Pancreas Stereotactic Body Radiation Therapy Research Articles

Novel MR-Guided Radiotherapy Elective Rotation for Radiation Oncology Trainees.

MR-guided adaptive radiation therapy (RT) is emerging as an integral treatment modality for certain applications and is poised to become an exciting opportunity for greater treatment precision and personalization. However, this is still a relatively nascent technology and only a few institutions and programs have access to this technology for clinical use and trainee education. To increase the diversity of elective offerings and improve the understanding of an MR-guided radiotherapy program, we initiated a unique MR-guided radiotherapy elective rotation for radiation oncology residents. During a representative four-week rotation, 21 simulations were completed by the resident on service. A plurality of simulations were for pancreas stereotactic body radiation therapy (SBRT; 48%) and a majority (71%) of simulations were for adaptive treatments. Additionally, 74 adaptive fractions were completed during this month, of which a significant majority (74%) were for pancreas SBRT. Of the non-adaptive fractions, the majority were for prostate SBRT and intensity-modulated radiation therapy (IMRT). Although many programs may offer training in some aspects of MR-guided radiotherapy as trainees rotate through certain disease sites, we hope this may serve as a blueprint to encourage programs with this technology to fully embrace training in essential competencies related to MR-guided radiotherapy. MR-guided radiotherapy has unique challenges that trainees need to understand to deliver treatment safely: geometric uncertainty, MRI to RT isocenter, and uncertainties with voxel size/tracking.

Fluence Map Prediction Using Deep Learning Models - Direct Plan Generation for Pancreas Stereotactic Body Radiation Therapy.

Purpose: Treatment planning for pancreas stereotactic body radiation therapy (SBRT) is a difficult and time-consuming task. In this study, we aim to develop a novel deep learning framework to generate clinical-quality plans by direct prediction of fluence maps from patient anatomy using convolutional neural networks (CNNs).Materials and Methods: Our proposed framework utilizes two CNNs to predict intensity-modulated radiation therapy fluence maps and generate deliverable plans: (1) Field-dose CNN predicts field-dose distributions in the region of interest using planning images and structure contours; (2) a fluence map CNN predicts the final fluence map per beam using the predicted field dose projected onto the beam's eye view. The predicted fluence maps were subsequently imported into the treatment planning system for leaf sequencing and final dose calculation (model-predicted plans). One hundred patients previously treated with pancreas SBRT were included in this retrospective study, and they were split into 85 training cases and 15 test cases. For each network, 10% of training data were randomly selected for model validation. Nine-beam benchmark plans with standardized target prescription and organ-at-risk constraints were planned by experienced clinical physicists and used as the gold standard to train the model. Model-predicted plans were compared with benchmark plans in terms of dosimetric endpoints, fluence map deliverability, and total monitor units.Results: The average time for fluence-map prediction per patient was 7.1 s. Comparing model-predicted plans with benchmark plans, target mean dose, maximum dose (0.1 cc), and D95% absolute differences in percentages of prescription were 0.1, 3.9, and 2.1%, respectively; organ-at-risk mean dose and maximum dose (0.1 cc) absolute differences were 0.2 and 4.4%, respectively. The predicted plans had fluence map gamma indices (97.69 ± 0.96% vs. 98.14 ± 0.74%) and total monitor units (2,122 ± 281 vs. 2,265 ± 373) that were comparable to the benchmark plans.Conclusions: We develop a novel deep learning framework for pancreas SBRT planning, which predicts a fluence map for each beam and can, therefore, bypass the lengthy inverse optimization process. The proposed framework could potentially change the paradigm of treatment planning by harnessing the power of deep learning to generate clinically deliverable plans in seconds.

Australasian Gastrointestinal Trials Group (AGITG) and Trans-Tasman Radiation Oncology Group (TROG) Guidelines for Pancreatic Stereotactic Body Radiation Therapy (SBRT)

PurposeNonrandomized data exploring pancreas stereotactic body radiation therapy (SBRT) has demonstrated excellent local control rates and low toxicity. Before commencing a randomized trial investigating pancreas SBRT, standardization of prescription dose, dose constraints, simulation technique, and clinical target volume delineation are required. Methods and MaterialsSpecialists in radiation oncology, medical oncology, hepatobiliary surgery, and gastroenterology attended 2 consecutive Australasian Gastrointestinal Trials Group workshops in 2017 and 2018. Sample cases were discussed during workshop contact with specifically invited international speakers highly experienced in pancreas SBRT. Furthermore, sample cases were contoured and planned between workshop contact to finalize dose constraints and clinical target volume delineation. ResultsOver 2 separate workshops, consensus was reached on dose and simulation technique. The working group recommended a dose prescription of 40 Gy in 5 fractions. Treatment delivery during end-expiratory breath hold with triple-phase contrast enhanced computed tomography was recommended. In addition, dose constraints, stepwise contouring guidelines, and an anatomic atlas for pancreatic SBRT were developed. ConclusionsPancreas SBRT is emerging as a promising treatment modality requiring prospective evaluation in randomized studies. This work attempts to standardize dose, simulation technique, and volume delineation to support the delivery of high quality SBRT in a multicenter study.

