Pneumonectomy After Induction Rx: Is it Safe? David J. Sugarbaker, M.D. Director, Chief, Division of Thoracic Surgery The Olga Keith Weiss Chair of Surgery of Medicine at,
Pneumonectomy after induction Rx Optimal treatment strategies for operable advanced stage lung cancer is still uncertain In patients with locally advanced lung cancer, improved resectability has been seen after concurrent chemoradiotherapy at, Chest x-ray courtesy of David J. Sugarbaker, M.D.
Challenges with pneumonectomy after induction therapy Chemoradiation may reduce pulmonary function and can result in significant fibrosis around key hilar structures Induction therapy may increase patient susceptibility to pulmonary edema and impair ability of bronchial stumps to heal Known complications/morbidity associated with pneumonectomy after induction therapy include: ARDS, pulmonary edema, broncho-pleural fistula, arrhythmias, prolonged air leak, vocal cord paralysis, and empyema Krasna MJ, Gamliel Z, Burrows WM, Sonett JR, Kwong KF, Edelman MJ, et al. Pneumonectomy for lung cancer after preoperative concurrent chemotherapy and high-dose radiation. Ann Thorac Surg. 2010;89(1):200-6; discussion 6. at,
INT 0139, 2009 Phase III trial Induction chemort followed by either surgery or definitive RT Mortality of 26% after pneumonectomy after induction Albain KS, Swann RS, Rusch VW, Turrisi AT, 3rd, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009;374(9687):379-86 at
Overall survival not improved Improved OS for patients undergoing lobectomy when compared to no resection No survival benefit in patients undergoing pneumonectomy when compared to no resection Albain KS, Swann RS, Rusch VW, Turrisi AT, 3rd, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009;374(9687):379-86 at
Intergroup 0139 5 year survival for ypn0 41% Survival benefit for downstaging 5 year survival for ypn+ 24% No surgery after induction: 8% Albain KS, Swann RS, Rusch VW, Turrisi AT, 3rd, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009;374(9687):379-86 at
Caglar et al, 2009 144 pts received concurrent chemoradiation (CRT) 100 CRT only 44 deemed resectable and underwent surgical resection Caglar HB, Baldini EH, Othus M et al. Outcomes of patients with Stage III nonsmall cell lung cancer treated with chemotherapy and radiation with and without surgery. Cancer 2009;115:4156 66. at
Caglar et al, 2009 32/44 pts (73%) with LN downstaging 2 year survival in surgical resection group was 73% 2 year survival in CRT only was 37% Caglar HB, Baldini EH, Othus M et al. Outcomes of patients with Stage III nonsmall cell lung cancer treated with chemotherapy and radiation with and without surgery. Cancer 2009;115:4156 66. at
Allen et al, 2008 Retrospective review, 73 pts Patients underwent pneumonectomy after induction chemort 6% 30 day mortality, 10% 100 day mortality Allen AM, Mentzer SJ, Yeap BY, Soto R, Baldini EH, Rabin MS, et al. Pneumonectomy after chemoradiation: the Dana-Farber Cancer Institute/Brigham and Women's Hospital experience. Cancer. 2008;112(5):1106-13. at
Allen et al, Conclusions Lymph node downstaging after induction chemort leads to improved survival Not all pts had N2 nodes so lymph node downstage rate could not be assessed in their study Trimodality approach should be done at high volume centers at, Allen AM, Mentzer SJ, Yeap BY, Soto R, Baldini EH, Rabin MS, et al. Pneumonectomy after chemoradiation: the Dana-Farber Cancer Institute/Brigham and Women's Hospital experience. Cancer. 2008;112(5):1106-13.
Does pneumonectomy after induction therapy improve survival? Daly et al, 2006 Retrospective review 30 patients undergoing pneumonectomy after chemort at, Daly BD, Fernando HC, Ketchedjian A, Dipetrillo TA, Kachnic LA, Morelli DM, et al. Pneumonectomy after high-dose radiation and concurrent chemotherapy for nonsmall cell lung cancer. Ann Thorac Surg. 2006;82(1):227-31.
