1. Introduction to: Lung Cancer Lorraine Martelli-Reid RN(EC),MN, NP-Adult Lung Disease Site Team Juravinski Cancer Centre

2. Objectives To understand the clinical presentation, risk factors and prognostic factors in relation to the management of patients with Lung Cancer To understand the diagnostics and staging of the diagnosis of Lung Cancer To understand the standard treatments in relation to the management of patients with Lung Cancer

3. Lung Cancer Statistics In 2008, an estimated 23,900 Canadians will be diagnosed with lung cancer and 20,200 will die of it. Lung cancer is the leading cause of cancer deaths in both men and women Lung cancer is the 2 nd most common type diagnosed in both men and women One in 12 men is expected to develop lung cancer during their lifetime and one in 13 will die of it. One in 16 women is expected to develop lung cancer during their lifetime and one in 18 is expected to die of it. Lung cancer incidence and death rates continue to climb among women while decreasing among men.

4. Risk Factors Smoking Risk declines after 5 years of non-smoking Passive smoking: an increase in RR of lung cancer ~25% Environmental exposure: 2 - 3% of all lung cancer cases 85% of lung cancer deaths can be attributed to smoking Higher incidence among those of African descent

5. Risk Factors Cont’d Occupational exposure arsenic, asbestos, ether, chromium, nickel, polycyclic aromatic compounds, radon, vinyl chloride Geography Clustering among men along coastal areas (industry and asbestos exposures) Indurstry: crude petroleum, coal, tars, combustion products, wood dust Diet: Possible protective effect from a diet rich in fresh fruit and vegetables. 2 RCTs show no benefit from alpha-tocopherol and harm from beta-carotene. Possible genetic predisposition

6. Prevention, Screening & Early Detection 85% of lung cancers are caused by smoking and thus can be prevented Decrease the number of new smokers Help present smokers quit <10% those with heavy asbestos exposure will develop mesothelioma, but 80% of those with pleural mesothelioma had heavy asbestos exposure There is currently no evidence that screening decreases the cost of lung cancer nor decreases mortality rates Early detection is difficult since presenting symptoms are common to other health problems

7. Most Common Signs & Symptoms at Diagnosis %

8. Signs of Tumor Spread Regional Tumor Spread Superior Vena Cava Syndrome (SVC) Hoarseness from laryngeal nerve paralysis Horner’s syndrome Pancoast syndrome Pleural effusion Pericardial effusion and tamponade Metastases or Paraneoplastic Syndromes Spread to liver, bone, adrenals, brain Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) Cachexia Hypertrophic osteoarthropathy (HPOA)

9. Diagnostics & Staging CXR CT scan of chest: If mediastinal lymph nodes are ≥ 1.5 cm, then sensitivity is 60- 70%, specificity is 70% → mediastinoscopy Bronchoscopy for tissue diagnosis EGFR and ALK mutation testing if stage 4 non-squamous NSCLC Mediastinoscopy to assess the level of lymph node involvement (not always needed) Positron Emission Tomography (PET) current indications in Lung Cancer Solitary pulmonary nodule-unable to obtain tissue diagnosis NSCLC-where curative surgical resection is being considered Stage III NSCLC- potentially curative combined chemo/rads Limited Stage SCLC- for evaluation, staging & potentially curative chemo/rads

10. PET as a Diagnostic Tool

11. Diagnostics & Staging Thorough history and physical assessment Smoking history: #pack years Co-existing health problems Change in usual symptoms Symptoms or findings of metastatic disease Performance status, weight loss CBC and Chemistries Hb (anemia), creat (kidney functioning), Na (SIADH), Ca, liver function tests, alk phos Pulmonary function tests Needed prior to surgery or radiation Bonescan, MRI brain and abdominal imaging (liver and adrenals) * if patient had a PET don’t need bonescan

12. Histology of Lung Cancer Small Cell20-25% Non-Small Cell 70-90% Squamous25% Adenocarcinoma40% Large Cell 10% Other 25% Mesothelioma not considered a true lung cancer Small Cell is declining Increased frequency of Adenocarcinoma in recent years

13. TNM Classification for NSCLC T1:Tumour ≤ 3 cm, surrounded by lung or visceral pleura, not more proximal than the lobar bronchus T1a: Tumour ≤ 2 cm T1b: Tumour > 2 but ≤ 3 cm T2: Tumour > 3 but ≤ 7 cm, or tumour with any of the following: invades visceral pleura, involves main bronchus ≥ 2 cm distal to the carina, atelectasis/obstructive pneumonia extending to hilum but not involving the entire lung T2a: Tumour > 2 but ≤ 5 cm T2b: Tumour > 5 but ≤ 7 cm

