Predictive immunohistochemical features for tumour response to chemoradiotherapy in rectal cancer

Abstract

Background Reduced expression of cluster of differentiation (CD) 133 and cyclo‐oxygenase (COX) 2, and increased density of CD8+ tumour‐infiltrating lymphocytes, are associated with a favourable tumour response to preoperative chemoradiotherapy (CRT). This study aimed to evaluate these markers in relation to tumour response after preoperative CRT in two rectal cancer cohorts. Methods Patients with low rectal cancer who underwent radical resection and preoperative short‐term CRT in 2001–2007 (retrospective cohort) and long‐term CRT in 2011–2017 (prospective cohort) were analysed. Pretreatment biopsies were stained immunohistochemically using antibodies to determine CD133 and COX‐2 expression, and increased CD8+ density. Outcome measures were tumour regression grade (TRG), tumour downstaging and survival. Results For 95 patients in the retrospective cohort, the incidence of TRG 3–4 was 67 per cent when two or three immunohistochemistry (IHC) features were present, but only 20 per cent when there were fewer features (P < 0·001). The incidence of tumour downstaging was higher in patients with at least two IHC features (43 versus 22 per cent with fewer features; P = 0·029). The 49 patients in the prospective cohort had similar rates to those in the retrospective cohort (TRG 3–4: 76 per cent for two or more IHC features versus 25 per cent with fewer features, P < 0·001; tumour downstaging: 57 versus 25 per cent respectively, P = 0·022). Local recurrence‐free survival rates in patients with more or fewer IHC features were similar in the retrospective and prospective cohort (P = 0·058 and P = 0·387 respectively). Conclusion Assessment of CD133, COX‐2 and CD8 could be useful in predicting a good response to preoperative CRT in patients with lower rectal cancer undergoing neoadjuvant therapy. Further studies are needed to validate the results in larger cohorts and investigate a survival benefit.

Tumour budding and CD8+ T cells: ‘attackers’ and ‘defenders’ in rectal cancer with and without neoadjuvant chemoradiotherapy

“…Pre‐operative CD8 + T cell counts have recently been shown to predict response after neoadjuvant therapy in rectal cancer 12 . Work by Huang and colleagues underlined these findings in the pre‐operative biopsy, showing that although tumour budding alone has an impact on regression after treatment, the combination of intratumoral infiltrating CD8 + T cells and tumour budding was associated more markedly with worse regression grading using the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) criteria 3 .…”

A Systematic Review of the Cyclooxygenase-2 (COX-2) Expression in Rectal Cancer Patients Treated with Preoperative Radiotherapy or Radiochemotherapy

“…Only the research by de Heer et al has found a significant association ( p = 0.06) between the COX-2 expression and grading; a poor grade of differentiation was associated with high COX-2 expression levels in pretreatment specimens; a high level of COX-2 expression was more often observed both in irradiated and non-irradiated adenocarcinomas [ 75 ]. Shinto et al also proved that low expression of COX-2 was an independent parameter that influenced tumor regression grade (TRG) [ 87 ]. According to the results of 75% of the analyzed studies, there is no significant correlation between COX-2 staining and age, gender, tumor downstaging, pT, pN, vascular invasion, tumor necrosis, Duke’s stage, number of tumors and further complications.…”

IMMUNOREACT 0: Biopsy‐based immune biomarkers as predictors of response to neoadjuvant therapy for rectal cancer—A systematic review and meta‐analysis

“…We failed to find any significant evidence demonstrating the association between CD4+ sTILs of pretreatment biopsy specimens and treatment response (OR 1.36, 95% CI 0.85-2.20; participants = 278; I 2 = 0%) (Figure S1A). presence of CD8+ cells and response to NT was extracted from eight studies for total CD8+ TILs, [16][17][18][28][29][30][31][32] five studies for CD8+ iTILs 15,19,[33][34][35] and three studies for CD8+ sTILs 15,19,32 (Figure 4). Patients that in pretreatment biopsy specimens had high levels of total CD8+ TILs (OR 2.25, 95% CI 1.64-3.08; participants = 690; I 2 = 58%, Figure 4A), CD8+ sTILs (OR 1.52, 95% CI 1.05-2.18; participants = 542; I 2 = 62%, Figure 4B), as well as CD8+ iTILs (OR 3.43, 95% CI 2.56-4.62; participants = 961; I 2 = 65%, Figure 4C), showed a significant correlation with good treatment response.…”