eMedicine Specialties > Emergency Medicine > Hematology & Oncology

Neoplasms, Lung

Mityanand Ramnarine, MD, Resident Physician, Department of Emergency Medicine, Albert Einstein College of Medicine at Long Island Jewish Medical Center
Gino A Farina, MD, Program Director, Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine

Updated: Oct 21, 2009

Introduction

Background

Lung cancer was a rare entity in the early 1900s, but, by the end of the century, the disease had become the leading cause of preventable death in the United States.¹ Lung cancer is the leading cause of cancer-related death in the United States. In 2006, the disease caused more than 158,000 deaths—more than colorectal, breast, and prostate cancers combined.² The type of lung cancer in the United States as well as in many other countries have also changed in the past few decades such that the frequency of adenocarcinoma has risen and that of squamous cell carcinoma has declined.

Pathophysiology

Both environmental exposure to particular agents and an individual's susceptibility to these agents are thought to contribute to one's risk of developing lung cancer. In the United States, active smoking is responsible for 90% of lung cancer cases. Occupational exposures to carcinogens account for approximately 9-15%. The most common occupational risk factor for lung cancer is exposure to asbestos. Studies have shown radon exposure to be associated with 10% of lung cancer cases, while outdoor air pollution accounts for perhaps 1-2%.³ In addition, preexisting nonmalignant lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and tuberculosis have all been shown to be associated with increased lung cancer rates.

The current multiple hit theory suggests that a series of toxic cellular insults disrupts orderly genetic reproduction. Symptoms ultimately develop from the uncontrolled disorganized growth that interferes with local or distant anatomy or physiologic processes.³

Lung cancer is divided into 2 main categories: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Upon diagnosis, 80% of all lung cancers are NSCLC, which is further divided into squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Adenocarcinoma overwhelmingly accounts for 40% of all cases of lung cancer. Squamous cell carcinoma is found in the central parts of the lung, whereas adenocarcinoma tumors are peripheral in origin. Large cell carcinoma composes only 15% of all lung cancers and appears to be decreasing in incidence because of improved diagnostic techniques.⁴

Non–small cell lung cancer. A cavitating right lower lobe squamous cell carcinoma.

Frequency

United States

In the United States, lung cancer is the second most common cancer in women, and it is second only to prostate cancer in men. In 2008, 215,000 lung cancer cases occurred and 161,000 deaths were expected.⁶ From 1991-2005, the incidence of lung cancer in men has decreased each year by 1.8%; however, the incidence has increased by 0.5% per year for women over that same period. Lung cancer death rates for US women are among the highest in the world. Although in the United States death rates among males are higher than among females, rates for US men are still lower than rates among men in several other countries.⁷

National trends indicate that death rates are declining in men and are leveling off in women; paralleling trends in smoking prevalence over the past 50 years. The prevalence of smoking is approximately 21.6% in the nation and has remained unchanged over the past 15 years.

International

Lung cancer is the most commonly diagnosed cancer worldwide, with more than 1.35 million new cases detected each year and 1.18 million deaths.⁸ Among all cancers, lung cancer now has the highest mortality rate in most countries, with industrialized regions such as North America and Europe having the highest rates. The incidence of lung cancer is growing. The highest incidence occurs in the United Kingdom and Poland, where it is more than 100 cases per 100,000 population per year. The lowest incidence rate occurs in Senegal and Nigeria, where it is less than 1 case per 100,000 population per year. With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China and India.

Mortality/Morbidity

Data compiled by the American Cancer Society shows lung cancer is, by far, the most common fatal cancer in men (31%) and in women (26%).

Data collected from 1995-2001 shows the 5-year relative survival rate for lung cancer was 15.7%, reflecting a steady but slow improvement from 12.5% in 1975.⁷

Despite advances in lung cancer therapy, the average 5-year survival rate is only 15%. However, the 5-year relative survival rate varies markedly depending on the stage at diagnosis:⁷

• 49% for local disease
• 16% for regional disease
• 2% for distant stage disease

Race

While lung cancer incidence rates are similar among African American and white women, lung cancer occurrence is approximately 45% higher among African American men than among white men.⁷ This increased incidence has been attributed to differences in smoking habits; however, recent evidence suggests a slight difference in susceptibility. From 1995-2001, the 5-year relative survival rate was 13% lower in African Americans compared with white individuals.⁷ This racial gap persisted within each stage at diagnosis for both men and women.