14. TNM Classification Cont’d T3: Tumour > 7 cm; or directly invading chest wall, diaphragm, phrenic nerve, mediastinal pleura, or parietal pericardium; or tumour in the main bronchus < 2 cm distal to the carina; or atelectasis/obstructive pneumonititis of entire lung; or separate tumour nodules in the same lobe T4: Tumour of any size with invasion of heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; or separate tumour nodules in a different ipsilateral lobe

15. TNM Classification Cont’d N0: Regional lymph nodes not involved N1: Ipsilateral peribronchial or hilar lymph nodes, Intrapulmonary lymph nodes by direct extension (stations 10-14) N2: Ipsilateral mediastinal and/or subcarinal lymph nodes (stations 5-9) N3: Contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph nodes (stations 2-4) M0: No distant metastases M1: Distant metastases present

16. Non-Small Cell Lung Cancer Stage 1 Stage 1A Stage 1B (T1aN0M0 or T1bN0M0) (T2aN0M0)

17. Non-Small Cell Lung Cancer Stage II Stage IIA Stage IIB (T2bN0M0 or T2aN1M0) (T2bN1M0 or T3N0M0) (N1=stations 10-14)

18. Non-Small Cell Lung Cancer Stage III Stage IIIA or Stage IIIB (T4N0M0, T3/T4N1M0, T2/3N2M0) (any TN3M0 or T4N2M0) N2=stations 2-9, ipsilateral N3=stations 1-9, contralateral

19. Non-Small Cell Lung Cancer Stage IV Stage IV (any T any N M1) Tumor has spread to other lung or beyond the chest

20. Lymph node station #’s and names

21. Non-Small Cell Lung Cancer Treatment Options and Prognosis StageTreatment Survival at 5 years Stage 1A/1B Surgical Resection1A ~ 67% 1B ~ 57% Stage 2A 2B Surgery alone vs Surgery + Adjuvant Chemo 45% ↑ 10- 60% 35% ↑ 15% 50% Stage 3A Surgery alone vs surgery + Adjuvant chemo Neoadjuvant chemo/rads + surgery Radiation alone vs Concurrent chemo/rads 21% ↑ 29% 21% ↑ 25%-45% 15% ↑ 30% (at 3 yrs) Stage 3B Radiation alone vs. Concurrent chemo/rads 10% ↑ 20% (at 3 years) Stage 4No treatment vs Chemotherapy or Radiation (symptoms) 15% ↑ 24% (at 1 year)

22. Chemotherapy for NSCLC In addition to diagnostics and staging ones performance status ECOG and % weight loss determine fitness for chemotherapy Cisplatin is the most active drug in NSCLC and SCLC Cisplatin doublet therapy is the first treatment of choice when weight loss is ≤ 5% and ECOG=0/1 Cisplatin is usually combined with Etoposide, Gemcitabine Carboplatin can be substituted for cisplatin in the presence of impaired kidney functioning but is inferior Other drugs: paclitaxel, docetaxel

23. Radiation for NSCLC Best responses are achieved when disease is treated to 60Gy daily over 6-7 weeks continuously Brachytherapy: High-dose rate (HDR) endobronchial brachytherapy is selected with airway obstruction and ≥moderate hemoptysis Seeds are placed close to the tumor and radiation is delivered over a few minutes to the area with little injury to adjacent tissue Delivered 1-2 weeks apart usually 2-3 sessions until symptoms are relieved

24. Treatment for Resected NSCLC Stages IIA, IIB, IIIA Cisplatin (C) Day 1 and Day 8 each cycle Vinorelbine (V) Day 1, 8, 15, 22 each cycle Day 1 & Day 8 = clinic visit, lab, 5 hrs Day 15 & Day 22 = lab, 1 ½ hrs Ondansetron post chemo X 5 doses days 1& 8 Dexamethasone post chemo X 4 doses days 1 & 8 Constipation prophylaxis first 14 days each cycle Cycle 1 MonTuesWedThursFriSat Day 1 CV Day 8 CV Day 15 V Day 22 V Repeat X 4

