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. 2023 Jun;128(11):2036-2043.
doi: 10.1038/s41416-023-02217-x. Epub 2023 Mar 25.

Pathological regression of primary tumour and metastatic lymph nodes following chemotherapy in resectable OG cancer: pooled analysis of two trials

Avani Athauda  1 , Matthew Nankivell  2 , Rupert Langer  3 , Susan Pritchard  4 , Ruth E Langley  2 , Katharina von Loga  1 , Naureen Starling  1 , Ian Chau  1 , David Cunningham  5 , Heike I Grabsch  6   7
Affiliations

Pathological regression of primary tumour and metastatic lymph nodes following chemotherapy in resectable OG cancer: pooled analysis of two trials

Avani Athauda et al. Br J Cancer. 2023 Jun.

Abstract

Background: No definitive largescale data exist evaluating the role of pathologically defined regression changes within the primary tumour and lymph nodes (LN) of resected oesophagogastric (OG) adenocarcinoma following neoadjuvant chemotherapy and the impact on survival.

Methods: Data and samples from two large prospective randomised trials (UK MRC OE05 and ST03) were pooled. Stained slides were available for central pathology review from 1619 patients. Mandard tumour regression grade (TRG) and regression of tumour within LNs (LNR: scored as present/absent) were assessed and correlated with overall survival (OS) using a Cox regression model. An exploratory analysis to define subgroups with distinct prognoses was conducted using a classification and regression tree (CART) analysis.

Results: Neither trial demonstrated a relationship between TRG score and the presence or absence of LNR. In univariable analysis, lower TRG, lower ypN stage, lower ypT stage, presence of LNR, presence of well/moderate tumour differentiation, and absence of tumour at resection margin were all associated with better OS. However, the multivariable analysis demonstrated that only ypN, ypT, grade of differentiation and resection margin (R0) were independent indicators of prognosis. Exploratory CART analysis identified six subgroups with 3-year OS ranging from 83% to 22%; with ypN stage being the most important single prognostic variable.

Conclusions: Pathological LN stage within the resection specimen was the single most important determiner of survival. Our results suggest that the assessment of regression changes within the primary tumour or LNs may not be necessary to define the prognosis further.

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Conflict of interest statement

DC: Research funding from MedImmune, AstraZeneca, Clovis, Eli Lily, 4SC, Bayer, Celgene, NIHR EME, and Roche; Scientific advisory board for OVIBIO. IC: Research funding from Eli-Lilly, Janssen-Cilag; Honorarium from Eli-Lilly, Eisai, Servier; Advisory board for Eli-Lilly, Bristol Meyers Squibb, MSD, Roche, Merck-Serono, AstraZeneca, OncXerna, Pierre Fabre, Boehringer Ingelheim, Incyte, Astella, GSK, Sotio, Eisai, Daiichi-Sankyo, Taiho, Servier. Naureen Starling: Research funding from Merck, AstraZeneca, BMS, Pfizer; honoraria from Merck-Serono, Novartis, MSD Oncology, Eli Lily, Pierre Fabre, Amgen, GSK, Servier; Advisory board for Pfizer, Servier, AstraZeneca, MSD Oncology, Novartis; travel funding from AstraZeneca, BMS, Eli Lily, Merck, Roche, MSD Oncology. HIG: Advisory board for AstraZeneca and BMS. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Consort diagram demonstrating the number of patients included in this analysis and sub-analyses.
TRG tumour regression grade, LNR lymph node regression, LN lymph node.
Fig. 2
Fig. 2. Overall survival by TRG grade.
a All patients combined, b patients from the OE05 trial, c patients from the ST03 trial, d corresponding table with 3-year survival rates.
Fig. 3
Fig. 3. Kaplan-Meier survival curves.
a Survival curves for pathological lymph node status (ypN-/ypN+). b Survival curves for pathological lymph node status with the presence or absence of lymph node regression (LNR+/LNR-). c Corresponding table to show 3-year survival rates for the four groups in graph b.
Fig. 4
Fig. 4. Exploratory CART analysis.
a Split in CART analysis tree occurs if adjusted P < 0.01. b Kaplan–Meier survival curves for test set (70%). c Kaplan–Meier survival curves for validation set (30%) with the corresponding table of 3-year survival rates for each cluster.
See this image and copyright information in PMC

References

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