LUNG CANCER

1. LUNG CANCER Dr. Başak Oyan-Uluç Yeditepe University Hospital Department of Medical Oncology

2. Lung Cancer • Uncontrolled growth of malignant cells in one or both lungs and tracheo-bronchial tree • A result of repeated carcinogenic irritation causing increased rates of cell replication • Proliferation of abnormal cells leads to hyperplasia, dysplasia or carcinoma in situ

4. Epidemiology • Second most common tumor • 1st cause of cancer deaths • In USA: Decreasing incidence and deaths in men; continued increase in women • Women are more prone to tobacco effects 1.5 times more likely to develop lung cancer than men with same smoking habits

5. Etiology • Smoking • Cause of 90% of lung cancers • Increase risk 30 times • Cumulative dose important (pack-years) • Cigars, pipes: increase risk 2 times • Chewing tobacco • >20 packs-year: 1/7 die from lung cancer • Incidence diverge from nonsmoking population at 10 packs-year. • Passive smoking: increases risk 2 fold, cause in 17% of lung cancers in non-smokers • Other tumors caused by smoking: Oral cavity, esophagus, larynx, bladder, renal, pancreas, cervical • Radiation exposure: • Increase risk of small cell lung cancer (SCLC) • Radon: assosiated with 6% of lung cancer

6. Etiology • Asbestos: • crocidolite and amosite: Most carcinogenic • Risk: 3-4x • Isolation, pipe fitters, mining • Asbestos and smoking: synergistic, risk 80-90x • Other substances: Arsenic, nickel, chromium, chlomethyl ether, air pollutants • Lung cancer: • Increased risk of a second lung cancer • Other cancers of upper aerodigestive tract also increased FIELD CANCERIZATION • Other lung diseases • Lung scars: tuberculosis, Scleroderma- bronchoalveolar cancer • Genetic factors: • High metabolizers of debrisoquine • Lack of µclass phenotype of glutathione transferase

7. Smoking Facts • Risk related to: • age of smoking onset • amount smoked • gender • product smoked • depth of inhalation

8. Pathology • Small cell lung cancer (SCLC) (15%) • 95% central or hilar • Widespread disease at diagnosis • Hematogenous metastasis: brain, bone marrow, liver • Pleural effusions common

9. Pathology • Non-small cell lung cancer (NSCLC)(85%) • Adenocarcinoma (50-60 % of NSCLC) • Most common cell type occurring in non-smokers • Spread widely outside thorax by hematogenous dissemination • Bronchoalveolar carcinoma: • Spreading pattern within bronchioles without evidence of invasion • Radiology: Infiltrative, frequently multicentric • More frequently in young, female nonsmokers • Squamous cell (20-25% of NSCLC) • Central location • Most likely to be localized early in disease • Large cell • Mix type

10. Uncommon tumors of the lung • Bronchial carcinoids • Cystic adenoid carcinomas • Carcinosarcomas • Mesotheliomas • Caused by exposure of asbestosis • Occur in lung, pleura, peritoneum, tunica vaginalis or albeuginea of testis • Spreads rapidly over pleura, encases lung parenchyma

11. Where does it spread? • Lymph Nodes • Brain • Bones • Liver • Lung/Pleura • Adrenal Gland • 40% of metastasis occurs in the Adrenal Gland

12. Symptoms • Cough • Dyspnea • Hemoptysis • Recurrent infections • Chest pain • Symptoms related to distantmetastases • Pain • Organ-related • General Symptoms • Weight loss • Fatigue

13. Syndromes/Symptoms secondary to regional metastases • Esophageal compression  Dysphagia • Laryngeal nerve paralysis Hoarseness • Symptomatic nerve paralysis  Horner’s syndrome • Cervical/thoracic nerve invasion  Pancoast syndrome • Lymphatic obstruction  Pleural effusion • Vascular obstruction  SVC syndrome • Pericardial/cardiac extension  Effusion, tamponade

14. Sympathetic pathway for pupillary innervation

15. Horner’s syndrome In dim light, the anisocoria is accentuated with the right pupil more miotic. The right upper lid is ptotic by 1.5 mm. Ptosis Miosis Anhidrosis

