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Paul De Leyn



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    MS 24 - Management of GGO-Containing Nodule (ID 546)

    • Event: WCLC 2017
    • Type: Mini Symposium
    • Track: Radiology/Staging/Screening
    • Presentations: 2
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      MS 24.02 - What Type of Surgery Should be Selected for GGO-Containing Tumors? (ID 7755)

      15:10 - 15:30  |  Presenting Author(s): Paul De Leyn

      • Abstract
      • Presentation
      • Slides

      Abstract:
      A ground glass opacity (GGO) is a radiographic finding defined as hazy, increased attenuation of the lung with preservation of bronchial vascular margin. A subsolid nodule (SSN) includes pure ground glass nodules and partsolid nodules in which both solid and ground glass components are present. These nodules are nowadays more commonly found with the introduction of CT screening programs. The optimal management of patients with SSN is of growing clinical concern. The newly (1) introduced adenocarcinoma classification makes a clear distinction between pre-invasive lesions (atypical adenomatous hyperplasia), adenocarcinoma in situ (AIS: ≤ 3cm pure lepidic growth without invasion), minimally invasive adenocarcinoma (MIA: ≤ 3cm lepidic growth with ≤ 5mm invasion) and invasive adenocarcinoma (IA) of different subtypes. Preinvasive lesions or MIA have an excellent survival and might be treated with sublobar resection. IA (especially certain subtypes) are more aggressive and should be treated with lobar resection combined with systematic nodal dissection. Pure GGO lesions can be non-specific inflammation, fibrosis or neoplasm. Recent guidelines (2) recommends for pure GGO nodules ≥6mm follow-up scan at 6 to 12 months and then every 2 years until 5 years. In a retrospective study (3) 83 patients with pure GGO lesion that had surgery and proved to be adenocarcinoma were described. 79,5 % were non IA and 20,5 % (IA). In a multivariate logistic regression analysis both preop GGO size on CT and pleural retraction were predictive factors for IA. Pure GGO lesions ≥ 10 mm should be resected if they persist or grow on follow-up CT. Partsolid nodules. When a nodule is partially solid or when in a GGO lesion a solid part appears, the risk of IA increases. In a prospective multicentric study Suzuki et al looked at radiologic criteria for predicting pathologic early (non-invasive) adenocarcinoma (4). In this study, the consolidation/tumor (C/T)ratio was measured in lung and mediastinal window settings. Radiologic non-invasive longadenocarcinoma could be defined as a subsolid nodule ≤2cm with a (C/T) ratio of 0.25 or less. Asamura et al (5) re-evaluated the radiology pathology correlation in this study in term of the prognosis. The radiologic criteria of a C/T ratio of 0.25 or less in tumor ≤3cm as well as 0.25 or less in tumors ≤2cm could be used to define a homogeneous group of patients with an excellent prognosis after surgery. These criteria can be used to select patients with early lung adenocarcinoma in which a sublobar resection (wedge or segmentectomy) would be safely indicated. For lesions with a tumor diameter of 2.0cm and a C/T ration >0.25 a prospective randomized fase III study comparing lobectomy and segmentectomy is ongoing (6). The incidence of N2 disease in clinical T1-T2N0 was evaluated (7). The incidence of unforeseen N2 disease was 1.5% in pure GGO lesions. N2 disease was found in 4.3% of semi solid tumors and 12.6% in pure solid tumors. In