1. Lung cancer

2. Epidemiology Incidence: Lung cancer is the most common cancer in the world Mortality: is the leading cause of cancer deaths in both men and women RO: -males: 1. -females: 4.

3. Epidemiology-USA

6. Etiology (risk factors) I. Environmental 1. Smoking is the primary risk factor for lung cancer accounting for 90% of cases in men and 70% in women It is a risk factor for both NSCLC (squamous cell carcinoma, adenocarcinoma, large cell carcinoma) and SCLC

7. In the US: Adenocarcinoma has been more common than squamous cell carcinoma in women since the 1950s and became the most common lung cancer diagnosis in men in 1990. There are many theories that may explain a relative decrease in squamous and small cell carcinomas and the increase in adenocarcinomas. The introduction of filter cigarettes in the mid-1950s may have contributed: 1. by allowing smaller carcinogens to be deposited in the lung periphery. 2. may have determined smokers to take larger puffs and retain smoke longer to compensate for the lower nicotine yield Plus, smoking low-tar filter cigarettes may increase the rate of adenocarcinoma because these cigarettes have a higher nitrate content, which has been shown to produce adenocarcinoma in laboratory animals.

8. Men who smoke one pack a day increase their risk 10 times compared with non-smokers. Men who smoke two packs a day increase their risk more than 25 times compared with non-smokers The lifetime risk of developing lung cancer in smokers is approximately 10% Cancer risk decreases slowly after quitting: 40% of newly diagnosed lung cancer occurs in former smokers (median abstinence duration 9 years)

9. Etiology 2. The second most important environmental risk factor is Rn (Radon) =a radioactive gas -from rocks -represents 40% from the background radiation -it is deposited in the airways -deposition in airways increased if bound to aerosols (for example smoke); smoking increases deposition 25 times 3. Asbestos- increases risk both for lung cancer and mesothelioma (of the pleura or peritoneum) 4. Exposure to radiation e.g. radiotherapy for breast cancer

10. Etiology 5. Industrial pollutants (Ni, Be) II. Genetic predisposition Why not all people who smoke develop lung cancer? - genetic polymorphism or deletion of genes of enzymes playing a role in detoxification of polycyclic aromatic hydrocarbons found in tobacco smoke

11. Classification Non-small cell lung cancer=NSCLC (80%)- consists of 3 main types: – Squamous cell carcinoma – Adenocarcinoma – Large cell carcinoma Small cell lung cancer=SCLC (=oat cell cancer) (20%) -different behavior (more aggressive) -early metastases

12. Special subtype: bronchioloalveolar carcinoma Rare: 2-9% of primary lung cancers Related to adenocarcinoma At first it is non-invasive tumor (carcinoma in situ), but eventually can produce metastases Tumor cells spread along the alveoles =>Produces dyspnea in a restrictive (not obstructive) way Smoking is a risk factor, but it is less important than in other histological subtypes Radiologic patterns: peripheral solitary nodule (43%); consolidation (30%), or diffuse disease (27%)

13. Extension Local: -invasion of the big mediastinal vessels -invasion of the pericardium -invasion of the laryngeal recurrent nerves -invasion of the pleura -invasion of chest wall (e.g. Pancoast tumor)

14. Pancoast tumor =superior sulcus tumor =malignant neoplasm of the thorax inlet with invasion of the chest wall and involvement of the brachial plexus and cervical sympathetic nerves. Symptoms: -severe pain in the shoulder region radiating toward the axilla, scapula and along the ulnar aspect of the muscles of the hand -atrophy of hand and arm muscles -Bernard-Horner syndrome (compression of sympathetic chain) - compression of the subclavian vein with oedema

15. Extension Lymphatic- -hilar -mediastinal (drainage crosses to the other side to) -scalene, supraclavicular

16. Extension Metastases- -brain -bone -liver

17. Symptoms a)Endobronchial tumors -cough, obstructive dyspnea, hemoptisis, obstructive pneumonia b)Peripheral tumors -longer asymptomatic evolution -pleural invasion=>pleuritic pain and cough; restrictive dyspnea; pulmonary abscess formation c)Compression/invasion of mediastinal/thoracic structures by primary tumor or lymph nodes -tracheal obstruction; dysphagia; dysphonia; paralysis of a hemidiaphragm by invasion of a phrenic nerve; superior vena cava obstruction; dyspnea by pleural exudate/or transsudate;

18. Symptoms d)Extrathoracic metastases -brain -liver -bone -suprarenals (asthenia) e) General symptoms (weight loss, asthenia) f) Paraneoplastic syndromes

19. Diagnosis Chest radiography Chest and upper abdominal CT or PET-CT (MRI not good for mobile organs such as the lung) Endobronchial biopsy or transbronchial biopsy Mediastinoscopy or thoracoscopy with biopsy for tumors not biopsiable bronchoscopically Pleural liquid, if present, must be tested for malignant cells- important for staging and thus treatment Brain MRI Pulmonary function testing

20. Treatment-NSCLC Resectable tumor=> lobectomy/unilateral pneumonectomy plus mediastinal lymphadenectomy +/- adjuvant chemotherapy or radiotherapy Unresectable tumor=> concomitant chemoradiation with or without reevaluation for surgery Metastatic lung cancer=>chemotherapy Endobronchial obstruction=> palliative desobstruction with: -stent -LASER -brachytherapy or external beam RT -photodynamic therapy Superior vena cava obstruction: -emergency palliative external beam radiotherapy or stent

21. Treatment-SCLC LIMITED-STAGE DISEASE=SCLC which is limited to a hemithorax and can be encompassed in one tolerable radiation field Stage I disease (only 5% of patients) (true stage I is after extensive testing, including mediastinoscopic lymphadenectomy)=> lobectomy Other limited disease=> chemoradiation EXTENSIVE-STAGE DISEASE Chemotherapy All patients who are in complete or partial response: prophylactic cranial irradiation

22. Screening Stage I lung cancer can be diagnosed using annual low dose CT scans No screening programs implemented yet; studies ongoing Warning: 1000 CTs of chest/abdomen=> 1 radio-induced cancer

23. Questions What are the risk factors of lung cancer? What are the symptoms of lung cancer? How is non-small cell lung cancer treated?