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3520 Background: Recent analyses highlight nonhierarchical outcomes using the 8 th Edition AJCC staging system for CC. For instance, the 5-year survival rate for stages I and IIIa patients (pts) closely align. Additionally, tumor deposits (TDs) have been established as significant prognostic indicators. The AJCCCCEP commissioned this study to develop an updated pathological staging system for CC focused specifically on pts without distant metastasis (M0), while retaining the existing stage IV classification. Methods: Individual patient data (IPD) from pts diagnosed with cc (2010- 2017) in the NCDB were divided into training (70%) and internal validation (30%) datasets. External validation used IPD from clinical trials. The primary endpoint was overall survival (OS). Risk classification development for M0 pts incorporated ungrouped data on pathologic T categories, the number of involved regional lymph nodes (LN+), and TD counts. Recursive partitioning and regression tree analyses were applied to construct hierarchical staging levels. Pre-specified criteria required survival probabilities to be consecutive and show clear separations using Kaplan-Meier (KM) estimates with pairwise log-rank test P of < 0.005 for the training and < 0.05 for validation analyses. Results: Data from 281,997 pts (median age 67 years, 50% male, 81% white, 55% T3, 19% T4, 44% N+, 26% M+, and 11% with ≥1 TD) were analyzed, with a median follow-up of 7.3 years. The updated staging system (Table) met pre-specified criteria, with all observed pairwise P < 0.0001 in the development and internal validation sets. KM OS curves displayed a hierarchical separation across all sub-levels after the 1 st year of diagnosis. Consistent results were seen in pts treated with adjuvant chemotherapy in 4 trials (all pair-wise P < 0.0001). Conclusions: The proposed pathological staging system for M0 pts fulfills pre-specified criteria for hierarchical risk stratification, validated both internally and externally, and provides an evidence-based update. Pending review process, the AJCCCCEP will recommend that these changes be made to the Version 9 staging protocol for colon cancer to improve prognostication for CC pts. Stage T, # of LN+, # of TD M % of pts 1y OS (CI), % 3y OS (CI), % 5y OS (CI), % I T1, 0, 0 0 5 96 (95-97) 91 (90-92) 84 (83-86) IIa T2, 0, 0 0 10 95 (94-95) 88 (88-89) 80 (79-81) IIb T1, 0, 1+T1, 1+, 0T2, 0, 1+T2, 1-4, 0T3, 0, 0 0 27 93 (92-93) 84 (84-85) 75 (75-76) IIIa T1, 1+, 1+T2, 1-4, 1+T2, 5+, 0T3, 0, 1+T3, 1-4, 0 0 14 92 (91-92) 80 (80-81) 71 (70-72) IIIb T2, 5+, 1+T3, 1-4, 1+T3, 5+, 0T4a, 0-4, 0T4b, 0-2, 0 0 13 86 (86-87) 69 (68-70) 58 (57-59) IIIc T3, 5+, 1+T4a, 0-4, 1+T4a, 5+, anyT4b, 0-2, 1+T4b, 3+, any 0 5 78 (77-80) 53 (51-54) 40 (38-41) IVa Any 1a 19 59 (58-60) 28 (28-29) 17 (16-18) IVb Any 1b 7 43 (42-44) 14 (13-14) 6 (6-7) CI: 95% confidence internal; Peritoneum involvement data were not available before 2018 in NCDB. Thus, IVa/b were based on 7 th Edition.

