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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]

Transarterial chemoembolization (TACE) is an option for downstaging or definitive therapy in Hepatocellular Carcinoma (HCC) according to the Barcelona Liver Classification (BCLC) guidelines. However, there has been considerable recent prospective evidence establishing the efficacy of external beam radiation (EBRT) as a non-invasive alternative. The objective of this study was to conduct a systematic review and meta-analysis of prospective randomized clinical trials to assess the clinical efficacy and safety of EBRT versus TACE for HCC as either a definitive therapy or as a bridge to transplant/surgery. We conducted a systematic review of the literature that included prospective randomized controlled trials comparing EBRT vs TACE in patients with HCC who were ineligible for upfront surgical resection or transplant that required either definitive therapy or downstaging prior to transplant. For EBRT both protons or photons as hypofractionation were allowed. Trials comparing EBRT vs TACE with progression after previous local therapy were allowed. Covidence, a software which pulls sources from PubMed and Embase, was used for the screening process. A random effects model was used for the meta-analysis. Outcomes analyzed included local control (LC), overall survival (OS), and progression free survival (PFS). Comparisons are reported as hazard ratios (HRs) with associated 95% confidence intervals. Relative Risk Ratios were used for grade 3+ toxicity was analyzed with the risk ratio of the number of occurrences of grade ≥ 3 toxicity in each group from each study. The inconsistency index (I2) assessed heterogeneity. Two authors independently screened 608 publications. Of these, after title screen and duplicate removal, only 3 studies met criteria for full text review with a total of 143 participants. This included the TRENDY trial, the Bush trial, and the Comito trials. The studies included patients with BCLC A or B disease, as none allowed macrovascular invasion. The EBRT protocols of the studies ranged from 3 to 15 fractions with a total dose of 30 to 75 Gy. The meta-analysis demonstrated that EBRT was associated with significantly improved LC over TACE (HR: 0.16, 95% CI = 0.08 to 0.34; I2 = 0%). There was no statistically significant difference in OS between EBRT and TACE (HR: 0.52, 95% CI = 0.26-1.02; I2 = 51%). EBRT was associated with improved PFS over TACE (HR: 0.37, 95% CI = 0.23-0.60; I2 = 0%). EBRT did not have a statistically significant difference in toxicity from TACE (RR: 0.86, 95% CI = 0.31-2.37; I2 = 57%). None of the analyses had statistically significant heterogeneity. The advantages of EBRT should be strongly considered and discussed as a first line option for patients with HCC ineligible for upfront surgical resection or as a bridging therapy. Additional prospective randomized controlled trials should be conducted to further investigate differences in outcomes along with additive combinations with systemic therapy. [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]