which makes it the leading cause of cancer deaths. In fact, each year more persons die of lung cancer than of prostate, breast, and colorectal cancer combined.
The incidence and mortality rate of lung cancer in men and women are closely correlated with tobacco use. In men, the incidence and mortality rates have been decreasing since the mid-1980s. From 1990 to 1998, the mortality rate decreased an average of 2.1% per year.
In women, however, the incidence and mortality rate have increased steadily since the 1960s. Fortunately, the increase in the mortality rate in women has begun to slow over the last few years.
African-Americans, particularly men, are more likely to develop and die of lung cancer than white Americans. In fact, the incidence and mortality rate in African-American men is 40% greater than white American men. In women, the incidence and mortality rate are similar.
Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, CA Cancer J Clin. 2002;52:23-47.
American Cancer Society Facts & Figures 2003, Atlanta, Ga., 2003.

4. Lung Cancer in Women Incidence (80,660 new cases in 2004)
Account for 12 percent of all new cases
Deaths increased 150% between 1974 and 1994 (68,510 in 2004)
More deaths from lung cancer than breast, ovarian and uterine cancers combined
Women are more susceptible to tobacco effects times more likely to develop lung cancer than men with same smoking habits
It is expected that a diagnosis of lung cancer will be made in approximately 80,660 women in the United States in This means that lung cancer is expected to account for 1 out of 8 new cases of cancer in women, an incidence comparable to colorectal cancer. Only breast cancer is more common accounting for about 1 out of 3 new cases of cancer in women.
The mortality rate in women with lung cancer has increased 50% since 1980 accounting for an estimated 68,510 deaths in The mortality rate for lung cancer in women is slightly greater than the mortality rates for breast, ovarian, and uterine cancers combined.
In women age 60 years and above, lung cancer is the leading cause of cancer death. This probably stems from the fact that the incidence of smoking in women began to increase around World War II.
Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, CA Cancer J Clin. 2002;52:23-47.
American Cancer Society Facts & Figures 2004, Atlanta, Ga., 2004.

5. Lung Cancer: What Causes It?
Smoking
Radiation Exposure
Environmental/ Occupational Exposure
Asbestos
Radon
Passive smoke
Numerous causes for lung cancer have been identified. The most important is tobacco use, particularly cigarette smoking, as at least 87% of persons with lung cancer have a positive smoking history.
Other causes include exposure to radiation, as well as environmental and occupational exposure. Asbestos, commonly used for decades in insulation and siding for buildings, is associated with a high risk for lung cancer. Although associated with rock mining, radon is another important cause for lung cancer, primarily because it can be found in many parts of the U.S. in homes with cracked basement walls and floors. Tobacco use poses a risk not only to those who smoke, but to those who are exposed to second-hand smoke as well, the so-called passive smokers.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

6. Lung Cancer: Smoking Facts
Tobacco use is the leading cause of lung cancer
87% of lung cancers are related to smoking
Risk related to:
amount smoked (pack years- # cigs/day x # yrs)
age of smoking onset
product smoked (tar/nicotine content, filters)
depth of inhalation
gender
Tobacco use is a strong risk factor for heart and lung disease and contributes to the high mortality rates associated with these diseases.
It is estimated that at least 87% of cases of lung cancer are related to smoking. The risk is related to the cumulative amount smoked or pack-years, which is determined by dividing the average number of cigarettes smoked per day by 20 then multiplying by the number of years. The age of smoking onset is also important, probably because the pack-year history is greater. Cigarettes higher in tar and nicotine content, especially those without a filter, and the depth of inhalation pose a greater risk. The risk of lung cancer decreases in proportion to the number of years after smoking cessation. Male gender is generally considered to be an adverse risk factor, although there is some disagreement.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

7. Lung Cancer: Screening
No proven effective screening tool
Chest X-ray commonly used
Clinical trials:
Low dose spiral chest CT scan
Sputum analysis
Chest X-ray
There currently is no tool or technique that has been shown to be effective for screening lung cancer. The most definitive investigation consisted of three randomized controlled trials for screening early lung cancer sponsored by the National Cancer Institute. These trials demonstrated that the addition of sputum cytology to a chest X-ray for high-risk outpatients every 4 months for 6 years conferred no mortality advantage compared to an annual chest X-ray alone. A twenty-year follow-up to these studies corroborated these findings. The data suggested that a chest X-ray may be a more effective test for early-stage lung cancer than previous reports had suggested. This has likely contributed to the continued use of a chest X-ray as a screening tool.
Sputum cytology is a simple method that can be effective to obtain a positive diagnosis of lung cancer. In the NIH-sponsored trials, sputum cytology alone detected 15% to 20% of lung cancers, although most of these were squamous cancers, which carry a less unfavorable prognosis. The reliability of sputum cytology, however, depends on the ability of the patient to produce a sufficient amount of sputum, as well as the size and histologic type of the tumor and its proximity to major airways.
A new approach to screening for lung cancer has recently been reported by the Early Lung Cancer Action Project (ELCAP). One thousand symptom-free heavy smokers over the age of 60 years underwent chest X-ray and low-dose spiral computed tomography (CT) screening. Non-calcified nodules suggestive of early lung cancer were detected at baseline in 23% of participants by low-dose spiral CT compared with 7% by chest X-ray. Malignant disease was detected in 2.7% by CT and 0.7% by chest X-ray and stage 1 malignant disease in 2.3% and 0.4%, respectively. These results clearly demonstrate the ability of low-dose spiral CT to greatly improve the detection of small non-calcified nodules at an earlier stage, thereby increasing the potential benefit of surgical resection. At present, however, there is no consensus as to the role of spiral CT scanning as a screening tool.
In summary, despite the results of the NCI-sponsored studies, most investigators believe that a person at high risk for developing lung cancer should undergo an annual chest X-ray. Sputum cytology may be worthwhile as an initial screen, but further use should be limited to those who demonstrate dysplasia.
Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller WE, Muhm JR. Lung cancer screening: the Mayo program. J Occup Med. 1986;28:
Marcus PM, Bergstralh EJ, Fagerstrom RM, et al. Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up. J Natl Cancer Inst. 2000;92:
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet. 1999;354:

