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    MS06 - An Interdisciplinary Approach to Optimal Nodal Staging (ID 69)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Staging
    • Presentations: 6
    • Now Available
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      MS06.01 - Radiologic Staging (Now Available) (ID 3467)

      11:00 - 12:30  |  Presenting Author(s): Jin Mo Goo

      • Abstract
      • Presentation
      • Slides

      Abstract

      Current definitions of borders for lymph node stations based on a few anatomic landmarks have limitations to explain the three-dimensional location of lymph nodes. Variability in the classification of lymph node stations (especially N1 vs N2 and N2 vs N3 categories) inevitably results in different management and also has an impact on database for the future revision of staging. Several articles have dealt with the ambiguity of the IASLC map and proposed recommendations. The Japan Lung Cancer Society and the Japanese Society for Radiation Oncology map provided more detailed description about the borders of lymph node stations (1).

      N2 vs N3

      1. Station 1 and 2

      - Proposal: Changing the lower border of #1 station (upper border of #2 station) to the thoracic inlet: upper border of the 1st ribs (anterior border of the 1st ribs on axial CT) (2) and manubrium

      2. Station 3a

      - Potential problem: Absence of sideness

      - Proposal: Split 3a to 3aR and 3aL with a left lateral border of the SVC (3) OR No change (like subcarinal lymph node)

      3. Station 3p

      Current border

      - Potential problem: Absence of sideness

      - Proposal: Right-sided lymph node OR No change (like subcarinal lymph node)

      4. Precarianl area (below the lower border of the azygos vein in the right side and upper rim of the left main pulmonary artery in the left side)

      - Current border: Lymph nodes located in the precarinal area is currently #10, hilar lymph nodes, but there is no description for the border between the right and left.

      - Proposal: Midline of the trachea

      N1 vs N2

      In the current IASLC lymph node map, the pleural reflection no longer serves as the border between nodal stations. However, still many physicians regard N2 lymph nodes as mediastinal lymph nodes, and a survey also support this trend (3). Therefore, if the IASLC abandons the notion that N2 lymph nodes are mediastinal lymph nodes, the current map needs only a minor modification. Instead, a clear announcement should be provided to avoid confusion from other researchers (2). If the IASLC regards N2 lymph nodes as mediastinal lymph nodes, major modifications are required.

      5. Station 4 and 10

      - Problematic area: Anterior aspect of the lower trachea and carina below the lower border of #4 lymph nodes are located in the mediastinum.

      6. Station 5 and 10

      - Problem: Pulmonary arteries are curved structures craniocaudally, and different interpretation of this border results in differeces among altases. The intersection of the left superior pumonary vein branch and left main pulmonary artery may serve as a clear border. If # 10 lymph nodes are classified as non-mediastinal lymph nodes, the border definition should also be modified.

      References

      1. Itazawa T, Tamaki Y, Komiyama T, et al. The Japan Lung Cancer Society-Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer. J Radiat Res 2017; 58:86-105.

      2. El-Sherief AH, Lau CT, Wu CC, Drake RL, Abbott GF, Rice TW. International association for the study of lung cancer (IASLC) lymph node map: radiologic review with CT illustration. Radiographics 2014; 34:1680-1691.

      3. El-Sherief AH, Lau CT, Obuchowski NA, Mehta AC, Rice TW, Blackstone EH. Cross-Disciplinary Analysis of Lymph Node Classification in Lung Cancer on CT Scanning. Chest 2017; 151:776-785.

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      MS06.02 - Endoscopic Nodal Staging (Now Available) (ID 3468)

      11:00 - 12:30  |  Presenting Author(s): Jose Sanz Santos

      • Abstract
      • Presentation
      • Slides

      Abstract

      1. INTRODUCTION.

      Endoscopic ultrasound (EUS) and endobronchial ultrasound (EBUS) were first described in the early 1980’s and 1990’s respectively. However, their incorporation into clinical practice began some years later, after the development of echoendoscopes and echobronchoscopes.

