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Purpose: Pancreatic cancer is the fourth leading cause of cancer-related death with a 10% 5-year overall survival rate (OS). Radiation therapy (RT) in addition to dose escalation improves the outcome by significantly increasing the OS at 2 and 3 years but is hindered by the toxicity of the duodenum. Our group showed that the insertion of hydrogel spacer reduces duodenal toxicity, but the complex anatomy and the demanding procedure make the benefits highly uncertain. Here, we investigated the feasibility of augmenting the workflow with intraoperative feedback to reduce the adverse effects of the uncertainties., Materials and Methods: We simulated three scenarios of the virtual spacer for four cadavers with two types of gross tumor volume (GTV) (small and large); first, the ideal injection; second, the nonideal injection that incorporates common spacer placement uncertainties; and third, the corrective injection that uses the simulation result from nonideal injection and is designed to compensate for the effect of uncertainties. We considered two common uncertainties: (1) "Narrowing" is defined as the injection of smaller spacer volume than planned. (2) "Missing part" is defined as failure to inject spacer in the ascending section of the duodenum. A total of 32 stereotactic body radiation therapy (SBRT) plans (33 Gy in 5 fractions) were designed, for four cadavers, two GTV sizes, and two types of uncertainties. The preinjection scenario for each case was compared with three scenarios of virtual spacer placement from the dosimetric and geometric points of view., Results: We found that the overlapping PTV space with the duodenum is an informative quantity for determining the effective location of the spacer. The ideal spacer distribution reduced the duodenal V33Gy for small and large GTV to less than 0.3 and 0.1cc, from an average of 3.3cc, and 1.2cc for the preinjection scenario. However, spacer placement uncertainties reduced the efficacy of the spacer in sparing the duodenum (duodenal V33Gy: 1.3 and 0.4cc). The separation between duodenum and GTV decreased by an average of 5.3 and 4.6 mm. The corrective feedback can effectively bring back the expected benefits from the ideal location of the spacer (averaged V33Gy of 0.4 and 0.1cc)., Conclusions: An informative feedback metric was introduced and used to mitigate the effect of spacer placement uncertainties and maximize the benefits of the EUS-guided procedure., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Toxicity dose-response models describe the correlation between dose delivered to an organ and a given toxic endpoint. Duodenal toxicity is a dose limiting factor in the treatment of pancreatic cancer with radiation but the relationship between dose and toxicity in the duodenum is not well understood. While there have been limited studies into duodenal toxicity through investigations of the volume of the organ receiving dose over a specific threshold, both dose-volume and dose-surface histograms lack spatial information about the dose distribution, which may be important in determining normal tissue response. Due to the complex geometry of the duodenum, previous methods for unwrapping tubular organs for spatial modeling of toxicity are insufficient. A geometrically robust method for producing 2D dose surface maps (DSMs), specifically for the duodenum, has been developed and tested in order to characterize the spatial dose distribution., Methods: The organ contour is defined using Delaunay triangulation. The user selects a start and end coordinate in the structure and a path is found by regulating both length and curvature. This path is discretized and rays are cast from each point on the plane normal to the vector between the previous and the next point on the path and the dose at the closest perimeter point recorded. These angular perimeter slices are "unwrapped" from the edge distal to the pancreas to ensure the high dose region (proximal to the tumor) falls in the centre of the dose map. Gamma analysis is used to quantify the robustness of this method and the effect of overlapping planes., Results: This method was used to extract DSMs for 15 duodena, with one esophagus case to illustrate the application to simpler geometries. Visual comparison indicates that a 30 × 30 map provides sufficient resolution to view gross spatial features of interest. A lookup table is created to store the area (cm 2 ) represented by each pixel in the DSMs in order to allow spatial descriptors in absolute size. The method described in this paper is robust, requires minimal human interaction, has been shown to be generalizable to simpler geometries, and uses readily available commercial software. The difference seen in DSMs due to overlapping planes is large and justifies the need for a solution that removes such planes., Conclusions: This is the first time 2D dose surface maps have been produced for the duodenum and provide spatial dose distribution information which can be explored to create models that may improve toxicity prediction in treatments for locally advanced pancreatic cancer.

Purpose: Uncontrolled local growth is the cause of death in ∼ 30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk., Methods: The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test., Results: Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6-53.8 and 34.9-52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning., Conclusions: Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.

Purpose: This study aims to evaluate the interfractional dose variations in the organs-at-risk (OARs) during pancreatic breathhold intensity-modulated radiotherapy (IMRT) and to assess the impacts of "planning organs-at-risk volume" (POV) structures generated by isotropically expanding the dose-limiting OARs, based on the comparison of the interfractional doses to the OARs between IMRT plans and conventional three-dimensional-conformal radiotherapy (3D-CRT) plans., Methods: Thirty repeat CT scans were acquired from ten consecutive patients who were receiving chemoradiotherapy for pancreatic cancer. Six IMRT plans for each patient with two levels of prescription (45 and 51 Gy in 15 fractions) and 3 POV margin sizes (5, 7, and 10 mm) were generated based on the initial CT scan under predetermined constraints. Two 3D-CRT plans (39 and 42 Gy in 15 fractions) were simultaneously generated. The dose distribution of all of the treatment plans was recalculated with the repeat CT scans. The interfractional dose variations in the three OARs (stomach, duodenum, and small intestine) were evaluated, and the absolute volumes ≥39 Gy (V39Gy) of the OARs in the IMRT plans were compared to those in the 3D-CRT plans. Regression analyses were performed to assess the relative impact of the factors of interest on the interfractional dose variations of the OARs., Results: Substantial dose excesses to the three OARs were observed at all of the prescription dose levels and the POV margin sizes on the repeat CT scans. The safety threshold based on the mean stomach V39Gy on the recalculated 39 Gy-3D-CRT plans was 1.9 ml. Statistically significant and marginally insignificant mean V39Gy values above the safety thresholds were observed in the stomach in the 51 Gy-IMRT plans (2.6 and 2.1 ml with the 5- and 7-mm PRV margins, respectively (P = 0.015 and 0.085)). Only in the case of the 10-mm POV margin did the metric fall below the safety threshold to 1.5 ml (P = 0.634). The duodenum and the small intestine did not violate the safety thresholds (1.4 and 3.8 ml, respectively). From the multiple regression analyses, only the margin size (P < 0.001) and the POV V39Gy (P < 0.001) were significantly associated with the distribution of recalculated V39Gy for the stomach. Multiple factors, including the margin size (P = 0.020) and the POV V39Gy (P < 0.001) were associated with the recalculated V39Gy for the duodenum. However, none of the POV parameters for the small intestine were associated with the recalculated V39Gy., Conclusions: Considerable interfractional dose variation was observed in three critical OARs. At the escalated prescription dose of breathhold IMRT, the dose variations could exceed the dose variations using 3D-CRT at the safe prescription dose level, indicating that a dose-escalation strategy based solely on the initial advantageous dose distribution in a breathhold IMRT can be problematic. Given the current limitations for predicting or coping with variation throughout the treatment course, the use of POV should be considered for safely delivering escalated doses to patients with pancreatic cancer.