Tissue Diagnosis and Staging for SBRT

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

3. Lung Cancer Staging Tissue Diagnosis

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

5. Survey of SBRT use in USA 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

7. Surgery for Early Lung Cancer Lobectomy Limited Resection

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

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

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 Takeda et al, Lung Cancer. 2012 ;77(1):77-82

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 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

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

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 Adams et al. Thorax; 2009; 64: 757-62

16. Lung ca staging (EBUS vs PET) • 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 Nakajima et al. J Thorac Oncol. 2010;5: 606–611

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

19. 81F, COPD, RUL SPN • Chest X-ray

20. 81F, COPD, RUL SPN • CT Mapping

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

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

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