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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Stereotactic ablative radiotherapy (SAbR) is commonly used for the treatment of gastrointestinal (GI) cancers. However, proximity to organs at risk (OARs) or retreatment can limit the safe delivery of SAbR. Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) is a strategy to deliver SAbR in pulses separated by 1-4 weeks to allow for adaptation, lower risk to OARs, and leverage potential benefits of immune responses. Here we present our initial experience with PULSAR for the treatment of patients with GI cancer. A single center retrospective study was conducted comprising all patients with GI cancer treated with PULSAR between 2020 and 2023. Eligibility for PULSAR treatment included retreatment after prior SAbR, palliation, treatment of high toxicity risk area, or continuation of systemic therapy during radiotherapy. Following an MR or CT simulation, patients were treated with 3 to 5 fractions administered at intervals of at least one week. Adaptive plans were created to preserve OAR constraints, account for change in tumor size, and/or escalate PTV dose, based on re-imaging for selective pulses. Treatment schedules, dosimetric features, and patient outcomes were reviewed. Twenty-two patients were treated with PULSAR, 73% for pancreaticobiliary cancer, and 50% for metastatic cancer across several sites (pancreas, colorectal, anus). Treatment intent was definitive in 64% (14). The most common indications for PULSAR were reirradiation after SAbR (n = 8, 36%) and high toxicity risk due to adjacent OARs (n = 8, 36%). Median total dose was 4000 cGy (range = 2400-5000), The median number of administered pulses was 5, at different schedules; monthly- 36% (8), biweekly- 32% (7), weekly- 27% (6), and every 3 weeks- 5% (1). Three patients were treated with online adaptive radiotherapy on MR-Linac and 5 patients with adaptive CT-Linac. The median PTV volume and margins were 37.67 cc (range = 15.7-1284.3) and 3 mm (range = 0-5), respectively. Concurrent systemic treatment was given to 36% (8), including chemotherapy (CHT) for 7 patients and immunotherapy for one patient. The median follow-up was 6.4 months. Two months after completion of treatment 18%, 35%, and 29% of evaluated patients had complete, partial response, and stable disease, respectively. Median overall survival (OS) was 20 months (95% CI), and progression-free survival (PFS) was 11.5 months (95% CI). Three patients (14%) progressed in the RT field within a median time of 11 months (range = 4-12). Acute grade 1-2 GI toxicity occurred in 18% of patients (4). One patient with pancreatic cancer and preexisting ulcer on anticoagulation had a grade 4 GI hemorrhage 2 months after treatment. The results of this patient series suggest that PULSAR used to treat GI cancers can safely deliver sufficient radiotherapy dose to achieve local control, especially in high-risk patients. Further prospective studies to validate these findings and better elucidate the benefits of PULSAR are warranted. [ABSTRACT FROM AUTHOR]

This work investigates the accuracy and consistency of three different breath-hold (BH) techniques for pancreatic cancer stereotactic ablative radiotherapy (SAbR). We hypothesize that surface-guided radiotherapy (SGRT)-based BH techniques can improve internal positional target accuracy and treatment efficiency compared to conventional spirometry-based deep inhalation breath hold (DIBH) for pancreatic SAbR. Treatment accuracy and efficiency were analyzed for 36 pancreatic cancer patients that underwent 5-fraction SAbR, 12 with active breathing coordinator (ABC)-enabled DIBH, 13 with SGRT-based DIBH, and 11 with SGRT-based expiration BH (ExBH). In the ABC DIBH workflow, respiratory motion was monitored via spirometry by comparing the inhalation volume to a set threshold. In SGRT-based BH, the live patient surface was compared to a reference surface with 3-mm and 3-degree limits for translational and rotational variations. For each patient, 1 to 6 implanted fiducials were used as the surrogates of the true target position for beam gating during treatment delivery. For each beam-on and every 30 degrees of gantry rotation thereafter, a triggered kilo-voltage (kV) image was acquired, and the fiducials were automatically detected and compared to their expected positions. Beam-on only occurred when triggered imaging verified that the fiducials were within a 3-mm margin, thus excessive BH attempts would translate to longer treatment time. To compare the targeting accuracy and precision between different breath hold techniques, the superior-inferior (SI) deviations (the only resolvable direction from 2D kV imaging) of the fiducials from their reference locations were extracted from over 1000 triggered kV images. Treatment efficiency was quantified via patient in-vault time tracked by an in-house Bluetooth-based real-time location system. SGRT ExBH and DIBH were found to be more accurate and consistent with 81.9% and 82.5% of the fiducial deviations within 3 mm (the typical PTV margin for pancreatic SAbR) and average fiducial locations of -0.07 ± 2.36 mm and 0.12 ± 2.46 mm, compared favorably with 68.1% and -1.11 ± 3.28 mm for ABC DIBH. Patients treated with SGRT-based BHs on average spent 8 minutes less in the vault with more consistent treatment durations (average in-vault time of 49 ± 11 minutes, 48 ± 11 minutes, and 56 ± 19 minutes for SGRT ExBH, SGRT DIBH, and ABC DIBH, respectively). In addition to facilitating faster and more uniform treatments, SGRT-based breath-hold techniques improved targeting accuracy and precision for pancreatic cancer SAbR as validated by intra-fractional fiducial tracking, proving its capacity as a viable replacement for spirometry breath hold techniques. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) for localized pancreatic ductal adenocarcinoma (PDAC) remains controversial, with conflicting data likely resulting in variable practice patterns. The Canopy Cancer Collective (CCC) is a learning health network of 14 institutions with high-volume multidisciplinary PDAC teams. To characterize the current state of RT for PDAC at high-volume, academic centers, radiation oncology faculty at CCC member institutions were surveyed. A survey focusing on RT practice patterns for localized PDAC was distributed to 18 faculty with expertise in gastrointestinal RT at CCC sites. Survey results are descriptively reported. The survey was completed by 17/18 (94%) faculty. Among respondents, the number of localized PDAC patients treated per year with RT included >50 (n=5, 29%), 26-50 (n=8, 47%), 10-25 (n=3, 18%), and <10 (n=1, 6%). Two (12%) respondents reported that they routinely offer pre-operative RT for resectable PDAC. Majority of respondents (n=15, 88%) indicated that pre-operative RT is offered to certain patients with borderline resectable pancreatic cancer (BPRC), but the specific proportion of BRPC patients receiving pre-operative RT was variable across respondents (median 70%, range: 10-100%). Similarly, majority of respondents (n=16, 94%) indicated that RT is offered as definitive treatment for certain patients with locally advanced pancreatic cancer (LAPC), but the specific proportion of LAPC patients receiving RT was also variable (median 80%, range: 20-100%), as was the estimated proportion of LAPC patients who eventually undergo resection (median 25%, range 2-50%). Table 1 summarizes the distribution of preferred planning techniques and target volumes used by respondents in both the pre-operative and definitive settings. Variation was also seen in use of fiducials (n=12, 71%), preferred motion management strategy (breath-hold: n=12, 71%; gating: n=5, 29%), systematic use of adjunctive imaging beyond CT for target delineation (MRI: n=6, 35%; PET: n=3, 18%), and use of prophylactic anti-emetics (n=5, 29%) and proton pump inhibitors (n=11, 65%). RT practice patterns for the treatment of localized PDAC remain disparate, with significant variation in institutional standards across stage of disease as well as in basic treatment parameters such as prescription dose and target volume design. A better understanding of the basis for such variation may help guide future avenues of study. [ABSTRACT FROM AUTHOR]