Citations

1564 Background: Adolescent and young adult (AYA) females with early-stage ER-negative and/or HER2-positive breast cancer commonly receive chemotherapy to reduce risk of recurrence. Fertility concerns, counseling, and preservation may influence chemotherapy decisions and time to chemotherapy (TTC) initiation. Methods: We surveyed AYA survivors of stage I–III premenopausal ER-negative and/or HER2-positive breast cancer treated at Kaiser Permanente Northern and Southern California (2013-2022). Fertility concerns were defined as not having completed desired family size or being unsure about having completed desired family size at diagnosis. We summarized receipt of fertility counseling, receipt of chemotherapy, and use of oocyte/embryo cryopreservation for fertility preservation (FP). Among fertility-concerned patients who received chemotherapy, TTC (days from diagnosis) was assessed separately for neoadjuvant chemotherapy (NAC) vs for adjuvant chemotherapy (AdjC). Time to NAC was natural log–transformed and modeled with multivariable log-linear regression to estimate relative differences in TTC, adjusting for stage, study site, ER, HER2, age, and diagnosis year. Results: Of 363 respondents, 197 (54%) had fertility concerns at diagnosis; 183/197 (93%) received chemotherapy, similar to 153/166 (92%) among those without concerns (p=0.7). Of the concerned chemotherapy recipients, 45 (25%) saw a fertility specialist but did not pursue FP while 55 (30%) underwent FP. For the 112 fertility-concerned NAC recipients, FP was associated with longer TTC than no fertility specialist counseling (mean=41 vs. 30 days; adjusted ratio=1.39; 95% CI 1.15–1.69), whereas fertility specialist counseling without FP was not (mean= 31 vs. 30 days, adjusted ratio=1.04; 95% CI 0.86–1.25). For the 71 fertility-concerned AdjC recipients, TTC was similar for patients who did not see a fertility specialist (mean=63 days), those who froze oocytes/embryos (mean=65 days), and those who saw a fertility specialist but did not pursue FP (mean=69 days). Conclusions: In this AYA breast cancer cohort, there was no evidence that fertility concerns led patients to decline chemotherapy. FP was associated with a modest delay in NAC initiation (<2 weeks on average). Time to chemotherapy (TTC) among 183 AYA patients with ER− and/or HER2+ breast cancer and fertility concerns. Fertility-focused care N (n=183) Neoadjuvant chemotherapy (n=112) Mean TTC, days Relative difference in TTC, adjusted ratio (95%CI) Adjuvant chemotherapy (n=71) Mean TTC, days No fertility counseling from a specialist 83 (45%) 55 (49%) 29.6 Reference 28 (39%) 62.6 Received fertility counseling from a specialist No fertility preservation 45 (25%) 28 (25%) 30.7 1.04 (0.86,1.25) 17 (24%) 68.6 Fertility preservation 55 (30%) 29 (26%) 41.2 1.39 (1.15,1.69) 26 (37%) 64.6

12007 Background: YAs with cancer, defined as those diagnosed prior to the age of 40, may experience greater symptom burden compared to those diagnosed at older ages. We evaluated the impact of an ePROM-triggered, CC-based, supportive care intervention on symptom burden in YAs with cancer. Methods: The Enhanced, Electronic Health Record-facilitated Cancer Symptom Control (E2C2) trial was a cluster-randomized, pragmatic trial (NCT03892967) that enrolled oncology patients seen at Mayo Clinic Rochester and within the Mayo Clinic Health System (sites in Minnesota and Wisconsin) between March 2019 and January 2023. Patients routinely reported the severity of six SPPADE symptoms (Sleep deficit, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue) on 11-point numerical rating scales. Symptom severity was classified as none to mild (0-3), moderate (4-6), or severe (7-10). Those with moderate or severe symptoms were offered symptom management education, while those with severe symptoms were also offered the option to work virtually with a symptom care manager. In this post hoc analysis, we examined the effects of the intervention on change in symptom scores among YAs and time to improvement to a mild/moderate level in those with at least one severe symptom. Results: Among 40,659 patients who responded to at least one survey, 2,598 were YAs and 38,061 were adults ≥ 40 years. Among YAs, 10.7%, 24.3%, and 65.1% were 18-24 years, 25-31 years, and 32-39 years, respectively. A greater proportion of YA patients were female (61.5% vs 57.0%), of a non-white race (12.4% vs 5.3%), living in an urban setting (65.7% vs 55.1%), single (36.4% vs 9.6%), on non-government insurance (78.1% vs 36.6%), employed (72.6% vs 37.4%), and had a Bachelor’s degree or greater (37.8% vs 28.3%, p < 0.001 for all). Fewer YA patients had metastatic disease compared to older patients (24.2% vs 35.2%, p < 0.001). Compared to a pre-intervention baseline, the mean change in symptom score for YA patients following the intervention demonstrated improvements in anxiety (-0.195) and depression (-0.168, p < 0.0001 for both), while physical function impairment worsened over the intervention period (0.101, p = 0.014). Compared to adults ≥ 40 years, YAs experienced greater intervention effects for management of depression ( p < 0.001), fatigue ( p = 0.01), pain ( p < 0.0001), and physical function impairment ( p < 0.0001). Among YAs with a severe symptom during the intervention period, median time to improvement to a mild/moderate level was longer for anxiety compared to those ≥ 40 years (3.5 vs 2.7 months, p = 0.009). Conclusions: Routine ePROM surveillance, coupled with CC-based symptom management, led to improvements in anxiety and depression among YAs with cancer, although, time to improvement was longer for anxiety compared to adults ≥ 40 years.

