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Flexible intramedullary nail fixation of pediatric femoral shaft fractures offers advantages such as shorter hospital stays, faster return to function, and less associated costs when compared with traction and casting. This study compared the biomechanical performance of three configurations: 2CS, 2CL, and 3CL. Thirty synthetic femur models with identical, length-unstable, spiral fractures were tested using a three-dimensional camera system to assess real-time micromotion. Three groups were analyzed: (a) 2CS – two 3.5 mm C- and S-shaped nails inserted anterograde, (b) 2CL – one ‘C’ and one ‘S’ shaped 3.5 mm titanium nail-inserted retrograde from a single lateral entry, (c) 3CL – two ‘C’ shaped 3.5 mm titanium nails inserted medially and laterally with a third ‘C’ shaped 2.5 mm nail placed retrograde from an anterolateral site. Torsional loading, cyclical loading, and load-to-failure tests were conducted. The 3CL configuration demonstrated superior biomechanical performance. It exhibited the highest torsional stiffness [0.67 ± 0.06 Nm/° for external rotation (ER), 0.404 = ± 0.06 Nm/° for internal rotation (IR); P = 0.002], least displacement (0.05 ± 0.02 vs. 0.30 ± 0.02 mm for 2CL and 0.57 ± 0.05 mm for 2CS; P = 0.012), and required the highest load-to-failure (162 ± 83 vs. 1064 ± 75 N for 2CL and 790 ± 34 N for 2CS; P = 0.016).The 3CL configuration provided superior strength and stability across all tests, supporting its role in the fixation of length-unstable pediatric femoral fractures.

Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.

This phase II trial of transoral surgery (TOS) with deintensified postoperative management in human papillomavirus (HPV)–associated oropharynx cancer (OPC) enrolled patients with resectable cT1-2 stage III/IV American Joint Committee on Cancer (AJCC) seventh edition p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (arm A); those with clear margins, 2-4 + LN, or ENE ≤1 mm were randomly assigned to 50 Gy (arm B) or 60 Gy (arm C); and those with involved margins, >4 + LN, or >1 mm ENE received weekly cisplatin and 60-66 Gy (arm D). Among 359 evaluable patients, the 54-month progression-free (PFS) and overall survival (OS) were 90.6% (90% CI, 87.2% to 93.1%) and 95.3% (93.0% to 96.9%), respectively. The 54-month PFS by arm was A 93.2% (79.6% to 97.8%; all four recurrences among N1 patients), B 94.9% (89.7% to 97.5%), C 90.2% (82.7% to 94.6%), and D 85.5% (77.5% to 90.8%). The 54-month OS by arm was A 97.1% (85.7% to 99.4%), B 97.9% (93.5% to 99.3%), C 95.1% (90.1% to 97.6%), and D 92.5% (86.9% to 95.7%). PFS or OS did not differ by primary site or smoking history. TOS and neck dissection with deintensified postoperative management results in outstanding 54-month PFS and OS. Among patients with favorable pathologic characteristics, those with N1 disease are at risk of late recurrence without radiation.

