Improving Pancreas RT Plans using Respiration-driven Anatomic Deformation

描述（由申请人提供）：胰腺癌是一种致死性癌症，超过85%的患者表现为局部晚期或转移性疾病。目前采用常规分割放射治疗（RT）治疗局部晚期胰腺癌（LAPC）的局部失败率为40- 70%。虽然当使用单次剂量为25戈伊的立体定向体部放射治疗（SBRT）时，局部无进展生存率接近100%，但GI毒性显著，因此未来试验需要低分割（3至5次）SBRT。SBRT治疗需要满足严格的正常组织约束的计划，由于肿瘤和关键器官的紧密接近，这是难以用常规计划策略实现的。呼吸诱导的器官运动使治疗计划进一步复杂化，呼吸诱导的器官运动迫使肿瘤周围的大边缘，增加了照射的正常组织的体积，从而增加了GI毒性的风险。显然需要新的治疗规划策略来克服这些问题。目标：为一种新策略收集初步剂量测定数据，该策略在“双实例”方法中利用呼吸驱动的解剖变形来改善胰腺治疗计划。长期目标是利用从这项试点补助金中获得的信息来筛选和治疗可能 从双实例规划方法中受益。研究方法：（1）使用磁共振（MR）和计算机断层扫描（CT）成像来量化患者在深吸气（INSP）和呼气（EXP）时屏住呼吸时腹部结构的几何运动和变形。(2)使用先进的变形图像配准算法映射INSP和EXP状态之间的失真，因此可以映射和分析治疗计划剂量分布。（三）、使用自由呼吸、仅EXP、仅INSP以及EXP和INSP的新型双实例组合优化计划，以研究在一种或多种情况下可以实现的胰腺肿瘤剂量的潜在改善，利用肿瘤和关键器官位置的相对变化。影响：这项初步研究的成功将为在后续临床试验中使用改进的技术奠定必要的基础，这些临床试验可在不增加毒性的情况下增加LAPC患者的剂量。

DESCRIPTION (provided by applicant): Pancreatic adenocarcinoma is a lethal cancer, with more than 85% of patients presenting with either locally advanced or metastatic disease. Current treatment of locally advanced pancreatic cancer (LAPC) with regular fractionated radiation therapy (RT) results in local failure rates of 40-70%. While local progression free survival approached 100% when stereotactic body radiation therapy (SBRT) with a single dose of 25 Gy was used, the GI toxicities were significant, thus requiring hypo-fractionated (3 to 5 fraction) SBRT for future trials. SBRT treatment requires plans to satisfy stringent normal tissue constraints that are difficult to achieve with conventional planning strategy due to the close proximity of tumor and critical organs. Treatment planning is further complicated by respiration-induced organ motion which forces large margins around tumor, increasing the volume of the normal tissue irradiated and thus increasing the risk of GI toxicity. New treatment planning strategies are clearly needed to overcome these problems. Goals: To gather preliminary dosimetric data for a novel strategy which makes use of respiration-driven anatomic deformation in a "dual instance" method to improve pancreatic treatment plans. The long-term objective is to use the information learned from this pilot grant to screen and treat patients that can potentially benefit from the Dual Instance planning method. Methods: (1) Use magnetic resonance (MR) and computed tomography (CT) imaging to quantify geometric motions and deformations in abdominal structures as patients hold their breath at deep inspiration (INSP) and expiration (EXP). (2) Use an advanced deformation image registration algorithm to map the distortions between INSP and EXP states, so treatment plan dose distributions can be mapped and analyzed. (3). Optimize plans using free breathing, EXP-only, INSP-only, and a novel dual-instance combination of EXP and INSP to study potential improvements in pancreatic tumor dose which can be achieved in one or more of these instances, taking advantage of relative shifts in tumor and critical organ positions. Impact: Success of this pilot study will lay the groud work necessary for use of the improved technique(s) in the follow-on clinical trials which escalate dose to patients with LAPC without increasing toxicity.