Navigational Bronchoscopy with Transbronchial Radiofrequency Ablation

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1 Navigational Bronchoscopy with Transbronchial Radiofrequency Ablation Katie S. Nason, MD MPH AATS Focus on Thoracic: Mastering Surgical Innovation October 28, 2017 No disclosures

2 Radiofrequency ablative therapy for lung cancer Thermal-based technology induces cellular death Highly resistant air-filled lung tissue & low resistant intraparenchymal tumor Insulating effect and traps heat within the targeted tumor Limiting damage to large amounts of normal tissue. Eradicate all viable malignant cells while sparing NORMAL SURROUNDING LUNG Principles of and Advances in Percutaneous Ablation Muneeb Ahmed, Christopher L. Brace, Fred T. Lee, S. Nahum Goldberg Radiology, 2011, Vol.258: , /radiol

3 Radiofrequency ablation (RFA) Alternative treatment method for early-stage lung cancer Poor surgical candidates Exhausted their maximum radiation therapy Oligometastasis from distant cancer or as a therapy for the local control of tumors.

4 Key elements of technical success

5 Technical Success at Ablation Study Procedure time RFA Carrafiello (2012) NR 43/43 (100) Lanuti (2009) 38/38 (100) Schneider (2012) 45 min 30/30 (100) Pennathur (2009) NR NR Local Recurrence & Metastasis Local Recurrence Time to local recurrence (mo) Metastasis Zemlyak (2010) 4/12 (33) 13 3/12 (25) Carrafiello (2012) 2/36 (6) Lanuti (2009) 12/38 (32) 75% by 6 Schneider (2012) 8/26 (31) 6 8/26 (31) Pennathur (2009) 35/100 (35) 15

6 Meta-analysis: Efficacy of Disease Control Zhu JC, Yan TD, Morris DL. A systematic review of radiofrequency ablation for lung tumors. Ann Surg Oncol 2008; 15:

7 Procedure related complications Pneumothorax req drainage Pulmonary artery pseudoaneurysm Bronchopleural fistula Hemoptysis Air embolism Rib fracture Pneumonia Diaphragm injury Hemothorax Lung abscess Nerve injury Needle tract seeding Pleural effusion Mortality (0-2.5%)

8 Zhu, J. C., et al. (2008). "A systematic review of radiofrequency ablation for lung tumors." 16 articles, 224 procedures, median 43.5/pub Pneumothorax 28% (4.5-61%); req chest tube 11% (3.3-39%) Hemoptysis % Pneumonia 9.5% (6-12%) Pleural effusion 13% (1.3 60%) Mortality 0-5.6% (median 0) Zhu, J. C., et al. (2008). Ann Surg Oncol 15(6):

9 Transbronchial Radiofrequency Ablation?SAME EFFICACY WITH REDUCED RISK PROFILE?

10 Ablate & resect trial w/ 3 different tip lengths Tanabe et al,. Chest 2010; 137:

11 20 patients 9 / 11 Age 58 to 88 (mean 76) Histology 12 adeno 6 squamous 1 undifferentiated 23 lesions ct1 2aN0M0 ( 5cm) Department of Cardiothoracic Surgery

12 Koizumi T, et al., Respiration 2015; 90:

13 Koizumi T, et al., Respiration 2015; 90:

14 Koizumi T, et al., Respiration 2015; 90:

15 Safe? Koizumi et al. (Respiration 2015; 90: 47-55) No serious adverse events, bleeding, arrhythmia, hyperthermia, hypoxemia or pneumothorax Two patients complained of weak chest pain during the treatment RFA discontinued, repositioned catheter, continued Radiographic consolidation in 3 cases with presenting with postprocedure fever Xie et al. (Respiration 2017; 94: ) 3 patients chest pain & fever (1/3) o/w NO major complications Suzuki et al (Bronchology Interv Pulmonol 2011; 18: ) 8 rabbits 1 hemoptysis, no pneumothorax, thermal injury, or death Tsushima et al. (Eur Respir J 2007; 29: ) 6 sheep No hemoptysis, pneumothorax, thermal injury or death

16 Effective? Median PFI 21 months with percutaneous RFA Progression-Free Survival Overall Survival 20 subjects, ct1 2aN0M0 Koizumi T, et al., Respiration 2015; 90:

17 Balancing Innovation and Safety Previous study complete ablation 7/18 with 90% ablation in 9 of 18 89% local control 32 patients; tumor size cm; open thoracotomy 12 complete ablation (38%); 16 (50%) scattered viable tumor cells 4 with >20% tumor viability All adenocarcinoma Schneider T, et al., The Annals of thoracic surgery 2009; 87: Schneider T, et al., EJCTS, 2011; 39:

18 Balancing Innovation and Safety Tanabe T, et al., Chest 2010; 137: Max ablation area w/1 cm tip = 12 x 10 mm Incomplete tumor cell killing

19 20 patients 9 / 11 Age 58 to 88 (mean 76) Histology 12 adeno 6 squamous 1 undifferentiated 23 lesions ct1 2aN0M0 ( 5cm) Department of Cardiothoracic Surgery

20 Balancing Innovation and Safety Wan J, et al., Oncol Rep 2016; 36:

21 Summary and Conclusions Transbronchial RFA Safe? Effective? Ready for wide-spread use? Further studies and innovation needed Increase ablation size Determine appropriate candidates

22 Navigational Bronchoscopy with Transbronchial Radiofrequency Ablation Katie S. Nason, MD MPH AATS Focus on Thoracic: Mastering Surgical Innovation October 28, 2017 No disclosures

23 Xie et al., Respiration 2017; 94:

24 Xie et al., Respiration 2017; 94:

25 Balancing Innovation and Safety serum levels of TNF-a, CCL-2 and CCL-4 were increased in patients with ICA immediately upon therapy compared to these values in patients with CA or healthy donors, thereby suggesting that these inflammatory factors might be used as biomarkers for RFA efficiency. Schneider T, Sevko A, Heussel CP, Umansky L, Beckhove P, Dienemann H, Safi S, Utikal J, Hoffmann H, Umansky V. Serum inflammatory factors and circulating immunosuppressive cells are predictive markers for efficacy of radiofrequency ablation in non-small-cell lung cancer. Clin Exp Immunol 2015; 180:

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