Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms Tumor

<p>This collection contains data from the Children’s Oncology Group (COG) Clinical Trial <a href="https://clinicaltrials.gov/ct2/show/NCT00379340">NCT00379340</a>, “Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms Tumor, " Study Chair: David Dix, MD. It was sponsored by NCI and performed by the Children's Oncology Group under study number AREN0533. This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV favorable histology 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/737">https://nctn-data-archive.nci.nih.gov/node/737</a>.</p><h3>Trial Description</h3><p>Patients with stage IV favorable histology Wilms tumor (FHWT), the majority of whom have pulmonary metastases, have inferior outcomes compared with those with localized disease. Their treatment is also complicated by a risk of late effects, including cardiac dysfunction, lung toxicity, musculoskeletal and soft tissue defects, and second malignancies. The AREN0533 study applied two separate strategies for risk stratification for patients with Stage III and IV favorable histology Wilms tumor. The first is the identification of patients with pulmonary nodules who can be spared bilateral pulmonary irradiation. Patients with Stage IV favorable histology Wilms tumor have a 4-year event-free survival (EFS) of 75% with chemotherapy and irradiation to sites of metastatic disease (most frequently in the lungs). European investigators are able to spare 75% of their patients with pulmonary nodules from irradiation based on the initial response to chemotherapy. The response of the lung metastases to 6 weeks of chemotherapy consisting of vincristine, dactinomycin, and doxorubicin (Regimen DD-4A) was used to determine if radiation of lung nodules is needed. Patients who had complete disappearance of their lung metastases (or who had tissue confirmation that the nodules do not contain viable tumor) at the Week 6 evaluation were considered rapid responders and continued with DD-4A. Patients who did not have complete resolution of pulmonary nodules by Chest CT underwent pulmonary irradiation and were switched to Regimen M (DD-4A variation with dactinomycin and doxorubicin given on the same day plus cyclophosphamide and etoposide). Central radiology review of the chest CTs were performed on all Stage IV patients with lung metastases at study enrollment and at Week 6. The second risk stratification variable was the allelic loss of 1p and 16q. Patients with Stage III and IV favorable histology Wilms tumor with loss of heterozygosity (LOH) of both 1p and 16q have a 4-yr EFS of 65%. Patients with LOH of 1p and 16q were assigned to Regimen M in an attempt to improve the 4-year EFS of this group of patients to 84%.</p><h3>Trial Outcomes</h3><p>Results of the trial have been reported in the following publications:</p><ul><li>Dix DB, Seibel NL, Chi YY, Khanna G, Gratias E, Anderson JR, Mullen EA, Geller JI, Kalapurakal JA, Paulino AC, Perlman EJ, Ehrlich PF, Malogolowkin M, Gastier-Foster JM, Wagner E, Grundy PE, Fernandez CV, Dome JS. Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children's Oncology Group AREN0533 Study. J Clin Oncol. 