Sex

Males have a higher incidence of lung cancer, which probably parallels differences in smoking prevalence. As a result of the cigarette smoking epidemic, lung cancer death rates showed a steady increase through 1990, then began to decline among men. The lung cancer death rate among US women, who began regular cigarette smoking later than men, has begun to plateau after increasing for many decades.

• During the last 10 years, the incidence of lung cancer has increased more rapidly in women than in men.
• Women have a higher incidence of localized disease at presentation and of adenocarcinoma.
• Women typically are younger when they present with symptoms.

Age

Lung cancer occurs predominately in persons aged 50-70 years.

Clinical

History

Lung cancer is often insidious, and it may produce no symptoms until the disease is well advanced. Early recognition of symptoms may be beneficial to outcome. Cough is reported to be the most common presenting symptom of lung cancer. Other respiratory symptoms include dyspnea, chest pain, and hemoptysis. Hemoptysis has been described as the one symptom often prompting more rapid presentation.⁹ At initial diagnosis, 20% of patients have localized disease, 25% of patients have regional metastasis, and 55% of patients have distant spread of disease. In addition, the patient's history may clue the physician in on a specific paraneoplastic syndrome (10-20% of patients).

Symptoms depend on location of cancer:¹⁰

• Endobronchial
  • Cough (45-75%)
  • Hemoptysis (57%)
  • Bronchial obstruction
  • Post obstructive complications (eg, pneumonitis, pneumonia, effusion)
• Mediastinal
  • Dyspnea
  • Postprandial coughing (esophageal)
  • Wheezing
  • Stridor (upper airway obstruction, 2-18%)
  • Hoarseness (left vocal cord paralysis due to recurrent laryngeal nerve impingement, 2-18%)
  • Chylothorax (thoracic duct)
  • Palpitations (pericardial)
  • Dysphagia (enlargement of the subcarinal lymph nodes can cause dysphagia by compressing the middle third of the esophagus)
• Pleural
  • Chest pain (27-49%)
  • Dyspnea (37-58%)
  • Cough (45-75%)
• Neurologic
  • Arm weakness and paresthesias (brachial plexus impingement)
  • Miosis ptosis and anhidrosis (cervical sympathetic chain, Horner syndrome)
  • Dyspnea (secondary to phrenic nerve paralysis)
• Metastatic (8-68%)
  • Weight loss
  • Cachexia
• Central nervous system
  • Headache
  • Altered mental status
  • Seizure
  • Meningismus
  • Ataxia
  • Nausea and/or vomiting
• Vascular
  • Phlebitis
  • Thromboembolism (Trousseau syndrome)
• Musculoskeletal
  • Bone pain (6-25%)
  • Spinal cord impingement

Physical

Subtle findings on physical examination may provide clues for early detection. About one third of patients present with symptoms as a result of distant metastases. The most common sites of distant metastasis from lung cancer are the bones; liver; adrenal glands and intra-abdominal lymph nodes; brain and spinal cord; and lymph nodes and skin. Lung cancer can metastasize to virtually any bone, although the axial skeleton and proximal long bones are most commonly involved.

