Topical treatment of actinic keratoses in organ transplant recipients: a feasibility study for SPOT (Squamous cell carcinoma Prevention in Organ transplant recipients using Topical treatments).
Topical treatment of actinic keratoses in organ transplant recipients: a feasibility study for SPOT (Squamous cell carcinoma Prevention in Organ transplant recipients using Topical treatments).
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DOI：
10.1111/bjd.20974
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发表时间：
2022-09
影响因子：
10.3
通讯作者：
Harwood, Catherine A.
中科院分区：
文献类型：
--
作者：
Zeeshaan-Ul Hasan;Ahmed, Ikhlaaq;Matin, Rubeta N.;Homer, Victoria;Lear, John T.;Ismail, Ferina;Whitmarsh, Tristan;Green, Adele C.;Thomson, Jason;Milligan, Alan;Hogan, Sarah;Van-de-Velde, Vanessa;Mitchell-Worsford, Liza;Kentley, Jonathan;Gaunt, Claire;Jefferson-Hulme, Yolande;Bowden, Sarah J.;Gaunt, Piers;Wheatley, Keith;Proby, Charlotte M.;Harwood, Catherine A.
器官移植受者（OTRs）发生皮肤鳞状细胞癌（cSCC）的风险显著增加。清除光化性角化病（AKs）通常被认为是cSCC预防的替代生物标志物。尽管有证据表明5% 5 -氟尿嘧啶（5 - FU）可能对免疫功能正常的患者具有化学保护作用，但在随机对照试验（rct）中，局部AK治疗的OTR - cSCC化学预防尚未进行研究。评估与设计未来OTRs局部cSCC化学预防的III期RCT相关的可行性、活动性和评估结果。在一项为期15个月的II期开放标签随机对照试验中，在预定区域有10个或更多ak的OTRs随机分为5‐FU、5%咪喹莫特（IMIQ）或防晒霜（防晒因子30+）。可行性结果包括随机、完成治疗和愿意再治疗的合格otr的比例。评估了AK活性[AK清除率，新的AK发展，以患者为中心的结果（毒性，健康相关生活质量，HRQoL）]和评估方法（临床与摄影）。40例otr患者903例ak随机分组。所有可行性结果均得到满足（56%的符合条件的OTRs被随机化，89%完成治疗，81%愿意再次治疗）。AK活性分析发现，5‐FU和IMIQ在AK清除和预防新AK方面优于防晒霜。探索性分析显示，5‐FU在清除和预防AK方面比IMIQ更有效。虽然5 - FU组毒性更大，但HRQoL结果相似。在OTRs中进行局部AK治疗用于cSCC化学预防的试验是可行的，AK活性结果支持在未来的III期试验中进一步研究基于5 - FU的治疗方法。与免疫正常人群相比，皮肤鳞状细胞癌（cSCC）在免疫功能低下个体（包括器官移植受者）中更为常见。防晒霜和5 -氟尿嘧啶（5 - FU）光化性角化病（AK）治疗的cSCC化学预防活性已在免疫功能正常人群的随机对照试验（rct）中得到证实，但在OTRs中未得到证实。AKs是cSCC的前体，其清除和预防通常被视为潜在cSCC化学预防活性的替代终点生物标志物。关于这个话题我们已经知道了什么？SPOT（使用局部治疗的OTRs SCC预防）证实了局部AK治疗的OTR - cSCC化学预防的随机对照试验是可行的。研究还表明，在清除和预防AK方面，外用5‐FU可能优于5%咪喹莫特和防晒霜。结合最近在普通人群中进行的几项随机对照试验的证据，这些数据为进一步研究基于5 - FU的局部化学预防方法在OTR - cSCC预防中的干预提供了令人信服的理论依据。这项研究补充了什么？清除光化性角化病（AK）通常被认为是CSCC预防的替代生物标志物。我们的目的是评估与设计未来OTRs局部CSCC化学预防的III期RCT相关的可行性、活动性和评估结果。我们的结论是，在OTRs中局部使用AK治疗CSCC化学预防是可行的，并且AK活性结果支持在未来的III期试验中进一步研究基于5 - FU的治疗方法。链接评论：Samimi先生。中华皮肤科杂志[J]；187:281 - 282。
The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a surrogate biomarker for cSCC prevention. OTR‐cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5‐fluorouracil (5‐FU) may be chemoprotective in immunocompetent patients. To assess the feasibility, activity and evaluation outcomes relevant to the design of a future phase III RCT of topical cSCC chemoprevention in OTRs. OTRs with 10 or more AKs in predefined areas were randomized 1 : 1 : 1 to topical 5‐FU, 5% imiquimod (IMIQ) or sunscreen (sun‐protective factor 30+) in a phase II, open‐label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomized, completing treatment and willing to be re‐treated. AK activity [AK clearance, new AK development, patient‐centred outcomes (toxicity, health‐related quality