Sections

Workup

Approach Considerations

In a patient with a long history of smoking or other risk factors for lung cancer, the presence of persistent respiratory symptoms should prompt a chest radiograph. Because benign conditions and metastatic malignancies can mimic lung cancer on radiographs, histologic confirmation is necessary. This can be achieved by sputum cytologic studies, bronchoscopy, or computed tomography (CT)-guided transthoracic needle biopsy of the mass, depending on the location of the tumor (see the image below).

Non–small cell lung cancer. Diagnostic approach for possible lung cancer.

View Media Gallery

Staging workup

Because of the importance of stage in the therapeutic decision-making process, all patients with non–small cell lung cancer (NSCLC) must be staged adequately. A complete staging workup for NSCLC should be carried out to evaluate the extent of disease. In the United States, the standard staging workup for NSCLC includes 7 main components (see the table below).

Staging workup for non–small cell lung cancer.

View Media Gallery

Information obtained from these tests can then be used to guide further testing (eg, imaging studies). Invasive staging procedures such as mediastinoscopy and mediastinotomy may be required to assess mediastinal lymph nodes in patients who are candidates for potentially curative surgical resection. Positron emission tomography (PET) scans may be useful in the detection of involved nodes, the presence of which may influence decisions about operability.

A study by Annema et al determined that among patients with suspected NSCLC, a combination of endosonography and surgical staging had a greater sensitivity for mediastinal nodal metastases than surgical staging alone.^[45]This resulted in fewer unnecessary thoracotomies.

See Non-Small Cell Lung Cancer Staging for summary tables.

See Lung Cancer Staging -- Radiologic Options, a Critical Images slideshow, to help identify stages of the disease process.

Other procedures

An electrocardiogram (ECG) is helpful in establishing baseline findings and differentiating clinical symptoms (eg, chest pain, dyspnea). Changing lung hemodynamics often alter ECG wave patterns.

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.

Laboratory Studies

For staging purposes, a complete blood count (CBC) should be obtained in every patient, especially before instituting chemotherapy. In an emergency setting, a CBC is not helpful in the initial evaluation. Obtain a CBC in patients with widely metastatic disease to aid in determining whether an infiltrate is potentially infectious. Obtain a CBC in patients with fever who have a recent history of chemotherapy to check for neutropenia (absolute neutrophil count < 1000/μL).

Lung cancers have a propensity to cause paraneoplastic syndromes (see the table below). Appropriate studies in such patients may include assays of serum electrolytes, blood urea nitrogen (BUN), creatinine, calcium, and magnesium.

Non–small cell lung cancer. Symptoms and signs of lung cancer.

View Media Gallery

The most common metabolic abnormality associated with NSCLC is hypercalcemia, which usually occurs with squamous cell carcinoma and results from secretion of parathyroid hormone–related peptide (PTH-rP) by the tumor. This can be distinguished from hyperparathyroidism by confirmation of normal serum parathyroid hormone (PTH) levels.

Other electrolyte abnormalities can include hyponatremia, in which case the syndrome of inappropriate antidiuretic hormone secretion (SIADH) should be considered. The combination of hyponatremia, serum osmolality < 280 mOsm/kg, and high urine osmolality is the hallmark of SIADH.

Liver function tests (aspirate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT], prothrombin time [PT]/international normalized ratio [INR]) and alkaline phosphatase level are usually not helpful initially. In patients with advanced disease, however, elevated results may be an indication of hepatic metastasis and bone metastasis, respectively.

Arterial blood gas (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.

Chest Radiography

A chest radiograph is usually the first test ordered in patients in whom a lung malignancy is suggested. Clues from the chest radiograph may suggest the diagnosis of lung cancer, but may not be helpful in identifying a histologic subtype. If the tumor is clearly visible and measurable, chest radiography can sometimes be used to monitor response to therapy.

Chest radiographs may show the following:

Pulmonary nodule, mass, or infiltrate (see the first image below)
Mediastinal widening
Atelectasis
Hilar enlargement
Pleural effusion (see the second image below)
Non–small cell lung cancer. Bronchoscopy. A large central lesion was diagnosed as non–small cell carcinoma.
View Media Gallery

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.

View Media Gallery

Popcorn calcification is usually a radiologic characteristic of benign lesions.

The percentage of patients found to have lung cancer incidentally through chest radiographs has been consistently low. Randomized controlled trials have shown that the use of screening chest radiographs does not reduce lung cancer mortality.^{[46, 47]}

Go to Imaging in Non-Small Cell Lung Cancer for complete information on this topic.

Computed Tomography

A chest CT scan (see the image below) is the standard for staging. The findings of CT scans of the chest and clinical presentation usually allow a presumptive differentiation between NSCLC and small cell lung cancer (SCLC). 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 SCLC and is seen in about 78% of cases.^[48]

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.

View Media Gallery

Common sites of spread of NSCLC include the liver and adrenals; hence, CT scanning of the chest and upper abdomen that includes the liver and adrenals is the minimum standard for a staging workup for a person newly diagnosed with NSCLC. Lung nodules incidentally detected on abdominal CT are often benign.^[49]

A CT scan or magnetic resonance imaging (MRI) scan of the brain may be required if neurologic symptoms or signs (eg, mental status change) are present. Most thoracic surgeons perform imaging of the brain before attempting definitive resection of a lung malignancy.

Go to Imaging in Non-Small Cell Lung Cancer for complete information on this topic.

Magnetic Resonance Imaging

MRI is most useful when evaluating a patient in whom spinal cord compression is suggested. In addition, brain MRI has a greater sensitivity than CT scan for detection of central nervous system (CNS) metastasis. MRI may be used when findings of superior sulcus and brachial plexus tumors are equivocal on CT scans.

Go to Imaging in Non-Small Cell Lung Cancer for complete information on this topic.

Bone Scintigraphy

The skeletal system is common site of metastases for lung cancers. If patients report bone pain or if their serum calcium and/or alkaline phosphatase levels are elevated, a bone scan should be obtained to search for bone metastases (see the image below).

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.

View Media Gallery

Positron Emission Tomography

PET scanning (see the image below) using fluoro-18–2-deoxyglucose (FDG) has proven to be an excellent modality for evaluating solitary pulmonary nodules and has been approved by the US Food and Drug Administration (FDA) for this indication. The average sensitivity and specificity of FDG-PET scanning for detecting a malignancy was reported to be 0.97 and 0.78, respectively.^[50]However, a meta-analysis by Deppen and colleagues found that FDG-PET had lower specificity for diagnosing malignancies in areas with endemic infectious lung disease compared with areas with nonendemic disease.^[51]

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.

View Media Gallery

Studies also suggest that PET scanning is useful for searching for systemic spread if other diagnostic modalities cannot clarify an abnormality that may change the treatment of the patient’s condition. However, false-positive and false-negative results occur.

Additional data have emerged that underscore the importance of PET scanning in patients with NSCLC. PET scans appear to be more sensitive, specific, and accurate than CT scans for staging mediastinal disease. Whereas radiographs and CT scans show images of structures, PET scans reveal the nature of the area under study. PET scans often detect abnormalities not demonstrated on CT scans.

Published reports suggest that staging of NSCLC may be influenced by PET scan results in up to 60% of the cases and that as many as 25% of cases may be upstaged after PET scanning.

Caution is required when interpreting the results of PET scans in patients who may be denied potentially curative surgical resection based on PET results.

Go to Imaging in Non-Small Cell Lung Cancer for complete information on this topic.

Sputum Cytologic Studies

Centrally located endobronchial tumors may exfoliate malignant cells into sputum. (This location and tendency to exfoliate are most common in squamous cell carcinomas [SCCs].) Therefore, sputum cytology can be a quick and inexpensive diagnostic test if results are positive. The false-positive rate for sputum cytology is 1%, but the false-negative rate is as high as 40%.

Sputum cytology does not provide reliable distinction between different histologic subtypes. Discordant results are often observed between cytologic and histologic findings of specimens obtained from bronchoscopy or transthoracic biopsy.

The diagnostic accuracy of sputum cytology depends 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.^[52]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. In one small study, a cytologic specimen was used to measure EGFR and KRAS mutations; however, this practice still needs to be validated.^[53]

Sputum cytology is suggested for high-risk patients in whom semi-invasive procedures such as bronchoscopy or transthoracic needle aspiration (see below) might pose a higher risk. Currently, however, with the development of advanced x-ray imaging techniques and biopsy procedures, sputum cytology is not commonly employed in the diagnosis of NSCLC.

Bronchoscopy

When a lung cancer is suggested, bronchoscopy provides a means for direct visualization of the tumor, allows determination of the extent of airway obstruction, and allows collection of diagnostic material under direct visualization with direct biopsy of the visualized tumor, bronchial brushings and washing, and transbronchial biopsies.

The decision 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).^[54]Bronchoscopy is the study of choice in patients with central tumors, with a combined sensitivity of 88%. 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.^[55]

Biopsy

Transthoracic needle biopsy, guided by CT or fluoroscopy, is preferred for tumors located in the periphery of the lungs because peripheral tumors may not be accessible through a bronchoscope. 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.

Diagnostic material can also be obtained from other abnormal sites (eg, enlarged palpable lymph nodes, liver, pleural or pericardial effusions, accessible bone lesions).

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.

Thoracoscopy and Mediastinoscopy

Thoracoscopy is usually reserved for tumors that remain undiagnosed after bronchoscopy or CT-guided biopsy. Thoracoscopy is also an important tool in the management of malignant pleural effusions.