11025 Background: Adjuvant endocrine therapy (AET) improves outcomes in HR+ breast cancer. Nonadherence to AET is common, but manual screening for nonadherence is fraught. High-specificity structured cancer electronic health record (EHR) data, particularly if it includes key variables like stage, could streamline these steps for both clinical care and research purposes. We conducted an analysis of approaches to identifying patients as eligible for a multi-site AET adherence study to understand how variation in structured data informatics-supported screening impacts coordinator time. Methods: Mayo Clinic implemented a two-step identification: (1) EHR structured data (diagnosis date, stage, ER/PR/HER2 positivity, medication script) to prescreen for eligibility; (2) SureScripts fills to flag nonadherence using proportion of days covered < 80% across early fills. Medical College of Wisconsin (MCW) implemented a more manual screening process for Step 1 using only medication scripts. Coordinators at both sites then conducted a medical record review to assess if the resulting list of patients had a plan to continue AET for at least two additional years. Opt-out clinician permission preceded patient contact; pharmacists delivered a patient reported outcome (PRO)-guided intervention and documented encounters. Results: At Mayo, 829 patients were prescreened for study eligibility through informatics workflow; 120 (14.5%) met eligibility criteria. At MCW, 1,763 patients were prescreened; 168 (9.5%) were eligible. EHR filters included non–breast cancer encounters (50% at MCW) and ineligible based on time since cancer (36% at Mayo; 26% at MCW). At Mayo, screening required 5.6 minutes/patient for experienced coordinators. At MCW, experienced coordinators averaged 6.67 minutes/patient and inexperienced coordinators averaged 9.33 minutes/patient. Conclusions: Structured EHR data, pharmacy-fill information, and standardized workflows allowed consistent prescreening, intervention and recruitment processes across sites. Higher-specificity informatics-supported screening reduced the percentage of patients requiring manual review and reduced coordinator screening time. It also supported timely provider-permission steps and patient outreach. These workflows were feasible to implement at both institutions, and study enrollment is ongoing. Clinical trial information: NCT06765707 .