Daly et al, 2006 Death in 4 pts, 13.3% Median survival 22 months, 5 year 33% 3yr survival after high-dose RT and concurrent chemotherapy without surgery as definitive tx for stage IIIA-N2 disease in INT 0139 33% 55% with N2 nodal downstaging but no correlation with survival at, Daly BD, Fernando HC, Ketchedjian A, Dipetrillo TA, Kachnic LA, Morelli DM, et al. Pneumonectomy after high-dose radiation and concurrent chemotherapy for nonsmall cell lung cancer. Ann Thorac Surg. 2006;82(1):227-31.
Bueno et al, 2000 Determine predictive value of nodal status at resection for stage IIIA N2+ All patients staged surgically Mediastinoscopy/anterior mediastinotomy 103 pts, restaged radiographically Bueno R, Richards WG, Swanson SJ, Jaklitsch MT, Lukanich JM, Mentzer SJ, et al. Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival. Ann Thorac Surg. 2000;70: 1826 1831 at
29/103 pts (28%) downstaged to N0, 5 year survival of 35.8% 74/103 pts (72%) pts with persistent disease with N1/N2 status, 5 year survival of 9% Recommend restaging with thoracoscopy, PET, lymph node biopsy via EUS at Bueno R, Richards WG, Swanson SJ, Jaklitsch MT, Lukanich JM, Mentzer SJ, et al. Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival. Ann Thorac Surg. 2000;70: 1826 1831
Restaging the mediastinum after induction therapy will allow the surgeon to prevent resection in patients with less survival benefit Methods to restage mediastinum include: VATS Redo mediastinoscopy PET EBUS at
Jaklitsch et al, 2013 Can VATS be used to restage ipsilateral mediastinal LN after neoadjuvant therapy? Prospective multi-institutional trial, 68 pts Jaklitsch MT, Gu L, Demmy T, Harpole DH, D Amico TA, McKenna RJ et al. Prospective phase II trial of preresection thoracoscopic mediastinal restaging after neoadjuvant therapy for IIIA (N2) non-small cell lung cancer: results of CALGB Protocol 39803. J Thorac Cardiovasc Surg 2013; 146:9 16. at
Jaklitsch et al, 2013 47 pts underwent VATS: 3 negative stations confirmed in 7 pts Persistent N2 in 16 pts 4 pts with pleural carcinomatosis 20 pts with obliterated nodal stations Recommend PET/EBUS as adjuncts in restaging Jaklitsch MT, Gu L, Demmy T, Harpole DH, D Amico TA, McKenna RJ et al. Prospective phase II trial of preresection thoracoscopic mediastinal restaging after neoadjuvant therapy for IIIA (N2) non-small cell lung cancer: results of CALGB Protocol 39803. J Thorac Cardiovasc Surg 2013; 146:9 16. at
De Waele, 2008 104 pts underwent redo mediastinoscopy after induction therapy 79 with chemotherapy, 25 with chemort Redo mediastinoscopy feasible in all pts except 1, died of hemorrhage Sensitivity 71%, specificity 100%, accuracy 84% De Waele M, Serra-Mitjans M, Hendriks J, et al. Accuracy and survival of repeat mediastinoscopy after induction therapy for non-small cell lung cancer in a combined series of 104 patients. Eur J Cardiothorac Surg 2008;33:824-8. at
Nasir et al, 2014 32 pts underwent induction chemotherapy,rt or both after staging with PET/CT EBUS then utilized for restaging Pts found to be N2 negative underwent thoracotomy and lymphadenectomy Nasir BS, Bryant AS, Minnich DJ, et al. The efficacy of restaging endobronchial ultrasound in patients with non-small cell lung cancer after preoperative therapy. Ann Thorac Surg. 2014;98:1008 12. at
Nasir et al, 2014 24 pts with negative EBUS, 3 underwent mediastinoscopy and 2 with persistent nodal disease 22 patients underwent thoracotomy and 1 pt was found to have N2 disease Negative predictive value of 88% Nasir BS, Bryant AS, Minnich DJ, et al. The efficacy of restaging endobronchial ultrasound in patients with non-small cell lung cancer after preoperative therapy. Ann Thorac Surg. 2014;98:1008 12. at
Conclusions Pneumonectomy after induction therapy is feasible and safe Careful patient selection, N2 disease status Restage patients after neoadjuvant therapy Should be performed by experienced surgeons at high volume centers at,
Thank you at,