Video-assisted thoracoscopy (VATS) 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.^[55]It is 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.^[55]Survival with assisted VATS is comparable to complete VATS and can be cost-effective.^[56]

Mediastinoscopy

Mediastinoscopy may be used to obtain tissue from cancer that has infiltrated into the mediastinum.^[57]It is usually performed to evaluate the status of enlarged mediastinal lymph nodes (seen on CT scan) before attempting definitive surgical resection of lung cancer.

Molecular Testing

Molecular testing forms an important part of the full pathologic evaluation of patients with metastatic non–small cell lung cancer (NSCLC), because very effective, less toxic, targeted treatments have become available for NSCLC with specific molecular abnormalities. Testing should include the following:

Epidermal growth factor receptor ( EGFR) mutation
Anaplastic lymphoma kinase ( ALK) rearrangement
BRAF V600E mutation
RET rearrangement
ROS-1 rearrangement
NTRK 1/2/3 gene fusion
MET exon 14 skipping
KRAS G12C mutation
Programmed death ligand 1 (PD-L1) expression

According to international evidence-based guidelines jointly published by the College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP), all lung cancer patients with adenocarcinomas should be tested for the genetic abnormalities that indicate suitability for treatment with targeted agents, irrespective of clinical variables such as sex, ethnicity, or smoking status.^[58] Clinical trial data demonstrate that patients who are tested for these abnormalities and treated with the appropriate targeted therapy have better outcomes.^[58]

Testing for driver mutations (eg, fusion, amplification, deletion) in the above-listed genes can be used to determine whether targeted therapy is appropriate. PD-L1 expression is based on the tumor proportion score (TPS), which is the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. Certain PD-L1 inhibitors may indicated in cases where the TPS is 1% or greater (eg, pembrolizumab), while others may be indicated in patients with a TPS of 50% or greater (eg, cemiplimab).

In 2013, the US Food and Drug Administration (FDA) approved the cobas EGFR Mutation Test, a companion diagnostic for erlotinib.^[59]This is the first FDA-approved companion diagnostic that can detect EGFR gene mutations. The mutation test allows physicians to identify patients with NSCLC who are candidates for receiving erlotinib as first-line therapy.

The safety and effectiveness of the cobas EGFR Mutation Test was established with clinical data from the EURTAC study and showed progression-free survival in patients with NSCLC who had specific types of EGFR mutations (exon 19 deletions or exon 21 [L858R] substitution mutations) for 10.4 months when they received erlotinib treatment, compared with 5.4 months for those who received standard therapy.^[60]

For more information, see Genetics of Non-Small Cell Lung Cancer.

Histologic Findings

The updated World Health Organization (WHO) classification of lung cancer is widely used. Non–small cell lung cancer (NSCLC) includes squamous cell carcinoma (SCC), adenocarcinoma, and large cell carcinoma. Some lung cancers exhibit two or more histologic patterns. SCC was previously the most common type of NSCLC, but adenocarcinoma appears to be increasing in incidence, especially in women.

SCC has a distinct dose-response relationship to tobacco smoking and usually develops in proximal airways, progressing through stages of squamous metaplasia to carcinoma in situ. Well-differentiated SCCs contain keratin pearls, while poorly differentiated SCCs may stain positive for keratin. Microscopic examination reveals cells with large, irregular nuclei and coarse nuclear chromatin with large nucleoli. Cells are arranged in sheets, and the presence of intercellular bridging is diagnostic.

Histologically, adenocarcinomas form glands and produce mucin. Mucin production can be identified with mucicarmine or periodic acid-Schiff staining. The WHO classification of lung cancer divides adenocarcinomas into (1) acinar, (2) papillary, (3) bronchoalveolar, and (4) mucus-secreting. Bronchoalveolar carcinoma is a distinct clinicopathologic entity that appears to arise from type II pneumocytes and may manifest as a solitary peripheral nodule, multifocal disease, or a pneumonic form, which can spread rapidly from one lobe to another.

Stage for stage, adenocarcinomas are associated with worse prognoses than SCCs, with the exception of T1 N0 M0 tumors.

Large cell carcinoma is the least common of all NSCLCs. It is composed of large cells with prominent nucleoli, and no mucin production or intercellular bridging is identified. Many tumors previously diagnosed as large cell carcinomas are identified as poorly differentiated adenocarcinomas or SCCs after advanced immunohistochemical staining, electron microscopy, and monoclonal antibody studies.

A variant of large cell carcinoma has been identified; it contains neuroendocrine features and is called large cell neuroendocrine carcinoma. Large cell neuroendocrine carcinomas are associated with a worse prognosis than large cell carcinomas.

WHO classification of epithelial lung tumors

WHO divides epithelial lung tumors into preinvasive lesions and invasive malignant lesions. Preinvasive lesions include the following:

Squamous dysplasia/carcinoma in situ
Atypical adenomatous hyperplasia
Diffuse idiopathic pulmonary neuroendocrine hyperplasia

Invasive malignant lesions include the following:

Squamous cell carcinoma – Variants, papillary, clear cell, small cell, basaloid
Small cell carcinoma – Variant, combined small cell carcinoma
Adenocarcinoma – Acinar, papillary, bronchoalveolar, nonmucinous (Clara cell/type II pneumocyte) type, mixed mucinous and nonmucinous (Clara cell/type II pneumocyte and goblet cell) type or intermediate cell type, solid adenocarcinoma with mucin formation, adenocarcinoma with mixed subtypes, variants, well-differentiated fetal adenocarcinoma, mucinous (colloid) adenocarcinoma, mucinous cystadenocarcinoma, signet-ring adenocarcinoma, clear cell adenocarcinoma
Large cell carcinoma – Variants, large cell neuroendocrine carcinoma, combined large cell neuroendocrine carcinoma, basaloid carcinoma, lymphoepitheliomalike carcinoma, clear cell carcinoma, large cell carcinoma with rhabdoid phenotype
Adenosquamous carcinoma
Carcinoma with sarcomatoid, pleomorphic, or sarcomatous elements - Carcinoma with spindle or giant cells, pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, pulmonary blastoma
Carcinoid tumors - Typical carcinoid, atypical carcinoid
Carcinoma of salivary gland type - Mucoepidermoid carcinoma, adenoid cystic carcinoma, others
Unclassified

Staging

The most important prognostic indicator in lung cancer is the extent of disease and lymph node involvement. The American Joint Committee for Cancer Staging and End Results Reporting has developed the TNM (tumor-node-metastasis) staging system, which takes into account the degree of spread of primary tumor, the extent of regional lymph node involvement, and the presence or absence of distant metastases (see the table below).^[61]The TNM system is used for all lung carcinomas except SCLCs.

AJCC TNM staging and grouping system

Primary tumor (T) involvement is as follows:

TX - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
Tis - Carcinoma in situ; squamous cell carcinoma in situ; adenocarcinoma in situ; adenocarcinoma with pure lepidic pattern, 3 cm or less in greatest dimension
T1 - Tumor 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (not in the main bronchus)
T1mi - Minimally invasive adenocarcinoma: adenocarcinoma (3 cm or less in greatest dimension) with a predominantly lepidic pattern and 5 mm or less invasion in greatest dimension
T1a - Tumor 1 cm or less in greatest dimension
T1b - Tumor more than 1 cm but 2 cm or less
T1c - Tumor more than 2 cm but 3 cm or less
T2 - Tumor more than 3 cm but 5 cm or less, or one with any of the following features:(1) Involves the main bronchus, regardless of distance to the carina, but without involvement of the carina; (2) Invades visceral pleura (PL1 or PL2); (3) Associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung
T2a - Tumor more than 3 cm but 4 cm or less
T2b - Tumor more than 4 cm but 5 cm or less
T3 - Tumor more than 5 cm but 7 cm or less, or one that invades any of the following: : parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary
T4 - Tumor more than 7 cm, or of any size that invades one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary

Lymph node (N) involvement is as follows:

NX - Regional nodes cannot be assessed
N0 - No regional node metastasis
N1 - Metastasis in ipsilateral peribronchial and/or ipsilateral hilar nodes and intrapulmonary nodes, including involvement by direct extension
N2 - Metastasis in ipsilateral mediastinal and/or subcarinal node
N3 - Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene node, or supraclavicular node

Metastatic (M) involvement is as follows:

MX - Distant metastasis cannot be assessed
M0 - No distant metastasis
M1 - Distant metastasis
M1a - Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodules or malignant pleural or pericardial effusion
M1b - Single extrathoracic metastasis in a single organ (including involvement of a single nonregional node)
M1c - Multiple extrathoracic metastases in one or more organs

AJCC prognostic groups for NSCLC comprise 4 stages, with further subdivision of stages into subtypes. These stages have important therapeutic and prognostic implications, which are discussed later.

Stage grouping of the TNM system is as follows:

Stage 0 - TisN0M0
Stage IA1- T1miN0M0 / T1aN0M0
Stage IA2 - T1bN0M0
Stage IA3 - T1cN0M0
Stage IB - T2aN0M0
Stage IIA - T2bN0M0
Stage IIB - T1aN1M0 / T1bN1M0 / T1cN1M0 / T2aN1M0 / T2bN1M0 / T3N0M0
Stage IIIA - T1aN2M0 / T1bN2M0 / T1cN2M0 / T2aN2M0 / T2bN2M0 /T3N1M0 / T4N0M0 / T4N1M0
Stage IIIB - T1aN3M0 / T1bN3M0 / T1cN3M0 / T2aN3M0 / T2bN3M0 / T3N2M0 / T4N2M0
Stage IIIC - T3N3M0 / T4N3M0
Stage IVA - Any T, any N, M1a or M1b
Stage IVB - Any T, any N, M1c
M1a designates metastasis within the thoracic cavity
M1b designates a single extrathoracic metastasis
M1c designates multiple extrathoracic metastases

Go to Imaging in Lung Cancer Staging and Non-Small Cell Lung Cancer Staging for complete information on this topic.