• Systemic findings
  • Unexplained weight loss
  • Low-grade fever
• Upper airway obstruction
  • Stridor
  • Wheezing
• Lower airway obstruction
  • Asymmetric breath sounds
  • Pleural effusion
  • Pneumothorax
  • Infiltrate
  • Post obstructive processes
• Respiratory insufficiency
  • Dyspnea and increased work of breathing
  • Retractions
  • Orthopnea
  • Cyanosis
• Extrapulmonary findings
  • Adenopathy
  • Clubbing
• Mechanical obstruction syndromes
  • Superior vena cava syndrome (usually small cell lung cancer) - Direct invasion by the primary tumor into the mediastinum or lymphatic spread with enlarged right paratracheal metastatic lymph nodes causes the syndrome.
    • Feeling of fullness in the head
    • Dyspnea
    • Cough
    • Dilated neck veins
    • Prominent venous pattern on the face and the chest
    • Upper extremity and facial edema
    • Papilledema
    • Facial cyanosis
    • Plethora
  • Pancoast tumor
    • Superior sulcus tumor that causes pain (eg, in the shoulder, medial forearm, arm, scapula)
    • Horner syndrome
    • Bone destruction
    • Hand muscle atrophy
  • Acute spinal cord compression
    • Paraplegia
    • Sensory deficits
    • Urinary incontinence or retention
    • Vertebral pain
• Paraneoplastic syndromes¹¹
  • Cushing syndrome
  • Lambert-Eaton myasthenic syndrome: Gradual onset of proximal lower extremity weakness; proximal upper extremity weakness is usually less noticeable. The syndrome may be worse in the morning and improve during the day. Although extraocular muscle involvement is uncommon, ptosis is often found.
  • Hypercalcemia
  • Syndrome of inappropriate antidiuretic hormone secretion
  • Enlargement of the extremities, and painful, swollen joints (hypertrophic osteoarthropathy)
• Ogilvie intestinal pseudo-obstruction
  • Nausea
  • Vomiting
  • Early satiety
  • Abdominal discomfort
  • Weight loss
  • Change in bowel habits

Causes

Clearly, because all lung cancers do not occur in smokers and the vast majority of smokers do not develop lung cancer, other etiological factors can independently or jointly in conjunction with smoking cause lung cancer. These factors include genetics, arsenic exposure, radiation exposure, and other environmental carcinogens.¹² Although genetic factors probably contribute in all populations, the contribution of other factors is population-specific. Some causes include the following:

• Smoking (in more than 90% of patients)
• Asbestos exposure
• Radon
• Halogen ether exposure
• Chronic interstitial pneumonitis
• Inorganic arsenic exposure
• Radioisotope exposure, ionizing radiation
• Atmospheric pollution
• Chromium, nickel exposure
• Vinyl chloride

Differential Diagnoses

Other Problems to Be Considered

Metastatic cancer
Granuloma
Hamartoma

Workup

Laboratory Studies

• Generally, a CBC is not helpful in the initial evaluation.
  • Obtain a CBC in patients with widely metastatic disease to aid in determining if an infiltrate is potentially infectious.
  • Obtain a CBC in patients with fever with recent history of chemotherapy to check for neutropenia (absolute neutrophil count <1000).
• Tests for electrolyte, BUN, creatinine, calcium, and magnesium levels are not helpful, except when specific paraneoplastic syndromes (eg, hypercalcemia, Cushing syndrome, syndrome of inappropriate antidiuretic hormone) are being considered.
• Can check serum levels of parathyroid hormone (PTH) or parathyroid hormone – related peptide (PTH-rP).
• Liver function tests (AST, ALT, GGT, PT/INR) and alkaline phosphatase are usually not helpful initially, but elevated results may be an indication of hepatic metastasis and bone metastasis, respectively.
• ABG levels are useful in the detection of respiratory failure (eg, acidosis, hypercarbia, hypoxia) in sick patients. Obtain ABG levels in patients with active systemic diseases or abnormal labored breathing.
• Sputum cytology is suggested for high-risk patients in which semi-invasive procedures such as bronchoscopy or transthoracic needle aspiration might pose a higher risk. The diagnostic accuracy of sputum cytology, however, is dependent on rigorous specimen sampling (at least 3 specimens) and preservation techniques, as well as on the location (central vs peripheral) and size of the tumor.¹³
  • The test detects 71% of central tumors but less than 50% of peripheral tumors; therefore, further testing must always follow a negative result.
  • Several large studies have not revealed that screening with sputum cytology and chest radiography is cost-effective in early detection.

