Lung Cancer

Kimberly M. Baker, MD Division of Pulmonary, Critical Care, & Occupational Medicine

Objectives
• • • • • • • Epidemiology Screening Risk Factors Solitary Pulmonary Nodules Pathology Presentation Diagnosis/Staging

Lung Cancer Stats
• 2007 cancer deaths:
– Lung cancer #1: 160,000 – Breast, colorectal & prostate combined: 120,000

• Women
– Surpassed breast cancer early in last decade – 1997: ~50% more women died from lung ca vs. breast ca (66,000 vs. 44,000)

• Aging pop means absolute #s will increase

U.S. Cancer: INCIDENCE by Leading Sites 2002
Lung and Bronchus 14 %
Colon and Rectum 11% Prostate 30% Bladder 7% BREAST 31% Colon and Rectum 12% Uterus 6%

Lung and Bronchus 12%

CA Cancer J Clin 2002; 52:23-47.

S.U.52:23-47 . Cancer: MORTALITY Leading Sites 2002 Lung and Bronchus 31% Colon and Rectum 10% Pancreas 5% PROSTATE 11 % Bladder 3 % All other sites 40 % Lung and Bronchus 25% BREAST 15 % Colon and Rectum 11 % Pancreas 6% Uterus 2 % All other sites 41 % CA Cancer J Clin 2002.

030 total new cancer cases • World-wide .8 (F) per 100.8% of total new cancer cases.620 total new cancer cases • US 173.04 million cases (1990) 12.Lung Cancer World-Wide (2004) • Iowa .1.000 population .2192 new lung cancer cases 16.368. Incidence=37.5 (M) and 10.770 new lung cancer cases 1.

1999. 1985-94 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Stage 1 Stage 2 Stage 3 Stage 4 Fry.Lung Cancer Stage. US National Cancer Database. 86:1867-76 . Cancer.

Lung Cancer Screening Which of the following decrease mortality in lung CA • Chest X-ray – Does not decrease mortality • Sputum cytology – Does not decrease mortality • Computerized Tomography – Does not decrease mortality – In high risk pts referral to study may be appropriate • Bottom-line – no screening has been shown to decrease mortality ACCP Lung Cancer Guidelines 2003 .

38: 453470 . 2000.Lung Cancer: Who Gets It? • Lung Cancer is UNIQUE among all malignancies in having a SINGLE risk factor which accounts for the highest percentage of attributable risk:: TOBACCO. A preventable cause of disease Rad Clin N Am.

Risk Factors for Lung Cancer • Cigarette Smoking. familial and dietary factors) .10-20x compared to lifetime nonsmoker • Additional risk factors – – – – – – Environmental (second hand smoke) Asbestos Radon Arsenic Ionizing radiation Others (scarring. Cigarette Smoking – Cause of 90% of lung cancers – Increases risk .

gender. concurrent exposures. race. family history.9 .1 relative risk female smokers: 11.Tobacco and Lung Cancer Risk • Tobacco smoke = 90% of lung cancer risk • STRENGTH of relationship established by – consistency of studies – clear dose-response relationship – biologic plausibility • RELATIVE RISK range 5 to 29 depending on age. • Generally: male smokers: 22.

4 11.Lung Cancer is an Environmental Problem • Smoking 28% of US men and 32% of US women smoke Smoking accounts for 80-90% of pulmonary malignancies Risk from smoking is cumulative and duration dependent producing a dose-dependent relationship Synergistically interacts with other risk factors • Relative Risk of Cancer due to Smoking Male Cigarette Smokers Female Cigarette Smokers Cigar Smokers Pipe Smokers 22.6 1.9 5.6 .

000 deaths/yr) . but lesser amounts compared to mainstream smoke – Risk is unknown as no unexposed control group exists – Difficult to document exposure levels. responder bias • Overall OR for lung cancer among passive smokers – 1.Lung Cancer is an Environmental Problem • Passive Smoking/Sidestream Smoke – Contains similar constituents.44 (95% CI)) Prospective Studies – 30% increased RR from smoking spouse • Responsible for 17% of lung cancers in nonsmokers (500-5.25 (95% CI) Case control studies – 1.

