Spacer Enabled Robust Radiation Therapy (SERRT)

胰腺导管腺癌是美国第12大最常见的恶性肿瘤，也是第三大恶性肿瘤。 癌症相关死亡的原因，5年总生存率（OS）非常低，不到10%。三分之一 患有不可切除的局部晚期胰腺癌（LAPC）的患者。对于LAPC，改进了本地 控制可以通过先进的放射治疗（RT）技术，使用剂量递增与强度 调强放射治疗（IMRT）和立体定向体部放射治疗（SBRT）。剂量递增的疗效是 局限于胰腺癌，主要是由于接近危险器官（OAR）。特别是，剂量限制 十二指肠与胰头（HOP）直接相邻，大多数腺癌发生在胰头。作为 结果，非常严格的计划治疗体积（PTV）边缘扩大的总肿瘤体积（GTV）是 规定的。即使如此，PTV也经常突出到十二指肠中，并且根据医生的判断被“剃掉”。 治疗医生，以避免伤害十二指肠，但在错过肿瘤的风险。此外，每天， 患者解剖结构的分数变化容易导致违反OAR约束，因此频繁的调整是 不可避免的目前迫切需要一种新的方法来允许在放射治疗中安全的剂量递增 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 以增加肿瘤和OAR之间的分离。我们将该手术命名为：Spacer Enabled Robust 放射治疗（SERRT）强调治疗：（i）对解剖变异稳健，（ii）放松 严格的PTV的要求，并增加OAR到PTV的距离，从而（iii）最大限度地减少 调整计划的频率。在我们目前的重点是将SERT应用于LAPC时，我们将重点放在 十二指肠是最重要的结构。我们已经证明了在一个新的环境中使用EUS的可行性。 应用于引导我们新开发的可吸收和不透射线的间隔器的植入，实现了1 十二指肠和HOP之间的间隔为1.5cm。该新型间隔件在锥形束CT（CBCT）中可见，并且可以被 在RT治疗过程后监测。我们预计新的间隔物将在大多数RT中彻底改变IGRT 目前使用车载CBCT的诊所。借助SERRT，我们将在术前（间隔器之前）进行创新 植入）介入计划，其包括放射治疗计划，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。SERT是一个新的 通过增加RT对设置和器官的稳健性来增强IGRT当前范例的过程 以系统的方式变化。如果成功，SERRT为剂量递增提供了新的变革潜力 这对于胰腺癌这样的毁灭性疾病来说是非常必要的。

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.