History of Surgery for Lung Cancer

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Welcome to Master Class for Oncologists Session 1: 7:30 AM - 8:15 AM San Francisco, CA October 23, 2009 Innovations in The Surgical Treatment of Lung Cancer Speaker: Scott J. Swanson, MD 2 Presenter Disclosure Information History of Surgery for Lung Cancer The following relationships exist related to this presentation: Scott Swanson is a consultant to Ethicon EndoSurgery Off Label/Investigational Discussion In accordance with Pri-Med Institute policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Evarts Graham (St Louis) reported the first successful pneumonectomy for lung cancer using a tourniquet technique in 1933. Churchill (Boston, 1950) suggested lobectomy was a good option for surgical treatment of lung cancer. 3 4 History of Surgery for Lung Cancer Innovations in the Surgical Treatment of Lung Cancer Bonfil-Roberts and Claggett (NY, Minneapolis, 1972) reported that segmentectomy was reasonable for small lung cancers. 1992, VATS lobectomy Currently, lobectomy with lymph node dissection is the gold standard for surgical treatment of lung cancer. Thoracoscopic technique Size of the resection: segmentectomy/wedge vs lobectomy Integrating chemotherapy, radiation therapy, and surgery Surgery for special populations Elderly Severe emphysema Alternatives to surgery Stereotactic radiation -- Cyberknife Radiofrequency ablation 5 6 1

Audience Response Question? What are reported advantages of a VATS lobectomy over a thoracotomy and lobectomy? 1. Lower cost, decreased need for general anesthesia, technically easier 2. Shorter anesthetic, simpler to learn, less manipulation of lung during surgery 3. Less need for operative equipment, more lymph nodes removed, shorter operative time 4. Decreased pain, decreased length of hospital stay and lower peri-operative complications Video-Assisted Thoracic Surgery (VATS) Definition- Via several small incisions (1-2 cm) Videoscopic camera Watching a TV monitor No rib spreading is permitted Lewis (NJ) reported the first lobectomy using this technique in 1992. 7 8 Video-Assisted Thoracic Surgery or VATS The Hope Reduced morbidity Reduced mortality Reduced length of stay Earlier return to regular activities WITHOUT compromise of the cancer operation morbidity VATS Example Initial View Right Upper Lobectomy Exposure 9 10 VATS Lobectomy Specimen Removal VATS Example Chest View after Specimen Removal 11 12 2

Survival Following Surgery for Stage I NSCLC Failure-Free Survival CALGB 39802 Author # Patients 5-year Survival Martini 128 72% Williams 461 71% Teramachi 121 71% Mountain 725 68% Naruke 536 65% Swanson SJ, et al. J Clin Oncol. 2007;25:4993-4997. 13 14 Video-Assisted Thoracic Surgery (VATS) Lobectomy Results in 1100 Patients Video-Assisted Thoracic Surgery (VATS) Lobectomy Results in 1100 Patients None 932 (84.7%) Air leak > 7d 56 (5.1%) AF 32 (2.9%) Serous drainage 14 (1.3%) Readmit 13 (1.2%) Pneumonia 13 (1.2%) SQ 12 (1.1%) MI 10 (0.9%) Empyema 4 (0.03%) Other 14 15 16 VATS Lobectomy Outcomes CALGB 39802 6 intergroup centers, 11 surgeons, 127 pts Peripheral, clinical stage 1A NSCLC 106/127 (83%) had stage I lung cancer Median procedure length: 130 min (47-428) 60% had biopsy at time of procedure Median chest tube duration: 3 d (1-14) VATS Lobectomy Outcomes CALGB 39802 Conversion 14/111 13% Mortality 3/97 3.1% Morbidity 8/97 8.2% SVT: 5/97 (5.2%) Bleeding: 2/97 (2.1%) Prolonged air leak: 1/97 (1%) 17 Swanson SJ, et al. J Clin Oncol. 2007;25:4993-4997. 18 Swanson SJ, et al. J Clin Oncol. 2007;25:4993-4997. 3

