Prognostic impact of additive chemotherapy after curative resection of metachronous colorectal liver metastasis: a single-centre retrospective study.

BACKGROUND: A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM. METHODS: In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables. RESULTS: Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23-0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16-10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29-5.65) as independent risk factors for OS. CONCLUSION: Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.

The local immune phenotype influences prognosis in patients with nodal-positive rectal cancer after neoadjuvant chemoradiation.

INDROCUTION: The local immune contexture in patients with locally advanced rectal cancer (LARC) has important prognostic value after neoadjuvant chemoradiation and surgical resection. In this study, we examined the prognostic role of Indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) according to the nodal stage of LARC patients. MASTERIAL AND METHODS: Expression of IDO1 and CD8 was evaluated through immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection. The average infiltration of IDO1+ and CD8+ cells was calculated and expressed as total scores as previously described. Kaplan-Meier curves were used to describe overall and disease-free survival. RESULTS: In nodal-positive tumours (N+), IDO-positivity was associated with a reduced disease-free survival (DFS) (p = 0.063) and CD8-positivity with an impaired OS (p = 0.024). Patients with a N+ LARC and a high total IDO1 score showed a clear advantage regarding five-year disease-free survival rates compared with patients with a low total IDO1 score (N+ 5y-DFS IDO1 high: 66.7% vs IDO low: 19%). We also detected better 5-years-OS rates in N+ LARC with a high total CD8 score (N+ 5y-OS CD8 high: 83.3% vs CD8 low: 32.3%). These survival benefits were not evident in patients with N-tumours. CONCLUSION: Analysis of the local CD8 and IDO1 expression influences prognosis in nodal-positive LARC patients after multimodal therapy and may be a helpful tool in specifying individual adjuvant treatment strategies according to different immune profiles.

Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe?

The prognostic value of the local immune phenotype in patients with colorectal cancer has been extensively studied. Neoadjuvant radiotherapy and/or chemotherapy may potentially influence these immune responses. In this study, we examined the prognostic role of indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) in locally advanced rectal carcinomas after neoadjuvant treatment. Expression of IDO1 and CD8 was evaluated by immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection. The average infiltration of IDO1+ and CD8+ cells was calculated along the tumour invasive front, in the tumour centre and within the neoplastic cells and expressed as total scores. Of the tumour specimens evaluable for immunohistochemistry, 100% showed CD8+ lymphocyte infiltration and 93.4% stained positive for IDO1. Total IDO1 score positively correlated with total CD8 score for all three subsites (p = 0.002, Kendall-tau-b 0.357). A high total CD8 score was positively correlated with lower ypUICC-stages (p = 0.047) and lower ypT-categories (p = 0.032). Total IDO1 expression showed a clear trend towards a lower risk of recurrence (p = 0.078). A high total IDO1 score was an independent prognostic marker for prolonged disease-free survival (HR 0.38, p = 0.046) and a high total CD8 score for favourable overall survival (HR 0.16, p = 0.029). Analysis of the local CD8 and IDO1 expression profile may be a helpful tool in predicting prognosis for patients with locally advanced rectal cancer following neoadjuvant chemoradiation.