      2. PROCEDURE.

      EBUS-TBNA allows the sampling of retrotracheal (3P), upper paratracheal (2L,2R), lower paratracheal (4L/4R) and subcarinal (7) nodal stations. Moreover, EBUS-TBNA can access hilar (10L/10R) and interlobar nodal stations (11L/11R). EUS-FNA can access stations 2 and 4, subaortic (5), 7, paraesophageal (8L/8R) and pulmonary ligament (9L/9R).

      EBUS-TBNA/EUS-FNA is usually performed under conscious sedation or general anaesthesia in an outpatient setting. The reported complications rate for EBUS and EUS is < 1%.

      The current international guidelines for preoperative mediastinal staging of lung cancer1 recommends, for an endoscopy-based mediastinal staging procedure, as a minimum requirement, sampling the largest LN in 4R, 4L and 7 stations, as well as positron emission tomography (PET) positive LNs within each of these stations. Thus, 3 nodes is the minimum sampling requirement for an endoscopy-based staging procedure.

      3. MEDIASTINAL STAGING OF LUNG CANCER THROUGH ENDOSONOGRAPHY.

      3.1 EUS-FNA

      Overall, the reported pooled sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of EUS-FNA for lung cancer staging is 0.83, 0.97, 0.78 and 0.98 respectively2.

      3.2 EBUS-TBNA

      Two meta-analysis focussed on EBUS-TBNA in lung cancer staging were published ten years ago3,4. Most of the studies included patients with abnormal mediastinum on CT and/or PET/CT and thereby a high prevalence of disease. The reported pooled sensitivity was 0.9 and 0.93, respectively, ranging from 0.69 to 0.99.

      More recently, two meta-analysis5,6 have analysed the usefulness of EBUS-TBNA in lung cancer staging in patients with radiologically normal mediastinum. Both have shown similar pooled results for sensitivity (0.49, 0.495) and NPV (0.99, 0.93) with a similar median prevalence of N2/N3 disease (15.2%, 12.8%).

      3.3 Combined EUS/EBUS

      EBUS and EUS are complementary techniques that can access to different nodal stations. Thus, combination of both techniques may result in an increase of the sensitivity. A meta-analysis that included 2395 patients7 reported a mean sensitivity of the combined approach of 0.86 with a mean NPV of 0.92. Depending on the order of both techniques, the addition of EUS(B) to EBUS increased sensitivity by 0.12, and addition of EBUS to EUS(B) increased sensitivity by 0.22. However, no differences in sensitivity and NPV were shown between studies that performed EBUS first and studies that performed EUS first.

      3.4 Combined EUS-B/EBUS

      Combining EBUS with EUS has several limitations: usually needs to be performed by two different operators (pulmonologist/thoracic surgeon or gastroenterologist), in different settings, increasing the cost and waiting time of the procedure. These problems can be solved using a single scope (EBUS), in the same setting, by the same operator, by introducing the EBUS scope into the esophagus (EUS(B)). Several studies have demonstrated that EUS(B) combined with EBUS-TBNA results in an increase of the sensitivity compared with EBUS-TBNA alone8.

      4. THE N1 ELEMENT

      On the last years, several lung-sparing treatments for lung cancer have been developed. To select candidates for these techniques, accurate staging not only of the mediastinal nodes but also of the hilar nodes is crucial. One of the advantages of EBUS-TBNA is the ability to access N1 nodes.

      A study conducted by Yasufuku et al.9 that included patients with clinically N0/N1 disease eligible for surgical resection demonstrated that EBUS-TBNA can accurately access the hilar and interlobar LNs with a reported sensitivity, specificity, diagnostic accuracy and NPV of 0.76, 1, 0.96, and 0.96 respectively.

      5. HOT TOPICS

      Currently there are two questions that have to be answered:

      5.1 Must the combination EBUS/EUS (B) be performed routinely? In which order?

      As mentioned before7, EUS (B) needs to be added to EBUS in 25 patients and EBUS to EUS (B) in 14 patients to detect one additional patient with mediastinal nodal disease that would not have been detected if only one test had been performed.

      5.2 After an EBUS-TBNA procedure showing no mediastinal involvement, must patients undergo confirmatory mediastinoscopy?

      One recent meta-analysis10 studied the rate of unforeseen N2 disease in patients with lung cancer with or without mediastinoscopy after negative endosonography. In patients with EBUS and or EUS alone, the rate of unforeseen N2 was 9.3% for EBUS, and 13.4% for EUS. In patients with confirmatory mediastinoscopy the rate of unforeseen N2 disease after negative findings of EBUS (plus mediastinoscopy) was 11.2%, and after negative EUS (plus mediastinoscopy) was 14.9%.

