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Sergi Call



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    MA08 - Pawing the Way to Improve Outcomes in Stage III NSCLC (ID 127)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      MA08.09 - Results of Trimodality Therapy for Patients with cN2 Lung Cancer Diagnosed by Video-Assisted Mediastinoscopic Lymphadenectomy (VAMLA) (Now Available) (ID 1295)

      15:15 - 16:45  |  Presenting Author(s): Sergi Call

      • Abstract
      • Presentation
      • Slides

      Background

      After a properly performed transcervical lymphadenectomy, invasive restaging of the mediastinum is unnecessary because 
there is no material left for a new biopsy. Therefore, when video-assisted mediastinoscopic lymphadenectomy (VAMLA) is used at primary staging, the only parameters to select patients for lung resection after induction therapy are: the stability of the primary tumor and the absence of extrathoracic disease assessed by PET-CT. The aim of this study is to analyze the results of those patients with cN2 NSCLC diagnosed by VAMLA who underwent trimodality treatment in terms of feasibility and survival.

      Method

      Prospective observational single-center study of 250 patients (206 men; median age, 65.7; range, 42-86) with NSCLC cN0-1 (by PET-CT) who underwent VAMLA from 01-2010 to 12-2017. Patients with cN2 diagnosed by VAMLA who underwent trimodality treatment (cisplatin-based chemotherapy concomitant with radical radiotherapy [mean 54Gy, range 40-70Gy] plus lung resection) were analyzed. Follow-up was completed in March 2019. Median follow-up for surviving patients was 39.5 months (range, 8-108). Survival analysis was performed by the Kaplan-Meier method; the log-rank test was used for comparisons. Patients who died within 90 days after resection were excluded from survival analyses. A p-value of less than 0.05 was considered significant. The IBM SPSS Statistics for Mac, version 20.0 was used.

      Result

      The rate of unsuspected N2-3 disease in the whole series was 14.5% (35 patients). 28 patients out of 35 were considered for trimodality treatment. The results of restaging based on the PET-CT were: disease progression in 8 (28.5%) (mostly distant metastases), and stability of the primary tumor or partial response in 20 patients (71.5%). Of 20 patients without progression, 13 (46.5%) underwent lung resection; the remaining 7 were considered unfit for surgery. Three- and 5-year survival rates for those candidates for chemoradiotherapy (n=28) were: 91.7% and 80.2%, respectively, for patients in whom complete lung resection was achieved; 34.3% and 0%, respectively, for those considered unfit for surgery; and 19% and 0%, respectively, for those with progression after chemoradiotherapy (p < 0.0001)(Figure 1).

      figure1.jpg

      Conclusion

      The use of VAMLA to select patients for trimodality treatment is feasible. Based on the results obtained (high rate of unsuspected cN2 diagnosed by VAMLA and prolonged survival of those patients in whom the trimodality treatment was accomplished), VAMLA should be included in the current staging algorithms, especially for those tumors with intermediate risk of N2 and normal mediastinum by PET-CT.

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    OA12 - Profiling the Multidisciplinary Management of Stage III NSCLC (ID 144)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      OA12.07 - Radicality of Lymphadenectomy in Lung Cancer According to Surgical Approach. Results from the Spanish Group of Video-Assisted Thoracic Surgery (Now Available) (ID 1062)

      15:45 - 17:15  |  Author(s): Sergi Call

      • Abstract
      • Presentation
      • Slides

      Background

      The minor standard of systematic nodal dissection (SND) in lung cancer surgery, which is the minimum recommended by the Union for International Cancer Control, requires the resection/sampling of, at least, 3 mediastinal (including subcarinal station) and 3 hilar/intrapulmonary lymph nodes (LN). The objective of this study is to analyze differences in intraoperative LN assessment in patients with surgically treated non-small cell lung cancer (NSCLC) according to surgical approach (open vs VATS), from the results of the Spanish Group of Video-Assisted Thoracic Surgery (GEVATS) database.

