Citations

639 Background: Large cohort studies have shown a survival benefit with the use of GLP1 receptor agonists (GLP1 RA) in cancer patients. The impact of GLP1 RA usage in breast cancer (BC) and the different subtypes is unknown. To investigate the potential influence of GLP1 RA usage on BC survival, a study was conducted on a large institutional database. Methods: A de-identified institutional database identified newly diagnosed Stage I, II, and III BC patients from 2005 to present and use of GLP1 RA. The study compared survival rates for BC patients with and without GLP1 RA and further stratified by BC subtype [ER+HER2-, HER2+, ER-PR-HER2-(triple negative BC (TNBC))], BMI, and age. Kaplan-Meier survival curves were used to estimate overall survival. This study analyzed de-identified data accessed through Mayo Clinic Platform Discover. Per 45 CFR 46.102, this activity did not require IRB review. Data was extracted using an established privacy-preserving protocol and de-identified via expert determination under the HIPAA Privacy Rule. Raw EHR data and other unreported data cannot be shared due to de-identification parameters. Results: 88015 BC patients were identified, of which 3919 (4.5%) received GLP1 RA. The 5-year survival rate was 98.5% with vs 85.5% without GLP1 RA (p-value <0.0001). The survival benefit persisted for different BMI’s and ages: BMI >30 (98.4% vs 85.1%), >25 (98.4% vs 85.4%), and age <50 (99.5% vs 89.3%) and >50 (98.1% vs 84.8%) [all p<0.0001]. 21770 patients with ER+ disease were identified, of which 1412 (6.5%) received GLP1 RA. The 5-year survival rate was 99.0% vs 87.7% (p-value <0.0001). The survival benefit persisted by BMI and age: BMI >30 (99.0% vs 86.2%), >25 (98.9% vs 87.1%) and age <50 (99.6% vs 90.5%) and >50 (98.7% vs 87.2%) [all p<0.0001]. 3599 patients with HER2+ disease were identified, of which 202 (5.6%) received GLP1 RA. The 5-year survival rate was 99.3% vs 80.1% (p-value <0.0001). The survival benefit persisted by stratification: BMI >30 (100.0% vs 80.0%, p-value <0.0004), and <25 (97.7% vs 76.2%, p-value <0.019), and age <50 (100% vs 87.0%, p-value <0.043) and > 50 (99.0% vs 77.2%, p-value <0.0002). 8389 patients with TNBC disease were identified, of which 360 (4.3%) received GLP1 RA. The 5-year survival rate was 91.0% vs 71.9% (p-value <0.0001). The survival benefit persisted by stratification: BMI >30 (96.4% vs 72.9%, p-value <0.0001), >25 (93.2% vs 71.8%, p-value <0.0001), and age <50 (96.0% vs 73.0%, p-value <0.0028) and >50 (88.9% vs 71.8%, p-value <0.0001). For those TNBC patients who received GLP1 RA, having a BMI >30 conferred a protective effect with a 5-year survival rate was 97.9 vs 89.8% (p-value <0.0014). Conclusions: The study suggests that GLP1-RA improves 5-year survival rates of patients with BC and this applies to all subtypes of BC. These results suggest that further study of the impact of GLP1-RA on BC patients is warranted.