See also Lung Cancer Staging -- Radiologic Options, a Critical Images slideshow, to help identify stages of the disease process.

Workup for Special Populations

Patients with CNS metastasis, immunosuppression, superior vena cava syndrome (SVCS), 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.^[62]

Patients with CNS metastasis and known cancer

Head CT scanning, with and without contrast enhancement to depict masses, may be indicated. Obtain a neurosurgical consultation. Admit patients for possible whole-brain irradiation or resection.

Headache and brain edema may respond to dexamethasone (10 mg IV). Seizures are treated with anticonvulsants, but patients with brain metastases and no history of seizures do not generally require anticonvulsant therapy.^[63]

Immunosuppressed patients 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.

Treatment with granulocyte colony-stimulating factor (G-CSF) may be appropriate for raising neutrophil levels. Consultation with an oncologist is indicated to begin G-CSF therapy.

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 SVCS

Lung cancer accounts for 60-80% of SVCS. Head elevation, cautious administration of fluids, and supplemental oxygen is indicated. Diuretics and glucocorticoids (methylprednisolone 125 mg 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.

Screening

Since the publication of the National Lung Screening Trial results in 2011, which demonstrated that annual low-dose computed tomography (LDCT) allows for early detection and reduces lung cancer mortality by 20%,^[64]screening for lung cancer in patients at high risk has become the standard of care in the United States.^[47]Over time, the trend has been to increase screening eligibility to a larger number of patients, by extending the age range and reducing the smoking history for screening eligibility. Currently, guidelines from the American Cancer Society (ACS), American College of Chest Physicians (CHEST), National Comprehensive Cancer Network (NCCN), and U.S. Preventive Services Task Force (USPSTF) provide similar criteria sets for offering annual screening with LDCT scanning (see the table below).^{[39, 65, 47, 66]}

Table. Criteria for lung cancer screening (Open Table in a new window)

Organization	Criteria set
American Cancer Society (2023)	• Asymptomatic • Age 50 to 80 years • Currently smoke or formerly smoked • ≥20 pack-year smoking history
CHEST (American College of Chest Physicians)(2021)	• Asymptomatic • Age 55 to 77 years with ≥30 pack-year smoking history or age 50-80 years with ≥20 pack-year smoking history • Currently smoke or quit within the past 15 years • Do not meet other criteria, but clinical risk prediction calculations/life expectancy estimates/life-year gained calculations suggest high net benefit from screening
National Comprehensive Cancer Network (2023)	• Age ≥50 y • ≥20 pack-year history of smoking cigarettes • Use of risk calculators may identify additional candidates for screening
U.S. Preventive Services Task Force (2021)	• Age 50 to 80 years • 20 pack-year smoking history • Currently smoke or have quit within the past 15 years • Do not have a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery.

American Cancer Society guidelines exclude patients from screening if they have any of the following^[39]:

Health conditions that may increase harm or hinder further evaluation, surgery, or other treatment for lung cancer.
Comorbid conditions that limit life expectancy to less than 5 years
Unwillingness to accept treatment for cancer detected by screening

In addition to smoking, the NCCN guidelines include the presence of one or more of the following additional factors as an indication of high risk^[65]:

Radon exposure (documented sustained and substantially elevated)
Occupational exposure to carcinogens (eg, silica, cadmium, asbestos, arsenic, beryllium, chromium, diesel fumes, nickel, coal smoke, soot)
Cancer history (eg, lymphomas, head and neck cancer; however, patients with previous lung cancer are ineligible for screening)
Family history of lung cancer in first-degree relatives
Disease history (chronic obstructive pulmonary disease [COPD] or pulmonary fibrosis)
Second-hand smoke exposure

The NCCN recommends using a risk calculator to enhance determination of risk status.

The NCCN notes that evidence from randomized trials supports screening up to age 77 years, but screening beyond age 77 years may be considered as long as the patient's functional status and comorbidity allow consideration for curative-intent therapy.^[65]

Using data from the National Health Interview Survey, Cheung et al estimated the number of US smokers eligible for screening on the basis of either USPSTF criteria or the Lung Cancer Risk Assessment Tool and the number of lung cancer deaths preventable with each method. They determined that with risk-based screening, more people would be screened and more deaths prevented. In 2015, risk-based screening would have prevented 5000 more lung cancer deaths than USPSTF-based screening.^[67] However, an analysis by Kumar et al concluded that risk-based screening provides only attenuated and modest benefits with respect to life-years, quality-adjusted life-years, and cost-effectiveness.^[68]

A randomized trial designed to assess the value of prolonged lung cancer screening beyond 5 years found LDCT screening benefit improved beyond the 5th year of screening, with a 58% reduced risk of lung cancer mortality (HR 0.42; 95% CI 0.22–0.79), and 32% reduction of overall mortality (HR 0.68; 95% CI 0.49–0.94).^[69]

Limitations of screening

In a 2013 analysis of data on 53,452 individuals at high risk for lung cancer, derived from the National Lung Screening Trial, Patz et al determined that performing lung screens with LDCT scanning carries a 22.5% probability of NSCLC overdiagnosis (ie, detection of indolent cancers), as well as an 18.5% probability of overdiagnosis for lung cancer in general. Patz et al concluded that overdiagnosis—which can lead to increases in treatment costs, anxiety, and treatment-related morbidity—should be a consideration when physicians are discussing the risks of LDCT lung cancer screening.^[70]

Subsequently, in a retrospective cohort analysis of data from the National Lung Screening Trial participants, Patz et al reported that patients whose initial LDCT scan is negative have a lower incidence of lung cancer and lung cancer-specific mortality. These authors proposed that a longer interval between screens might be warranted in patients whose initial LDCT screening scan is negative.^[71]

In this study, lung cancer incidence per 100,000 person-years was 371.88 in the 19,066 participants with a negative LDCT, versus 661.23 in the overall cohort of 26,231 participants. Lung cancer–related mortality rates per 100 000 person-years were 185.82 versus 277.20 for the two cohorts, respectively.^[71]

In a study by Kinsinger et al of lung cancer screening in 2106 patients at Veterans Health Administration medical centers, LDCT identified nodules in 59.7% of screened patients, but just 1.5% of patients had lung cancer diagnosed within 330 days. The rate of false-positive test results was 97.5%. These authors concluded that implementing a lung cancer screening program for Veterans Health Administration patients "would potentially require substantial resources and effort by clinical staff and facilities for an uncertain benefit of reduced mortality from lung cancer."^[72]

Risk models for screening

A study by researchers from the National Cancer Institute (NCI) and the American Cancer Society that reviewed nine risk prediction models determined that the following four models were more accurate than the others for predicting lung cancer risk and for selecting patients who had ever-smoked for lung cancer screening:

Bach model
Ovarian Cancer Screening Trial Model 2012 (PLCO-M2012)
Lung Cancer Risk Assessment Tool (LCRAT)
Lung Cancer Death Risk Assessment Tool (LCDRAT)

Although the researchers concluded that that any of those models could be used to select US smokers who are at the greatest risk for lung cancer incidence or death, all the models have limitations. The Bach model does not account for race/ethnicity, family history of lung cancer, or presence of chronic obstructive pulmonary disease; the PLCO-M2012 model underestimated lung cancer risk in people of Hispanic descent by a factor of 2 to 3, and the LCRAT and LCDRAT models both underestimated risk in the "Asian/other" subgroup.^[73]

Biomarker screening

A collaborative study has identified and validated a panel of circulating protein biomarkers that may improve lung cancer risk assessment and may be used to define eligibility for CT screening.^[74]Using prediagnostic blood samples from patients at high risk for lung cancer, the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer created a risk assessment tool consists of a panel of the following proteins:

Cancer antigen 125
Carcinoembryonic antigen
Cytokeratin-19 fragment
The precursor of surfactant protein B

In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls, an integrated risk prediction model that combined smoking exposure with the biomarker panel score identified 40 of the 63 lung cancer cases, corresponding to a sensitivity of 0.63. By comparison, the US Preventive Services Task Force screening criteria demonstrated a sensitivity of 0.42 for these cases.^[74]