a multivariate analysis, tumors with any GGO components were less likely to have N2 disease (Odds ratio 0.14, 0.001). A recent study (8) used a nomogram for predicting the risk of IA in patients with solitary peripheral subsolid nodules. In a multivariate analysis the occurrence of IA was significantly correlated with lesion size, spiculation, vascular convergence and pleural tag. There are different subtypes of IA. The micropapillary and solid types are aggressive subtypes with a high rate of N2 (9). These types cannot be used for sublobar resection. Huang et al (10) analyzed histology obtained by CT guided needle biopsy or EBUS. Concordant subtyping of adenocarcinoma between the predominant pattern on resections and biopsy section was only observed in 58.6% of the cases. For high grade adenocarcinoma detection, preoperative biopsy had a low sensitivity (16.5%). So preoperative obtained histology cannot show us which type of resection we should perform. The degree of invasion is often overestimated in frozen section. However, frozen section has a high specificity for micropapillary and subsolid pattern (11). If this subtype is found during surgery by frozen section, lobectomy and lymph node dissection should be performed. Conclusion By modern imaging subsolid nodules containing GGO lesions are more often seen. When the C/T ratio is more than 50% there is a high risk of IA with certain subtypes which are very aggressive. These lesions should be managed by lobectomy and lymph node dissection until results from prospective studies are known. For lesions ≤2cm, with C/T ratio ≤25% wedge or segmentectomy can be the appropriate intervention. When a limited resection is performed, the margins and the lymph nodes should be examined by frozen section. 1.Travis WD, Brambilla E, Noguchi M et al. International Association for the Study of Lung cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thorac Oncol 2011;6:244-285 2.MacMahon H, Naidich D, Goo JM et al. Guidelines for management of incidental pulmonary nodules detected on CT images : from the Fleischner Society 2017. Radiology 2017;284:228-243 3.Moon Y, Sung SW, Lee KW et al. Pure ground-glass opacity on chest computed tomography: predictive factors for invasive adenocarcinoma. J Thorac Dis 2016;8:1561-1570 4.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 5.Asamura H, Hishida T, Suzuki K et al. Radiographically determined noninvasive adenocarcinoma of the lung : survival outcomes of Japan Vlinical Oncology Group 0201. J. Thorac Cardiovasc Surg 2013;146:24-30 6.Nakamura K, Saji H, Okada M 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 7.Gao SJ, Kim AW, Puchalsky JT et al. Indications for invasive mediastinal staging in patients with early non-small cell lung cancer staged with PET-CT. Lung Cancer 2017;109:36-41 8.Jin C, Cao J, Cai Y et al. A nomogram for predicting the risk of invasive pulmonary adenocarcinoma for patients with solitary peripheral subsolid lesions. J Thorac Cardiovasc Surg 2017;153:462-9 9.Hung JJ, Yeh YC, Wu YC et al. Factors predicting occult lymph node metastasis in completely resected lung adenocarcinoma of 3 cm or smaller. Europ J Cardio-Thorac Surg 2016;50:329-336 10.Huang KY, Ko PZ, Yao CW et al. Inaccuracy of lung adenocarcinoma subtyping using preoperative biopsy specimens. J Thorac Cardiovasc Surg 2017;154:332-9 11.Yeh YC, Nitadori JI, Kadota K et al. Using frozen section to identify histologic patterns in stage I lung adenocarcinoma ≤3 cm: accuracy and interobserver agreement. Histopathology 2015;66:922-938