1110 Background: CDK4/6 inhibitors with endocrine therapy are widely used for HR+/HER2– metastatic breast cancer (BC). While studies have shown similar progression-free outcomes across agents, overall survival (OS) data are limited. Since OS is a definitive endpoint and BMI may influence outcomes, this study examines BMI-dependent OS differences among CDK4/6 inhibitors. Methods: A retrospective cohort study was conducted using the Mayo Clinic Platform full AMC1 dataset. Postmenopausal women with BC receiving palbociclib/ribociclib/abemaciclib plus aromatase inhibitor (AI) were included. Patients with prior use of fulvestrant, anthracyclines, radiation therapy, GnRH agonists, or history of MACE, heart failure, myocardial infarction, or stroke before BC diagnosis were excluded. Patients were stratified by BMI and CDK4/6 inhibitor. The primary outcome was 5-year OS. Results: Among 1,989 patients (palbociclib: 868; ribociclib: 465; abemaciclib: 656), palbociclib was associated with significantly worse OS compared to ribociclib in BMI <25 (HR 2.91; 95% CI: 1.76–4.79; P < 0.01) and BMI ≥30 (HR 1.91; 95% CI: 1.21–3.01; P < 0.01). Compared to abemaciclib, palbociclib showed worse OS: BMI <25 (HR 1.73; P < 0.01), BMI 25–30 (HR 1.56; P < 0.01), and BMI ≥30 (HR 1.82; P < 0.01). No significant OS differences were observed between ribociclib and abemaciclib. Palbociclib patients were older, particularly in BMI <25 (Cohen's D = 0.39 vs. ribociclib; 0.27 vs. abemaciclib) and BMI ≥30 (0.28 vs. ribociclib; 0.23 vs. abemaciclib). In the BMI 25–30 group, palbociclib group was also older than ribociclib group (Cohen's D = 0.26). Conclusions: In postmenopausal BC patients on AIs and CDK4/6 inhibitors, palbociclib was associated with worse OS in BMI < 25 and BMI ≥ 30 groups, while ribociclib and abemaciclib showed similar outcomes across BMI groups. Palbociclib patients were older than those on other drugs, which may partially confound results; however, in the BMI 25–30 group, despite similar age differences, no survival difference was observed between palbociclib and ribociclib, suggesting age alone may have limited impact. These findings indicate a potential interaction between BMI and drug choice, and highlight the need for prospective studies to confirm and adjust for these variables. Limitations include the observational design and inability to perform multivariable regression analyses to adjust for confounders. Overall survival comparisons by CDK4/6 inhibitor and BMI subgroup. Comparison BMI Group Hazard Ratio (95% CI) P-value Palbociclib vs Ribociclib <25 2.91 (1.76 – 4.79) < 0.01 25 – 30 1.34 (0.87 – 2.071) 0.17 ≥30 1.91 (1.21 – 3.01) < 0.01 Palbociclib vs Abemaciclib <25 1.73 (1.29 – 2.32) < 0.01 25 – 30 1.56 (1.09 – 2.23) < 0.01 ≥30 1.82 (1.15 – 2.88) < 0.01 Ribociclib vs Abemaciclib <25 1.27 (0.81 – 1.99) 0.29 25 – 30 0.87 (0.54 – 1.43) 0.59 ≥30 1.05 (0.63 – 1.75) 0.85

10585 Background: Prior studies suggest that thyroid cancer (TC) survivors may have an elevated risk of secondary malignancies. However, whether this risk differs by TC histology, specifically with breast cancer (BC), remains unclear. We aimed to investigate the association between TC subtype—papillary thyroid carcinoma (PTC) versus medullary thyroid carcinoma (MTC)—and subsequent BC risk, adjusting for demographic factors. Methods: We conducted a retrospective cohort study using the SEER (2000–2022), including adults with a primary, microscopically confirmed PTC or MTC. Subsequent BC occurrence was defined as a binary outcome (yes/no). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for MTC versus PTC, controlling for age (<50 vs ≥50 years), sex, and race. Stratified analyses by age and race were also performed. Stata 15 was used for statistical analyses. Results: 14,840 patients (14,563 PTC, 277 MTC) were included. MTC patients were older (mean 59.08±12.66 vs 56.16±12.98 years, p<0.001) and had a higher proportion of males (44.4% vs 29.4%, p<0.001). The overall incidence of secondary BC was lower in MTC patients (7.6% vs 22.5%, p<0.001). In unadjusted logistic regression, MTC was associated with significantly lower BC risk (OR=0.28, 95% CI: 0.18–0.44, p<0.001). After adjustment, MTC remained significantly protective (aOR=0.34, 95% CI: 0.22–0.55, p<0.001). Stratified analyses demonstrated consistent findings across age groups (<50: aOR=0.10, 95% CI: 0.03–0.42; ≥50: aOR=0.34, 95% CI: 0.21–0.54), , as well as white and Hispanic patients. Conclusions: Survivors of MTC have a substantially lower risk of developing secondary BC compared to PTC survivors. This association persists after adjustment for age, sex, and race, and is consistent across age and most racial subgroups. However, different BC types were not assessed due to limited number of BC patients among MTC survivors, and the small MTC sample size and potential survival differences between groups may affect the results. These findings highlight a possible effect of TC subtype on BC risk, suggesting the potential influence of underlying biological or genetic mechanisms. Baseline demographic characteristics of patients with papillary and medullary thyroid carcinoma. Characteristic Papillary Thyroid Carcinoma (PTC) (N=14,563) Medullary Thyroid Carcinoma (MTC) (N=277) P-value Age at Diagnosis 0.0002* Mean ± SD, years 56.16 ± 12.98 59.08 ± 12.66 Median, years 57 61 Sex, n (%) <0.001† Female 10,288 (70.6) 154 (55.6) Male 4,275 (29.4) 123 (44.4) Race, n (%) 0.015† White 10,263 (70.5) 197 (71.1) Black 921 (6.3) 15 (5.4) American Indian 77 (0.5) 1 (0.4) Asian 1,379 (9.5) 13 (4.7) Hispanic 1,903 (13.1) 50 (18.1) SD: Standard Deviation. *P-value from two-sample t-test (equal variances assumed). †P-value from chi-square test for the overall distribution across categories.