8. Lung Cancer: Clinical Presentation
Local Symptoms
cough
dyspnea
hemoptysis
recurrent infections
chest pain
The clinical features of lung cancer are generally divided into anatomic regions since this generally parallels the extent and spread of the disease. Patients without symptoms at presentation are generally those with the best prognosis since this suggests early stage disease. Unfortunately, most patients are symptomatic at presentation.
Cough and dyspnea are the most common presenting local symptoms. Persistent cough often arises from tumors involving the larger airways. Dyspnea typically occurs when endobronchial obstruction with poor ventilation occurs. While an infectious process should be ruled out, especially in the presence of purulent sputum and possibly fever, incomplete or short-lived resolution of these symptoms with empiric antibiotics should cause further diagnostic work-up for lung cancer.
Hemoptysis can also be seen, especially in middle-age or older persons. Chest and shoulder pain may also occur and may be indicative of the tumor location.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

9. Lung Cancer: Clinical Presentation
Syndromes/Symptoms secondary to regional metastases:
Esophageal compression  dysphagia
Laryngeal nerve paralysis  hoarseness
Symptomatic nerve paralysis  Horner’s syndrome
Cervical/thoracic nerve invasion  Pancoast syndrome
Lymphatic obstruction  pleural effusion
Vascular obstruction  SVC syndrome
Pericardial/cardiac extension  effusion, tamponade
Paraneoplastic syndromes occur more frequently in patients with lung cancer than any other tumor. Various symptoms and syndromes arise primarily from involvement of the mediastinum and associated structures.
Nodal involvement or tumor invasion of the posterior mediastinum can lead to esophageal obstruction resulting in dysphagia. Tumors that invade the lymph nodes in the mediastinum may encase nerves leading to dysfunction of the diaphragm and vocal cords, as well as hoarseness. Pleural effusion can result from retrograde lymphatic spread or visceral pleural invasion.
Involvement of the sympathetic nerve trunk can result in Horner’s syndrome affecting the eye and eyelid and causing facial paralysis. Pancoast’s syndrome is seen when the tumor extends beyond the superior sulcus to the brachial plexus resulting in neuritic arm pain and atrophy of the muscles of the arm and hand. Superior vena cava syndrome represents mediastinal involvement and often presents as periorbital and facial edema, particularly early in the morning. Patients may also complain of headache that is associated with cerebral edema. Venous obstruction may occur leading to new vessel formation on the anterior chest wall. Direct invasion of the pericardium or metastases to it can lead to a malignant pericardial effusion with signs and symptoms of cardiac tamponade.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

10. Lung Cancer: Clinical Presentation
Symptoms secondary to distant metastases
pain
organ-related
General Symptoms
weight loss
fatigue
Distant metastases cause relatively non-specific systemic manifestations that are common to all advanced tumors. The observed symptoms correlate with the nerves and organs affected. For example, bone pain can result from bone metastases, although other causes are possible. Weight loss, cachexia, and fatigue are commonly seen. Weight loss is associated with poor prognosis. Irrespective of their cause, such symptoms require prompt treatment to improve prognosis and/or quality of life.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

11. Lung Cancer: Metastatic Sites
Lymph nodes
Brain
Bones
Liver
Lung/pleura
Adrenal gland
Lung cancer is capable of metastasizing to virtually any organ. The most common sites of spread include the lymph nodes, brain, bones, liver, lung, pleura, and adrenal gland. Metastases to the adrenal gland occur in approximately 40% of patients with lung cancer and are typically asymptomatic.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:

12. Lung Cancer: Paraneoplastic Syndromes
Non Small Cell Lung Cancer
hypercalcemia
skeletal-connective tissue syndromes
Small Cell Lung Cancer
inappropriate secretion of ADH
ectopic ACTH secretion
neurologic/myopathic syndromes
Paraneoplastic syndromes in patients with lung cancer can involve the endocrine, neurologic, skeletal, hematologic, and cutaneous systems. The spectrum of paraneoplastic syndromes that occurs with non-small cell lung cancer differs somewhat from those observed with small cell lung cancer.
Hypercalcemia is common in non-small cell lung cancer due to ectopic production of parathyroid hormone. Hypertrophic pulmonary osteoarthropathy (HPO) occurs frequently in non-small cell lung cancer. Bone and joint pains are the symptoms that are typically seen first, although digital clubbing may be present without other symptoms. Symptoms are usually very responsive to aspirin and other non-steroidal anti-inflammatory agents.
Hypercalcemia and HPO are not commonly seen in small cell lung cancer. Most patients with small cell lung cancer have an elevated serum antidiuretic hormone concentration. Only 10% fulfill the criteria for the syndrome of inappropriate antidiuretic hormone (SIADH) and only 5% exhibit symptoms. Increased levels of adrenocorticotropic hormone (ACTH) are seen in up to 50% of patients with lung cancer, although only 5% develop Cushing’s syndrome. A low serum sodium level is an adverse prognostic factor and patients with Cushing’s syndrome have a limited survival.
Neurologic paraneoplastic syndromes include sensory, sensorimotor, and autoimmune neuropathies and encephalomyelitis. Symptoms may precede the diagnosis of small cell lung cancer and are often the presenting complaint. They may also be the initial sign of relapse from remission. The severity of neurologic symptoms is unrelated to tumor bulk and often does not improve despite successful antitumor therapy.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:

13. Lung Cancer: Diagnosis
History and Physical exam
Diagnostic tests
Chest x-ray
Biopsy (bronchoscopy, needle biopsy, surgery)
Staging tests
CT chest/abdomen
Bone scan
Bone marrow aspiration
PET scan
The diagnosis of lung cancer requires the combined approach of a history and physical examination with appropriate diagnostic and staging tests. A detailed history and accurate physical examination remain the most important steps in assessing a patient with lung cancer. A thorough smoking history, family history, and occupational/ environmental history must be obtained. Symptoms must be carefully evaluated as they may indicate the presence and extent of disease.
The chest X-ray remains the most valuable tool in the diagnosis of lung cancer. Except in rare situations, a normal chest X-ray effectively rules out lung cancer. Conversely, the presence of malignancy can be suggested by peripheral nodules, hilar and mediastinal changes suggestive of lymphadenopathy or pleural effusions, and endobronchial obstruction.
Various techniques are used to stage or determine the extent of lung cancer. Computed tomography (CT) can be used to confirm abnormalities seen on chest X-ray, to detect early (< 1 cm) lesions not visible on chest X-ray, and to assess spread to the mediastinum. It can also be used to suggest areas of local invasion of the primary tumor, as well as to detect abnormalities below the diaphragm, especially metastases to the liver and adrenal glands. Abnormalities seen on CT scan, unless associated with unequivocal signs of malignancy, should be confirmed by more invasive cytologic or histologic investigation.
A bone scan is positive for metastatic disease in up to 40% of patients with lung small cell lung cancer at the time of diagnosis. Most of these patients are asymptomatic. If the findings are equivocal, further diagnostic work-up with a plain X-ray, CT, or MRI may be needed.
The bone marrow is involved in 15% to 30% of patients with small cell lung cancer at presentation. Since it is uncommon for the bone marrow to be the only site of metastatic disease, a routine bone marrow examination rarely modifies staging. In some centers, bone marrow aspiration has been replaced by MRI or positron emission tomography (PET) scanning to confirm abnormalities identified by the bone scan.
PET scanning is a promising technique to stage lung cancer. As it is based on the uptake of radioactive glucose in metabolically active cells, it is used to determine differences in the metabolism of normal and neoplastic cells. However, since granulomatous inflammation can be metabolically active, whereas bronchoalveolar carcinomas may be metabolically inactive, the usefulness of PET imaging in diagnosing with absolute certainty the etiology of a solitary pulmonary nodule is limited. Nonetheless, most reports demonstrate higher accuracy with PET imaging than with CT imaging and bone scanning to identify occult metastatic disease in the mediastinum and distant sites.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Pieterman RM, van Putten JWG, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med. 2000;343:

14. Lung Cancer: Prognostic Factors
Stage at diagnosis
Performance status
Numerous factors have been evaluated to determine their prognostic utility for lung cancer. These include the presence or absence of molecular genetic markers, growth factors and receptors, and pathologic features such as angiogenesis and cell proliferation. None has been shown to be as useful as the stage of the disease, which remains the prognostic benchmark. Stage is also useful for treatment planning as well as a means of communicating among healthcare professionals and patients.
Another highly consistent prognostic factor is the patient’s performance status. Several validated methods are available including Karnofsky, Zubrod, and the Eastern Cooperative Oncology Group scales. Weight loss and gender (females fare better than males) are also useful prognostic factors. Age does not appear to be an independent prognostic factor.
Mountain CF. The International System for Staging Lung Cancer. Semin Surg Oncol. 2000;18:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:
Bunn PA Jr., Mault J, Kelly K. Adjuvant and neoadjuvant chemotherapy for non-small cell lung cancer. Chest. 2000;117:119S-122S.

15. Lung Cancer: Cell Types
Non Small Cell Lung Cancer (NSCLC)
Small Cell Lung Cancer (SCLC)
Lung cancer is divided into two general types: non-small cell lung cancer and small cell lung cancer. The diagnostic differentiation of non-small lung cancer from small lung cancer is important as they have different natural histories and respond differently to specific treatments.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

16. Non Small Cell Lung Cancer (NSCLC)
80% of all lung cancers
Better survival rates when found in early stages
Non-small lung cancer represents approximately 80% of all cases of lung cancer. Patient survival is better with early stage disease. For example, the 5-year survival rate is approximately 60% to 80% for patients with stage I lung cancer compared with less than 1% for stage IV lung cancer.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:
Mountain CF. The International System for Staging Lung Cancer. Semin Surg Oncol. 2000;18:

17. NSCLC: Histologic Cell Types
Adenocarcinoma
Squamous Cell Carcinoma
Large Cell Carcinoma
Non-small cell lung cancer is a group of histologically related cell types, including adenocarcinoma, squamous cell (epidermoid) carcinoma, and large cell carcinoma.
Adenocarcinoma accounts for 40% of all cases of non-small cell lung cancer with the majority of the remainder consisting of squamous cell carcinoma. Squamous cell carcinoma tends to occur centrally near main-stem bronchi, while adenocarcinomas and large cell carcinomas are usually located peripherally and are unrelated to the bronchi. Squamous cell carcinoma tends to be slow-growing and it is estimated that up to 3 to 4 years are required from the development of in situ carcinoma to clinically apparent tumor.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

