Background
Lung cancer was a rare entity in the early 1900s but has since become far more prevalent. The prevalence of lung cancer is second only to that of prostate cancer in men and breast cancer in women. By the end of the 1900s, lung cancer had become the leading cause of preventable death in the United States,[1] and recently, it surpassed heart disease as the leading cause of smoking-related mortality.
Lung cancers are generally divided into 2 main categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of all lung cancers. NSCLC is divided further into adenocarcinoma, squamous cell carcinoma (SCC), and large cell carcinoma histologies. (See Pathophysiology.)
Lung cancer is the leading cause of cancer-related mortality in both men and women not only in the United States but also throughout the world. In 2006, the disease caused more than 158,000 deaths in the United States—more than colorectal, breast, and prostate cancers combined.[2] The type of lung cancer in the United States, as well as in many other countries, have also changed in the past few decades: the frequency of adenocarcinoma has risen, and that of SCC has declined. (See Epidemiology.)
Most lung carcinomas are diagnosed at an advanced stage, conferring a poor prognosis. The need to diagnose lung cancer at an early and potentially curable stage is thus obvious. (See Prognosis.) In addition, most patients who develop lung cancer have been smokers and have smoking-related damage to the heart and lungs, making aggressive surgical or multimodality therapies less viable options.
Lung cancer is often insidious, and it may produce no symptoms until the disease is well advanced. Approximately 7-10% of patients with lung cancer are asymptomatic, and their cancers are diagnosed incidentally after a chest radiograph performed for other reasons. Systemic findings may include unexplained weight loss and low-grade fever. Numerous signs may be associated with NSCLC. (See Clinical Presentation.)
Because of the importance of stage on 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. (See Workup.)
Treatment primarily involves surgery, chemotherapy, or radiation therapy. Because most lung cancers cannot be cured with currently available therapeutic modalities, the appropriate application of skilled palliative care is an important part of the treatment of patients with NSCLC. (See Treatment and Management.)
Go to Small Cell Lung Cancer for complete information on this topic.
Pathophysiology
Both exposure (environmental or occupational) to particular agents and an individual’s susceptibility to these agents are thought to contribute to one’s risk of developing lung cancer. In the United States, active smoking is responsible for 90% of lung cancer cases. Occupational exposures to carcinogens account for approximately 9-15% of lung cancer cases.
Exposure to carcinogens
Tobacco smoke contains more than 300 harmful substances with at least 40 known potent carcinogens. Poly-aromatic hydrocarbons and the nitrosamine-NNK are known to cause DNA damage by forming DNA adducts in animal models. Benzo-A-pyrine also appears to induce molecular signaling such as AKT, as well as inducing mutations in p53 and other tumor suppressor genes.
The most common occupational risk factor for lung cancer is exposure to asbestos. Studies have shown radon exposure to be associated with 10% of lung cancer cases, while outdoor air pollution accounts for perhaps 1-2%.[3] In addition, preexisting nonmalignant lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and tuberculosis have all been shown to be associated with increased lung cancer rates.
The current multiple hit theory suggests that a series of toxic cellular insults disrupts orderly genetic reproduction. Symptoms ultimately develop from the uncontrolled disorganized growth that interferes with local or distant anatomy or physiologic processes.[3]
A study by Ito et al assessed the shift in histologic types of lung cancer in Japan and the United States in relation to the shift from nonfiltered to filtered cigarettes.[4] The study determined that the shift in cigarette types only altered the most frequent type of lung cancer, shifting from SCC to adenocarcinoma.
Genetic susceptibility
Recently, advanced molecular techniques have identified amplification of oncogenes and inactivation of tumor suppressor genes in NSCLC. The most important abnormalities detected are mutations involving the ras family of oncogenes. The ras oncogene family has 3 members: H-ras, K-ras, and N-ras. These genes encode a protein on the inner surface of the cell membrane with GTPase activity and may be involved in signal transduction.
Studies performed on mice suggest the involvement of ras mutations in the molecular pathogenesis of NSCLC. Studies in humans suggest that ras activation contributes to tumor progression in persons with lung cancer. The ras gene mutations occur almost exclusively in adenocarcinoma and are found in 30% of such cases. These mutations were not identified in adenocarcinomas that developed in persons who do not smoke. The K-ras mutation appears to be an independent prognostic factor.
Studies are ongoing to develop management plans according to the presence or absence of ras gene mutations.
Other molecular abnormalities found in NSCLC include mutations in c-myc and c-raf among oncogenes and retinoblastoma (Rb) and p53 among tumor suppressor genes.
