1. Tissue Diagnosis and Staging for SBRT 2012 Lung Cancer Summit – Focus on Thoracic Surgery: Lung Cancer Kazuhiro Yasufuku Director, Interventional Thoracic Surgery Program Assistant Professor, University of Toronto Division of Thoracic Surgery, Toronto General Hospital 1 Boston Marriott Copley Place, Boston, MANovember 17th, 2012

2. Disclosure Educational and research grants from Olympus Medical Systems Corp. Consultant for Olympus America Inc. Consultant for Intuitive Surgical Inc. Novadaq Corp. Veran Medical Technologies 2

3. Lung Cancer 3 Tissue Diagnosis Staging

4. Treatment for Stage I NSCLC Anatomic resection is the gold standard Local control ~90% Overall Survival ~60-80% Medically inoperable stage I patients represent a big challenge Up to 25% of all stage I patients Untreated 5 year Overall Survival 5-10% Conventionally fractionated RT a poor second choice (~30 treatments over 6 weeks) 30-60% local control 4

5. Survey of SBRT use in USA 5 1600 American radiation oncologists Of 1373 contactable physicians, 551 responses (40.1%) received 63.9% of physicians using SBRT of whom nearly half adopted it in 2008 or later most common disease sites were lung (89.3%), spine (67.5%), and liver (54.5%) tumors Cancer 2011;117:4566–72

6. Princess Margaret Hospital SBRT Criteria Ongoing phase II (2004 – present) Pts deemed medically inoperable by a thoracic surgeon ECOG PS 0-3 NSCLC T1 or T2 lesion, <5cm N0 M0 PET –ve elsewhere Previous thoracic RT acceptable provided no significant overlap No lower limit for lung function 6

7. Surgery for Early Lung Cancer 7 LobectomyLimited Resection

8. CALGB 140503 Phase III Randomized Trial of Lobectomy vs Sublobar Resection for Small (<2cm) Peripheral NSCLC 8 Randomization Surgery Confirmation of NSCLC on Path N0 status on frozen section (4R, 7, 10R on right) (5or6, 7, 10L on left) LobectomyLimited Resection

9. Options for high-risk pts with stage I NSCLC Sublobar resection (wedge or segmentectomy) Surgery provides tumor histology Lymph node sampling/dissection may provide identification of other occult disease Better pathological staging may inform decision of an adjuvant regimen Better loco-regional control SBRT May result in better QOL Since better loco-regional control may not translate into better survival 9

10. Diagnostic tools for peripheral lung nodules Clinical History Old Films Chest CT FDG-PET CT guided TTNA Bronchoscopy (EBUS, Navigational bronchoscopy, etc) Surgery 10

11. Is tissue Dx mandatory prior to SBRT? Stereotactic body radiotherapy (SBRT) SPN clinically diagnosed as lung cancer with no path confirmation: comparison with NSCLC Comparison of outcomes of Bx proven NSCLC (n=115) vs SPN clinically diagnosed as lung cancer (CDLC) (n=58) treated with SBRT (2005-2011) Treatment outcome of CDLC group was almost identical to that of NSCLC SBRT can be legitimately applied to CDLC, provided that they are carefully diagnosed by integrating various clinical findings 11 Takeda et al, Lung Cancer. 2012 ;77(1):77-82 3y Local ControlRegional-freeMets-freeCause-specific Survival Overall Survival NSCLC80%88%70%74%54% CDLC87%91%74%71%57%

12. Mediastinal Staging Clinical staging can markedly differ from pathologic staging 24% clinically overstaged 20% clinically understaged 190 cN2 patients: 38% pN0 / pN1, 6% pN3 119 cN2 patients: 14% with pN2 ATS/ERS/ESTS: obtain pathologic evaluation in patients thought to be a surgical candidate before thoracotomy 12 Bülzebruck et al, Cancer 1992; 70: 1102 Watanabe et al, Ann Thorac Surg 1991; 51: 253 Am J Respir Crit Care Med 1997; 156: 320 Cerfolio et al Ann Thorac Surg 2005; 80: 1207 De Leyn et al, Eur J Cardiothorac Surg 2007; 32: 1

13. Surgical Staging (Cervical Mediastinoscopy) Considered “Gold Standard” Sensitivity 80%, Specificity 100% FN rate 10% Downside Invasive Unable to reach posterior subcarinal LN, #5, #6 Non-operable candidates may have to undergo surgical staging 13

14. Endoscopic Staging (EBUS-TBNA) Access to all LN stations accessible by Med as well as N1 nodes A minimally invasive modality which can be performed under LA Performed in over 1800 centres 14

15. Lung ca mediastinal staging EBUS-TBNA Systematic Review and Meta-analysis 10 studies (n=817) Sensitivity = 0.88 (95%CI, 0.79-0.94), Specificity = 1.00 (95%CI, 0.92-1.00) Results compare favorably with published results for PET and CT 15 Adams et al. Thorax; 2009; 64: 757-62

16. Lung ca staging (EBUS vs PET) SensitivityNPV StudyYearNumberCriteriaEBUSPETEBUSPET Yasufuku et al2006102Potentially operable pts92.38097.491.5 Hwangbo et al2009117Potentially operable pts907096.785.2 Herth et al200897PET, CT negative8998.9 Bauwens et al2008106PET positive9397 Rintoul et al2009109PET positive91 60 16 EBUS-TBNA compared to PET Two studies in potentially operable patients show that EBUS is superior to PET or CT for LN staging EBUS spares invasive procedures Tissue confirmation of PET-positive lesions is recommended to prove that the lesions are truly malignant

17. EBUS-TBNA in non-operable pt with NSCLC pursuing radiotherapy as primary treatment 49 pts with NSCLC considered for Carbon Ion Radiotherapy (CIRT) with abnormal PET-CT accumulations in mediastinum and/or hilum 17 Nakajima et al. J Thorac Oncol. 2010;5: 606–611

18. EBUS-TBNA in non-operable pt with NSCLC pursuing radiotherapy as primary treatment 18 Nakajima et al. J Thorac Oncol. 2010;5: 606–611 43 pts had N0 disease Dx accuracy 93.9%

19. 81F, COPD, RUL SPN Chest X-ray 19

20. 81F, COPD, RUL SPN CT Mapping 20

21. 81F, COPD, RUL SPN TBNA, TBBx, Brush, Wash – squamous cell ca EBUS-TBNA – N0 disease 21

22. Summary The need for SBRT is increasing in an aging population The success depends primarily on accurate staging prior to SBRT Accurate LN staging by EBUS-TBNA will allow opportunities for high-risk inoperable pts with NSCLC to undergo minimally invasive treatment 22

23. 23 Division of Thoracic Surgery Toronto General Hospital University Health Network Kazuhiro Yasufuku, MD, PhD, FCCP kazuhiro.yasufuku@uhn.ca Thank you