Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

<p>This collection contains data from the Children’s Oncology Group (COG) Clinical Trial <a href="https://clinicaltrials.gov/ct2/show/NCT00945009"> NCT00945009</a>, “Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor, " Study Chair: Peter F. Ehrlich, M.D. M.S.C. It was sponsored by NCI and performed by the Children's Oncology Group under study number AREN0534. This phase III trial studies how well combination chemotherapy and surgery work in treating young patients with Wilms tumor. Select patient-level clinical data from this trial is available via the following link: <a href="https://nctn-data-archive.nci.nih.gov/node/728">https://nctn-data-archive.nci.nih.gov/node/728</a>.</p><h3>Trial Description</h3><p>Children with bilateral Wilms tumor account for 5-7% of all patients with Wilms tumor. Certain patients, with syndromes associated with Wilms tumor development, have been identified to be at increased risk for bilateral tumors. Due to an increased risk for renal failure, patients with bilateral disease at presentation are treated with preoperative chemotherapy in order to preserve renal parenchyma. Although this recommendation was made nearly 30 years ago, patients with bilateral tumors have not been formally studied in prior cooperative trials. Recent evidence suggests that survival of these patients is inferior to similar patients with unilateral tumor. This study is designed to improve the survival of these children, while continuing the emphasis on preserving renal function. Patients were enrolled and imaging studies were centrally reviewed to assess for bilateral renal lesions. They were treated with 3-drug induction chemotherapy (vincristine, dactinomycin, and doxorubicin) for 6 or 12 weeks based on radiographic response followed by surgery and further chemotherapy determined by histology. Radiation therapy was provided for postchemotherapy stage III and IV disease. One hundred eighty-nine of 208 patients were evaluable. Four-year EFS and OS were 82.1% (95% CI: 73.5%–90.8%) and 94.9% (95% CI: 90.1%–99.7%. Twenty-three patients relapsed and 7 had disease progression. After induction chemotherapy 163 of 189 (84.0%) underwent definitive surgical treatment in at least 1 kidney by 12 weeks and 39% retained parts of both kidneys. Surgical approaches included: unilateral total nephrectomy with contralateral partial nephrectomy (48%), bilateral partial nephrectomy (35%), unilateral total nephrectomy (10.5%), unilateral partial nephrectomy (4%), and bilateral total nephrectomies (2.5%). This treatment approach including standardized 3-drug preoperative chemotherapy, surgical resection within 12 weeks of diagnosis and response and histology-based postoperative therapy improved EFS and OS and preservation of renal parenchyma compared with historical outcomes for children with bilateral Wilms tumor.</p><p>Before enrollment, real-time central review of diagnostic imaging, pathology (if obtained), and operative notes confirmed the status of BWT. After 6 weeks, cross-sectional imaging was performed and a tumor response was assigned for each kidney. After 4 chemotherapy cycles (12 weeks), repeat cross sectional imaging was performed and definitive surgery was required. Response was based on the Response Evaluation Criteria in Solid Tumor (RECIST 1.1) modified to include 3 lesions per kidney.