Implementing and Improving Pancreas SBRT: One Challenge at a Time

The role of stereotactic body radiotherapy (SBRT) is being investigated as an alternative to long-course chemoradiation in select patients with locally advanced pancreatic cancer. Implementation of this technique is complex and fraught with challenges including the proximity of dose sensitive organs, target visibility for image guidance and respiratory motion. Pancreas SBRT was introduced at our institution in 2015 and the technique has undergone multiple iterations since with the goal of improving outcomes. The aim of our current work is to establish optimal respiratory motion management for pancreas SBRT. Initially, all pancreas SBRT cases were treated with a 3 fraction regimen (21-36 Gy) using abdominal compression to minimize respiratory motion. Patients were required to have a biliary stent in situ or fiducial markers implanted prior to simulation for image guidance. Based on our initial local control and toxicity results, institutional policy changed to a 5 fraction regimen (30-50 Gy). Abdominal compression is beneficial for minimizing motion and immobilizing the patient; however, there is a concern that it also causes anatomic deformation to organs at risk (OARs) such as the stomach and duodenum, moving them closer to the target. Thus, an upfront motion assessment was introduced to determine if motion management was necessary. At the time of planning, a free breathing low dose 4D computed tomography (4DCT) scan is acquired to quantify the pancreatic motion using the fiducials. If motion amplitude is <5mm, planning proceeds without abdominal compression, potentially eliminating the problem of moving the OARs into the high dose region. If on free breathing, the motion amplitude is >5mm, either abdominal compression or Active Breathing Coordinator (ABC) is required. For patients where ABC treatment is an option, breath hold and stability assessments will follow to confirm they are suitable candidates. Performing motion assessment prior to CT simulation allows for a more personalized approach to treating patients with pancreas SBRT. Treating patients without the abdominal plate provides greater comfort for patients and has potential dosimetric benefits for OARs. As access to MRI for simulation/planning increases, the free breathing option can readily be built upon as it does not rely on any treatment accessories. Unfortunately, motion evaluation is currently limited to patients with fiducials because stents are not reliable surrogates for motion as they are quite mobile themselves. Interpreting a complex decision tree like this can be confusing for those performing the simulation, making communication and education integral to the success of the program. To date, 18 patients have undergone motion assessment. Five patients were treated free-breathing, 12 patients with abdominal compression, and 1 with ABC. The 12 patients simulated with abdominal compression had an average motion reduction of 9.2 mm to 5.2 mm, confirming the effectiveness of abdominal compression. To quantify intrafraction motion for the free-breathing option, post treatment Cone Beam Computed Tomography (CBCT) images were acquired after every fraction. Upon analysis of the CBCT data, an average overall shift of only 1.5 mm was seen, suggesting there are no issues with stability. The development of 3 different methods for treating SBRT pancreas has resulted in an approach tailored to individual patient’s motion management needs and prepared us for future technological innovations.

A Collimator Setting Optimization Algorithm for Dual-Arc Volumetric Modulated Arc Therapy in Pancreas Stereotactic Body Radiation Therapy.

Purpose:To optimize collimator setting to improve dosimetric quality of pancreas volumetric modulated arc therapy plan for stereotactic body radiation therapy.Materials and Methods:Fifty-five volumetric modulated arc therapy cases in stereotactic body radiation therapy of pancreas were retrospectively included in this study with internal review board approval. Different from the routine practice of initializing collimator settings with a template, the proposed algorithm simultaneously optimizes the collimator angles and jaw positions that are customized to the patient geometry. Specifically, this algorithm includes 2 key steps: (1) an iterative optimization algorithm via simulated annealing that generates a set of potential collimator settings from 39 cases with pancreas stereotactic body radiation therapy, and (2) a multi-leaf collimator modulation scoring system that makes the final decision of the optimal collimator settings (collimator angles and jaw positions) based on organs at risk sparing criteria. For validation, the other 16 cases with pancreas stereotactic body radiation therapy were analyzed. Two plans were generated for each validation case, with one plan optimized using the proposed algorithm (Planopt) and the other plan with the template setting (Planconv). Each plan was optimized with 2 full arcs and the same set of constraints for the same case. Dosimetric results were analyzed and compared, including target dose coverage, conformity, organs at risk maximum dose, and modulation complexity score. All results were tested by Wilcoxon signed rank tests, and the statistical significance level was set to .05.Results:Both plan groups had comparable target dose coverage and mean doses of all organs at risk. However, organs at risk (stomach, duodenum, large/small bowel) maximum dose sparing (D0.1 cc and D0.03 cc) was improved in Planopt compared to Planconv. Planopt also showed lower modulation complexity score, which suggests better capability of handling complex shape and sparing organs at risk .Conclusions:The proposed collimator settings optimization algorithm successfully improved dosimetric performance for dual-arc pancreas volumetric modulated arc therapy plans in stereotactic body radiation therapy of pancreas. This algorithm has the capability of immediate clinical application.

Technical Assessment of an Automated Treatment Planning on Dose Escalation of Pancreas Stereotactic Body Radiotherapy.

