FOURTH EDITION
`
`Cancer
`Management:
`A Multidisciplinary
`Approach
`Medical, Surgical, & Radiation Oncology
`
`Edited by
`
`Richard Pazdur, MD
`Director, Division of Oncology Drug Products
`Center fo r Drug Evaluation and Research
`US Food and Drug Administ rat ion
`
`Lawrence R. Coia, MD
`Chairman, Department of Radiation Oncology
`Community Medical Center, Toms River, New Jersey
`An affiliate of Sai nt Barnabas Health Care System
`
`William J. Hoskins, MD
`Deputy Physician in C hief, Disease Management T earn
`C hief, Gynecology Service
`Memorial Sloan-Kettering Cancer C enter
`
`Lawrence D. Wagman, MD
`C hairman, Division of Surgery
`City of Hope National Medical C enter
`
`And the editors of the journal O NCOLOGY
`
`PRB
`
`MEL V I L L E .N Y
`
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`Note to the reader
`The information in this volume has been carefully reviewed for accuracy of
`dosage and indications. Before prescribing any drug, however, the clinician
`should consult the manufacturer's current package labeling for accepted
`indications, absolute dosage recommendations, and other information perti(cid:173)
`nent to the safe and effective use of the product described. This is especially
`important when drugs are given in combination or as an adjunct to other forms
`of therapy. Furthermore, some of the medications described herein, as well
`as some of the indications mentioned, had not been approved by the US Food
`and Drug Administration at the time of publication. This possibility should be
`borne in mind before prescribing or recommending any drug or regimen.
`
`The views expressed are the result of independent work and do not
`necessarily represent the views or findings of the United States Food and
`Drug Administration or the United States.
`
`Copyright © 2000 by PRR, Inc. All rights reserved. This book is protected by copyright.
`No part of it may be reproduced in any manner or by any means, electronic or
`mechanical, without the written permission of the publisher.
`
`Library of Congress Catalog Card Number 99-075070
`ISBN Number 1-891483-05-6
`
`For information on obtaining additional copies of this volume, contact the publishers,
`PRR, Inc., 48 South Service Road, Melville, NY 11747
`
`Printed on acid-free paper
`
`Pim
`
`MELVILLE, NY
`
`Publishers of
`ONCOLOGY
`Oncology News International
`Managed Care & Cancer
`Primary Care & Cancer
`InTouch-The Good Health Guide to
`Cancer Prevention and Treatment
`Cancer Consultations
`
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`I
`1,
`
`i! j
`~ t
`H
`I !
`
`~ l r ~ i I
`
`CHAPTER 6
`
`Non- small-cell lung
`cancer and
`mesothelioma
`
`Fadlo R. Khuri, MD, Robert J. McKenna,Jr., MD, and Benjamin Movsas, MD
`
`In the United States, lung cancer has been the leading cause of cancer death in
`men for ye3/s, and since 1988 it also has become the number one cause· of
`cancer death in women. It is estimated that, in 2000, 171,600 new cases of lung
`cancer will be diagnosed, and 158,900 deaths due to this disease will occur.
`This exceeds the combined number of deaths from the second, third, and fourth
`leading causes of cancer (breast, prostate, and colon cancer, respectively) .
`
`Lung cancer appears to develop from ~ stem cell that can differentiate along ·
`multiple lines. Although multiple cell types are often found within a single
`lung tumor, one type usually predominates. Based on therapeutic approach,
`there are two major subdivisions of lung cancer: SCLC, for which chemo(cid:173)
`therapy is the primary treatment, and NSCLC, which, in its early stages (I and
`·
`II), is treated primarily with surgery.
`
`This chapter will focus on the diagnosis, staging, pathology, and treatment of
`NSCLC, including carcinoid tumors of the lung, while chapter 7 will provide
`information on the staging, pathology and pathophysiology, and treatment of
`the far less common SCLC. In addition, this chapter will also provide basic
`information on the epidemiology, etiology, screening and prevention, and signs
`and symptoms of lung cancer in general, as well as the pulmonary evaluation
`of lung cancer patients. This chapter will conclude with a brief discussion of
`mesothelioma.
