1605
See ((Small cell carcinomas of the lung))
Almost 2.2 million cases diagnosed each year worldwide.
More than half of all new cases of lung cancer occur in Asia, and the frequency of occurrence in male is double that of females.
Accounts for approximately 14% of all cancer diagnoses, and is the deadliest types, causing 25% of cancer deaths in the US in 2017.
Lung cancer is the leading cause of cancer related mortality is worldwide contributing to about 1.8 million deaths in 2020.
In 2020 alone and estimated 253,537 new lung cancers in 159,641 for date related deaths have been reported in the US.
The leading cause of death from cancer worldwide, 18.4% overall cancer deaths, and causes more deaths than breast, colorectal, and cervical cancers combined.
Lung cancer is leading cause of cancer related mortality in the US and worldwide.
In 2023 an estimated 200,00 new cases of lung and bronchial cancer will be diagnosed, and approximately 130,000 deaths will occur in the US.
Five year survival rates for lung cancer only 22. 9%, partly because most patients have advanced disease at diagnosis.
Lung cancer incidence and mortality rates are highest in developed countries.
Most common cause of cancer death in the US and worldwide, causing as many deaths as the next 4 most deadly cancers, including breast, prostate, colon, and pancreas cancers.
Lung cancer is the leading cause of cancer related deaths in the US, attributed to approximately 44.7 deaths per hundred thousand persons annually.
1.4 million deaths annually worldwide.
Most cases occur in the sixth through eighth decades of life.
Represents 13.5% of all new cancer diagnoses in the US.
Only 26% of all patients with non-small cell lung cancer are alive at five years or more after diagnosis.
Non-small cell lung cancer is the most common type of lung cancer, comprising approximately 80-85% of lung cancer cases.
Two thirds of lung cancer cases occur in individuals 65 years of age or older.
Estimated 228,000 new cases and 142000 deaths in 2019 in the U.S.
Lifetime risk for developing some form of lung cancer in the US is approximately 6.8%.
Accounted for 60.1 new cases of cancer And 48.4 deaths per 100,000 people in the US 2007-2011.
Accounted for 29% of all cancer deaths in 2008 (ACS).
Accounts for about 13.5% of all cancer diagnoses an approximately 27% of all cancer deaths.
The three main types of NSCLC are large cell carcinoma, 10%, squamous cell carcinoma,25%, and adenocarcinoma, 40%, with numerous less frequent subtypes.
Smoking responsible for approximately 80%-90% of all cancers of the lung.
Tobacco smoke contains over 60 carcinogens, primarily polycyclic aromatic hydrocarbons and a role in, and is known to create bulky adducts at purine bases, distorting the DNA helix and predisposes to C-A transversions, which is the basis for the single based substitute signature.
Almost half of new cases are diagnosed in women and approximately 30-40% of cases diagnosed in patients older than 70 years.
A study of lung cancer in younger adults has found a trend of higher lung cancer rates in women, compared with men.
The increase is driven by cases of adenocarcinoma of the lung.
They found that the female-to-male incidence rate ratio (IRR) has significantly crossed over from men to women in many countries,
In the US the incidence is higher in young women than that in their male counterparts.
Average age-adjusted incidence for lung cancer is 73.39 per 100,000 for African Americans and 54.31 per 100,000 for whites.
American Cancer Society estimated probability of lung cancer among males is .03% from birth to 39 years of age, 1.08% from 40-59 years, and 5.75% from 60-79 years.
Peak incidence of new cases occurs in patients 65-74 years, and the median age of diagnosis at 70 years.
Study show delayed treatment of more than eight weeks in patients with lung cancer results in increased mortality.
Men more likely to develop and die of lung cancer than women.
Accounts for 30% of deaths from cancer in the U.S.
Five-year survival rate 18% is significantly lower than colon, 65%, breast-cancer 90%, and prostate cancer 99%.
Only 15% of patients are diagnosed at early-stage, and the five-year survival rate decreases to 4% for patients with cancer that is spread to distant sites.
The incidence among women has increased 600% in past 80 years.
Surpassed breast, ovarian, and uterine cancers combined as a cause of death in women.
Accounts for more deaths than the second and third cancer killers, breast and colon combined.
Death rates among women in the U.S. is among the highest in the world.
Death rates in men and falling since 1990.
Approximately 95% of lung cancer patients die of their disease.
There is a 10-20 fold increase risk of cancer in smokers.
The risk of cancer differs by age, smoking intensity, and smoking duration.
The risk of lung cancer increases with combined exposure to toxins and cigarette smoking.
