Hellström Vivan C, Enström Ylva, von Zur-Mühlen Bengt, Hagberg Hans, Laurell Anna, Nyberg Filippa, Bäckman Lars, Opelz Gerhard, Döhler Bernd, Holmberg Lars, Tufveson Gunnar, Enblad Gunilla, Lorant Tomas
a Department of Surgical Sciences, Section of Transplantation Surgery , Uppsala University , Uppsala , Sweden ;
b Department of Medical Sciences, Section of Dermatology and Venereology , Uppsala University , Uppsala , Sweden ;
Acta Oncol. 2016 Jun;55(6):774-81. doi: 10.3109/0284186X.2015.1130855. Epub 2016 Jan 29.
Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial. Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564). Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p = 0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines. Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.
背景 实体器官移植受者发生恶性肿瘤的风险增加。这项前瞻性、观察性、单臂研究的目的是探讨在接受移植且患有移植后恶性肿瘤的患者的免疫抑制方案中添加雷帕霉素哺乳动物靶点(mTOR)抑制剂的可行性。在试验过程中,改善移植后恶性肿瘤的识别以及确保对这些患者进行充分的肿瘤治疗的必要性变得明显。由于该试验,对所有肾移植或肾胰联合移植后患有恶性肿瘤的患者实施了肿瘤学和免疫抑制治疗的多学科团队(MDT)评估。
材料和方法 在瑞典乌普萨拉大学医院,一个由移植外科医生、肾病学家、肿瘤学家和皮肤科医生组成的MDT对2006年9月至2012年7月期间诊断为恶性肿瘤的120例肾移植或肾胰联合移植受者进行了评估。为了识别所有恶性肿瘤,该人群与地区肿瘤登记处(RTR)进行了关联。我们记录了转换为mTOR抑制剂的可能性以及最初计划的肿瘤管理调整的频率。所有患者均随访三年。(ClinicalTrials.gov:NCT02241564)
结果 在120例患者中的76例(63%)中,有可能转换为mTOR抑制剂。7例患者(6%)的免疫抑制被中断,3例患者(2%)的免疫抑制降低,120例患者中的34例(28%)保持不变。与RTR关联后,移植后恶性肿瘤的识别显著增加(p = 0.015)。44例实体或血液系统恶性肿瘤患者中的23例(52%)最初推荐的肿瘤治疗得到调整;其中36例患者(82%)按照国家指南进行治疗。
结论 在三分之二的患者中,免疫抑制治疗可以改为具有抗肿瘤作用的mTOR抑制剂,用于患有移植后恶性肿瘤的移植患者。使用地区肿瘤登记处大大改善了移植后恶性肿瘤患者的识别,表明移植登记处可能未及时报告移植后恶性肿瘤。