Background:Stereotactic body radiotherapy has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly radiosensitive normal tissues usually causes the labor-intensive planning process and may impede further escalation of the prescription dose.Purpose:The present study aims to evaluate the consistency and efficiency of Pinnacle Auto-Planning for pancreas stereotactic body radiotherapy with original prescription and escalated prescription.Methods:Twenty-four patients with pancreatic cancer treated with stereotactic body radiotherapy were studied retrospectively. The prescription is 40 Gy over 5 consecutive fractions. Most of patients (n = 21) also had 3 other different dose-level targets (6 Gy/fraction, 5 Gy/fraction, and 4 Gy/fraction). Two types of plans were generated by Pinnacle Auto-Planning with the original prescription (8 Gy/fraction, 6 Gy/fraction, 5 Gy/fraction, and 4 Gy/fraction) and escalated prescription (9 Gy/fraction, 7 Gy/fraction, 6 Gy/fraction, and 5 Gy/fraction), respectively. The same Auto-Planning template, including beam geometry, intensity-modulated radiotherapy objectives and intensity-modulated radiotherapy optimization parameters, were utilized for all the auto-plans in each prescription group. The intensity-modulated radiotherapy objectives do not include any manually created structures. Dosimetric parameters including percentage volume of PTV receiving 100% of the prescription dose, percentage volume of PTV receiving 93% of the prescription dose, and consistency of the dose-volume histograms of the target volumes were assessed. Dmax and D1 cc of highly radiosensitive organs were also evaluated.Results:For all the pancreas stereotactic body radiotherapy plans with the original or escalated prescriptions, auto-plans met institutional dose constraints for critical organs, such as the duodenum, small intestine, and stomach. Furthermore, auto-plans resulted in acceptable planning target volume coverage for all targets with different prescription levels. All the plans were generated in a one-attempt manner, and very little human intervention is necessary to achieve such plan quality.Conclusions:Pinnacle3 Auto-Planning consistently and efficiently generate acceptable treatment plans for multitarget pancreas stereotactic body radiotherapy with or without dose escalation and may play a more important role in treatment planning in the future.

Daily breathing inconsistency in pancreas SBRT: a 4DCT study.

Stereotactic body radiation therapy (SBRT) treatments of pancreatic cancer typically employ relatively small margins. This study characterizes the motion of high visibility structures in close proximity to the pancreas to determine how much the motion envelope of such a structure changes due to respiratory variation between fractions. Fanbeam, four-dimensional computed tomography (4DCT) studies acquired initially for planning and again prior to each treatment for 6 patients were used to fully characterize the change in motion of high-contrast structures in close proximity to the pancreas. Three of the six patients investigated had structures that showed a change in motion over the course of treatment that would not have been covered when using the typical 3 mm planning target volume (PTV) margins. For most of these large changes in motion envelope, a 4 mm uniform PTV margin would have allowed for coverage of the tumor. Half of the patients showed a change in motion envelope greater than would be covered by the commonly used PTV margins in pancreas SBRT. This shows that the impact of small margins must be very carefully considered during the planning process.

Geometric Reproducibility of Fiducial Markers and Efficacy of a Patient-Specific Margin Design Using Active Breath Hold for Pancreas Stereotactic Body Radiation Therapy

In patients undergoing SBRT for pancreatic adenocarcinoma using an active breathing control (ABC), the reproducibility of fiducial positioning between breath-holds is unclear. We characterized this variation by acquiring multiple breath-hold CTs at time of simulation and analyzed whether a patient-specific margin based on this variation would help account for intra-fraction variation at time of treatment. We analyzed five pancreatic cancer patients who underwent SBRT for pancreatic adenocarcinoma and who were treated with ABC. At time of simulation, 3-additional breath-hold scans were acquired immediately after the primary contrast-enhanced planning CT with 2-mm slice thickness. To characterize the variability in tumor position between breath-holds, fiducial centroids from the planning CT were used as the reference and compared to the fiducial centroids from the additional breath-hold CTs. Both the average excursions in fiducial position (Sim Varavg) and the maximum excursions in fiducial position (Sim Varmax) were calculated. For treatment planning for each patient, the amount of variation in each direction between breath-holds was applied as a margin to the GTV, followed by an additional 2-mm margin to determine the final PTV. The difference in volume between this method versus directly expanding the GTV by a uniform 2-mm expansion was calculated. During 5-fraction treatment, 20-27 breath-hold CBCTs were acquired for each patient. The intrafraction variation in fiducial position was calculated using the same method as above, using the initial CBCT for that fraction as the reference CT and using similar metrics to characterize fiducial position variation (Tx Varavg and Tx Varmax). The adequacy of a direct 2-mm expansion on the GTV was analyzed by evaluating the percentage of fiducial locations within 2-mm of variability on CBCTs. Table 1 summarizes the breath-hold reproducibility averaged over all five patients at CT sim and treatment. By applying the variation seen during multiple breath-holds at time of simulation to the GTV volume before further expanding by 2 mm, the final PTV volume increased by 19.5 ± 7.0% as compared to a uniform 2-mm expansion off of the GTV. However, by using this patient-specific margin, 95% of the all fiducial locations during treatment were encompassed within this volume, while a uniform 2-mm expansion only covered the fiducials 80% in both LR and AP directions and 60% in the SI direction.Abstract SU_18_2175; Table 1Inter-BH reproducibilityLR (mm)AP (mm)SI (mm)Sim Varavg0.8 ± 0.51.0 ± 0.41.5 ± 0.7Sim Varmax1.2 ± 0.71.4 ± 0.52.3 ± 0.6Tx Varavg1.2 ± 0.51.4 ± 0.62.1 ± 0.4Tx Varmax4.7 ± 2.15.5 ± 3.06.4 ± 2.4 Open table in a new tab Variation in tumor position exists between breath-holds when treating with ABC. Acquiring multiple breath-hold CTs during simulation can help quantify inter-breath-hold reproducibility and can provide a patient specific margin design to compensate for the variation in tumor position between breath-holds at time of treatment.

