Antitumour immunity invoked by hepatic arterial infusion of first-line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8-12 years of follow-up.

Jūratė Šaltytė Benth,Lise L Berven,Hanna Abrahamsson,Julia S Johansen,Benny V Jensen,Dorte L Nielsen,Anne H Ree,Finn O Larsen,Jakob S Johansen

doi:10.1002/ijc.32847

Abstract

In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.

Highlights

In colorectal cancer (CRC), dissemination into systemic disease remains the main therapeutic challenge
2 patients had the CRC liver metastases (CLM) converted to resectable disease at post-1st seq, another 3 at post-2nd seq and yet 28 at post-3rd seq, altogether of whom 30 proceeded to CLM ablation because 3 patients with complete treatment response remained radiologically free of disease
In order to improve the selection of patients with isolated, primarily unresectable CLM for curative-intent ablation following chemotherapy, a better understanding of the underlying biology and the development of molecular markers for long-term therapeutic benefit are needed.[41]

Summary

Introduction

In colorectal cancer (CRC), dissemination into systemic disease remains the main therapeutic challenge. Improved surgical techniques[1,2] and the introduction of perioperative oxaliplatinbased chemotherapy[3,4] have enabled an increasing number of patients with liver-confined metastatic disease to undergo treatment with potentially curative intent, metastatic recurrence occurs in a high percentage of cases. The role of HAI chemotherapy in clinical practice still remains controversial, but trials that randomise between this and modern systemic therapy are ongoing.[24,25]

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Results

Conclusion