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H. Hoffmann

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    SC08 - IASLC- ESTS Joint Symposium: The Borderline Patient (ID 332)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Pulmonology
    • Presentations: 4
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      SC08.01 - Impact and Management of Co-Morbidities (ID 6628)

      16:00 - 17:30  |  Author(s): A. Brunelli

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Introduction Due to general ageing population, many patients with lung cancer are elderly and with frequent underlying co-morbidities. The most frequent co-morbidities associated with lung cancer are cardiac (i.e. coronary artery disease) and pulmonary diseases (i.e. COPD). Cardiac co-morbidity Coronary artery disease (CAD) is present in approximately 10-15% of lung resection candidates. The risk of major adverse cardiac events (MACE) and cardiac mortality is 4-fold higher in patients with previous history of CAD1 and patients with a previous coronary stent procedure within 1 year from lung resection had MACE and mortality rates of 9.3% and 7.7% after surgery, respectively2. Cardiac evaluation is therefore particularly important in this population to optimize their treatment and reduce surgical risk. A specific cardiac risk score was recently developed and is named Thoracic RCRI (ThRCRI). Patients in the highest class of risk had a incidence of MACE of 23% versus only 1.5% in those in the lowest class of risk1. These findings were subsequently validated by a number of independent studies. Detailed evaluation for coronary heart disease is not recommended in patients who have an acceptable exercise tolerance and with low cardiac risk score. For patients whose exercise capacity is limited, those with a ThRCRI > 1.5 or those with known or newly suspected cardiac condition, non-invasive cardiac evaluation is recommended as per AHA/ACC guidelines3 to identify patients needing more invasive interventions. Appropriately aggressive cardiac interventions should be instituted prior to surgery only in patients who would need them irrespective of the planned surgery. However, prophylactic coronary revascularization prior to surgery in patients who otherwise do not need such a procedure does not appear to reduce perioperative risk4. Pulmonary co-morbidity Approximately 20-25% of patients with early stage lung cancer have a concomitant moderate to severe COPD (FEV1<80% and FEV1/FVC ratio < 70%). Many studies have shown the association between FEV1 or predicted postoperative FEV1 (ppoFEV1), and surgical risk. In particular the risk of pulmonary morbidity and mortality has been shown to increase when FEV1 is below 50-60% or ppoFEV1< 30-40%. However, recent evidence has shown that even patients with moderate to severe COPD and lung cancer can undergo safely to lung resection. In these patients, the resection of the most affected parenchyma containing the tumor may determine a minimal loss or even an improvement in respiratory mechanics and elastic recoil, similar to what happens in typical end-staged emphysema patients candidates to lung volume reduction surgery. Nearly one third of COPD patients may actually improve their FEV1 3 months after pulmonary lobectomy for cancer. Therefore, although a reduced FEV1 or ppoFEV1 is associated with increased morbidity and mortality, most recent guidelines recommended against using this parameter alone to exclude patients from surgery even in case of very low values5,6. Patients with idiopathic pulmonary fibrosis (IPF) and lung cancer are a more challenging population to manage. Surgical treatment of these patients is high risk for postoperative acute exacerbations of IPF, which is associated with 80-100% mortality rate. The postoperative mortality rate of these patients has been reported to range between 7 and 18%. Moreover, long-term prognosis of IPF itself affects long term survival following surgery for cancer. Additional fitness tests Carbon monoxide lung diffusion capacity (DLCO) appears to be a more sensitive indicator of poor pulmonary function and more reliably associated with postoperative respiratory complications and mortality. Until recently, DLCO measurement has been mainly reserved to patients with abnormal FEV1. However, recent studies have shown that FEV1 and DLCO are poorly correlated and that more than 40% of patients with normal FEV1 (>80%) may have reduced DLCO. A low DLCO or ppoDLCO is a reliable predictor of