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.

Public Health Relevance

Pancreatic cancer, a lethal disease with a cumulative 5 year survival <5%, is often treated with radiation therapy since the majority of patients are inoperable. Critical normal tissues (stomach, duodenum and bowel) limit the dose which can be delivered to the tumor due to significant untoward GI side-effects, thereby limiting effectiveness of treatment. Respiratory motion usually requires irradiation of larger volumes, further compounding this problem. This research proposes a novel MRI-based planning approach to take advantage of respiratory motion to spread the normal tissue dose out, thereby allowing delivery of higher tumor doses without increasing toxicity, eventually leading to improved local control and/or rates of resection in some patients.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Small Research Grants (R03)
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Biomedical Imaging Technology Study Section (BMIT)
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Deye, James
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Cedars-Sinai Medical Center
Los Angeles
United States
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