Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study

Eliza R C Hagens, Mark I van Berge Henegouwen, Johanna W van Sandick, Miguel A Cuesta, Donald L van der Peet, Joos Heisterkamp, Grard A P Nieuwenhuijzen, Camiel Rosman, Joris J G Scheepers, Meindert N Sosef, Richard van Hillegersberg, Sjoerd M Lagarde, Magnus Nilsson, Jari Räsänen, Philippe Nafteux, Piet Pattyn, Arnulf H Hölscher, Wolfgang Schröder, Paul M Schneider, Christophe Mariette, Carlo Castoro, Luigi Bonavina, Riccardo Rosati, Giovanni de Manzoni, Sandro Mattioli, Josep Roig Garcia, Manuel Pera, Michael Griffin, Paul Wilkerson, M Asif Chaudry, Bruno Sgromo, Olga Tucker, Edward Cheong, Krishna Moorthy, Thomas N Walsh, John Reynolds, Yuji Tachimori, Haruhiro Inoue, Hisahiro Matsubara, Shin-Ichi Kosugi, Haiquan Chen, Simon Y K Law, C S Pramesh, Shailesh P Puntambekar, Sudish Murthy, Philip Linden, Wayne L Hofstetter, Madhan K Kuppusamy, K Robert Shen, Gail E Darling, Flávio D Sabino, Peter P Grimminger, Sybren L Meijer, Jacques J G H M Bergman, Maarten C C M Hulshof, Hanneke W M van Laarhoven, Banafsche Mearadji, Roel J Bennink, Jouke T Annema, Marcel G W Dijkgraaf, Suzanne S Gisbertz, Eliza R C Hagens, Mark I van Berge Henegouwen, Johanna W van Sandick, Miguel A Cuesta, Donald L van der Peet, Joos Heisterkamp, Grard A P Nieuwenhuijzen, Camiel Rosman, Joris J G Scheepers, Meindert N Sosef, Richard van Hillegersberg, Sjoerd M Lagarde, Magnus Nilsson, Jari Räsänen, Philippe Nafteux, Piet Pattyn, Arnulf H Hölscher, Wolfgang Schröder, Paul M Schneider, Christophe Mariette, Carlo Castoro, Luigi Bonavina, Riccardo Rosati, Giovanni de Manzoni, Sandro Mattioli, Josep Roig Garcia, Manuel Pera, Michael Griffin, Paul Wilkerson, M Asif Chaudry, Bruno Sgromo, Olga Tucker, Edward Cheong, Krishna Moorthy, Thomas N Walsh, John Reynolds, Yuji Tachimori, Haruhiro Inoue, Hisahiro Matsubara, Shin-Ichi Kosugi, Haiquan Chen, Simon Y K Law, C S Pramesh, Shailesh P Puntambekar, Sudish Murthy, Philip Linden, Wayne L Hofstetter, Madhan K Kuppusamy, K Robert Shen, Gail E Darling, Flávio D Sabino, Peter P Grimminger, Sybren L Meijer, Jacques J G H M Bergman, Maarten C C M Hulshof, Hanneke W M van Laarhoven, Banafsche Mearadji, Roel J Bennink, Jouke T Annema, Marcel G W Dijkgraaf, Suzanne S Gisbertz

Abstract

Background: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients.

Methods: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival.

Discussion: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics.

Trial registration: NCT03222895 , date of registration: July 19th, 2017.

Keywords: Esophageal cancer; Esophagectomy; Lymph node metastases; Lymphadenectomy.

Conflict of interest statement

SL Is a member of the editiorial board (Associate Editor) of this journal. The other authors declare that they have no competing interests. The funding bodies did not have any role in the design of the study and will not have any role in collection, analysis, and interpretation of data and in writing the manuscript.

Figures

Fig. 1
Fig. 1
Classification of lymph node stations.

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