25. Treatment for Stage IV NSCLC First line recommendation: The combination of a platinum agent with either vinorelbine, gemcitabine, paclitaxel For non-squamous histology-If an EGFR mutation is detected then erlotinib is recommended The decision to use a particular regimen should be influenced by the clinical setting and the toxicity of the regimen chosen 3 drugs are not better than 2 drugs There is disagreement regarding the optimum treatment for those >70 yrs. There is conflicting evidence regarding the use of non-platinum doublets Carboplatin substituted for Cisplatin is not as effective, but is less toxic

26. Other Treatments Targeting epidermal growth factor receptors (EGFR) EGFR gene is frequently expressed in NSCLC Mutations present that encode for tyrosine kinase Occur more frequently in adenocarcinoma, women, Asians and patients who have never smoked EGFR, ALK, KRAS, and EML4-ALK genes Erlotinib=Tarceva Gefitinib=Iressa

27. Side Effects + Monitoring For resected early stage NSCLC on adjuvant chemotherapy Fatigue Anemia Post-thoracotomy pain Peripheral neuropathy Depression

28. Side Effects + Monitoring For Stage III receiving concurrent cisplatin + etoposide + radiation Esophagitis Fatigue Post treatment radiation pneumonitis Onset 2-6 months post treatment Acute onset of cough/SOB CXR demonstrates pneumonitis Treat with prednisone +/- antibiotics

29. Side Effects and Monitoring For Tarceva: Most Common 75% rash Acne-like and a strong reason for discontinuation Rash management protocols 54% diarrhea 52% fatigue + anorexia 41% dyspnea 33% nausea + cough 23% vomiting

30. Small Cell Lung Cancer Limited Stage: involves one lung, mediastinum, ipsilateral supraclavicular fossa and can be encompassed by one radiation treatment field Extensive Stage: disease spread beyond the chest or malignant pleural/pericardial effusion

31. Small Cell Lung Cancer Treatment Options and Prognosis StageTreatmentPrognosis at 5 years Limited Stage Concurrent chemo/rads + prophylactic cranial radiation NO Surgery 20-25% Extensive Stage Palliative Chemotherapy 5%

32. SCLC Treatments For Limited Stage: Cisplatin + Etoposide concurrently with radiation to chest (45Gy) If CR after 4 cycles will proceed to 6 cycles Followed by PCI For Extensive Stage: Cisplatin + Etoposide Other chemo drugs possible

33. Side Effects + Monitoring Delayed effects of PCI Onset can be 2-5 yrs post treatment Cerebral atrophy Dementia Confusion Personality changes

34. Mesothelioma Mesotheliomas arise from the serosal lining outside of the lungs within the chest or outside the bowel within the abdomen. About 100 new cases of malignant mesothelioma appear in Canada each year Malignant mesothelioma is usually not curable; overall survival is approximately 1 year Etiology/Risks Crocidolite (Cape blue asbestos), the main cancer causing form of asbestos, is associated with over 90% of pleural and peritoneal mesotheliomas asbestos industry; dockyard workers, especially if they dismantle asbestos-insulated steam piping; those who handle and manufacture asbestos compounds; insulators and steam fitters; and those in demolition and construction industries

35. Mesothelioma Symptoms are due to tumor growth and invasion of surrounding tissues: pleural effusion, ascites, or pericardial effusion Chest pain may be caused by invasion of the chest wall Pleural effusion causes collapse of adjacent lung and shortness of breath fever, night sweats and weight loss Treatment % of patients may have a temporary shrinkage of the disease with currently available drugs. Chemotherapy with pemetrexed

36. Mesothelioma Staging Stage I: Disease confined within the capsule of the parietal pleura (i.e., ipsilateral pleura, lung, pericardium, and diaphragm). Stage II: All of stage I with positive intrathoracic (N1 or N2) lymph nodes. Stage III: Local extension of disease into the following areas, e.g., chest wall or mediastinum, heart or through the diaphragm or peritoneum, with or without extrathoracic or contralateral (N3) lymph node involvement. Stage IV: Distant metastatic disease.

37. Treatment Surgery is rare unless there is only one plaque and a lobe of lung can be removed % of patients may have a temporary shrinkage of the disease with currently available drugs. Chemotherapy with cisplatin + pemetrexed (Alimta)* has an improved median survival of 13.3 months vs. 10 months with cisplatin alone Cisplatin has also been combined with gemcitabine, vinorelbine or vinorelbine, but with no survival advantage * Alimta only covered by Workers Compensation if asbestos exposure occurred in Canada