16. Diagnosis • History and Physical exam • Diagnostic tests • Chest x-ray • Pathological evaluation by: • Sputum cytology • Flexible fiberoptic bronchoscopy • Percutanous and transbronchial needle biopsy • Lymph node metastases • Staging tests • CT chest/abdomen • Bone scan • Bone marrow aspiration • PET scan

17. Bronchoscopy

18. Bronchoscopy

19. Biopsy

20. Solitary pulmonary nodule (SPN) • A lesion that is both within and surrounded by pulmonary parenchyma • Size: < 3-4 cm • The major question that follows detection of a SPN: Whether the lesion may be malignant?

21. Evaluation of solitary pulmonary nodule Diagnostic strategy: • Maximize chance of detecting cancer • Minimize chance of performing a unnecessary thoracotomy if the nodule is benign Characteristics that define a solitary pulmonary nodule • A peripheral lung mass <3-4 cm • Asymptomatic • Physical examination: normal • CBC, LFT: normal

23. Likelihood that a nodule is malignant- Clinical Features - • Age: Risk increases with age <35 years 2% 35-39 years 3% 40-49 years 15% 50-59 years 43% ≥ 60 years ≥50% • Smoking history

24. Likelihood that a nodule is malignant- Radiographic Features - • Density • Malignant: <147 Hounsfield units (HU) • Benign: >167 HU • Calcification • Eccentric: carcinoma arising in an old granulomatous lesion (ie, a "scar" carcinoma) • Benign calcifications • “Popcorn" calcification • Laminated (concentric) calcification • Central calcification • Diffuse, homogeneous calcification • Size(risk increases with size) < 3 mm 0.2% 4-7 mm 0.9% 8-20 mm 18% >20 mm 50% • Border Malignant: More irregular and spiculated borders • Growth (Volume doubling time) <20 days <1% 20-400 days 30-50% >400 days <1% • Ground glass appearance • Frequently malignant (40-60%)

26. Evaluation of solitary pulmonary nodule • Serial CT scans • Metabolic imaging (PET/CT) • Nodule sampling  • Bronchoscopy • Percutaneous needle aspiration

27. SPN algorithm

28. Management of lung cancer • Accurate diagnosis • SCLC • NSCLC • Staging • Selection of treatment modality

29. Staging • Bone scan • Spinal MRI • Brain CT or MRI • Mediastinoscopy • PET, PET/CT • Bone marrow aspiration and biopsy

30. NSCLC • 80% of all lung cancers are NSCLC • Survival is improved when found at an early stage • Three distinct types of NSCLC • Treatments are the same

31. Staging and Treatment of NSCLC-Simplified

32. NSCLCStage I  2 cm Ib T2 N0 M0 Ia T1 N0 M0 Any of the following: T >3 cm T + visceral pleural involvement T + distal atelectasis T  3 cm T= main bronchial involvement  2 cm distal to carina No lobar bronchusinvolvement N0: no lymph node involvementM0: no distant metastasis

33. NSCLCStage II  2 cm IIb T2 N1 M0 IIa T1 N1 M0 T3 N0 M0 Any of the following: T+ main bronchial involvement < 2 cm distal to carina T (any size) invading chest wall, diaphragm, mediastinal pleura, or pericardium T + totalatelectasis N1: ipsilateral peribronchial and/or ipsilateral hilar nodes involvedM0: no distant metastasis

34. OR OR OR OR T2 NSCLC Stage IIIa <2 cm  2 cm T1 N2 M0 T2 N2 M0 T3 N1 M0 T3 N2 M0 T  3 cm T  chest wall(or diaphragm) T + visceral pleura involved T  mediastinal pleura (or pericardium) T + atelectasis T  3 cmNo lobar-bronchus involvement N1: ipsilateral peribronchial and/or ipsilateral hilar nodes involved N2: ipsilateral mediastinal and/or subcarinal nodes involved M0: no distant metastasis

35. 7% Stage II 31% Stage III 24% Stage I 38% Stage IV NSCLC - Stages at Presentation Fry WA, et al. Cancer. 1996;77:1949-1995.

