Association of T-cell infiltration assessed in pretherapeutic biopsies (PTB) of patients with locally advanced rectal adenocarcinoma (LARC) with tumor response and relapse after chemoradiotherapy (CRT) and rectal surgery

Van den Eynde, Marc;El Sissy, Carine;Kirilovsky, Amos;Marliot, Florence;Pages, Franck;et.al.
(2017) 2017 ASCO Annual Meeting — Location: (United States) Chicago, IL (2.June.2017)

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  • Van den Eynde, MarcUCLouvain
    Author
  • El Sissy, Carine
    Author
  • Kirilovsky, Amos
    Author
  • Marliot, Florence
    Author
  • Dragean, CristinaUCLouvain
    Author
  • Danse, EtienneUCLouvain
    Author
  • Denis, Marie ArmelleUCLouvain
    Author
  • Kartheuser, AlexUCLouvain
    Author
  • Remue, Christopheorcid-logoUCLouvain
    Author
  • Léonard, DanielUCLouvain
    Author
  • Bachmann, RaduUCLouvain
    Author
  • Baldin, PamélaUCLouvain
    Author
  • De Cuyper, AstridUCLouvain
    Author
  • Humblet, YvesUCLouvain
    Author
  • Scalliet, PierreUCLouvain
    Author
  • Mourin, AnneUCLouvain
    Author
  • Pages, Franck
    Author
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Abstract
Background: Pre-operative CRT followed by total mesorectal excision (TME) is nowadays the standard of care for patient with LARC (cT3-T4N0 or cTxN+). Currently, pathologic complete response occurs in +/- 15% after CRT. Colorectal cancer T-cell infiltration is a strong prognostic factor for survival after primary tumor resection. Our aim was to determine whether T-cell infiltration in PTB could be predictive of tumor response and relapse after CRT + TME. Methods: Between 1999 and 2012, patients with LARC who underwent CRT + TME and with available clinical follow-up and PTB (with sufficient tumor cells density) were identified at the Cliniques universitaires St-Luc. The density of CD3 (T cells) and CD8 (cytotoxic) was quantified on immunostained PTB slides and analyzed with a dedicated image analysis software on whole-slide imaging. Comparisons were made using the Wilcoxon-Mann-Whitney test. Cumulative disease-free survival (DFS) was performed using the Kaplan-Meier estimator and compared by log-rank tests. Cox regression we used for uni- and multi-variate analysis. P value of less than 0.05 was considered statistically significant. Results: 154 patients (sex ratio M/F 1.8; mean age 65 years-old; upper (20%), mid (29%) and low rectum (51%), synchronous metastases (11%)) were analyzed. High CD3 and CD8 PTB densities were significantly associated with a higher pathological response (Dworak 3-4) and lower ypTNM stage after CRT +TME (p < 0,05). Higher CD3 and CD8 PTB densities were associated with higher patient DFS (CD3: HR = 2,30 (CI95%:1,15-4,59) p = 0,02; CD8: HR = 1,95 (CI95%: 1,01-3,75) p = 0,04). These results were confirmed in uni and multivariate analysis. CD3 and CD8 PTB densities added to pathological response (ypTNM/Dworak) but also clinical response (ycTNM) after CRT + TME increases significantly the accuracy prediction of tumor relapse. Conclusions: Pretherapeutic T-cell infiltration of LARC is predictive of tumor response and relapse after CRT +TME. This biomarker could be helpful for patient treatment decision. It must be validated in larger patient cohorts.
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Van den Eynde, M., El Sissy, C., Kirilovsky, A., Marliot, F., Haicheur, N., Dragean, C., Danse, E., Denis, M. A., Kartheuser, A., Remue, C., Léonard, D., Bachmann, R., Baldin, P., De Cuyper, A., Humblet, Y., Scalliet, P., Mourin, A., Galon, J., & Pages, F. (2017). Association of T-cell infiltration assessed in pretherapeutic biopsies (PTB) of patients with locally advanced rectal adenocarcinoma (LARC) with tumor response and relapse after chemoradiotherapy (CRT) and rectal surgery. Journal of Clinical Oncology, 35, 3599. https://doi.org/10.1200/JCO.2017.35.15_suppl.3599 (Original work published 2017)