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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.

Objectives: To evaluate the performance of noninvasive, elastic scattering spectroscopy, algorithm-powered device (DermaSensor) to detect melanoma and basal and squamous cell cancers in the primary care setting. Patients & Methods: DERM-SUCCESS, a blinded, prospective, multicenter pivotal study, enrolled adult patients between August 17, 2020, and December 9, 2021, with lesions that their primary care physicians (PCPs) suspected of skin cancer at clinics in the US (n = 18) and Australia (n = 4). These lesions were assessed by PCPs and scanned with the DermaSensor device. Biopsy specimens were collected, and histopathologic analysis was performed by dermatopathologists. The diagnostic performance of the device, dermatopathologist discordance, and subgroup analyses of clinical interest were calculated. Results: Of the 1579 skin lesions enrolled, dermatopathologic analysis identified 224 (14.2%) cancers. Device sensitivity was 95.5% (95% CI, 91.7%-97.6%) overall and 96.3% (92.9%-98.4%) for patients in the FDA-approved age group 40 years and older (90.2% for melanoma, 97.8% for basal cell carcinoma, and 97.7% for squamous cell carcinoma). Device specificity was 20.7%. The negative predictive value was 96.6%, and the positive predictive value was 16.6% (NNB 6). The device misclassified as “ monitor ” rather than “ investigate further ” 4 keratinocyte carcinomas and 4 melanomas in patients aged 40 years or older (n = 8, 0.5% of lesions, 3.7% of cancers biopsied). Conclusions: The DermaSensor device is an easy-to-use, point-of-care, hand-held skin cancer adjunctive diagnostic device with high sensitivity and NPV to help inform PCP decision-making about skin lesions suspicious for cancer that need further evaluation and those that may be monitored.

Barriers to incorporating pharmacogenetics into routine clinical practice in the United States are well documented. Initial surveys by the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2009 and 2010 identified barriers across four key domains that have hindered the widespread adoption of clinical pharmacogenetic testing. These are presented verbatim as: (i) absence of a definition of the processes required to interpret genotype information and to translate genetic information into clinical actions; (ii) need for recommended drug/gene pairs to implement clinically now; (iii) clinician resistance to consider pharmacogenetic information at the bedside; and (iv) concerns about test costs and reimbursement. Over time, many of these challenges have been overcome, and clinical pharmacogenetic testing has subsequently reached broader implementation. Despite this progress, several barriers remain that block further adoption. This narrative review used authors' expertise and experience to identify and describe current barriers to pharmacogenetic implementation across seven domains in the United States: equity and inclusion; guidelines and supporting evidence; regulatory agency oversight; payer coverage and insurance; availability of quality pharmacogenetic tests; electronic health records; and provider and patient education. Within each domain, it revisits past successes and challenges and explores remaining barriers. We also propose solutions to address ongoing challenges across these domains, including further expansion of recommendations beyond pharmacogenetic‐specific guidelines, standards for designing clinical decision support tools, and broader pharmacogenetics education. Addressing these remaining obstacles directs work to enable broader adoption of clinical pharmacogenetic implementation to ultimately improve patient outcomes.

This case series describes a distinctive inspiratory noise observed during sleep in patients with IgLON5-antibody disease.

AbstractSecure messaging platforms were designed to optimize healthcare communication by providing asynchronous, bidirectional, Health Insurance Portability and Accountability Act‐compliant text messaging options. Proponents argue that these platforms streamline workflows, foster coordination across multidisciplinary teams, and improve patient safety. However, critics highlight their potential to disrupt workflows through overwhelming message volumes and task interruptions, increased risk for miscommunication, and possible detrimental impacts on patient care. While secure messaging shows promise for modernizing hospital communication, it requires institutional guidelines and thoughtful use to mitigate inefficiencies and risks.