18. NSCLC: TNM Staging Stage Ia T1 N0 M0 Ib T2 N0 M0 IIa T1 N1 M0
IIb T2 N1 M0
T3 N0-1 M  
IIIa T1-3 N1 M0
IIIb Any T4 any N3 M0  
IV Any M1
T = tumor size (T1< 3cm,T2 >3cm + atelectasis), tumor site ( T3 extension to pleura, chest wall, pericardium or total atelectasis) , local involvement
(T 4 invasion of mediastinum or pleural effusion);
N = lymph node spread N1 bronchopulmonary, N2 (ipsilateral mediastinal) and N3 (contralateral or supraclavicular);
M = absence (M0) or presence (M1) of metastases
A system for stage grouping of non-small cell lung cancer by primary tumor, regional lymph node, and distant metastasis (TNM) was developed by the International System for Staging Lung Cancer in This system has been revised recently to address heterogeneity issues among stages and the need for more specific stage categories.
The TNM system provides information related to the extent of disease. The ‘T’ component reflects the tumor size and invasiveness. T values range from 0 to 4; T0 indicates no evidence of primary tumor, while T4 indicates extensive extra-pulmonary extension.
The ‘N’ component indicates the absence or presence and extent of regional lymph node metastasis. N values range from 0 to 3; N0 indicates no regional lymph node metastasis, while N3 indicates metastasis to contralateral hilar and ipsilateral and contralateral supraclavicular/scalene lymph nodes.
The ‘M’ component defines the absence or presence of tumor spread to distant lymph nodes or or organ sites. M values range from 0 to 1; M0 disease indicates no distant metastasis, while M1 indicates the presence of distant metastasis.
Determination of each component of the TNM staging may be based on clinical, surgical-pathologic, or retreatment information. Clinical staging is based on all information obtained before treatment is instituted or a decision for no treatment is made. Surgical-pathologic staging information is obtained from pathological examination of resected specimens. Retreatment staging stems from an evaluation of disease extent following initial or induction therapies.
Mountain CF. The International System for Staging Lung Cancer. Semin Surg Oncol. 2000;18:
Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest. 1997;111:

19. NSCLC: Treatment Surgery Radiation Mediastinoscopy
Video-assisted Thoracoscopy (VAT)
Thoracotomy: Lobectomy. Pneumonectomy
Radiation
External Beam
Brachytherapy
Several surgical procedures have been used to treat non-small cell lung cancer. First introduced in 1954, mediastinoscopy was subsequently refined such that a transcervical incision is made to allow access to most lymph nodes. Mediastinoscopy is indicated when mediastinal lymph nodes greater than 1 cm are present. Mediastinoscopy remains the most accurate lymph node staging technique to assess superior mediastinal lymph nodes. Morbidity, primarily infection, pneumothorax, and major bleeding, occurs in up to 3% of patients. The mortality rate is less than 0.1%.
Video-assisted thoracoscopy (VATS) is one of the most common thoracic surgical procedures. The primary advantage of VATS is the reduced surgical trauma and postoperative pain associated with thoracotomy, while allowing more complete staging for lung cancer. It allows assessment of suspicious adenopathy in areas inaccessible to conventional mediastinoscopy, as well as the entire pleural cavity. The absolute indications for VATS have yet to be firmly defined.
Thoracotomy is used for pulmonary resection. The type and location of the incision is dependent on the stage of disease. Lobectomy and pneumonectomy have been the principal types of thoracotomy for decades. Recently, however, there is a trend to perform less radical resections in an effort to preserve as much pulmonary parenchyma as possible while performing an adequate and complete resection of the tumor. As such, more than 95% of tumors can be accurately diagnosed and staged prior to thoracotomy.
Radiation therapy, utilizing either external beam or brachytherapy, is a viable option for those who cannot tolerate or who refuse surgical resection of early-stage non-small cell lung cancer. Treatment with external beam radiotherapy is given using opposed anterior and posterior beams to balance the toxicity to the lung and other structures. Acute side effects that occur during external beam radiotherapy are organ-specific and relate to the fractionation scheme, total dose, and use of sequential or concomitant chemotherapy or radiosensitizers. Acute side effects typically manifest in the second to third week of treatment, although reactions may be delayed for 1 to 3 months. Brachytherapy is another treatment modality that is used for both curative and palliative intent. The 5-year survival rate of radiotherapy approaches 40% in early-stage disease. Local recurrence with radiotherapy is significantly higher and the survival rate is lower with radiotherapy compared with surgical resection.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Zorn GL, Nesbitt JC. Surgical management of early stage lung cancer. Semin Surg Oncol. 2000;18:

20. NSCLC: Treatment Chemotherapy Standard Cisplatin, Carboplatin
Newer agents: Gemcitabine, Paclitaxel, Docetaxel, Vinorelbine, Irinotecan used alone and in combination
Since most patients with non-small cell lung cancer present with stage IV disease at initial diagnosis and there is no known curative therapy for these patients, the primary goal is to maximize survival time and maintain an acceptable quality of life. Since stage IV disease is a metastatic disease, systemic therapy is required. Local therapy is generally used to palliate specific sites of disease.
Older chemotherapy trials that utilized alkylating agents typically showed a detrimental effect in non-small cell lung cancer. Since that time, platinum-based therapy with either cisplatin or carboplatin has been the standard. A meta-analysis of 52 randomized clinical trials involving 9387 patients showed a benefit with chemotherapy. For example, chemotherapy with surgery reduced the risk of death 13% compared with surgery alone. Similar results were observed for chemotherapy plus radiotherapy compared with radiotherapy alone. A 27% reduction in the risk of death was observed when chemotherapy was combined with supportive care versus supportive care alone.
Several newer agents have shown an improved benefit over platinum-based therapies. Monotherapy with gemcitabine, vinorelbine, or irinotecan have produced objective responses of 20% to 27% in advanced non-small cell lung cancer. In stage IIIb and stage IV non-small cell lung cancer, monotherapy with one of these agents resulted in a median survival of about 40 weeks with about 40% of patients alive at 1 year. Combination therapy with cisplatin or carboplatin increased the response rates compared with cisplatin or carboplatin alone. For example, a 1-year survival rate of 35% to 40% is achieved with vinorelbine plus cisplatin, paclitaxel plus carboplatin and gemcitabine plus cisplatin.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ. 1995;311:
Bunn P Jr., Kelly K. New combinations in the treatment of lung cancer. A time for optimism. Chest. 2000;117:138S-143S

