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For patients with oligometastatic colorectal cancer (CRC), aggressive local therapy of isolated metastases, particularly in the liver, has been associated with long-term progression-free and overall survival (OS) primarily based on retrospective evidence. However, in patients with limited metastatic CRC that is deemed inoperable or those with additional disease outside of the liver or lungs, the role of local ablative therapies, including microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), to render patients disease free is less clear. Further, despite the long history of treating oligometastatic CRC with local therapy, which is provider biased and not evidence based, questions remain regarding the benefit of extending the paradigm of metastatic directed therapy to patients with more extensive disease. This trial seeks to use a pragmatic multimodality approach that mirrors the current clinical dilemma. This study is designed to evaluate the safety and efficacy of adding total ablative therapy (TAT) of all sites of disease to standard of care systemic treatment in those with limited metastatic CRC. A022101/NRG-GI009 is a National Clinical Trials Network randomized phase III study planned to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable) with ≤4 sites of metastatic disease on baseline imaging. Liver-only metastatic disease is not permitted, and lesions must be amenable to any combination of surgical resection, MWA, and/or SBRT with SBRT required for at least 1 lesion. Patients receive first-line systemic therapy for 16-26 weeks and are then randomized 1:1, stratified by number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and presence of metastatic disease outside the liver/lungs in at least 1 site. Patients in Arm 1 will receive TAT consisting of treatment of all metastatic sites with SBRT ± MWA ± surgical resection followed by standard of care systemic therapy. Patients in Arm 2 will continue with standard of care systemic therapy alone. The primary endpoint is OS. Secondary endpoints include event-free survival, treatment-related toxicities, and local recurrence with exploratory biomarker analyses. The study needs 346 evaluable patients combined in the 2 arms to demonstrate an improvement in OS with a hazard ratio of 0.7 to provide 80% power with a one-sided alpha of 5%. The trial utilizes a group sequential design with two interim analyses (25% and 50% of events) for futility. The trial activated in January 2023 and recruitment is ongoing. TBD TBD [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) is associated with significant efficacy in the treatment of thoracic malignancies. Yet, it has been linked with potentially limiting cardiotoxicity, including anecdotal reports of profound hypertension (HTN) which may cause additional morbidity. Yet, the long-term incidence, and implications of HTN development in patients requiring thoracic RT are unknown. From a large cohort of consecutive patients with esophageal cancer treated with thoracic RT at a comprehensive cancer center from 2007 to 2019, we assessed the incidence and outcomes of new/incident or worsened HTN [systolic blood pressure (SBP) cutoff, 130 mmHg, based on AHA definitions]. New HTN was defined as elevated SBP post RT initiation on 2 consecutive outpatient visits 3 months apart or initiation of antihypertensive therapy; and worsened HTN as an increase in grade by Common Terminology Criteria for Adverse Events v5.0 or increase in antihypertensive therapy. Secondary outcomes included major adverse cardiovascular events (MACE), defined as arrhythmia, heart failure, myocardial infarction, stroke, and sudden death; as well as overall survival, by HTN status. Landmark analyses, excluding patients with elevated SBPs within 3 months prior to RT (undiagnosed HTN); and those treated with surgery were performed. Multivariate regression was used to define the relation between clinical and RT measures, and outcomes. Further, we assessed the effect of thoracic aorta RT dose on post-RT outcomes. Overall, 238 RT treated patients (82.8% male; median age 63) were identified. Most patients had lower esophageal/gastroesophageal junction (GEJ) tumors (86.9%), T3-4 (78.2%), node positive disease (67.2%), and adenocarcinoma diagnosis (83.6%). Over a median follow-up of 33 months, 55.9% developed new or worsened HTN (median time to HTN, 4 months; median SBP increase 8.9 mmHg). Cumulative incidence of new or worsened HTN by 1 year was 28.8%, and 52.1%, respectively. In landmark analysis, excluding those with undiagnosed HTN, the cumulative incidence of new or worsened HTN was 29.1%, and 45.8%, respectively, by 1 year. On multivariate analysis, only higher disease stage and IMRT-use associated with incident HTN development (P <0.05). Aorta V5 RT-dose trended toward association with incident HTN (P = 0.06). Whole heart (V5, V10), left atrium (V5, V10, V15, V20), age, and lower use of IMRT were most consistently associated with MACE (P <0.05 for all). In multivariate models, outside of traditional factors, incident HTN remained associated with improved overall survival (HR: 0.48, P<0.001). This relation remained even after accounting for surgical resection and disease related factors. Among patients with esophageal cancer, RT increases HTN risk even within 1-year of treatment. The development of HTN appears to confer a protective effect on long-term survival. [ABSTRACT FROM AUTHOR]

Patients with a Child-Pugh score (CP) of B7 or higher are under-represented in otherwise robust prospective data supporting the use of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). We report the outcomes and toxicity after SBRT for CP ≥B7 HCC patients. HCC patients with CP ≥B7 who received liver SBRT at our center 2015-2022 were included. Patients were treated with fiducial-less, photon based SBRT using 4D-CT with abdominal compression. The primary endpoint was overall survival (OS). Secondary endpoints were decline in CP score by ≥2 points at 6 months, freedom from local progression (FFLP) defined as progression of treated lesion, intrahepatic progression free survival (IH-PFS, progression outside of treated lesion), and distant PFS. Kaplan-Meier method was used for survival estimates and Cox proportional hazards models for intergroup comparisons. Thirty-one HCC patients with CP ≥B7 were included. Median age was 67.7 years (range = 33.5 – 85.9), 29% patients were ECOG≥2, 45% had macrovascular invasion (MVI), and 65%, 23%, 6% and 6% patients were CP classes B7, B8, B9 and C10, respectively. The median maximal tumor dimension was 5.3 cm (range = 2.0 – 16.9), and the median gross tumor volume (GTV) was 79.9 cc (range = 11.3 – 1771.6). Median radiation (RT) dose was 40 Gy (range = 22.5 – 50) in 5 fractions, with 8 patients receiving a biological equivalent dose (BED) > 100 Gy, and 39% receiving systemic therapy. SBRT was well tolerated with 26% patients having any grade toxicity (most commonly nausea; 16%) and no ≥ grade 3 toxicity. None had classic radiation-induced liver disease. The median OS and 1-year OS rate were 7.6 months and 35%, respectively. On univariate analysis, higher RT dose (Hazard ratio (HR) 0.76; 95% CI = 0.60-0.96), BED>100 Gy (HR = 0.20; 95% CI = 0.04-0.60), higher GTV Dmean (HR = 0.95; 95% CI = 0.91-0.99), and lower Liver Dmean (HR = 0.88; 95% CI = 0.80-0.97) were associated with significantly improved OS (all p<.05). Higher Liver-GTV Dmean increased the risk of death, but the difference was not statistically significant (HR = 1.14; 95% CI = 1.00-1.30; p = 0.06). FFLP, IH-PFS, and distant PFS at 1 year were 83%, 51% and 82%, respectively. About 58% patients had any increase in CP score, with 26% increasing by ≥2 points. The increase in CP score was independent of tumor size, performance status, MVI, RT dose, or baseline cirrhosis. Liver-GTV Dmean was higher in patients with increase in CP ≥2, but not statistically significant (15.0 Gy vs 12.8 Gy, p = 0.06). Two patients had a liver transplant after SBRT, with a 1-year OS of 100%. SBRT for CP ≥B7 patients is well tolerated and provides excellent local control. Higher tumor BED and lower dose to normal liver improved OS in our patient population. SBRT should be considered in the multidisciplinary treatment of advanced HCCs as well as a bridge to transplant for these patients. Enrollment in prospective clinical trials should be considered. [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]