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ABSTRACT Background Multimodality therapy incorporating a combination of cytoreductive surgery (CRS), intraperitoneal (IP) and systemic therapy continues to evolve for peritoneal carcinomatosis (PC) However, treatment and outcomes vary depending on tumor of origin. Aims To develop Appropriate Use Criteria (AUC) guidelines to facilitate treatment decision‐making for patients with PC based on available evidence. Materials and Methods The American Radium Society (ARS) multidisciplinary expert panel performed a comprehensive systematic review. Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) methodology was used. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in seven representative clinical scenarios through a well‐established modified Delphi consensus methodology. Results Treatment of PC is often treated with a combination of CRS and IP ± systemic chemotherapy but specific recommendations exist for different tumor types and outcomes vary. Discussion Treatment of PC is complex and varies depending on origin of primary tumor and extent of disease. These AUC assist in patient and treatment selection for different clinical scenarios. Conclusion A summary of recommendations is outlined to guide practitioners on the management of PC from different tumor origins.

Objectives: Esophageal cancer (EC) often presents with dysphagia due to tumor obstruction. Esophageal stenting has the potential of palliating dysphagia, improving nutrition, preventing aspiration, and improving quality of life (QoL) but may be associated with risks. The present systematic review and guidelines are intended to assist treatment decision-making when considering stent placement in patients with EC based on the available evidence. Methods: Using the population, intervention, comparator, outcome, timing and study design framework, the evidence was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included prospective phase II-III trials and retrospective analyses published between January 1, 2010 and December 3, 2024 in the Ovid Medline database. These references were assessed by American Radium Society (ARS) Appropriate Use Criteria (AUC) methodology. RAND-UCLA consensus methodology was used to rate the appropriateness of the use of stents. Results: ARS AUC recommendations include (1) esophageal stenting is usually not appropriate in patients with early-stage EC in whom upfront surgery is planned; (2) esophageal stenting is usually not appropriate in patients with locally-advanced EC in whom neoadjuvant/perioperative therapy and esophagectomy or definitive chemoradiation is planned; (3) esophageal stenting may be appropriate in the setting of metastatic EC, especially in patients with short life expectancy with limited treatment options; (4) esophageal stenting is usually not appropriate for benign stricture following curative-intent therapy; (5) esophageal stenting is usually not appropriate for locally recurrent tumor in the setting of prior radiation; and (6) esophageal stenting is usually appropriate for management of tracheoesophageal fistula before curative-intent treatment. Conclusions: This ARS AUC summary provides guidelines for the use of esophageal stents in patients with EC provides based on available evidence.

Objectives: Cervical esophageal cancer (CEC) is an uncommon malignancy accounting for <5% of all esophageal carcinomas. Treatment of CEC varies and is adapted from established regimens used for squamous cell carcinoma (SCC) or the lower esophageal and head and neck. The present systematic review and guidelines are intended to assist treatment decision making for patients with CEC based on the available evidence. Methods: Using the Population, Intervention, Comparator, Outcome, Timing, and Study Design (PICOTS) framework, the evidence regarding treatment outcomes was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included prospective Phase II to III trials and retrospective analyses published between January 1, 2013 and February 23, 2024 in the Ovid Medline database. These references were assessed through the American Radium Society (ARS) Appropriate Use Criteria (AUC) methodology. A systematic review PRISMA 2020 checklist confirmed the completion of essential elements. RAND-UCLA consensus methodology was used by the expert panel to rate the appropriateness of the treatment options. Results: ARS AUC recommendations include (1) larynx preservation using endoscopic resection (EMR or ESD) alone for the typical case with pT1a cN0 cM0 CEC, (2) definitive CRT for the typical case with cT1bN0M0 in patients who cannot undergo endoscopic resection, (3) larynx-preserving using definitive CRT (with or without induction chemotherapy) for the typical case with nonmetastatic locally advanced CEC (advanced T-stage tumors or involved lymph nodes), with surgery reserved for those patients with incomplete response or locoregional recurrence. Conclusions: This ARS AUC summary provides guidelines for the management of SCC of the cervical esophagus provides based on available evidence. Topics that warrant further investigation include optimization of (1) patient selection; (2) multimodality therapies including chemotherapy, immunotherapy, and targeted agents; (3) radiation dose, schedule, and treatment volume; and (4) supportive care for patients with CEC. Ongoing trials continue to improve outcomes for patients with CEC.

(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan–Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar’s test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions.