OBJECTIVE The purpose of this study was to identify risk factors for mechanical complications following complex spinal reconstruction for spondylectomy of primary spinal column tumors. METHODS A retrospective chart review identified patients treated with spondylectomy for primary spinal column tumors in the thoracic or lumbar spine followed by posterior instrumentation and anterior column reconstruction. Variables collected included basic demographics, smoking status, chronic steroid use, frailty (Charlson Comorbidity Index), extent of resection, Weinstein-Boriani-Biagini classification, tumor volume, Spine Instability Neoplastic Score, anterior column reconstruction and fixation techniques, rod characteristics, Hounsfield units (HUs), and neoadjuvant/adjuvant chemoradiation. RESULTS Twenty-five patients were included (14 men, 11 women) with an average (± SD) age of 45 ± 18 years, BMI of 28 ± 5.7, and follow-up of 6.0 ± 6.2 years. Primary spinal column tumor pathology included chordoma (40%), chondrosarcoma (16%), giant cell tumor (16%), osteosarcoma (16%), osteoblastoma (8%), and aneurysmal bone cyst (4%). Six patients (24%) experienced mechanical complications, including rod fractures (n = 5) and distal junctional failure (n = 1). Of the 6 patients with mechanical complications, 4 (67%) underwent reoperation. The length of follow-up was the only statistically significant risk factor for patients with mechanical complications (average 11 years) compared to those without complications (average 4.4 years, p = 0.047). Average HUs were 144 for mechanical complication patients versus 180 for those without (p = 0.08). Anterior column reconstruction materials included a titanium cage (13 patients, 3 failures), structural allograft (6 patients, 2 failures), vascularized fibular strut autograft (6 patients, no failures), nonvascularized structural autograft (5 patients, 1 failure), vascularized rib autograft (5 patients, 2 failures), and a polyetheretherketone cage (2 patients, no failures). The vascularized fibular strut autograft had a 0% mechanical failure rate, but this did not reach statistical significance (p = 0.28). Twelve patients (48%) had anterior fixation placed, with a 17% rate of mechanical complications (p = 0.65). Five patients (20%) had > 2-rod constructs, with a 20% mechanical complication rate (p = 0.99). CONCLUSIONS Reconstruction following primary spinal column tumor resection is a significant challenge, as evident by a high rate of mechanical complications and instrumentation failure. Future studies are needed with larger sample sizes to identify techniques that may mitigate the risk of failure.

LBA1551 Background: Traditional cancer therapy is primarily delivered in clinical settings, imposing logistical, emotional, and financial burdens, particularly on rural and underserved patients. While international studies have demonstrated the safety of home-based chemotherapy, no randomized U.S. trials have evaluated this approach. Mayo Clinic’s CCBW program aims to expand access to high-quality cancer care by providing in-home cancer treatment, lab testing, telemedicine, remote patient monitoring, command center and paramedic support. This pragmatic randomized controlled trial evaluates feasibility and impact of home-based versus in-clinic cancer directed therapy on patient preference, acceptability, safety, and patient-reported outcomes. Methods: Adult patients (ECOG 0-2) receiving chemotherapy or hormonal therapy at Mayo Clinic Florida were randomized 1:1 after confirmation of treatment tolerance in clinic to receive (1) home-based care for 24 weeks or (2) in-clinic care for 8 weeks followed by home-based care for 16 weeks. Target accrual is 200 patients. A planned interim analysis after 50 enrollments assessed accrual, data completeness, technical challenges, safety, and study outcomes. The primary endpoint is patient ratings of their overall cancer care experience (0–10 scale, CAHPS Cancer Care Survey) at 8 weeks. 200 patients provide 80% power to detect a 0.45 standard deviation difference in mean ratings between arms with a 2-sided 2-sample t-test (α=0.05) and 20% missing data rate. Secondary endpoints are patient preference, comfort with home infusions, treatment worthwhileness, functional/symptom assessments (EORTC QLQ-F17, PRO-CTCAE, GP5), grade ≥3 AEs, hospitalizations, and overall survival. Cost is a tertiary endpoint. The trial is IRB-approved (#23001719) and registered (NCT05969860). Results: Enrollment began 8/23/23. As of 2/21/25, 52 patients (26 per arm) were enrolled and 36 started protocol treatment. Common cancers were breast (38%), colorectal (21%), prostate (19%), and multiple myeloma (14%). 64% (28/44) of patients were female; 84% identified as White, 14% as Black, and 2% as multiple races. Median distance to clinic was 20 miles (range 2-66). After 8 weeks, patients in both arms rated their overall cancer care experience highly (mean [SD]=9.69 [0.85] versus 9.54 [0.66] for home-based vs. in-clinic care, n=26). After 24 weeks, 73% preferred home-based care, 18% had no preference, and 9% preferred in-clinic care; 100% felt comfortable with home infusions. No grade ≥3 AEs related to location of care have occurred. Conclusions: Early findings support the feasibility, safety, and high patient acceptability of home-based cancer therapy. No safety concerns related to care location were observed and most patients preferred home-based treatment. Ongoing accrual and analysis will assess clinical outcomes and cost implications. Clinical trial information: NCT05969860 .