8513 Background: The MET pathway is a known mediator of EGFR-TKI resistance and represents a therapeutic vulnerability to select MET-TKIs. Savo is an oral, highly selective MET-TKI that, when combined with osi, has the potential to overcome MET-driven resistance after progressive disease (PD) on osi. The Phase 2 SAVANNAH study has demonstrated clinically meaningful activity with the combination of savo + osi in patients (pts) with EGFR-mutated (EGFRm) advanced NSCLC and MET overexpression/amplification (NCT03778229). Isolating the efficacy of savo in the use of savo + osi is a key question for this combination. Methods: A subset of SAVANNAH included eligible pts who had EGFRm advanced NSCLC with MET overexpression (IHC 3+ intensity in ≥90% of tumor cells [IHC3+/≥90%]) and/or amplification (≥10 MET gene copies by FISH [FISH10+]) after PD on first-line (1L) osi; asymptomatic stable brain metastases (treated/untreated) were allowed. Pts were randomized 2:1 (double-blind) to savo 300 mg BID + osi 80 mg QD, or savo 300 mg BID + PBO (stratified by investigator [INV] assessed baseline [BL] brain metastases [yes/no]), until INV-assessed PD per RECIST 1.1. Brain imaging occurred at BL and PD; pts with brain metastases were re-imaged at each tumor assessment to PD. Endpoints included objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS) by BICR and INV; CNS PFS, and presence/absence of CNS lesions at PD by BICR. Results: Overall, 73 pts were randomized (savo + osi n=48; savo + PBO n=25). At BL, median age: 67 vs 65 years, female: 73% vs 64%, White: 73% vs 52% in the savo + osi and savo + PBO arms, respectively. Efficacy outcomes (ORR, DoR, and PFS) were higher with savo + osi than savo + PBO (Table). CNS PFS events by CNS BICR occurred in 5/14 (36% savo + osi) and 2/4 pts (50% savo + PBO). In pts without BL brain metastases, none of the 13 pts (savo + osi) with RECIST PD by BICR had a new CNS lesion; 6/11 pts in the savo + PBO arm developed a new CNS lesion. Conclusions: In EGFRm advanced NSCLC with MET IHC3+/≥90% and/or FISH10+ status after PD on 1L osi, efficacy of savo 300 mg BID + osi was numerically greater than savo + PBO and showed promising CNS activity. To date, this is one of the largest randomized data sets presented evaluating an oral MET-TKI in EGFRm NSCLC. Efficacy findings from SAVANNAH suggest that targeting both EGFR and MET is key and support further investigation of savo + osi and CNS activity in the Phase 3 SAFFRON study. Clinical trial information: NCT03778229 . Assessment Savo + osi (n=48) Savo + placebo (n=25) ORR, % (95% CI) BICR 58 (43, 72) 16 (5, 36) INV 54 (39, 69) 24 (9, 45) DoR, mo, median (95% CI) BICR 11.8 (6.0, NC) 4.5 (2.6, NC) INV 8.0 (4.9, 11.7) 4.2 (2.6, NC) PFS, mo, median (95% CI) BICR 8.3 (5.8, 15.1) 3.6 (1.4, 5.7) INV 7.6 (5.6, 11.0) 2.7 (1.4, 4.1) BICR, blinded independent central review; CI, confidence interval; mo, months; NC, not calculable.

e16457 Background: Patients with inoperable stage II-III pancreatic cancer commonly undergo sequential stereotactic body radiation therapy (SBRT) and chemotherapy. However, there is variability in clinical outcomes, and the predictors of high-risk patients with rapid tumor progression (within 3 months) and poor overall survival (OS) despite treatment are not well characterized. We developed a radiomic (imaging-derived features) signature (RS) that predicts rapid progression. We then investigated clinical characteristics, including pathologic features and treatments received, and RS in a combined analysis to develop and validate the highest-performing model to predict OS from the time of SBRT initiation. We identified the most predictive feature from the combined model that best predicts OS. Methods: In our retrospective study, we examined a cohort of 124 stage II-III pancreatic cancer patients who underwent sequential SBRT and systemic chemotherapy and had pre-treatment pancreatic protocol computed tomography (CT) imaging. We examined 10 clinical features and extracted 900 radiomic features from each segmented tumor per patient using PyRadiomics. Dividing our cohort into training and test sets (60:40), we built a prediction model for rapid tumor progression using radiomic data on the training set (n = 74), applying a LASSO-based algorithm for feature selection and 5-fold cross-validation for parameter optimization. We validated the model performance on the held-out test set (n = 50) and generated the RS for predicting rapid progression. We examined the performance of clinical features and RS in predicting OS in univariate and multivariate Cox regression models. Results: Analysis on our cohort (57 men, 67 women; mean age 67 ± 11 years) generated a 43-feature RS that predicted rapid tumor progression (AUC 0.83, 95% CI: 0.70–0.94) in the test set. High RS was a significant predictor of mortality with hazard ratio (HR) 2.22 (95% CI: 1.32–3.73, p = 0.003) within the first year and 2.85 (95% CI: 1.35–6.03, p = 0.006) thereafter. Non-intensive chemotherapy increased only early mortality risk (HR 1.95, 95% CI: 1.08–3.53, p = 0.03), while older age was significant in later years (HR 1.80, 95% CI: 1.02–3.15, p = 0.04). Conclusions: CT-derived RS accurately predicted rapid tumor progression in stage II-III pancreatic cancer patients undergoing SBRT sequentially with chemotherapy. High RS was the strongest prognostic indicator for increased mortality risk, suggesting its utility for guiding treatment or selection for clinical trials.