      REFERENCES:

      1.De Leyn, et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small cell lung cancer. Eur J Cardiothorac Surg. 2014 May;45(5):787-98.

      2.Micanes CG, et al. Endoscopic ultrasound-guided fine-needel aspiration for non-small cell lung cancer staging. A systematic review and metaanalysis. Chest 2007;131:539-548.

      3.Gu P, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis. Eur J Cancer. 2009 May;45(8):1389-9.

      4.Dong X, et al. Endobronchial ultrasound-guided transbronchial needle aspiration in the mediastinal staging of non-small cell lung cancer: a meta-analysis. Ann Thorac Surg 2013;96:1502-07.

      5.Leong TL, et al. Preoperative staging by EBUS in cN0/N1 lung cancer systematic review and meta-analysis. J Bronchol Intervent Pulmonol [Epub ahead of print]

      6.El-Osta H, et al. Endobronchial ultrasound for nodal staging of patients with non-small-cell lung cáncer with radiologically normal mediastinum a meta-analyisis. Ann Am Thorac Soc 2018;15:864-874.

      7.Korevaar DA, et al. Added value of combined endobronchial and oesophagueal endosonography for mediastinal nodal staging in lung cancer: a systematic review and meta-analysis. Lancet Respir Med 2016;4:960-68.

      8.Dhooria S, et al. Utility and safety of endoscopic ultrasound with bronchoscope-guided fine-needle aspiration in mediastinal lymph node sampling: systematic review and meta-analysis. Respir Care 2015;60(7):1040-1050.

      9.Yasufuku K, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for differentiating N0 versus N1 lung cancer. Ann Thorac Surg 2013;96:1756-60.

      10.Bousema JE, et al. Unforeseen N2 disease after negative endosonography findings with or without confirmatory mediastinoscopy in resectable non-small cell lung cancer: a systematic review and meta-analysis. J Thorac Oncol. 2019 Jun;14(6):979-992

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      MS06.03 - Pathologic Staging: Operative Events (Now Available) (ID 3469)

      11:00 - 12:30  |  Presenting Author(s): Thomas A. D'Amico

      • Abstract
      • Presentation
      • Slides

      Abstract

      Accurate pathologic nodal staging, a powerful prognostic factor after resection of lung cancer, requires thorough examination of the mediastinal lymph nodes. Accurate pathologic staging of lung cancer requires effective collaboration between the surgery and pathology teams. There is a quality gap in pathologic nodal staging from three sources: poor surgical lymph node examination practice (failure to collect nodes), problems in the pathologic transfer of specimens (loss in transit or improper communication of the source of specimens), and poor pathology examination practice (incomplete examination or inaccurate and inconsistent reporting).

      Adequacy of mediastinal lymph node dissection (MLND) during resection for lung is an important quality measure that is not universally met in the US. For most patients with lung cancer, mediastinal lymph node dissection or systematic sampling is recommended at the time of resection, but it is only infrequently performed. For example, 62% of pathologic N0 and N1 non-small cell lung cancer resections in the US SEER database have no mediastinal lymph nodes examined.

      There is also significant discordance between surgeon claims of the extent of mediastinal lymphadenectomy and verifiable lymph node examination from pathology reports. Review of pathology reports in one study suggested that only 8% of all resections meet systematic sampling criteria, 50% have random sampling, and 42% have no mediastinal lymph nodes examined. However, a blinded independent audit of the surgeons’ operation notes suggested that 29% of cases had described a mediastinal lymph node dissection procedure.

      Some surgeons utilize a strategy of using several pathologic variables to determine the need for MLND during resection for non-small cell lung cancer. The premise is that it is an important goal to “minimize surgical trauma”. However, most surgeons would agree that there is not significant trauma related to the dissection of clinically negative lymph nodes, and that the incremental trauma related to MLND is itself minimal.