21. NSCLC: Treatment by Stage
Description
Treatment Options
Stage I a/b
Tumor of any size is found only in the lung
Surgery
Stage II a/b
Tumor has spread to lymph nodes associated with the lung
Stage III a
Tumor has spread to the lymph nodes in the tracheal area, including chest wall and diaphragm
Chemotherapy followed by radiation or surgery
Stage III b
Tumor has spread to the lymph nodes on the opposite lung or in the neck
Combination of chemotherapy and radiation
Stage IV
Tumor has spread beyond the chest
Chemotherapy and/or palliative (maintenance) care
The treatment of non-small cell lung cancer is guided by the stage of the disease. Surgical resection remains the primary treatment for stages I and II since the tumor size is small and lymphatic spread, if present, has not extended beyond the bronchopulmonary and hilar lymph nodes. In most cases, lobectomy is the appropriate resection procedure required. However, when the primary tumor or lymph node involvement extends to the proximal bronchus or proximal pulmonary artery or across the major fissure, a pneumonectomy is indicated. Although clinical trials are currently underway, current data indicate that adjuvant chemotherapy and/or radiotherapy offers no significant survival benefit in patients with stage I or II disease.
Radiotherapy alone has been the traditional method of treatment for stage IIIA non-small cell lung cancer. However, radiotherapy is not always able to kill all tumor cells within the irradiated field and distant metastases are unaffected. In fact, numerous clinical trials have shown that preoperative radiotherapy alone does not improve long-term survival and has no role as a single induction modality in the management of marginally resectable or unresectable stage IIIA disease. For this reason, induction chemotherapy or the combination of radiotherapy and chemotherapy is appropriate. The role of surgery for stage IIIA disease is somewhat controversial at present. If the staging process indicates that complete excision of the tumor and affected lymph nodes is possible, then surgery should be performed, but preceded with chemotherapy with or without radiotherapy.
Surgery for stage IIIB and IV disease is of essentially no curative value due to the widespread nature of the disease. The role of surgery is, therefore, limited to debulking large tumors to palliate symptoms. For this reason, induction chemotherapy or the combination of radiotherapy and chemotherapy is appropriate. For stage IV disease, the use of newer chemotherapy agents has provided some hope that the survival of these patients might be improved. Nonetheless, in most instances at present, the role of chemotherapy and/or radiotherapy is to palliate symptoms. Bronchoscopy or pleurodesis might also be used to manage other metastatic complications.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Mountain CF. The International System for Staging Lung Cancer. Semin Surg Oncol. 2000;18:

22. NSCLC: Treatment Outcomes
Stage I II
IIIa
IIIb IV
5-Year Survival
60-80%
40-50%
25-30%
5-10%
<1%
The 5-year survival rates for non-small cell lung cancer are highest with early stage disease and lowest for advanced disease. Patients with stage I disease have a 5-year survival rate of 60% to 80% compared with 40% to 50% for those with stage II disease. The 5-year survival rate for patients with stage IIIA disease is 25% to 30% compared with 5% to 10% for stage IIIB disease. Fewer than 1% of patients with stage IV disease survive 5 years.
Mountain CF. The International System for Staging Lung Cancer. Semin Surg Oncol. 2000;18:

23. NSCLC: Research Chemotherapy/Biotherapy Radiation Multimodality
New agents
Novel therapies
Radiation
Dosing and scheduling
New techniques
Multimodality
Early stage and locally advanced disease
Refining therapies
Research efforts to improve the outcomes of patients with non-small cell lung cancer are on-going. The addition of the taxanes paclitaxel and docetaxel, the antimetabolite gemcitabine, the topoisomerase I inhibitor irinotecan, and the vinca alkaloid vinorelbine have led to improved survival. Agents such as tegafur and uracil (UFT), oxaliplatin, and amifostine, as well as new combinations of chemotherapy agents are being studied. Investigational agents include tirapazamine and multitargeted antifolate.
Other agents, including immune stimulators and vaccines have also been studied mostly with disappointing results. Bacille Calmette-Guérin (BCG) administered into the pleural cavity in stage I non-small cell lung cancer has shown no benefit and, in fact, may actually decrease the disease-free interval. Levamisole has been studied with no demonstrable benefit in epithelial lung cancer and in combination with BCG as adjuvant therapy for stage II and III adenocarcinoma and large cell carcinoma. Trials of interferon-, -, - alone or in combination with chemotherapy have not shown any benefit. Similarly, interleukins have failed to provide significant effects.
Agents that act on the known as well as postulated biologic mechanisms of cancer are under investigation. Such agents include monoclonal antibodies and matrix metalloproteinase inhibitors, as well as those that affect gene transfer and alteration, peptide growth factors, epidermal growth factors, nerve growth factor, and insulin-like growth factor 1.
The role of radiotherapy continues to evolve as more data and new techniques become available. Various doses and schedules are being studied alone or in combination with other therapies. Altered fractionation radiotherapy, that is radiotherapy other than the standard 1.8 to 2 Gy delivered once daily, 5 times per week for 6 to 7 weeks, is being evaluated. Alterations include hyperfractionation, hypofractionation, accelerated radiotherapy, and continuous hyperfractionation accelerated radiotherapy (CHART). The basic goal of altered fractionation radiotherapy is to deliver a higher total dose of radiation to improve the local outcome without increasing late normal tissue toxicity. Such schemes exploit the significant differences in the capacity of late-responding and early-responding tissues to repair radiation cellular damage. Other evolving radiotherapies include the combined use of different radiotherapy techniques, three-dimensional conformal radiotherapy, and the use of radio sensitizers and radio protectors.
Also under investigation is the use of multimodality therapy using sequential chemotherapy and radiotherapy. The use of induction or neoadjuvant chemotherapy is based on the suggestion that early use of chemotherapy may lower the systemic tumor burden and prevent the growth of microscopic systemic disease. At the same time, bulky locoregional macroscopic disease is decreased and treated more effectively by subsequent surgery, radiotherapy, or both.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Bunn PA Jr., Kelly K. New combinations in the treatment of lung cancer. A time for optimism. Chest. 2000;117:138S-143S.
Bunn PA Jr., Soriano A, Johnson G, Heasley L. New therapeutic strategies for lung cancer. Biology and molecular biology come of age. Chest. 2000;117:163S-168S.