`
`NON-SMALL-CELL LUNG CANCER
`
`Non-small-cell tumors account for approximately 80% of all lung cancers. The
`three major tumor types included under this category are adenocarcinoma,
`squamous cell carcinoma, and large-cell carcinoma.
`
`Epidemiology
`
`Gender In 1984, there were 87 cases of lung cancer per 100,000 men, and in
`1994 this number decreased to 74 cases per 100,000 men. Although lung cancer
`
`NON-SMALL-CELL LUNG CANCER AND MESOTHELIOMA
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`incidence had been rising in women, the rate of increase has begun to slow
`recently. In 1995, there were 43 cases of lung cancer per 100,000 women.
`Age Although the age at which lung cancer patients are diagnosed varies widely,
`the median age at diagnosis is approximately 60 years.
`Race In the United States, the highest incidence of lung cancer is found in
`Hawaiians and African-Americans.
`Geography There are geographic variations in the incidence of lung cancer,
`with the highest rates worldwide observed in Scotland and Wales, and the
`highest rates in the United States found in northern urban areas and along the
`southern coast from Texas to Florida.
`Survival The.overall 5-year survival rate for lung, cancer is 14%.
`
`Etiology and risk factors
`G;igarette smoking Approximately 870/o of all cases of lung cancer are related
`to cigarette smoking. There is a relatively strong dose-response relationship
`between cigarette smoking and the development of this cancer. An individual
`who smokes one pack of cigarettes daily has a 20-fold increased risk of devel(cid:173)
`oping lung cancer compared to a nonsmoker. The greater the number of ciga(cid:173)
`rettes smoked on a daily basis ·and the greater the number of years of smoking,
`the greater is the risk of developing lung cancer.
`Overall, there has been a decrease in the incidence of cigarette smoking from
`1974 through 1992. Smoking cessation decreases the risk of developing lung
`cancer, but a significant decrease in risk does not occur until approximately 5
`years after stopping. In addition, the risk of developing lung cancer in former
`smokers remains higher than the risk in nonsmokers for at least 25 years. The
`benefit of smoking cessation is greater if it occurs at a younger age.
`Smoking cessation is difficult. Recent data have suggested that certain indi(cid:173)
`viduals have an increased risk of addiction to nicotine based on a variety of
`hereditary factors. Nevertheless, millions of former smokers have quit suc(cid:173)
`cessfully. Smoking cessation programs that address both physical withdrawal
`from nicotine and psychological dependence appear to be more effective than
`either of these approaches alone. In addition, continued efforts are needed to
`prevent adolescents and preadolescents from beginning to smoke or to en(cid:173)
`courage them to quit after a brief period of experimentation.
`Several cancer centers have recently reported that more than half of their pa(cid:173)
`tie~ts with newly diagnosed lung cancer are former smokers, having quit more
`than a year before diagno$is. Healthy exsmokers represent a large group of
`individuals who may benefit from effective tools for early detection · and/or
`chemoprevention of lung cancer.
`Second-hand smoke Not only is smoking risky for those who smoke, but it also
`poses a hazard to nonsmokers who either live or work with smokers. It is
`
`92
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`C_ANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
`
`; . .
`I ! '
`I,
`,:
`i ;
`,,
`
`; ,
`
`I! ii I
`i
`!
`
`~ I
`
`I I
`f
`I
`I
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`estimated that approximately 3,000 lung cancer deaths per year in the United
`States an~ due to second-hand smoke. Individuals who live in a household with
`a smoker have a 30% increase in the incidence of lung cancer compared to
`nonsmokers who do not live in such an environment.
