Purpose/Objective(s) Dose-escalated radiotherapy is increasingly used in the treatment of pancreatic cancer, however approaches to target delineation vary widely. We present the first North American cooperative group consensus contouring atlas for dose-escalated pancreatic cancer radiotherapy. Materials/Methods NRG Oncology recruited an expert international panel comprising 17 radiation oncologists, 2 surgeons and 1 radiologist. Participants used software to contour high and low risk clinical target volumes (CTV) on three representative cases: a borderline resectable head tumor, a locally advanced head tumor, and a tail tumor. Simultaneous truth and performance level estimation (STAPLE) volumes were created, representing probabilistic weighted global aggregated results. Contours were analyzed using DICE3D similarity coefficients and mean/max distance against STAPLE volumes, and guidelines were reviewed with the entire multidisciplinary panel. Results 15 radiation oncologists contoured a total of 45 volumes. The gross tumor volume (GTV) for the borderline head, locally advanced head, and tail tumor cases were 156.7 cc, 58.2 cc and 9.0 cc, respectively. The high and low risk STAPLE CTVs were 355.7 cc/591.5 cc, 141.5 cc/267.9 cc, and 32.4 cc/182.6 cc, and the DICE3D similarity coefficients (SD) were 0.80(0.06)/0.79(0.11), 0.82(0.07)/0.78(0.10), and 0.74(0.14)/0.45(0.17), respectively. The mean and max distance from STAPLE volume for the high-risk CTV for the 3 cases was 4.2 mm/12.0 mm, 3.3 mm/7.8 mm and 2.7 mm/6.5 mm and for the low-risk CTV were 5.4 mm/14.7 mm, 4.8 mm/11.2 mm and 15.9 mm/51.1 mm. Consensus volumes were agreed upon. High-risk CTVs comprised the tumor plus abutting vessel (celiac and branches, superior mesenteric, splenic, and portal). The low-risk CTV covered areas of perineural and perivascular spread, starting superiorly at (tail) or 1 cm above (head) the celiac takeoff and extended inferiorly to the superior mesenteric artery (SMA) at the level of the first jejunal takeoff. For head tumors, the lateral volume encompassed 1 cm around the celiac, SMA, superior mesenteric vein (SMV) and included the common hepatic artery and medial portal vein. For tail tumors, the body and tail of the pancreas were included, along with the splenic vessels and the takeoffs of celiac and SMA. Detailed dose prescription and normal organ constraints will be provided at time of presentation. Conclusion Through multidisciplinary and international collaboration from pancreatic cancer experts, we created consensus contouring guidelines for dose-escalated pancreatic cancer radiotherapy, reflecting current knowledge of recurrence patterns, and considering novel treatment techniques. These volumes can be used to standardize practice across clinical settings and in prospective trials seeking to define the role of radiotherapy in pancreas cancer.

Purpose/Objective(s) In patients with resectable pancreatic ductal adenocarcinoma (PDAC) who undergo neoadjuvant therapy, the “A-B-C-D-E” classification was developed to prognosticate patient outcomes based on CA19-9 dynamics. In this schema, type A represents an always decreasing CA19-9 level to normalization; type B, bidirectional CA19-9 dynamics to normalization; type C, a consistently normal level; type D, any decrease without normalization; and type E, a rising CA 19-9. Whether such a system applies to prediction of outcomes in patients undergoing definitive chemoradiation (CRT) after upfront chemotherapy in the unresectable setting is unclear. As such, we herein report CA 19-9 dynamics during CRT and describe the association of CA 19-9 response types with prognosis in patients with unresectable PDAC. Materials/Methods Patients diagnosed with localized PDAC who received neoadjuvant chemotherapy followed by consolidative chemoradiation between 2018 and 2023 who were ultimately not resection candidates were included. CA 19-9 measurements from time of diagnosis through completion of CRT were analyzed and grouped into CA 19-9 response types based on the “A-B-C-D-E” system. Overall survival (OS) and progression-free survival (PFS) were measured from completion of radiotherapy. Kaplan-Meier analysis was used to estimate event probabilities. Outcomes were compared using the log-rank test. Cox proportional hazards regression analysis was used for univariable analysis. Results Thirty-eight patients with BRPC or LAPC treated with neoadjuvant chemotherapy followed by consolidative chemoradiotherapy who ultimately were not resected were eligible for analysis. Most patients (N = 36, 95%) received either neoadjuvant FOLFIRINOX or gemcitabine-based chemotherapy and capecitabine monotherapy concurrent with radiotherapy. Median baseline CA 19-9 was 124.1 U/ml. Median OS and PFS were 8.3 months and 2.2 months, respectively. Using the A-B-C-D-E classification, patients were grouped into two categories: CA 19-9 dynamics with normalization (A, B, and C) and without normalization (D, E). Median OS for response types with CA 19-9 normalization was 27.5 months and 6.5 months for response types with failure of CA 19-9 normalization (p = 0.017). Median PFS for response types with normalization was 4 months and 1.8 months for response types without normalization (p = 0.037). On univariate analysis, response types with CA 19-9 normalization was significantly associated with improved OS (p = 0.024, HR = 3.126, 95% CI = 1.164-8.397) and PFS (p = 0.043, HR = 2.238, 95% CI = 1.025-4.886) as compared to response types without CA 19-9 normalization. Conclusion The clinical utility of CA 19-9 in unresectable PDAC as a prognostic biomarker is not well characterized. By using the A-B-C-D-E classification of CA 19-9 dynamics during neoadjuvant chemotherapy, this study demonstrates that response types with CA 19-9 normalization are associated with improved OS and PFS in this setting.