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      MS 24.03 - When to Operate GGO-Containing Tumors? (ID 7756)

      15:30 - 15:50  |  Presenting Author(s): Paul De Leyn

      • Abstract
      • Presentation
      • Slides

      Abstract:
      With the advent of Chest CT screening, the identification of abnormalities has increased substantially. In addition to very small nodules of indeterminate significance, “ground glass opacities” (GGO) are often seen. Numerous series have been collected around the world attempting to define characteristics that predict the malignant potential of these GGOs. It is clear that a substantial fraction includes a component of invasive adenocarcinoma and warrant resection for cure prior to developing disseminated cancer. This presentation will review the literature for developing a rational algorithm for selection of those patients requiring which operation, as well as review outcomes. 1. Radiological determinants of malignancy using high-resolution CT and CT/PET 2. Criteria for patient section for resection or observation 3. Techniques for pre-resection localization for intraoperative identification of lesion 4. Appropriate selection lesions for extent of resection (lobe, segment or non-anatomic wedge) 5. Approach for resection 6. Outcomes after treatment Selected References Matsunaga T, Suziki K, Takamochi K, Oh S. What is the radiological definition of part-solid tumor in lung cancer? Eur J Cardiothorac Surg 2017; 51:242-247 Eguchi T, Kondo R, Kakkami S, Matsushita M, Yoshizawa A, Hara D, Matsuoka S, Tkeda T, et al. CT attenuation predicts the growth of pure GGO nodules Lung Can 2014;84:242-247 Suzuki K, Asamura H, Kusumoto M, Kondo H, Tsuchiya R. Early peripheral lung cancer: prognostic significance of GGO on thin section CT scan Ann Thorac Surg 2002;74:1635-9 Lee S, Leem C, Kim T, Lee K, Chung J, Jheon WS, Lee C. The long term follow-up of GGO detected on thin-section CT Respir Med 2013;107:904-10 Suzuki K, Shimohira M, Hashizume T, Ozawa Y, Sobue R, Mimura M, Mori Y, Ijima H, Watanabe K, Yano M, Yoshioka H, Shibamoto Y. Usefulness of CT-guided hookwire marking before VATS for small pulmonary lesions J Med Imag Rad Oncol 2014; 58:657-662. Mong-Wei L, Yao-Hui T, Yee-Fan L, Min-Shu H, Wei-Chun K, Jo-Yu C, Hsao-Hsun H, Yeun-Chung C, Jin-Shing C. Comuted tomography-guided patent blue vital dye localization of pulmonary nodules in uniportal thoracoscopy J Cardiovasc Surg 2016; 152:535-44 Fukui M, Suziki K, Matsunaga T, Oh S, Takamochi K. Surgical intervention for GGO-dominant lesions: observation or outright resection? Pan J Clin Oncol 2017;18:1-6 Cao C, Gupta S, Chandrakumar D, Tian D, Black D, Yan T. Meta-analysis of intentional sublobar resections versus lobectomy for very early stage non-small cell lung cancer Ann Cardiothorac Surg 2014; 3:134-141 Kodama K, Higashiyayma M, Tkami K, Oda K, Okami J, Maeda J, Koyama M, Nakayama T. Treatment strategy for patients with small peripheral lung lesions: Prospective study Eur J Cardiothoracic Surg2008; 34:1068-74 Yoshioka M, Ichiguchi O. Selection of sublobar resection for c-stage1A non-small cell lung cancer based on a combination of structural imaging by CT and functional imaging by FDG-PET Ann Thorac Cardiovasc Surg 2009; 15:82-8. Kohno T, Fujimoro S, Kishi K, Fujii T. Safe and effective minimally invasive approaches for small GGOs Ann Thorac Surg 2010; 89; 1114-7 Tsutani Y, Miyata Y, Nakayama H, Okurmura S, Adachi S, Yoshimura M, Okada M. Appropriate sublobar resection choice for GGO-dominant clinical stage 1A lung Adenocarcinoma Chest 2014; 145:66-71 Sook Y, Sung S, Mankoong M, Park K. The effectiveness of mediastinal node evaluation in a patient with GGO tumor J Thorac Dis 2016; 8:2617-2623 Wei S, Khao K, Guo C, Mei J, Pu Q, Ma L, Che G, Chen G, Wu Z, Wang Y, Kuo Y, Lin Y, Li W Lui L. Diagnosis and surgical treatment of lung GGO: a review of 663 cases. Sichan Da Xue Bao Yi Xue Ban 2017:48:359-362 Moon Y, Lee K, Moon S, Park J. Sublobar resection margin does not affect recurrence of clinical N0 non-small cell lung cancer presenting as GGO. World J Surg 2017;41:472-9 Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K. Surgical Management of Multifocal Ground-Glass Opacities of the Lung: Correlation of Clinicopathologic and Radiologic Findings Thorac Cardiovasc Surg 2017; 65:142-14 Shimada Y, Saji H, Otani K, Maehara S, Maeda J, Yoshida K, Kato Y, Hagiwara M, Kakihana M, Kajiwara N, Ohira T, Akata S, Ikeda N. Survival of a surgical series of lung cancer patients with synchronous multiple ground-glass opacities, and the management of their residual lesions Lung Cancer 88 (2015) 174-180

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    OA 16 - Treatment Strategies and Follow Up (ID 686)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Early Stage NSCLC
    • Presentations: 1
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      OA 16.06 - Mediastinal Staging by Videomediastinoscopy in Clinical N1 Non-Small Cell Lung Cancer: A Prospective Multicentre Study (ID 8454)

      15:25 - 15:35  |  Author(s): Paul De Leyn

      • Abstract
      • Presentation
      • Slides

      Background:
      A fourth of patients with cN1-NSCLC based on PET-CT imaging are at risk for occult mediastinal nodal involvement. In a previous prospective study, endosonography alone had an unsatisfactory sensitivity (38%) to detect mediastinal nodal disease. This prospective multicenter trial investigated the sensitivity of preoperative mediastinal staging by video-assisted mediastinoscopy (VAM) in patients with cN1 (suspected) NSCLC.