2018 Jun 1;36(16):1564-1570. doi: <a href="https://doi.org/10.1200/JCO.2017.77.1931">10.1200/JCO.2017.77.1931</a>. Epub 2018 Apr 16. PMID: 29659330; PMCID: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075846/">PMC6075846</a>.</li><li>Dix, D. B., Fernandez, C. V., Chi, Y.-Y., Mullen, E. A., Geller, J. I., Gratias, E. J., Khanna, G., Kalapurakal, J. A., Perlman, E. J., Seibel, N. L., Ehrlich, P. F., Malogolowkin, M., Anderson, J., Gastier-Foster, J., Shamberger, R. C., Kim, Y., Grundy, P. E., & Dome, J. S. (2019). Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children’s Oncology Group AREN0532 and AREN0533 Study Report. In Journal of Clinical Oncology (Vol. 37, Issue 30, pp. 2769–2777). American Society of Clinical Oncology (ASCO). <a href="https://doi.org/10.1200/jco.18.01972">https://doi.org/10.1200/jco.18.01972</a></li></ul>

<p>本数据集汇聚了儿童肿瘤学小组（COG）临床试验数据，该试验编号为NCT00379340，题为‘对于新诊断的III或IV期有利的组织学Wilms瘤的儿童，联合化疗是否联合放射治疗的治疗方法研究’，研究主席为David Dix博士。该试验由NCI资助，并由儿童肿瘤学小组在研究编号AREN0533下执行。本III期试验旨在探究联合化疗（是否联合放射治疗）在治疗新诊断的III或IV期有利的组织学Wilms瘤儿童中的疗效。通过以下链接可获取该试验的病人级别临床数据：<a href="https://nctn-data-archive.nci.nih.gov/node/737">https://nctn-data-archive.nci.nih.gov/node/737</a>。</p><h3>试验描述</h3><p>患有IV期有利组织学Wilms瘤（FHWT）的患者，其中大多数患者伴有肺转移，其预后较局部疾病患者差。治疗过程中，患者还面临晚期效应的风险，包括心脏功能障碍、肺毒性、骨骼肌肉和软组织缺陷，以及继发性恶性肿瘤。AREN0533研究针对III期和IV期有利组织学Wilms瘤患者应用了两种独立的风险分层策略。第一种策略是识别出可以避免双侧肺照射的患有肺结节的患者。患有IV期有利组织学Wilms瘤的患者在接受化疗和照射转移性疾病部位（最常见于肺部）后，4年无事件生存率（EFS）为75%。欧洲研究者根据化疗的初始反应，能够避免75%的肺结节患者的放射治疗。通过评估第6周化疗（包括长春新碱、放线菌素D和多柔比星[方案DD-4A]）对肺转移的响应，来确定是否需要对肺结节进行放射治疗。在第6周评估时，肺转移完全消失（或组织学证实结节不含有活性肿瘤）的患者被视为快速响应者，并继续接受DD-4A方案。在第6周胸部CT检查未显示肺结节完全消散的患者接受了肺照射，并改为接受方案M（DD-4A方案的变化，在同一天给予放线菌素D和多柔比星，加上环磷酰胺和依托泊苷）。所有III期和IV期有利组织学Wilms瘤患者，包括研究入组和第6周的患者，都进行了胸部CT的中心放射学复查。第二种风险分层变量是1p和16q的等位基因丢失。III期和IV期有利组织学Wilms瘤患者中，1p和16q的杂合性丢失（LOH）的患者，4年EFS为65%。1p和16q的LOH患者被分配到方案M，旨在将这一患者群体的4年EFS提高到84%。</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>Dix DB, Seibel NL, Chi YY, Khanna G, Gratias E, Anderson JR, Mullen EA, Geller JI, Kalapurakal JA, Paulino AC, Perlman EJ, Ehrlich PF, Malogolowkin M, Gastier-Foster JM, Wagner E, Grundy PE, Fernandez CV, Dome JS. Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children’s Oncology Group AREN0533 Study. J Clin Oncol. 2018 Jun 1;36(16):1564-1570. doi: <a href="https://doi.org/10.1200/JCO.2017.77.1931">10.1200/JCO.2017.77.1931</a>. Epub 2018 Apr 16. PMID: 29659330; PMCID: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075846/">PMC6075846</a>.</li><li>Dix, D. B., Fernandez, C. V., Chi, Y.-Y., Mullen, E. A., Geller, J. I., Gratias, E. J., Khanna, G., Kalapurakal, J. A., Perlman, E. J., Seibel, N. L., Ehrlich, P. F., Malogolowkin, M., Anderson, J., Gastier-Foster, J., Shamberger, R. C., Kim, Y., Grundy, P. E., &amp; Dome, J. S. (2019). Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children’s Oncology Group AREN0532 and AREN0533 Study Report. In Journal of Clinical Oncology (Vol. 37, Issue 30, pp. 2769–2777). American Society of Clinical Oncology (ASCO). <a href="https://doi.org/10.1200/jco.18.01972">https://doi.org/10.1200/jco.18.01972</a></li></ul>