Imaging Studies

• The percentage of patients found to have lung cancer incidentally through chest radiographs has been consistently low. Clues from the chest radiograph may suggest the diagnosis of lung cancer, but may not be helpful in identifying a histologic subtype. Chest radiographs may show the following:
  • Pulmonary nodule, mass, or infiltrate

Non–small cell lung cancer. Bronchoscopy. A large central lesion was diagnosed as non–small cell carcinoma.

• Mediastinal widening
• Atelectasis
• Hilar enlargement
• Pleural effusion

Non–small cell lung cancer. Left pleural effusion and volume loss secondary to non–small cell carcinoma of the left lower lobe. The pleural effusion was sampled and found to be malignant; therefore, the lesion is inoperable.

• A chest CT scan is the standard for staging. The findings of CT scans of the chest and clinical presentation usually allow a presumptive differentiation between SCLC and NSCLC. Massive lymphadenopathy and direct mediastinal invasion are commonly associated with small cell carcinoma. A mass in or adjacent to the hilum is a particular characteristic of small cell cancer and is seen in about 78% of cases.¹⁴

Lung cancer, small cell. Contrast-enhanced CT scan of the chest shows a large left lung and a hilar mass, with invasion of the left pulmonary artery.

• PET scanning using fluoro-18–2-deoxyglucose (FDG) has proven to be an excellent modality for evaluating solitary pulmonary nodules. The average sensitivity and specificity of FDG-PET scanning for detecting a malignancy was reported to be 0.97 and 0.78, respectively.¹⁵

Lung cancer, small cell. Coronal positron emission tomogram shows abnormal areas of increased metabolic activity in the left hilar and left adrenal regions consistent with a hilar tumor with left adrenal metastasis.

• Obtain head CT scans, in patients with mental status change, when applicable.
• Bone scanning, when applicable.

Lung cancer, small cell. Whole-body nuclear medicine bone scanning with anterior and posterior images reveal multiple abnormal areas of increased radiotracer activity in the pelvis, spine, ribs, and left scapula. These findings are consistent with bony metastatic disease. The bones are commonly affected in patients with small-cell lung cancer.

• Experience with MRI is limited. Generally, an MRI is used only when findings of superior sulcus and brachial plexus tumors are equivocal on CT scans.

Other Tests

• Electrocardiography
  • An ECG is helpful in establishing baseline findings and differentiating clinical symptoms (eg, chest pain, dyspnea).
  • Changing lung hemodynamics often alter ECG wave patterns.
• Spirometry
  • Bedside tests for peak expiratory flow provide good indicators of significant airflow obstruction.
  • Lung cancer is more closely linked to chronic obstructive pulmonary disease with airflow compromise than to the disease without significant airway obstruction.

Procedures

• Excisional biopsy of an accessible node, or biopsy of accessible bone lesion
• Needle thoracentesis (ultrasound guided)
  • Needle thoracentesis is both diagnostic and therapeutic in patients presenting with respiratory distress. Thoracentesis has a sensitivity of only 80% with a specificity greater than 90%. In patients suspected of having lung cancer who have an accessible pleural effusion, if the pleural fluid cytology finding is negative (after at least 2 thoracenteses), thoracoscopy is recommended as the next step to aid in diagnosis.
• Video-assisted thoracoscopy
  • Video-assisted thoracoscopy is a newer modality that may be used to sample small peripheral tumors (less than 2 cm in diameter), pleural tumors, or pleural effusions for diagnostic or staging purposes.¹⁶
  • Safe and can provide a definitive diagnosis with a high degree of accuracy and minimal risk to the patient. The reported sensitivity rate ranges between 0.80 and 0.99, the specificity rate ranges between 0.93 and 1, and the negative predictive value ranges between 0.93 and 0.96.¹⁶
• Flexible bronchoscopy
  • The decision about whether to pursue a diagnostic bronchoscopy for a lesion that is suspected of being lung cancer largely depends on the location of the lesion (central vs peripheral).¹⁷ This is the study of choice in patients with central tumors, with a combined sensitivity of 88% with this type of tumor. The addition of transbronchial needle aspiration with endobronchial ultrasound to obtain cytology or histology samples when there is submucosal tumor spread or peribronchial tumor causing extrinsic compression further increases the sensitivity of bronchoscopy.¹⁶
• Transthoracic needle biopsy
  • CT or fluoroscopically guided transthoracic biopsy is best for peripheral lung lesions. A positive finding for cancer is reliable; however, the false-negative rate is high at 26%, and, thus, transthoracic biopsy is generally not useful in ruling out cancer.
• Mediastinoscopy may be used to obtain tissue from cancer that has infiltrated into the mediastinum.¹⁸
• Thoracotomy is indicated only for diagnosis and treatment of clearly resectable NSCLC.