Classification of lung cancer
Lung cancers are generally divided into 2 main categories: SCLC and NSCLC. NSCLC accounts for approximately 85% of all lung cancers. NSCLC is divided further into adenocarcinoma, SCC, and large cell carcinoma histologies. All share similar treatment approaches and prognoses but have distinct histologic and clinical characteristics.
Adenocarcinoma, arising from the bronchial mucosal glands, is the most frequent non-small cell lung cancer in the United States, representing 35-40% of all lung cancers. It usually occurs in a peripheral location within the lung. Adenocarcinoma is the most common histologic subtype, and may manifest as a “scar carcinoma.” This is the subtype observed most commonly in persons who do not smoke. This type may manifest as multifocal tumors in a bronchoalveolar form.
Bronchoalveolar carcinoma is a distinct subtype of adenocarcinoma with a classic manifestation as an interstitial lung disease on chest radiograph. Bronchoalveolar carcinoma arises from type II pneumocytes and grows along alveolar septa. This subtype may manifest as a solitary peripheral nodule, multifocal disease, or a rapidly progressing pneumonic form. A characteristic finding in persons with advanced disease is voluminous watery sputum.
SCC accounts for 25-30% of all lung cancers. Whereas adenocarcinoma tumors are peripheral in origin, SCC is found in the central parts of the lung (see the image below). The classic manifestation is a cavitary lesion in a proximal bronchus. This type is characterized histologically by the presence of keratin pearls and can be detected with cytologic studies because it has a tendency to exfoliate. It is the type most often associated with hypercalcemia.
Non–small cell lung cancer. A cavitating right lower lobe squamous cell carcinoma. Large cell carcinoma accounts for 10-15% of lung cancers, typically manifesting as a large peripheral mass on chest radiograph; it appears to be decreasing in incidence because of improved diagnostic techniques.[5] Histologically, this type has sheets of highly atypical cells with focal necrosis, with no evidence of keratinization (typical of SCC) or gland formation (typical of adenocarcinomas).
Improved histopathologic procedures and the use of electron microscopy allow for most large cell tumors to be identified as undifferentiated adenocarcinomas and less frequently as SCCs. Large cell undifferentiated cancers have the same prognosis as do adenocarcinomas and are combined with them in clinical trials.
SCLC is also divided into several types, including pure small cell, mixed small cell, and combined small cell. SCLC is usually more aggressive than NSCLC and presents as a central lesion with hilar and mediastinal invasion along with regional adenopathy. It is not uncommon for patients with SCLC to already have metastatic disease at initial diagnosis. The most common sites of metastasis of lung cancer are the bones, liver, adrenal glands, pericardium, brain, and spinal cord.[6]
Etiology
Causes of lung cancer include the following:
- Smoking (78% in men, 90% in women)
- Asbestos exposure
- Radon exposure
- Halogen ether exposure
- Chronic interstitial pneumonitis
- Inorganic arsenic exposure
- Radioisotope exposure, ionizing radiation
- Atmospheric pollution
- Chromium, nickel exposure
- Vinyl chloride
Unlike many other malignancies, whose causes are largely unknown, lung cancer is known to be caused by tobacco smoking in as many as 90% of patients.
Because not all smokers develop lung cancer and not all lung cancer patients have a history of smoking, other factors (eg, genetic susceptibility see Pathophysiology, arsenic exposure, radiation exposure, and other environmental carcinogens[7] ) also play a causative role, either independently or in conjunction with smoking. Genetic factors probably contribute in all populations, but the contribution of other factors is population-specific.
A study by Bagnardi et al determined that alcohol is not an independent factor in the etiology of lung cancer.[8]
Smoking
Smoking prevalence in the United States has gradually declined over last 4 decades. In 2008, there were an estimated 46 million active smokers in the United States, with highest prevalence among Native Americans and lowest prevalence among Hispanic and Asian Americans. Overall, the prevalence was highest in adults aged 25 years or older with low educational attainment.[9] Worldwide, the incidence of smoking in developing countries is on the rise, with almost 320 million smokers in China alone.
The development of lung cancer is directly related to number of cigarettes smoked, length of smoking history, and the tar and nicotine content of the cigarettes. Risk is highest among current smokers and lowest among nonsmokers. A large trial showed that persistent smokers had a 16-fold elevated lung cancer risk, which was further doubled in those who started smoking when younger than 16 years.[10] The age-adjusted incidence rates range from 4.8-20.8 per 100,000 among nonsmokers to 140-362 among active smokers.