OBJECTIVE The purpose of this study was to evaluate the risks and benefits of removing painful pelvic/iliac screws in spine fusion surgery patients. METHODS A retrospective review identified patients who had traditional iliac and S2-alar-iliac (S2AI) screws removed for pain. The minimum follow-up was 24 months. RESULTS Fifty-two patients (75% women) were included with a mean age of 63 years, BMI of 28, and follow-up of 65 months. Most of the removed screws were S2AI (83%) compared with traditional iliac screws (17%). Forty-three patients (83%) had improvement in their pelvic screw related–pain following removal. Eight patients (15%) experienced lumbosacral mechanical complications following pelvic screw removal including sacral fracture (n = 3, 6%) and/or L4–5 or L5–S1 rod fracture (n = 7, 13%). On multivariable analysis, risk factors for mechanical complications following pelvic screw removal included a longer fusion construct (OR 1.34, p = 0.035), greater postoperative L4–S1 lordosis (OR 1.14, p = 0.04, ideal cutoff > 40°), and lack of bone morphogenetic protein (BMP; OR 0.03, p = 0.02). Ten patients (19%) underwent subsequent SI joint fusion following pelvic screw removal, and higher standing pelvic incidence (OR 1.10, p = 0.03) was the only independent predictor of SI fusion. CONCLUSIONS Removal of painful pelvic screws resulted in a high rate of postoperative pain relief, albeit with a risk of lumbosacral mechanical complications and subsequent SI joint fusion. Patients at risk for lumbosacral mechanical complications following pelvic screw removal included those with longer fusion constructs, more lordosis from L4 to S1 (> 40°), and lack of BMP. Patients at risk for receiving an instrumented SI joint fusion following pelvic screw removal included those with a higher pelvic incidence.

3553 Background: Vilastobart (XTX101) is tumor-activated, high affinity, Fc-enhanced aCTLA-4 designed to focus activity toward the tumor and minimize systemic adverse events. Fc-enhancement augments FcγR co-engagement on antigen presenting cells and has been linked with efficacy of aCTLA-4 combinations in patients (pts) with microsatellite stable (MSS) colorectal cancer (CRC) and other tumors [Fakih ASCO GI 2025]. Vilastobart was generally well-tolerated and demonstrated evidence of anti-tumor activity in pts with immunologically “cold” advanced solid tumors, both as a monotherapy and in combination with atezolizumab [Davar SITC 2024]. Methods: Phase 2 of the NCT04896697 study evaluated the initial recommended Phase 2 dose of vilastobart 100 mg Q6W in combination with atezolizumab 1200 mg Q3W in pts with MSS CRC who had at least 1 prior chemotherapy regimen in the metastatic setting, excluding pts with prior immune checkpoint inhibitors. Pts with (LM) and without liver metastasis (NLM) were eligible. Tumor biopsies were obtained before and during treatment for translational analyses. Results: As of January 13, 2025, 40 pts were dosed in Phase 2. Median age was 55 (25-82) and 70% of pts had 3 or more prior lines of therapy. Of the 24 enrolled NLM pts, 11 were response-evaluable with an available on-treatment scan as of the data cut. In these 11 pts, two confirmed and one unconfirmed partial response (PR) were reported, all accompanied by significant decreases in ctDNA and serum tumor marker CEA and with each pt ongoing on therapy, for a preliminary ORR of 27%. One additional pt (with peritoneal metastasis) had a 24% reduction in target lesions (first scan) and was ongoing on therapy. Of the 16 enrolled LM pts, 7 were response evaluable, with one stable disease and another pt reporting a mixed response with significant serum tumor marker reductions, both ongoing on therapy. Of note, one LM pt in Phase 1C dose escalation treated with vilastobart (150 mg Q6W) combination had a confirmed PR with LM resolution. Six pts (15%) reported G3+ treatment-related adverse events (TRAEs), with two G4 laboratory TRAEs and no G5 TRAEs. Only three pts discontinued therapy for TRAEs. TRAEs occurring in ≥10% (all grade) or ≥5% (G3) of pts are summarized in the Table. Conclusions: The combination of vilastobart, a novel tumor-activated, Fc-enhanced a-CTLA-4, and atezolizumab demonstrated initial evidence of anti-tumor activity in late line, metastatic MSS CRC where immune checkpoint blockade has historically been relatively ineffective. Vilastobart was observed to have a differentiated safety profile distinct from systemically active a-CTLA-4, consistent with tumor-selective activation. Clinical trial information: NCT04896697 . AE term All Graden (%) Grade 3n (%) Fatigue 12 (30%) 0 Diarrhea 8 (20%) 0 Infusion related reactions 5 (13%) 0 Pyrexia 4 (10%) 0 ALT increased 4 (10%) 0 AST increased 4 (10%) 1 (3%) Colitis 2 (5%) 2 (5%)