Video-Assisted Thoracic Surgery or VATS VATS vs Thoracotomy Fewer complications Hoksch 1 Less pain Walker 2 Better quality of life Sugiura 3 Better PFTs Nakata 4 Less pneumonia Whitson 5 Earlier recovery Demmy 6 Easier for octogenarians McVay 7 Video-Assisted Thoracic Surgery or VATS VATS vs Thoracotomy Reduced stress response Reduced post-op C-reactive protein Reduced IL-6 levels Enhanced cellular immune function (better neutrophil and monocyte function) 19 20 Craig SR, et al. Eur J Cardiothor Surg. 2001;20:455-463. Video-Assisted Thoracic Surgery or VATS VATS vs Thoracotomy Adjuvant Chemotherapy for Stages IB-IIIa ANITA Trial Less lab charges Less anesthesia charges Less disposable equipment charges Less hospital charges Less complications N 0 N 1 N 2 Douillard et al 21 Nakajima J, et al. Cancer. 2000;89(11 Suppl):2497-2501. 22 Douillard JY, et al. Lancet Oncol. 2006;7:719-727. VATS Lobectomy Improved Chemotherapy Tolerance VATS Lobectomy Summary LOS: 4 d Morbidity: Afib, 10%, prolonged leak, 7%, pneumonia, 2% Pain at 2 weeks: No pain med: 50% Ibuprofen: 40% Codeine type rx: 10% Chemotherapy: Completed full course on time: 73% All 4 intended cycles: 85% Discharge: 34% home within 3 d 96/144 home without assistance 40/144 home with nursing assistance; 36/40 brief VNA visit 3x/wk for 2 wk 8/144 (5.6%) discharged to rehab Current evidence would suggest that a lobectomy done using thoracoscopic or VATS approach is preferred for stage I and possibly stage II NSCLC. Long term survival is at least as good as with an open approach. The operation does require technical competence. 23 Nicastri, Swanson. JTCS March 2008 24 4

Audience Response Question? What are reported advantages of a video-assisted thoracic surgery lobectomy over a thoracotomy and lobectomy? 1. Lower cost, decreased need for general anesthesia, technically easier 2. Shorter anesthetic, simpler to learn, less manipulation of lung during surgery 3. Less need for operative equipment, more lymph nodes removed, shorter operative time 4. Decreased pain, decreased length of hospital stay and lower peri-operative complications Audience Response Question? What is the current standard of care for treatment of a 2.0 cm non-small cell lung cancer, specifically what operation is best? 1. Lobectomy 2. Segmentectomy 3. Wedge resection 4. Radiofrequency ablation 5. Stereotactic radiation 25 26 Lobectomy vs Wedge Resection LCSG Trial Size of Resection for Lung Cancer Lung Cancer Study Group: lobectomy vs wedge or segment: 3-5 times local recurrence 20% worse survival (for less than lobectomy) Therefore, lobectomy = gold standard Ginsberg RJ, et al. Ann Thorac Surg. 1995;60:615-623. 27 28 Lobectomy vs Sublobar Resection for Stage I NSCLC Size of Resection for Lung Cancer Data are equivocal and screening finds small masses that might be treated as well with a lesser resection. Therefore, revisit question of lobectomy or a sublobar resection (wedge or segmentectomy). 29 Schuchert MJ, et al. Ann Thorac Surg. 2007;84:926-932. 30 5

CALGB 140503 A phase III randomized trial of lobectomy vs sublobar resection for small ( 2 cm) peripheral NSLC Nasser Altorki PI CALGB, ACOSOG, SWOG, NCIC, RTOG Objectives Primary: determine disease-free survival Secondary Determine overall survival Pulmonary function at 6 months Radiologic endpoints: PET predictors of outcome, CT f/u Size of Surgical Resection for Stage I NSCLC Summary Standard of care for stage I NSCLC is a lobectomy. However, for tumors 2 cm consideration should be given for a segmentectomy (preferred) or wedge resection. 31 32 Size of Surgical Resection for Stage I NSCLC Summary Segment vs Lobe Better pulmonary function Metachronous cancers Synchronous cancers Without compromising survival The best way to consider this option is in the setting of a clinical trial (CALGB 140503). Audience Response Question? What is the current standard of care for treatment of a 2.0 cm non-small cell lung cancer, specifically what operation is best? 1. Lobectomy 2. Segmentectomy 3. Wedge resection 4. Radiofrequency ablation 5. Stereotactic radiation 33 34 Lung Cancer: Stage At Diagnosis Multi-Modal Therapy for Stage IIIa Disease 18% IV? III I + II 18% 35 39% SEER, 1998 25% 36 6

Multi-Modal Therapy for Stage IIIa Disease CT-RT vs CT-RT-S Multi-Modal Therapy for Stage IIIa Disease CT-RT vs CT-RT-S 37 38 Multi-Modal Therapy for Stage IIIa Disease CT-RT vs CT-RT-S Lobectomy Following Induction Therapy is Significantly Superior to Chemoradiation Only 39 40 Multi-Modal Therapy for Stage IIIa Disease CT-RT vs CT-RT-S Multi-Modal Therapy for Stage IIIa Disease 41 42 7

