LUNG CANCER

1. LUNG CANCER Marianna Strakhan, MD Attending Physician Department of Hematology/Oncology Jacobi Medical Center Bronx, NY March 30, 2010

2. Incidence • 2nd most common type of malignancy in the U.S. among both men and women • Most common form of cancer mortality in the U.S. in both men and women • In 2007 – approximately 215,000 new cases of Lung cancer were diagnosed in the U.S, with 162,000 deaths • Between 1990 and 2003 – incidence of lung cancer have remained stable in men, however in women, incidence increased by 60% (incidence in African american females being partially higher than white females). **Incidence increase is seen among large portion of never-smokers, healthy, and active women)

3. Incidence • Although deaths have begun decreasing in MEN (likely due to decrease in smoking), mortality in WOMEN has reached a plateau • Almost ½ of all cancer deaths now occur in women • 10 – 15% of lung cancer victims are non-smokers. Among that group, women are 2-3x more likely than men to get the disease

4. Incidence • Median age of diagnosis is 66 y.o. in both women and men. • More of the patients <50 y.o. at time of diagnosis were women • In women, 45% of all lung cancers were adenocarcinoma, followed by 22% small cell cancer, 21% squamous cell, rest as other subtypes (in men, squamous subtype is most common, followed by adeno, followed by small cell)

6. Risk Factors • Cigarette smoking - in the U.S, nearly 25% of women smoke - some studies suggest women have more difficulty quitting smoking than men – risk is increased 10 – 30 x than in non-smokers - smoking > or = 25 cig/day increases risk more than smoking less than 25 cig/day - age at onset of smoking - degree of inhalation correlates with risk of developing disease - Tar and nicotine content of cigarettes - use of unfiltered cigarettes - smoking cessation decreases risk significantly, with decline in risk starting > 5 years of abstinence. - after 15 years, risk is reduced by 80%. The longer one the person is not smoking, the lower the risk becomes – however risk still remains higher than in never smokers • 2nd hand smoke - the longer the exposure the higher the risk - approximately 17% of all lung cancer in never smokers is due to second hand smoking during the person’s childhood and adolescence - risk doubles with 25 or > years of exposure - ban of smoking in restaurants/enclosed spaces decreases undesired exposure of non-smokers

7. Risk Factors • Asbestos • Radon • Arsenic • Ionizing radiation • Polycyclic aromatic hydrocarbons • Nickel • Pulmonary Fibrosis • HIV infection • Family History • Beta Carotene (initially used for chemoprevention, noted to be associated with higher risk of lung cancer in smokers) • Race (African Americans and Hawaiians have higher risk of lung cancer incidence among persons who smoke <30 cig/day, no difference between the races among persons smoking >30 cig/day)

8. Risk Factors *Lung cancer in women is a biologically and genetically different disease than in men: • Genes that cause women to be more vulnerable to the harmful effects of tobacco smoke • Differences in how the chemicals in tobacco are metabolized (broken down) by the body • Changes to genes that control cell growth, which may result in the development of cancer • A decreased ability of the body to repair damaged DNA, as DNA damage can promote the development of cancer • Hormones, such as estrogen, which could directly or indirectly affect cancer growth

9. Signs and Symptoms • Cough • Hemoptysis • Dyspnea • Chest Pain • Hoarseness (due to involvement of recurrent laryngeal nerve) • SVC syndrome (dilated neck veins, facial edema) – due to pressure on SVC by the tumor • Pancoast’s syndrome – pain in shoulder or arm, Horner’s syndrome (miosis, ptosis, anhidrosis), atrophy of hand muscles • Weight loss • Paraneoplastic syndromes -example: Hypercalcemia in Squamous cell ca SIADH in Small Cell Ca • Thrombosis • Leucocytosis and thrombocytosis

10. SVC Syndrome Etiology: -result of compression of SVC by either malignancy (RUL mass) or thrombosis (mainly due to use of intravascular device) -most common etiology is lung cancer -may also be due to infections (TB, etc..) or hematological malignancies such as lymphoma/leukemia Signs/Symptoms: -symptoms may develop over weeks or longer -increased venous pressure leads to edema of head, neck and arms -headache -cyanosis -cough, dyspnea -dysphasia, stridor