Female nonsmokers more likely to develop lung cancer than men nonsmokers.
Women over represented among young patients with lung cancer.
Black males have the highest incidence of death rates from lung cancer.
Black individuals develop non-small lung cancer five years earlier than their European American count parts.
The major carcinogenic compounds in highway exhaust are small PM2.5 and nitrogen oxides, both of which exist at higher levels in black communities, and both of which are associated with increased lung cancer incidence and mortality.
Women have better survival rates regardless of the stage at the time of diagnosis.
Female smokers have a higher percentage of adenocarcinoma and small cell lung cancer than male smokers.
About 90% of cases are the results of cumulative aberrant epigenetic and genetic damage to the respiratory epithelium chronically exposed to carcinogens in tobacco.
Incidence in lung cancer in smokers with COPD is 4-5 times that reported in smokers without COPD or with chronic bronchitis alone.
More than 75% of patients present with advanced stage with limited therapeutic options.
40% present in stage IV, 30% present in stage III.
Risk increased in proportion to the degree of airway obstruction in moderate to severe COPD.
Incidence increased in non smokers with impaired lung function, so the presence of airway obstruction may be an independent as well as an additive risk factor for the development of lung cancer.
Five-year survival rate of approximately 25% of all stages combined.
Localized disease associated with a 5 year survival rate of approximately 50%, but only 15% of lung cancer cases of diagnosed at this early stage.
CYP1A1, a cytochrome P-450 gene that catalyzes the metabolic activation of tobacco related precarcinogens, is higher in content in lung tumor tissue of female vs. male smokers.
In a small proportion of lung cancer patients ALK rearrangements are present and is a result of a small inversion within chromosome 2p, leading to a fusion of a portion of the EML4 gene with exons 20 through 29 of ALK.
The risk of lung cancer in women who smoke is higher than in men who are the same age and who smoke the same amount.
Fewer than 15% of patients are younger than 50 years.
Median cumulative cigarette consumption among smokers under the age of 50 years with lung cancer was 30 pack years (Gadgeel).
Cigarette smoking is responsible for 87% of lung cancer deaths and 70% in women.
Approximately 85-90% of cases caused by cigarette smoking.
Cigarette smoke contains many carcinogenic chemical such as nitrosamines, and benzopyrene.
The risk of lung cancer increases with the number of packs of cigarettes smoked per day and the number of years of smoking.
Smoking in combination with exposure to factors such as asbestos found in shipyards, migraines, automobile shops, textile plants and cement plants, construction and insulation sites have a synergistic effect in the risk of lung cancer.
Patients who smoke and have asbestos exposure have a 50 fold relative risk of lung cancer compared to an exposed nonsmokers.
Nonsmokers exposed to cigarette smoke have an increased relative risk of developing lung cancer from secondhand smoke at 1.05-1.24.
Radon is estimated by the US Environmental Protection Agency to be the main cause of lung cancer in nonsmokers, and the WHO concluded that outdoor air pollution is a leading environmental cause of lung cancer deaths.
Asbestos is estimated to be the cause of 3-4% of lung cancers.
Possible risk factors for lung cancer include: Lung inflammation and scarring, previous inflammation from tuberculosis, family history, and exposure to carcinogens such as polycyclic aromatic hydrocarbons, chromium, nickel, organic arsenic compounds, cadmium, beryllium, silica, and diesel fuels.
Mutational signatures that result in errors in DNA replication and repair that increase the risk of lung cancer include: SBBS1, SBS2, SBS 6, and SBS 13.
BCG vaccination correlates with a lower risk of lung cancer.
Risk of lung cancer is almost doubled in individuals with family history of lung cancer, potentially related to exposure to tobacco or environmental carcinogens, or shared genetic susceptibility.
Patients with first-degree relatives who have received lung cancer diagnoses are 2-6 times the risk of patients whose 1st° relatives do not develop lung cancer.
Cure rate a dismal 1%, and the 5-year survival rate is only slightly higher than the cure rate.
African Americans develop lung cancer at a much earlier age than their white counterparts.
African Americans have a lower survival rate after correction for stage in treatment.
With the same age and smoking history, a black person has a higher risk for lung cancer than a white person.
Asian individuals had a unique phenotype that makes him more responsive to certain drugs (Mok TS).
Overall survival 5-year survival for non-small cell cancer of the lung is 14%.
Overall 5-year survival for patients stage I and II lung cancer approaches 50% and 30%, respectively.
One sixth of lung cancers found at autopsy are clinical unrecognized and unrelated to the individual’s death.