000 mesotheliomas/yr 4-6.Lung Cancer is an Environmental Problem • Occupational Agents Associated with Lung Cancer Radon (workplace) (non-workplace) Asbestos 6x risk alone.4-1.7 2.3% increased RR 1% lifetime excess risk 10-15% of all lung cancers RR=1. 59x risk with smoking Chloromethyl Ether Arsenic Formaldehyde Talc 3.000 Lung Cancers/yr Cadmium Chromate Terpenes .

and 70 yo  .4 fold risk of lung cancer in relatives of patients with lung cancer Modeling of epidemiologic data suggests.2. 60.  Mendelian pattern of co-dominant inheritance  Rare autosomal gene  Carriers have an early age of lung cancer onset  Accounts for 69%. and 22% of the cumulative incidence of lung cancer up to 50.Lung Cancer May be a Biologic Problem  Epidemiologic data . 47%.

and survived longer – risk significantly increased regardless of smoking history if there is a positive family history • Genetic Risk of Lung Cancer Ambrosone.Gender. RR 2. Ferguson 1990. consumed fewer cigarettes. Perrot 2000 – Multiple studies have demonstrated a familial clustering of lung cancer.4 . 1990. Sellers. less likely to be current or former smokers. have more adenocarcinoma. Family and Lung Cancer • Women and Lung Cancer – younger. 1993.

vascular. rheumatoid . infectious.Solitary Pulmonary Nodule “Coin lesion” • Intraparenchymal lesion < 3cm – Lung lesion > 3cm = masses • • • • 1:500 radiographs contains nodule 90% are asymptomatic 150.000 per year Differential = neoplastic. inflammatory.

Solitary Pulmonary Nodule Variable Low Intermediate High Diameter (cm) Age (yr) Smoking <1. thoracic surgeon .2 45-60 ≤ 20 cig/day ≥ 2.5-2.5 <45 Never 1.resection • High risk – surgical resection • Intermediate – individualize • Referral to nodule “expert” if uncertain – Pulmonologist.3 >60 > 20 cig/day Cessation Characteristics of nodule ≥ 7 yrs Smooth < 7 years Scalloped Never quit Spiculated • Low risk – follow q3-6 months on CT for 24 months – If grows .

30.1%. central. • Bronchioloalveolar (adenocarcinoma subset) – Squamous Cell Carcinoma . histologically look for gland formation.81.Types of Lung Cancer • Non-Small Cell . Typical and Atypical • Small Cell . commonly associated with hypercalcemia. most common.18.30%. peripheral.7%.< 1% . non-smoker.2% – Arises submucosally in the airways. can achieve very large size. smoker. metastasizes early. hemoptysis. quickly metastasizes to mediastinal nodes and systemically.4% – Carcinoid .8% – Adenocarcinoma . bronchogenic. frequently cavitate. – Large Cell Carcinoma . histologically look for keratin. histologically look for monotonous tumor histology • Mesothelioma .9.

Lung Cancer Histology National Cancer Data Base 1985-1994 ALL OTHER/ UNKNOWN 12. 1999 29. 8% LARGE CELL 11.1% ADENOCARCINOMA .3% SMALL CELL 17.1% 29.5% SQUAMOUS CELL Fry.

Clinical Presentation of Lung Cancer • Only about 6-10% are asymptomatic at time of diagnosis • Symptoms: – Primary lesion – Intrathoracic spread – Distant metastases – Paraneoplastic syndrome .

• History and Physical Exam Diagnosis of Lung Cancer – Asymptomatic 6% – Symptoms from primary tumor 27% • • • • • • • • • Fatigue. weight loss Hoarseness Dysphagia Wheezing 80-85% 8-61% 7-40% 20-33% 6-31% 55-88% 3-13% 1-5% 2% – Signs • Clubbing. HPO 6-13% • Pleural Effusion 12-33% • Neurologic Changes 4-21% . lethargy Cough Dyspnea Chest Pain Hemoptysis Anorexia.

lymphangitic spread. obstructive pneumonia. pleural or pericardial effusion) • Hemoptysis 27-57% • Chest pain 25-50% • Weight loss (8-68%)--poor prognosis .Symptoms Due to Primary Lesion • Cough 45-75% (hard to differentiate from COPD) • Sputum production not specific – Increased in some cases bronchoalveolar cell • Dyspnea 1/2 to 1/3 pts (large airway obstruction.