36. Management of NSCLC • Staging to determine resectability (tumor can be surgically removed with clear margins) • Patient evaluation for operability (patient is capable of withstanding such a procedure)

37. Management of NSCLC • Surgery: Mainstay of treatment • Primary mode of therapy in stage I and II • Resectability: determined by extent of tumor • Operability: Overall medical condition of patient • ½ of NSCLC patients: operable • ½ of tumors in operable patients are resectable (25% of all patients) • ½ of patients with resectable tumors survive 5 years (12% of all patients, 25% of operable patients)

38. Determinants of resectable disease: Signs of unresectable NSCLC • Distant metastases, including metastases to opposite lung • Persistant pleural effussions with malignant cells • Cytological examination: positive for malgnant cells in 65% • Superior vena cava obstruction • Involvement of following structures: • Supraclavicular and neck lymph nodes (N3) • Contralateral mediastinal lymph nodes (N2) • Recurrent laryngel nerve • Tracheal wall • Main stem bronchus <2 cm from carina (resectable by sleeve resection technique)

39. Determinants of operability: Signs of inoperability • Age and mental status: not factors • Cardiac status • Uncontrolled cardiac failure • Uncontrolled arrhytmia • Recent myocardial infarction (within 6 months) • Pulmonary status: the patients ability to tolerate resection of part of or all of a lung must be determined • Pulmonary hypertension • Inadequate pulmonary reserve

40. Prognosis • TNM staging • Performance status • Weight loss • Tumor histology: not influence prognosis • Molecular prognostic factors • Supressor oncogene alterations: poor prognosis • Mutated p53: 50% in NSCLC, in almost all with SCLC • Dominant oncogene overexpression (c-mys, k-ras, erb-B2): poor prognosis

41. Survival Stage 5-year Survival I 60-80% II 40-50% IIIa 25-30% IIIb 5-10% IV <1%

42. SCLC • Most aggressive type of lung cancer • Responds to chemotherapy andradiation • Recurrence rates are high

43. Staging of SCLC • Limited Stage Tumor is in one lung, the mediastinumand lymph nodes that can be radiatedusing a single radiation port. • Extensive Stage Tumor has spread beyond one lung, themediastinum and local lymph nodes. Common distant sites of metastases are the adrenals, bone, liver, bone marrow, and brain.

44. Management of SCLC Limited stage: • Radiotherapy and concomitant chemotherapy • Prophylactic brain irradiation • Rarely: Surgery • <5%: Stage I, II • 30%: stage IIIA, IIIB Extensive stage: Chemotherapy

45. SCLC: Survival • Limited Disease: • Median survival 18-20 months • 5-year survival 10% • Extensive Disease: • Median survival 10-12 months • 5-year survival 1-2%

46. Complications • Treatment related: • Chemotherapy • Radiotherapy • Infection • Disease related • Superior vena cava syndrome • Brain metastasis • Carcinomatosis leptomeningitis • Paraneoplastic syndromes

47. What are Paraneoplastic Syndromes? • Heterogeneous group of disorders • Cause symptoms independent of: • Tumor invasion/metastasis • Infection • Ischemia • Metabolic/nutritional deficits • Tumor treatment

48. Mechanism

49. Paraneoplastic Syndromes • Cancer cachexia • Fatigue • Electrolyte dysfunction • Endocrine dysfunction • Neurological dysfunction* • Cutaneous lesions* • Hematological dysfunction • Coagulation dysfunction • Fever • Hepatic dysfunction • Renal dysfunction

50. Most common paraneoplastic syndromes in lung cancer-1 • Hypercalcemia • Mostly in squamous cell carcinoma • Hypertrophic osteoartropathy • Clubbing + periosteal proliferation of tubular bones • Associated with lung cancer and other lung disease • Clinically: • Symmetrical painful arthropathy • Usually involves ankles, wrists and elbows • Metacarpal, metatarsal and phalangeal bones may also be involved • Tx: If inoperable tm  NSAID, bisphosphonates