Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan

Abstract

Background and purposes: Early biomarkers of tumour response are needed to discriminate between responders and non-responders to radiotherapy. We evaluated the ability of ceramide, a bioactive sphingolipid, to predict tumour sensitivity in patients treated by hypofractionated stereotactic body radiation therapy (SBRT) combined with irinotecan chemotherapy.

Materials and methods: Plasma levels of total ceramide and of its subspecies were measured before and during treatment in 35 patients with liver and lung oligometastases of colorectal cancer included in a phase II trial. Cer levels were quantified by LC-ESI-MS/MS and compared to tumour volume response evaluated one year later by CT-scan.

Results: Pretreatment plasma ceramide levels were not indicative of tumour response. Nevertheless, the levels of total ceramide and of its 4 main subspecies were significantly higher at days 3 and 10 of treatment in objective responders than in non-responders. According to Kaplan-Meier curves, almost complete tumour control was achieved at 1year in patients with increased total ceramide levels whereas 50% of patients with decreased levels experienced an increase in tumour volume.

Conclusions: Total plasma ceramide is a promising biomarker of tumour response to SBRT combined with irinotecan that should enable to segregate patients with high risk of tumour escape.

Keywords: Biomarker; Ceramide; Irinotecan; Metastases; Stereotactic radiotherapy.