10610 Background: The role for genetic testing (GT) for prostate cancer (PCa) patients (pts) has expanded to find pts with germline pathogenic variants (PV) for therapeutic opportunities given FDA-approvals for PARP inhibitors in metastatic PCa as well as understanding familial cancer risk and opportunities for tailored screening and risk reduction. The PROMISE Registry (NCT04995198) was set up as a genetic registry to partner with PCa pts for rapid access to a new standard of care given insurance coverage and clinical implementation were initially major barriers. A second goal is to characterize disease features and treatment outcomes to inform management and provide updates about novel therapeutic clinical trials, both of which remain important to rare genetic variant carriers. Methods: PROMISE is a US decentralized prospective PCa genetic registry initiated in 2021 with initial phase to enroll and provide clinical-grade germline genetic testing (30 gene cancer-specific panel) to 5,000 PCa pts to identify ~500 PCa pts with variants of interest (pathogenic variants, PV, and variants of uncertain significance, VUS) in DNA repair genes for long-term clinical follow-up of 15 years (LTFU). Here, we report the initial phase testing results and identification of the LTFU cohort. Study design and enrollment strategy have been reported separately. Results: Between 2021-2026, 7,275 pts with any stage PCa across 50 US states self-consented to PROMISE, of which 5,674 (78%) of pts completed genetic testing, indicating feasibility of patient-directed, decentralized enrollment. We have identified 495 (8.7%) pts for LTFU. Baseline data is reported for n=367 (Table 1, will be updated at time of presentation). The most frequently observed PV/LPV variants being in CHEK2 (25%) , BRCA2 (23%) , ATM (12%) , and BRCA1 (4.6%). At the time of PCa diagnosis, the majority of LTFU pts had non-metastatic disease, with 47% of pts with Gleason>7, median PSA of 5 ng/mL, and median time from diagnosis to PROMISE GT of 25 months. Conclusions: PROMISE is a nationwide decentralized PCa genetic registry that has completed initial goal to recruit 5,000 PCa pts to offer germline genetic testing and recruit a cohort of 500 for LTFU. Data about diagnosis characteristics are reported, and analysis of ongoing disease course, treatment response/outcomes and overall survival is being collected. Clinical trial information: NCT04995198 . Long-term follow-up participant demographics. Characteristic Overall, N = 367 Age at Diagnosis (yrs) 63 (57, 69) Race N = 361 (6, nr) Asian, American Indian or Alaska Native, Multiracial, Other 22 (6.0%) Black or African American 22 (6.0%) White 317 (86%) Disease State at Diagnosis N = 348 (19, nr) Metastatic 46 (13%) Non-metastatic 302 (87%) Time from Diagnosis to PROMISE GT (months) 25 (4, 82) Gleason Score N = 280 (87, nr) </= 7 148 (53%) >7 132 (47%) PSA At Diagnosis (ng/mL) 5 (0, 10) (88, nr) Subjects with baseline data entered. nr=not reported. Median (Q1, Q3); n (%).

10522 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. While antiviral and metabolic therapies have reduced incidence, scalable pharmacologic strategies for primary prevention (PP) remain a critical unmet need. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated preclinical antitumor activity and the potential to mitigate hepatic lipotoxicity while promoting metabolic reprogramming to stabilize cirrhosis. However, while chemoprevention signals are observed in metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes, the efficacy of GLP-1RAs for PP across diverse liver disease etiologies remains underexplored. To address this gap, we conducted a global, multicenter analysis on the efficacy and safety of GLP-1RAs for the PP of HCC in a pan-etiology high-risk cohort. Methods: A retrospective cohort study was conducted using the TriNetX database (150M patients across 108 health organizations). Adults 18–90 years at elevated HCC risk with ≥ 1 risk factor (chronic viral hepatitis, cirrhosis, MASLD, alcohol use disorder, or hereditary liver disorders) were identified. Cohort A (≥3 months of GLP-1RA) was propensity score-matched 1:1 with Cohort B (non-users) on demographics, HbA1c, BMI, and MELD-Na scores. The primary endpoint was incident HCC, and secondary endpoints were incidence of gastrointestinal (GI) side effects. We employed a 3-month lag period to mitigate immortal time bias. Time-to-event outcomes were assessed via Kaplan-Meier analysis and Cox proportional hazards models. Sensitivity & subgroup analyses were performed to confirm robustness across non-metabolic etiologies. Results: After matching, 592,718 patients were analyzed (296,359 per cohort). Median follow-up was 2,450 days for GLP-1RA users vs 2,114 days for non-users. GLP-1RA use was associated with a 73% reduction in incident HCC (140/296,345 events vs 432/296,198) [HR 0.271 (0.224-0.328)], (NNT=1,015). Notably, the protective effect was most pronounced in non-diabetics [HR 0.179 (0.140-0.229)] and lean patients (BMI < 29) [HR 0.161 (0.103-0.252)]. Risk reductions were sustained across all etiologies, including alcohol liver disease (HR 0.379), cirrhosis (HR 0.456), chronic viral hepatitis (HR 0.477), and MASLD (HR 0.605). GLP-1RA use was associated with a significant increase in GI adverse events. Conclusions: GLP-1RA use was associated with a 73% reduction in incident HCC, consistent across subgroups. The enhanced benefit in non-diabetic and lean cohorts suggests a direct anti-neoplastic mechanism independent of weight loss or glycemic control. The NNT of 1,015 highlights the substantial public health impact of GLP-1RA therapy in preventing a high-mortality malignancy. These findings warrant prospective validation.