Daily Adaptive Magnetic Resonance Image Guidance Protects the Duodenum from Dose Constraint Violations Associated with Interfraction Stomach Deformation in Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer

Magnetic Resonance Image guided (MRI-g) radiation therapy provides better soft tissue visualization than cone beam computed tomography (CBCT) and allows for daily online adaptive radiotherapy (OART) in the treatment of locally advanced pancreatic cancer (LAPC). Using MRI-g stereotactic body radiation therapy (SBRT) to treat LAPC, we hypothesized that stomach distention would correlate with dose increases to organs-at-risk (OARs) when online adaptation was not utilized. Meanwhile, we hypothesized that OART would protect against dose constraint violations to OARs. We identified ten patients who received pancreas SBRT to a dose of 33-40 Gy in 5 fractions. The patients were instructed to avoid oral intake other than sips of water for at least 3 hours prior to treatment. Dose was prescribed to achieve 90% coverage of planning tumor volume at 100% isodose (PTV100). After each fraction’s setup MRI, the target position was aligned by 3-dimensional shifts, the normal anatomy was re-contoured, and the original radiotherapy plan was recalculated to make a non-adaptive plan. A re-optimized (adaptive) plan was then generated for each fraction and renormalized to 90% coverage of PTV100. Target and OAR doses between non-adaptive and adaptive plans were compared by paired t-test and McNemar tests to assess the dosimetric impact of daily adaptation. A linear random-coefficient model correlated changes in stomach volumes to changes in OAR objective doses. Sixty-eight percent of non-adaptive fractions met both point maxima and V33 dose constraints to the duodenum compared with 87% of adaptive fractions (p=0.0013). The original stomach volume (OSV) mean was 286 cc, with a range from 126cc-856cc. The mean interfraction change from the OSV was +147cc, with a range from -404cc to +1,271 cc. The mean percentage change from the OSV was 53%, with a range from -47% to 334%. For non-adaptive plans, interfraction increase in stomach volume correlated with higher duodenum V33 (p=0.021), duodenum maximum dose (p=0.105), stomach V33 (p=0.004), and stomach maximum dose (p=0.009). No correlation was observed between stomach volume and dose to visceral OARs for the adaptive plans. In SBRT for LAPC, interfraction variations in stomach volume occur despite precautions and correlate with increased dose to the duodenum in non-adaptive plans, leading to significant dose constraint violations. OART limits dose to the duodenum and contributes to safe SBRT dose escalation.Abstract SU_20_2197; Table 1Analysis of OAR constraint violations for non-adaptive (NA) and adaptive (A) plansBoth NA and A meet OAR constraints, n (%)Only NA meets constraints, n (%)Only A meets constraints, n (%)Neither NA nor A meets constraints, n (%)p-valueDuodenumDmax < 38 Gy28 (56)4 (8)15 (30)3 (6)0.019V33 < 1 cc32 (64)4 (8)12 (24)2 (4)0.077StomachDmax < 38 Gy40 (80)3 (6)4 (8)3 (6)1V33 < 1 cc37 (74)3 (6)5 (10)5 (10)0.727BowelDmax < 38 Gy44 (88)5 (10)1 (2)0 (0)0.219All OAR constraints met14 (28)9 (18)15 (30)12 (24)0.221 Open table in a new tab

Dosimetric Benefits and Practical Pitfalls of Daily Online Adaptive MRI-Guided Stereotactic Radiation Therapy for Pancreatic Cancer

PurposeMagnetic resonance imaging guided (MRI-g) radiation therapy provides visualization of the target and organs at risk (OARs), allowing for daily online adaptive radiation therapy (OART). We hypothesized that MRI-g OART would improve OAR sparing and target coverage in patients with pancreatic cancer treated with stereotactic body radiation therapy (SBRT). Methods and MaterialsTen patients received pancreas SBRT to a dose of 33 to 40 Gy in 5 fractions. The dose was prescribed to 90% coverage of the planning target volume at 100% isodose (PTV100). After each fraction's setup magnetic resonance imaging scan, the target position was aligned by 3-dimensional shifts, the normal anatomy was recontoured, and the original radiation therapy plan was recalculated to create a nonadaptive plan. A reoptimized (adaptive) plan was then generated for each fraction and renormalized to 90% coverage of PTV100. Target and OAR doses between nonadaptive and adaptive plans were compared to assess the dosimetric impact of daily adaptation. ResultsThe PTV100 mean for adaptive and nonadaptive techniques was 90% and 80.4% (range, 46%-97%), respectively (P = .0008). Point maximum (Dmax) 38 Gy duodenum objectives were met in 43 adaptive fractions compared with 32 nonadaptive fractions (P = .022). Both PTV100 ≥90% and all OAR objectives were achieved in 28 adaptive fractions compared with only 3 nonadaptive fractions. For nonadaptive plans, interfraction increases in stomach volume correlated with higher stomach V33 (P = .004), stomach Dmax (P = .009), duodenum V33 (P = .021), and duodenum Dmax (P = .105). No correlation was observed between stomach volume and OAR doses for adaptive plans. OART plans with Dmax violations of the spinal cord (20 Gy) in 4 fractions and large bowel (38 Gy) in 5 fractions were identified (although not delivered). ConclusionsMRI-g OART improves target coverage and OAR sparing for pancreas SBRT. This benefit partially results from mitigation of interfraction variability in stomach volume. Caution must be exercised to evaluate all OARs near the treatment area.