      Method

      Prospective multicenter cohort study of anatomic pulmonary resections (n=3533) performed from 20/12/16 to 20/03/18. Exclusions criteria were: indications different from NSCLC, previous lung cancer, synchronous tumors and induction therapy. Patients who did not meet the criteria for SND but had no nodal involvement were coded as pathologic (p)Nx (instead of pN0). Corresponding tests for homogeneity were performed. Multiple logistic regression analysis was used to determine the odds ratio (OR) and 95% confidence interval (95%CI). Stata/SE vs 13 statistical package was used for data analysis. Significance was considered when p<0.05.

      Result

      2532 patients were analyzed (1801 men [71.1%]; median age: 67 years). SND was performed in 65%, with a median of LN resected/sampled of 7 (IQR 4-12) and a rate of pN2 of 9.5%. Table1 summarizes results from bivariate analysis.Independent risk factors for thoracotomy at multivariate analysis (OR; 95%CI) were: squamous cell carcinoma vs adenocarcinoma (1.3; 1.04-1.68), staging mediastinoscopy (2.8; 1.83-4.22), LN resected (1.02; 1.00-1.04), SND (1.4; 1.07-1.8), tumour >3cm (1.8; 1.5-2.2), central tumour (2.5; 2.0-3.1); pN1 (1.5; 1.1-2.1) and pN2 (1.6; 1.1-2.3). A significantly higher proportion of nodal upstaging was observed in thoracotomy group: from cN0 to pN1/pN2, and from cN1 to pN2 (table1).

      figure1.jpg

      Conclusion

      The intensity of lymphadenectomy in GEVATS was superior in the thoracotomy approach. Therefore, intraoperative lymph node evaluation performed at VATS should improve to have better prognostic information and indicate adjuvant therapy.

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    WS05 - Staging Workshop Part 2: The Importance of Invasive Nodal Staging in Thoracic Malignancies (ID 106)

    • Event: WCLC 2019
    • Type: Workshop
    • Track: Staging
    • Presentations: 1
    • Now Available
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      WS05.01 - Invasive Pre-Operative Staging of Lung Cancer (Now Available) (ID 3684)

      15:45 - 17:15  |  Presenting Author(s): Sergi Call

      • Abstract
      • Presentation
      • Slides

      Abstract

      Although reliable mediastinal staging is essential for the management of NSCLC, the optimal approach to invasive mediastinal staging remains controversial.

      According on the current guidelines, preoperative invasive mediastinal staging can be omitted if all the following criteria apply: a) primary tumour located in the outer third of the lung; b) largest diameter of the tumour is ≤3 cm; c) absence of intrathoracic lymph node(s) on CT and PET (1,2). The rationale is that, in this situation, the rate of unsuspected pathologic mediastinal nodal disease is < 10% (3,4).

      When tumours are classified as clinical (c) N2-3 on PET-CT, the risk of mediastinal nodal involvement is at least 60% (1). In this situation, it is mandatory to pathologically confirm all abnormalities detected by CT or PET starting with an endosonography method (EBUS-FNA, EUS-FNA or their combination) and to reserve mediastinoscopy to validate their negative results (1,2).