10030 Background: CABO is a multi-targeted kinase inhibitor of VEGFR2, c-MET, AXL and RET and has shown clinical evidence of activity in two prior studies of adult and pediatric patients with advanced OS. We report results of a feasibility cohort of CABO + MAP chemotherapy in patients with newly diagnosed high-risk OS. Methods: Patients <40 years, body surface area ≥ 0.8 m 2 and new diagnosis of high-grade OS with metastatic disease and resectable primary tumor were eligible. Patients were enrolled to two CABO dose levels (Dose Level 1 (DL1) 25 mg/m 2 /day, maximum 40 mg/day; Dose Level 2 (DL2) 35 mg/m 2 /day; maximum 60 mg/day) using a modified IQ 3+3 design. CABO was orally administered concomitantly with six 35-day cycles of MAP (cisplatin 60 mg/m 2 on days 1-2 (cycles 1-4), doxorubicin 37.5 mg/m 2 on days 1-2 (with dexrazoxane), methotrexate 12 g/m 2 on days 22, 29) and for 24 weeks as maintenance monotherapy. CABO was held after 7 weeks and resumed during 4 th MAP cycle to allow for primary tumor resection and metastatic surgeries. Dose-limiting toxicities (DLT) were assessed during weeks 1-6 of treatment; additional monitoring for post-surgical complications was conducted through completion of 4 th MAP cycle. The primary endpoint for this cohort was feasibility of combination therapy. Results: Ten patients (median age 11.5 years, 70% male) were enrolled and treated with CABO + MAP (DL1, n=4; DL2, n=6). Median cumulative doses of all MAP agents were maintained throughout treatment with no dose reductions. Concomitant dosing of CABO with MAP was tolerated with no protocol-specified DLTs occurring during the evaluation period. DL2 (35 mg/m 2 ) was established as the recommended dose for further study of combination therapy. Commonly reported adverse events included hematologic toxicities, febrile neutropenia, and alanine/aspartate aminotransferase (AST/ALT) elevation. Interruption of CABO was required in 6 patients for Grade 3+ AST/ALT elevation following methotrexate (n=3), wound complications (n=3), and Grade 3 pneumothorax (n=1). Wounds included two Grade 3 port site events and one Grade 1 primary tumor resection site; two patients later resumed CABO after healing without wound recurrence. Dose reduction of CABO was required in one patient for Grade 4 amylase elevation. Conclusions: The combination of CABO + MAP is feasible with no protocol-specified DLTs during the evaluation period. Generalizability is limited based on cohort size. Further evaluation of CABO + MAP is ongoing in a phase II/III randomized efficacy study in newly diagnosed standard and high-risk patients using CABO dose of 35 mg/m 2 /day (max 60 mg), with delayed initiation of CABO in patients with port placement and early safety monitoring for wound-related events, as well as full study monitoring of dose delivery, wound complications and systemic toxicity. Clinical trial information: NCT05691478 .

Purpose of review Normocalcemic primary hyperparathyroidism (NPHPT) is defined by persistently elevated parathyroid hormone (PTH) levels in the presence of normal total and ionized serum calcium after excluding secondary causes of PTH elevation. Increasing use of biochemical screening has led to growing recognition of this phenotype, yet uncertainties remain regarding its natural history, diagnostic criteria, and optimal management. Recent findings NPHPT shares several clinical features with hypercalcemic primary hyperparathyroidism (HPHPT). Substantial rates of osteoporosis, fragility fractures, and nephrolithiasis are reported. Diagnosis requires repeated biochemical measurements, confirmation of normal ionized calcium, and rigorous exclusion of secondary causes such as vitamin D insufficiency, chronic kidney disease, malabsorption, and medication effects. Preoperative localization may also be more difficult than in HPHPT due to smaller adenomas and higher prevalence of multigland disease. Summary Parathyroidectomy appears safe and effective in selected individuals. However, NPHPT may carry a greater risk of recurrence than HPHPT. Improvements in bone mineral density (BMD) and quality of life (QOL) have been reported after surgery, although renal outcomes remain less certain. This review summarizes current evidence on the epidemiology, diagnosis, clinical manifestations, and management of NPHPT and highlights key areas requiring further study.