Treatment & Management

[Guideline] Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May. 143 (5 Suppl):e142S-e165S. [QxMD MEDLINE Link]. [Full Text].
Rowell NP, Williams CJ. Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable): a systematic review. Thorax. 2001 Aug. 56(8):628-38. [QxMD MEDLINE Link].
Strand TE, Brunsvig PF, Johannessen DC, et al. Potentially curative radiotherapy for non-small-cell lung cancer in Norway: a population-based study of survival. Int J Radiat Oncol Biol Phys. 2011 May 1. 80(1):133-41. [QxMD MEDLINE Link].
Wang HM, Liao ZX, Komaki R, et al. Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy. Ann Oncol. 2013 Jan 8. [QxMD MEDLINE Link].
Rosen G. A History of Public Health: Expanded Edition. Baltimore, MD.: The Johns Hopkins University Press; 1993.
Cancer Facts & Figures 2023. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf. Accessed: February 15, 2023.
National Research Council, Committee on Health Risks of Exposure to Radon, Board on Radiation Effects Research, Commission on Life Sciences. Health effects of exposure to radon (BEIR VI). Washington, DC.: National Academy Press.; 1999.
Ito H, Matsuo K, Tanaka H, et al. Nonfilter and filter cigarette consumption and the incidence of lung cancer by histological type in Japan and the United States: analysis of 30-year data from population-based cancer registries. Int J Cancer. 2011 Apr 15. 128(8):1918-28. [QxMD MEDLINE Link].
Zhang J, Fujimoto J, Zhang J, et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 2014 Oct 10. 346(6206):256-9. [QxMD MEDLINE Link].
de Bruin EC, McGranahan N, Mitter R, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science. 2014 Oct 10. 346(6206):251-6. [QxMD MEDLINE Link].
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008 May. 83(5):584-94. [QxMD MEDLINE Link]. [Full Text].
Nelson R. Lung Cancer Rates Surging in Never-Smokers. Medscape Medical News. Available at http://www.medscape.com/viewarticle/850708. September 9, 2015; Accessed: February 15, 2023.
Beckett WS. Epidemiology and etiology of lung cancer. Clin Chest Med. 1993 Mar. 14(1):1-15. [QxMD MEDLINE Link].
Bagnardi V, Rota M, Botteri E, et al. Alcohol consumption and lung cancer risk in never smokers: a meta-analysis. Ann Oncol. 2011 Dec. 22(12):2631-9. [QxMD MEDLINE Link].
Current Cigarette Smoking Among Adults in the United States. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm. March 17, 2022; Accessed: February 15, 2023.
GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019. Lancet. 2021 Jun 19. 397 (10292):2337-2360. [QxMD MEDLINE Link]. [Full Text].
Ginsberg RJ, Vokes EE, Raben A. Non-small cell lung cancer. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven;. 1997:858-911.
Vainshelboim B, Lima RM, Kokkinos P, Myers J. Cardiorespiratory Fitness, Lung Cancer Incidence, and Cancer Mortality in Male Smokers. Am J Prev Med. 2019 Nov. 57 (5):659-666. [QxMD MEDLINE Link].
Zhong L, Goldberg MS, Parent ME, Hanley JA. Exposure to environmental tobacco smoke and the risk of lung cancer: a meta-analysis. Lung Cancer. 2000 Jan. 27(1):3-18. [QxMD MEDLINE Link].
Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD. Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May. 143(5 Suppl):e1S-29S. [QxMD MEDLINE Link].
Hou W, Fu J, Ge Y, Du J, Hua S. Incidence and risk of lung cancer in HIV-infected patients. J Cancer Res Clin Oncol. 2013 Nov. 139(11):1781-94. [QxMD MEDLINE Link].
Cortes-Jofre M, Rueda JR, Corsini-Munoz G, Fonseca-Cortes C, Caraballoso M, Bonfill Cosp X. Drugs for preventing lung cancer in healthy people. Cochrane Database Syst Rev. 2012 Oct 17. 10:CD002141. [QxMD MEDLINE Link].
Ries L, Eisner M, Kosary C. Cancer statistics review, 1975-2002. National Cancer Institute.; 2005.
World Health Organization, International Agency for Research on Cancer. Globocan 2020: Lung Cancer. International Agency for Research on Cancer. Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed: February 15, 2023.
Jemal A, Miller KD, Ma J, Siegel RL, Fedewa SA, Islami F, et al. Higher Lung Cancer Incidence in Young Women Than Young Men in the United States. N Engl J Med. 2018 May 24. 378 (21):1999-2009. [QxMD MEDLINE Link].
SEER Stat Fact Sheets: Lung and Bronchus Cancer. Surveillance, Epidemiology, and End Results Program. Available at http://seer.cancer.gov/statfacts/html/lungb.html. Accessed: February 15, 2023.
Jonnalagadda S, Smith C, Mhango G, Wisnivesky JP. The Number of Lymph Node Metastases as a Prognostic Factor in Patients With N1 Non-small Cell Lung Cancer. Chest. 2011 Aug. 140(2):433-40. [QxMD MEDLINE Link]. [Full Text].
Mostertz W, Stevenson M, Acharya C, et al. Age- and sex-specific genomic profiles in non-small cell lung cancer. JAMA. 2010 Feb 10. 303(6):535-43. [QxMD MEDLINE Link].
Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010 Jan 21. 340:b5569. [QxMD MEDLINE Link]. [Full Text].
Ferketich AK, Niland JC, Mamet R, et al. Smoking status and survival in the national comprehensive cancer network non-small cell lung cancer cohort. Cancer. 2012 Sep 28. [QxMD MEDLINE Link].
Chlebowski RT, Schwartz AG, Wakelee H, Anderson GL, Stefanick ML, Manson JE, et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009 Oct 10. 374 (9697):1243-51. [QxMD MEDLINE Link]. [Full Text].
Bouchardy C, Benhamou S, Schaffar R, et al. Lung cancer mortality risk among breast cancer patients treated with anti-estrogens. Cancer. 2011 Mar 15. 117(6):1288-95. [QxMD MEDLINE Link].
Rothwell PM, Fowkes GR, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials. Lancet. Dec 7/2010; Early online publication. [Full Text].
Hofman V, Bonnetaud C, Ilie MI, et al. Preoperative circulating tumor cell detection using the isolation by size of epithelial tumor cell method for patients with lung cancer is a new prognostic biomarker. Clin Cancer Res. 2011 Feb 15. 17(4):827-35. [QxMD MEDLINE Link].
Wicha MS, Hayes DF. Circulating tumor cells: not all detected cells are bad and not all bad cells are detected. J Clin Oncol. 2011 Apr 20. 29(12):1508-11. [QxMD MEDLINE Link].
Lopez Guerra JL, Gomez DR, Lin SH, et al. Risk factors for local and regional recurrence in patients with resected N0-N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy. Ann Oncol. 2012 Sep 20. [QxMD MEDLINE Link].
Kadota K, Nitadori JI, Sarkaria IS, et al. Thyroid transcription factor-1 expression is an independent predictor of recurrence and correlates with the IASLC/ATS/ERS histologic classification in patients with stage I lung adenocarcinoma. Cancer. 2012 Oct 23. [QxMD MEDLINE Link].
Nitadori J, Bograd AJ, Kadota K, et al. Impact of Micropapillary Histologic Subtype in Selecting Limited Resection vs Lobectomy for Lung Adenocarcinoma of 2cm or Smaller. J Natl Cancer Inst. 2013 Aug 21. 105(16):1212-20. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Wolf AMD, Oeffinger KC, Shih TY, Walter LC, Church TR, Fontham ETH, et al. Screening for lung cancer: 2023 guideline update from the American Cancer Society. CA Cancer J Clin. 2023 Nov 1. [QxMD MEDLINE Link]. [Full Text].
Corner J, Hopkinson J, Fitzsimmons D, Barclay S, Muers M. Is late diagnosis of lung cancer inevitable? Interview study of patients' recollections of symptoms before diagnosis. Thorax. 2005 Apr. 60(4):314-9. [QxMD MEDLINE Link]. [Full Text].
Ejaz S, Vassilopoulou-Sellin R, Busaidy NL, et al. Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion: the University of Texas MD Anderson Cancer Center Experience. Cancer. 2011 Oct 1. 117(19):4381-9. [QxMD MEDLINE Link]. [Full Text].
Fadel E, Missenard G, Court C, et al. Long-term outcomes of en bloc resection of non-small cell lung cancer invading the thoracic inlet and spine. Ann Thorac Surg. 2011 Sep. 92(3):1024-30; discussion 1030. [QxMD MEDLINE Link].
Patel AM, Davila DG, Peters SG. Paraneoplastic syndromes associated with lung cancer. Mayo Clin Proc. 1993 Mar. 68(3):278-87. [QxMD MEDLINE Link].
Sher T, Dy GK, Adjei AA. Small cell lung cancer. Mayo Clin Proc. 2008 Mar. 83(3):355-67. [QxMD MEDLINE Link].
Annema JT, van Meerbeeck JP, Rintoul RC, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA. 2010 Nov 24. 304(20):2245-52. [QxMD MEDLINE Link].
Oken MM, Hocking WG, Kvale PA, et al. Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA. 2011 Nov 2. 306(17):1865-73. [QxMD MEDLINE Link].
[Guideline] Mazzone PJ, Silvestri GA, Souter LH, Caverly TJ, Kanne JP, Katki HA, et al. Screening for Lung Cancer: CHEST Guideline and Expert Panel Report. Chest. 2021 Nov. 160 (5):e427-e494. [QxMD MEDLINE Link]. [Full Text].
Foster BB, Muller NL, Miller RR, et al. Neuroendocrine carcinomas of the lung: clinical, radiologic and pathologic correlation. Radiology. 1989. 170:441-445.
Alpert JB, Fantauzzi JP, Melamud K, Greenwood H, Naidich DP, Ko JP. Clinical Significance of Lung Nodules Reported on Abdominal CT. AJR Am J Roentgenol. 2012 Apr. 198(4):793-9. [QxMD MEDLINE Link].
Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA. 2001 Feb 21. 285(7):914-24. [QxMD MEDLINE Link].
Deppen SA, Blume JD, Kensinger CD, et al. Accuracy of FDG-PET to diagnose lung cancer in areas with infectious lung disease: a meta-analysis. JAMA. 2014 Sep 24. 312(12):1227-36. [QxMD MEDLINE Link].
Erkilic S, Ozsarac C, Kullu S. Sputum cytology for the diagnosis of lung cancer. Comparison of smear and modified cell block methods. Acta Cytol. 2003 Nov-Dec. 47(6):1023-7. [QxMD MEDLINE Link].
Billah S, Stewart J, Staerkel G, et al. EGFR and KRAS mutations in lung carcinoma: molecular testing by using cytology specimens. Cancer Cytopathol. 2011 Apr 25. 119(2):111-7. [QxMD MEDLINE Link].
