Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma
Authors: Henckens Sofie P G , Liu Dajia , Gisbertz Suzanne S , Kalff Marianne C , Anderegg Maarten C J , Crull David , Daams Freek , van Dalsen Annette D , Dekker Jan Willem T , van Det Marc J , van Duijvendijk Peter , Eshuis Wietse J , Groenendijk Richard P R , Haveman Jan Willem , van Hillegersberg Richard , Luyer Misha D P , Olthof Pim B , Pierie Jean-Pierre E N , Plat Victor D , Rosman Camiel , Ruurda Jelle P , van Sandick Johanna W , Sosef Meindert N , Voeten Daan M , Vijgen Guy H E J , Bijlsma Maarten F , Meijer Sybren L , Hulshof Maarten C C M , Oyarce Cesar , Lagarde Sjoerd M , van Laarhoven Hanneke W M , van Berge Henegouwen Mark I ,   IVORY study group, Baas Peter C , Bahadoer Renu R , Belt Eric J T , Brattinga Baukje , Claassen Linda , Ćosović Admira , Drost Manon , van Esser Stijn , Gaspersz Marcia P , Görgec Burak , Hartgrink Henk H , van der Harst Erwin , Heisterkamp Joos , Kelder Wendy , Kingma B Feike , Koemans Willem J , Kouwenhoven Ewout A , Lecot Frederik , van der Linden Philip P , Nieuwenhuijzen Grard A P , van Oijen Martijn G H , van der Peet Donald L , Pierik E G J M Robert , Polat Fatih , Scheer Rene , Slootmans Cettela A M , Sosef Odin V , de Steur Wobbe O , Stockmann Hein B A C , Stoop Fanny J , Vugts Guusje , Weeda Víola B , Wiezer Marinus J 
Published: February 2024

Abstract

Background
This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status (TRG-ypN score; TRG1-ypN0, TRG&gt;1-ypN0, TRG1-ypN+ and TRG&gt;1-ypN+), with recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma.

Methods
This Dutch nationwide cohort study included patients treated with neoadjuvant chemoradiotherapy followed by oesophagectomy for distal oesophageal or gastro-oesophageal junctional adenocarcinoma between 2007 and 2016. The primary endpoint was the association of Mandard score and TRG-ypN score with recurrence patterns (rate, location, and time to recurrence). The secondary endpoint was overall survival.

Results
Among 2746 inclusions, recurrence rates increased with higher Mandard scores (TRG1 30.6%, TRG2 44.9%, TRG3 52.9%, TRG4 61.4%, TRG5 58.2%; P &lt; 0.001). Among patients with recurrent disease, the distribution (locoregional versus distant) was the same for the different TRG groups. Patients with TRG1 developed more brain recurrences (17.7 versus 9.8%; P = 0.001) and had a longer mean overall survival (44 versus 35 months; P &lt; 0.001) than those with TRG&gt;1. The TRG&gt;1-ypN+ group had the highest recurrence rate (64.9%) and worst overall survival (mean 27 months). Compared with the TRG&gt;1-ypN0 group, patients with TRG1-ypN+ had a higher risk of recurrence (51.9 versus 39.6%; P &lt; 0.001) and worse mean overall survival (33 versus 41 months; P &lt; 0.001).

Conclusion
Improved tumour response to neoadjuvant therapy was associated with lower recurrence rates and higher overall survival rates. Among patients with recurrent disease, TRG1 was associated with a higher incidence of brain recurrence than TRG&gt;1. Residual nodal disease influenced prognosis more negatively than residual disease at the primary tumour site.