OBJECTIVE Frailty is a known predictor of adverse outcomes in pituitary surgery, yet its impact regarding craniopharyngioma remains unclear. The authors assessed preoperative frailty, measured by the 11-factor modified frailty index (mFI-11), and its association with perioperative morbidity among adult patients undergoing craniopharyngioma surgery. METHODS Using the Registry for Adenomas of the Pituitary and Related Disorders (RAPID) database, the authors performed a retrospective cohort study of the records of patients ≥ 18 years of age who underwent craniopharyngioma surgery between June 2007 and November 2024. Patients were stratified into the following categories according to their numeric mFI-11 score: fit (scores 0 and 1), managing well (scores 2 and 3), and mildly frail (scores 4–6). Primary outcomes included hospital length of stay (LOS) and discharge disposition. Secondary outcomes included 90-day readmission, surgical outcomes, and complications. Multivariable analyses were performed to identify independent predictors of hospital LOS and non-home discharge, adjusting for age, surgeon experience, American Society of Anesthesiologists class, complications, and surgical approach. RESULTS Among 278 patients (221 fit, 43 managing well, 14 mildly frail), higher-frailty patients were older (mean age 47.8 ± 16.1 years in fit vs 60.1 ± 12.5 years in managing well vs 67.6 ± 8 years in mildly frail, p < 0.001) and more likely to present urgently (24.2% vs 36.4% vs 78.6%, p = 0.001). Gross-total resection was achieved less frequently in frail patients (44.8% vs 24.3% vs 23.1%, p = 0.030). Overall complication rates were similar; however, increasing frailty was associated with higher rates of postoperative mortality (0% vs 2.8% [1/36] vs 7.7% [1/13], p = 0.018), pneumonia (0.5% [1/195] vs 2.8% [1/36] vs 15.4% [2/13], p = 0.006), and reintubation (2.6% [5/195] vs 2.8% [1/36] vs 30.8% [4/13], p = 0.002). Higher frailty was associated with a stepwise rise in median [IQR] LOS (5 [3–8] days vs 7 [4–12] days vs 13 [6.5–21.8] days, p < 0.001) and remained an independent predictor of extended LOS on multivariable analysis (β = 1.729 per point, p = 0.006). Rates of non-home discharge showed a similar pattern (9.2% vs 30.0% vs 64.3%, p < 0.001), with frailty independently predicting non-home discharge (OR 2.352, 95% CI 1.527–3.822). Unplanned 90-day readmission rates were significantly higher in the mildly frail cohorts (22.5% vs 45.7% vs 53.8%, p = 0.002). CONCLUSIONS The mFI-11 scores independently predicted perioperative morbidity following craniopharyngioma resection. Incorporating frailty screening into preoperative screening may improve risk stratification, family and patient counseling, and discharge planning.

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.

Objectives: We evaluated agreement between human papillomavirus (HPV) tests performed on self-collected vaginal and clinician-collected cervical specimens to advance HPV self-collection as a cervical cancer screening option in our health care system. Methods: This diagnostic accuracy study was conducted at an academic medical center. Participants were 25–65 years old with upcoming colposcopy appointments. One cohort (n = 79) self-collected a vaginal specimen in the clinic immediately before a clinician-collected cervical specimen. The second cohort (n = 115) self-collected a vaginal specimen at home, mailed it in, and had a clinician-collected cervical specimen in the clinic. Paired specimens were evaluated for total (TPA), positive (PPA), and negative (NPA) percentage agreement. Extreme temperature stability studies were also conducted. Results: Compared with clinician-collected cervical specimens, in-clinic self-collected vaginal specimens showed a TPA, PPA, and NPA of 98%, 100%, and 97% for HPV16; 99%, 100%, and 99% for HPV18; 86%, 94%, and 79% for high-risk other (HRO) HPV. The TPA, PPA, and NPA for at-home self-collected vaginal specimens compared with clinician-collected cervical specimens were 94%, 79%, and 96% for HPV16; 95%, 43%, and 98% for HPV18; 89%, 80%, and 93% for HRO. Vaginal specimens showed prolonged stability and were unaffected by extreme temperatures. Conclusions: In general, in-clinic and at-home self-collected vaginal HPV specimens for HPV screening demonstrate high agreement with clinician-collected cervical specimens, with the exception of low PPA in the at-home self-collected vaginal HPV18 subgroup. Our findings support the use of HPV self-collection as a practical option to expand access to cervical cancer screening.