`As be sto s exposure is another risk factor for lung cancer. Cigarette smokers
`who are exposed to asbestos develop lung cancer at an extremely high rate.
`Exposure to asbestos also is a major risk factor for the development of meso(cid:173)
`thelioma (see discussiori of this cancer below) .
`Radioactive dust and radon exposure Uranium miners who have been ex(cid:173)
`posed to radioactive dust and radon gas also have an increased incidence of
`lung cancer. Although there has been some controversy about the risk posed
`by exposure to residential radon gas, a recent study conducted in Sweden
`showed an increased incidence of lung cancer in individuals who were ex(cid:173)
`posed to a high level of r8:don in their homes.
`
`Screening and prevention
`
`Screening
`Three randomized screening trials conducted in the United States in the 1970s
`failed to show a survival advantage for individuals who were screened by spu(cid:173)
`tum cytology for lung cancer. Despite the fact that these US trials were not
`designed to evaluate chest x-ray as a screening tool, the results led most ex(cid:173)
`. perts to conclude that screening for lung cancer was not worthwhile. In addi(cid:173)
`tion, most investigators recommended that research efforts and resources be
`allocated to the prevention of lung c.ancer.
`A more recent, randomized, prospective trial from Czechoslovakia showed that
`screening with a chest x-ray increased the diagnosis of early-stage lung cancer
`and reduced mortality from lung cancer. Studies are currently underway to evaluate
`chest CT scan for lung cancer screening. Several recent reports fromJapan, Ger(cid:173)
`many, and the United States have documented the ability of low-dose spiral
`CT scans to detect lung cancer at an early stage. Kaneko screened male smokers
`> 50 years. Of the 15 cancers detected by CT scan, only 4 were seen on chest
`x-ray; 14 of the 15 cancers were stage I with an avencge diameter of 1.6 cm.
`Ohmatsu found 35 lung cancers (37% detection rate) with 9,452 CT scans. Of
`these, 27 were stage IA. These patients had a 3-year survival rate of 83%.
`Also, consideration has recently been given to conducting a larger trial to evalu(cid:173)
`ate screening with long-term annual chest x-rays. It has been estimated that
`· this type of study could result in a 13% reduction in lung cancer mortality,
`which would translate into approximately 18,000 lives saved on an annual
`basis. Despite the renewed interest in screening for lung cancer, at present
`routine screening is not recommended.
`The lack of demonstrated benefit for the older screening approaches should ·
`not be misinterpreted as nihilism about the early detection of patients with
`
`NON-SMALL-CELL LUNG CANCER AND MESOTHELIOMA
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`lung cancer. Patients at risk (current and former smokers) who present with
`symptoms consistent with lung cancer deserve appropriate evaluation . The
`lack of resolution of radiographic abnormalities on a chest x-ray obtained after ,
`the completion of empiric antibiotic therapy for pneumonia should prompt
`further evaluation for possible lung cancer. Failure to do so constitutes inap(cid:173)
`propriate therapeutic nihilism.
`
`Chemoprevention ·
`Second primary lung tumors develop at the rate of 1 %-30/o annually for the first
`5 years following resection of stage I lung cancer. The retinoid 13-cis-retinoic
`acid (isotretinoin) has reduced the incidence of second primary cancer in head
`and neck cancer patients.
`This observation served as the basis for an intergroup randomized trial
`that is assessing the ability of 13-cis-retinoic acid to prevent the occur(cid:173)
`rence of a- second primary cancer in patients with completely resected
`stage I lung cancer. This trial has completed accrual (1,486 patients have
`been enrolled) . Although final results are not yet available, early findings
`have demonstrated a higher-than -expected recurrence rate in patients with
`early-stage lung cancer.
`Two recent randomized trials evaluating the administration of 13-carotene in
`heavy smokers have shown that, contrary to expectation, the risk of death
`from lung cancer was increased in the treated population. Prior epiderpiologic
`data had suggested a correlation between low dietary 13-carotene intake and an
`increased risk of lung cancer. The reason for the apparent discrepancy be(cid:173)
`tween these findings and the results of the randomized trials is unknown. One
`possibility is that dietary substances other than or in addition to 13-carotene are
`the active chemop!eventive agents.