TPS1657 Background: Cancer treatments are traditionally administered in clinical settings, which can isolate patients from their familiar environments and exacerbate physical, psychosocial, and financial burdens. Travel requirements further amplify these challenges, particularly for underserved populations. Studies indicate that patients prefer receiving care at home, and international models have demonstrated the safety of home-delivered chemotherapy since the 1990s; however, no U.S. clinical trial data exists. In response, Mayo Clinic has developed the Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) program, a distributed cancer care delivery model that expands access to quality cancer care by bringing it to the home environment, providing in-home cancer treatment, lab testing, telemedicine, and community paramedic support. This trial evaluates the safety, acceptability, and impact of home-based subcutaneous (SC) nivolumab (Nivo) administration compared to in-clinic treatment within the CCBW initiative. Methods: This open-label, single-arm trial evaluates the impact of SC Nivo administration location—home versus infusion center—on patient reported cancer care experience, patient-preferred treatment location, acceptability, safety, and patient-reported outcomes. Eligible adult patients (ECOG 0-1) receiving IV Nivo for an FDA-approved indication and residing within 75 miles of Mayo Clinic Florida will transition to SC Nivo, receiving two initial in-clinic cycles. If tolerated without injection reactions, four cycles will be administered at home before resuming in-clinic treatment. Exclusion criteria include concurrent investigational/standard treatments or contraindications to immunotherapy. Fifty patients will be enrolled, with an estimated 75% (n=38) providing cancer care ratings after 8 weeks in-clinic and 8 weeks at-home, offering 85% power to detect a mean difference in ratings of 0.50 standard deviations. The primary endpoint is within-patient change in cancer care rating (0–10 scale, CAHPS Cancer Care Survey) comparing 8 weeks of in-clinic vs. at-home care. Secondary endpoints include patient-preferred treatment location, comfort with home injections, safety (grade 3+ adverse events), function (EORTC QLQ-F17), symptoms (PRO-CTCAE), side effect impact (GP5), and healthcare utilization (ER visits, hospitalizations). Cost will be assessed as a tertiary endpoint. The trial has FDA approval (IND #170079), Mayo Clinic IRB approval (#23009663), and ClinicalTrials.gov registration (NCT06265285). Enrollment began in April 2024, with an expected accrual period of 24 months. To date, 10 patients have been enrolled, and final analysis is expected 2.5 years after trial activation. Clinical trial information: NCT06265285 .