Citations

Study Design This study is part of the AO Spine Metastatic Tumor Research and Outcomes Network [MTRON], an international multicenter prospective observational registry including patients with spinal metastases. Objectives This study aims to elucidate the incidence of surgical complications, their risk factors and consequent effects on survival outcomes, hospital length of stay, and overall health-related quality of life (HRQOL) parameters in a large cohort of patients affected by spinal metastases who were surgically treated. Methods Available data from February 2017 to July 2023 were analyzed. The primary outcome of this study was the evaluation of the incidence of intraoperative and postoperative adverse events (AEs). The secondary outcomes included the assessment of risk factors for surgery-related AEs and the impact of AEs on survival, length of hospital stay and quality of life. Results Among the 1267 patients analyzed, 6.9% experienced intraoperative AEs and 19.3% experienced at least 1 postoperative AE. Several factors resulted to be associated to the occurrence of postoperative AEs: age, smoking habit, poor Eastern Cooperative Oncology Group (ECOG) Performance status, previous radiation therapy at the index target, duration of surgery, number of instrumented levels, simultaneous anterior and posterior approach, presence of metastases at other sites, multiple spinal metastases. Postoperative AEs were associated with reduced survival rates, increased hospital length of stay and poorer HRQOL outcomes, particularly in domains such as neurological function and mental health. In general, surgery substantially improves HRQOL across multiple domains, with these benefits persisting over time despite the occurrence of AEs. However, patients with preoperative risk factors, including comorbidities, smoking, neurological impairment, and prior radiation therapy, experienced less improvement. Conclusions The negative impact of AEs on overall survival and HRQOL could be associated with the presence of some preoperative parameters of frailty that are detected as risk factors for AEs occurrence. This finding emphasizes the need for personalized preoperative assessments and optimized perioperative care strategies.

Background: Supracondylar humerus fractures (SCH) are the most common type of elbow fracture in children, with many cases requiring surgery. Treatment of postoperative pain for SCH has high variability, but can often be treated effectively with minimal or no opioids. Furthermore, there is significant morbidity related to pediatric opioid consumption. The goal of this study was to characterize prescription patterns in the United States following closed reduction and percutaneous pinning (CRPP) of SCH. Methods: All patients aged 10 or younger years who underwent CRPP of SCH from January 2010 to December 2021 were identified in the PearlDiver Mariner Claims Database. The primary outcome was postoperative pain medication prescriptions in the 30 days following SCH CRPP. Patient demographics, prescription duration, and morphine milligram equivalents (MME) were analyzed. Multivariable-log-binomial mixed regression models were constructed to assess factors associated with increased opioid prescription. Results: In total, 43,611 SCH CRPP cases in patients aged 10 or younger were identified from 2010 to 2021. Throughout the study period, 48.6% of patients (21,191/43,611) received and filled a narcotic pain prescription. The percentage of patients receiving opioid medication decreased from 54.7% in 2010 to 27.4% in 2021. Opioid prescriptions totaled a mean of 6.1±2.1 days of narcotics with a mean of 79.2 MME prescribed per patient. Increased patient age, increased Elixhauser comorbidity index, and Medicaid insurance were all associated with increased opioid prescription (P<0.001). Living in the Northeast, increased family income, and commercial insurance were associated with decreased opioid prescriptions (P<0.001). Conclusions: Nearly half of the patients over the past decade treated with CRPP for SCH received a narcotic prescription. However, there has been a steady decline in the proportion of patients being prescribed opioids, with only 27.4% receiving opioids in 2021. Further, patients with increased comorbidities or those insured by Medicaid with lower mean family income may be at risk for increased opioid prescription. While efforts have been made to reduce opioid overprescribing, there continues to be room for further reduction in opioid utilization after CRPP for SCH moving forward.