Abstract Background Whether outcomes of germline BRCA1/2 (gBRCA1/2)-associated breast cancer differ compared with sporadic tumors is controversial. We explored the impact of gBRCA1/2 pathogenic variant (PV) status beyond established prognostic features. Methods We conducted 2 retrospective, matched cohort studies comparing gBRCA1/2 PV carriers and noncarriers with HER2-negative, stage I-III breast cancer (Clinical Outcomes Quality Database [COQD] cohort: 185 carriers, 555 noncarriers; Young Women’s Breast Cancer Study [YWS] cohort: 113 carriers, 226 noncarriers). Matching factors were age, stage, hormone receptor status, and year of diagnosis. Clinicopathological features, treatments, and survival outcomes were compared between carriers and noncarriers. Results Most patients in COQD had stage I-II disease (87.2%), and more carriers than noncarriers had genetic testing before diagnosis (33% vs 5.6%, P &lt; .001). In YWS, 22.7% of patients had stage III tumors, and few were tested before diagnosis (14.8% of carriers vs 1.7% of noncarriers; P &lt; .001). Carriers in COQD received chemotherapy more often than noncarriers (81.1 vs 67.0%, P &lt; .001), including platinum (P = .010); the proportion was similar for carriers and noncarriers in YWS. After adjusting for chemotherapy, relapse-free survival was longer in carriers than noncarriers in COQD (adjusted hazard ratio = 0.48 [95% CI = 0.26 to 0.87], P = .016), and a favorable trend was observed for other survival outcomes in both cohorts. Triple-negative tumors appeared to drive the differences. Conclusions We observed a trend toward improved outcomes in gBRCA1/2 PV carriers compared with noncarriers. These findings suggest that carriers should not receive more aggressive treatment solely based on their germline mutation status. Prospective clinical trials in this population are warranted.

Sacral stress fractures are rare in athletes, present as nonspecific gluteal and/or back pain, and are often missed on radiographs. Standard treatment includes activity modification, physical therapy, and pain medications. However, prolonged recovery and recurrence remain concerns in athletes. There is evidence for the use of extracorporeal shockwave therapy (ESWT) in the treatment of stress fractures, and platelet-rich plasma (PRP) has also shown promise in accelerating bony healing. This case report describes a 48-year-old male triathlete with a recurrent sacral stress fracture unresponsive to conservative management. Following MRI diagnosis, he underwent sequential ESWT and PRP injection, resulting in successful return to competitive training levels at 8-weeks post-treatment. Although an MRI at 3-months post-treatment showed persistent bony edema, his PROMIS-Pain Interference (PI) and Global Pain Scale (GPS) scores improved from 54 to 40 and 62/100 to 4/100, respectively. There is currently no published literature on the sequential use of ESWT and PRP for the treatment of sacral stress fractures. To our knowledge, this is the first documented case of this novel treatment, suggesting a potential role for combination therapy in such injuries. Further research is warranted to validate the efficacy and long-term outcomes of this emerging therapeutic approach in athletic populations.

Introduction Lynch syndrome (LS) is a hereditary cancer syndrome that increases risk for colorectal and other cancers. We hypothesize that vaccines against tumor-associated antigens CEA, MUC1, and brachyury, simultaneously delivered in an adenovirus serotype-5 vector (Tri-Ad5) combined with the immune-enhancing IL-15 receptor superagonist nogapendekin-alfa-inbakicept (NAI) will reduce the incidence of colorectal neoplasms in LS carriers. Methods In this ongoing phase IIB double-blind placebo-controlled trial, two open-label safety phases (SPs) assessed safety of Tri-Ad5 alone (SP1, n=10) and with added NAI (SP2, n=10). A randomized controlled trial (RCT) follows the SPs. After baseline colonoscopy, vaccine dosing occurs at weeks 0, 4 and 8; Tri-Ad5 alone in SP1 and Tri-Ad5 plus NAI in SP2, with identical boosters at Week 52. The RCT phase participants (n=138) were randomized to receive Tri-Ad5 plus NAI or placebo. All participants complete colonoscopy at Weeks 52 and 104 for assessment of the primary endpoint: cumulative colorectal neoplasm incidence. Secondary endpoints include safety, tolerability, and immunogenicity. Results All 20 SP participants (median age 57.5 (range 42–75), 70% female, 15% minority) received all prime and booster series. SP1 participants reported 139 adverse events (AEs) and SP2 participants reported 178. AEs were predominantly grade 1; no treatment-related serious adverse events (SAEs) occurred. The most common treatment-related AEs were reactogenic events including grade 3 rash (without skin necrosis or breakdown) at NAI injection site (100% of SP2 participants). The RCT phase (n=138) recently completed accrual. Discussion In LS carriers without active cancer, the combination of Tri-Ad5 + NAI was well-tolerated; the RCT phase is ongoing. Clinical Trial Registration https://clinicaltrials.gov/study/ , identifier NCT05419011.