Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma

<p>This collection contains data from the Children’s Oncology Group (COG) Clinical Trial <a href="https://clinicaltrials.gov/ct2/show/NCT01026220">NCT01026220</a>, “Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma". Principal Investigator: Kara Kelly, MD (pediatric oncologist and the Chair of Roswell Park Oishei Children’s Cancer and Blood Disorders Program, Buffalo, NY). It was sponsored by NCI and performed by the Children's Oncology Group under study number AHOD0831. This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin lymphoma. Therapeutic agents used on trial include 1 or more of the following: Biological: bleomycin sulfate; Drug: doxorubicin hydrochloride; Drug: liposomal vincristine sulfate; Drug: vinorelbine tartrate; Drug: cyclophosphamide; Drug: etoposide phosphate; Drug: prednisone; Biological: filgrastimDrug: ifosfamide. Select patient-level clinical data from this trial is available via the following link: <a href="https://urldefense.proofpoint.com/v2/url?u=https-3A__nctn-2Ddata-2Darchive.nci.nih.gov_node_1137&d=DwMF-g&c=27AKQ-AFTMvLXtgZ7shZqsfSXu-Fwzpqk4BoASshREk&r=ToZnZI1LUBsGvnucRq6iJA&m=P9Tu1oIqIT-R_u0jfBNKy_loMEtRRLjl0SUi3U2jyaY&s=h58ipUeHC4Tx1q6FaNHzVJB3zs7N29M3TcIsNlX-DKg&e=">https://nctn-data-archive.nci.nih.gov/node/1137</a>.</p><p><strong>Trial Primary Objective</strong>:</p><p>I. To maintain the overall survival (as defined by 4-year "second-event" free survival) for subjects with high risk Hodgkin lymphoma at or above 95%.</p><p><strong>Trial Secondary Objectives</strong>:</p><p>I. To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or above 93%.</p><p>II. To maintain comparable overall survival (as defined by 4-year "second-event" free survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response to the initial 2 cycles of ABVE-PC* by intensifying therapy through the addition of 2 cycles of ifosfamide/vinorelbine in those with a slow early response.</p><p>III. To investigate whether very early response assessment measured by FDG-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.</p><p>IV. To describe the patterns of relapse after ABVE-PC* and risk-adapted radiotherapy.</p><p><strong>Trial Description and Outcomes</strong></p><p>The AHOD0831 study for pediatric patients with high risk Hodgkin lymphoma tested a response-based approach designed to limit cumulative alkylator exposure and reduce radiation volumes. 166 patients were enrolled in this study from December 2009 to January 2012, of whom 165 were eligible and 141 completed the trial. This dataset contains the images from the 165 eligible patients.  Study dates were approximately 2009-2017.</p><p>Patients (Stage IIIB/IVB) received two cycles of ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide). Rapid early responders [RER, no positron emission tomography (PET) activity above mediastinal blood pool] were consolidated with 2 cycles of ABVE-PC. Slow early responders(SER) received 2 cycles of ifosfamide/vinorelbine and 2 cycles of ABVE-PC.