Chinese Clinical Oncology

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The efficacy of asparaginase-based chemotherapy combined with radiotherapy among stage ⅠE/ⅡE ENKTL patients and its relationship to asparagine synthetase expression

TANG Lanhua, TANG Youhong, LIU Yiping, LIU Wei, YI Pingyong, ZHONG Meizuo.
  

  1. Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China
  • Received:2015-08-17 Revised:2015-11-22 Online:2016-02-29 Published:2016-02-29
  • Contact: ZHONG Meizuo

Abstract: Objective To explore the efficacy of L-asparaginase(L-ASP)based chemotherapy combined with radiotherapy(RT) treating stageⅠE/ⅡE extranodal NK/T-cell lymphoma, nasal type(ENKTL) and the correlation between efficacy and the expression of asparagine synthetase(ASNS). Methods We retrospectively reviewed 119 patients with stage ⅠE/ⅡE ENKTL from May 2008 to July 2013. The efficacy of RT group(n=27), CHOP chemotherapy combined with RT(RT+CHOP) group(n=33) and L-ASP-based chemotherapy combined with RT(RT+L-ASP) group(n=59) were compared. The involved-field radiotherapy dose was between 50 Gy to 60 Gy. L-ASP 6000 U/m2 was intravenously dropped from d1 to d7.We also detected the mRNA and protein level of ASNS by RTPCR and immunochemistry in RT+L-ASP group. Results The results showed that response rate(RR) in RT+L-ASP group was 91.5%, significantly higher than 74.1% in RT group, and 69.7% in RT+CHOP group(P=0.007, P=0.030). The median overall survival(OS) of RT+L-ASP group was 49 months, higher than 28 months of RT group(P=0.017), and 31 months of RT+CHOP group(P=0.077). The median progression free survival(PFS) of RT+LASP group was 47 months, higher than 25 months of RT group and 17 months of RT+CHOP group with significant difference(P=0.018,P<0.001). Cox regression model showed that therapies and short term efficacy were independent factors influencing PFS of ENKTL. The most common side effects of the 3 groups were hepatic and renal dysfunction, and myelosuppression. Eight patients in RT+LASP group showed anaphylactic reaction. The expression of both ASNS mRNA and protein were lower in patients with better responses. ASNS mRNA was negatively correlated with OS and PFS and protein were both highly negatively(r=-0.65, P=0.01; r=-0.60, P=0.004), as well as ASNS protein(r=-0.77, P<0.001; r=-0.71,P<0.001). Conclusion L-ASP-based chemotherapy combined with RT can improve efficacy of ENKTL patients with stageⅠE/ⅡE, better than RT alone or CHOP chemotherapy in combination with RT. And the expression of ASNS, especially in protein level can serve as a L-ASP efficacy predictor for stageⅠE/ⅡE ENKTL.

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