Purpose/Objective(s) Proximity of organs at risk (OAR) has led to interest in protracted-fractionation (PF: 15 to 25 fractions) courses employing moderate hypofractionation (MHF: 3-4 Gy/fraction) for the treatment of pancreatic adenocarcinoma, as an alternative to the limitations of classical SBRT. However, underdosing of target volumes near their interfaces with OARs is still seen even with PF-MHF courses. The impact of compromised (relative to the prescription dose) target coverage and global target dose heterogeneity on tumor control probability is an active area of investigation. We report our institution’s initial treatment planning experience with PF-MHF in pancreatic cancer. Materials/Methods We retrospectively reviewed radiation courses for pancreatic cancer planned with a PF-MHF approach: 45 Gy in 25 fractions (1.8 Gy/fraction) to PTV with 75 Gy (3 Gy/fraction) as an integrated boost to the GTV. We included patients treated with unresected disease as well as patients treated for local recurrence following surgery. We then collected describing dosimetric parameters for the GTV: D99.9%, D0.1cc, Dmean, V75, and V60Gy. To assess global DVH characteristics, we also calculated the generalized equivalent uniform dose (gEUD) value, using two different a values (-5 and -15). For the intact pancreas plans, we evaluated whether the gEUD differed depending on the location of tumor (head/uncinate versus body/tail). Results There was a total of 27 plans included in our analysis: 15 and 12 intact and resected pancreas plans, respectively. The median and range of collected dosimetric parameters are as follows: D99.9% 50.1 Gy (35.0 – 77.2 Gy), D0.1cc 81.3 Gy (77.9 – 91.6Gy), Dmean 74.7 Gy (70.8 – 78.6 Gy), V75 Gy 71.2% (50.99 - 100%), and V60 Gy 92.48% (79.28 – 100%). Assuming an a value of -5 and -15, the median (range) gEUD values were 71.0 Gy (61.5 – 78.6 Gy) and 63.2 Gy (49.4 – 78.6 Gy), respectively. For the intact pancreas plans, there were no statistically significant differences in the mean gEUDs between head/uncinate (n = 7) and body/tail (n = 8) plans even if factoring in the GTV volumes. Conclusion Although the dose was escalated within the GTV, the relatively low coverage by the prescription dose, and correspondingly low gEUD values, especially for highly negative a values, illustrate that the PF-MHF approach is associated with numerically significant dosimetric compromise. One consideration is to prioritize gEUD optimization for further refinement. Continued investigation of how dose heterogeneity impacts local control is also warranted.