(OA06) Interfraction Variations in Stomach Volume Increase Dose to Stomach and Duodenum in Pancreas Stereotactic Body Radiotherapy and Is Mitigated by Daily Adaptive Magnetic Resonance Image Guided Radiation Therapy

Magnetic Resonance Image Guided Radiation Therapy (MR-IGRT) permits clear daily visualization of the target and organs at risk (OARs) for daily dose adaptation. Using MR-IGRT with Cobalt-60 for locally advanced pancreatic cancer (LAPC) stereotactic body radiation therapy (SBRT), we noticed varied stomach volumes despite precautions not to eat prior to treatment. We hypothesized that larger stomach volumes would be associated with higher doses to OARs and that online adaptive re-planning would reduce OAR doses while maintaining prescription dose coverage. Ten LAPC patients received five fraction SBRT totaling 33-40Gy as limited by OAR constraints. Patients were instructed to avoid food and drink only sips of water for at least 3 hours prior to treatment. Treatment plans provided 90% coverage of the planning target volume (PTV) at prescription isodose (PID). While patients could have received adaptive or non-adaptive radiotherapy with MR-IGRT, all fifty fractions underwent simulated adaptation. First the original (as planned) doses were compared to the dose delivered only after 3D couch shifts (non-adaptive). An adaptive plan was created for each fraction mimicking the process for daily adaptive radiotherapy. Specifically, contours were adjusted to the anatomy visualized on the setup MRI for each fraction, and a “warm start” optimization run was performed to find a new optimizer solution with the day’s updated contours starting with the original optimizer objectives and control points. Adaptive plans were normalized to 90% PTV coverage at PID. We used linear regression and Bayesian approach to evaluate the association between changes in stomach volume and changes in radiation dose to visceral OARs for both non-adaptive and adaptive planning techniques. Only 8 non-adaptive MR-IGRT fractions maintained at least 90% PTV coverage compared to all 50 adaptive MR-IGRT fractions, and 23 non-adaptive fractions met all OAR objectives compared to 29 adaptive fractions. The original stomach volume (OSV) mean was 285.98cc, with a range from 125.6cc-855.8cc. The mean interfraction change from the OSV was +146.8cc, with a range from -403.76cc to +1271.13cc and a standard deviation of 245.57cc. The mean percentage change from the OSV was 53.2%, with a range from -47.18% to 334.32% and a standard deviation of 68.82%. Eight interfraction changes in stomach volume were greater than 500cc. For non-adaptive plans, Bayesian approach revealed a significant association between percentage increases in stomach volume and increased stomach V33 (p=.0041), stomach maximum dose (p=.0095) and duodenum V33 (p=.0208). Adaptive MR-IGRT showed no association between percentage increases in stomach volume and increased stomach V33 (p=.2763), stomach maximum dose (p=.3174) or duodenum V33 (p=.7736). This study demonstrates that for SBRT of LAPC, interfraction variations in stomach volume occur despite standard precautions and are associated with increased dose to the stomach and duodenum in non-adaptive plans. Adaptive planning limits dose to the stomach and duodenum and may permit safe SBRT dose escalation.

Dosimetric analysis of stereotactic body radiation therapy for pancreatic cancer using MR-guided Tri-60Co unit, MR-guided LINAC, and conventional LINAC-based plans

Abstract Purpose This study aims to perform a dosimetric comparison of 2 magnetic resonance (MR)-guided radiation therapy systems capable of performing online adaptive radiation therapy versus a conventional radiation therapy system for pancreas stereotactic body radiation therapy. Methods and materials Ten cases of patients with pancreatic adenocarcinoma previously treated in our institution were used for this analysis. MR-guided tri-cobalt 60 therapy (MR-cobalt) and MR-LINAC plans were generated and compared with conventional LINAC (volumetric modulated arc therapy) plans. The prescription dose was 40 Gy in 5 fractions covering 95% of the planning tumor volume for the 30 plans. The same organs at risk (OARs) dose constraints were used in all plans. Dose-volume–based indices were used to compare PTV coverage and OAR sparing. Results The conformity index of 40 Gy in 5 fractions covering 95% of the planning tumor volume demonstrated higher conformity in both LINAC-based plans compared with MR-cobalt plans. Although there was no difference in mean conformity index between LINAC and MR-LINAC plans (1.08 in both), there was a large difference between LINAC and MR-cobalt plans (1.08 vs 1.52). Overall, 79%, 72%, and 78% of critical structure dosimetric constraints were met with LINAC, MR-cobalt, and MR-LINAC plans, respectively. The MR-cobalt plans delivered more doses to all OARs compared with the LINAC plans. In contrast, the doses to the OARs of the MR-LINAC plans were similar to LINAC plans except in 2 cases: liver mean dose (MR-LINAC, 2 .8 Gy vs LINAC, 2.1 Gy) and volume of duodenum receiving at least 15 Gy (MR-LINAC, 13.2 mL vs LINAC, 15.4 mL). Both differences are likely not clinically significant. Conclusion This study demonstrates that dosimetrically similar plans were achieved with conventional LINAC and MR-LINAC, whereas doses to OARs were statistically higher for MR-cobalt compared with conventional LINAC plans because of low-dose spillage. Given the improved tumor-tracking capabilities of MR-LINAC, further studies should evaluate potential benefits of adaptive radiation therapy–capable MR-guided LINAC treatment.