`In any event, these therapeutically negative trials have demonstrated a proof
`of principle that it is possible to modify lung cancer risk in smokers; what is
`needed now are agents that will reduee rather than increase this risk.
`Educational programs While the information from the intergroup random(cid:173)
`ized chemoprevention study is being collected, it is important to continue edu(cid:173)
`cational efforts to prevent adolescents from starting to smoke cigarettes and to
`advocate smoking cessation in active smokers. Some experts believe that edu(cid:173)
`cational programs must begin during childhood, probably between the ages of
`6 and 10 years.
`
`Signs and symptoms
`The clinical manifestations of lung cancer depend on the location and extent
`of the tumor. In patients who have localized dis ease , the most common
`symptorris are related to obstruction of major airways, infiltration of lung pa(cid:173)
`renchym?,, and invasion of surrounding structures, including the chest wall,
`major blood vessels, and viscera.
`
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`CANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
`
`,_. ,,.
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`Cough is a major ·manifestation of lung cancer. However, it is important to
`remember that the majority oflung cancer patients are current or former smok(cid:173)
`ers, and may have a cough related to chronic irritation of the upper and/ or
`lower airways froJ:D: cigarette smoke. Therefore, smokers should be asked
`whether there has been a change in their cough, such as an increase in fre(cid:173)
`quency or severity.
`Dyspnea and he moptysis Increasing dyspnea and hemoptysis may be signs
`of lung cancer.
`
`Pneumonia Postobstructive pneumonia secondary to partial or complete bron(cid:173)
`chial obstruction occurs relatively frequently in association with lung cancer. It
`is important to obtain repeat chest :x-rays in adults who have been treated for
`pneumonia to be certain that the::radiog:r;iphic abnormalities have cleared
`completely.
`·
`\
`Pleural effusion Lung cancer inay ·spread to the pleural surface, resulting in
`pleural effusion and increased dyspnea.
`Chest pain Approximately 5% of lung tumors invade the chest wall. The re(cid:173)
`sultant pain is a better predidor of chest wall invasion· than are chest CT find(cid:173)
`ings. An individual who cdmplains of persistent chest pain should have a ches_t
`x-r.ay to exclude the pr'esenc·e ofperipheral lung cancer that has invaded the
`chest wall.
`Sh<>Ulde r and arm pain Apical ~inqts that infiltrate surrounding structures
`(also called Pancoast's fumo•r~) produce shoulder and/or.arm pairi as a result of
`br~chial ple~us col1l,pres.siori;TU0?,.9r$. in the apical lung segments may be-diffi(cid:173)
`cult tq .detect 01;1. a _routj.p.e chest x~.ray; therefore, a person who complains of
`persistent shoulder pain; particularly . with signs of rn~µrologic involvement,
`should have a CT scan of the chest to look for an apical tumor. ·It is also impor(cid:173)
`tant to exariiirie the lung apex 'fu bone films obtained to evaluate shoulder
`pain.
`· •• :
`
`Horner's syn·dr~me Invasion of the sympathetic ganglion by an apical lung
`tumor causes H6rner's syridroriie (ptosis, myosis~ arid ipsifateral ·anhydrosis).'
`Hoarsene.ss secon(iary to vo~al cqrq. par~13is or p~ralysis occurs when tumors
`and lymph node metastases compr~s~ ,t.pe rncu.qent laryngeal nerve. This situ(cid:173)
`ation is more common on the h~ft side, where the recurrent laryngeal nerve
`passes under the aortic · arch, but it may also occur with high lesions on the
`right side of the mediastinum:
`Other symptoms of tumor compression Lung tumors may also cause dys(cid:173)
`phagia by compression or invasion of the esophagus or superior vena cava
`syndrome by compression or invasion of this vascular structure.
