LUNG CANCER

NON SMALL CELL LUNG CANCER

General Introduction

Lung cancer is the most common cause of cancer mortality worldwide for both men and women, causing approximately 1.2 million deaths per year. The GLOBOCAN 2002 project reports the worldwide incidence, mortality and prevalence of various cancer sites across the globe. http://www-dep.iarc.fr/GLOBOCAN_frame.htm

In India, the Indian Council of Medical Research initiated a network of cancer registries across the country under the National Cancer Registry Programme in Dec 1981. As per the consolidated report of Population based cancer registry it was seen that lung cancer was the leading site in Bhopal, Delhi and Mumbai while it was the second leading site in Chennai and Bangalore.
http://www.icmr.nic.in/ncrp/report_pop_2001-04/cancer_p_based.htm

In India, the true incidence has been difficult to estimate due to a variety of reasons, however there has been no doubt that both the absolute and relative frequency of lung cancer have risen dramatically. Lung cancer has remained predominantly a disease of males with a male:female ratio of 7:1. Around 80% of lung cancer patients come from the rural areas. Forty per cent of patients of lung cancer are less than 50 years of age and 11% are less than 40 years. [2]
http://medind.nic.in/iae/t04/i4/iaet04i4p269.pdf

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Risk Factors

Smoking - Tobacco smoke is the primary cause of over 80% of lung cancers. The risk of a lifetime smoker developing lung cancer is 23 times greater than a non-smoker, and this risk directly increases with the number of cigarettes smoked per day. Pipe and cigar smokers who inhale have similar mortality rates to that of cigarette smokers. The risk of lung cancer in an ex-smoker falls to the same level as a non-smoker after about 15 years. It is estimated that one third of lung cancers in non-smokers result from passive exposure to cigarette smoke.

Radon Gas - Exposure to the naturally occurring radioactive gas radon, which may accumulate int o the foundations of buildings from soil emissions, is another potential cause of lung cancer. Scientists estimate it may cause one in 20 lung cancer cases.

Radiation therapy — Radiation therapy can increase the risk of a second primary lung cancer in patients who have been treated for other malignancies. In women who receive RT following a mastectomy for breast cancer, there appears to be an increased risk of lung cancer among smokers. Similarly, RT for Hodgkin lymphoma has been associated with an increased risk of secondary lung cancer

Asbestos - Death from lung cancer is about seven times more likely to occur among asbestos workers than among the general population. Exposure to asbestos fibers is an important risk factor for lung cancer. Asbestos workers who smoke have a very high lung cancer risk: 50 to 90 times greater than that of people in general. Both smokers and nonsmokers exposed to asbestos also have a greater risk of Mesothelioma

Chemical Exposure - Exposure to chemicals such as arsenic, vinyl chloride, nickel chromate, coal products and chloromethyl ethers, significantly increase the risk of developing lung cancer.

Recurring Inflammation- Tuberculosis and some types of pneumonia often leave scarred areas on the lung. This scarring increases the risk of the person developing the adenocarcinoma type of lung cancer.

Pulmonary fibrosis — Several studies have shown that the risk for lung cancer is increased about sevenfold patients with pulmonary fibrosis. This increased risk appears to be independent of smoking

Talcum Powder- While no increased risk of lung cancer has been found from the use of cosmetic talcum powder, some studies of talc miners and millers suggest a higher risk of lung cancer and other respiratory diseases from their exposure to industrial grade talc. Talcum powder is made from talc, a mineral that in its natural form may contain asbestos. By law since 1973, all home-use talcum products (baby, body, and facial powders) have been asbestos-free.

Other Mineral Exposures- People with silicosis and berylliosis (lung diseases caused by breathing in certain minerals) also have an increased risk of lung cancer.

Personal and Family History- People who have lung cancer have an increased risk of another lung cancer. Brothers, sisters and children of those who have had lung cancer may have a slightly higher risk of lung cancer themselves. However, it is difficult to say how much of this excess risk is due to inherited factors and how much is due to environmental tobacco smoke.

Vitamin A Deficiency or Excess- People who do not get enough vitamin A are at increased risk of lung cancer. On the other hand, taking too much vitamin A may also increase lung cancer risk.

Diet - A low consumption of fruit and vegetables (particularly green vegetables and carrots) has been associated with an increased risk of lung cancer. Studies suggest that lung cancer may be prevented by dietary micronutrients such as carotenoids, vitamin C, vitamin E, and selenium.