Although tobacco smoking is the major cause of lung cancer, it is now believed that males and females may differ in their susceptibility to carcinogenic effects of tobacco smoke. This difference may be due to differences in DNA repair mechanisms. Although still considered controversial, it is well known that women are more likely to develop adenocarcinomas and that, stage for stage, women live longer. In addition, differences in response to certain biologic therapies (eg, epidermal growth factor [EGF] inhibitors) and antiangiogenic agents have been observed between sexes.
The risk of lung cancer declines slowly after smoking cessation. Long-term follow-up studies show that the relative risk remains high in the first 10 years after cessation and gradually declines to 2-fold approximately 30 years after cessation. This long-term risk explains the development of almost 50% of United States lung cancer cases in past smokers.
A minority of lung cancers develop in those who have never smoked. These lung cancers are genetically distinct from smoking-related NSCLC, and this distinction may have therapeutic implications. The observed genetic differences include a lower frequency of K-ras and a higher frequency of mutations in EGF receptor and likely are responsible for the higher efficacy of EGF receptor inhibitors in this patient population.
Cigarette smoke containing the carcinogenic N -nitrosamines and aromatic polycyclic hydrocarbons can be inhaled passively by nonsmokers (secondhand smoke); urinary levels of these carcinogens are 1-5% of those found in active smokers. As many as 25% of the lung cancers in persons who do not smoke are believed to be caused by secondhand smoke.[11]
The US Environmental Protection Agency has recognized passive smoking as a potential carcinogen. About 3000 cases of lung cancer appear to be related to passive exposure. This awareness has led to local ordinances restricting smoking in enclosed public places, including restaurants and government buildings.
Asbestos exposure
The silicate type of asbestos fiber is an important carcinogen. Asbestos exposure has been shown to be strongly associated with the causation of lung cancer, malignant pleural mesothelioma, and pulmonary fibrosis. It increases the risk of developing lung cancer by as much as 5 times.
Tobacco smoke and asbestos exposure act synergistically, and the risk of developing lung cancer for persons who currently smoke tobacco and have a history of asbestos exposure approaches 80-90 times that of control populations.
Radon exposure
Radon is an inert gas produced as a result of uranium decay. Radon exposure is a well-established risk factor for lung cancer in uranium miners. Approximately 2-3% of lung cancers annually are estimated to be caused by radon exposure. Household exposure to radon, however, has never been clearly shown to cause lung cancer.
The US National Research Council’s report of the Sixth Committee on Biological Effects of Ionizing Radiation has estimated that radon exposure causes 2100 new lung cancers each year, while it contributes to lung cancer causation in approximately 9100 persons who smoke.
HIV infection
A recent report from the State of Texas Health Department suggested a 6.5-fold increase in lung cancer in patients infected with HIV.[12] Other large series do not support an increased prevalence of lung cancers in subjects with HIV infection.[13]
Other environmental agents
Beryllium, nickel, copper, chromium, and cadmium have all been implicated in causing lung cancer.
Dietary fiber and vegetables have been suggested as protective from lung cancer. Although diets rich in fruits and vegetables appear to be associated with lower rates of lung cancer, trials of supplemental beta-carotene, alone or in combination with vitamin E or retinyl palmitate, in persons at high risk for lung cancer found that this supplementation actually increased the incidence of lung cancers.
Epidemiology
United States statistics
In the United States, lung cancer is the second most common cancer in women, and it is second only to prostate cancer in men. In 2008, 215,000 lung cancer cases occurred and 161,000 deaths were expected.[14] The American Cancer Society projected that 219,440 cancers of the lung and bronchus would be diagnosed in the United States in 2009, with 116,090 cases in males and 103,350 cases in females.[15]
From 1991-2005, the incidence of lung cancer in men has decreased each year by 1.8%; however, the incidence has increased by 0.5% per year for women over that same period. Lung cancer death rates for US women are among the highest in the world. Although in the United States death rates among males are higher than among females, rates for US men are still lower than rates among men in several other countries.[16]
These trends in US death rates parallel trends in smoking prevalence over the past 50 years. Overall, the prevalence of smoking is approximately 21.6% in the United States and has remained unchanged over the past 15 years.
International statistics
Lung cancer is the most commonly diagnosed cancer worldwide,[17] and its incidence continues to grow. In 2007, an estimated 1.5 million new cases of lung cancer were diagnosed globally, accounting for approximately 12% of the global cancer burden. An estimated 1.35 million lung cancer deaths occurred in 2007. Among all cancers, lung cancer now has the highest mortality rate in most countries, with industrialized regions such as North America and Europe having the highest rates.