      Regarding those tumours with an intermediate risk of N2-3 disease (and normal mediastinum by CT and PET) the rate of unsuspected N2 disease is: 20%-42%, for tumours classified as cN1, and 6%- 22.2% for tumours classified as cN0 and tumour size greater than 3cm (5-8). For these clinical scenarios, there is a little disagreement between American and European guidelines about the best staging procedure to start with. The American College of Chest Physicians (ACCP) guidelines suggest endosonography methods over surgical procedures (1), and the European Society of Thoracic Surgeons (ESTS) guidelines describe that the choice between mediastinoscopy with biopsies, or with pre-surgical lymphadenectomies or endoscopic staging by EBUS/EUS with FNA depends on local expertise (1,2). Regarding the accuracy of invasive mediastinal staging methods in this type of patients (clinical N0 disease by PET-CT), minimally invasive endoscopic techniques have a poor sensitivity (0.17-0.41) (5,9). On the other hand, due to the fact that performance of mediastinoscopy is investigator dependent, there is an important heterogeneity in the reported sensitivity and negative predictive values : 0.32 to 0.97 and 0.8 to 0.99, respectively (2). Transcervical lymphadenectomies (video-assisted mediastinoscopic lymphadenectomy[VAMLA] and transcervical extended mediastinal lymphadenectomy[TEMLA]) are the only pre-surgical staging procedures with the highest sensitivity and negative predictive value reported to date for those patients with normal mediastinum by PET and CT: 0.88-0.96 and 0.94-0.99, respectively (8-10). Focusing oncN1 tumors, endosonography methods have a reported sensitivity ranging from 0.38 to 0.43. (5,6). This sensitivity increased to 0.73 by adding a confirmatory mediastinoscopy to validate negative endosonographies (6). Based on the results from the first prospective multicentre study (ASTER III) to evaluate the performance of surgical mediastinal staging (by mediastinoscopy or by VAMLA) in patients with cN1, the superiority of surgical method was confirmed obtaining a global sensitivity of 0.73 and a negative predictive value of 0.92 (7). Regarding those tumours with high SUVmax, cN0 but size greater than 3cm and specially in adenocarcinomas the rate of unsuspected N2 is: 6%-14.8% (3,4). A recent prospective study to validate the feasibility and accuracy of VAMLA reported a rate of 22.2% of unsuspected N2 disease for cN0 tumour >3cm (19% N2 tumours and 3,2% N3 tumours) (8). Therefore, based on this results, it is recommendable to validate negative results of endosonographies with a surgical procedure in the same line of those patients with tumours classified as cN1.

      Conclusions

      Currently, surgical methods are mainly indicated to validate negative results of minimally invasive endoscopic techniques for those tumours with high suspicion of mediastinal involvement by PET-CT. Based on the latest evidence, mediastinoscopy and, especially, transcervical lymphadenectomies are the most reliable staging methods for the subgroup of patients with intermediate risk of N2 disease and normal mediastinum by PET and CT. Consequently, future staging algorithms should recommend surgical methods as the preferred technique for this subset of patients.

      References

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

      2. Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143: e211S-e250S

      3. Wang J, Welch K, Wang L, et al. Negative predictive value of positron emission tomography and computed tomography for stage T1-2N0 non-small-cell lung cancer: a meta-analysis. Clin Lung Cancer 2012;13:81-9.

      4. Gómez-Caro A, Boada M, Cabañas M, et al. False-negative rate after positron emission tomography/ computer tomography scan for mediastinal staging in cI stage non-small-cell lung cancer. Eur J Cardiothorac Surg 2012;42:93-100

      5. Yasufuku K, Nakajima T, Waddell T, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for differentiating N0 versus N1 lung cancer. Ann Thorac Surg 2013;96:1756-1760.

      6. Dooms C, Tournoy KG, Schuurbiers O, et al. Endosonography for mediastinal nodal staging of clinical N1 non-small cell lung cancer: a prospective multicenter study. Chest 2015;147:209-2015.

      7. Decaluwé H, Dooms C, D'Journo XB, et al. Mediastinal staging by videomediastinoscopy in clinical N1 non-small cell lung cancer: a prospective multicentre study. Eur Respir J 2017;50: 1701493

      8. Call S, Obiols C, Rami-Porta R, et al. Video-assisted mediastinoscopic lymphadenectomy for staging non-small cell lung cancer. Ann Thorac Surg 2016;101:1326-33

      9. Vial M, O’Connell O, Grosu H, et al. Diagnostic performance of endobronchial ultrasound-guided mediastinal lymph node sampling in early stage non-small cell lung cancer: A prospective study. Respirology 2018;23:76-81.

      10. Zielinski M, Hauer L, Hauer J, et al. Transcervical extended mediastinal lymphadenectomy (TEMLA) for staging of non-small-cell lung cancer (NSCLC). Pneumonol Alergol Pol 2011;79:196–206.

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