Stereotactic Body Radiation Therapy in Pancreas Adenocarcinoma Demonstrates Minimal Acute and Late Toxicity

Stereotactic body radiation therapy (SBRT) has been increasingly utilized in the management of pancreatic cancer (PCA). Treatment-related toxicity is a limiting factor in dose escalation and treatment planning. We describe our institutional experience of reportable adverse events following PCA SBRT. A retrospective analysis of 295 PCA patients treated with 5-fraction SBRT from 2010-2016 was performed. All patients included in the cohort had >3 months of documented follow-up from time of SBRT, unless death occurred prior to that time. Toxicities were graded using CTCAE v3.0. Acute and late toxicities were defined as occurring within or after 90 days of SBRT, respectively. The median patient age was 66 (range 36-90). The majority of patients were diagnosed with locally advanced PCA (58%), while the remainder had borderline resectable (26%), resected (12%), or metastatic (2%) disease. The median radiation dose was 33Gy in 5 fractions (range 20-33), and the median PTV was 74cc (range 0.56-313). Volumetric-modulated arc therapy (VMAT) was used in 15% of SBRT cases, and active breathing control (ABC) was implemented in 82%. 47% of the patients received ≥4 months of upfront chemotherapy, and over half (52%) underwent surgical resection. The median follow-up time was 11.9mo (range 1.0-73.3). Late toxicity data was available for 96% of patients. Rates of acute and late grade ≥2 gastritis, fistula, enteritis, or ulcer toxicities were 4.1% and 6.1% respectively. The median time to these toxicities was 2.3mo and 9.1mo. The rates of overall grade ≥3 acute and late toxicities were 10.2% and 15.9%. Among patients who were surgically resected, the grade ≥3 acute and late toxicity rates were 12.5% and 13.8%, and among patients who were not surgical candidates, the rates were 7.7% and 18.9%. Of these grade ≥3 toxicities, the most common included bowel/biliary obstruction (40.3%), gastrointestinal bleed (10.4%), and hepatic/abdominal abscesses (10.4%). There were 6 cases of grade 5 toxicity, all of which were acute. Two patients died of GI bleeds, one during SBRT to liver metastases at an outside institution 2.5 months after pancreas SBRT and the other 1.5 months after surgical resection. For the remaining grade 5 adverse events, patients died after hospitalization for bowel obstruction, septic joint from a fall, acute respiratory distress syndrome 24hrs post-operatively, and post-endoscopic retrograde cholangio-pancreatography-related sepsis. Our institution's experience suggests that pancreas SBRT is well tolerated, with 3 cases (1%) of grade 5 toxicity potentially attributable to SBRT. Further analysis may lead to improved dose constraints and treatment planning.

PTV Hot-Spot Volume is Associated With Improved Pathologic Response After Neoadjuvant Stereotactic Body Radiation Therapy for Pancreatic Cancer

Stereotactic Body Radiation Therapy (SBRT) has been used in pancreatic adenocarcinoma (PCA) patients to improve local control but the optimal dose is unclear. At our institution, 6.6 Gy x 5 has been our standard prescription, with varying levels of “hot-spots” depending on patient anatomy. Our study aimed to characterize the hot-spot within the planning target volume (PTV) and investigate the association between hot-spot volume and surgical pathology response. Dose and volume relationships were queried for all PCA patients treated with neoadjuvant SBRT that underwent surgery at our institute from 2010 to 2016 from Oncospace. Patients whose PTV prescription was <30 Gy and went to surgery within 2 weeks from SBRT were excluded. PTV hot-spot (V35) was defined as PTV volume (cc) receiving at least 35 Gy, with the PTV defined as the gross target volume with a 2mm expansion. The primary outcome of complete response was characterized as 1) complete (CR), 2) near complete (NC), 3) moderate response (MR), and poor response (PR) from post-surgical resection by pathology review. Co-variates included chemotherapy duration (< 4 months vs ≥ 4 months), time from SBRT to surgery (weeks), active breathing control (ABC) status (free-breathing vs breath-hold), and GTV volume (cc). Ordinal logistic regression was performed to identify the association between V35 and pathologic outcomes. Of 120 patients who completed neoadjuvant SBRT underwent surgery, 102 were identified with criteria above. Among these patients, 58% (n = 60) received chemotherapy longer than 4 months, and 75% (n = 77) had breath-hold during treatment. Neoadjuvant pancreas SBRT was prescribed to a dose of 30 - 33 Gy in 5 fractions, the mean GTV size was 35 cc (range, 10 – 107 cc), and went to surgery within 8 weeks after SBRT (range, 2 – 27 weeks). Seven percent (n = 8) had a pathologic CR, 33% (n = 34) NC, 41% (n = 42) MR and 18% (n = 18) had PR. The dose coverage for hot-spot (V35) was 33cc (range, 5 – 99 cc). Among patients who were treated with active breath-hold, the mean V35 for CR, NC, MR and PR group were 50, 39, 30, 32 cc, respectively. Increased size of hot-spot (V35) was associated with improved pathologic complete response group (OR = 1.02, 95% CI 1 – 1.04, P = 0.05). Such correlation was not found among free-breathing patients. Size of hot-spot (V35) with ABC management suggests an association with improved pathologic response among neoadjuvant SBRT pancreatic cancer patients. Higher dose in free-breathing patients was not associated with local control perhaps due to larger targets with margin because of free-breathing status. Our analysis supports further dose escalation with ABC management during SBRT planning.

