Metabolic tumor constitution is superior to tumor regression grading for evaluating response to neoadjuvant therapy of esophageal adenocarcinoma patients

Achim Buck, Verena M. Prade, Thomas Kunzke, Annette Feuchtinger, Dino Kröll, Marcus Feith, Bastian Dislich, Benjamin Balluff, Rupert Langer, Axel Walch

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The response to neoadjuvant therapy can vary widely between individual patients. Histopathological tumor regression grading (TRG) is a strong factor for treatment response and survival prognosis of esophageal adenocarcinoma (EAC) patients following neoadjuvant treatment and surgery. However, TRG systems are usually based on the estimation of residual tumor but do not consider stromal or metabolic changes after treatment. Spatial metabolomics analysis is a powerful tool for molecular tissue phenotyping but has not been used so far in the context of neoadjuvant treatment of esophageal cancer. We used imaging mass spectrometry to assess the potential of spatial metabolomics on tumor and stroma tissue for evaluating therapy response of neoadjuvant-treated EAC patients. With an accuracy of 89.7%, the binary classifier trained on spatial tumor metabolite data proved to be superior for stratifying patients when compared with histopathological response assessment, which had an accuracy of 70.5%. Sensitivities and specificities for the poor and favorable survival patient groups ranged from 84.9% to 93.3% using the metabolic classifier and from 62.2% to 78.1% using TRG. The tumor classifier was the only significant prognostic factor (HR 3.38, 95% CI 1.40–8.12, p = 0.007) when adjusted for clinicopathological parameters such as TRG (HR 1.01, 95% CI 0.67–1.53, p = 0.968) or stromal classifier (HR 1.86, 95% CI 0.81–4.25, p = 0.143). The classifier even allowed us to further stratify patients within the TRG1–3 categories. The underlying mechanisms of response to treatment have been figured out through network analysis. In summary, metabolic response evaluation outperformed histopathological response evaluation in our study with regard to prognostic stratification. This finding indicates that the metabolic constitution of the tumor may have a greater impact on patient survival than the quantity of residual tumor cells or the stroma.

Original languageEnglish
Pages (from-to)202-213
Number of pages12
JournalJournal of Pathology
Volume256
Issue number2
DOIs
StatePublished - Feb 2022
Externally publishedYes

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