Arroliga AC, Matthay RA. The role of bronchoscopy in lung cancer. Clin Chest Med. 1993 Mar. 14(1):87-98. [QxMD MEDLINE Link].
Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer: summary of published evidence. Chest. 2003 Jan. 123(1 Suppl):115S-128S. [QxMD MEDLINE Link].
He J, Shao W, Cao C, et al. Long-term outcome and cost-effectiveness of complete versus assisted video-assisted thoracic surgery for non-small cell lung cancer. J Surg Oncol. 2011 Aug 1. 104(2):162-8. [QxMD MEDLINE Link].
Mentzer SJ, Swanson SJ, DeCamp MM, Bueno R, Sugarbaker DJ. Mediastinoscopy, thoracoscopy, and video-assisted thoracic surgery in the diagnosis and staging of lung cancer. Chest. 1997 Oct. 112(4 Suppl):239S-241S. [QxMD MEDLINE Link].
[Guideline] Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, et al. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med. 2018 Mar. 142 (3):321-346. [QxMD MEDLINE Link]. [Full Text].
Chustecka Z. FDA approves companion genetic diagnostic test for Tarceva in NSCLC. Medscape Medical News. May 14, 2013. [Full Text].
Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar. 13(3):239-46. [QxMD MEDLINE Link].
American Joint Committee on Cancer. Lung. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, et al, eds. AJCC Cancer Staging Handbook. 8th ed. Chicago, Ill: Springer; 2017. Chapter 25.
Tintinalli JE. Emergency complications of malignancy. Emergency Medicine: A Comprehensive Guide. 2004. 1319-1368.
Halfdanarson TR, Hogan WJ, Moynihan TJ. Oncologic emergencies: diagnosis and treatment. Mayo Clin Proc. 2006 Jun. 81(6):835-48. [QxMD MEDLINE Link].
National Lung Screening Trial Research Team., Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4. 365 (5):395-409. [QxMD MEDLINE Link]. [Full Text].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Lung Cancer Screening. Available at http://www.nccn.org/professionals/physician_gls/pdf/lung_screening.pdf. Version 2.2024 — October 18, 2023; Accessed: November 2, 2023.
[Guideline] U.S. Preventive Services Task Force. Final Recommendation Statement: Lung Cancer: Screening. Available at https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/lung-cancer-screening. March 9, 2021; Accessed: June 7, 2023.
Cheung LC, Katki HA, Chaturvedi AK, Jemal A, Berg CD. Preventing Lung Cancer Mortality by Computed Tomography Screening: The Effect of Risk-Based Versus U.S. Preventive Services Task Force Eligibility Criteria, 2005–2015. Ann Intern Med. 2 January 2018. [Full Text].
Kumar V, Cohen JT, van Klaveren D, Soeteman DI, Wong JB, Neumann PJ, et al. Risk-Targeted Lung Cancer Screening: A Cost-Effectiveness Analysis. Ann Intern Med. 2 January 2018. [Full Text].
Pastorino U, Silva M, Sestini S, Sabia F, Boeri M, Cantarutti A, et al. Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy. Ann Oncol. 2019 Jun 5. [QxMD MEDLINE Link]. [Full Text].
Patz EF Jr, Pinsky P, Gatsonis C, et al. Overdiagnosis in low-dose computed tomography screening for lung cancer. JAMA Intern Med. 2013 Dec 9. [QxMD MEDLINE Link].
Patz EF Jr, Greco E, Gatsonis C, Pinsky P, Kramer BS, Aberle DR. Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial. Lancet Oncol. 2016 Mar 18. [QxMD MEDLINE Link].
Kinsinger LS, Anderson C, Kim J, Larson M, Chan SH, King HA, et al. Implementation of Lung Cancer Screening in the Veterans Health Administration. JAMA Intern Med. 2017 Jan 30. [QxMD MEDLINE Link]. [Full Text].
Katki HA, Kovalchik SA, Petito LC, Cheung LC, Jacobs E, Jemal A, et al. Implications of Nine Risk Prediction Models for Selecting Ever-Smokers for Computed Tomography Lung Cancer Screening. Ann Intern Med. 15 May 2018. [Full Text].
Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer., Guida F, Sun N, Bantis LE, et al. Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins. JAMA Oncol. 2018 Jul 12. e182078. [QxMD MEDLINE Link].
Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22. 350(4):351-60. [QxMD MEDLINE Link].
Saw SPL, Ong BH, Chua KLM, Takano A, Tan DSW. Revisiting neoadjuvant therapy in non-small-cell lung cancer. Lancet Oncol. 2021 Nov. 22 (11):e501-e516. [QxMD MEDLINE Link].
FDA approves neoadjuvant nivolumab and platinum-doublet chemotherapy for early-stage non-small cell lung cancer. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvant-nivolumab-and-platinum-doublet-chemotherapy-early-stage-non-small-cell-lung. March 4, 2022; Accessed: April 27, 2023.
Forde PM, et al; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26. 386 (21):1973-1985. [QxMD MEDLINE Link]. [Full Text].
Greer JA, Jackson VA, Meier DE, Temel JS. Early integration of palliative care services with standard oncology care for patients with advanced cancer. CA Cancer J Clin. 2013 Sep. 63(5):349-63. [QxMD MEDLINE Link].
Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010 Aug 19. 363(8):733-42. [QxMD MEDLINE Link].
[Guideline] Detterbeck FC, Lewis SZ, Diekemper R, Addrizzo-Harris D, Alberts WM. Executive Summary: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May. 143(5 Suppl):7S-37S. [QxMD MEDLINE Link]. [Full Text].
Yang CF, Kumar A, Gulack BC, Mulvihill MS, Hartwig MG, Wang X, et al. Long-term outcomes after lobectomy for non-small cell lung cancer when unsuspected pN2 disease is found: A National Cancer Data Base analysis. J Thorac Cardiovasc Surg. 2016 May. 151 (5):1380-8. [QxMD MEDLINE Link].
Okada M, Nakayama H, Okumura S, et al. Multicenter analysis of high-resolution computed tomography and positron emission tomography/computed tomography findings to choose therapeutic strategies for clinical stage IA lung adenocarcinoma. J Thorac Cardiovasc Surg. 2011 Jun. 141(6):1384-91. [QxMD MEDLINE Link].
Ma Z, Dong A, Fan J, Cheng H. Does sleeve lobectomy concomitant with or without pulmonary artery reconstruction (double sleeve) have favorable results for non-small cell lung cancer compared with pneumonectomy? A meta-analysis. Eur J Cardiothorac Surg. 2007 Jul. 32(1):20-8. [QxMD MEDLINE Link].
Kates M, Swanson S, Wisnivesky JP. Survival following lobectomy and limited resection for the treatment of stage I non-small cell lung cancer<=1 cm in size: a review of SEER data. Chest. 2011 Mar. 139(3):491-6. [QxMD MEDLINE Link].
Altorki N, Wang X, Kozono D, Watt C, Landrenau R, Wigle D, et al. Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Feb 9. 388 (6):489-498. [QxMD MEDLINE Link].
Comparison of Different Types of Surgery in Treating Patients With Stage IA Non-Small Cell Lung Cancer. National Cancer Institute. Available at https://clinicaltrials.gov/ct2/show/NCT00499330. November 17, 2022; Accessed: April 27, 2023.
Yendamuri S, Sharma R, Demmy M, et al. Temporal trends in outcomes following sublobar and lobar resections for small (= 2 cm) non-small cell lung cancers--a Surveillance Epidemiology End Results database analysis. J Surg Res. 2013 Jul. 183(1):27-32. [QxMD MEDLINE Link].
Okami J, Ito Y, Higashiyama M, et al. Sublobar resection provides an equivalent survival after lobectomy in elderly patients with early lung cancer. Ann Thorac Surg. 2010 Nov. 90(5):1651-6. [QxMD MEDLINE Link].
Wolf AS, Richards WG, Jaklitsch MT, et al. Lobectomy versus sublobar resection for small (2 cm or less) non-small cell lung cancers. Ann Thorac Surg. 2011 Nov. 92(5):1819-23; discussion 1824-5. [QxMD MEDLINE Link].
Cattaneo SM, Park BJ, Wilton AS, et al. Use of video-assisted thoracic surgery for lobectomy in the elderly results in fewer complications. Ann Thorac Surg. 2008 Jan. 85(1):231-5; discussion 235-6. [QxMD MEDLINE Link].
[Guideline] National Comprehensive Cancer Network. National Comprehensive Cancer Network. Non-Small Cell Lung Cancer. NCCN. Available at https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Version 1.2022 — December 7, 2021; Accessed: February 9, 2022.
Swanson SJ, Herndon JE 2nd, D'Amico TA, et al. Video-assisted thoracic surgery lobectomy: report of CALGB 39802--a prospective, multi-institution feasibility study. J Clin Oncol. 2007 Nov 1. 25(31):4993-7. [QxMD MEDLINE Link].
Darling GE, Allen MS, Decker PA, et al. Number of lymph nodes harvested from a mediastinal lymphadenectomy: results of the randomized, prospective American College of Surgeons Oncology Group Z0030 trial. Chest. 2011 May. 139(5):1124-9. [QxMD MEDLINE Link]. [Full Text].
Allen JW, Farooq A, O'Brien TF, Osarogiagbon RU. Quality of surgical resection for nonsmall cell lung cancer in a US metropolitan area. Cancer. 2011 Jan 1. 117(1):134-42. [QxMD MEDLINE Link].
Yun YH, Kim YA, Min YH, et al. Health-Related Quality of Life in Disease-Free Survivors of Surgically Treated Lung Cancer Compared With the General Population. Ann Surg. 2012 Mar 30. [QxMD MEDLINE Link].
Dosoretz DE, Katin MJ, Blitzer PH, et al. Radiation therapy in the management of medically inoperable carcinoma of the lung: results and implications for future treatment strategies. Int J Radiat Oncol Biol Phys. 1992. 24(1):3-9. [QxMD MEDLINE Link].
Jeremic B, Milicic B, Milisavljevic S. Clinical prognostic factors in patients with locally advanced (stage III) nonsmall cell lung cancer treated with hyperfractionated radiation therapy with and without concurrent chemotherapy: single-Institution Experience in 600 Patients. Cancer. 2011 Jan 10. [QxMD MEDLINE Link].
Sigel K, Lurslurchachai L, Bonomi M, et al. Effectiveness of radiation therapy alone for elderly patients with unresected stage III non-small cell lung cancer. Lung Cancer. 2013 Sep 4. [QxMD MEDLINE Link].
