A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol
A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol
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DOI：
10.1186/s12885-016-2765-4
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发表时间：
2016-09-13
期刊：
影响因子：
3.8
通讯作者：
Hawkins, Maria A.
中科院分区：
文献类型：
--
作者：
Holyoake, Daniel L. P.;Ward, Elizabeth;Hawkins, Maria A.
背景：在英国，边界可切除的胰腺癌的标准治疗方法是手术加辅助化疗，但切除率和切除率都不能令人满意，总体存活率仍然很低。单臂研究的Meta分析显示了新辅助化疗-放射治疗的潜力，但胰腺癌的相对放射抵抗意味着常规剂量方案的疗效有限。立体定向放射治疗具有足够的精确度和精密度，能够实现术前切缘强化剂量的递增，以提高切缘清晰率和局部疾病控制率。方法/设计：SPARC是一项“滚动六”设计的单臂研究，旨在建立切缘强化立体定向放射治疗在切缘阳性的高风险胰腺癌切除前的最大耐受剂量。符合条件的患者将患有经组织学或细胞学证实的胰腺癌，根据国家综合癌症网络标准，胰腺癌被定义为边缘可切除，或可手术的肿瘤与血管接触，增加了切缘阳性的风险。将从最多5个治疗中心招募最多24名患者，并采用“六滚动”设计，以最大限度地减少延误，并在剂量递增期间促进持续招募。放射治疗每天分5次进行，如果合适，手术将在放射治疗后5-6周进行。边缘密集放射治疗的概念包括一种系统的方法，以确定肿瘤血管浸润区同时综合增强的目标体积，并将研究多达4个放射剂量水平。最大耐受剂量被定义为6名患者中不超过1名患者或3名患者中0名患者经历剂量限制性毒性的最高剂量。次要终点包括切除率、切缘状态、有效率、总生存期和12个月和24个月的无进展生存期。翻译工作将包括对胰腺癌立体定向放射治疗的细胞学和体液免疫反应的探索性分析。通过试验前测试案例和试验中的审查，加强目标定义和放射治疗计划的放射治疗质量保证。从2015年4月开始招募。讨论：这项前瞻性多中心研究旨在建立手术切缘阳性的高风险胰腺癌患者术前切缘强化立体定向放射治疗的最大耐受量，以期随后与其他新辅助治疗方案进行明确的比较。
Background: Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies shows the potential of neo-adjuvant chemo-radiotherapy but the relative radioresistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic radiotherapy achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of clear resection margins and local disease control.Methods/Design: SPARC is a "rolling-six" design single-arm study to establish the maximum tolerated dose for margin-intensive stereotactic radiotherapy before resection of pancreatic cancer at high risk of positive resection margins. Eligible patients will have histologically or cytologically proven pancreatic cancer defined as borderline-resectable per National Comprehensive Cancer Network criteria or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres and a 'rolling-six' design is utilised to minimise delays and facilitate ongoing recruitment during dose-escalation. Radiotherapy will be delivered in 5 daily fractions and surgery, if appropriate, will take place 5-6 weeks after radiotherapy. The margin-intense radiotherapy concept includes a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration, and up to 4 radiotherapy dose levels will be investigated. Maximum tolerated dose is defined as the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. Secondary endpoints include resection rate, resection margin status, response rate, overall survival and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to stereotactic radiotherapy in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015.Discussion: This prospective multi-centre study aims to establish the maximum tolerated dose of pre-operative margin-intensified stereotactic radiotherapy in pancreatic cancer at high risk of positive resection margins with a view to subsequent definitive comparison with other neoadjuvant treatment options.