Management of Non Small Cell Lung Cancers

Etiology, Presentation, Screening, Evaluation and Management options for Early, Advanced Non Small Cell Lung Cancers

1. Management of Lung Cancers (NSCLC) Dr. Pradeep Dhanasekaran MCh Postgraduate Prof. M. P. Vishwanathan MS MCh Prof. D. Suresh Kumar, MS(AIIMS), DNB, MCh , DNB Unit TN Govt Multi SuperSpeciality Hospital, Chennai 01 March 2019

2. Overview Background Etiology Diagnosis Staging Metastatic Workup Management protocol Surgical techniques 3/01/2019 2

3. History Dr. Alton Ochsner MD Ernst Wynder and Evarts Graham 3/01/2019 3 Richard Peto and Richard Doll

4. Carcinoma Lung Most common cause of cancer death worldwide 13% of all cancers 26% of all cancer deaths 5 year Overall Survival 18% (IARC) NICPR India Lung is 2 nd most common in men, 4 th in females 9.3% of all cancer deaths 5 year OS is 5% 3/01/2019 4

5. Etiology Almost 90% - Strong association with Smoking (7 times; equal in both sex; India- RR 2.45, Passive smoking RR 1.16) 10% - Occupational hazards (Asbestos, Radon, cadmium, chromium, beryllium, nickel, arsenic and vinyl chloride) Outdoor Air pollution 1-2% COPD, Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis 3/01/2019 5

6. Disease Course 16% present in Localized stage I 37% in Regional disease Stages II 40% present in Advanced stage IV 3/01/2019 6 Pulmonary Symptoms Cough 75% Dyspnea 50 – 60% Hemoptysis 25 -40% Wheeze/Stridor Pneumonic Symptoms

7. 3/01/2019 7 Extrapulmonary Thoracic Symptoms Chest wall pain Pleuritic pain Radicular arm pain Shoulder pain Horner’s Syndrome SVC Syndrome Chronic Hiccoughs Aspiration pneumonitis Voice change and Hoarseness Pericardial Effusion Backpain Dysphagia Extrathoracic Symptoms Paraneoplastic Syndromes SIADH, Hypercalcemia, Cushing’s Lambert Eaton Myasthenic syndrome Clubbing HPOA Metastatic Symptoms 10% develop Brain metastases Head ache, Focal neurologic deficits 25% develop bony metastases Spine, Pelvis, Ribs and Sternum Hepatic and Adrenal metastases Skin and Soft tissue metastases 8%

8. Screening 1993 – 2001 : PLCO Trial (ages 55 to 74, Chest X ray as screening) – no survival or mortality benefit National Lung Screening Trial (ages 55 to 74 with 30 pack years; Chest X ray or Low Dose CT) – 20% reduction in mortality in LDCT arm Ages 55 to 80 Healthy smokers or Former smokers >30 pack years Quit < 15 years Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening; NEJM Aug 4,2011 3/01/2019 8

9. Harms 20-50% rate of finding small nodules, which are benign in 97% Reporting should be based on Lung-RADS algorithm 3/01/2019 9

10. Category Findings Probability of Malignancy Management Incomplete Part or all of lungs cannot be evaluated n/a Additional lung screening images 1 Negative No nodules/ nodules with specific calcifications < 1% Annual LDCT Screening 2 Benign Solid/part solid nodule < 6 mm GGN < 20 mm < 1% Annual LDCT Screening 3 Probably Benign Solid/part solid nodule >6 but <8mm GGN > 20 mm 1 – 2% 6 month LDCT 4A Suspicious Solid/part solid nodule >8 but <15 mm Endobronchial nodule 5 – 15% 3 month LDCT; +/- PET CT 4B Suspicious Solid nodule > 15 mm > 15% CECT Chest +/- PET CT +/- Tissue Sampling 3/01/2019 10