Feasibility study of ultrasound imaging for stereotactic body radiation therapy with active breathing coordinator in pancreatic cancer.

PurposeStereotactic body radiation therapy (SBRT) allows for high radiation doses to be delivered to the pancreatic tumors with limited toxicity. Nevertheless, the respiratory motion of the pancreas introduces major uncertainty during SBRT. Ultrasound imaging is a non‐ionizing, non‐invasive, and real‐time technique for intrafraction monitoring. A configuration is not available to place the ultrasound probe during pancreas SBRT for monitoring.Methods and MaterialsAn arm‐bridge system was designed and built. A CT scan of the bridge‐held ultrasound probe was acquired and fused to ten previously treated pancreatic SBRT patient CTs as virtual simulation CTs. Both step‐and‐shoot intensity‐modulated radiation therapy (IMRT) and volumetric‐modulated arc therapy (VMAT) planning were performed on virtual simulation CT. The accuracy of our tracking algorithm was evaluated by programmed motion phantom with simulated breath‐hold 3D movement. An IRB‐approved volunteer study was also performed to evaluate feasibility of system setup. Three healthy subjects underwent the same patient setup required for pancreas SBRT with active breath control (ABC). 4D ultrasound images were acquired for monitoring. Ten breath‐hold cycles were monitored for both phantom and volunteers. For the phantom study, the target motion tracked by ultrasound was compared with motion tracked by the infrared camera. For the volunteer study, the reproducibility of ABC breath‐hold was assessed.ResultsThe volunteer study results showed that the arm‐bridge system allows placement of an ultrasound probe. The ultrasound monitoring showed less than 2 mm reproducibility of ABC breath‐hold in healthy volunteers. The phantom monitoring accuracy is 0.14 ± 0.08 mm, 0.04 ± 0.1 mm, and 0.25 ± 0.09 mm in three directions. On dosimetry part, 100% of virtual simulation plans passed protocol criteria.ConclusionsOur ultrasound system can be potentially used for real‐time monitoring during pancreas SBRT without compromising planning quality. The phantom study showed high monitoring accuracy of the system, and the volunteer study showed feasibility of the clinical workflow.

Triphasic contrast enhanced CT simulation with bolus tracking for pancreas SBRT target delineation

PurposeBolus-tracked multiphasic contrast computed tomography (CT) is often used in diagnostic radiology to enhance the visibility of pancreas tumors, but is uncommon in radiation therapy pancreas CT simulation, and its impact on gross tumor volume (GTV) delineation is unknown. This study evaluates the lesion conspicuity and consistency of pancreas stereotactic body radiation therapy (SBRT) GTVs contoured in the different contrast phases of triphasic CT simulation scans. Methods and materialsTriphasic, bolus-tracked planning CT simulation scans of 10 consecutive pancreas SBRT patients were acquired, yielding images of the pancreas during the late arterial (LA), portal venous (PV), and either the early arterial or delayed phase. GTVs were contoured on each phase by a gastrointestinal-specialized radiation oncologist and reviewed by a fellowship-trained abdominal radiologist who specializes in pancreatic imaging. The volumes of the registered GTVs, their overlap ratio, and the 3-dimensional margin expansions necessary for each GTV to fully encompass GTVs from the other phases were calculated. The contrast difference between tumor and normal pancreas was measured, and 2 radiation oncologists rank-ordered the phases according to their value for the lesion-contouring task. ResultsTumor-to-pancreas enhancement was on average much larger for the LA and PV than the delayed phase or early arterial phases; the LA and PV phases were also consistently preferred by the radiation oncologists. Enhancement differences among the phases resulted in highly variable GTV volumes with no observed trends. Overlap ratios ranged from 18% to 75% across all 3 phases, improving to 43% to 91% when considering only the preferred LA and PV phases. GTV expansions necessary to encompass all GTVs ranged from 0.3 to 1.8 cm for all 3 phases, improving slightly to 0.1 to 1.4 cm when considering just the LA and PV phases. ConclusionsFor pancreas SBRT, we recommend combining the GTVs from a multiphasic CT simulation with bolus-tracking, including, at a minimum, a Boolean “OR” of the LA and PV phases.

Dosimetric Evaluation of Magnetic Resonance–Image Guided Radiation Therapy 3-Source Co-60 and Linear Accelerator–Based Intensity Modulated Radiation Therapy Plans for Pancreas Stereotactic Body Radiation Therapy

Dosimetric Evaluation of Magnetic Resonance–Image Guided Radiation Therapy 3-Source Co-60 and Linear Accelerator–Based Intensity Modulated Radiation Therapy Plans for Pancreas Stereotactic Body Radiation Therapy

Stereotactic body radiation for pancreatic cancer: results of an international survey of practice patterns