Several differences exist in lung cancer incidence according to geographic area. The highest incidence occurs in the United Kingdom and Poland (>100 cases per 100,000 population per year). The lowest incidence rate occurs in Senegal and Nigeria (< 1 case per 100,000 population per year). With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China and India.
Generally, global lung cancer trends have followed the trends in smoking, with a lag time of several decades. Lung cancer incidence has been declining in several countries, including the United States, Canada, the United Kingdom, and Australia, following the decreasing rate of smoking. Lung cancer incidence among women, however, continues to increase in several parts of the globe, although it has begun to plateau in the United States. Notably, despite a very low rate of smoking, Chinese females have a higher incidence of lung cancer than European females.
Age distribution for NSCLC
Lung cancer occurs predominately in persons aged 50-70 years. The probability of developing lung cancer remains very low until age 39 years in both sexes. It then slowly starts to rise and peaks among those older than 70 years. The risk of developing lung cancer remains higher among men in all age groups after age 40 years.
Sex distribution for NSCLC
Lung cancer is more common in men than in women. In the United States, Northern Europe, and Western Europe, the prevalence of lung cancer has been decreasing in men. In Eastern and Southern European countries, the incidence of lung cancer has been rapidly increasing. Most Western countries have encountered a disturbing trend of increasing prevalence in women and younger patients. Women have a higher incidence of localized disease at presentation and of adenocarcinoma and typically are younger when they present with symptoms.
In the United States, the probability of developing lung cancer remains equal in both sexes until age 39 years (0.03% or approximately 1 in 3,000). It then starts to increase among men compared with women, reaching a maximum in those older than 70 years (6.74% vs 4.61% or 1 in 15 vs 1 in 22, among men and women respectively).
Prevalence of NSCLC by race
Whereas lung cancer incidence rates are similar among African American and white women, lung cancer occurrence is approximately 45% higher among African American men than among white men.[16] This increased incidence has been attributed to differences in smoking habits; however, recent evidence suggests a slight difference in susceptibility.
From 1995-2001, the 5-year relative survival rate was 13% lower in African Americans compared with white individuals.[16] This racial gap persisted within each stage at diagnosis for both men and women.
Trends in 5-year survival rates in lung cancer from 1975-2003 revealed that while modest gains occurred in 5-year survival rates among whites, survival rates remained unchanged in the African American population. Current 5-year survival rates are estimated to be 16% among whites and 13% among non-whites.
Prognosis
Lung cancer is highly lethal. Data compiled by the American Cancer Society show lung cancer to be, by far, the most common fatal cancer in men (31%) and in women (26%). The American Cancer Society projected that deaths related to lung cancer would total 159,390 (88,900 in males and 70,490 in females) in the United States in 2009, accounting for 28% of all cancer-related deaths.[2] Worldwide, an estimated 1,351,000 deaths due to lung cancer occurred in 2007 (975,000 in men and 376,000 in females).
In Europe, the 5-year overall survival rate is 8%, similar to that of the developing world. The highest recorded 5-year patient survival rates are observed in the United States. US data collected from 1995-2001 indicate that the 5-year relative survival rate for lung cancer was 15.7%, reflecting a steady but slow improvement from 12.5% in 1975.[16] However, the 5-year relative survival rate varies markedly, depending on how advanced the disease is at diagnosis:
- 49% for local disease
- 16% for regional disease
- 2% for distant stage disease
Estimated 5-year survival rates for specific stages of disease are as follows:
- Stage IA - 75%
- Stage IB - 55%
- Stage IIA - 50%
- Stage IIB - 40%
- Stage IIIA - 10-35%
- Stage IIIB - Less than 5%
- Stage IV - Less than 5%
Prognostic factors for NSCLC are summarized in the image below.
Non–small cell lung cancer. Prognostic factors for lung cancer. A retrospective Surveillance, Epidemiology, and End Results (SEER) data analysis suggests that the number of nodes with cancer may be predictive of survival.[18]
Patients with in situ and stage I lung cancer may respond to surgery. Their prognosis is far better than that of patients with more advanced disease. In patients with radiologically occult lung neoplasms, the 5-year survival rate is 24-26%; in those with abnormal chest radiographic findings, the rate is 12%. If the cancer is nonresectable, the prognosis is poor, with a mean survival rate of 8-14 months.
Mostertz et al found that in some patient populations, the oncogenic pathway activation profile of the tumor can have prognostic significance.[19] Retrospective analysis of 787 patients with predominantly early-stage NSCLC, using gene expression profiling, showed the following:
- In patients younger than 70 years, high-risk patients, with the shortest recurrence-free survival, demonstrated increased activation of the Src and tumor necrosis factor (TNF) pathways.