cardiopulmonary morbidity and mortality not only in patients with COPD but also in those with normal respiratory function. This is the rationale behind the most recent recommendations to measure DLCO systematically in all lung resection candidates. Cardiopulmonary exercise test: Cardiopulmonary exercise test is the gold standard in preoperative evaluation of lung resection candidates. In addition to the most frequently used parameter, VO2max, it provides several other direct and derived measures that permit, in case of a limited aerobic reserve, to precisely identify possible deficits in the oxygen transport system. Several series have shown that a VO2max>20 mL/kg/min is safe for every extent of resection, whilst values < 10 mL/kg/min are associated with a high risk of potoperative mortality. We recently found that VO2max<12 mL/kg/min was associated with 13% in-hospital mortality rate following open major anatomic lung resections7. A parameter, which has gained recent interest in our specialty is the minute ventilation to carbon dioxide output (VE/VCO2) slope, also named as ventilatory efficiency slope. VE/VCO2 slope can be increased due to either pulmonary or cardiac diseases. Several studies have shown that a value greater than 35 is associated with increased respiratory complications and mortality after lung resection. We found that the mortality rate of patients with VE/VCO2>35 was 7% versus only 0.6% of those with lower values. The association between this parameter and respiratory complications remained the same for patients with and without COPD and for those with VO2max greater or lower than 15 mL/kg/min. VATS and sublobar resections Videoassisted thoracoscopic surgery (VATS) has been recommended as the approach of choice for stage I lung cancer patients. Several studies showed that this approach is associated with lower incidence of complications, shorter hospital stay and in some cases lower mortality rates compared to thoracotomy. The benefits of VATS are particularly evident in patients with poor pulmonary function. Large series found that the difference in pulmonary complication rates after lobectomy by VATS versus thoracotomy was present only in patients with a FEV1<60%. Burt and coll.8 found that patients with ppoFEV1<40% or ppoDLCO<40% and submitted to VATS lobectomy had a markedly reduced incidence of mortality compared to those operated on through thoracotomy (ppoFEV1<40%: 0.7% vs. 4.8%, p=0.003; ppoDLCO<40%: 2% vs. 5.2%, p=0.003). Recent evidences have shown that anatomic segmentectomies provide equivalent oncologic results compared to lobectomy for tumours smaller than 2 cm, whilst preserving much more respiratory function and being associated with lower incidence of postoperative complications9,10. This extent of resection appears therefore ideal for patients with a limited baseline pulmonary function. Selected references 1. Brunelli A, et al. Recalibration of the revised cardiac risk index in lung resection candidates. Ann Thorac Surg. 2010;90(1):199-203. 2. Fernandez FG, et al. Incremental risk of prior coronary arterial stents for pulmonary resection. Ann Thorac Surg. 2013 Apr;95(4):1212-8 3. Fleisher LA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation 2007: 116(17): 418-499. 4. McFalls EO, et al. Coronary-artery revascularization before elective major vascular surgery. N Eng J Med 2004; 351(27): 2795-2804 5. Brunelli A, et al. ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy). Eur Respir J 2009; 34:17-41. 6. Brunelli A, et al. Physiologic Evaluation of the Patient With Lung Cancer Being Considered for Resectional Surgery: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013 May;143(5 Suppl):e166S-90S 7. Brunelli A, et al. Peak Oxygen Consumption During Cardiopulmonary Exercise Test Improves Risk Stratification in Candidates to Major Lung Resection. Chest 2009; 135:1260-1267. 8. Burt BM, et al. Thoracoscopic lobectomy is associated with acceptable morbidity and mortality in patients with predicted postoperative forced expiratory volume in 1 second or diffusing capacity for carbon monoxide less than 40% of normal. J Thorac Cardiovasc Surg. 2014 Jul;148(1):19-28 9. Okada M, et al. Radical sublobar resection for small-sized non-small cell lung cancer: a multicenter study. J Thorac Cardiovasc Surg. 2006 Oct;132(4):769-75 10. Yano M, et al. Survival of 1737 lobectomy-tolerable patients who underwent limited resection for cStage IA non-small-cell lung cancer. Eur J Cardiothorac Surg. 2015 Jan;47(1):135-42