2558 Background: Clinical validation studies have shown that early dynamic changes in circulating tumor DNA (ctDNA) tumor fraction (TF) can predict clinical outcomes. Yet few studies have evaluated the clinical value of longitudinal monitoring throughout the course of treatment. Here we evaluate longitudinal changes in ctDNA TF and clinical outcomes in an advanced real-world pan-cancer cohort of patients (pts) treated with immune checkpoint inhibitors (ICIs). Methods: The cohort included deidentified pts from the Tempus clinicogenomic database with stage IIIB or IV solid tumors who underwent ctDNA NGS and were treated with an FDA-approved ICI +/- chemotherapy (CT). Pts had a pre-treatment baseline liquid biopsy (T0) and ≥1 on-treatment sample Ti within 21-180 days of ICI. xM for treatment response monitoring estimates TF via an ensemble algorithm that incorporates variant and copy number information. Response status was determined at each on-treatment timepoint Ti relative to T0. Pts were classified as a Molecular Responder (MR) if TF < 1% at T0 and Ti or if TF decreased by ≥ 50% from T0 to Ti; otherwise, they were classified as a Molecular Non-Responder (nMR). Pts with TF < 0.09% at T0 and Ti were classified as ctDNA not detected. The longitudinal cohort included pts with ≥2 on-treatment timepoints, further classified based on the most frequent classification across each Ti as longitudinal MR, longitudinal nMR and longitudinal ctDNA not detected. If no classification was dominant, the most recent classification was used. Real-world overall survival (rwOS) was defined from T1 to death and assessed by log-rank test. Results: The full cohort of 84 pts with > 10 solid tumors included 34.5% (n = 29) NSCLC and 16.7% (n = 14) SCLC. The majority of pts (59.5%, n = 50) received ICI+CT, (64.0% first-line [1L]), and 40.5% (n = 34) ICI-only (35.3% 1L). rwOS was longer for 53 MRs vs. 18 nMRs (median not reached vs. 7.0 months, P < 0.005); 13 pts had no ctDNA detected. The longitudinal subcohort of 35 pts was 31.4% (n = 11) NSCLC, 20.0% (n = 7) prostate cancer, and 14.3% (n = 5) SCLC; 45.7% (n = 16) ICI+CT (56.3% 1L), 54.3% (n = 19) ICI-only (31.6% 1L). On average, pts had 3 on-treatment liquid biopsies, with a median time between on-treatment samples of 91 days. Twelve pts were longitudinal nMRs (10 MR or ctDNA not detected at T1), 18 longitudinal MRs, and 5 longitudinal no ctDNA detected. There were 6 death events in the longitudinal nMRs, 3 in the longitudinal MRs (all > 18 months after T1), and no death events in the longitudinal no ctDNA detected group. Longitudinal MRs had longer rwOS than longitudinal nMRs (median 37.4 months vs 8.7 months, P < 0.005). Conclusions: Longitudinal nMR was associated with worse survival compared to longitudinal MR. Longitudinal, molecular biomarker dynamics may be a useful clinical treatment decision tool for monitoring treatment response to ICI therapy.

TPS1143 Background: Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) have revolutionized the treatment of patients (pts) with germline BRCA1/2 (gBRCA)-associated HER2-negative BC. However, resistance eventually occurs in almost all pts. Tumor-associated macrophages (TAMs), a key component of the BC tumor microenvironment, are highly immunosuppressive and associated with poor clinical outcomes. In preclinical immunocompetent models of BRCA-associated BC, PARP inhibition induces suppressive CSF-1R+ TAMs, contributing to resistance, so that combining anti-CSF-1R therapy with PARPi significantly enhances progression free survival (PFS) compared to PARPi monotherapy (190d vs 92d). Axatilimab (SNDX-6352; Ab969.g2), a humanized IgG4 monoclonal antibody targeting CSF-1R, reduces TAMs, potentially slowing tumor growth and enhancing anti-tumor immunity. In the Phase I SNDX-6352-0502 study for advanced solid tumors, axatilimab showed tolerability at the highest dose (6 mg/kg), with biomarker modulation observed at doses as low as 1 mg/kg. Axatilimab is FDA-approved for chronic graft-versus-host disease (cGVHD). Methods: AXALAP (NCT06488378) is a non-randomized open-label, proof-of-concept phase 1 study designed to evaluate axatilimab 1mg/kg or 3mg/kg every 2 weeks in combination with olaparib 300 mg twice daily in pts with somatic or germline BRCA1/2 - and PALB2 -associated HER2-negative metastatic BC. Patients must be PARPi naïve, or have not progressed on prior PARPi, and have received up to 2 prior lines of chemotherapy for metastatic disease. Pts will receive a two-week lead-in of olaparib monotherapy, followed by combined olaparib and axatilimab. Pts will undergo mandatory tumor biopsies pre-treatment, after the 2-week olaparib lead-in, and after 2 cycles of olaparib/axatilimab, with an optional biopsy at time-of-progression. Primary objectives are to establish the maximum tolerated dose (MTD) and recommended phase 2 dose and to assess the safety and tolerability of axatilimab and olaparib. Secondary objectives include assessment of changes in CSF-1R+ CD163+ macrophage levels after olaparib monotherapy and after 2 cycles of combination treatment at the MTD; to determine the objective response rate and the median PFS of the combination per RECIST 1.1 criteria. The MTD will be determined by Bayesian Optimal Interval (BOIN) design. Pts will be treated in cohorts of 3 with a maximum of 10 at each dose. If the MTD is identified as 3mg/kg, we will complete enrollment of 10 pts at 1 mg/kg to assess biological effectiveness and clinical efficacy of the lower dose. We expect to treat up to 20 pts, who will receive study treatment until development of unacceptable toxicity or disease progression. Enrollment began on 5/2024 at Dana-Farber Cancer Institute and the trial will also open at Beth Israel Deaconess Medical Center and Mayo Clinic-Rochester. Clinical trial information: NCT03604692 .