- In women, high-risk patients demonstrated increased activation of the invasiveness and signal transducer and activator of transcription 3 (STAT3) pathways.
- Multivariate analyses confirmed the independent clinical relevance of the pathway-based subphenotypes in women and patients younger than 70 years.
A meta-analysis by Parsons et al suggests that smoking cessation after diagnosis of early-stage lung cancer may improve prognosis, probably by reducing cancer progression. Life table modelling on the basis of data from 9 studies gave an estimated 5-year survival rate of 33% in 65-year-old patients with early-stage NSCLC who continued to smoke compared with 70% in those who quit smoking.[20]
Secondary analyses of the Women’s Health Initiative (WHI) randomized, placebo-controlled trial, performed on patients taking daily conjugated equine estrogen (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg), found that women diagnosed with NSCLC who take estrogen-progestin had an increased mortality compared with women who have NSCLC and do not take hormone therapy.[21]
The analyses included 16,608 multiethnic postmenopausal women aged 50-79 years and assessed the association of hormone therapy on lung cancer incidence and mortality. Confirmation of lung cancers was completed by medical record review. Results showed that the use of CEE plus MPA for more than 5 years increased a woman’s risk for NSCLC. This area deserves more attention and study to determine the risks and benefits of hormone therapy for postmenopausal women who smoke.
A review of 8 trials by Rothwell et al found that allocation to aspirin reduced death caused by cancer. Individual patient data were available from 7 of the 8 trials. Benefit was apparent after 5 years of follow-up. The 20-year risk of cancer death was also lower in the aspirin group for all solid cancers. A latent period of 5 years was observed before risk of death was decreased for esophageal, pancreatic, brain, and lung cancers. A more delayed latent period was observed for stomach, colorectal, and prostate cancer.
Benefit was only seen for adenocarcinomas in lung and esophageal cancers. The overall effect on 20-year risk of cancer death was greatest for adenocarcinomas.[22]
A study by Bouchardy et al found that patients who had received antiestrogen treatment for breast cancer had a lower lung cancer mortality rate.[23]
Patient Education
Advise patients that, among all measures, smoking cessation is most important. Smoking cessation by others who share the patient’s home, car, or both is also important. According to published data, the use of nicotine alternatives (eg, gum, patch, spray) instead of cigarettes reduces the incidence of lung cancer. However, it does not affect the incidence of ischemic heart disease.
Advise the patient to avoid asbestos exposure. Consider prophylactic administration of retinoids, such as beta-carotene.
For patient education information, see the Cancer and Tumors Center, as well as Lung Cancer, Bronchoscopy, and Understanding Lung Cancer Medications.
Rosen G. A History of Public Health: Expanded Edition. Baltimore, MD.: The Johns Hopkins University Press; 1993.
American Cancer Society. Cancer Facts and Figures 2009. American Cancer Society. Available at http://ww2.cancer.org/downloads/STT/500809web.pdf. Accessed February 9, 2011.
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, Koestler DC, Ombao H, Fulton J, 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. Apr 15 2011;128(8):1918-28. [Medline].
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. May 2008;83(5):584-94. [Medline]. [Full Text].
Sher T, Dy GK, Adjei AA. Small cell lung cancer. Mayo Clin Proc. Mar 2008;83(3):355-67. [Medline].
Beckett WS. Epidemiology and etiology of lung cancer. Clin Chest Med. Mar 1993;14(1):1-15. [Medline].
Bagnardi V, Rota M, Botteri E, et al. Alcohol consumption and lung cancer risk in never smokers: a meta-analysis. Ann Oncol. Dec 2011;22(12):2631-9. [Medline].
Cigarette smoking among adults and trends in smoking cessation - United States, 2008. MMWR Morb Mortal Wkly Rep. Nov 13 2009;58(44):1227-32. [Medline]. [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.
Zhong L, Goldberg MS, Parent ME, Hanley JA. Exposure to environmental tobacco smoke and the risk of lung cancer: a meta-analysis. Lung Cancer. Jan 2000;27(1):3-18. [Medline].
Parker MS, Leveno DM, Campbell TJ, et al. AIDS-related bronchogenic carcinoma: fact or fiction?. Chest. Jan 1998;113(1):154-61. [Medline].
Tirelli U, Spina M, Sandri S, et al. Lung carcinoma in 36 patients with human immunodeficiency virus infection. The Italian Cooperative Group on AIDS and Tumors. Cancer. Feb 1 2000;88(3):563-9. [Medline].