10582 Background: Breast cancer is the most common cancer in young women, with an increasing incidence over the past two decades. This study aims to evaluate the characteristics of young-onset breast cancers among patients aged ≤50 and compare tumor characteristics by germline mutation carrier status. Methods: Patients with breast cancer diagnosis ≤50 years old and evaluated across the Mayo Clinic enterprise between 2000 and 2024 were identified through the prospective Mayo Clinic Breast Cancer Study and the institutional tumor registry. Demographics, tumor characteristics, and clinical outcomes were obtained and described using summary statistics. Germline pathogenic or likely pathogenic variant (PV) carrier status for 5 established breast cancer predisposition genes (BRCA1, BRCA2, ATM, CHEK2 and PALB2) was available in a subset of unselected patients who consented to participation in sequencing studies at Mayo Clinic. Clinical characteristics were compared between PV carriers in each gene and non-carriers utilizing Chi-square test. All tests were two-sided and p-value less than 0.05 was considered statistically significant. Results: Among 8,462 patients (8435 women, 27 men) with breast cancer diagnosis at age ≤50 in the study, the median age of diagnosis of breast cancer was 44 years (range 18 – 49). At diagnosis, 84% had invasive disease, 43% of the tumors were high-grade, 15.8% had triple-negative breast cancer (TNBC), more than two-thirds (67.5%) presented with stage I or II breast cancer, and 3.7% had bilateral breast cancer. Among the 2,527 patients who consented to germline sequencing, 10.1% were found to be carriers of PVs; these included BRCA1 (3.3%), BRCA2 (2.7%), CHEK2 (2.3%), ATM (1.3%), and PALB2 (0.6%). Compared to non-carriers, a significant enrichment (p<0.05) of invasive breast cancer (92.6% vs. 83.3%) and high grade tumors (61.7% vs. 31.4%) were noted in BRCA1 PV carriers, and of bilateral breast cancer (13.4% vs. 3.8%) and high grade tumors (46.4% vs. 31.4%) in BRCA2 PV carriers. After exclusion of in-situ disease, proportion of TNBC was observed to be significantly higher in BRCA1 (61.3%), BRCA2 (15.5%) and PALB2 (30.7%) PV carriers compared to non-carriers (11.2%), whereas >90% of ATM or CHEK2 PV carriers had ER+ breast cancer and none had TNBC. A significant difference in stage at presentation was not observed by germline PV carrier status. Conclusions: The high frequency (>10%) of PVs in young-onset breast cancer underscores the importance for genetic testing in this population. The observed differences in breast cancer phenotypes based on germline PV carrier status among young-women may have significant implications for clinical outcomes and needs to be further explored.

7014 Background: Mosun is a CD20xCD3 bispecific antibody that can be administered in the outpatient setting for a fixed duration. Intravenous Mosun is approved for the treatment of relapsed/refractory FL after ≥2 prior lines of therapy. Mosun SC achieved high response rates with manageable safety in patients with 3L+ FL in a pivotal Phase II study (Bartlett et al. ASH 2024). We report the efficacy and safety of Mosun SC in patients with previously untreated high-tumor burden FL in the Phase II MorningSun study (NCT05207670). Methods: Patients with previously untreated high-tumor burden FL, per GELF criteria, were enrolled into this cohort. Mosun SC was administered with step-up dosing in Cycle (C)1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg) then 45mg on D1 for up to 17 cycles (1 year; 21-day cycles). Patients with a partial or complete metabolic response (CMR) after C17 could receive additional Mosun maintenance therapy (45mg every 8 weeks for up to 1 year). Corticosteroid prophylaxis to reduce the risk of cytokine release syndrome (CRS) was mandatory in C1–2 and optional thereafter. The primary endpoint was progression-free survival (PFS) rate at 24 months. Key secondary endpoints included objective response rate (ORR), time to response (TTR), and safety. Results: As of May 29, 2024, 102 patients were enrolled; 55 patients had completed initial treatment (17 cycles), 31 had discontinued (most commonly due to progressive disease [n=19] and adverse events [AEs; n=4]), and 16 were ongoing initial treatment. Forty-two patients received maintenance treatment, and this was ongoing in 38 patients. Median age was 65 years (range: 24–86); 52.0% of patients were female. Most patients had Ann Arbor stage III/IV (91.2%) and a FLIPI score ≥2 (78.4%). Median duration of follow-up was 13.9 months. The 12-month PFS rate was 82.8% (95% confidence interval [CI]: 73.0–89.3). ORR was 87.3%; 60.8% of patients had a CMR. Among the 89 patients with a response, the median TTR was 2.7 months (range: 1.2–5.8). The most common AEs (≥30%) were injection-site reaction (57.8%), fatigue (42.2%), CRS (34.3%), headache (31.4%), and nausea (30.4%). Grade ≥3 AEs and serious AEs (SAEs) were reported in 44.1% and 29.4% of patients, respectively. CRS events were all Grade 1/2 and SAE of CRS occurred in 10.8% of patients (Table); all events resolved. Conclusions: Mosun SC demonstrated promising efficacy in patients with previously untreated high-tumor burden FL. The manageable safety profile, including rate of CRS, supports the administration of fixed duration Mosun SC in an outpatient setting. Additional data, including cytokine profiling and T/B/NK dynamics, will be presented. Clinical trial information: NCT05207670 . CRS events, n (%) PatientsN=102 Any grade 35 (34.3) Grade12 30 (29.4)5 (4.9) SAE 11 (10.8) ManagementSteroidsTocilizumabSteroids + tocilizumabFluidsICU admission 8 (7.8)6 (5.9)3 (2.9)3 (2.9)2 (2.0)