Treatment

Prehospital Care

• No specific prehospital care is needed for patients with lung cancer.
• All prehospital personnel should inquire about the patient's resuscitation directives.

Emergency Department Care

All patients thought to have lung cancer should be encouraged to obtain follow-up care with their primary care physician. In almost all cases, document the possible diagnosis and discuss it with the patient. Definitive treatment of the underlying cancer is not the purview of the ED.

Treatment is based on symptoms, as follows:

• Upper airway obstruction
  • Admit the patient to the intensive care unit.
  • Prepare for intubation and/or cricothyrotomy.
  • Obtain ears, nose, and throat and/or surgical consultation for fiberoptic laryngoscopy or intraoperative tracheostomy.
• Hemoptysis
  • Administer supplemental oxygen and perform suctioning.
  • If a threat of imminent demise exists, consider placing a double-lumen endotracheal tube.
  • Position the patient with the bleeding hemithorax in a dependent location.
  • Perform ABG and CBC (type and crossmatching) coagulation studies if the bleeding is more than trivial.
  • A pulmonologist may have to perform fiberoptic bronchoscopy.
  • Admit patients, except those with the most minor bleeding, to the intensive care unit.
• Pain control: See Special Concerns for workup and treatment of patients with CNS metastasis and cancer; infections in those with immunosuppression, Pancoast tumor, or Ogilvie intestinal pseudo-obstruction; or pain in those with severe cancer.

Consultations

• Consult an oncologist if cancer is present.
• Ear, nose, and throat; thoracic; general; orthopedic; vascular; and/or neurosurgical or neurological services may be required to address complications caused by spread of the disease.

Medication

Treatment differs according to the histologic type of cancer, the stage at presentation, and the patient’s functional status.

Chemotherapeutic agents

Because of a greater emphasis on outpatient therapies, patients taking chemotherapeutic agents frequently are seen in the ED.

Gemcitabine (Gemzar)

Cytidine analog, after intracellular metabolism to active nucleotide, inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. Cell-cycle specific for S phase.

Dosing

Adult

1000 mg/m² IV given over 30 min on days 1, 8, 15 of a 28-d cycle or 1250 mg/m² IV on days 1 and 8 of a 21-d cycle

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause myelosuppression (particularly thrombocytopenia); toxicities include flulike syndrome, LFT abnormality, maculopapular rash, pruritus, nausea, vomiting, dyspnea, hematuria, proteinuria, and hemolytic uremic syndrome; clearance reduced in women and elderly individuals

Cyclophosphamide (Cytoxan, Neosar)

Chemically related to nitrogen mustards; as an alkylating agent, the mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Dosing

Adult

40-50 mg/kg IV in divided doses over 2-5 d; other IV regimens include 10-15 mg/kg q7-10d or 3-5 mg/kg twice weekly; oral cyclophosphamide doses usually are 1-5 mg/kg

Pediatric

Administer as in adults

Interactions

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase the half-life while decreasing metabolite concentrations; may increase the effect of anticoagulants; coadministration with high doses of phenobarbital may increase the rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity

Contraindications

Documented hypersensitivity; severely depressed bone marrow function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Regularly examine the hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine the urine for RBCs, which may precede hemorrhagic cystitis; adverse effects include SIADH and pneumonitis

Doxorubicin (Adriamycin, Rubex)

Inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA; combination of these two events can, in turn, inhibit growth of neoplastic cells.