11. Diagnosis Risk Factors (Age, Smoking, Family history, COPD) Clinical features Imaging ( Spiculations , Upper lobe, Nodes) PET False positive in TB, fungal infections, Rheumatoid nodules and sarcoidosis False negative in Ground glass opacities, Carcinoids and small lesions <1cm 3/01/2019 11

12. Solitary Pulmonary Nodule 3/01/2019 12

13. Solitary Pulmonary Nodule Solitary lesion <3 cm in diameter, surrounded by normal lung, not associated with lymphadenopathy or pleural effusion. 3/01/2019 13

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15. Staging 3/01/2019 15

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24. Work Up False positive rate of Clinical Evaluation is 50% Incidence of occult distant metastases based on clinical Intrathoracic stage Stage I - < 5% Stage II – 15 – 20% Stage III – 25 – 30% Metastatic Workup with PET CT and Brain MRI is Optimal 3/01/2019 24

25. Staging Evaluation 3/01/2019 25

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29. Chamberlain procedure 3/01/2019 29

30. Broncho FNA EBUS FNA 3/01/2019 30

31. Treatment Recommendations Stage I, II No tumors T1a – T1c, T2a –T2b Stage II, N1 positive T1 –T2 N1 disease Locally Invasive Tumors T3/T4 N0/N1 Pancoast Tumors Stage III N2/N3 disease Incidental N2 Discrete N2/N3 Infiltrative Stage III Stage IV M1 disease 3/01/2019 31

32. History of Surgery 1933 – Graham and Singer – First Pneumonectomy 1939 – Brunn – Lobectomy 1939 – Churchill and Belsey – Segmentectomy 1952 – Allsion – Sleeve Lobectomy 3/01/2019 32

33. Principles of Surgery LOBECTOMY SUBLOBAR RESECTIONS Segmentectomy Wedge Resection SLEEVE RESECTIONS 3/01/2019 33 Pneumonectomy in Extensive main stem bronchus involvement Upper lobe lesion invading PA to lower lobe Adherence to proximal, extrapericardial PA

34. Nodal Staging Minimum of 6 nodes/stations (3 mediastinal) Primary Site Nodal stations Right Upper & Middle 7, 2R and 4R Right Lower 7, 4R, 8 and 9 Left Upper 7, 5 and 6 Left Lower 7, 8 and 9 3/01/2019 34

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36. Stage I, II (N0 disease) Stage 5 year survival IA1 (T1a N0) 90% IA2 (T1b N0) 85% IA3 (T1c N0) 80% IB (T2a N0) 73% IIA (T2b N0) 65% Surgical Resection (LOBECTOMY) Minimally Invasive preferred Systematic nodal sampling (N1 with Ipsilateral N2) No role for Adjuvant Chemo or RT in IA, IB No Survival benefit with Mediastinal staging in Stage I Recurrence Rate 20% in 5 years 3/01/2019 36

37. Sublobar Resections ( Segmentectomy /Wedge Resection) Tumors < 1 cm Elderly patients with Tumors < 2cm Pure GGO lesions Poor or Medically Unfit Predicted PO FEV1 < 30% Predicted PO DLCO < 30% Functional capacity < 22m on stair climbing test Margins more than tumor diameter or at least 2 cm margin 3/01/2019 37

38. 3/01/2019 38 SBRT Local control rate 90% 5 yr OS 29% Vs Surgery 59% RTOG 0236/RTOG 0813 RFA Local Control 60% 5 yr OS 30%

39. Stage IIB (N1 disease) 5 year OS 56% Surgery (LOBECTOMY with complete mediastinal staging) Followed by Adjuvant Chemotherapy (Cisplatin Based) Cisplatin with Vinorelbine / Docetaxel / Gemecitabine 4 cycles Only role for PORT is Bronchial Margin positivity ANITA Trial 16% disadvantage with PORT in chemo arm 3/01/2019 39