Introductory paragraph The extracellular Calcium-sensing receptor (CaSR) regulates cellular responsiveness to physiological changes in ionized calcium (Ca 2+ ) concentrations. The CaSR is expressed in the brain, including in hypothalamic growth hormone stimulating GHRH and anorectic POMC neurons that control growth and energy homeostasis. We embryonically deleted the Casr gene in neurons to create Neuron CaSR -/- mice to delineate the role of this receptor in regulating growth, skeletal development, and energy metabolism. Neuron CaSR -/- mice had reduced size, weight and bone mass compared to littermate controls, with a dysregulated growth hormone axis. They also showed increased adiposity and circulating leptin levels, leptin resistance, and decreased glucose tolerance, along with reduced expression of the anorectic precursor peptide POMC and secondary increases in the expression of the anorectic peptide AgRP in the hypothalamus of Neuron CaSR -/- mice. Knockdown of CaSR in adult mice specifically in the hypothalamic arcuate nucleus, where GHRH, POMC and AgRP neurons reside, also resulted in increased body weight, adiposity, leptin resistance, and glucose intolerance, and reduced bone mass. Together these data suggest that neuronal CaSR critically regulates energy and skeletal metabolism and body growth by modulating hypothalamic function, representing a new paradigm for central integration of calcaemic activities with body function.

Abstract Background Hospital‐at‐home programs (HaH) in the United States have evolved to include a virtual‐hybrid delivery model, where all physician encounters are virtual and partnered with a home care team. Objective To examine whether a virtual hybrid HaH program enabled by technology has similar clinical outcomes to traditional brick‐and‐mortar (B&M) hospital care. Methods We conducted a pragmatic trial at three hospitals, randomizing 1150 acutely ill patients requiring hospital care between July 10, 2023, and October 31, 2023 one‐to‐one into two groups: intervention (HaH) and control (B&M). The primary analysis was an intention‐to‐treat non‐inferiority analysis of the primary outcome, which was a composite of 30‐day all‐cause mortality and unplanned readmissions. Secondary outcomes included 30‐day readmission, all‐cause mortality, and patient experience. Results The mean age was 67.8 (standard deviation [SD] 16.3) years, and 52.2% were female. The primary outcome occurred in 99 (17.3%) HaH patients and 114 (19.8%) B&M patients (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.63–1.14, p = .28), meeting the non‐inferiority criterion. Thirty‐day unplanned readmission occurred in 84 (14.7%) HaH patients and 101 (17.5%) B&M patients (OR 0.81, 95% CI 0.59–1.11, p = .19). Thirty‐day all‐cause mortality occurred in 25 (4.4%) HaH patients and 19 (3.3%) B&M patients (OR 1.34, 95% CI 0.73–2.46, p = .35). No HaH patients died while receiving their hospital care at home. HaH program was associated with a higher likelihood of patients reporting feeling extremely comfortable or very comfortable (84.4% HaH; 60.9% B&M, p = .001). Conclusion A hybrid HaH model is a safe and comfortable alternative to traditional B&M hospital care.