`Some tumors may result in wheezing or stridor secondary to compression or
`invasion of the trachea, and may also cause signs of cardiac tamponade sec(cid:173)
`ondary to involvement of the pericardial surface and subsequent accumulation
`of pericardia! fluid.
`
`NON-SMALL-CELL LUNG CANCER AND MESOTHELIOMA
`
`9S
`
`' .
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`l
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`•
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`•
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`\.~'-J
`
`Sig ns and symptoms of metastatic diseas e Lung cancer can metastasize to
`multiple sites, the most common of which are bone, liver, brain, lung (con(cid:173)
`tralateral or ipsilateral), and adrenal glands.
`Lung cancer patients who have brain metastases may complain of headaches
`or specific neurologic symptoms, or family members may notice a decrease in
`the patient's mental acuity. Also, metastatic lung cancer may cause spinal cord
`compression, resulting in a characteristic sequence of symptoms : pain, followed
`by motor dysfunction, followed by sensory symptoms. The patient may have
`any or all of these symptoms.
`It is important to note that patients who complain of band-like pain encircling
`one or both sides of the trunk may have spinal cord compression. In addition,
`coughing and sneezing may cause significant exacerbation of pain from spinal
`cord compression.
`Bone x-rays and/ or a bone scan are warranted in lung cancer patients who
`complain of persistent pain in the trunk or extremities. MRI of the spine is the
`most effective way to evaluate suspected spinal cord compression.
`Lung cancer frequently metastasizes to the adrenal glands, and occasionally, this
`may cause flank pain. However, in general, adrenal metastases are asymptomatic.
`It is relatively uncommon for adrenal metastases to result in adrenal insufficiency.
`Systemic paraneoplastic symptoms Lung cancer is commonly associated
`with systemic manifestations, including weight loss (with or without anorexia).
`In addition, patients frequently complain of fatigue and generalized weakness.
`Specific ne urologic syndromes, such as Lambert-Eaton syndrome (see
`chapter 46), cortical cerebellar degeneration, and peripheral neuropathy, may
`·
`occur in lung cancer patients, but these are relatively rare.
`Clubbing Although clubbing may occur in a variety of conditions, it is impor(cid:173)
`tant for the clinician to evaluate a patient's hands, because if clubbing is noted,
`obtaining a chest x -ray may result in the early diagnosis of lung cancer.
`Hypertrophic osteoart~ropathy A relatively small percentage of patients
`with lung cancer may present with symptomatic hypertrophic osteoarth~opa(cid:173)
`thy. In this syndrome, periosteal inflammation results in pain in affected areas,
`most commonly, the ankles and knees.
`Carcinoid syndrome is extremely uncommon in patients who have a :bron(cid:173)
`chial carcinoid tumor. Most of these patients are asymptomatic (tumors are
`found by x-ray) , and a few have cough from an endobronchial lesion.
`
`Staging and prognosis
`
`Staging
`The staging of lung cancer must be conducted in a methodical and detailed
`manner in order · to permit appropriate therapeutic recommendations to be
`
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`made and to allow treatment results from different institutions to be compared.
`The TNM staging system, recently updated by Mountain (Table 1), applies
`equally well to all histologies. However, TNM staging is generally not utilized
`in SCLC, as it does not predict well for survival. Rather, SCLC is generally
`staged as limited (MO~ or extensive (Ml) disease.
`
`Stage is commonly reported as either clinical or pathologic. The formet is
`based on noninvasive (or minimally invasive) tests, while the latter is based on
`tissue obtained during surgery (see "Diagnosis and preoperative staging evalu-
`. ation" below).
`
`Prognostic factors
`Stage The most important prognostic factor in lung cancer is the stage of disease.