11. SVC Syndrome

12. SVC Syndrome

13. SVC Syndrome Diagnosis -CXR (mediastinal widening, mediastinal mass) -CT neck/chest -ultrasound/doppler to r/o thrombosis of SVC Treatment -Oxygen -elevation of the upper body -diuretics, fluid restriction -anticoagulation if thrombosis -biopsy – obtain pathology prior to treatment -*chemotherapy -radiation therapy -steroids (benefits unproven) -endovascular stents (if conventional therapy unsuccessful) Prognosis -patients with malignant obstruction of SVC have Overall survival of <7 months

14. Pathology • Adenocarcinoma (including bronchioloalveolar carcinoma) — 38% • Squamous cell carcinoma — 20% • Large cell carcinoma — 5% • Small cell carcinoma -13% • Other non-small cell carcinomas (not further classified) -18% • Other (mesothelioma, carcinoids)-6%

15. NSC Lung Cancer • Adenocarcinoma -Bronchioloalveolar subtype (more common in never smokers and women) • Squamous cell Carcinoma -Centrally located -Often cavitates • Large Cell Carcinoma *prognosis is similar among the subtypes

16. Staging – NSC Lung Cancer

17. Small Cell Lung Cancer • Typically centrally located • Comprises 13% of all lung cancers • Smoking is a major risk factor • s/s: cough, dyspnea, weight loss, chest pain • Approximately 70% present with metastatic disease at diagnosis • Frequent mets to liver, bone, bone marrow, brain • Overall prognosis is poor

18. Staging – Small Cell Lung Cancer • Limited Stage -disease confined to ipsilateral hemithorax -confined to a single radiotherapy port • Extensive Stage -evidence of disease outside of ipsilateral hemithorax -disease which can not be covered by a single radiotherapy port

19. Mesothelioma • Rare type of cancer • Almost always caused by exposure to asbestos • Malignant cells develop in the mesothelium– the lining of the body’s organs (example: pleura) • There is no association between mesothelioma and smoking, although smoking greatly increases risk of asbestos induced cancer

20. Screening • NO SCREENING TEST (CXR, CT, OR SPUTUM CYTOLOGY) HAS BEEN SHOWN TO REDUCE MORTALITY FROM LUNG CANCER

21. Diagnosis • History and Physical • Laboratory studies • Radiographic Imaging (CT, PET, bone scan) • Tissue sampling

22. Imaging

23. Imaging

24. Treatment • Approach to treatment is multifactorial • Depends on: • type of cancer (Non-small cell including subtype or small cell) • stage of disease • patient’s age • performance status • patient’s smoking status • patient’s preference • Options include: • Surgery • Radiation therapy • Chemotherapy • Combination of above

25. PharmacologyChemotherapy side –effects • Carboplatin – neuropathy, renal toxicity • Cisplatin – neuropathy, renal toxicity, renal wasting of electrolytes, hearing loss • Paclitaxel – neuropathy, allergic reactions to cremaphor (preservative), chest pain, fluid retention • Navelbine – neurotoxicity, cytopenias, fatigue * all – cytopenias, nausea/vomiting, hair loss, fatigue

26. IPASS Study • EGFR inhibitor (Iressa in Europe, oral form -Tarceva in U.S.) • Compared with standard chemotherapy (Carbo/Taxol) • Found that in women, Asian descent, non-smokers, with adenocarcinoma, with EGFR mutation – PFS >3x higher with EGFR inhibitor than with standard chemotherapy.

27. Prognosis • NSC Lung Cancer: 5 year overall survival: -Stage I – 50-60% -Stage IV – 1% -Stage IV disease median survival 9 months • Small Cell Lung Cancer: 5 year overall survival: -Limited disease – 20% -Extensive disease - <1%

28. Prognosis • stage specific survival rates are better in women than in men in both NSC and small cell lung cancer • women who underwent surgical resection of disease had longer O.S. than men with same stage and surgery

29. THANK YOU