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28. 366(26):2443-54. [QxMD MEDLINE Link]. [Full Text].
Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K. Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study. J Thorac Oncol. 2007 Jul. 2(7 Suppl 3):S94-100. [QxMD MEDLINE Link].
Grills IS, Mangona VS, Welsh R, et al. Outcomes after stereotactic lung radiotherapy or wedge resection for stage I non-small-cell lung cancer. J Clin Oncol. 2010 Feb 20. 28(6):928-35. [QxMD MEDLINE Link].
Lencioni R, Crocetti L, Cioni R, Suh R, Glenn D, Regge D. Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study). Lancet Oncol. 2008 Jul. 9(7):621-8. [QxMD MEDLINE Link].
Muirhead R, van der Weide L, van Sornsen de Koste JR, Cover KS, Senan S. Use of megavoltage cine-images for studying intra-thoracic motion during radiotherapy for locally advanced lung cancer. Radiother Oncol. 2011 May. 99(2):155-60. [QxMD MEDLINE Link].
PORT Meta-analysis Trialists Group. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. Lancet. 1998 Jul 25. 352(9124):257-63. [QxMD MEDLINE Link].
Rusch VW, Albain KS, Crowley JJ, et al. Surgical resection of stage IIIA and stage IIIB non-small-cell lung cancer after concurrent induction chemoradiotherapy. A Southwest Oncology Group trial. J Thorac Cardiovasc Surg. 1993 Jan. 105(1):97-104; discussion 104-6. [QxMD MEDLINE Link].
Azzoli CG, Temin S, Aliff T, et al. 2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer. J Clin Oncol. 2011 Oct 1. 29(28):3825-31. [QxMD MEDLINE Link]. [Full Text].
Rosell R, Gomez-Codina J, Camps C, et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med. 1994. 330:153-158. [QxMD MEDLINE Link].
Roth JA, Fossella F, Komaki R, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst. 1994. 86:673-680. [QxMD MEDLINE Link].
Sigel K, Mhango G, Cohen J, et al. Outcomes After Adjuvant Platinum-based Chemotherapy in Elderly NSCLC Patients with T4 Disease. Ann Surg Oncol. 2012 Nov 1. [QxMD MEDLINE Link].
NSCLC Meta-Analyses collaborative Group. Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol. 2008 Oct 1. 26(28):4617-25. [QxMD MEDLINE Link].
Marino P, Pampallona S, Preatoni A, et al. Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature. Chest. 1994 Sep. 106(3):861-5. [QxMD MEDLINE Link].
Wanders R, Steevens J, Botterweck A, et al. Treatment with curative intent of stage III non-small cell lung cancer patients of 75 years: a prospective population-based study. Eur J Cancer. 2011 Dec. 47(18):2691-7. [QxMD MEDLINE Link].
Wisnivesky JP, Smith CB, Packer S, et al. Survival and risk of adverse events in older patients receiving postoperative adjuvant chemotherapy for resected stages II-IIIA lung cancer: observational cohort study. BMJ. 2011 Jul 14. 343:d4013. [QxMD MEDLINE Link]. [Full Text].
Weick JK, Crowley J, Natale RB, et al. A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1991 Jul. 9(7):1157-62. [QxMD MEDLINE Link].
Rajeswaran A, Trojan A, Burnand B, Giannelli M. Efficacy and side effects of cisplatin- and carboplatin-based doublet chemotherapeutic regimens versus non-platinum-based doublet chemotherapeutic regimens as first line treatment of metastatic non-small cell lung carcinoma: a systematic review of randomized controlled trials. Lung Cancer. 2008 Jan. 59(1):1-11. [QxMD MEDLINE Link].
Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10. 346 (2):92-8. [QxMD MEDLINE Link]. [Full Text].
Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10. 30(17):2055-62. [QxMD MEDLINE Link].
Le Chevalier T, Scagliotti G, Natale R, et al. Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: a meta-analysis of survival outcomes. Lung Cancer. 2005 Jan. 47(1):69-80. [QxMD MEDLINE Link].
Quoix E, Zalcman G, Oster JP, et al. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17. 378(9796):1079-88. [QxMD MEDLINE Link].
Pallis AG, Karampeazis A, Vamvakas L, et al. Efficacy and treatment tolerance in older patients with NSCLC: a meta-analysis of five phase III randomized trials conducted by the Hellenic Oncology Research Group. Ann Oncol. 2011 Nov. 22(11):2448-55. [QxMD MEDLINE Link].
Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20. 26(21):3543-51. [QxMD MEDLINE Link].
Holm B, Mellemgaard A, Skov T, Skov BG. Different impact of excision repair cross-complementation group 1 on survival in male and female patients with inoperable non-small-cell lung cancer treated with carboplatin and gemcitabine. J Clin Oncol. 2009 Sep 10. 27(26):4254-9. [QxMD MEDLINE Link].
FDA approves atezolizumab as adjuvant treatment for non-small cell lung cancer. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-adjuvant-treatment-non-small-cell-lung-cancer. October 15, 2021; Accessed: February 16, 2023.
Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23. 384(9944):665-73. [QxMD MEDLINE Link].
Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Feb 1. 27(4):591-8. [QxMD MEDLINE Link].
Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1. 22(9):1589-97. [QxMD MEDLINE Link].
Ramlau R, Gorbunova V, Ciuleanu TE, et al. Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol. 2012 Oct 10. 30(29):3640-7. [QxMD MEDLINE Link].
Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990 Oct 4. 323(14):940-5. [QxMD MEDLINE Link].
Le Chevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst. 1991 Mar 20. 83(6):417-23. [QxMD MEDLINE Link].
Albain KS, Rusch VW, Crowley JJ, et al. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805. J Clin Oncol. 1995 Aug. 13(8):1880-92. [QxMD MEDLINE Link].
Schaake-Koning C, van den Bogaert W, Dalesio O, et al. Effects of concomitant cisplatin and radiotherapy on inoperable non- small-cell lung cancer. N Engl J Med. 1992 Feb 20. 326(8):524-30. [QxMD MEDLINE Link].
Albain KS, Swann RS, Rusch VR, et al. Phase III study of concurrent chemotherapy and radiotherapy (CT/RT) vs CT/RT followed by surgical resection for stage IIIA(pN2) non-small cell lung cancer (NSCLC): Outcomes update of North American Intergroup 0139 (RTOG 9309). J Clin Oncol. 2005. 23:624s.
Curran WJ, Scott C, Langer C, et al. Long-term benefit is observed in a phase III comparison of sequential vs concurrent chemo-radiation for patients with unresected stage III non small cell lung cancer: RTOG 9410 (abstract). Proc Am Soc Clin Oncol. 2003. 22:621a.
Curran WJ, Scott C, Langer C, et al. Phase III Comparison of Sequential vs Concurrent Chemoradiation for Patients (Pts) with Unresected Stage III Non-Small Cell Lung Cancer (NSCLC): Initial Report of Radiation Therapy Oncology Group (RTOG) 9410. Proc Am Soc Clin Oncol. 2000. 19:484a.
Belani CP, Choy H, Bonomi P, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1. 23(25):5883-91. [QxMD MEDLINE Link].
Johnson DH, Paul DM, Hande KR, et al. Paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a phase II trial. J Clin Oncol. 1996 Jul. 14(7):2054-60. [QxMD MEDLINE Link].
Langer CJ, Leighton JC, Comis RL, et al. Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis. J Clin Oncol. 1995 Aug. 13(8):1860-70. [QxMD MEDLINE Link].
Hanna N, Neubauer M, Yiannoutsos C, et al. Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology. J Clin Oncol. 2008 Dec 10. 26(35):5755-60. [QxMD MEDLINE Link].
Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5. 103(19):1452-60. [QxMD MEDLINE Link]. [Full Text].
Antonia SJ, et al; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16. 377 (20):1919-1929. [QxMD MEDLINE Link].
Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2020 Feb. 15 (2):288-293. [QxMD MEDLINE Link]. [Full Text].
Schumacher A, Riesenbeck D, Braunheim M, et al. Combined modality treatment for locally advanced non-small cell lung cancer: preoperative chemoradiation does not result in a poorer quality of life. Lung Cancer. 2004 Apr. 44(1):89-97. [QxMD MEDLINE Link].
van Meerbeeck JP, Kramer GW, Van Schil PE, Legrand C, Smit EF, Schramel F, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst. 2007 Mar 21. 99 (6):442-50. [QxMD MEDLINE Link].
Daly BD, Ebright MI, Walkey AJ, et al. Impact of neoadjuvant chemoradiotherapy followed by surgical resection on node-negative T3 and T4 non-small cell lung cancer. J Thorac Cardiovasc Surg. 2011 Jun. 141(6):1392-7. [QxMD MEDLINE Link].
[Guideline] Adjuvant Chemotherapy and Adjuvant Radiation Therapy for Stages I-IIIA Resectable Non-Small Cell Lung Cancer. American Society of Clinical Oncology. Available at https://www.asco.org/practice-patients/guidelines/thoracic-cancer#/10226. January 10, 2022; Accessed: February 9, 2022.
Li BT, Smit EF, Goto Y, and the, DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20. 386 (3):241-251. [QxMD MEDLINE Link]. [Full Text].
Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRAS^G12C Somatic Mutations across Race, Sex, and Cancer Type. N Engl J Med. 2021 Jan 14. 384 (2):185-187. [QxMD MEDLINE Link].
Drilon A, Siena S, Dziadziuszko R, et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb. 21 (2):261-270. [QxMD MEDLINE Link]. [Full Text].
Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb. 21 (2):271-282. [QxMD MEDLINE Link]. [Full Text].
FDA Approves Cemiplimab-rwlc for Patients With NSCLC and High PD-L1 Expression. The ASCO Post. Available at https://ascopost.com/news/february-2021/fda-approves-cemiplimab-rwlc-for-patients-with-nsclc-and-high-pd-l1-expression/. February 22, 2021; Accessed: March 4, 2021.
Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009 Sep 3. 361(10):958-67. [QxMD MEDLINE Link].
Sequist LV, Yang JC, Yamamoto N, et al. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Jul 1. [QxMD MEDLINE Link].