Abstract Abdominally based free flaps are commonly utilized in the context of breast reconstruction. Historically, postoperative care of these patients involved liberal amounts of intravenous fluid administration; however, overadministration of fluids puts patients at risk of developing flap edema via fluid shifts, electrolyte imbalances, wound dehiscence, and other sequelae. The purpose of this study is to assess fluid administration trends in this cohort at the authors' institution and assess its impact on patient outcomes. A retrospective review was performed on patients who underwent free-flap breast reconstruction. Patient demographics and hospitalization data were collected, and type of abdominal flap and reconstruction timing was noted. Perioperative fluid administration volumes were tracked, and primary outcomes included complication rate and type (e.g., acute blood loss anemia [ABLA], partial/total flap loss, etc.). Multivariable logistic regression was performed to assess the impact of fluid volume on patient outcomes. A total of 115 patients (mean age of 51.3 ± 10.5 years) underwent 188 abdominally based free flaps. Deep inferior epigastric artery perforator flaps were performed most often (n = 91), followed by muscle-sparing transverse rectus abdominis flaps (n = 88). Multivariable logistic regression demonstrated that high perioperative fluid administration (≥9,000 mL) was associated with increased odds of medical complications (odds ratio [OR] = 21.7; confidence interval [CI]: 5.54–84.5; p < 0.001). Patients with high fluid administration volumes experienced an increased (but nonstatistically significant) flap complication rate (OR = 2.96; CI: 0.89–9.88; p = 0.08) and developed ABLA at a higher rate (OR = 15.86; CI: 5.30–46.4; p < 0.001). High-volume resuscitation (≥9,000 mL) was associated with increased odds of ABLA as well as a greater likelihood of medical and flap complications in patients undergoing abdominally based free flaps for breast reconstruction. These data should be used to guide the development of protocols within institutions, which perform free flaps for breast reconstruction.

Background/Objectives: Although Osgood–Schlatter disease (OSD) is often self-limiting following apophyseal closure, it may cause persistent symptoms into adulthood, affecting physical and functional activities. The purpose of this systematic review is to summarize the current evidence on the efficacy of hyperosmolar dextrose injection for patients with OSD unresponsive to conservative treatment. Methods: Multiple databases were searched for studies investigating the efficacy of hyperosmolar dextrose injection in patients with OSD. Two reviewers independently extracted data and evaluated the risk of bias. Meta-analyses were performed to compare hyperosmolar dextrose injection with placebo injections. Results: Four studies including three randomized controlled trials (RCTs) and one case series involving a total of 166 (162 males and 4 females) patients with 184 knees were included in this review. At three months, there was no significant difference in patient-reported improvement from baseline between hyperosmolar dextrose injection and placebo injections (standardized mean difference [SMD] = 1.92, 95% confidence interval [CI], −0.12 to 3.96; I2 = 96.2%). However, a meta-analysis of two RCTs including athletic pediatric patients found a pooled risk ratio of 2.11 (95% CI: 1.12 to 3.98, I2 = 30.73%) for pain-free return to sports at three months. In addition, at one year, a meta-analysis of two RCTs showed greater patient-reported improvement from baseline with hyperosmolar dextrose injection compared to placebo (SMD = 1.09, 95% CI, 0.62 to 1.56; I2= 0%). Conclusions: Based on the limited number of RCTs, although no improvement in patient-reported outcomes is seen at three months, hyperosmolar dextrose injection may safely facilitate a pain-free return to sports at three months and lead to patient-reported improvement at one year. However, further high-quality RCTs are needed to substantiate these findings.