Dubey S, Powell CA. Update in lung cancer 2008. Am J Respir Crit Care Med. May 15 2009;179(10):860-8. [Medline]. [Full Text].
American Cancer Society. Statistics for 2006. Available at http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2006. Accessed January 11, 2011.
Ries L, Eisner M, Kosary C. Cancer statistics review, 1975-2002. National Cancer Institute.; 2005.
World Health Organization, International Agency for Research on Cancer. World cancer report. Lyon, France: 2003.
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. Aug 2011;140(2):433-40. [Medline]. [Full Text].
Mostertz W, Stevenson M, Acharya C, Chan I, Walters K, Lamlertthon W, et al. Age- and sex-specific genomic profiles in non-small cell lung cancer. JAMA. Feb 10 2010;303(6):535-43. [Medline].
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. Jan 21 2010;340:b5569. [Medline]. [Full Text].
Chlebowski RT, Schwartz WH, Anderson GL, Stefanick ML, Manson JE, Chien JW, et al. Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women's Health Initiative randomized clinical trial2009 American Society of Clinical Oncology (ASCO) Annual Meeting. J Clin Oncol. 2009;27(suppl; abstr CRA1500):18s. [Full Text].
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].
Bouchardy C, Benhamou S, Schaffar R, Verkooijen HM, Fioretta G, Schubert H, et al. Lung cancer mortality risk among breast cancer patients treated with anti-estrogens. Cancer. Mar 15 2011;117(6):1288-95. [Medline].
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. Apr 2005;60(4):314-9. [Medline]. [Full Text].
Spiro SG, Gould MK, Colice GL. Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest. Sep 2007;132(3 Suppl):149S-160S. [Medline].
Patel AM, Davila DG, Peters SG. Paraneoplastic syndromes associated with lung cancer. Mayo Clin Proc. Mar 1993;68(3):278-87. [Medline].
[Guideline] Alberts WM. Diagnosis and management of lung cancer executive summary: ACCP evidence-based clinical practice guidelines (2nd Edition). Chest. Sep 2007;132(3 Suppl):1S-19S. [Medline]. [Full Text].
[Guideline] Spiro SG, Gould MK, Colice GL. Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest. Sep 2007;132(3 Suppl):149S-160S. [Medline]. [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. Sep 2011;92(3):1024-30; discussion 1030. [Medline].
Annema JT, van Meerbeeck JP, Rintoul RC, Dooms C, Deschepper E, Dekkers OM, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA. Nov 24 2010;304(20):2245-52. [Medline].
Hofman V, Bonnetaud C, Ilie MI, Vielh P, Vignaud JM, Fléjou JF, 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. Feb 15 2011;17(4):827-35. [Medline].
Wicha MS, Hayes DF. Circulating tumor cells: not all detected cells are bad and not all bad cells are detected. J Clin Oncol. Apr 20 2011;29(12):1508-11. [Medline].
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. Feb 3 2011;[Medline].
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. Nov 2 2011;306(17):1865-73. [Medline].
Erkiliç S, Ozsaraç C, Küllü S. Sputum cytology for the diagnosis of lung cancer. Comparison of smear and modified cell block methods. Acta Cytol. Nov-Dec 2003;47(6):1023-7. [Medline].
Billah S, Stewart J, Staerkel G, et al. EGFR and KRAS mutations in lung carcinoma: molecular testing by using cytology specimens. Cancer Cytopathol. Apr 25 2011;119(2):111-7. [Medline].
Arroliga AC, Matthay RA. The role of bronchoscopy in lung cancer. Clin Chest Med. Mar 1993;14(1):87-98. [Medline].
Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer: summary of published evidence. Chest. Jan 2003;123(1 Suppl):115S-128S. [Medline].
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. Aug 1 2011;104(2):162-8. [Medline].
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. Apr 2012;198(4):793-9. [Medline].
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Lung Cancer Screening, v 1.2012. Available at http://www.nccn.org. Accessed 10/28/11.
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. Feb 21 2001;285(7):914-24. [Medline].
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. Oct 1997;112(4 Suppl):239S-241S. [Medline].
American Joint Committee on Cancer. Lung. In: Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, eds. AJCC Cancer Staging Handbook. 7th ed. Chicago, Ill: Springer; 2010:Chapter 25.
Tintinalli JE. Emergency complications of malignancy. In: Emergency Medicine: A Comprehensive Guide. 2004:1319-1368.
Halfdanarson TR, Hogan WJ, Moynihan TJ. Oncologic emergencies: diagnosis and treatment. Mayo Clin Proc. Jun 2006;81(6):835-48. [Medline].