40. Locally Invasive T3/T4 N0/N1 T3 Lesions En Bloc Surgical Resection Followed by Adjuvant Chemotherapy PORT has no PFS/OS benefit in N0/N1 Indicated in N2 T4 Lesions Resectable T4 (>7 cm) Resection f/b Adjuvant Chemotherapy/ Chemoradiation based on margin status Unresectable T4 Definitive Chemoradiotherapy Pancoast Tumors Chemoradiotherapy Cisplatin + Etoposide with 45 Gy RT Followed by Surgery 3/01/2019 40

41. Infiltrative Stage III Good PS – Definitive Concurrent Chemoradiation followed by Durvalumab (Improve OS of 4% at 2 years Poor PS – Sequential therapy, RT alone or palliative systemic treatment RT alone RTOG 7301 – 60 Gy in 6 weeks RTOG 8311 – 79.2 Gy Accelerated # EORTC – CHART 54 Gy /1.5Gy/3# daily RTOG 7301 – 60 Gy RTOG 9311 – 70 – 90Gy with 3D Conf RT RTOG 0617 – no absolute benefit with 74Gy In concurrent chemo setting No benefit over 60 Gy 3/01/2019 41

42. Concurrent ChemoRT RTOG 9410 Median OS and Local control rates better West Japan Lung Cancer Group Concurrent vs Sequential – concurrent better median survival Cisplatin/Etoposide or Carboplatin/paclitaxel combinations No role for Neoadjuvant or Induction Chemotherapy before Chemoradiation No role for Adjuvant Chemotherapy after Chemoradiation Role for Adjuvant Immune checkpoint inhibition (PACIFIC STUDY) Durvalumab – longer PFS, no increase in toxicity OS to be determined PFS decline in EGFR mutation patients ?no benefit 3/01/2019 42

43. Stage IV 3/01/2019 43

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48. Stage IV Pleural/Pericardial effusion – positive – Pleurodesis / ambulatory small catheter drainage/ pericardial window 3/01/2019 48

49. Pleurodesis 3/01/2019 49

50. Oligometastases ( 1 to 3) Curative Intent possible Surgical resection of primary and secondary sites with adjuvant chemotherapy and Brain RT (if Secondary in brain) Secondary cancers/ Metachronous – Different histology, > 4 years apart. Same histology, within 2 years – Recurrence 3/01/2019 50

51. Nutshell Stage I and II (T1 -T2, N0/N1) – Surgery f/b adjuvant chemotherapy (RT in margin positive) Stage IIB T3 N0 – Same as above Stage IIIA T3/T4 N0/N1 – Preoperative Chemoradiation f/b Surgery Pancoast’s – Same as above Stage IIIB and IIIC (N2/N3 disease) – Definitive Chemoradiation f/b Durvalumab Stage IV – Mutation testing – Systemic therapy with chemotherapy or Targeted agents 3/01/2019 51

52. Our Experience – Case 1 3/01/2019 52 Ponraj 55/M Bx inconclusive Left Lower lobectomy AdenoCA Workup Metastases to bone Systemic chemotherapy EGFR Negative

53. Our Experience – Case 2 3/01/2019 53 Mohd Azharudeen 24/M Rt LL Carcinoid Rt Lower Lobectomy f/b Observation

54. Our Experience – Case 3 3/01/2019 54 Mr. Pitchaikani SCC Left LL lung (N2) Post ChemoRT Residue Left Lower Lobectomy f/b observation

55. Our Experience – Case 4 3/01/2019 55 Muthulakshmi 65/F Adeno CA Left LL lung Left lower lobectomy with nodal dissection pT1b N0 Observation

56. Prevention Control of sale and advertisement Imitations and graphic warnings on products Avoid smoking in indoor places Organized smoking cessation intervention program Abstinence medications ( Vareniciline , Bupropion, nicotine patch, gums, lozenges, inhaler & sprays) No benefits from Antioxidants 3/01/2019 56

57. Thank You 3/01/2019 57