</p><p>Radiotherapy was administered to sites of initial bulk and/or SER. By intent-to-treat analysis, 4-year second event-free survival (EFS; freedom from second relapse or malignancy) was 91.9% [95% confidence interval(CI): 86.1 – 95.3%], below the projected baseline of 95% (P = 0.038). Five-year first EFS and overall survival (OS) rates are 79.1% (95% CI: 71.5 –84.8%) and 95% (95% CI: 88.8 – 97.8%). Eight of 11 SER patients with persistent PET positive lesions at the end of chemotherapy had clinical evidence of active disease (3 biopsy-proven, 5 with progressive disease or later relapses). Although this response-directed approach did not reach the ambitiously high pre-specified target for second EFS, EFS and OS rates are comparable with results of recent trials despite the reduction in radiotherapy volumes from historical involved fields. Persistent PET at end of chemotherapy identifies a cohort at an especially high risk for relapse/early progression.</p><p><strong>Trial Publication</strong></p><p>Results of the trial have been reported in the following publication:</p><ul><li>Kelly KM, Cole PD, Pei Q, Bush R, Roberts KB, Hodgson DC, McCarten KM, Cho SY, Schwartz C. Response-adapted therapy for the treatment of children with newly diagnosed high risk Hodgkin lymphoma (AHOD0831): a report from the Children's Oncology Group. Br J Haematol. 2019 Oct;187(1):39-48. <a href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.16014">doi: 10.1111/bjh.16014</a>. Epub 2019 Jun 10. <a href="https://pubmed.ncbi.nlm.nih.gov/31180135/">PMID: 31180135</a>; PMCID: PMC6857800.</li></ul>

<p>本数据集收录了儿童肿瘤学组（COG）临床试验<a href="https://clinicaltrials.gov/ct2/show/NCT01026220">NCT01026220</a>，即“针对新诊断霍奇金淋巴瘤的年轻患者联合化疗和放疗治疗”的数据。主要研究者为卡拉·凯利博士（儿科肿瘤学家，罗兹威尔·帕克奥伊希儿童癌症和血液病项目主席，纽约州布法罗）。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AHOD0831下实施。此III期临床试验旨在探究联合化疗与放疗联合使用治疗新诊断霍奇金淋巴瘤年轻患者的疗效。试验中使用的治疗药物包括以下之一或多个：生物制剂：博来霉素硫酸盐；药物：盐酸多柔比星；药物：脂质体长春瑞宾硫酸盐；药物：长春瑞宾酒石酸盐；药物：环磷酰胺；药物：磷酸酯依托泊苷；药物：泼尼松；生物制剂：非格司亭；药物：异环磷酰胺。可通过以下链接获取此试验的患者级临床数据：<a href="https://urldefense.proofpoint.com/v2/url?u=https-3A__nctn-2Ddata-2Darchive.nci.nih.gov_node_1137&amp;d=DwMF-g&amp;c=27AKQ-AFTMvLXtgZ7shZqsfSXu-Fwzpqk4BoASshREk&amp;r=ToZnZI1LUBsGvnucRq6iJA&amp;m=P9Tu1oIqIT-R_u0jfBNKy_loMEtRRLjl0SUi3U2jyaY&amp;s=h58ipUeHC4Tx1q6FaNHzVJB3zs7N29M3TcIsNlX-DKg&amp;e="">https://nctn-data-archive.nci.nih.gov/node/1137</a></p><p><strong>试验主要目标</strong></p><p>Ⅰ. 保持高风险霍奇金淋巴瘤患者总体生存率（以4年“第二次事件”无病生存率为标准）在95%或以上。</p><p><strong>试验次要目标</strong></p><p>Ⅰ. 保持高风险霍奇金淋巴瘤患者3年无病生存率在93%或以上。</p><p>Ⅱ. 通过增加2个周期异环磷酰胺/长春瑞宾化疗，提高对初始2个周期ABVE-PC*反应迅速或缓慢的患者治疗效果，以保持高风险霍奇金淋巴瘤患者总体生存率（以4年“第二次事件”无病生存率为标准）相当。</p><p>Ⅲ. 研究在1个周期化疗后通过FDG-PET评估的早期反应是否能够识别出未来试验中可研究的患者群体，并且与目前定义的2周期后RER可区分。</p><p>Ⅳ. 描述ABVE-PC*和风险分层放疗后的复发模式。</p><p><strong>试验描述与结果</strong></p><p>AHOD0831研究针对高风险霍奇金淋巴瘤的儿童患者，测试了一种基于反应的治疗方法，旨在限制累积的烷化剂暴露并减少放疗体积。2009年12月至2012年1月期间，共有166名患者被纳入本研究，其中165名符合条件，141名完成了试验。本数据集包含165名符合条件患者的图像。研究日期约为2009-2017年。</p><p>患者（IIIB/IVB期）接受了2个周期的ABVE-PC（多柔比星、博来霉素、长春瑞宾、依托泊苷、泼尼松、环磷酰胺）。快速早期反应者（RER，无正电子发射断层扫描（PET）活动超过纵隔血液池）接受了2个周期的ABVE-PC巩固治疗。缓慢早期反应者（SER）接受了2个周期的异环磷酰胺/长春瑞宾和2个周期的ABVE-PC。</p><p>放疗针对初始肿块部位和/或SER部位。根据意向治疗分析，4年第二次无病生存率（EFS；无第二次复发或恶病质）为91.9%（95%置信区间（CI）：86.1 – 95.3%），低于预期的95%基线水平（P = 0.038）。5年第一次EFS和总生存率（OS）分别为79.1%（95% CI：71.5 –84.8%）和95%（95% CI：88.8 – 97.8%）。11名SER患者在化疗结束时持续存在PET阳性病变，其中8名有临床活动性疾病的证据（3例活检证实，5例疾病进展或后续复发）。尽管这种以反应为基础的治疗方法未达到预定的第二次EFS的雄心勃勃的高目标，但EFS和OS率与最近试验的结果相当，尽管放疗体积从历史受累野有所减少。化疗结束时持续的PET识别出处于特别高风险复发/早期进展的患者群体。</p><p><strong>试验发表</strong></p><p>试验结果已发表在以下出版物中：</p><ul><li>凯利KM，科尔PD，裴Q，布斯R，罗伯茨KB，霍奇森DC，麦卡滕KM，赵SY，施瓦茨C.针对新诊断高风险霍奇金淋巴瘤的儿童患者反应性治疗（AHOD0831）：儿童肿瘤学组报告。血液病学杂志。2019年10月；187（1）：39-48。doi: 10.1111/bjh.16014。Epub 2019年6月10日。PMID: 31180135；PMCID: PMC6857800。</li></ul>