Spacer Enabled Robust Radiation Therapy (SERRT)

胰腺导管腺癌是美国第12位最常见的恶性肿瘤，居第三位。 癌症相关死亡原因，5年总存活率(OS)非常低，不到10%。三分之一的人 患有无法切除的局部晚期胰腺癌(LAPC)的患者。对于LAPC，改进了本地 可以通过先进的放射治疗(RT)技术实现控制，使用剂量随强度递增 调强放射治疗(IMRT)和立体定向全身放射治疗(SBRT)。剂量递增的效果是 仅限于胰腺癌，主要是由于靠近危险器官(OAR)。特别是，剂量限制 十二指肠与胰头(HOP)直接相邻，大多数腺癌都发生在那里。作为一名 结果，非常严密的计划治疗体积(PTV)边缘扩张的大体肿瘤体积(GTV)是 开了处方。即便如此，PTV通常会伸入十二指肠，并由医生自行决定是否“剃毛” 治疗医生要避免损伤十二指肠，但要冒着漏诊肿瘤的风险。此外，每天，国际间 患者解剖结构的微小变化很容易导致违反OAR限制，因此频繁的适应 无可避免。迫切需要一种新的方法来允许放射治疗中的安全剂量递增 治疗胰腺癌。我们建议通过系统的间隔物植入来增强当前的IGRT范例 以增加肿瘤与浆膜间的分离。我们将该过程命名为：间隔启用健壮 放射治疗(SERRT)强调一种治疗：(I)对解剖变异有抵抗力，(Ii)放松 紧凑的PTV的要求，并增加了到PTV的桨距离，从而(Iii)将 计划调整的频率。在我们目前将SERRT应用于LAPC的过程中，我们将重点放在 十二指肠，流行的关键结构。我们已经证明了在新的 应用于指导我们新开发的可吸收和不透射线间隔物的植入，达到1 十二指肠与啤酒花之间的距离为cm。这种新型间隔物在锥束CT(CBCT)中是可见的，并且可以 在RT治疗疗程后监测。我们预计新的间隔物将彻底改变大多数RT中的IGRT 目前使用机载CBCT的诊所。有了SERRT，我们将创新术前(在间隔之前 植入)介入计划，包括放射治疗计划以及术中 (在间隔物植入期间)成像反馈，以支持间隔物的最佳植入。SERRT是一种新的 通过增加RT对设置和器官的健壮性来增强当前IGRT范式的过程 有系统地变化。如果成功，SERRT为剂量升级提供了新的变革性潜力 对于像胰腺癌这样的毁灭性疾病来说，这是非常需要的。

Pancreatic ductal adenocarcinoma, the 12th most common malignancy in the USA, is the third leading cause of cancer-related death, with a very low 5-year overall survival (OS) rate of less than 10%. One-third of patients present with unresectable, locally advanced, pancreatic cancer (LAPC). For LAPC, improved local control may be achieved by advanced radiation therapy (RT) techniques, using dose-escalation with intensity modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT). Efficacy of dose escalation is limited in pancreatic cancer, primarily due to proximity of an organ at risk (OAR). In particular, the dose-limiting duodenum is directly adjacent to the head of the pancreas (HOP), where most adenocarcinomas occur. As a result, very tight planning treatment volume (PTV) margin expansion of the gross tumor volume (GTV) is prescribed. Even so, the PTV often protrudes into the duodenum, and is “shaved” at the discretion of the treating physician to avoid injuring the duodenum, but at the risk of missing the tumor. In addition, daily, inter- fraction variation of patient anatomy readily leads to violation of OAR constraints, thus frequent adaptations are inevitable. There is an urgent need for a new approach to allow safe dose escalation in the radiation therapy for pancreatic cancer. We propose to augment the current IGRT paradigm with systematic spacer implantation to increase the separation between the tumor and OAR. We name the procedure: Spacer Enabled Robust Radiation Therapy (SERRT) to emphasis a treatment that: (i) is robust against anatomic variations, (ii) relaxes the requirement of a tight PTV, and increases the OAR distances to the PTV, and thereby (iii) minimizes the frequency of plan adaptation. In our present focus on applying SERRT to LAPC, we direct our emphasis on the duodenum, the prevalent critical structure. We have demonstrated the feasibility of using EUS in a new application to guide the implantation of our newly developed absorbable and radiopaque spacer, achieving 1 cm separation between duodenum and HOP. The novel spacer is visible in cone beam CT (CBCT), and can be monitored following the RT treatment course. We expect the new spacer to revolutionize IGRT in most RT clinics which currently use onboard CBCT. With SERRT, we will innovate preoperative (before spacer implantation) intervention planning that incorporates a radiation treatment plan, as well as intraoperative (during spacer implantation) imaging feedback, to support optimal implantation of the spacer. SERRT is a new process that augments the current paradigm of IGRT by increasing robustness of RT against setup and organ variations in a systematic fashion. If successful, SERRT offers new transformative potential for dose escalation that is much needed for a devastating disease such as pancreatic cancer.