      Other strategies to obviate MLND have been suggested. Sentinel lymph node identification has been proved unsuccessful for lung cancer; sentinel technologies do not reliably identify a single lymph node, and N2 disease may still be present even when the sentinel node is negative. In any case, that strategy was tested in an era when only N2 patients could receive adjuvant chemothererapy, and the strategy was based on finding micromestastic disease, not limiting surgical trauma. In an era where N1 disease and tumor size both direct adjuvant therapy, the effort to limit lymphadenectomy is even less useful and this practice should be scrutinized. Even in major cancer centers, the targets of ten lymph nodes and three N2 stations is not universally met.

      In summary, patients with cT2 or > N0 lung cancer should undergo pre-resectional staging with either endobronchial ultrasound or mediastinoscopy. At the time of anatomic resection, adequate management of mediastinal lymph nodes should also be performed, either complete mediastinal lymph node dissection (favored) or rigorous systematic mediastinal lymph node sampling, with the goal of at least 3 N2 stations, and at least 10 lymph nodes.

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      MS06.04 - Approaches to Overcoming the Nodal Staging Quality Gap (Now Available) (ID 3470)

      11:00 - 12:30  |  Presenting Author(s): Ray Osarogiagbon

      • Abstract
      • Presentation
      • Slides

      Abstract

      MS 06 04: Approaches to Overcoming the Nodal Staging Quality Gap: Extended Abstract.

      The importance of pathologic nodal staging. Surgical resection remains the most important curative-intent treatment modality for non-small cell lung cancer (NSCLC), with 75-85% of 5 year survivors having undergone resection. For such patients, the status of nodal involvement is the most important prognostic factor, which also has implications for subsequent management, since patients with any nodal involvement (pN1-3) benefit from adjuvant chemotherapy and those with mediastinal nodal involvement (pN2-3) may benefit from adjuvant radiation therapy. Nodal staging also influences risk-stratification for clinical trials eligibility.

      Defining nodal staging quality. There are no universally accepted criteria for defining nodal staging quality, but various professional organizations, including the American College of Surgeons Oncology Group (ACOSOG), the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC), the American College of Surgeons Commission on Cancer (CoC), the European Society for Thoracic Surgery (ESTS), the International Association for the Study of Lung Cancer (IASLC) and the National Comprehensive Cancer Network (NCCN) have all proposed slightly different measures of the quality of pathologic staging, including nodal staging parameters.1

      The nodal staging quality gap. Despite the importance of pathologic nodal stage, the quality of application of nodal staging is highly variable. Three examples are: non-examination of lymph nodes in resection specimens (pNX) which exists in 12-18% of resections; non-examination of mediastinal lymph nodes, which is reported in up to 50% of resections; failure to achieve aggregate nodal staging quality requirements, such as the NCCN definition of quality, which is achieved in as few as 4% of surgical resections in population-based cohorts in the United States.2

      Survival implications. pNX resections have significantly inferior survival to pN0 resections, and are more similar to resections for pN1 NSCLC; pN0 and pN1 resections without examination of mediastinal nodes have 14% lower adjusted 5-year survival than those with at least one examined mediastinal lymph node; and achievement of all 4 elements of the NCCN definition of resection quality (anatomic resection, negative margins, examination of at least 1 hilar/intrapulmonary lymph node and at least 3 mediastinal nodal stations) is associated with 30% lower hazard of death within 5 years.3

      Causes of the gap, corrective interventions. The nodal staging quality gap can be localized to events during the surgical operation, the transfer of resection specimens and the pathology examination. Effective interventions must correct the problem at all its potential sites of origin. In the ‘chain of responsibility’ conceptual model, any breakdown in the surgical retrieval of lymph nodes, labeling of specimens, transfer of specimens, gross retrieval of lymph nodes from submitted material and pathologic examination of the retrieved material can break down the quality and accuracy of the final pathology report which is used for all subsequent oncologic care decision-making. Devices such as pre-labeled specimen collection kits are able to prevent breakdown at all links of this chain: they significantly increase the thoroughness of lymph node evaluation; rates of attainment of nodal staging quality measures; and survival. However, their impact on retrieval of intrapulmonary lymph nodes is limited.