3553 Background: Immuno-STATs are modular fusion proteins designed for the selective activation of tumor antigen specific CD8+ T cells. CUE-102, the second Immuno-STAT in clinical trials, is composed of a human leukocyte antigen (HLA) complex, HLA-A*0201, a peptide epitope derived from the Wilms Tumor 1 (WT1) protein, and 4 molecules of reduced affinity human interleukin-2 (IL-2). In preclinical studies CUE-102 binds, activates and expands WT1-specific CD8+ T cells with the potential to enhance anti-tumor immunity in patients with WT1+ cancers. Here we present the results of the dose-finding portion (Part A) of the CUE-102-01 study. Methods: CUE-102-01 is a 2 part phase 1 study. HLA-A*02:01 positive patients with WT1+ advanced colorectal (CRC), gastric (GA) and gastroesophageal junction (GEJ), pancreatic (PDAC) or ovarian (OvCa) tumors refractory to standard therapies were eligible for participation. WT1 status is determined by IHC via central testing. CUE-102 monotherapy was administered intravenously every three weeks in doses ranging from 1 mg/kg to 8 mg/kg following 3+3 design rules with a Bayesian Logistic Regression Model overlay. Dose levels that exhibit an immune or tumor response may be expanded to further characterize activity and toxicity as allowed by safety rules. Results: Dose escalation was successfully completed in 28 patients with CRC (17), PDAC (6), GA/GEJ (3) and OvCa (2). No DLTs were observed. Three dose levels (2, 4 and 8 mg/kg) exhibited evidence of immune activity and were expanded up to 9 patients each for further evaluation. CUE-102 was well-tolerated with > 96% of treatment-related adverse events (TRAEs) grade ≤2. The most common TRAEs, were fatigue, infusion reactions, nausea and vomiting. There were no cases of CRS Grade ≥ 2. Preliminary PK data demonstrate dose dependent increases in exposure across the dose range assessed. Preliminary analysis of patient samples demonstrates selective expansion of WT1-specific CD8+ T cells. Stable disease of ≥ 6 weeks (range 6-36 weeks), as determined by RECIST 1.1, has been observed in 10 of 23 patients (DCR 43.5%). Conclusions: CUE-102 is a novel T cell engager that demonstrates acceptable tolerability, favorable PK, and supportive preliminary PD readouts. No DLTs or drug-related SAEs have been observed in doses up to 8 mg/kg as of the data cut-off. Adverse events have been manageable and consistent with the CUE-102 mechanism of action and underlying disease. Early signs of disease stabilization and anti-tumor activity in late-stage patients are encouraging. Part B is a dose expansion that further evaluates safety, PK/PD, recommended phase 2 dose (RP2D), antitumor efficacy and is currently enrolling patients. Clinical trial information: NCT05360680 .

736 Background: Patients with dMMR/MSI-H gastrointestinal (GI) cancer occasionally receive neoadjuvant immunotherapy (NIT) due to various clinical considerations. To systematically evaluate the outcome of these patients, we initiated the DREAM-GI national database, intending to harness real-world data to provide crucial insights into the outcomes, safety profile, and response patterns of dMMR/MSI-H GI cancer patients undergoing NIT. Herein, we present the initial findings. Methods: We developed a centralized database to collect de-identified clinical data from patients with dMMR/MSI-H GI cancers receiving NIT. We collected data retrospectively and prospectively through September 15, 2023. Results: The current report includes 50 patients with a median age of 67 years (range 32 to 90); 21 (42%) were female, 9 (18%) were Black, and the remaining were White. The cohort included the following tumor types- 31 (62%) colorectal, 7 (14%) gastroesophageal, and 12 (24 %) pancreaticobiliary. Most patients had localized disease (34, 68%), while the rest had oligometastatic disease. NIT consisted of pembrolizumab monotherapy in 40 (80%) patients, ipilimumab plus nivolumab in 8 (16%), and nivolumab plus chemotherapy in 2 (4%) patients. Most patients, 33 (66%), were treatment-naive. The median duration of NIT was 6 months (range: 1.5 to 55), with a time to best response of 3 months (range: 1.5 to 12). Among 47 evaluable patients, the best responses were as follows: an overall response rate of 75% (35/47), consisting of radiologic complete response (CR) in 20 (43%), pathologic CR in 4 (9%), and partial response in 11 (24%). The median progression-free survival and overall survival were not reached after a median follow-up of 14 months (range: 2-80), calculated from the date of the first immunotherapy dose to the last follow-up or death. Among 24 patients achieving CR, all remained progression-free after a median follow-up of 25.5 months (range: 3-80). Stable and progressive diseases were observed in 7 (15%) and 5 (10%) patients, respectively. Only 5 (10%) patients underwent surgery following NIT, with 4 (80%) achieving pathologic CR. The reasons for not proceeding with surgery were comorbidities in 40 (80%) patients, disease extent in 4 (8%), and patient refusal in 1 (2%). Out of the 12 patients who expired at the data cut-off, 1 was due to immunotherapy-related pneumonitis, 6 due to disease progression, and the remainder from underlying comorbidities. Conclusions: Our study underscores the remarkable response rates and durability of responses achieved with NIT in patients with dMMR/MSI-H GI cancers. Progression on NIT was infrequent. These real-world data support further investigation into non-operative approaches for patients with dMMR/MSI-H GI cancers.