Dosing

Adult

40-75 mg/m² IV, depending on whether drug is used alone or in combination

Pediatric

Administer as in adults

Interactions

May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity

Contraindications

Documented hypersensitivity; severe heart failure; cardiomyopathy; impaired cardiac function; preexisting myelosuppression

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function; adverse effects include pancytopenia, ECG changes, nausea, and vomiting

Vincristine (Oncovin)

Mechanism of action is uncertain; may involve a decrease in reticuloendothelial cell function or an increase in platelet production. However, neither of these mechanisms fully explains the effect in thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

Dosing

Adult

1.4 mg/m² IV qwk

Pediatric

<10 kg: 0.05 mg/kg IV qwk
>10 kg: 2 mg/m² IV qwk

Interactions

Acute pulmonary reaction may occur when taken with mitomycin-C

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with severe cardiopulmonary or hepatic impairment and patients with preexisting neuromuscular disease; adverse effects include leukopenia, peripheral neuropathy, constipation, and abdominal pain

Etoposide (Toposar)

Inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in the late S or early G₂ portion of cell cycle; do not administer IT.

Dosing

Adult

Ranges from 35 mg/m²/d for 4 d to 50 mg/m²/d for 5 d IV; PO route is twice the IV dose rounded to the nearest 50 mg

Pediatric

Administer as in adults

Interactions

May prolong the effects of warfarin and increase the clearance of methotrexate; cyclosporine and etoposide have additive effects in the cytotoxicity of tumor cells

Contraindications

Documented hypersensitivity; IT administration may cause death

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Bleeding, severe myelosuppression, alopecia, and nausea may occur

Cisplatin (Platinol)

Inhibits DNA synthesis and, thus, cell proliferation by causing DNA cross-linking and denaturation of the double helix.

Dosing

Adult

120 mg/m² IV

Pediatric

Administer as in adults

Interactions

Increases toxicity of bleomycin and ethacrynic acid

Contraindications

Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Ensure adequate hydration before and 24 h after cisplatin administration to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, neurotoxicity, nausea, and vomiting may occur

Antineoplastic Agent, Alkylating Agent

Carboplatin

Analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication. Binds to protein and other compounds containing SH group. Cytotoxicity can occur at any stage of the cell cycle, but cell is most vulnerable to action of these drugs in G1 and S phase.
Has same efficacy as cisplatin but with better toxicity profile. Main advantages over cisplatin include less nephrotoxicity and ototoxicity not requiring extensive prehydration, less likely to induce nausea and vomiting, but more likely to induce myelotoxicity.

Dose is based on the following formula: total dose (mg) = (target AUC) x (GFR+25) where AUC (area under plasma concentration-time curve) is expressed in mg/mL/min and GFR (glomerular filtration rate) is expressed in mL/min.

Dosing

Adult

Can be dosed on basis of body surface area, but current formulas take into account patient's renal function; one such formula is Calvert formula

Pediatric

Not established

Interactions

Nephrotoxicity increases with aminoglycosides and other nephrotoxic drugs

Contraindications

Documented hypersensitivity; bone marrow suppression

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monitor bone marrow function

Follow-up

Further Inpatient Care

• Inpatient treatment should be tailored to the specific presenting problem.
• Surgery is the treatment of choice for patients with NSCLC stages I through IIIA.⁴ In addition, patients with resected lung cancer have a high risk of relapse and are treated with adjuvant chemotherapy.¹⁹ Patients with stage IIIB and IV NSCLC are usually offered chemotherapy with the option of surgery.
• Chemotherapy is the mainstay for treatment of SCLC. Several chemotherapeutic agents, including doxorubicin, methotrexate, vincristine, cyclophosphamide, etoposide, cisplatin, and carboplatin, produce single-agent response rates of 30% or greater in patients with SCLC. Combination regimens yield higher responses and superior survival compared with the use of single agents. Currently, etoposide plus cisplatin (EP) is the regimen of choice for patients with limited-stage disease because of the superior efficacy of cisplatin versus carboplatin and because of the favorable toxicity profile of EP.²⁰ Combination therapy with radiation and chemotherapy significantly improves survival in patients with limited-stage disease SCLC. The current standard chemotherapy for extended-stage disease SCLC is EP.²⁰

Further Outpatient Care

• Speak directly with the patient's personal physician to suggest prompt follow-up for the patient thought to have new-onset lung cancer.
• Schedule follow-up clinical appointments for patients who do not have primary care physicians.