      Specific interventions are also required to improve pathologic retrieval of intrapulmonary lymph nodes, given evidence that up to 90% of pulmonary resection specimens have lymph nodes discarded without examination, approximately 30% of which have metastasis, including in 12% of patients reported as having pN0. Patients with discarded intrapulmonary lymph node metastasis have worse survival than those without, irrespective of their pathologic nodal stage. Even in the mediastinal nodal dissection arm of the ACOSOG Z0030 trial, in which there was extensive evaluation of hilar and mediastinal lymph nodes, poor examination of intrapulmonary lymph nodes was common and had significant negative survival impact.4 Novel, anatomically sound gross dissection methods designed to focus on retrieval of lymph nodes in the peri-bronchial tree with particular emphasis on sites of bronchial bifurcation, significantly improve the yield of lymph nodes and decrease the incidence of discarded lymph nodes. Therefore, combining surgery with lymph node specimen collection kits and improved gross dissection methods is necessary to comprehensively overcome the nodal staging quality gap.

      What are the putative pathways for survival impact? Correct prognostication by more accurate risk-stratification, although beneficial in itself, would only impact on stage-stratified survival, without changing survival in aggregate populations. The finding of aggregate survival differences suggests benefit beyond mere stage re-categorization. One likely mechanism is improvement in identification of candidates for adjuvant therapy, which then provides an indirect means of risk-mitigation. However, given the larger reduction in hazard for death when surgical specimen collection kits are used, than would be expected from adjuvant therapy benefits alone, another plausible hypothesis is an inherent benefit of resecting oligo-metastatic lymph node disease. This hypothesis requires further testing. Interestingly, it fits the emerging understanding of suboptimal nodal staging as a type of incomplete resection (R-uncertain) and the IASLC’s proposal for creating a new category of ‘R-uncertain’ resections, the overwhelming majority of which are caused by poor nodal staging.5

      The emerging ability to conduct tests for minimal residual disease such as with cell-free DNA will provide a means of directly testing this hypothesis. If proven, it would open a pathway to future clinical trials of novel adjuvant treatments, such as checkpoint inhibitor therapy and other immunomodulatory treatments for these residually high-risk patients.

      References

      Smeltzer MP, et al. Association of Pathologic Nodal Staging Quality With Survival Among Patients With Non-Small Cell Lung Cancer After Resection With Curative Intent. JAMA Oncol. 2018 Jan 1;4(1):80-87.

      Allen JW, et al. Quality of surgical resection for nonsmall cell lung cancer in a US metropolitan area. Cancer. 2011 Jan 1; 117(1):134-42.

      Osarogiagbon RU, et al. Prognostic Value of National Comprehensive Cancer Network Lung Cancer Resection Quality Criteria. Ann Thorac Surg. 2017 May; 103(5):1557-1565.

      Osarogiagbon RU, et al. Survival Implications of Variation in the Thoroughness of Pathologic Lymph Node Examination in American College of Surgeons Oncology Group Z0030 (Alliance). Ann Thorac Surg. 2016 Aug;102(2):363-9.

      Rami-Porta, et al. Complete resection in lung cancer surgery: proposed definition. Lung Cancer. 2005 Jul;49(1):25-33.

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      MS06.05 - Transcervical Lymphadenectomies (Now Available) (ID 3471)

      11:00 - 12:30  |  Presenting Author(s): Marcin Zielinski

      • Abstract
      • Presentation
      • Slides

      Abstract

      Abstract

      Introduction:

      The aim of his study is to analyze the issue of transcervical lympadenectomies for Non-Small-Cell Lung Cancer performed by the techniques of Video-Assisted Mediastinoscopic Lymphadenectomy (VAMLA) and Transcervical Extended Mediastinal Lymphadenectomy (TEMLA).

      Methods

      The Pubmed search was performed and there were 27 articles found on VAMLA and 33 articles on TEMLA. After further analysis there were 13 original article on VAMLA and 18 original articles on TEMLA. In the current paper all proven and possible advantages of transcervical lymphadenectomies representd by VAMLA and TEMLA are described.