Purpose/Objective(s) The role of neoadjuvant radiation therapy (NRT) for pancreatic ductal adenocarcinoma (PDAC) is poorly defined. The publication of the Phase II Alliance A021501 clinical trial (AT), evaluating the role of neoadjuvant SBRT for PDAC patients, may have resulted in a non-uniform shift in practice patterns across the country. Founded in 2019, the Canopy Cancer Collective (CCC) is the first oncology learning health network to improve PDAC outcomes and to discuss best practices. Herein, we report how NRT practice patterns (CCC database), and physician opinions (survey) were impacted by the AT. Materials/Methods A survey of the impact of A201501 on NRT SBRT practice patterns in PDAC was distributed to 17 radiation oncology (RO) faculty across 14 CCC sites. To assess the AT impact in a more objective manner, the CCC patient registry was also queried and the de-identified limited-field data was analyzed under CCC data sharing agreements. Results The survey was completed by 78% cancer centers and 82% RO faculty. Overall, 71.5% faculty reported no change in their confidence in benefit of NRT in borderline resectable PDAC patients due to the results of the AT, and 43% reported no impact on the utilization of neoadjuvant SBRT. Forty three percent reported decreased SBRT utilization and 14% no longer offer SBRT. The two latter groups reported favoring either dose-escalated (33%) or standard chemoradiation (44%) over SBRT. Fifty seven percent reported no impact on their utilization of pancreas SBRT for all PDAC patients and the remaining 43% reported offering SBRT less often. Among 4,512 PDAC patients recorded in the CCC registry between 1/2020 and 2/2024, the median age was 60.5 years (range = 57-64). Fifty two percent of the patients were male and 85% had good performance status (ECOG 0-1). Among those, 608 patients had a surgery between 1/2020-12/2023 and 90 (15%) underwent NRT. Of those, 10% were staged resectable, 40% borderline resectable, and 37% locally advanced. SBRT was the NRT of choice in 50% of resectable, 60% of borderline resectable and 75% of locally advanced stages. The ratio of NRT to surgery has declined since 2020: 20% (9/44) in 2020, 15% (16/105) in 2021, 17% (44/253) in 2022, and 10% (21/206) in 2023. However, 69% (62/90) of these NRT patients were treated with SBRT and its utilization has consistently increased since 2020: 44% in 2020, 62% in 2021, 70% in 2022 and 80% in 2023. Conclusion There is less enthusiasm among ROs regarding NRT in PDAC, but when offered in our CCC sites, SBRT is increasingly chosen over conventional fractionation. There is a paucity of randomized neoadjuvant trials to address this area of ongoing debate.

Purpose: The administration of dose-escalated radiation for pancreatic adenocarcinoma remains challenging because of the proximity of dose-limiting stomach and bowel, particularly the duodenum for pancreatic head tumors. We explore whether endoscopic injection of a temporary, absorbable hydrogel into the pancreatico-duodenal (PD) groove is safe and feasible for the purpose of increasing spatial separation between pancreatic head tumors and the duodenum. Methods and Materials: Six patients with localized pancreatic adenocarcinoma underwent endoscopic injection of hydrogel into the PD groove. Safety was assessed based on the incidence of procedure-related adverse events resulting in a delay of radiation therapy initiation. Feasibility was defined as the ability to create spatial separation between the pancreas and duodenum, as assessed on simulation CT. Results: All 6 patients were able to undergo endoscopic injection of hydrogel into the PD groove. No device-related events were experienced at any point in follow-up. Presence of hydrogel in the PD groove was apparent on simulation CT in all 6 patients. Mean space created by the hydrogel was 7.7 mm +/- 2.4 mm. In 3 patients who underwent Whipple resection, presence of hydrogel in the PD groove Conclusions: Endoscopic injection of hydrogel into the PD groove is safe and feasible. Characterization of the dosimetric benefit that this technique may offer in the setting of dose-escalated radiation should also be pursued, as should the ability of such dosimetric benefit (c) 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Purpose/Objective(s ): To report on patient characteristics and external beam radiotherapy treatment patterns among patients treated definitively for primary breast cancer at a major cancer center in Rwanda since the inception of the cancer center. Materials/Method s: The cohort included patients receiving radiotherapy for primary breast cancer from 8/2018 to 1/2024 at a major cancer center in Rwanda. All patients received external beam radiation (EBRT) in the form of volumetric arc therapy (VMAT) in the definitive setting. Patients received systemic therapy in either the neoadjuvant or adjuvant setting at the discretion of the treating teams. Patient characteristics, prognostic markers, and treatment patterns and fractionation regimens, were identified and analyzed. Result s: 290 patients met inclusion criteria. Median age was 52 years (range 25 – 95 years). 143 (49%) tumors were left breast and 147 (51%) were right breast. Median distance traveled to and from the hospital for care was 47km (range 10km-1100km). 8.5% of patients held private health insurance only, another 8.5% of patients had a combination of public and private insurance, and the majority of patients (83%) were solely publicly insured. The median number of children per patient was 4, median weight in kg was 70.5, and median age at menarche was 15 years.166 (57%) patients were status post mastectomy and underwent chest wall RT. Of these patients, 157 (95%) also underwent lymph node RT. There were 123 (42%) patients post breast conserving surgery who underwent whole breast RT. Of the patients treated with whole breast RT, 80 (65%) patients also underwent lymph node RT. Additionally, 34 (28%) of these patients underwent tumor bed boost as part of the whole breast RT regimen. Of the 290 total patients, 1 underwent axillary RT only (0.3%). Regarding fractionation regimen, 223 (77 %) patients received 50 Gy in 25 fractions, 58 (20%) patients received 40-42 Gy in 15-16 fractions, and 9 (3%) patients received 16-32 Gy in 5-10 fractions. Conclusio n: Our institution is a critical resource for cancer treatment in the region. Over half of our primary breast cancer patients present in the post-mastectomy setting. Most patients with primary breast cancer who present to this center underwent standard fractionation treatment regimens with regional nodal irradiation.