      Method:
      Consecutive patients with operable and resectable cN1 (suspected) non-small cell lung cancer (NSCLC) underwent a VAM or VAM-lymphadenectomy (VAMLA). All patients underwent FDG–PET and CT-scan. The primary study outcome was sensitivity to detect N2-disease. Secondary endpoints were the prevalence of N2-disease, negative predictive value (NPV) and accuracy of VAM(LA).

      Result:
      Figure 1 Out of 105 patients with cN1 on imaging, 26% eventually had N2-disease. Invasive mediastinal staging with VAM(LA) reached sensitivity of 73% to detect N2-disease. The median number of assessed lymph node stations during VAM(LA) was 4. In 96% ≥3 stations were assessed. VAMLA was performed in 31%, 69% underwent VAM.

      N Prevalence of mediastinal disease Sensitivity OR(95%CI) Negative Predictive Value OR(95%CI) Negative Posttest probability OR(95%CI)
      Dooms et al. Chest. 2014; 147(1): 209–15. Endosonography alone 100 24% 0.38 (0.18-0.57) 0.81 (0.71-0.91) 0.19 (0.13-0.27)
      Endosonograpy, if negative followed by mediastionoscopy 0.73 (0.55-0.91) 0.91 (0.83-0.98) 0.09 (0.04-0.17)
      Current Study Mediastinoscopy 105 26% 0.73 (0.54-0.86) 0.92 (0.83-0.97) 0.08 (0.03-0.17)




      Conclusion:
      VAM(LA) has a satisfactory sensitivity of 73% to detect mediastinal nodal disease in cN1-NSCLC and could be the technique of choice for pre-resection mediastinal lymph node assessment in this patient group with 26% chance of occult positive mediastinal nodes after negative PET-CT. (ClinicalTrials.gov NCT02222194)

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    P1.13 - Radiology/Staging/Screening (ID 699)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.13-007 - Is Central Lung Tumor Location Really Predictive for Occult Mediastinal Nodal Disease in (Suspected) NSCLC Staged cN0 on PET-CT?  (ID 8779)

      09:30 - 09:30  |  Author(s): Paul De Leyn

      • Abstract

      Background:
      Based on a 20-30% prevalence of occult mediastinal disease, current guidelines recommend preoperative invasive mediastinal staging in patients with central tumour location and negative mediastinum on PET-CT. A uniform definition of central tumour location is lacking. Our objective was to determine the best definition in predicting occult mediastinal disease.

      Method:
      A single institution prospective database was queried for patients with (suspected) NSCLC staged cN0 after PET-CT and referred to invasive staging and/or primary surgery. We evaluated 5 definitions of central tumour location (table 1).

      Result:
      Between 2005 and 2015, 822 patients were eligible. Radio-occult lesions were excluded from analysis (n=9). Preoperative histology was NSCLC in 49% and unknown in 51%. The lesion was subsolid in 7%. Tumour stage was cT1, cT2, cT3 and cT4 in 43%, 28% 17% and 11%, respectively. Invasive mediastinal staging (EBUS and/or mediastinoscopy) was performed in 31%. Surgical resection was performed in 97%, a median of 5 (IQR 3-6) nodal stations were examined. The final pathology was squamous NSCLC, non-squamous NSCLC, or other in 38%, 54% and 7%, respectively. Any nodal upstaging was found in 21% (13% pN1 and 8% pN2-3). Central tumour location demonstrated, compared to peripheral location, a 4 times higher risk for any nodal upstaging but not for N2-3 upstaging (table 1).

      Conclusion:
      When modern PET-CT fusion imaging points at clinical N0 NSCLC, the prevalence of occult mediastinal nodal disease was only 8% in our patient cohort. None of the five definitions of centrality we studied was predictive for occult pN2-N3. Overall nodal upstaging was 21%, however, and all definitions of centrality then had discriminatory value. These data question whether the indication of preoperative invasive mediastinal staging should be based on centrality alone. Table 1 Figure 1