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. Jun 2011;141(6):1384-91. [Medline].
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. Jul 2007;32(1):20-8. [Medline].
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. Mar 2011;139(3):491-6. [Medline].
Clinical Trials PDQ. Phase III Randomized Study of Lobectomy Versus Sublobar Resection in Patients With Small Peripheral Stage IA Non-Small Cell Lung Cancer. Available at http://www.cancer.gov/clinicaltrials/CALGB-140503. Accessed February 9, 2011.
Phase III Randomized Study of Lobectomy Versus Sublobar Resection in Patients With Small Peripheral Stage IA Non-Small Cell Lung Cancer. National Cancer Institute. Available at http://www.cancer.gov/clinicaltrials/CALGB-140503. Accessed February 9, 2011.
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. Nov 2011;92(5):1819-23; discussion 1824-5. [Medline].
Cattaneo SM, Park BJ, Wilton AS, Seshan VE, Bains MS, Downey RJ, et al. Use of video-assisted thoracic surgery for lobectomy in the elderly results in fewer complications. Ann Thorac Surg. Jan 2008;85(1):231-5; discussion 235-6. [Medline].
National Comprehensive Cancer Network. NSCLC Practice Guidelines, v 2.2009. Available at www.nccn.org. Accessed May 2009.
Swanson SJ, Herndon JE 2nd, D'Amico TA, Demmy TL, McKenna RJ Jr, Green MR, et al. Video-assisted thoracic surgery lobectomy: report of CALGB 39802--a prospective, multi-institution feasibility study. J Clin Oncol. Nov 1 2007;25(31):4993-7. [Medline].
Allen MS, Darling GE, et al. Number of lymph nodes harvested from a mediastinal lymphadenectomy: Results of the randomized, prospective ACOSOG ZOO30 trial ACOSOG ZOO30 Study Group ASCO Meeting Abstracts. Jun 20 2007;7555.
Allen JW, Farooq A, O'Brien TF, Osarogiagbon RU. Quality of surgical resection for nonsmall cell lung cancer in a US metropolitan area. Cancer. Jan 1 2011;117(1):134-42. [Medline].
Yun YH, Kim YA, Min YH, Chang YJ, Lee J, Kim MS, et al. Health-Related Quality of Life in Disease-Free Survivors of Surgically Treated Lung Cancer Compared With the General Population. Ann Surg. Mar 30 2012;[Medline].
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. Aug 2001;56(8):628-38. [Medline].
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. May 1 2011;80(1):133-41. [Medline].
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. [Medline].
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. Jan 10 2011;[Medline].
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. Jul 2007;2(7 Suppl 3):S94-100. [Medline].
Grills IS, Mangona VS, Welsh R, Chmielewski G, McInerney E, Martin S, et al. Outcomes after stereotactic lung radiotherapy or wedge resection for stage I non-small-cell lung cancer. J Clin Oncol. Feb 20 2010;28(6):928-35. [Medline].
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. Jul 2008;9(7):621-8. [Medline].
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. Jul 25 1998;352(9124):257-63. [Medline].
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. Jan 1993;105(1):97-104; discussion 104-6. [Medline].
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. Jul 14 2011;343:d4013. [Medline]. [Full Text].
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. May 2011;99(2):155-60. [Medline].
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. [Medline].
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. [Medline].
[Best Evidence] 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. Oct 1 2008;26(28):4617-25. [Medline].
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. Sep 1994;106(3):861-5. [Medline].
Delbaldo C, Michiels S, Syz N, Soria JC, Le Chevalier T, Pignon JP. Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA. Jul 28 2004;292(4):470-84. [Medline].
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. Jul 1991;9(7):1157-62. [Medline].
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. Jan 2008;59(1):1-11. [Medline].
Le Chevalier T, Scagliotti G, Natale R, Danson S, Rosell R, Stahel 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. Jan 2005;47(1):69-80. [Medline].
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. Sep 17 2011;378(9796):1079-88. [Medline].
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. Nov 2011;22(11):2448-55. [Medline].
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. Dec 2011;47(18):2691-7. [Medline].
[Best Evidence] Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, 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. Jul 20 2008;26(21):3543-51. [Medline].
[Best Evidence] Fidias PM, Dakhil SR, Lyss AP, Loesch DM, Waterhouse DM, 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. Feb 1 2009;27(4):591-8. [Medline].
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. May 1 2004;22(9):1589-97. [Medline].
[Best Evidence] 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. Sep 10 2009;27(26):4254-9. [Medline].