Deterrence/Prevention

• Among all measures, smoking cessation is most important in the prevention of lung cancer. Although the relative risk of cancer does not decline to baseline levels for as long as 10 years after cessation, linked conditions (eg, chronic bronchitis, chronic obstructive pulmonary disease) show more rapid improvement or stabilization.²¹
• Combining nicotine replacement, bupropion, and social or behavioral support can increase the quit rate to 35%.²²
• Exposure to second-hand smoke and other respiratory toxins in the workplace has decreased as a result of federal legislation.
• Workers exposed to asbestos or radioactive materials should always wear required safety equipment.
• Some studies have shown a reduction in lung cancer incidence with daily use of aspirin. This reflects similar studies showing nonsteroidal anti-inflammatory drugs (NSAIDs) effect of lower colorectal and adenoma incidence.²³

Complications

• Metastatic disease
• Local recurrence

Prognosis

• Patients with in situ and stage I lung cancer may respond to surgery. Their prognosis is far better than that of patients with more advanced disease.
• In patients with radiologically occult lung neoplasms, the 5-year survival rate is 24-26%; in those with abnormal chest radiographic findings, the rate is 12%.
• If the cancer is nonresectable, the prognosis is poor, with a mean survival rate of 8-14 months.

Patient Education

• Advise patients that, among all measures, smoking cessation is most important. Smoking cessation by others who share the patient's home, car, or both is also important.
• According to published data, the use of nicotine alternatives (eg, gum, patch, spray) instead of cigarettes reduces the incidence of lung cancer. However, it does not affect the incidence of ischemic heart disease.
• Advise the patient to avoid asbestos exposure.
• Consider prophylactic administration of retinoids, such as beta-carotene.
• For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Lung Cancer, Bronchoscopy, and Understanding Lung Cancer Medications.

Miscellaneous

Medicolegal Pitfalls

• Delayed diagnosis due to a failure to disclose abnormal chest radiographic findings or to recommend follow-up care has resulted in litigation. Even if the findings are unrelated to the current clinical scenario, discuss them with the patient, and arrange follow-up care. Written records are very important.

Special Concerns

• Patients with CNS metastasis, immunosuppression, superior vena cava syndrome, Pancoast tumor, and/or Ogilvie intestinal pseudo-obstruction may require specific workup, as described below. If no pathologic process is present, discharge the patient with a prescription for continuous analgesic use until follow-up care can be arranged with the patient's personal physician.²⁴
• Patients with CNS metastasis and known cancer
  • Head CT scanning, with and without contrast enhancement to depict masses, may be indicated.
  • Headache and brain edema may respond to dexamethasone (10 mg IV).
  • Obtain a neurosurgical consultation, and contact the patient's physician.
  • Admit patients for possible whole-brain irradiation or resection.
  • Seizures are treated with anticonvulsants, but patients with brain metastases and no history of seizures do not generally require anticonvulsant therapy.²⁵
• Immunosuppressed patient with cancer and infections
  • Obtain a CBC for evaluation of neutropenia and other blood cell derangements.
  • Assess electrolyte levels for signs of dehydration.
  • The chest radiograph may show only subtle infiltrate.
  • If diarrhea is present, perform urinalysis with a culture, blood cultures with samples from peripheral sites, cultures with samples from any indwelling catheters, and stool cultures for Clostridium difficile.
  • Administer broad-spectrum empiric antibiotics (eg, piperacillin, gentamicin, second- or third-generation cephalosporin) and an aminoglycoside. If the patient has a penicillin allergy, replace penicillin with carbapenem (if mild penicillin allergy) or aztreonam.
  • Consultation with an oncologist is indicated to begin granulocyte colony-stimulating factor.
• Patients with Pancoast tumor
  • An MRI is superior to a CT scan in depicting superior sulcus tumors.
  • Admit the patient for transthoracic needle aspiration.
  • Perform bronchoscopy if endobronchial involvement is present.
• Patients with superior vena cava syndrome
  • Lung cancer accounts for 60-80% of superior vena cava syndrome.
  • Head elevation, cautious administration of fluids, and supplemental oxygen is indicated.
  • Diuretics and glucocorticoids (methylprednisolone 125mg IV) may help with symptoms, but their roles are unclear.
  • Definitive treatment is usually by radiotherapy or chemotherapy and/or vena caval stenting.
• Patients with Ogilvie intestinal pseudo-obstruction
  • Abdominal radiograph shows massive dilation of the colon and small intestine, with or without air-fluid levels.
  • Check electrolyte levels and correct abnormalities.
  • Place a nasogastric tube and rectal tube.
  • Admit the patient for possible colonic decompression and treatment of the underlying cause (eg, lung cancer producing autoantibodies to the myenteric neural plexus).
  • For cancer patients with severe pain and advanced disease, administer opioid analgesics. Nasogastric tube and rectal tube placement may help with pain.