`
`Performance status and weight loss Within a given disease stage, the Iiext
`most important prognostic factors are performance status and recent weight
`loss. The two scales used to define performance status are the Eastern Coop(cid:173)
`erative Oncology Group (ECOG) performance status system and the
`Karnofsky system (see Appendix 3). In short, patients who are ambulatory
`have a significantly longer survival than those who are nonambulatory.
`Similarly, patients who have lost> 5% of body weight during the preceding
`3-6 months have a worse prognosis· than patients who have not lost a signifi(cid:173)
`cant amount of weight:
`
`Molecular prognostic factors Several studies published over the last decade .
`have indicated that mutations of ras proto-oncogenes, particularly K-ras, por(cid:173)
`tend a poor prognosis .in individuals with stage IV NSCLC. Accordingly, re(cid:173)
`search has focused on developing molecularly targeted therapeutic approaches
`to the rasproto-oncogenes, in particular, the farnesyl transferase inhibitors (see
`"Promising novel agents" page I 13).
`Of equal relevance was the completion of large studies by Pastorino et al and
`· Kwiatowski et al evaluating the prognosti~ importance of immunocytochemi(cid:173)
`cal and molecular pathologic markers in stage I NSCLC. The findings of these
`two studies suggest that pathologic invasion and extent of surgical resection
`may yield the most critical prognostic information, but mutation of the K-ras
`oncogene and absence of expression of the H-ras p21 proto-oncogene may
`augment the pathologic information obtained.
`
`Diagnosis and preoperative staging evaluation
`
`History and physical examination
`The diagnosis and preoperative staging oflung cancer begin with a good history
`and physical examination. When obtaining the history, the clinician should
`keep in mind the tendency for lung cancer to involve major airways and other
`central structures. Similarly, the patterns of metastatic dissemination and
`systemic manifestations must be considered when conducting the physical
`examination.
`
`NON-SMALL-CELL LUNG CANCER AND MESOTHELIOMA
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`TABLE I: TNM stag ing of lung cancer
`Prim a ry turnor (T)
`Tumor proven by the presence of malignant cells in bronchopulmon ary
`TX
`secretions but not visualized roentgenographically or bronchoscopically,
`or any tumor that cannot be assessed, as in pretreatment staging
`No evidence of prima ry tumor
`Carcinoma in situ
`Tumor ~ 3.0 cm in greatest dimension, surrounded by lung or visceral pleura,
`and without evidence of invasion proximal to a lobar bronchus at bronchoscopy
`Tumor > 3.0 cm in greatest dimension, or tumor of any size that either invad e s
`the visceral pleura or has associated atelectasis or obstructive pneumonitis
`extending to the hilar region (but involving less than the entire lung) . At
`bronchoscopy, the proximal extent of d e monstrabl e tumor must be within a
`lobar bronchus or at least 2.0 cm distal to the carina.
`Tumor of any size with direct extension into the ·chest wall (including sup e rior
`sulcus tumors), diaphragm, or mediastinal pleura or pericardium without
`involving the heart, great vessels, trachea , esophagus, or verte bral body;
`or tumor in the main bronchus within 2 c m of, but not involving, the carin a
`Tumor of any size with invasion of the mediastinum or involving th e heart,
`great vessels , trachea, esophagus, vertebral body, or carina; or presence of
`ma lignant pleural effusion
`Re gi onal lyrn ph nod es ( N)
`Regional lymph nodes cannot be assessed
`NX
`No demonstrable metastasis to regional lymph nodes
`NO
`Metastasis to lymph nodes in the peribronchial and/or ipsilateral hilar region,
`NI
`including direct extension
`Me tastasis to ipsilateral mediastinal and subcarinal lymph nodes
`Metastasis to contralateral mediastinal, contralateral hilar, ipsilater al or
`contralateral scalene, or supraclavicular lymph nodes
`Dis t ant metastasis (M )
`Distant metastasis cannot be assessed
`MX
`No distant metastasis
`MO
`Distant metastasis
`Ml
`Stage g roupi ng
`Occult carcinom a
`Stage 0
`Stage IA
`Stage 1B
`Stage IIA
`Stage 11B
`
`\
`
`. ' f 1.
