Abstract
We previously have shown the feasibility of duodenum sparing using a biodegradable hydrogel spacer in pancreatic cancer radiation therapy. In this study, we propose an overlap volume histogram (OVH) prediction model to select patients who might benefit from hydrogel placement and to predict the hydrogel spacing required to achieve clinical constraints. OVH metrics for the duodenum were collected from the stereotactic body radiation therapy plans of 232 patients with unresectable pancreatic cancer (33Gy in 5 fractions). OVH metrics L9cc and L3cc were defined as the tumor volume expansion distance at which 9cm3 and 3cm3 volumes of the duodenum overlap with tumor. D9cc and D3cc of the duodenum were defined as the dose-volume histogram dose to 9cm3 and 3cm3, respectively, of the duodenum. Prediction models were established by linear regression between Lx and Dx, where x=3cm3 and 9cm3. OVH thresholds were obtained for predicting the target spacer thickness. The accuracy of the prediction model was then evaluated using treatment plans on pre-and post-hydrogel injection computed tomography scans from 2 cadaver specimens and 6 patients with previously treated locally advanced pancreatic cancer with simulated spacer. Linear regression analysis showed a significant correlation between Lx and Dx (r2=0.51 and 0.51 for L3cc-D3cc and L9cc-D9cc, respectively; both P<.01). The OVH thresholds were Lˆ3cc=7mm and Lˆ9cc=13mm. The observed planning doses D3cc and D9cc of duodenum from pre-and post-hydrogel injection computed tomography scans of cadaver specimens and clinical patients with simulated spacer using predicted target spacer thickness were within the OVH model prediction range. Our model may predict which patients require placement of a hydrogel spacer before stereotactic body radiation therapy to meet predefined dose constraints. Furthermore, by predicting the required target hydrogel thickness, the spacer injection can be better guided to improve efficacy.
Highlights
Pancreatic cancer is the third most common cause of cancer-related death and remains the most devastating cancer, with a 5-year relative survival rate of merely 8% in the United States [1]
We propose an overlap volume histogram (OVH) prediction model and workflow to guide the selection of patients with borderline resectable or locally advanced pancreatic cancer (BR/LAPC) without duodenal invasion who may benefit from placement of a hydrogel spacer to achieve predetermined clinical dose constraints
For patients flagged by the model for whom spacer placement would be recommended to achieve a clinically acceptable plan, the prediction model can be used to predict a minimum target spacer thickness needed to separate the duodenum from the planning target volume (PTV) in the head of the pancreas (HOP)
Summary
Pancreatic cancer is the third most common cause of cancer-related death and remains the most devastating cancer, with a 5-year relative survival rate of merely 8% in the United States [1]. In other sites in body, physical separation between the target and adjacent organs at risk (OARs) has evolved into an effective method of reducing the dose to the OAR and the toxicity of dose-escalated radiation therapy. This has been most successfully demonstrated in the use of a hydrogel for spacing the rectum from the prostate in the treatment of prostate cancer [12,13,14,15]. In a phase-3 study of dose-escalated IMRT for prostate cancer, physical separation of the rectum from the prostate using a hydrogel spacer significantly decreased the dose delivered to the rectum and resulted in reduced toxicity and improved quality of life for patients undergoing spacer placement [14]
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