For pancreatic cancer patients that undergo neoadjuvant chemoradiation followed by oncologic resection of the primary tumor, mutations in key biological pathways are associated with OS and PFS. Characterizing the importance of common pathway mutations may become increasingly valuable to help categorize less commonly mutated genes assayed by NGS.

RGPT successfully tracked fiducial marker motion for DIBH SBRT liver treatment. Despite target drift during DIBH, the uncertainty of our DIBH SBRT procedure was sufficient to cover target motion throughout treatment. Based on the target drift value, a maximum of 25 seconds for breath hold time should be employed. Utilizing a tighter gating tolerance of 3 mm SI and 2 mm radially has the potential to maintain target coverage while significantly reducing OAR dose. Aggregated RGPT-derived data may provide optimal treatment planning parameters such as variable uncertainty based on target location.

Local therapy in patients with post-transplantation oligorecurrence (<3 mets) of HCC may delay disease progression and improve survival.

Few pancreatic cancer trials involving RT report local TTE endpoints, with significant heterogeneity in endpoints used and their definitions. Development of consensus endpoint definitions will be critical for future PDAC trial design.

IMPROVE is a prospective multicenter pilot study. It evaluates whether routine physician review of patient-reported outcomes measures (PROMs) during radiotherapy alters physicians' perception of cancer patients' treatment-related toxicity and influences symptom management.We are enrolling patients with thoracic or gastrointestinal cancers amenable to conventional-fractionated radiotherapy. Patients may receive concurrent chemotherapy. Patients report (1) symptoms, using PRO-CTCAE measures, (2) the most burdensome symptom, and (3) how symptoms interfere with daily activities. Patients complete the measures before seeing their physician during each on-treatment visit. During weekly visits and before reviewing the patient's PROMs, physicians rate the symptom burden for each patient from 0 to 10, using available clinical data. These data include vital signs, lab work, physical exams, nursing assessments, and physicians' clinical judgment. After reviewing the patients' PROMs, physicians re-rate each patient's symptom burden and report any changes in recommended interventions. Changes could include (1) additional counseling, (2) new medications or interventions, (3) referrals to other services, or (4) further testing or evaluation. After each patient's course of radiotherapy, providers complete a Clinician Feedback Form about the impact of PROM review on symptom perception and management during treatment. This study commenced November 11, 2020 at a multi-site tertiary academic cancer center (using electronic or paper questionnaires) and July 21, 2021 at a multi-site community cancer center (using paper forms).To be determined.To be determined.

Compared to historical data, pre-operative RT does not appear to significantly increase the risk of PsA development after PD. More data on the impact of pre-operative radiation dose-fraction regimen and longer follow-up are needed.

The proposed platform has been successfully utilized for precision setup for FLASH IORT in a preclinical laboratory setting. Evaluation of FLASH effects in IORT setup will be an important step in the potential translation of FLASH IORT, where only one high-dose fraction can be delivered.

In patients with localized PDAC who undergo pre-operative SBRT for BRPC/LAPC, targeting the TV may help reduce locoregional recurrence. More data and longer follow-up are needed to verify these findings and inform whether the TV may serve as a new standard for target volume delineation in this setting.

Herein, we characterized the frequency of somatic mutations associated with DSB repair genes in patients with BRPC/LAPC. Data analysis on outcomes related to radiation response in patients with mutations in DDR pathways is ongoing, but will likely also benefit from multi-institutional efforts to increase the power to answer this question.