Gilotrif (afatinib [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. January, 2018. Available at [Full Text].
Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug. 16 (8):897-907. [QxMD MEDLINE Link].
Lynch TJ, Bell DW, Sordella R. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20. 350(21):2129-39. [QxMD MEDLINE Link].
Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005 Oct 29-Nov 4. 366(9496):1527-37. [QxMD MEDLINE Link].
Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7. 110 (1):55-62. [QxMD MEDLINE Link]. [Full Text].
Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24. 362 (25):2380-8. [QxMD MEDLINE Link]. [Full Text].
Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3. 361(10):947-57. [QxMD MEDLINE Link].
Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker Analyses and Final Overall Survival Results From a Phase III, Randomized, Open-Label, First-Line Study of Gefitinib Versus Carboplatin/Paclitaxel in Clinically Selected Patients With Advanced Non-Small-Cell Lung Cancer in Asia (IPASS). J Clin Oncol. 2011 Jul 20. 29(21):2866-74. [QxMD MEDLINE Link].
Shepherd FA, Pereira J, Ciuleanu TE, et al. A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. J Clin Oncol. 2004. Vol 22, No 14S (July 15 Supplement):Abstract 7022.
Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14. 353(2):123-32. [QxMD MEDLINE Link].
Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug. 12(8):735-42. [QxMD MEDLINE Link].
Gridelli C, Ciardiello F, Gallo C, et al. First-Line Erlotinib Followed by Second-Line Cisplatin-Gemcitabine Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The TORCH Randomized Trial. J Clin Oncol. 2012 Aug 20. 30(24):3002-11. [QxMD MEDLINE Link].
Herbst RS, Ansari R, Bustin F, et al. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011 May 28. 377(9780):1846-54. [QxMD MEDLINE Link].
Hirsch FR, Kabbinavar F, Eisen T, et al. A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer. J Clin Oncol. 2011 Sep 10. 29(26):3567-73. [QxMD MEDLINE Link]. [Full Text].
Nakagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec. 20 (12):1655-1669. [QxMD MEDLINE Link].
Tagrisso (osimertinib) [package insert]. Wilmington, DE 19850: AstraZeneca Pharmaceuticals LP. December 2020. Available at [Full Text].
Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11. 378 (2):113-125. [QxMD MEDLINE Link]. [Full Text].
Wu YL, et al; ADAURA Investigators. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Oct 29. 383 (18):1711-1723. [QxMD MEDLINE Link].
Tsuboi M, Herbst RS, John T, and the, ADAURA Investigators. Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. N Engl J Med. 2023 Jun 4. [QxMD MEDLINE Link].
Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov. 18 (11):1454-1466. [QxMD MEDLINE Link].
Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, et al. Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. J Clin Oncol. 2018 Aug 1. 36 (22):2244-2250. [QxMD MEDLINE Link].
Pirker R, Szczesna A, von Pawel J, et al. FLEX: A randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2008. 26:1006s (Abstract).
Pirker R, Pereira JR, von Pawel J, et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol. 2012 Jan. 13(1):33-42. [QxMD MEDLINE Link].
FDA grants accelerated approval to amivantamab-vmjw for metastatic non-small cell lung cancer. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-amivantamab-vmjw-metastatic-non-small-cell-lung-cancer. May 21, 2021; Accessed: July 15, 2021.
Ramalingam SS, Zhou C, Kim TM, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic NSCLC (mNSCLC): additional results from platinum-pretreated patients (pts) and EXCLAIM cohort of phase 1/2 study (abstract 9014). J Clin Oncol. 2021. 39(suppl 15):[Full Text].
Rosa K. Takeda to Voluntarily Withdraw Mobocertinib for EGFR Exon 20 Insertion+ NSCLC. OncLive. Available at https://www.onclive.com/view/takeda-to-voluntarily-withdraw-mobocertinib-for-egfr-exon-20-insertion-nsclc. October 2, 2023; Accessed: October 11, 2023.
Enhertu (trastuzumab deruxtecan) [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc. August 2022. Available at [Full Text].
Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, et al. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 Jun 24. 384 (25):2371-2381. [QxMD MEDLINE Link].
Jänne PA, Riely GJ, Gadgeel SM, Heist RS, Ou SI, Pacheco JM, et al. Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS(G12C) Mutation. N Engl J Med. 2022 Jul 14. 387 (2):120-131. [QxMD MEDLINE Link].
Augtyro (repotrectinib) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. November 2023. Available at [Full Text].
Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20. 371 (21):1963-71. [QxMD MEDLINE Link]. [Full Text].
Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22. 379 (21):2040-2051. [QxMD MEDLINE Link].
de Boer RH, Arrieta O, Yang CH, et al. Vandetanib Plus Pemetrexed for the Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Phase III Trial. J Clin Oncol. 2011 Mar 10. 29(8):1067-74. [QxMD MEDLINE Link].
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14. 355(24):2542-50. [QxMD MEDLINE Link].
Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009 Mar 10. 27(8):1227-34. [QxMD MEDLINE Link].
Soria JC, Mauguen A, Reck M, et al. Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol. 2012 Nov 23. [QxMD MEDLINE Link].
Stark, Angela. FDA approves first biosimilar for the treatment of cancer. FDA News Release. 09/14/2017. Available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm576112.htm.
Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23. 384 (9944):665-73. [QxMD MEDLINE Link].
Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28. 363(18):1693-703. [QxMD MEDLINE Link]. [Full Text].
Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013 Jun 20. 368(25):2385-94. [QxMD MEDLINE Link].
Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, et al. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial. J Clin Oncol. 2017 May 5. JCO2016715904. [QxMD MEDLINE Link].
Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27. 370(13):1189-97. [QxMD MEDLINE Link]. [Full Text].
Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Mar 4. 389 (10072):917-929. [QxMD MEDLINE Link].
Cho BC, et al. ASCEND-8: A Randomized Phase 1 Study of Ceritinib, 450 mg or 600 mg, Taken with a Low-Fat Meal versus 750 mg in Fasted State in Patients with Anaplastic Lymphoma Kinase (ALK)-Rearranged Metastatic Non-Small Cell Lung Cancer (NSCLC). J Thorac Oncol. 2017 Sep. 12 (9):1357-1367. [QxMD MEDLINE Link]. [Full Text].
Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug 31. 377 (9):829-838. [QxMD MEDLINE Link]. [Full Text].
Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017 Jul 1. 390 (10089):29-39. [QxMD MEDLINE Link]. [Full Text].
Solomon BJ, Besse B, Bauer TM, Felip E, Soo RA, Camidge DR, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018 Nov 6. [QxMD MEDLINE Link].
FDA approves lorlatinib for metastatic ALK-positive NSCLC. FDA. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-lorlatinib-metastatic-alk-positive-nsclc. March 3, 2021; Accessed: March 4, 2021.
Reck M, Schenker M, Lee KH, Provencio M, Nishio M, Lesniewski-Kmak K, et al. Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial. Eur J Cancer. 2019 Jul. 116:137-147. [QxMD MEDLINE Link]. [Full Text].
Paz-Ares LG, Ramalingam SS, Ciuleanu TE, et al. First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. J Thorac Oncol. 2022 Feb. 17 (2):289-308. [QxMD MEDLINE Link]. [Full Text].
Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb. 22 (2):198-211. [QxMD MEDLINE Link]. [Full Text].
Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9. 373 (2):123-35. [QxMD MEDLINE Link]. [Full Text].
Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21. 372 (21):2018-28. [QxMD MEDLINE Link].
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Oct 8. [QxMD MEDLINE Link]. [Full Text].
Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 Apr 4. [QxMD MEDLINE Link].
Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016 Nov. 17 (11):1497-1508. [QxMD MEDLINE Link].
Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9. 387 (10027):1540-50. [QxMD MEDLINE Link].
Gandhi L, et al; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31. 378(22):2078-2092. [QxMD MEDLINE Link]. [Full Text].
Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30. 387 (10030):1837-46. [QxMD MEDLINE Link].
Barlesi F, Park K, Ciardiello F, von Pawel J, Gadgeel S, Hida T, et al. A randomized phase 3 study of atezolizumab (an engineered anti-PDL1 antibody) compared to docetaxel in patients with locally advanced or metastatic non-small cell lung cancer who have failed platinum therapy - "OAK". ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT02008227. January 9, 2019; Accessed: June 15, 2019.
Tecentriq (atezolizumab) [package insert]. South San Francisco, CA: Genentech, Inc. May 2020. Available at [Full Text].
Johnson ML, Cho BC, Luft A, and the, POSEIDON investigators. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2022 Nov 3. JCO2200975. [QxMD MEDLINE Link]. [Full Text].
Planchard D, Besse B, Groen HJM, Souquet PJ, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016 Jul. 17 (7):984-993. [QxMD MEDLINE Link]. [Full Text].
Retevmo (selpercatinib) [package insert]. Indianapolis, IN: Eli Lilly. 2020 May. Available at [Full Text].
Gavreto (pralsetinib) [package insert]. Cambridge, MA: Blueprint Medicines Corporation. September 2020. Available at [Full Text].