Lung Cancer Common Metastatic Sites Site Pleura Other Lung Heart Liver Adrenals Bone Kidney Chest Wall CNS Esophagus Sputum SqCCa 34 21 25 25 25 20 21 20 18 13 3 AdenoCa 60 60 36 41 50 36 23 20 37 8 6 .

atrophy of hand muscles. rib destruction. & T2 nerve roots . T1. pain in C8.Symptoms Due to Intrathoracic Spread • • • • Pleural effusion: dyspnea Pericardial effusion: dyspnea Hoarseness (2-18%)(left sided) Superior Vena Cava (SVC) Syndrome (4%) – Headache or fullness. physical findings – Small cell ca most common cause • Brachial Plexis (Pancoast) – Horner’s syndrome.

pelvis • Hepatic mets: weakness. also ribs. wt loss – Poor prognosis • Brain mets: lung is initial site (>70%) symptomatic brain tumors – Headache. personality change. focal neurologic signs.Distant Metastases Symptoms • Bone mets: pain – Usually spine. N/V. confusion. seizures • Adrenal mets: asymptomatic – 2/3 of adrenal masses are benign .

Paraneoplastic Syndromes • Non-metastatic systemic symptoms • Production of biologically active compounds either by tumor or response to tumor • Occur in 10-20% • Types – – – – Hypercalcemia (bone mets or squamous cell-PTH) Clubbing or HPO (a/w adenocarcinoma) SIADH or ectopic ACTH production Neurologic Syndromes (Eaton-Lambert (Small Cell). cortical cerebellar degeneration . peripheral neuropathy.

Hypercalcemia. Cerebellar Degeneration. Cushing’s Syndrome – Neurologic .Hypercoagulability. Anemia Am J Resp Crit Care Med.cachexia.Clinical Syndromes in Lung Cancer • PARANEOPLASTIC SYNDROMES – Systemic . Peripheral neuropathy – Cutaneous .Eaton Lambert. weight loss – Endocrine . SIADH. 1997. . 156:320-332. Hypertrophic Osteoarthropathy – Hematologic .clubbing.

the likelihood of finding metastatic disease on exhaustive imaging and testing work-up is low . METASTATIC Disease • COMPLETE History and Physical • POSITIVE Findings .DETERMINE LOCAL vs.direct further evaluation – If initial comprehensive clinical evaluation is negative.Diagnosis of Lung Cancer • Initial Evaluation: – GOAL .

Diagnostic Biopsy in Lung Cancer • Why Biopsy? – – – – Exclude Nonmalignant Disease Differentiate Small Cell vs. Non-small Cell Staging Direct Palliative Therapy • What Lesion To Biopsy? – Lesion which will result in most advanced stage .

How To Get Tissue for Diagnosis • Sputum Cytology • Transthoracic Needle Biopsy • Fiberoptic Bronchoscopy • Mediastinoscopy • Video-Assisted Thoracotomy / Wedge Resection .

Sputum Cytology Diagnostic in 75% of symptomatic central tumor No Staging Data .

Transthoracic Needle Biopsy Diagnostic Rate: 60-95% Small Lesions Difficult Thoracentesi Rate s Diagnostic : 40-70% T4 if positive for tumor cells .

Fiberoptic Bronchoscopy Endobronchial view of normal LLL (left) and obstructing tumor of lateral/posterior basal segments (right). Dx = squamous cell .

On right. . On left obstructing lesion of apical segment = adeno Ca.Fiberoptic Bronchoscopy Endobronchial view of RUL. extrinsic compression RUL = small cell.

Used primarily for NODAL STAGING. total complication rate 1-2%. .Cervical Mediastinoscopy and VATS Samples paratracheal and sub-carinal nodes. Overall safe.

Staging Lung Cancer. WHY? • Patient Prognostication • Guide Therapy • Standardize Communication – Multidisciplinary and Inter-disciplinary treatment clinics – Research .

Staging NSC Lung Cancer The T factor • T1 . or with atelectasis.0 cm.0 cm. mediastinal pleura. Mountain. main bronchus within 2 cm carina.< 3.>3. heart/great vessels.Mediastinal invasion.Invades chest wall. diaphragm. or pleural involvement • T3 . 111:1710-17 . pneumonitis. malignant effusion. surrounded by lung • T2 . Satellite nodule. • T4 . Chest 1997.

• M0 .Ipsilateral mediastinal or subcarinal N3 .Staging . hilar.No node mets.no metastasis • M1 . Chest 1997.N and M factors • • • • N0 .Ipsilateral hilar N2 . N1 .Contralateral mediastinal.Distant metastasis including contralateral lung Mountain. Scalene or supraclavicular nodes. 111:1710-17 .