</p><h3>Trial Outcomes</h3><p>Results of the trial have been reported in the following publication:</p><ul><li>Ehrlich P, Chi YY, Chintagumpala MM, Hoffer FA, Perlman EJ, Kalapurakal JA, Warwick A, Shamberger RC, Khanna G, Hamilton TE, Gow KW, Paulino AC, Gratias EJ, Mullen EA, Geller JI, Grundy PE, Fernandez CV, Ritchey ML, Dome JS. Results of the First Prospective Multi-institutional Treatment Study in Children With Bilateral Wilms Tumor (AREN0534): A Report From the Children's Oncology Group. Ann Surg. 2017 Sep;266(3):470-478. doi: <a href="https://doi.org/10.1097/SLA.0000000000002356">10.1097/SLA.0000000000002356</a>. Erratum in: Ann Surg. 2018 Mar;267(3):e64. PMID: 28795993; PMCID: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629006/">PMC5629006</a>.</li><li>Ehrlich PF, Chi YY, Chintagumpala MM, Hoffer FA, Perlman EJ, Kalapurakal JA, Tornwall B, Warwick A, Shamberger RC, Khanna G, Hamilton TE, Gow KW, Paulino AC, Gratias EJ, Mullen EA, Geller JI, Grundy PE, Fernandez CV, Dome JS. Results of Treatment for Patients With Multicentric or Bilaterally Predisposed Unilateral Wilms Tumor (AREN0534): A report from the Children's Oncology Group. Cancer. 2020 Aug 1;126(15):3516-3525. doi: <a href="https://doi.org/10.1002/cncr.32958">10.1002/cncr.32958</a>. Epub 2020 May 27. PMID: 32459384; PMCID: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769115/">PMC7769115</a>.</li></ul>

<p>本数据集收录了来自儿童肿瘤学组（Children’s Oncology Group，COG）临床试验<a href="https://clinicaltrials.gov/ct2/show/NCT00945009">NCT00945009</a>，“联合化疗及手术治疗年轻Wilms肿瘤患者”，“研究主席：Peter F. Ehrlich，医学博士，硕士。该研究由美国国家癌症研究所（NCI）资助，并由儿童肿瘤学组在研究编号AREN0534下执行。此III期临床试验旨在探讨联合化疗及手术联合治疗年轻Wilms肿瘤患者的疗效。通过以下链接可获取此试验中选取的患者级临床数据：<a href="https://nctn-data-archive.nci.nih.gov/node/728">https://nctn-data-archive.nci.nih.gov/node/728</a>。</a></p><h3>试验描述</h3><p>双侧Wilms肿瘤患者占所有Wilms肿瘤患者的5-7%。某些与Wilms肿瘤发展相关的综合征患者被确认为患双侧肿瘤的风险增加。鉴于肾衰竭的风险增加，呈现双侧疾病的患者在术前接受化疗以保留肾实质。尽管这一建议近30年前就已提出，但双侧肿瘤患者尚未在先前的合作试验中得到正式研究。近期证据表明，这些患者的生存率劣于单侧肿瘤的类似患者。本研究旨在提高这些儿童的生存率，同时继续强调保护肾功能。患者被纳入研究，并进行影像学检查以评估双侧肾脏病变。根据影像学反应，患者接受为期6或12周的3药诱导化疗（长春新碱、放线菌素D和多柔比星），随后进行手术和基于组织学结果的进一步化疗。对于化疗后III期和IV期疾病，提供放射治疗。208名患者中有189名可评估。4年EFS和OS分别为82.1%（95% CI：73.5%-90.8%）和94.9%（95% CI：90.1%-99.7%。23名患者复发，7名患者疾病进展。在诱导化疗后，189名患者中的163名（84.0%）在12周内至少接受了一次肾脏的确定性手术，其中39%保留了双肾的部分肾实质。手术方式包括：单侧全肾切除术加对侧部分肾切除术（48%）、双侧部分肾切除术（35%）、单侧全肾切除术（10.5%）、单侧部分肾切除术（4%）和双侧全肾切除术（2.5%）。包括标准化3药术前化疗、在诊断及反应后12周内进行手术切除以及基于组织学结果的术后治疗这一治疗方案，与历史数据相比，显著提高了双侧Wilms肿瘤儿童的EFS、OS和肾实质的保留率。</p><p>在入组前，对诊断影像学、病理学（如获取）和手术记录进行实时中心审查，以确认双侧Wilms肿瘤（BWT）的状态。6周后，进行横断面影像学检查，并为每个肾脏分配肿瘤反应。在4个化疗周期（12周）后，重复进行横断面影像学检查，并需进行确定性手术。反应基于实体瘤反应评价标准（RECIST 1.1）的修改版，每个肾脏包括3个病变。</p><h3>试验结果</h3><p>试验结果已在以下出版物中报道：</p><ul><li>Ehrlich P, Chi YY, Chintagumpala MM, Hoffer FA, Perlman EJ, Kalapurakal JA, Warwick A, Shamberger RC, Khanna G, Hamilton TE, Gow KW, Paulino AC, Gratias EJ, Mullen EA, Geller JI, Grundy PE, Fernandez CV, Ritchey ML, Dome JS. 首项多机构前瞻性治疗研究儿童双侧Wilms肿瘤的结果（AREN0534）：儿童肿瘤学组报告. Ann Surg. 2017年9月；266(3):470-478. doi: 10.1097/SLA.0000000000002356. PMID: 28795993; PMCID: PMC5629006.</li><li>Ehrlich PF, Chi YY, Chintagumpala MM, Hoffer FA, Perlman EJ, Kalapurakal JA, Tornwall B, Warwick A, Shamberger RC, Khanna G, Hamilton TE, Gow KW, Paulino AC, Gratias EJ, Mullen EA, Geller JI, Grundy PE, Fernandez CV, Dome JS. 具有多中心或双侧易感性单侧Wilms肿瘤患者治疗的结果（AREN0534）：儿童肿瘤学组报告. Cancer. 2020年8月1日；126(15):3516-3525. doi: 10.1002/cncr.32958. Epub 2020年5月27日. PMID: 32459384; PMCID: PMC7769115.</li></ul>