FDA Approves First Targeted Therapy to Treat Aggressive Form of Lung Cancer. U.S. Food & Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-aggressive-form-lung-cancer. May 6, 2020; Accessed: May 12, 2020.
FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. FDA. Available at https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-tepotinib-metastatic-non-small-cell-lung-cancer. February 3, 2021; Accessed: February 24, 2021.
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10. 375 (19):1823-1833. [QxMD MEDLINE Link]. [Full Text].
Berner F, Bomze D, Diem S, et al. Association of Checkpoint Inhibitor-Induced Toxic Effects With Shared Cancer and Tissue Antigens in Non-Small Cell Lung Cancer. JAMA Oncol. 2019 Apr 25. [QxMD MEDLINE Link]. [Full Text].
[Guideline] National Comprehensive Cancer Network. Management of Immunotherapy-Related Toxicities. NCCN. Available at https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. Version 4.2021 — September 27, 2021; Accessed: February 9, 2022.
[Guideline] Donington J, et al, for the Thoracic Oncology Network of the American College of Chest Physicians and the Workforce on Evidence-Based Surgery of the Society of Thoracic Surgeons. American College of Chest Physicians and Society of Thoracic Surgeons consensus statement for evaluation and management for high-risk patients with stage I non-small cell lung cancer. Chest. 2012 Dec. 142 (6):1620-1635. [QxMD MEDLINE Link]. [Full Text].
Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008 Jul 20. 26(21):3552-9. [QxMD MEDLINE Link].
Strauss GM, Herndon JE 2nd, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1. 26(31):5043-51. [QxMD MEDLINE Link]. [Full Text].
Gore EM, Bae K, Wong SJ, et al. Phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small-cell lung cancer: primary analysis of radiation therapy oncology group study RTOG 0214. J Clin Oncol. 2011 Jan 20. 29(3):272-8. [QxMD MEDLINE Link].
Sun A, Bae K, Gore EM, et al. Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis. J Clin Oncol. 2011 Jan 20. 29(3):279-86. [QxMD MEDLINE Link].
Lynch TJ, Patel T, Dreisbach L, et al. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010 Feb 20. 28(6):911-7. [QxMD MEDLINE Link].
Biesma B, Wymenga AN, Vincent A, et al. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study. Ann Oncol. 2011 Jul. 22(7):1520-7. [QxMD MEDLINE Link].
Raz DJ, Lanuti M, Gaissert HC, et al. Outcomes of patients with isolated adrenal metastasis from non-small cell lung carcinoma. Ann Thorac Surg. 2011 Nov. 92(5):1788-92; discussion 1793. [QxMD MEDLINE Link].
Ciuleanu T, Brodowicz T, Zielinski C, et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009 Oct 24. 374(9699):1432-40. [QxMD MEDLINE Link].
Belani CP, Brodowicz T, Ciuleanu TE, et al. Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): results from a randomised, double-blind, phase 3 study. Lancet Oncol. 2012 Mar. 13(3):292-9. [QxMD MEDLINE Link].
Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar. 13(3):247-55. [QxMD MEDLINE Link].
[Guideline] Hanna N, Johnson D, Temin S, Baker S Jr, Brahmer J, Ellis PM, et al. Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017 Aug 14. JCO2017746065. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Hanna NH, Schneider BJ, Temin S, Baker S Jr, Brahmer J, Ellis PM, et al. Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update. J Clin Oncol. 2020 May 10. 38 (14):1608-1632. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Hanna NH, Robinson AG, Temin S, Baker S Jr, Brahmer JR, Ellis PM, et al. Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Joint Guideline Update. J Clin Oncol. 2021 Feb 16. JCO2003570. [QxMD MEDLINE Link]. [Full Text].
Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999 Mar 4. 340(9):685-91. [QxMD MEDLINE Link].
Mallin R. Smoking cessation: integration of behavioral and drug therapies. Am Fam Physician. 2002 Mar 15. 65(6):1107-14. [QxMD MEDLINE Link].
Moysich KB, Menezes RJ, Ronsani A, et al. Regular aspirin use and lung cancer risk. BMC Cancer. 2002 Nov 26. 2:31. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Eberhardt WE, De Ruysscher D, Weder W, Le Péchoux C, De Leyn P, Hoffmann H, et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol. 2015 Aug. 26 (8):1573-88. [QxMD MEDLINE Link].
[Guideline] Kalemkerian GP, Narula N, Kennedy EB, Biermann WA, Donington J, Leighl NB, et al. Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Clin Oncol. 2018 Mar 20. 36 (9):911-919. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Rodrigues G, Choy H, Bradley J, Rosenzweig KE, Bogart J, Curran WJ Jr, et al. Adjuvant radiation therapy in locally advanced non-small cell lung cancer: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based clinical practice guideline. Pract Radiat Oncol. 2015 May-Jun. 5 (3):149-55. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Rodrigues G, Choy H, Bradley J, Rosenzweig KE, Bogart J, Curran WJ Jr, et al. Definitive radiation therapy in locally advanced non-small cell lung cancer: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based clinical practice guideline. Pract Radiat Oncol. 2015 May-Jun. 5 (3):141-8. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Bezjak A, Temin S, Franklin G, Giaccone G, Govindan R, Johnson ML, et al. Definitive and Adjuvant Radiotherapy in Locally Advanced Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. J Clin Oncol. 2015 Jun 20. 33 (18):2100-5. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Hendriks L E, Kerr K, Menis J, et al. on behalf of the ESMO Guidelines Committee. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. ESMO. Available at https://www.esmo.org/guidelines/guidelines-by-topic/lung-and-chest-tumours/oncogene-addicted-metastatic-non-small-cell-lung-cancer. January 23, 2023; Accessed: February 22, 2023.
[Guideline] Schneider BJ, Ismaila N, Aerts J, et al. Lung Cancer Surveillance After Definitive Curative-Intent Therapy. American Society of Clinical Oncology. Available at https://old-prod.asco.org/practice-patients/guidelines/thoracic-cancer#/142246. December 12, 2019; Accessed: February 20, 2023.
Planchard D, Kim TM, Mazieres J, Quoix E, Riely G, Barlesi F, et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 May. 17 (5):642-50. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Non–small cell lung cancer. Symptoms and signs of lung cancer.
Non–small cell lung cancer. Diagnostic approach for possible lung cancer.
Staging workup for non–small cell lung cancer.
Treatment recommendations and future research directions in the management of non–small cell lung cancer.
Non–small cell lung cancer. Performance status scales for patients with cancer.
Non–small cell lung cancer. Prognostic factors for lung cancer.
Non–small cell lung cancer. Bronchoscopy. A large central lesion was diagnosed as non–small cell carcinoma.
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.
Non–small cell lung cancer. Left upper collapse is almost always secondary to endobronchial bronchogenic carcinoma.
Non–small cell lung cancer. Complete left lung collapse secondary to bronchogenic carcinoma of left mainstem bronchus.
Non–small cell lung cancer. A cavitating right lower lobe squamous cell carcinoma.
Non–small cell lung cancer. CT scan shows cavitation and air-fluid level.
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.
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.
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.
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.
Lung squamous carcinoma 4x: low power magnification of moderately differentiated squamous cell carcinoma showing irregular nests of tumor cells with focal areas of keratinization (pink-orange areas).
Lung squamous carcinoma 20x: higher power magnification of moderately differentiated squamous cell carcinoma showing focal areas of keratinization (pink-orange areas) just to the right of center.
Lung adenocarcinoma 4x: low power magnification of moderately differentiated adenocarcinoma showing rounded nests of pale staining tumor cells with gland lumina within some of the clusters.

of 19

Author

Winston W Tan, MD, FACP Associate Professor of Medicine, Mayo Medical School; Consultant and Person-in-Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic Jacksonville; Vice Chairman, Division of Hematology/Oncology Education, Chair, Cancer Survivorship Program, Associate Chair, Department of Medicine Faculty Development, Mayo Clinic Florida; Vice President, Florida Society of Clinical Oncology

Winston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Philippine Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Syed Huq, MD Fellow, Division of Hematology-Oncology, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Ellis Fischel Cancer Center

Syed Huq, MD is a member of the following medical societies: American Medical Informatics Association, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Nagla Abdel Karim, MD, PhD Director of Early Therapeutics, Inova Schar Cancer Institute; Professor of Medicine, University of Virginia School of Medicine

Nagla Abdel Karim, MD, PhD is a member of the following medical societies: American Medical Association, American Society of Clinical Oncology, Egyptian American Medical Association, Egyptian Cancer Society, International Association for the Study of Lung Cancer

Disclosure: Nothing to disclose.

Acknowledgements

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