of life, HRQoL)] and evaluation methodology (clinical vs. photographic) were assessed. Forty OTRs with 903 AKs were randomized. All feasibility outcomes were met (56% of eligible OTRs were randomized; 89% completed treatment; 81% were willing to be re‐treated). AK activity analyses found 5‐FU and IMIQ were superior to sunscreen for AK clearance and prevention of new AKs. 5‐FU was more effective than IMIQ in AK clearance and prevention in exploratory analyses. Although toxicity was greater with 5‐FU, HRQoL outcomes were similar. Trials of topical AK treatments in OTRs for cSCC chemoprevention are feasible and AK activity results support further investigation of 5‐FU‐based treatments in future phase III trials. Cutaneous squamous cell carcinoma (cSCC) is significantly more common in immunocompromised individuals including organ transplant recipients (OTRs) compared with immunocompetent populations. cSCC chemoprevention activity of sunscreen and 5‐fluorouracil‐based (5‐FU) actinic keratosis (AK) treatments has been demonstrated in randomized controlled trials (RCTs) in immunocompetent populations but not in OTRs. AKs are cSCC precursors and their clearance and prevention are generally regarded as surrogate endpoint biomarkers for potential cSCC chemoprevention activity. What is already known about this topic? SPOT (SCC Prevention in OTRs using Topical treatments) has confirmed that RCTs of OTR‐cSCC chemoprevention with topical AK treatments are feasible. It also suggests that topical 5‐FU may be superior to 5% imiquimod and sunscreen in AK clearance and prevention. Together with recent evidence from several RCTs in the general population, these data provide a compelling rationale for further studies of intervention with 5‐FU‐based topical chemoprevention approaches in OTR‐cSCC prevention. What does this study add? Clearance of actinic keratoses (AK) is generally regarded as a surrogate biomarker for CSCC prevention. Our aim is to assess feasibility, activity and evaluation outcomes relevant to design of a future phase III RCT of topical CSCC chemoprevention in OTRs. We have concluded that trials of topical AK treatments in OTRs for CSCC chemoprevention are feasible and AK activity results support further investigation of 5‐FU‐based treatments in future phase III trials. Linked Comment: M. Samimi. Br J Dermatol 2022; 187:281–282.
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DOI：
10.1111/jdv.14267
发表时间：
2017-08-01
影响因子：
9.2
作者：
Dirschka, T.;Pellacani, G.;Gupta, G.
通讯作者：
Gupta, G.
影响因子：
158.5
作者：
Chen, Andrew C.;Martin, Andrew J.;Damian, Diona L.
通讯作者：
Damian, Diona L.
影响因子：
13.8
作者：
Cornejo, Christine M.;Jambusaria-Pahlajani, Anokhi;Ruiz, Emily S.
通讯作者：
Ruiz, Emily S.
影响因子：
10.3
作者：
Ismail, F.;Mitchell, L.;Harwood, C. A.
通讯作者：
Harwood, C. A.
DOI：
10.1067/s0190-9622(03)01831-0
发表时间：
2003-09-01
影响因子：
13.8
作者：
de Sévaux, RGL;Smit, JV;Hoitsma, AJ
通讯作者：
Hoitsma, AJ