Abstract Rationale: Ongoing healthcare staffing shortages have prompted new care paradigms that incorporate remote care delivery to support timely detection of patient physiological deterioration through mechanisms other than clinician bedside evaluations. In partnership with institutional Information Technology, our team has developed a unique clinical informatics environment, known as the Advanced Medical Practice (AMP) platform, that incorporates data from multiple sources and platforms and supports remote observation of patients from the electronic intensive care unit(eICU). AMP takes advantage of technologies outside of vendor-supported EHRs, and its advanced user-interface design reduces information overload while incorporating real-time data from novel devices and sensors. We partnered with the hospital practice to co-develop a score within the AMP platform(Clinical Events Detection and Response[CEDAR]) that incorporates heart rate, blood pressure, respiratory rate, and SpO2 to stratify patient risk and generate deterioration alerts for the electronic ICU(eICU) team. This formative evaluation employed an implementation science approach to refine CEDAR and ensure it is acceptable to users and can be feasibly implemented in practice. Methods: The study team conducted this pilot work in the eICU at Mayo Clinic (Rochester, MN). We observed the eICU workflow and documented feedback from eICU staff in fieldnotes. eICU staff were asked to log issues in a tracking file during shifts. Issues were reviewed daily and discussed at multidisciplinary team meetings weekly. Observation and tracking data were coded to constructs in the Consolidated Framework for Implementation Research(CFIR 2.0) framework and mapped to Expert Recommendations for Implementation Change(ERIC) strategies that targeted key determinants. Results: Between 9/23/24 and 10/25/24 we completed 25 days of observations. Most identified issues related to technical/design issues like unclear vital trigger alerts (CFIR: Innovation trialability and design); staff knowledge of CEDAR functionality and attitudes about functionality, complexity, or relative advantage compared to current systems (CFIR: Inner setting access to knowledge and information and relative advantage); and difficulties incorporating CEDAR into workflow(CFIR: Inner setting/compatibility). Implementation strategies mapped to CFIR determinants included promoting adaptability of customized interface features; staging implementation scale-up with iterative improvements; providing local technical assistance; assessing for readiness and identifying facilitators and barriers; and conducting educational outreach visits. Conclusions: Formative evaluation during pilot studies are a critical step in the process of intervention development and testing. User engagement and frameworks from implementation science can identify issues of feasibility and inform strategies to ensure acceptability prior to intervention scale-up in clinical practice and readiness for conducting larger implementation studies.

Importance Many older adults with advanced cancer never communicate goals of care or treatment preferences to their clinicians, raising the risk that care received will not match their values. Scalable models of care may help surmount this barrier. Objective To test whether a combined patient and clinician intervention increased the rate of advance care planning (ACP) documentation in large health care systems. Design, Setting, and Participants This stepped-wedge cluster randomized clinical trial using an open cohort design included patients aged 65 years or older with advanced cancer seen at oncology clinics in 3 health care systems located in the US South, Midwest, and Mid-Atlantic regions from April 1, 2020, to November 30, 2022. Data collection ended in 2024. Intervention The intervention involved delivering brief evidence-based patient-facing video decision aids available in 25 languages as well as goals-of-care communication training to oncology clinicians. Patients in the control period received usual care. Main Outcomes and Measures The primary outcome was ACP documentation, which included any electronic health record documentation of a goals-of-care conversation, palliative care, hospice, or limitation of life-sustaining treatments, identified via a validated natural language processing program. Analysis was performed on an intention-to-treat basis. Results Twenty-nine practices, comprising 13 800 unique eligible patients with a total of 29 357 repeated measurements, were included (mean [SD] age, 74.5 [6.6] years; 52.3% men [15 344 of 29 357 measurements]). The proportion of patients with ACP documentation was greater in the intervention phase compared with the usual care phase (adjusted rate difference, 6.8% [95% CI, 2.8%-10.8%]; P &amp;lt; .001). ACP documentation in the intervention phase occurred among 3980 of 15 754 patients (25.3%) (goals-of-care conversation, 21.4% [3377 of 15 754]; palliative care, 9.6% [1517 of 15 754]; hospice, 5.4% [847 of 15 754]; and limitation of life-sustaining treatments, 7.2% [1128 of 15 754]). In comparison, ACP documentation in the usual care phase occurred among 2834 of 13 603 patients (20.8%) (goals-of-care conversation, 16.8% [2281 of 13 603]; palliative care, 9.5% [1287 of 13 603]; hospice, 5.3% [724 of 13 603]; and limitation of life-sustaining treatments, 8.4% [1149 of 13 603]). Conclusions and Relevance In this stepped-wedge cluster randomized clinical trial for older adults with advanced cancer, a bundled evidence-based decision aid and communication training intervention increased the proportion of older patients with ACP documentation. This approach offers an innovative paradigm with a clinically meaningful increase in ACP documentation, a widely used quality metric that reflects high-quality patient-centered care delivery. Trial Registration ClinicalTrials.gov Identifier: NCT03609177