`
`i.
`
`r .
`
`. .,
`
`TO
`Tis
`Tl
`
`T2
`
`T3
`
`T4
`
`N2
`N 3
`
`MO
`NO
`TX
`MO
`NO
`Tis
`MO
`NO
`Tl
`MO
`NO
`T2
`MO
`NI
`Tl
`MO
`NI
`T2
`MO
`NO
`T3
`MO
`NI
`T3
`MO
`N2
`Tl-3
`MO
`N3
`AnyT
`MO
`Any N
`T4
`Ml
`Any N
`AnyT
`Stage IV
`Fro m Mo untain CF: Revisions in th e inte rnational syste m fo r staging lung canc e r. Ch e st 111 (6) : 1710-
`
`Stage IIIA
`
`St age 1118
`
`17 17, 199 7.
`
`9 8
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`Patients should be questioned ~pecifically about the presence of palpable masses,
`bone pain, headache, or changes in vision. Careful auscultation and percussion
`may suggest the presence of atelectasis or a pleural effusion. Also, auscultation
`of the chest may show evidence of large airway obstruction and pulmonary
`consolidation. An enlarged liver may indicate hepatic metastases.
`Examination of supraclavicular fossa Clinicians should be careful to exam(cid:173)
`ine the supraclavicular fossa, as detection of an enlarged lymph node in this
`area may provide the means for establishing a tissue diagnosis.
`
`In addition, identification of supraclavicular lymph node metastases has im(cid:173)
`portant therapeutic and prognostic implications. In particular, supraclavicular
`nodal metastases immediately eliminate the patient from consideration for
`surgery.
`
`Imaging studies
`Chest x-rays should always be done in a high-risk patient with new respi(cid:173)
`ratory symptoms. Not only are PA and lateral chest x-rays of fundamental
`importance in assessing the local extent of the primary tumor, but also they
`may provide valuable information regarding metastatic disease.
`The chest x-ray should be inspected for the presence of a pleural effusion or
`synchronous pulmonary nodules, and the bones should be examined for evi(cid:173)
`dence of osseous metastases. A widened mediastinum usually indicates meta(cid:173)
`static disease within the mediastinal lymph .nodes. Comparison with previous
`x-rays is frequently helpful and well worth the effort expended in their retrieval.
`Chest CT A CT scan of the chest, including the liver and adrenal glands, is
`performed routinely to further define the primary tumor and to identify
`lymphatic or parenchymal metastases. Metastatic tumor is found in approxi(cid:173)
`mately 8% of mediastinal lymph nodes< 1 cm iµ greatest diameter, 30% of
`nodes 1-2 cm in greatest diameter, and 60% of those > 2 cm. Benign enlarge(cid:173)
`ment of mediastinal nodes is more common in patients with postobstructive
`infection. Histologic documentation of the presence or absence of tumor within
`the mediastinal lymph nodes is necessary when~ver this information will change
`treatment recommendations.
`
`It is important to remember that patients with persistent symptoms, such as
`cough and dyspnea, who haye a normal chest x-ray may be harboring a cen(cid:173)
`tral lesion that is not obvious on chest x-ray but can be easily detected by chest
`CT. Also, as mentioned above, apical tumors (Pancoast's tumors) may be diffi(cid:173)
`cult to detect on a chest radiograph but are usually readily apparent on a CT
`scan.
`PET Current data suggest that PET may be very helpful for the evaluation of
`lung masses, lymph nodes, and distant metastases. When a lung mass "lights
`up" on a PET scan, there is a 90%-95% chance that it is cancerous. The positive
`predictive value of a PET scan is lower in areas with a high prevalence of
`granulomatous disease. If the mass is at least 1 cm and cannot be imaged by
`· PET scanning, there is only a 5% chance that it is.malignant. Both the sensitivity
`and specificity of PET for detecting nodal metastases are approximately 90%.