AbstractThe liver is a common site of cancer metastases. Systemic therapy is widely accepted as the standard treatment for liver metastases (LM), although select patients with liver oligometastases may be candidates for potentially curative liver resection. Recent data support the role of nonsurgical local therapies such as ablation, external beam radiotherapy, embolization, and hepatic artery infusion therapy for management of LM. Additionally, for patients with advanced, symptomatic LM, local therapies may provide palliative benefit. The American Radium Society gastrointestinal expert panel, including members representing radiation oncology, interventional radiology, surgical oncology, and medical oncology, performed a systemic review and developed Appropriate Use Criteria for the use of nonsurgical local therapies for LM. Preferred Reporting Items for Systematic reviews and Meta‐Analyses methodology was used. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in seven representative clinical scenarios through a well‐established consensus methodology (modified Delphi). A summary of recommendations is outlined to guide practitioners on the use of nonsurgical local therapies for patients with LM.

105 Background: Patients with potentially resectable dMMR/MSI-H colon cancer (CC) often receive neoadjuvant immunotherapy (IO) if co-morbid conditions or the extent of disease preclude upfront surgery. We investigated the outcome of such patients treated in a real-world setting. Methods: This is a single-center retrospective study that included patients with dMMR/MSI-H localized and oligometastatic CC receiving neoadjuvant IO between January 1, 2016, and July 31, 2022 with a data cut-off date of September 15, 2022. Electronic charts were reviewed to gather data on patient characteristics, tumor characteristics, detailed treatment, toxicity, treatment response, and survival. The response was assessed by radiologic studies, endoscopy, pathology in resected patients, and circulating tumor DNA. Results: The study included 24 patients with a median age of 69 years (range, 32 to 91); 12 (50%) patients were female, and 5 (21%) patients were African American. Among the patients included, 12 (50%) had localized CC (9 of whom had clinical stage III disease), and the rest had oligometastatic CC. The reasons for not undergoing upfront surgery were co-morbidity in 12 patients (50%), disease extent in 11 (46%), and both in 1 (4%). Four patients (17%) received the ipilimumab/nivolumab combination, and the rest received pembrolizumab. Most patients (63%) received IO in the first-line setting. The median duration of IO and the time to best response were 7.5 months (range, 2 to 55) and 3 months (range, 3 to 12), respectively. Among 23 evaluable patients, the overall response rate (ORR) was 74 % (17/23), with complete response (CR) in 13 (57%), and partial response (PR) in 4 (17%) patients. Response assessment is pending in 1 patient. Four patients (17%) had stable disease (SD), and 2 patients (8 %) experienced progressive disease (PD) on IO (1 with localized and the other with metastatic CC). The median progression-free survival (PFS) and overall survival (OS) did not reach for the whole group after a median follow-up of 12.5 months (range, 2 to 69 months), with 19/24 (79 %) patients remaining progression-free. Three patients underwent surgery with 2/3 achieving pathological CR. Among the 12 patients with localized CC, ORR was 73% (6 CR, 2 PR, 2 SD, 1 PD, and 1 assessment pending); median PFS and OS were not reached after a median follow-up of 9 months (range, 2 to 45) with 1 patient experiencing progression on IO at the time of data cut-off. No unexpected toxicity was observed. Conclusions: In this small cohort of patients with dMMR/MSI-H localized and oligometastatic CC, most patients showed deep and durable responses to neoadjuvant IO, obviating the need for surgery. Progression on IO was rare. This real-world data support investigating a non-operative paradigm in patients with dMMR/MSI-H localized and oligometastatic CC.