OBJECTIVE Craniopharyngiomas are benign intracranial tumors that can be difficult to manage operatively and often result in postoperative complications and prolonged recovery. Understanding the factors that influence length of stay (LOS), discharge disposition, and readmission can guide perioperative planning and patient counseling. The authors examined the clinical, radiographic, and surgical predictors of extended LOS (eLOS), nonhome discharge, 90-day readmission, and hospitalization ratio (HR) after craniopharyngioma resection using a large, multicenter cohort. METHODS A retrospective analysis was conducted using the Registry of Adenomas of the Pituitary and Related Disorders database, encompassing 469 patients who underwent craniopharyngioma resection at 14 US academic centers from 2011 to 2025. Patients were stratified by 4 outcomes: eLOS (> 75th percentile), discharge to home versus skilled nursing facility/rehabilitation, 90-day hospital readmission, and hospitalization ratio (i.e., integration of initial and readmission LOS). Multivariable logistic regression models identified independent predictors for each outcome among patient and surgical variables. RESULTS An eLOS (> 10 days) was independently associated with preoperative memory loss (OR 3.75, 95% CI 1.95–7.21), gait imbalance (OR 5.90, 95% CI 1.53–22.70), and postoperative complications (OR 4.07, 95% CI 2.34–7.06). The use of a nasoseptal flap was protective against an eLOS (OR 0.52, 95% CI 0.28–0.93). Discharge to home was predicted by an endoscopic approach (OR 3.87, 95% CI 1.78–8.44) and postoperative intact thirst (OR 2.22, 95% CI 1.05–4.66) and negatively predicted by preoperative diabetes mellitus (OR 0.21, 95% CI 0.09–0.50), LOS (OR 0.87, 95% CI 0.84–0.91), and postoperative cognitive dysfunction (OR 0.30, 95% CI 0.13–0.72). Among 385 patients with follow-up data, a 90-day readmission was independently associated with postoperative complications (OR 5.62, 95% CI 3.12–10.13), preexisting coronary artery disease (OR 4.30, 95% CI 1.46–12.69), and postoperative cognitive dysfunction (OR 3.33, 95% CI 1.76–6.44). A higher HR was associated with diabetes mellitus (unstandardized B 0.059, 95% CI 0.010–0.108, p = 0.02), postoperative complications (unstandardized B 0.054, 95% CI 0.021–0.086, p = 0.001), and postoperative cognitive dysfunction (unstandardized B 0.049, 95% CI 0.006–0.092, p = 0.02). Tumor pathologic subtype and size, prior treatment, extent of resection, and surgeon experience were not directly predictive of outcomes. CONCLUSIONS Cognitive and functional status, systemic comorbidities, and postoperative complications, in addition to surgical approach, are important predictors of the early clinical course after craniopharyngioma surgery. Early identification of high-risk patients may help to guide treatment decisions, improve discharge planning, and reduce healthcare utilization.

The word humility is derived from the Latin word humus, meaning “ground” or “soil.” Romans equated humility with being grounded. Perhaps because it contradicts our natural tendencies toward self-preservation, humility remains an often misunderstood and underappreciated virtue. It is foreign to many, especially in today’s society, which is so focused on self-promotion. However, it is truly one of the most important and powerful virtues that a person can possess and practice. Humility is a just assessment of ourselves and the world around us. It is not thinking less of oneself; rather, it is actually thinking less about oneself. In looking beyond ourselves, we can obtain an honest estimate of our limitations and what is needed to remain patient-centered. In approaching our profession with humility, we more closely honor the privileges of caring for patients, teaching others, innovating, and advancing science. The aim of this article is to show how humility nurtures our development in all aspects of medicine. A humble clinician maintains a steadfast focus on their patient, a humble educator emphasizes the learner, a humble researcher respects science through their honesty and integrity, and a humble innovator does not let pride blind them, recognizing that innovation without humility is doomed to fail. In addition to being a superpower in medicine, humility blesses us with the wisdom and gratitude that come from experiencing, living for, and working for something bigger than ourselves. Gratitude has been considered the father of all virtues, and our ability to be truly grateful requires a core of humility.