      Results

      The proven advantages of VAMLA and TEMLA:

      1. Superior diagnostic value in discovery of the metastatic mediastinal nodes for staging and restaging of NSCLC.

      2. bilateral mediastinal lymphadenectomy, more extensive than the techniques of lymphadenectomy used during standard thoracotomy or Video-Assisted Thoracic Surgery (VATS) approaches.

      Possible advantages include:

      1. Improved selection of patients for pulmonary resection for NSCLC

      2. Combination of VAMLA/TEMLA with VATS pulmonary resection,

      3. Combination of VAMLA/TEMLA with esophegeal resection,

      4. Combination of TEMLA and Stereotactic Radiotherapy (SBRT) for advanced NSCLC

      5. The use of TEMLA for preoperative staging of mesothelioma,

      6. Combination of TEMLA and pulmonary lobectomy through a sole transcevical approach

      7. Resection of various metastatic tumors, including thyroid cancer and metastatic mediastinal nodes.

      8. Possible impact of VAMLA/TEMLA on improvement of survival for NSCLC patients, which is the most important issue. In case of VAMLA superior survival of patients operated on with the use pulmonary resection with VAMLA in comparison to the pulmonary resection with addition of standard mediastinoscopy. In case of TEMLA no reports on survival has been published, yet

      Disadvantages of VAMLA/TEMLA include

      1. Possible complications, especially the left recurrent nerve palsy

      2. Possible delay or elimination of some patients from pulmonary resection due to postoperative complication in case of negative result of VAMLA/TEMLA

      3. Scar in the neck (cosmetic)

      4. Demanding surgical technique

      Conclusions

      1. Bilateral transcervical lymphadenectomies representd by VAMLA and TEMLA are more extensive than the techniques of lymphadenectomy used during standard thoracotomy or Video-Assisted Thoracic Surgery (VATS) approaches and superior to the other techniques of staging and restaging of NSCLC in regard to the diagnostic value.

      2. There are several other possible advantages of TEMLA/VAMLA for the treatment of NSCLC, esophageal cancer, mediastinal tumors and malignant mesothelioma.

      3. Possible impact of VAMLA/TEMLA on survival of NSCLC has not been proven, yet.

      References

      Hurtgen M, Friedel G, Toomes H et al: Radical video-assisted mediastinoscopic lymphadenectomy (VAMLA) – technique and first results. Eur J Cardiothorac Surg 2002;21:348-51

      Zielinski M, Szlubowski A, Kołodziej M, Orzechowski S, Laczynska E, Pankowski J, Jakubiak M, Obrochta A. Comparison of endobronchial ultrasound and/or endoesophageal ultrasound with transcervical extended mediastinal lymphadenectomy for staging and restaging of non-small-cell lung cancer. J Thorac Oncol. 2013 May;8(5):630-6.

      Zielinski M, Hauer J, Hauer L, Pankowski J, Nabialek T, Szlubowski A. Staging algorithm for diffuse malignant pleural mesothelioma. Interact Cardiovasc Thorac Surg. 2010;10:185-9

      Zieliński M, Pankowski J, Hauer L et al: The right upper lobe pulmonary resection performed through the transcervical approach. Eur J Cardiothorac Surg. 2007;32:766-769

      Singh AK, Hennon M, Ma SJ, Demmy TL, Picone A, Dexter EU, Nwogu C, Attwood K, Tan W,, Hermann GM, Fung-Kee-Fung S, Malhotra HK, Yendamuri S, Gomez-Suescun JA. A pilot study of stereotactic body radiation therapy (SBRT) after surgery for stage III non-small cell lung cancer. BMC Cancer. 2018 Nov 29;18(1):1183. doi: 10.1186/s12885-018-5039-5.

      Turna A, Demirkaya A, Ozkul S, Oz B, Gurses A, Kaynak K. Video-assisted mediastinoscopic lymphadenectomy is associated with better survival than mediastinoscopy in patients with resected non-small cell lung cancer. J Thorac Cardiovasc Surg. 2013 Oct;146(4):774-80. doi: 10.1016/j.jtcvs.2013.04.036. Epub 2013 Jun 15.

      Li X, Wang W,, Zhou Y, Yang D, Wu J, Zhang B, Wu Z, Tang J.. Efficacy comparison of transcervical video-assisted mediastinoscopic lymphadenectomy combined with left transthoracic esophagectomy versus right transthoracic esophagectomy for esophageal cancer treatment. World J Surg Oncol. 2018 Feb 9;16(1):25. doi: 10.1186/s12957-017-1268-3.

