Abstract：
OBJECTIVE: Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects.
METHODS: A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.
RESULTS: We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required.
CONCLUSIONS: The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.
METHODS: A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.
RESULTS: We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required.
CONCLUSIONS: The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.
摘要：
目的：米托坦是治疗小儿肾上腺皮质肿瘤（pACC）的重要基石，但在儿科年龄组中使用该药物的经验仍然有限，目前的实践没有强有力的证据指导。因此,我们已经收集了pACC专家关于米托坦适应症的国际共识声明，治疗,以及不良反应的管理。
方法：在国际网络组织ENSAT-PACT和ICPACT的pACC专家联盟内，使用了带有三轮问卷的德尔菲方法来创建21项最终共识声明。
结果：我们将陈述分为4组：环境，适应症,治疗,和不利影响。对于III期和IV期以及不完全切除/肿瘤溢出的晚期pACC，我们达成了米托坦治疗的明确共识。对于II期患者，米托坦通常不适用。开始米托坦治疗的时机取决于患者的临床状况和计划治疗的设置。我们建议起始剂量为50mg/kg/d（1500mg/m²/d），可增加至4000mg/m2/d。血液水平应在14-20mg/L之间。米托坦治疗的持续时间取决于临床风险概况和耐受性。在开始治疗后不久，几乎所有需要糖皮质激素替代治疗的患者都会导致肾上腺功能不全。由于米托坦的不良反应范围很广，可能危及生命，频繁的临床和神经系统检查（每2至4周），同时需要评估和评估实验室值。
结论：德尔菲方法使我们能够提出专家共识声明，这可以指导临床医生，进一步适应当地规范和个体患者设置。为了产生证据,构建良好的研究应该是未来努力的重点。
方法：在国际网络组织ENSAT-PACT和ICPACT的pACC专家联盟内，使用了带有三轮问卷的德尔菲方法来创建21项最终共识声明。
结果：我们将陈述分为4组：环境，适应症,治疗,和不利影响。对于III期和IV期以及不完全切除/肿瘤溢出的晚期pACC，我们达成了米托坦治疗的明确共识。对于II期患者，米托坦通常不适用。开始米托坦治疗的时机取决于患者的临床状况和计划治疗的设置。我们建议起始剂量为50mg/kg/d（1500mg/m²/d），可增加至4000mg/m2/d。血液水平应在14-20mg/L之间。米托坦治疗的持续时间取决于临床风险概况和耐受性。在开始治疗后不久，几乎所有需要糖皮质激素替代治疗的患者都会导致肾上腺功能不全。由于米托坦的不良反应范围很广，可能危及生命，频繁的临床和神经系统检查（每2至4周），同时需要评估和评估实验室值。
结论：德尔菲方法使我们能够提出专家共识声明，这可以指导临床医生，进一步适应当地规范和个体患者设置。为了产生证据,构建良好的研究应该是未来努力的重点。