Abstract Introduction: Monitoring minimal residual disease (MRD) is critical in multiple myeloma (MM) to predict outcomes and guide therapy. Traditional bone marrow (BM) aspirates for MRD detection are invasive and limited by sample quality. We therefore explored cell-free DNA (cfDNA) fragmentation as a less invasive alternative for MRD detection. Methods: We performed 30-40X whole-genome sequencing (WGS) on peripheral blood cfDNA from 45 MM patients, collecting baseline (n = 45) and follow-up samples (n = 98) from eight Canadian sites (M4 and IMMAGINE studies) and one U.S. site (SPORE study), plus 25 healthy controls. Samples were collected post-induction therapy (n = 13), 100 days post-autologous stem cell transplantation (ACST, n = 36), and during maintenance therapy (n = 49). Multiparameter flow cytometry (MFC) MRD testing was conducted on 77 samples. We evaluated insert size metrics and MM-specific chromatin accessibility (from Ordoñez et al., 2020) using Griffin (described in Doebley et al., 2022). Results: Baseline samples had a higher proportion of short fragments (20-150 bp) than follow-up samples (p = 0.0037) and healthy controls (p = 0.019). A fragment score (FS) based on weighted fragment distribution (per Vessies et al., 2022) was highest at baseline (mean = -0.384), followed by MRD-positive (mean = -0.495) and MRD-negative (mean = -0.550) samples. MRD-negative FS was lower than baseline samples (p &lt; 0.001) but higher than healthy controls (mean = -0.639; p = 0.016). Baseline samples had lower coverage at MM-specific chromatin regions than MRD timepoints (p &lt; 0.05; baseline mean = 0.982; MRD-positive = 0.989; MRD-negative = 0.994; healthy = 0.993), suggesting higher transcriptional activity pre-treatment. MRD-negative samples had higher coverage than MRD-positive cases (p &lt; 0.01). Using logistic regression, we assessed the predictive performance of FS and coverage at MM-specific sites. FS alone achieved an AUC of 0.632 (sensitivity [SN] 39.4%, specificity [SP] 92.1%, accuracy [AC] 67.6%). Coverage yielded an AUC of 0.681 (SN 75.8%, SP 60.5%, AC 67.6%). Combining FS and coverage at MM sites improved performance (AUC = 0.734; SN 48.5%, SP 92.1%, AC 71.8%). We next evaluated whether adjusting the BM tumor cell percentage cutoff by MFC could improve performance. At 0.017% (1 in 5, 789 cells) for MRD positivity, the combined model’s accuracy reached 83% with an AUC of 0.757 (SN 17%, SP 97%). Conclusions: cfDNA fragmentomic analysis achieved high specificity (92-97%) in detecting MRD, providing a less invasive alternative to facilitate serial monitoring. While sensitivity remains an area for improvement, the high specificity of cfDNA makes it valuable for confirming MRD negativity and reducing invasive procedures. Future efforts aim to enhance sensitivity by integrating additional fragmentomic features. Citation Format: Dor D. Abelman, Jenna Eagles, Aimee Wong, Saumil Shah, Stephanie Pedersen, Stephenie Prokopec, David S. Scott, Sarah Bridges, Darrell White, Irwindeep Sandhu, Kevin Song, Esteban Braggio, Alli Murugesan, Anthony Reiman, Suzanne Trudel, Trevor J. Pugh. Tumor-independent monitoring of minimal residual disease in multiple myeloma using cfDNA fragmentomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3250.

PURPOSE Survival for patients with melanoma has recently improved. The propensity of melanoma to metastasize to the brain remains a common and serious feature of this disease. The purposes of this study were to evaluate prognostic factors for patients with newly diagnosed melanoma brain metastases (MBMs) in a large cohort treated with modern multimodal therapies, compare those results with those in prior eras, and update the Melanoma Graded Prognostic Assessment (GPA). METHODS Univariable and multivariable (MVA) analyses of prognostic factors and treatments associated with survival were performed on 1,796 patients with newly diagnosed MBM treated between January 01, 2015, and December 31, 2021, using a multi-institutional retrospective database. Multiple imputation was used to address missingness of potential predictors. Significant variables in combined MVA were used to update the Melanoma GPA. Comparisons were made with legacy cohorts. RESULTS Median survivals for cohorts A (1985-2007, n = 481), B (2006-2015, n = 823), and C (2015-2021, n = 1,796) were 6.7, 9.8, and 16.6 months and median follow-up times were 40.1, 43.6, and 48.8 months, respectively. In combined MVA, significant prognostic factors for survival were higher Karnofsky Performance Status, fewer MBMs, absence of extracranial metastases, lower serum lactate dehydrogenase, and no immunotherapy before MBM. These factors were incorporated into the updated Melanoma GPA. The combined median and 3-year survivals for patients with GPA 0-1, 1.5-2, and 2.5-4.0 were 5.4, 13.2, and 43.2 months and 12.4%, 28.8%, and 51.6%, respectively. CONCLUSION Prognostic factors have changed and survival has improved for patients with MBM but varies widely by GPA. The updated Melanoma GPA calculator (BrainMetGPA), available free online, can be used to estimate survival, individualize treatment, stratify clinical trials, guide surveillance, and augment clinical trial eligibility. Multidisciplinary treatment is essential. Trials are needed to elucidate the optimal sequencing of various therapeutic modalities.