`
`NON-SMALL-CELL LUNG CANCER AND MESOTHELIOMA
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`Several trials have evaluated the prognostic significance of fluorodeoxyglucose
`(FDG) uptake on PET scan in NSCLC. Most of these studies used a
`standardized uptake value (SUV), a semiquantitative measurement of FDG
`uptake. Utilizing multivariate Cox analysis, these studies noted that SUV,
`particularly when > 7, was a highly important prognostic factor. Other
`studies indicated that the use of PET combined with chest CT was almost
`as sensitive as surgery alone in the evaluation of pathologically positive
`mediastinal lymph nodes .
`Adrenal gland biopsy The adrenal gland may be the sole site of metastatic
`disease in as many as 100/o cif patients with NSCLC. Therefore, an enlarged or
`deformed adrenal gland should be biopsied. Patients should not be assumed to
`have metastatic disease and denied a potentially curative operation on the ba(cid:173)
`sis of a scan; histologic confirmation must be obtained.
`
`Obtaining a tissue diagnosis
`The next step is to try to obtain a histologic or cytologic diagnosis of the ra(cid:173)
`diologic lesion, altho_ugh preoperative histologic diagnosis need not be ob(cid:173)
`tained in a patient with a new, peripheral lung mass and no evidence of distant
`or locoregional metastases (see below).
`Central lesions Although .collecting sputum cytologies for 3 consecutive days
`frequently provides a cytologic diagnosis for central lesions, most clinicians
`proceed directly to bronchoscopy. In centrally located lesions, this procedure
`establishes a cytologic and/ or histologic diagnosis in 80%-85% of cases. In
`addition, bronchoscopy may provide important staging information, such as
`whether the tumor involves the distal trachea or carina, and may help plan the
`appropriate operation (lobectomy or sleeve resection vs pneumonectomy) .
`Pe riphe ral lesions Bronchoscopy is less likely to yield a diagnosis in patients
`with peripherally located lesions. The false-,negative rate in such cases may
`range from 20% to 50%.
`A CT-guided needle biopsy may diagnose up to 900/o of peripheral lung cancers.
`However, needle biopsy is usually reserved for patients who are not candi(cid:173)
`dates for an operation due to distant metastatic disease or poor performance
`status. If the patient is a candidate for surgery, resection is gE:nerally recom(cid:173)
`mended for any suspicious mass whether the needle biopsy is positive or
`nondiagnostic. Therefore, for patients with a suspicious peripheral lesion that
`is not invading the chest wall and is not associated with mediastinal adenopa(cid:173)
`thy, it is reasonable to proceed directly to surgery.
`Mediastinoscopy provides not only a histo_logic diagnosis but also yields
`important staging information. If multiple lymph node levels contain tumor,
`most thoracic surgeons would not proceed directly to operation, but rather,
`would offer these patients neoadjuvant therapy as part of a clinical trial. Al(cid:173)
`ternatively, such patients could receive nonoperc).tive primary therapy. How(cid:173)
`ever, if only one ipsilateral nodal level is positive for metastatic tumor, many
`surgeons will perform a pulmonary resection and lymph node dissection and
`advise participation in an adjuvant therapy trial. Involvement of contralateral
`
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`TABLE 2: Selective indications for medi a stjnoscopy
`
`Enlarged N I or N2 lymph nodes on chest CT scan
`Centrally located tumors
`
`Poorl.y differentiated tumors
`
`T3 tumors
`Patients who are marginal _candidates for resection
`
`mediastinal lymph nodes (stage IIIB) is generally thought to contraindicate
`surgery even when preceded by neoadjuvant therapy. Table 2 lists selective
`indications for mediastinoscopy.
`Thorace ntesis and thoracoscopy Individuals who have pleur