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. Aug 19 2010;363(8):733-42. [Medline].
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. Oct 4 1990;323(14):940-5. [Medline].
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. Mar 20 1991;83(6):417-23. [Medline].
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. Aug 1995;13(8):1880-92. [Medline].
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. Feb 20 1992;326(8):524-30. [Medline].
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, Scott C, Travis P, Haluschak J, 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. Sep 1 2005;23(25):5883-91. [Medline].
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. Jul 1996;14(7):2054-60. [Medline].
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. Aug 1995;13(8):1860-70. [Medline].
[Best Evidence] Hanna N, Neubauer M, Yiannoutsos C, McGarry R, Arseneau J, Ansari R, 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. Dec 10 2008;26(35):5755-60. [Medline].
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. Oct 5 2011;103(19):1452-60. [Medline]. [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. Apr 2004;44(1):89-97. [Medline].
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. Jun 2011;141(6):1392-7. [Medline].
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. May 20 2004;350(21):2129-39. [Medline].
Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, 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. Oct 29-Nov 4 2005;366(9496):1527-37. [Medline].
[Best Evidence] Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. Sep 3 2009;361(10):947-57. [Medline].
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. Jul 20 2011;29(21):2866-74. [Medline].
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, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. Jul 14 2005;353(2):123-32. [Medline].
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. Aug 2011;12(8):735-42. [Medline].
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. May 28 2011;377(9780):1846-54. [Medline].
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. Sep 10 2011;29(26):3567-73. [Medline]. [Full Text].
Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. Sep 3 2009;361(10):958-67. [Medline].
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).
de Boer RH, Arrieta O, Yang CH, Gottfried M, Chan V, Raats J, 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. Mar 10 2011;29(8):1067-74. [Medline].
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. Jan 2012;13(1):33-42. [Medline].
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. Dec 14 2006;355(24):2542-50. [Medline].
[Best Evidence] Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, 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. Mar 10 2009;27(8):1227-34. [Medline].
[Best Evidence] Karp DD, Paz-Ares LG, Novello S, Haluska P, Garland L, Cardenal F, et al. Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer. J Clin Oncol. May 20 2009;27(15):2516-22. [Medline].
Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. Oct 28 2010;363(18):1693-703. [Medline]. [Full Text].
[Best Evidence] Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. Jul 20 2008;26(21):3552-9. [Medline].
[Best Evidence] Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, 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. Nov 1 2008;26(31):5043-51. [Medline]. [Full Text].
Gore EM, Bae K, Wong SJ, Sun A, Bonner JA, Schild SE, 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. Jan 20 2011;29(3):272-8. [Medline].
Sun A, Bae K, Gore EM, Movsas B, Wong SJ, Meyers CA, 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. Jan 20 2011;29(3):279-86. [Medline].
[Best Evidence] Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, 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. Feb 20 2010;28(6):911-7. [Medline].
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. Jul 2011;22(7):1520-7. [Medline].
Raz DJ, Lanuti M, Gaissert HC, et al. Outcomes of patients with isolated adrenal metastasis from non-small cell lung carcinoma. Ann Thorac Surg. Nov 2011;92(5):1788-92; discussion 1793. [Medline].
[Guideline] Azzoli CG, Baker S Jr, Temin S, Pao W, Aliff T, Brahmer J, et al. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. Dec 20 2009;27(36):6251-66. [Medline]. [Full Text].
Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, 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. Oct 24 2009;374(9699):1432-40. [Medline].
Mallin R. Smoking cessation: integration of behavioral and drug therapies. Am Fam Physician. Mar 15 2002;65(6):1107-14. [Medline].
Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. Mar 4 1999;340(9):685-91. [Medline].
Moysich KB, Menezes RJ, Ronsani A, Swede H, Reid ME, Cummings KM, et al. Regular aspirin use and lung cancer risk. BMC Cancer. Nov 26 2002;2:31. [Medline]. [Full Text].
Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med. Jun 29 2011;[Medline].
Jacobs PC, Gondrie MJ, van der Graaf Y, de Koning HJ, Isgum I, van Ginneken B, et al. Coronary Artery Calcium Can Predict All-Cause Mortality and Cardiovascular Events on Low-Dose CT Screening for Lung Cancer. AJR Am J Roentgenol. Mar 2012;198(3):505-11. [Medline].
Gohagan J, Marcus P, Fagerstrom R, Pinsky P, Kramer B, Prorok P. Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph: the Lung Screening Study of the National Cancer Institute. Chest. Jul 2004;126(1):114-21. [Medline].
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. Jan 22 2004;350(4):351-60. [Medline].
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