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      SC08.02 - Emphysema as a Limiting Factor for Lung Resection: How Far We Can Go? (ID 6629)

      16:00 - 17:30  |  Author(s): W. Weder

      • Abstract
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      Abstract not provided

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      SC08.03 - Surgical Issues in the Borderline Patient: Sublobar versus Standard Resection (ID 6630)

      16:00 - 17:30  |  Author(s): D. Harpole

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      SC08.04 - SABR Versus Surgery (ID 6631)

      16:00 - 17:30  |  Author(s): N. Ikeda, T. Ohira, N. Kajiwara

      • Abstract
      • Presentation
      • Slides

      Abstract:
      In recent years, the number of early stage lung cancers has enormously increased and this tendency is more prominent in octogenarians. Both curability and non-inavasiveness should be required for such situation. Surgery is the standard treatment for early stage lung cancer and VATS lobectomy or sublobar resection have been routinely performed for selected patients to maintain performance status[1)]. Especially, the indication of sublobar resection is considered to be related to the aggressive nature of tumors, thus several studies by HRCT findings and PET-CT were performed to predict the invasive nature as well as clinical stage. In JCOG 0201, 545 case who received lobectomy and mediastinal lymph node dissection due to stage I NSCLC were enrolled prospectively. Pathological non-invasive cancer (both vascular and lymphatic invasion negative) was evaluated by the consolidation/tumor ratio on preoperative HRCT. Adenocarcinoma <2.0 cm with <0.25 consolidation to the maximum tumor diameter (35 patients, 12.1%) revealed pathological non-invasiveness in 98.7% (95% CI: 93.2–100.0%), and this criterion could be used for radiological early lung cancer[2)]. The prognostic study of cases enrolled in JCOG0201 revealed that 5 year OS and RFS survivals of the entire patients were 90.6% and 84.7%, respectively. The 5-year OS of radiologic early and invasive adenocarcinomas were 97.1% and 92.4%, respectively (p=0.259). If the consolidation/tumor ratio lower than 0.5 in cT1a-b was used as a cutoff, the 5-year OS of radiologic early (121 patients, 22.2%) was 96.7% and invasive adenocarcinomas, 88.9% (p<0.01)[3)]. Based on the criteria of radiologic early cancer obtained by JCOG0201, randomised phase 3 trial to evaluate non-inferiority in OS of segmentectomy compared to lobectomy (JCOG0802)[4)]. The maxSUV of the primary tumor on PET/CT could be used as a prognostic marker of early stage lung cancer. Analyses of 610 resected stage IA adecocarcinoma showed that maxSUV and GGO ratio cutoffs to predict recurrence were 2.9 and 25%, respectively. They were also related to nodal metastasis, histological tumor invasiveness and recurrence. The 5-year RFS of cases with maxSUV <2.9 (n=456) was 95%, while cases with maxSUV>2.9 (n=154), 72% (p<0.001)[5)]. Surgical management of early stage lung cancer should be selected by based on the tumor size, GGO ratio and maxSUV to predict the biological malignancy of each case. Streotactic ablative radiotherapy (SABR) has attained importance for efficacy and safety for the treatment of early cancers located in the peripheral lung. There are two representative randomised phase 3 trial (STARS and ROSEL) to compare SABR and surgery. Eligible patients of these studies were T1-2a (<4cm) N0M0 and a total of 58 cases were registered (31 received SABR and 27, surgery). The combined analysis of these two studies revealed that 3 year OS in SABR (95%) was superior to that of surgery (79%) (p=0.037) and RFS at 3 years was similar; 86% in SBRT and 80% in surgery (p=0.54). Only 10% of cases in SBRT group suffered grade 3 toxicity but 44% of surgery group developed grade 3 and 4 toxicities. The pooled analysis of the two studies showed SBRT had similar treatment efficacy to that of surgery in spite of the small sample size[6)]. Japan Clinical Oncology Group evaluated the efficacy and safety of SBRT for operable/inoperable T1N0M0 patients (JCOG 0403). A total of 164 patients (100 inoperable and 64 inoperable) were treated by 48 Gy. The 3 year OS was 59.9% in inoperable patients and 76.5% in operable patients[7)]. Investigations into the effectiveness of SABR for operable patients as well as the optimal indication, dose and fraction should be clarified by prospective manner. SABR has become a radical treatment for inoperable stage I lung cancer. In addition, if operable cases treated by SABR in JCOG0403 show favorable outcome, further comparable trial of SABR versus less invasive surgery should be warranted. References 1) Committee for Scientific Affairs The Japanese Association for Thoracic Surgery, Thoracic and cardiovascular surgery in Japan during 2013 : Annual report by the Japanese Association for Thoracic Surgery. Gen Thorac Cardiovasc Surg.2015;63:670-701. 2) Suzuki K, Koike T, Asakawa T, et al.: A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol 2011;6:751-756 3) Asamura H, Hishida T, Suzuki K, et al. Radiographically determined noninvasive adenocarcinoma of the lung: Survival outcomes of Japan Clinical Oncology Group 0201 J Thorac Cardiovasc Surg 2013;146:24-30 4) Nakamura K, Saji H, Nakajima R, et.al. A Phase III Randomized Trial of Lobectomy Versus Limited Resection for Small-sized Peripheral Non-small Cell Lung Cancer (JCOG0802/WJOG4607L) Jpn J Clin Oncol 2010;40:271–274 5) Uehara H, Tsutani Y, Okumura S, et al. Prognostic Role of Positron Emission Tomographyand High-Resolution Computed Tomography in Clinical Stage IA Lung Adenocarcinoma Ann Thorac Surg 2013;96:1958–1965 6) Chang JY, Senan S, Paul MA et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: A pooled analysis of two randomized trials. Lancet Oncol 2015;16:630–637. 7) Nagata Y, Hiraoka M, Shibata T, et al. Prospective trial of stereotactic body radiation therapy for both operable and inoperable T1N0M0 non-small cell lung cancer: Japan Clinical Oncology Group Study JCOG0403. Int J Radiat Oncol Biol Phys 2015;93;989-996.

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    IA01 - Multidisciplinary Diagnosis of Lung Cancer in the Era of Molecular Medicine (ID 284)

    • Event: WCLC 2016
    • Type: Interactive Session
    • Track: Biology/Pathology
    • Presentations: 1
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      IA01.03 - What Every Lung Pathologist Needs to Know About Thoracic Surgery (ID 6516)

      11:00 - 12:30  |  Author(s): H. Hoffmann

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      Abstract not provided

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