6008 Background: ATC patients present with advanced, often surgically unresectable disease with historically dismal prognosis. Median PFS and OS of DT without pembrolizumab were 6.7 and 13.5 months, respectively, in the ROAR trial. Neoadjuvant DTP achieved locoregional control without radical surgery in a retrospective series of BRAF m-ATC patients, providing rationale to evaluate efficacy and safety in a phase 2 prospective trial. Methods: In this single-arm multicenter phase 2 trial, patients with BRAF m-ATC stage IVB/IVC were enrolled in 5 US centers. Following a 3-6 week run-in with D (150 mg BID) and T (2 mg daily), P (200 mg Q3W) was added, with restaging every three (21-day) cycles. Post-operatively, patients continued P (or DTP) with radiotherapy or transitioned directly to adjuvant DTP (up to 26 cycles). Primary endpoints included R0/R1 resection rate (historically 5%) and overall survival (OS). Secondary endpoints included RECIST 1.1 response after DTP and progression-free survival (PFS). Results: Between 9/2021-1/2025, 42 patients were enrolled; 36 are included in the current analysis (3 not evaluable, 3 pending surgery) (Table). Patients received median 4 (range: 2-7) neoadjuvant DTP cycles, with 26 (72%) achieving radiographic PR/CR. 30 patients (83%) had surgery after neoadjuvant DTP, achieving R0/R1 resection in 29/30 (97%). Mean surgical morbidity score (0-4 scale, 4=unresectable) improved from 3.3 to 1.6 after DTP (p<0.01). Complete ATC pathologic response occurred in 20/30 patients (67%), while 10/30 (33%) had residual ATC in the surgical specimen. Postoperatively, 11/30 (37%) received adjuvant neck radiation, and 28/36 (78%) completed a median of 11 (range: 1-26) adjuvant DTP cycles. With median follow up 18 months, 15/36 (42%) patients died. Median OS was 20 months (95% CI: 12.6-NR); 1- and 2-year OS were 71% and 48%. Complete pathologic responders had better 2-year OS than those with residual ATC (69% vs. 22%, p=0.02). Median PFS was 13.9 months (95% CI, 7.5-NR); 1- and 2-year PFS were 57% and 36%. Grade 5 adverse events occurred in 8 patients (22%), including one possible (duodenal perforation), one probable (kidney injury with sepsis), and 6 unlikely/unrelated treatment-related deaths. Conclusions: Neoadjuvant DTP enables surgical resection in BRAF m-ATC compared with historical controls, and leads to improved PFS and OS. This approach should now be considered a standard of care for BRAF m-ATC. Clinical trial information: NCT04675710 . Total N=36 Age (y), median (range) 67 (46-86) Stage IVB/IVC, n (%) 15 (42%)/21 (58%) Best RECIST response neoadjuvant phase, n (%) CR 2 (6%) PR 24 (67%) SD 6 (17%) PD 4 (11%) Percent change target lesion diameter, mean (95% CI) -44% (-54%, -34%) Surgical morbidity score change, mean (95% CI) -1.7 (-2.1, -1.3)