3 definite predictors of survival-performance status, stage of disease and weight loss.
Tumor size in lung cancer is not as good a prognostic factor for adenocarcinoma as it is for squamous cell carcinoma
5-10% diagnosed in patients under 50 years of age.
Younger patients present with more advanced stage than older patients.
Median age at diagnosis in the United States is approximately 70 years.
The median age at diagnosis has been increasing over the last few decades.
Patients with multiple primary lung cancers have a better survival than thosse with intrapulmonary metastases.
Women tend to be younger than men at the time of diagnosis.
86% of deaths attributable to cigarette smoking.
With tumors smaller than 2 cm up to 20% have N2 status.
Despite the removal of all visible tumor, cancer recurs in most patients with metastases to intrapleural or extrapleural lymph nodes.
Elevated expression of vascular endothelial growth factor and other pro angiogenic factors are significant prognostic markers in non-small cell lung cancer and are associated with early postoperative relapse and reduced survival.
Guidelines recommend testing for EGFR mutations and ALK fusions in all patients with advanced adenocarcinoma regardless of gender, race, smoking history or other clinical factors.
Testing for EGFR and ALK is not recommended for lung cancers the lack in the adenocarcinoma component.
Both primary and metastatic lesions are equally suitable for testing for biomarkers.
Approximately 40% of patients who undergo resection for NSCLC without overt metastases (pT1-2, No, Mo, Ro) relapse within 24 months after surgery.
Appropriate surgical resection considered for patients stage I, II and IIIa disease if considered medically operable.
Surgical resection for the majority is a lobectomy, however 4% require a lobectomy and 6.5% require a pneumonectomy for complete resection.
For patients with centrally located tumors a sleeve resection is equivalent, if not better than, pneumonectomy.
Sublobar resection with wedge resection or segmentectomy can be considered for individuals with impaired pulmonary function or other comorbidities are contraindications to lobectomy.
Surgical resections should include peribronchial, hilar (N1), and mediastinal (N2) lymph node sampling or dissection.
Adenocarcinoma most frequent cell type among patients with early onset lung carcinoma.
Adenocarcinoma is the leading cell subtype in young male and female patients with lung cancer.
Adenocarcinoma is the most frequent type occurring in non-smokers and is usually found in the periphery of the lung and starts in mucus secreting cells.
Epidermal growth factor receptor (EGFR) gene mutations frequent in adenocarcinoma of the lung in nonsmokers and are implicated in the development of such lesions.
EGFR mutations in lung cancer account for 40% of adenocarcinomas of the lung in East Asians and about 15% in Caucasians and African Americans.
Tyrosine kinases usually given as a front-line therapy for metastatic lung cancer with EGFR mutations, but resistance emerges after a median of 1 year.
Alterations in genes, such as EGFR, KRAS, ALK, MET, HER2, ROS1, and RET have been shown to promote non-small cell lung cancer formation and our target for cancer treatment.
Adenocarcinoma of the lung has increased circulating protein concentration of exosomes compared to a control group (Rabinowitz).
Tumor derived exosomes are small membrane vesicles of endocytic origin released by the tumor and found in the peripheral blood.
Squamous cell carcinoma is the most frequent type of lung cancer in older men.
Mediastinoscopy is the standard of care for preoperative mediastinal staging in NSCLC.
Mediastinoscopy reported sensitivity and specificity of 87% and 100%, respectively.
Mediastinoscopy reveals that 3-16% of patients with CT scan mediastinal lymph nodes less than 1 cm have tumor involvement.
Mediastinoscopy reveals that 30% of patients with enlarged nodes on CT scan do not have neoplastic changes.
Endobronchial ultrasound guided trans bronchial needle aspirate and trans esophageal endoscopic ultrasound guided fine needle aspiration have advantages over conventional bronchoscopy and blind transbronchial needle aspirate biopsies for sampling mediastinal lymph nodes.
Mediastinal staging in lung cancer with bronchial endoscopic ultrasound guided fine needle aspiration followed by surgical staging, nodal metastases were found in 50% of patients, compared to 35% of patients randomized to surgical staging alone :Thoracotomy was futile in 7% of patients with endobronchial ultrasound biopsies compared to 18% of surgically staged patients (Tournoy KG et al).
Endobronchial ultrasound guided trans bronchial needle aspirate biopsies had better accuracy for nodal staging versus CT scans and pet scans: 94% versus 77%, and 96% versus 73% (Tupayachi MG et al).
