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

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.

Reply to Rizzatti et al.

“…Ideally, such a restaging algorithm should take into account LN distribution based on both patient and disease characteristics, and enable targeting of the LNs that are most likely to be affected. The results of the ongoing TIGER studya study on the LN distribution in resectable esophageal cancer after neoadjuvant therapymay serve to develop such tool [4].…”

Distribution of Lymph Node Metastases in Esophageal Carcinoma Patients Undergoing Upfront Surgery: A Systematic Review

“…If we want to determine the exact distribution pattern of esophageal cancer, large well-designed prospective studies are needed. One initiative of such a study is the multinational prospective TIGER study (ClinicalTrials.gov Identifier: NCT03222895) [50].…”

Extent and consequences of lymphadenectomy in oesophageal cancer surgery: case vignette survey

“…Eighty participants completed the survey. middle and lower mediastinal paraoesophageal (11 and 12), pulmonary ligament (13), paracardial (14), left gastric artery (15), coeliac trunk (16) and the common hepatic artery LN stations (18). In case LN metastases were found in a field outside the routine LND field, the upper paratracheal LNs (increase of 40%), the cervical paraoesophageal LNs (increase of 34%) and the lower paratracheal LNs (increase of 33%) would most frequently be added to the routine LND (figure 2).…”

“…The diameter of the circle indicates the percentage of surgeons that dissect the station with routine LND (left) and based on suspicious LN metastases (right). Anatomical figure was adapted from the TIGER study protocol with permission of the authors 15. LN, lymph node; LND, lymph node dissection.…”