Opelz Gerhard, Unterrainer Christian, Süsal Caner, Döhler Bernd
Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
Nephrol Dial Transplant. 2016 Aug;31(8):1360-7. doi: 10.1093/ndt/gfw088. Epub 2016 May 4.
Evidence is limited regarding the effect of de novo therapy with mammalian target of rapamycin (mTOR) inhibitors on cancer risk after kidney transplantation.
Collaborative Transplant Study data from 78 146 adult recipients of first deceased-donor kidney transplants (1999-2013) were analysed (4279 mTOR inhibitor, 73 867 no mTOR inhibitor) using standard methods. Propensity score matching was performed for analysis of basal cell and squamous cell skin cancer.
Standardized incidence ratios (SIR) versus a matched non-transplant population showed reduced tumour incidence in recipients with de novo mTOR inhibitor therapy compared with no mTOR inhibitor for non-melanoma skin cancer (NMSC) (SIR 5.1 versus 6.1; P =0.019) but not non-NMSC cancers (SIR 1.6 versus 1.7; P =0.35). Within propensity score-matched groups (n = 4265), multivariable Cox regression analysis showed a trend to reduced NMSC with mTOR inhibition [hazard ratio (HR) 0.77; P =0.063] but not for all non-NMSC tumours (HR 0.94; P= 0.59). A significant effect for mTOR inhibition was observed for basal cell carcinoma of the skin (HR 0.56; P= 0.004) but not squamous cell carcinoma (HR 0.87; P= 0.54).
De novo mTOR inhibition was associated with a substantially and significantly reduced risk of basal cell carcinoma of the skin after kidney transplantation. A significant reduction of the incidence of other cancers was not found.
关于雷帕霉素哺乳动物靶点(mTOR)抑制剂的从头治疗对肾移植后癌症风险的影响,证据有限。
采用标准方法分析了协作移植研究中78146例首次接受死亡供者肾移植的成年受者(1999 - 2013年)的数据(4279例使用mTOR抑制剂,73867例未使用mTOR抑制剂)。进行倾向评分匹配以分析基底细胞癌和鳞状细胞皮肤癌。
与匹配的非移植人群相比,标准化发病率(SIR)显示,与未使用mTOR抑制剂的受者相比,接受从头mTOR抑制剂治疗的受者非黑色素瘤皮肤癌(NMSC)的肿瘤发病率降低(SIR为5.1对6.1;P = 0.019),但非NMSC癌症发病率未降低(SIR为1.6对1.7;P = 0.35)。在倾向评分匹配组(n = 4265)中,多变量Cox回归分析显示,mTOR抑制有降低NMSC的趋势[风险比(HR)0.77;P = 0.063],但对所有非NMSC肿瘤无此趋势(HR 0.94;P = 0.59)。观察到mTOR抑制对皮肤基底细胞癌有显著影响(HR 0.56;P = 0.004),但对鳞状细胞癌无显著影响(HR 0.87;P = 0.54)。
从头mTOR抑制与肾移植后皮肤基底细胞癌风险大幅显著降低相关。未发现其他癌症发病率有显著降低。