CT scan accuracy for lymph node involvement in the mediastinum has an overall sensitivity and specificity of 79% and 78%, respectively.
CT of the thorax has limited ability to distinguish between malignant and benign disease, and has difficulty in evaluation tumors with significant atelectasis and in assessing tumor invasiveness.
MRI not better than CT imaging with respect to staging of the mediastinum.
PET san overall 20% improvement in ability to stage the mediastinum compared to CT scans.
PET scans reliable and accurate for detecting mediastinum lymph nodes of less than 1 cm with sensitivity and specificity of 97% and 82%, respectively.
Adenocarcinoma most frequent histological type beginning in the 1980’s.
Peripheral lung adenocarcinoma smaller than 3 cm frequently recur, resulting in cancer death with the 5-year disease free survival for T1N0 disease approximately 63%.
No statistical relationship between tumors less than or equal to 3 cm and survival patients with 3 cm masses have the same outcome as patients with 1 cm nodules.
Approximately 19% of peripheral lung cancer missed on chest radiographs and the observed average size of the lesions were 1.6 cm.
Chemotherapy before surgery is presently the established treatment for resectable stage IIIA NSCLC.
Survival is much improved with induction chemotherapy plus surgical resection than with resection alone in stage IIIA disease.
In close proximity to or involving the carina as with an operative mortality of 15%.
In close proximity to or involving the carina have an overall 5-year-survival of 42%. The 5-year-survival in patients without nodal involvement is 51% and 32% for patients with N1 disease and 12% for N2/N3 disease.
The five year survival for localized disease is roughly 63% whereas for distant disease it is 8%.
Only 25% of patients can undergo complete resection of disease, with a recurrence rate of 50%.
Radiation alone for advanced disease rarely produces complete remissions and associated with median survival range of 6-11 months, with 5-year survival rates of only 3-10%
Response rate in advanced disease to combination chemotherapy ranges from 15-22% with 1-year survival rates of 31-36%.
Platinum containing chemotherapy doublets have reached a plateau in metastastic cancer with an overall response rate of 25-35%, time to progression 4-6 months, median survival 8-10 months, 1-year survival of 30-40% and 2-year survival rate of 10-15%
Approximately one fourth of symptoms present at the time of diagnosis are related to the primary tumor itself.
Centrally located lung tumors are frequently associated with cough, hemoptysis, atelectasis and post obstructive pneumonia.
Common symptoms include: cough, dyspnea, weight loss, and chest pain, with symptoms more likely in patients with COPD.
The incidence of new lung cancer is low after pneumonia: approximately 1% within 90 days and 2% over five years-suggesting routine chest x-rays after pneumonia for detecting lung cancer is not warranted although patients over the age of 50 years and smokers should be targeted for such follow-up (Tang KL et al).
9.2% incidence of new lung cancer after pneumonia with five-year follow-up (Mortensen EM et al).
The relative 5-year survival rate for women with lung cancer is 18.2% compared to 14.5% in men (Ries,LAG).
Improved survival for women is independent to stage or histology.
Women’s Health Initiative (WHI)-effects of conjugated equine estrogen plus medroxyprogesterone in 16,608 postmenopausal women revealed that the incidence of non-small cell lung cancer and mortality during 5.6 years of intervention and 2.4 years of additional follow-up revealed: no significant difference in lung cancer incidence compared to placebo, but mortality after a lung cancer diagnosis was significantly higher in patients receiving combined hormone therapy .
Women’s Health Initiative (WHI)-in the above study women in the hormone therapy group were 60% more likely to die from lung cancer during the follow-up period then were women in the placebo group.
Women’s Health Initiative (WHI)-in the above study women taking hormone therapy and who were current smokers had a high risk of dying from lung cancer with the mortality rate after diagnosis of 3.4% among smokers compared to 2.3% among smokers in the placebo group.
Peripheral cancers may cause chest pain by chest wall, spine or brachial plexus extension.
Patients with peripheral lesions may present with pleural effusions.
Patients with large lesions may have cavitation and abscess formation.
Approximately 2% of patients present with paraneoplastic syndromes, particularly with small cell or squamous histologies.
Treatment with bevacizumab, combined with chemotherapy improves the response rate, progression free survival, and overall survival in patients with advanced non-squamous non-small cell lung cancers.
Treatment modalities vary from surgery, radiation, chemotherapy, neoadjuvant therapy, periadjuvant therapy, immunotherapy, and ate best addressed on the individual types of lung cancer: Non-small cell, lung cancer, small cell lung cancer, ALK positive lung cancer, squamous cell, adenocarcinoma, etc.