Clinical Outcome and Biological Predictors of Relapse After Nephrectomy Only for Very Low-risk Wilms Tumor: A Report From Children's Oncology Group AREN0532.
Clinical Outcome and Biological Predictors of Relapse After Nephrectomy Only for Very Low-risk Wilms Tumor: A Report From Children's Oncology Group AREN0532.
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DOI：
10.1097/sla.0000000000001716
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发表时间：
2017-04
影响因子：
9
通讯作者：
Shamberger RC
中科院分区：
文献类型：
--
作者：
Fernandez CV;Perlman EJ;Mullen EA;Chi YY;Hamilton TE;Gow KW;Ferrer FA;Barnhart DC;Ehrlich PF;Khanna G;Kalapurakal JA;Bocking T;Huff V;Tian J;Geller JI;Grundy PE;Anderson JR;Dome JS;Shamberger RC
旨在确定极低风险肾母细胞瘤（定义为肾切除重量<550g且诊断时年龄<2岁的I期组织学有利的肾母细胞瘤）肾切除术后单独观察是否会产生令人满意的无事件生存率和总生存率，并将复发与生物标志物相关联。 AREN0532 研究纳入了经病理学、诊断影像和手术报告集中审查证实的极低风险维尔姆斯瘤患者。肾切除术后，对患者进行随访，未进行辅助化疗。对可评估的肿瘤进行 WT1 突变、1p 和 16q 拷贝丢失、1q 拷贝增益和 11p15 印记分析。该研究发现 4 年 EFS 从 87% 降低至 75%，总生存率从 95% 降低至 88%。共有 116 名符合条件的患者入组，中位随访时间为 80 个月（范围：5-97 个月）。 12名患者复发。估计 4 年无事件生存率为 89.7%（95% 置信区间 84.1–95.2%），总生存率为 100%。首先复发的部位是肺（n = 5）、瘤床（n = 4）和腹部（n = 2），其中对侧肾脏（n = 1）有一个异时性肿瘤，复发者的中位时间为 4.3 个月（范围 2.3-44 个月）。叶内（P = 0.46）或叶周休息（P = 1.0）的存在与复发无关（P = 0.16）。 1q 增益、1p 和 16q 缺失以及 WT1 突变状态与复发无关。 11p15 甲基化状态与复发相关（20% 复发与杂合性丧失，25% 复发与印记丢失，3.3% 复发与正常印记保留（P = 0.011））。大多数符合极低风险标准的患者可以仅通过肾切除术安全地进行治疗，从而减少化疗的暴露。应考虑扩大针对低风险肾母细胞瘤的单独观察策略，结合临床特征和生物标志物。
To determine if observation alone after nephrectomy in very low-risk Wilms tumor (defined as stage I favorable histology Wilms tumors with nephrectomy weight <550g and age at diagnosis <2 years) results in satisfactory event-free survival and overall survival, and to correlate relapse with biomarkers. The AREN0532 study enrolled patients with very low-risk Wilms tumor confirmed by central review of pathology, diagnostic imaging, and surgical reports. After nephrectomy, patients were followed without adjuvant chemotherapy. Evaluable tumors were analyzed for WT1mutation, 1p and 16q copy loss, 1q copy gain, and 11p15 imprinting. The study was powered to detect a reduction in 4-year EFS from 87% to 75% and overall survival from 95% to 88%. A total of 116 eligible patients enrolled with a median follow up of 80 months (range: 5–97 months). Twelve patients relapsed. Estimated 4-year event-free survival was 89.7% (95% confidence interval 84.1–95.2%) and overall survival was 100%. First sites of relapse were lung (n = 5), tumor bed (n = 4), and abdomen (n = 2), with one metachronous tumor in the contralateral kidney (n = 1) at a median time of 4.3 months for those who relapsed (range 2.3–44 months). The presence of intralobar (P = 0.46) or perilobar rests (P = 1.0) were not associated with relapse (P = 0.16). 1q gain, 1p and 16q loss, and WT1 mutation status were not associated with relapse. 11p15 methylation status was associated relapse (20% relapse with loss of heterozygosity, 25% with loss of imprinting, and 3.3% relapse with retention of the normal imprinting (P = 0.011)). Most patients meeting very low-risk criteria can be safely managed by nephrectomy alone with resultant reduced exposure to chemotherapy. Expansion of an observation alone strategy for low-risk Wilms tumor incorporating both clinical features and biomarkers should be considered.