      Call S, Obiols C, Rami-Porta R, Trujilo-Reyes JC, Iglesias M, Saumench R, Gonzalez-Pont G, Serra-Mitjans M, Belda-Sanchís J. Video-Assisted Mediastinoscopic Lymphadenectomy for Staging Non-Small Cell Lung Cancer. Ann Thorac Surg. 2016 Apr;101(4):1326-33. doi: 10.1016/j.athoracsur.2015.10.073. Epub 2016 Jan 21.

      .Kim HJ, Kim YH, Choi SH, Kim HR, Kim DK, Park SI. Video-assisted mediastinoscopic lymphadenectomy combined with minimally invasive pulmonary resection for left-sided lung cancer: feasibility and clinical impacts on surgical outcomes†. Eur J Cardiothorac Surg. 2016 Jan;49(1):308-13. doi: 10.1093/ejcts/ezv077. Epub 2015 Mar 11

      Zielinski M. Transcervical Resection of the Mediastinal Tumors. In Zielinski M, Rami-Porta R (eds). Transcervical Approach in Thoracic Surgery. Springer 2014, pages 141-148.

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      MS06.06 - The Concept of Complete Resection (Now Available) (ID 3472)

      11:00 - 12:30  |  Presenting Author(s): John G Edwards

      • Abstract
      • Presentation
      • Slides

      Abstract

      The basis of the definition of complete resection is the Union for International Cancer Control (UICC) residual tumor classification (R classification), which considers the presence or absence of tumor in the primary site, lymph nodes and distant site following treatment. It has established clinical relevance, reflects the effectiveness of treatment, may be used to determine whether further therapy is indicated and has established prognostic relevance in lung cancer [1-3]. However, there are deficiencies in that locoregional recurrence may occur after an apparent R0 resection. The Complete Resection Subcommittee was tasked by the IASLC Staging Committee in 2001 to prepare a proposal of the definition of complete resection, based on expert opinion. The proposal that was derived [4] proposed the term uncertain resection, R(un), according to the following criteria:

      An uncertain resection is defined when resection margins are proved to be free of disease microscopically, but one of the following applies:

      (a) The intraoperative lymph node evaluation has been less rigorous than systematic nodal dissection or lobe-specific systematic nodal dissection.

      (b) The highest mediastinal node removed is positive.

      (c) The bronchial margin shows carcinoma in situ.

      (d) Pleural lavage cytology is positive (R1 cy+).

      In addition, this proposal considered cases with positive pleural lavage cytology (PLC) as R(un), rather than R1, and cases with extracapsular extension of tumor in nodes removed separately, or those at the margin of the main lung specimen, were considered R1, rather than R0.

      The analysis of the proposed R Classification using the database informing the 8thEdition of the TNM was presented at the 18thWorld Conference on Lung Cancer. The predominant reason for re-classification as R(un), performed in 56% of cases, was less than systematic nodal dissection (96% of cases). Survival in the R(un) category was significantly worse than R0 in node positive cases (median survival 50 and 70 months respectively, Hazard Ratio 1.27, Figure). The status of the highest lymph node station also had prognostic significance in pN2 cases (HR 1.32). Further work, that will require the submission of high quality data to the IASLC Lung Cancer Staging Project, will investigate again the impact of the individual R factors, particularly those for which the prevalence (or data completeness) in the previous dataset was low. Participation by institutions worldwide is essential to ensure success [5].

      However, there are several aspects about R Factor assessment that require clarification. These are being considered by the R Factor Subcommittee of the Staging and Prognostic Factors Committee. A survey of the current application and interpretation of the R Classification for NSCLC has been designed. The R Factor Sub-Committee will be determining and disseminating best methodological practice for intra-operative and histopathological aspects of R factor assessment.

      figure4.jpg

      References:

      1. Brierley JD, Gospodarowicz MK, Wittekind Ch (eds). UICC TNM Classification of Malignant Tumours, 8th edition. Oxford:Wiley Blackwell; 2017; p:10-11.

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