224P - Soluble interleukin 6 receptor: a serum biomarker predicting preoperative chemoradiotherapy efficacy for oesophageal cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Oesophageal Cancer
Translational Research
Presenter Ken Kato
Authors K. Kato1, Y. Makuuchi2, K. Honda3, Y. Osaka2, T. Kojima4, K. Furuta5, H. Igaki6, H. Daiko7, A. Tsuchida2, T. Yamada3
  • 1National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2Tird Department Of Surgery, Tokyo Medical University, 1600023 - Tokyo/JP
  • 3Division Of Chemotherapy And Clinical Research, National Cancer Center Research Institute, 104-0045 - Tokyo/JP
  • 4Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 5Department Of Clinical Research, National Cancer Center Hospital, Tokyo/JP
  • 6Esophageal Surgery Division, National Cancer Center Hospital, Tokyo/JP
  • 7Esophageal Surgery Division, National Cancer Center Hospital East, Kashiwa/JP

Abstract

Background

Preoperative chemoradiotherapy (PCRT) was one of the standard care for resectable esophageal cancer. Because there is tendency of high morbidity at surgery after PCRT, risk benefit balance for PCRT should be considered.Predictive marker which can select the patients who have more benefit for PCRT is needed.

Methods

To identify a biomarker to predict efficacy of preoperative PCRT for esophageal cancer, expression profiles of serum proteins were determined. The expression levels of 84 serum proteins in 37 patients (7 responders to PCRT and 30 poor-responders) weremeasured. Responders were defined as the patients whom two third or more cancer was pathologically degenerated at the time of operation. The usefulness of biomarkers was validated with two independent retrospective cohorts (PCRT and preoperative chemotherapy (PCT) by cisplatin and 5-FU) and two phase II clinical cohorts (PCRT and PCT with docetaxel, cisplatin and 5-FU) (n = 187).

Results

In a discovery cohort, the expression levels of six proteins [macrophage inflammatory protein beta 1 (MIP1B), soluble interleukin 6 receptor (sIL6R), macrophage inflammatory protein alpha1 (MIP1A), insulin, interferon alpha 2 (IFNA2) and matrix metalloproteinase 3 (MMP3)] were significantly different between responders and poor-responders to PCRT. The most predictive factor for survival was soluble interleukin 6 receptor (sIL6R) (p = 0.008, log-rank test); sIL6R in poor-responders was higher than in responders (p = 0.005, Student's t-test). The increases of sIL6R in poor-responder who underwent PCRT were confirmed in a etrospective cohort (n = 38), and a phase II clinical trial (n = 26). However, sIL6R levels of patients who underwent PCT only in a retrospective cohort (cisplatin and 5FU n = 100) and a phase II clinical trial (docetaxel, cisplatin and 5FU, n = 23) were not significantly different.

Conclusion

Serum sIL6R have a potential to be a predictive biomarker for PCRT in esophageal cancer patients, not for preoperative chemotherapy.

Disclosure

All authors have declared no conflicts of interest.