Multimedia

Media file 1: Non–small cell lung cancer. Bronchoscopy. A large central lesion was diagnosed as non–small cell carcinoma.

Media file 2: Non–small cell lung cancer. Left pleural effusion and volume loss secondary to non–small cell carcinoma of the left lower lobe. The pleural effusion was sampled and found to be malignant; therefore, the lesion is inoperable.

Media file 3: Non–small cell lung cancer. Left upper collapse is almost always secondary to endobronchial bronchogenic carcinoma.

Media file 4: Non–small cell lung cancer. Complete left lung collapse secondary to bronchogenic carcinoma of left mainstem bronchus.

Media file 5: Non–small cell lung cancer. A cavitating right lower lobe squamous cell carcinoma.

Media file 6: Non–small cell lung cancer. CT scan shows cavitation and air-fluid level.

Media file 7: Non–small cell lung cancer. Patient has right lower lobe opacity. This is not well circumscribed and was found to be a squamous cell carcinoma.

Media file 8: Lung cancer, small cell. Contrast-enhanced CT scan of the chest shows a large left lung and a hilar mass, with invasion of the left pulmonary artery.

Media file 9: Lung cancer, small cell. Coronal positron emission tomogram shows abnormal areas of increased metabolic activity in the left hilar and left adrenal regions consistent with a hilar tumor with left adrenal metastasis.

Media file 10: Lung cancer, small cell. Whole-body nuclear medicine bone scanning with anterior and posterior images reveal multiple abnormal areas of increased radiotracer activity in the pelvis, spine, ribs, and left scapula. These findings are consistent with bony metastatic disease. The bones are commonly affected in patients with small-cell lung cancer.

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Keywords

lung neoplasm, bronchogenic carcinoma, lung cancer, lung malignancy, adenocarcinoma, squamous cell carcinoma, SCC, oat cell carcinoma, large cell carcinoma, smoking, tobacco, passive smoke, secondhand smoke, SCLC, NSCLC

Contributor Information and Disclosures

Author

Mityanand Ramnarine, MD, Resident Physician, Department of Emergency Medicine, Albert Einstein College of Medicine at Long Island Jewish Medical Center
Mityanand Ramnarine, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Gino A Farina, MD, Program Director, Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine
Gino A Farina, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Edmond A Hooker II, MD, DrPH, FAAEM, Assistant Professor, Department of Health Services Administration, Xavier University; Associate Clinical Professor, Department of Emergency Medicine, University of Louisville; Assistant Clinical Professor, Department of Emergency Medicine, Wright State University
Edmond A Hooker II, MD, DrPH, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American Public Health Association, Society for Academic Emergency Medicine, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center
Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, University Hospitals, Case Medical Center
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Peter T Porrello, MD, and Tamas Peredy, MD, to the development and writing of this article.

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