General Anatomy

Regional Nodal Anatomy

Superior mediastinal nodes
1. highest mediastinal
2. upper paratracheal
3. pre-vascular and retrotracheal
4. lower paratracheal (including azygos nodes)

Aortic nodes
5. subaortic (aortopulmonary window)
6. para-aortic (ascending aorta or phrenic)

Inferior mediastinal nodes
7. subcarinal
8. para-oesophageal (below carina)
9. pulmonary ligament

N1 nodes
10. hilar
11. interlobar
12. lobar
13. segmental
14. subsegmental

N2 ipsilateral nodes (stations 1-9)

N3 contralateral or supraclavicular nodes

tnm.jpg

Pathology

The WHO Classification of Lung cancers, revised in 2004 recognises[3] the following histologic subtypes

1. Squamous cell carcinoma

Variants: papillary, clear cell, small cell, basaloid

2. Small cell carcinoma

Variant: combined small cell carcinoma

3. Adenocarcinoma

Adenocarcinoma, mixed subtype
Acinar adenocarcinoma
Papillary adenocarcinoma
Bronchioloalveolar carcinoma
Variants: nonmucinous, mucinous, mixed nonmucinous and mucinous or indeterminate
Solid adenocarcinoma with mucin production
Variants: fetal adenocarcinoma, mucinous ("colloid") carcinoma, mucinous cystadenocarcinoma, signet ring adenocarcinoma, clear cell adenocarcinoma

4. Large cell carcinoma

Variants: large cell neuroendocrine carcinoma, combined large cell neuroendocrine carcinoma, basaloid carcinoma, lymphoepithelioma-like carcinoma, clear cell carcinoma, large cell carcinoma with rhaboid phenotype

5. Adenosquamous carcinoma

6. Sarcomatoid carcinoma

Variants: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, pulmonary blastoma

7. Carcinoid tumor

Variants: typical carcinoid, atypical carcinoid

8. Salivary gland tumors

Variants: mucoepidermoid carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma

Staging

TNM staging system for lung cancer (7th edition 2009)

Primary tumor (T)

T1 - Tumor 3 cm diameter, surrounded by lung or visceral pleura, without invasion more proximal than lobar bronchus
T1a - Tumor 2 cm in diameter
T1b - Tumor >2 cm but 3 cm in diameter

T2 - Tumor >3 cm but 7 cm, or tumor with any of the following features: Involves main bronchus, 2 cm distal to carina, Invades visceral pleura, Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the
entire lung

T2a - Tumor >3 cm but 5 cm
T2b - Tumor >5 cm but 7 cm

T3 - Tumor >7 cm or any of the following: Directly invades any of the following: chest wall, diaphragm, phrenic nerve, mediastinal
pleura, parietal pericardium, main bronchus <2 cm from carina (without involvement of carina) , Atelectasis or obstructive
pneumonitis of the entire lung, Separate tumor nodules in the same lobe

T4 - Tumor of any size that invades the mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral
body, carina, or with separate tumor nodules in a different ipsilateral lobe

Regional lymph nodes (N)

N0 - No regional lymph node metastases
N1 - Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension
N2 - Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
N3 - Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).

Distant metastasis (M)

M0 - No distant metastasis
M1 - Distant metastasis
M1a - Separate tumor nodule(s) in a contralateral lobe; tumor with pleural nodules or malignant pleural or pericardial effusion
M1b - Distant metastasis

Stage groupings

Stage IA: T1a-T1b N0 M0
Stage IB: T2a N0 M0
Stage IIA: T1a,T1b,T2a N1 M0
T2b N0 M0
Stage IIB: T2b N1 M0
T3 N0 M0
Stage IIIA: T1a,T1b,T2a,T2b N2 M0
T3 N1,N2 M0
T4 N0,N1 M0
Stage IIIB: T4 N2 M0
Any T N3 M0
Stage IV: Any T Any N M1a or M1b

Screening

US Preventive Services Task Force
Evidence is insufficient to recommend for or against screening asymptomatic persons for lung cancer with either low dose computerized tomography, chest x-ray, sputum cytology, or a combination of these tests.

American College of Chest Physicians
Recommends against the use of low dose CT, chest radiographs, or sputum cytology for lung cancer screening, including smokers or others at high risk, except in the context of a clinical trial.

American Cancer Society
Informed individual decision-making; if testing is chosen, spiral CT should be performed only in centers with multidisciplinary specialties experienced in screening and treatment.

American Academy of Family Physicians
Recommends against the use of chest x-ray and/or sputum cytology in asymptomatic persons.

Canadian Task Force on the Periodic Health Examination
Recommends against the use of chest x-ray in asymptomatic persons. Evidence is insufficient to recommend for or against screening with spiral CT in asymptomatic persons.

Treatment Criteria

CRITERIA OF MEDICAL (IN)OPERABILITY

surgical-assessment-intraoperative-staging

Treatment

How to select a patient for EGFR-TKI treatment
A discussion on how to select a patient of lung cancer for EGFR TKI therapy.

Follow Up

References

Bibliography
1. Damhuis RA, Schutte PR. Resection rates and postoperative mortality in 7899 patients with lung cancer. Eur Respir J 1996;9:97-100
2. D. Behera and T. Balamugesh. Lung Cancer in India. Indian J Chest Dis Allied Sci 2004; 46 : 269-281 http://medind.nic.in/iae/t04/i4/iaet04i4p269.pdf
3. Travis, WD, Brambilla, E, Muller-Hermlink, HK, Harris, CC (eds). World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. IARC Press. Lyon 2004
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