Stereotactic body radiotherapy (SBRT) is an emerging treatment option for borderline resectable and locally advanced, unresectable pancreatic cancer (PCA). However, no standardized guidelines for treatment exist and patterns of SBRT use for PCA are unclear. Radiation oncologists known to use SBRT in the setting of PCA were invited to complete a 26-item Web-based survey on practice patterns. Thirty of the 36 (83 %) invited radiation oncologists completed the survey. Of the responders, 86 % treat with 6–8 Gy ×5 fractions. The majority (93 %) of responders use four-dimensional computed tomography (4D-CT) for simulation, with 50 % using gating for breathing motion. Two thirds of radiation oncologists use fiducials for tumor localization. Most (79 %) responders noted an improvement in patient-reported pain after SBRT. Approximately, 59 % report difficulty obtaining insurance clearance for pancreas SBRT in the absence of a clinical trial. The largest variations in practice were related to gross tumor volume (GTV) to planning target volume (PTV) expansions and management of respiratory motion. SBRT is increasingly used for PCA. The data presented here indicate that the majority of radiation oncologists treat with 6–8 Gy ×5 fractions and use fiducials with 4D-CT simulation for localization and planning. Although the majority of the surveyed physicians prefer SBRT to standard radiation, it may be underutilized due to the difficulty of obtaining insurance approval outside of a clinical trial. Our investigation documents current pancreas SBRT practice patterns and highlights the need for prospective clinical trials as a means to develop consensus guidelines for this emerging treatment.

SU‐C‐BRB‐02: Automatic Planning as a Potential Strategy for Dose Escalation for Pancreas SBRT?

Purpose:Stereotactic body radiation therapy (SBRT) has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly radiosensitive normal tissues usually causes the labor‐intensive planning process, and may impede further escalation of the prescription dose. The present study evaluates the potential of an automatic planning system as a dose escalation strategy.Methods:Ten pancreatic cancer patients treated with SBRT were studied retrospectively. SBRT was delivered over 5 consecutive fractions with 6 ∼ 8Gy/fraction. Two plans were generated by Pinnacle Auto‐Planning with the original prescription and escalated prescription, respectively. Escalated prescription adds 1 Gy/fraction to the original prescription. Manually‐created planning volumes were excluded in the optimization goals in order to assess the planning efficiency and quality simultaneously. Critical organs with closest proximity were used to determine the plan normalization to ensure the OAR sparing. Dosimetric parameters including D100, and conformity index (CI) were assessed.Results:Auto‐plans directly generate acceptable plans for 70% of the cases without necessity of further improvement, and two more iterations at most are necessary for the rest of the cases. For the pancreas SBRT plans with the original prescription, autoplans resulted in favorable target coverage and PTV conformity (D100 = 96.3% ± 1.48%; CI = 0.88 ± 0.06). For the plans with the escalated prescriptions, no significant target under‐dosage was observed, and PTV conformity remains reasonable (D100 = 93.3% ± 3.8%, and CI = 0.84 ± 0.05).Conclusion:Automatic planning, without substantial human‐intervention process, results in reasonable PTV coverage and PTV conformity on the premise of adequate OAR sparing for the pancreas SBRT plans with escalated prescription. The results highlight the potential of autoplanning as a dose escalation strategy for pancreas SBRT treatment planning. Further investigations with a larger number of patients are necessary.The project is partially supported by Philips Medical Systems

SU‐F‐R‐47: Quantitative Shape Relationship Analysis of PTV Modification for Critical Anatomy Sparing and Its Impact On Pathologic Response for Neoadjuvant Stereotactic Radiotherapy for Pancreatic Cancer

Purpose:Stereotactic body radiation therapy (SBRT) may be used to increase surgery candidacy in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. However, the planning target volume (PTV) may need to be limited to avoid toxicity when the gross tumor volume (GTV) is anatomically involved with surrounding critical structures. Our study aims to characterize the coverage of GTV and investigate the association between modified PTV and pathologic (pCR) or near pathologic (npCR) complete response rates determined from the surgical specimen.Methods:Patients treated with neoadjuvant pancreas SBRT followed by surgery from 2010–2015 were selected from Oncospace. Overlap volume histogram (OVH) analysis was performed to determine the extent of compromise of the PTV from both the GTV and a standard target (GTV+3mm). Subsequently, normalized overlap volume (%) was calculated for: (1) GTV‐PTV, and (2) GTV+3mm expansion‐PTV. A logistic regression model was used to identify the association between the overlap ratios and ≥ npCR(pCR/npCR) stratified by active breathing control (ABC) versus free‐breathing status.Results:Eighty‐one (BRPC: n=42, LAPC: n=39) patients were available for analysis. Nearly 40% (31/81) had ≥npCR and 75% (61/81) were able to complete ABC. Mean coverage of the GTV‐PTV was 92.6% (range, 59.9%–100%, SD = 8.68) and coverage of the GTV+3mm expansion‐PTV was 85. 2% (range, 59.9% −100.0%, SD= 8.67). Among the patients with ABC, every 10% increase in GTV coverage doubled the odds to have ≥npCR (OR = 1.82, p=0.06). Coverage of GTV+3mm expansion was not associated with ≥npCR regardless of ABC status.Conclusion:Preferential sparing of critical anatomy over GTV‐PTV coverage with ABC management suggests worse ≥npCR rates for neoadjuvant SBRT in BRPC and LAPC. Limiting the GTV and GTV+3mm expansion in free‐breathing patients was not associated with pathologic response perhaps due to larger GTV definitions as a result of motion artifacts in free‐breathing CT scans.Collaboration with Toshiba, Elekta, and Phillips