Resolution of Histologic Involvement Predicts Improved Survival Following Induction Therapy for Stage III disease ACCP Guidelines for Stage IIIa (N2) NSCLC 43 N0 vs N+ Adeno vs non-adeno Bueno R, et al. Ann Thorac Surg. 2000;70:1826-1831. 44 If N2 disease is found at surgery and complete resection is possible: Resection followed by chemotherapy and possibly RT If N2 disease is found prior to resection refer for multimodality therapy: Induction therapy followed by surgery should only be done as part of a clinical trial Pt should not have pneumonectomy following chemoradiation. Surgery or radiation only is not recommended. Primary treatment should be chemoradiation. Treatment of Stage IIIa NSLC Summary Controversial ACCP guideline: definitive chemoradiotherapy is primary treatment choice. Surgical resection is not recommended However, induction therapy followed by lobectomy may give the best outcome Surgery for Special Populations What about.. Limited pulmonary reserve Elderly: patients > 70 45 46 Limited Pulmonary Reserve High risk is variable definition Pre-operative FEV1 < 50% predicted Predicted post-operative FEV1 < 800 ml following lobectomy Pre-operative DLCO < 50% predicted VO2 max < 15 ml/m 2 Conventional = best supportive care Anatomic Pattern of Emphysema Heterogeneous 47 48 8

Innovative Treatment for High Risk Patients Innovative Treatment for High Risk Patients Evidence basis for treatment decisions in this setting is limited. Video-assisted thoracic surgery (VATS) lobectomy or segmentectomy is preferable particularly if ventilation/perfusion scan suggests minimal function in target lung ( 10%). Shaw, Swanson et al. Ann Thor Surg March 2007 Combined LVRS and lung cancer surgery: 11 patients with NSCLC Preop mean FEV1 < 35% No deaths Median LOS = 5 days 49 50 McKenna RJ Jr, et al. Chest. 1996;110:885-888. U Pitt Brachytherapy Innovative Treatment for High Risk Patients 51 I 125 sewn into Vicryl mesh 10,000-12,000 cg to a depth of 0.5 cm depth 52 Wedge + brachytherapy does appear to decrease local recurrence rates relative to wedge alone. Landreneau Ann Thorac Surg Feb 2006 McKenna RJ JR, et al. Ann Thor Surg. 2008;85:S733-S736. Current American College of Surgeon s Oncology Group (ACOSOG) trial is ongoing to confirm this. Radiofrequency Ablation (RFA) Thermal Lesion 7 Days Post-RFA The application of high frequency electric currents to heat and coagulate target tissue Thermal lesion Hemorrhagic rim Bronchiole 53 54 9

PET Assessment of RFA Audience Response Question? Assessment of region of RFA with PET scanning RFA lesion did not take up the radiolabeled glucose (18-FDG); inflammatory response to RFA surrounding the thermal lesion did take up the FDG What is the best treatment option for an otherwise fit 80 year-old patient with a 3.5 cm non-small cell lung cancer? 1. Best supportive care 2. External beam radiation 3. Stereotactic radiation 4. VATS lobectomy 5. Radiofrequency ablation 55 56 Innovative Treatment for Elderly Patients Innovative Treatment for Elderly Patients Data are limited in this setting. Surveillance Epidemiology and End Results (SEER) data suggest if patient is over 72 then wedge and lobectomy have similar survival outcomes Mery CM, et al. Chest. 2005;128:237-245. Video-assisted thoracic surgery (VATS) lobectomy is feasible and has excellent outcomes. Shaw, Swanson et al Ann Thor Surg March 2007 McKenna Am Surg Sept 2005 Video-assisted thoracic surgery (VATS) lobectomy in octogenarians: 159 patients Mortality, 2.5% Mean LOS, 5.6 days Alternative treatment in this population has not been examined. 57 58 McVay CL, et al. Am Surg. 2005;71:791-793. Audience Response Question? What is the best treatment option for an otherwise fit 80 year-old patient with a 3.5 cm non-small cell lung cancer? 1. Best supportive care 2. External beam radiation 3. Stereotactic radiation 4. VATS lobectomy 5. Radiofrequency ablation Innovative Treatment in Special Populations Summary Surgical treatment appears feasible and relatively safe although careful diagnostic work-up and surgical expertise is important. Minimally invasive options may be particularly useful. Alternative treatment may be of benefit but adequate data are currently not available to make informed decisions. 59 60 10

Questions & Answers Thank you for attending Master Class for Oncologists? 62 11