24. Small Cell Lung Cancer (SCLC)
Most aggressive lung cancer
Responsive to chemotherapy and radiation but recurrence rate is high even in early stage
Although similar to non-small cell lung cancer in many ways, small cell lung cancer has some important differences. Small cell lung cancer is more aggressive in that it grows rapidly, has a large growth fraction, and is widely disseminated at diagnosis. If left untreated, patients have a median survival of only 6 to 17 weeks. Fortunately, small cell lung cancer is more responsive to single agent and combination chemotherapy. Radiotherapy plays an important role in the management of small cell lung cancer, whereas surgery plays a minor role. Despite optimum treatment, the 5-year survival rate is less than 10% due to the high relapse rate.
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

25. SCLC: Cell Types Oat Cell Intermediate Combined
Based on the World Health Organization histologic classification system, small cell lung cancer is divided into three subtypes: oat cell, intermediate cell, and combined oat cell (small cell lung cancer combined with squamous or adenocarcinoma). Since the oat cell and intermediate cell types behave identically, an alternative system was developed by the International Association for the Study of Lung Cancer. This system recognizes 3 types: pure small cell and 2 less common variants, mixed small cell and large cell carcinoma and combined small cell carcinoma.
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

26. SCLC: Staging Limited Stage Extensive Stage
Defined as tumor involvement of one lung, the mediastinum and ipsilateral and/or contralateral supraclavicular lymph nodes or disease that can be encompassed in a single radiotherapy port.
Extensive Stage
Defined as tumor that has spread beyond one lung, mediastinum, and supraclavicular lymph nodes. Common distant sites of metastases are the adrenals, bone, liver, bone marrow, and brain.
Since surgery plays a minor role in the management of small cell lung cancer, the TNM system for staging non-small cell lung cancer is not used for small cell lung cancer. Instead, the simpler Veterans Administration Lung Study Group (VALSG) system is used. This system identifies patients as having either limited disease or extensive disease.
Limited disease is confined to one side of the chest and can be encompassed in a tolerable radiation field. All other disease is categorized as extensive disease, which is seen in 60% to 70% of patients with small cell lung cancer.
Although the VALSG system is widely used, some investigators have advocated the incorporation of subclassifications to better predict patient survival.
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:

27. SCLC: Treatment Limited Disease Extensive Disease Chemotherapy
Concomitant Radiation
Prophylactic Cranial Irradiation
Extensive Disease
Palliative radiation
The treatment of small cell lung cancer has not changed significantly over the past few decades. Two studies in the 1960s established a limited role for surgery. Other studies with radiotherapy alone yielded inadequate results, while cyclophosphamide was shown to significantly improve survival versus supportive care. Subsequently, the combination of cyclophosphamide and radiotherapy demonstrated superior efficacy compared with either treatment alone.
Thus, the management of patients with limited disease consists of combined chemotherapy and radiotherapy. The two are generally administered concomitantly since survival is thought to be superior versus sequential therapy. However, toxicity is more likely with concomitant therapy, which mandates that the patient’s ability to tolerate concomitant therapy be considered.
Since brain metastases are found in 10% of patients with small cell lung cancer at diagnosis and in 50% to 80% of those who survive 2 years, prophylactic cranial irradiation is recommended for those who achieve a complete or near complete response to induction therapy.
Without treatment, fewer than 10% of patients with extensive disease survive 2 years from the time of diagnosis. Chemotherapy produces an overall response rate of 60% to 80% with a median survival time of 6 to 12 months. Although relapse is inevitable, patients with a good performance status should be offered additional chemotherapy. Radiotherapy, on the other hand, has been shown to not affect survival. Its role, therefore, is for symptomatic palliation.
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:

28. SCLC: Treatment Chemotherapy:
Most commonly used initial regimen: Cisplatin or Carboplatin plus Etoposide x 4-6 cycles
Newer agents under evaluation: Topotecan, Paclitaxel, Docetaxel, Irinotecan, Gemcitabine
Following the establishment of cyclophosphamide as beneficial in small cell lung cancer, numerous agents and combinations of agents have been studied in clinical trials. Examples include anthracyclines, vinca alkaloids, alkylating agents, antimetabolites, epipodophyllotoxins, taxanes, and camptothecins. The roles of many of the newer agents, such as docetaxel, paclitaxel, irinotecan, topotecan, and gemcitabine are under evaluation.
Currently, the most commonly used initial chemotherapy regimen is a combination of either cisplatin or carboplatin with etoposide for 4 to 6 cycles. Response rates with cisplatin and etoposide of 55% in patients previously treated with a combination of cyclophosphamide, doxorubicin, and vincristine (CAV) and 86% in newly diagnosed patients have been reported. The combination of carboplatin and etoposide produces a response in 77% and 58% of patients with limited and extensive disease small cell lung cancer, respectively. The addition of two cycles of consolidation chemotherapy with cisplatin and etoposide has been shown to improve survival in patients responding to cyclophosphamide, doxorubicin, and vincristine.
Toxicity, particularly myelosuppression, has been a problem with many of the chemotherapy combinations, but is less frequent with the combination of cisplatin or carboplatin with etoposide. Furthermore, the concomitant administration of cisplatin and etoposide with radiotherapy causes less esophagitis and interstitial pneumonitis.
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:

29. SCLC: Treatment Outcomes
Limited Disease
median survival months
5-year survival 10%
Extensive Disease
median survival months
5-year survival %
Despite modest gains in the management of small cell lung cancer, the prognosis remains grim. The median survival for patients with limited disease is only 18 to 20 months with only 10% surviving 5 years.
Patients with extensive disease survive a median of 10 to 12 months from the time of diagnosis. Only 1 or 2 percent survive 5 years.
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:

30. SCLC: Research
Goal: To improve disease-free interval and length of survival
New agents
Vaccines
Radiation schedules
Prophylactic Cranial Irradiation
The clear goal for the management of small cell lung cancer is to improve the disease-free interval and the overall length of survival. Numerous therapeutic approaches are under investigation with this goal in mind.
New chemotherapy agents as well as some agents used for other types of cancer are being investigated as are different combinations and treatment schedules. One area of active research is dose intensification whereby protective agents are administered to allow higher doses of chemotherapy to be administered. Protective agents include corticosteroids, gastroprotective agents, antibiotics, and hematopoietic growth factors such as filgrastim, sargramostim, and oprelvekin. The results of such approaches have been mixed.
Studies with biologic response modifiers, such as interferon and interleukin-2, have provided disappointing results. In fact, there is the suggestion that interferon may enhance radiation-induced lung injury.
Several vaccines are also being investigated as a means of augmenting the otherwise modest immune response normally observed in small cell lung cancer. One of these, an antiidiotypic antibody or a type of enhanced antibody directed against the tumor antigen, has shown some promise, particularly in limited disease, when compared with an historic matched control group.
The role of radiation also continues to be evaluated. Since chemotherapy is reasonably effective in killing metastatic cells, while resistant cells typically reside within the primary tumor, radiation administered to the primary site may be advantageous. Also, since the rapidly dividing nature of tumor cells makes them more sensitive to smaller doses of radiation than normal cells, more frequent administration of smaller doses of radiation is under study.
Finally, prophylactic cranial irradiation is under study to determine the appropriate timing and dose, especially when administered without concomitant chemotherapy.
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

31. Advanced Lung Cancer: Supportive Care
Treatment Modalities for Palliation
Chemotherapy
Radiation
Symptom Management
Dyspnea
Fatigue
Pain
In light of the poor prognosis for patients with advanced lung cancer, effective palliation is an important objective. One study of inoperable patients with non-small cell lung cancer found that two-thirds needed immediate local palliation and one-half of those with no thoracic symptoms at presentation required subsequent local treatment. Furthermore, since palliation is more difficult once local complications such as superior vena cava obstruction, obstructive pneumonia, or lobar collapse become serious, a watch and wait approach is appropriate for only a minority of patients.
Chemotherapy often improves the quality of life when used for palliation in patients with advanced lung cancer even in the absence of a measurable tumor response. Those more likely to achieve palliative benefit from chemotherapy are those with good performance status, females, age 70 years or older, low tumor burden, normal lactate dehydrogenase and serum calcium levels, and a hemoglobin greater than 11 g/dL.
Radiotherapy is also of demonstrated, sustainable palliative benefit. Symptoms such as hemoptysis and pain are more effectively palliated, while dyspnea and poor performance status tend to be refractory.
While numerous symptoms and paraneoplastic syndromes may be experienced by patients with advanced lung cancer, dyspnea, fatigue, and pain, are appropriate targets for palliative treatment.
Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Murren J, Glatstein E, Pass HI. Small cell lung cancer. In: DeVita VT Jr , Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott-Raven; 2001:
Feld R, Ginsberg RJ, Payne DG, Shepherd FA. Lung. In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:

32. Dyspnea Management Assessment Activity planning Medications
Corticosteroids
Opioids
Oxygen therapy
Non-traditional/investigational therapies
Acupuncture
Massage
Exercise
The assessment of dyspnea is difficult due to its completely subjective nature. Unlike hypertension or hyperglycemia, there is no reliable measure of dyspnea, including blood gases. The assessment, therefore, is confined to patient comments or responses to questions or observations regarding functional capabilities. Asking questions such as “Do you feel like you are getting enough air?” or “Do you have any difficulty breathing?” is often helpful. The current intensity of breathlessness should be explored as well as the impact of dyspnea on activities of daily living. The patient should be asked how far s/he can walk, how many steps can be climbed, which activities around the house can be done, etc. The patient can also be asked to note the severity and/or intensity of symptoms on a 0 to 10 visual-analog scale. Another assessment approach involves determining what alleviates the breathlessness, emotional and social effects, and accompanying symptoms. The physical assessment should focus mainly on the respiratory and cardiac systems to identify potential underlying causes such as pericardial effusion or superior vena cava syndrome.
The management of dyspnea involves anticipatory symptom avoidance and relief. To avoid anticipated symptoms, patients can be assisted with specific functions to minimize muscle effort and the consequent development of dyspnea. In addition, the patient should be encouraged to perform functions at times of the day where personal experience indicates dyspnea and other symptoms such as fatigue are less likely. This is typically in the morning.
Corticosteroids have been suggested as being highly effective; there are, however, no controlled clinical trials to support this observation. Several trials demonstrate the beneficial effects of opioids for relief of dyspnea. However, the optimal type, dose, and modality of administration has not been determined. The toxicity of systemic opioids may be a limitation; unfortunately, nebulized opioids appear to be of no benefit. Last, the role of supplemental opioids in a patient who experiences dyspnea while receiving opioids is unclear.
While oxygen therapy is of demonstrated benefit in patients with chronic obstructive pulmonary disease, its role in cancer-related dyspnea is not clear. Although most authorities do not advocate its use in this setting, one author has suggested performing multiple double-blind crossovers between oxygen and air over a period of an hour in an individual patient to assess if the patient is responsive to oxygen.
Various complementary and alternative measures have been utilized to manage dyspnea. Some benefit has been demonstrated with acupuncture, acupressure, and behavioral therapies. Anecdotal experience indicates that other approaches may also be helpful.
Bruera E, Ripamonti C. Dyspnea in patients with advanced cancer. In: Berger A, Portenoy R, Weissman D, eds. Principles and Practice of Supportive Oncology. Philadelphia, Pa: Lippincott-Raven Publishers; 1998:
Wickham R. Dyspnea: Recognizing and managing an invisible problem. Oncol Nurs Forum. 2002;29:

33. Fatigue Management Assessment Activity Planning Exercise Sleep aids
Stimulants
Anemia management
Iron supplements
Epoetin alfa
Fatigue is one of the most common complaints of patients with cancer. The effective management of fatigue is dependent on its detailed characterization and the factors most likely to be the cause in a particular patient. The multidimensional assessment of fatigue, which captures multiple characteristics and manifestations of fatigue and its impact on function, is more informative than the measurement of severity alone. The multidimensional assessment may generally be accomplished by asking three questions: “Are you experiencing any fatigue?” and “If yes, how severe has it been on average during the past week on a 0 to 10 scale?” as well as “How is the fatigue interfering with your ability to function?” An effort should be made to identify the causes of fatigue. Comorbidities such as depression, delirium, and anxiety should be appropriately managed, when present.
The effective management of fatigue utilizes pharmacologic and non-pharmacologic measures. Activity planning is an important management approach. Once identified, activities that predictably cause fatigue should be interspersed with brief periods of rest. Since most patients feel less fatigued in the morning, most activities should be accomplished at this time, if possible.
Exercise may actually be beneficial in relieving fatigue. An exercise program tailored to the patient’s age and medical condition should be implemented gradually and include a light to moderate workout several days a week. Exercise within 6 hours of bedtime should be avoided, however.
Sleep hygiene should be assessed to identify factors that may be interfering with sleep. Late afternoon or early evening naps should be avoided. The establishment of a specific bedtime and wake time, along with routine procedures prior to sleep are often helpful.
Psychostimulants, such as methylphenidate, pemoline, and dextroamphetamine, have shown some efficacy for non-cancer-related fatigue. Their use must be carefully monitored to avoid insomnia and other complications, including anorexia, anxiety, delirium, and tachycardia.
Anemia is a common complication of cancer since numerous chemotherapy agents cause myelosuppression. Whole blood transfusion was routinely utilized until concerns regarding the safety of blood supplies became a major issue. Recent trials with epoetin alfa administered three times per week demonstrate significant improvements in energy level, activity level, functional status, and overall quality of life. These responses have been shown to be directly related to the magnitude of the increase in the hemoglobin level. Concomitant iron supplementation is required to avoid a functional iron deficiency.
Portenoy RK, Itri LM. Cancer-related fatigue: Guidelines for evaluation and management. Oncologist. 1999;4:1-10.
Buchsel PC, Murphy BJ, Newton SA. Epoetin alfa: Current and future indications and nursing implications. Clin J Oncol Nurs. 2002;6:

34. Pain Management Assessment Medications:
Opioids
NSAIDS
Corticosteroids
Nonpharmacologic Interventions:
Heat/cold
Topical agents
Massage
Behavioral Therapy
Pain is a common, yet generally undertreated, complication of cancer. Identifying the etiology of pain is essential to its effective management. The goals of the initial assessment, much the same as they are for dyspnea and fatigue, are to characterize the pathophysiology of the pain, to determine the intensity of the pain, and to determine its impact on the patient’s ability to function. Factors that may influence analgesic response or result in persistent pain should be assessed and managed, if possible.
A three-step framework for pain management based on pain severity has been established by the World Health Organization. For mild pain, acetaminophen or a non-steroidal anti-inflammatory agent may be used initially. If pain relief is unsatisfactory, a more potent analgesic may be used. Most patients with cancer who have pain do not achieve an adequate response with this initial therapy and must be managed with an opioid.
Opioids are the mainstay for management of most moderate to severe pain in patients with cancer. Unfortunately, the use of opioids is often avoided or they are used ineffectively since their long-term use is widely believed to lead to addiction. This is an incorrect belief. While long-term use is likely to cause tolerance and physical dependence, psychological dependence, i.e., addiction, is uncommon. Similarly, respiratory depression is often a concern, although this too is unlikely since the opioid dose is generally titrated over a long period. Morphine is most commonly used, but other opioids such as oxycodone, hydromorphone, and fentanyl are also effective. The key to the management of pain is to prevent it rather than to treat it once it has occurred, a clinical practice similar to nausea and vomiting. Thus, the administration of an opioid on a fixed schedule in fully effective doses is required. Supplemental doses may be administered as needed for break-through pain.
Numerous adjuvant analgesics have been used for the wide variety of pain syndromes seen in patients with cancer. These include antidepressants, anticonvulsants, local anesthetics, corticosteroids, bisphosphonates, and others. Corticosteroids have gained wide acceptance for the management of cancer pain of bone, visceral, and neuropathic origin.
Non-pharmacologic interventions may also be helpful, particularly for musculoskeletal pain. These include heat, cold, and massage. The use of heat on recently irradiated tissue is contraindicated, however, and cold should not be applied to patients with peripheral vascular disease or on tissue damaged by radiotherapy. Massage has direct mechanical effects on tissues and enhances relaxation when applied gently. Tumor masses should not be aggressively manipulated.
Behavioral therapy is an important part of a multimodal approach to pain management since it gives the patient a sense of control and helps to develop coping skills. Such interventions should be introduced early in the course of the illness as they are more likely to be learned and practiced by patients while they have sufficient strength and energy.
National Cancer Institute. Pain (PDQ®) Health Professional Version. Available at: Accessed September 12, 2002.

35. Lung Cancer: Conclusions
Smoking cessation is essential for prevention of lung cancer.
New screening tools offer promise for detection of early lung tumors.
Clinical trials are testing promising new treatments.
New treatments offer improved efficacy and fewer side effects.
Treatment can palliate symptoms and improve quality of life.
In summary, since tobacco is a causative factor in at least 80% of patients with lung cancer, smoking cessation and its avoidance are essential for preventing or reducing the risk of lung cancer. New screening tools, such as low-dose spiral CT, offer some promise for the detection of early lung tumors. Further study is needed to clarify their roles in routine clinical practice.
Although progress in improving patient outcomes has been slow, particularly for small cell lung cancer, a variety of new treatments are being actively investigated. These include new chemotherapy agents as well as agents that alter the biologic response to tumor development and growth. While improving efficacy is a clear goal for these new therapies, so, too, is decreased toxicity.
Last, while generally intended to improve survival, treatment is often used to palliate symptoms and improve the quality of life.