T4NOMO.Putting It all Together • • • • • IA . Chest 1997. 111:1710-17 T .T3N1MO. T1-3 N2MO Communication • IIIB .AnyT AnyN M1 Mountain. T3NOMO IIIA .T2N1MO. T1Treatment 4N3MO Prognosis • IV .T2NOMO IIA .T1NOMO N IB .T1N1MO Final M Stage IIB .STAGE PARADIGM .

Everything else .Staging System • Small Cell Lung Cancer – Limited .Confined to one hemithorax and regional lymph nodes – Extensive .

Diagnostic Evaluation • Confirmation of tumor • Type of tumor • Staging for surgical resection – Nonsmall cell: • T= tumor characteristics (size. etc) • N=nodes hilum. mediastinum • M= presence or absence of distant mets – Small cell: • Disease limited to hemithorax or outside hemithorax • Functional evaluation: tolerate surgery? . location.

II .Surgical Resection +/Neoadjuvant Chemo / XRT • Stage IIIB. IV. poor operative candidates – combined chemotherapy and radiation therapy – Symptom-directed therapy • Patient Preference.Surgical Resection • Stage IIIA . XRT for Symptoms .How Can Non-Small-Cell Lung Cancer Be Treated? • Stage I. Poor Performance Status – Best Supportive Care.

030) (n=1.Survival Based on Clinical Staging 100 80 cIA cIB cIIA cIIB cIIIA cIIIB cIV (n=687) (n=1.427) Survival (%) 60 40 20 0 0 12 24 36 48 60 Time (Months) .189) (n=29) (n=357) (n=511) (n=1.

XRT – Median Survival <1 year .Treating Small Cell Lung Cancer • Limited Disease .Combined Chemotherapy and Radiation therapy – Goal : Cure – Prognosis if treated 20-30% 5 year survival • Extensive Disease (majority of patients) – Palliative Chemotherapy +/.

Adrenals Suspected cord or Thoracic Outlet Involvement CBC Liver Function (AST. Nodal Involvement. Liver. Ca+) Bone Metastasis If Suspected Brain Metastasis Metabolic Assessment • Bone Scan • Head CT/MRI • PET Scan . Other nodules. LDH) Chemistry (Alk Phos. Nodal Involvement Tumor Size.Non-Invasive Staging • Chest X-Ray • Computed Tomography • Magnetic Resonance Imaging (Chest) • Blood Tests Tumor Size. ALT.

Diagnostic Procedures • Sputum Cytology • Bronchoscopy 66% sens 99% specific 60-80% >2cm. peripheral. 90% <1cm. 15-20% • Percutaneous Needle Aspirate 75-95% • Mediastinoscopy 25-40% in all patients 85-95% if mediastinum involved • Thoracentesis • Thoracoscopy • Scalene and Supraclavicular Node Biopsy 40-70% 100% 90% if node palpable . central.

1) Identify patients with a prohibitively high surgical risk due to lung disease 2) Identify patients for whom prophylactic measures may decrease the risk of respiratory complications 3) Identify patients for whom further physiologic assessment is necessary to clarify existing impairment and operative risk – Current Recommendations MVV >50% predicted FEV1 > 2L or predicted post-op FEV1 >0.Physiologic Staging • Pulmonary Function Testing – Used as a general screening tool to.8L PaCO2 < 45 torr PaO2 > 50 torr .

stents . chemo.RadRx or chemo. palliative Rx • Unresectable tumors compromising the airway: – Laser bronchoscopy. Stage IIIa: resection and investigational protocol Stage IIIb or IV: unresectable.General Approach to Treatment • Small cell: chemotherapy/radiation • Nonsmall cell: – – – – Stage I: resection Stage II: resection +/. cryotherapy.

chemotherapy . .poor prognosis • Solitary pulmonary nodule • Very common and found incidentally • Risks to be assess and nodule followed.possible cure – Small cell .surgical .Conclusions • Lung cancer is the most deadly of cancers – 160.000 deaths per year • Two general types of lung cancer – Non-small cell .

Questions? Kim Baker kimberly-baker@uiowa.edu .

References • Diagnosis and Management of Lung Cancer: ACCP Evidence-Based Guidelines Chest 2003. .Jan (123) suppl 1s-337s • Solitary Pulmonary Nodule NEJM 2003 348:25 2535-42.

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