Citations

ABSTRACT Purpose To explore the opioid decision‐making process of prescribers in primary care, surgery, and subspecialty pain management. Methods This was a multistage qualitative‐qualitative study with clinicians involved in opioid prescribing and management from a single healthcare organization with locations in Minnesota, Florida, Arizona, and Wisconsin. Clinicians in this study included physicians, nurse practitioners (NPs), and physician assistants (PAs) practicing in primary care, surgery, or pain medicine. The interview guide was organized in three domains of a conceptual model for opioid use: (1) prescriber characteristics, (2) patient characteristics, and (3) practice environment characteristics. Individual interviews ( N = 20) were performed first, and data were summarized using a rapid template‐based approach. Subsequently, focus groups (FGs) ( N = 4) were conducted with an additional 21 clinicians to confirm and explore interview results. Data from interviews and FGs were analyzed using a common codebook. Results Findings were organized as decision factors into the three domains. Factors in the prescriber domain included characteristics such as formal pain management training, as well as factors that influenced knowledge and beliefs (e.g., advice from or observation of supervising clinicians and expert colleagues). Decision factors in the patient domain included patient pain etiology, comorbid medical or mental health conditions, and demographic characteristics. Clinicians' perceptions of these factors, such as viewing older age as having lesser risk for opioid misuse, influenced prescribing decisions. Clinicians also described challenges associated with “legacy patients” whose therapy was previously managed by a different clinician. Primary care clinicians, in particular, expressed difficulties managing post‐surgical or trauma‐related pain after care transition. Relevant decision factors reported by prescribers in the practice environment domain included guidelines and practice oversight. Most participants reported practicing in an environment that promoted conservative opioid use and having access to standardized institutional guidelines that reduced perceived decision‐making burden. Clinicians described how they used prescribing guidelines to help them communicate with patients about opioid use and prescribing decisions. Conclusions Intersecting prescriber, patient, and practice environment factors shape opioid analgesic prescribing decisions. Available resources in the practice environment, including peer input and institutional guidelines, may support clinician decision‐making and conversations with patients at the point of care, including in cases where patients have complex histories or personal characteristics that influence decision making.

PURPOSE In immunoglobulin light chain (AL) amyloidosis, amyloid fibrils cause organ dysfunction. Anselamimab, a monoclonal antibody, selectively binds to amyloid fibrils, accelerating their clearance. METHODS Newly diagnosed patients with European modification of Mayo 2004 stage IIIa or IIIb AL amyloidosis were randomly assigned to receive anselamimab or placebo with cyclophosphamide, bortezomib, and dexamethasone (with or without daratumumab). The primary end point was a hierarchical composite of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVHs), analyzed using the Finkelstein-Schoenfeld test and win ratio estimation. RESULTS Among 406 randomly assigned patients, the primary end point win ratio for anselamimab versus placebo was 1.11 (95% CI, 0.83, 1.50; P = .332) and the hazard ratio (HR) for ACM was 0.80 (95% CI, 0.57, 1.13; P = .290). CVH rates in the anselamimab and placebo groups were 0.59 (95% CI, 0.42, 0.83) and 0.89 (95% CI, 0.55, 1.43), respectively ( P = .145). Among patients with kappa isotype (n = 72), the win ratio was 2.06 (95% CI, 0.98, 4.31; P = .100) and anselamimab reduced ACM by 62% versus placebo (HR, 0.38; 95% CI, 0.17 to 0.86; nominal P = .012), and CVH by 71% (IRR, 0.29; 95% CI, 0.10 to 0.87; nominal P = .028) with improvements in Kansas City Cardiomyopathy Questionnaire-Overall Score. There was no clinical benefit observed in the lambda population. Anselamimab was generally well-tolerated; safety data were comparable between treatment arms overall. CONCLUSION Treatment with anselamimab, an antifibril antibody used alongside antiplasma cell dyscrasia therapy, while not meeting the primary end point in the overall population, significantly improved ACM and CVH in patients with kappa AL, potentially offering a new therapeutic option for this isotype.

Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

TPS655 Background: Early (14-28 day) on-treatment suppression of tumor proliferation during neoadjuvant endocrine therapy (NET) is strongly associated with favorable long-term outcomes in estrogen receptor–positive (ER+) HER2– breast cancer. In premenopausal women, tamoxifen with or without ovarian function suppression (OFS) results in suboptimal Ki-67 suppression compared with aromatase inhibitor + OFS. (Z)-endoxifen (ENDX), the active metabolite of tamoxifen, dually inhibits ER signaling and PKCβ1-mediated AKT activation, supporting its evaluation as an alternative NET strategy in this population. Methods: EVANGELINE (NCT05607004) is an ongoing, multicenter, open-label Phase 2 study evaluating daily 40 mg ENDX plus goserelin administered every 28 days as neoadjuvant therapy in premenopausal women with ER+/HER2–, cT2–3, cN0–1 breast cancer. The primary objective is to determine the proportion of patients with baseline Ki-67 >10% who achieve Ki-67 ≤10% after 4 weeks of therapy. A Simon two-stage design is used to test whether the Week 4 Ki-67 ≤10% rate is at least 65%, with 20 patients enrolled into the first stage and, if promising, another 25 patients enrolled into the second stage (cohort A). A parallel cohort of 20 patients with baseline Ki-67 ≤10% (cohort B) is enrolled to assess objective response rate (ORR) at 24 weeks per RECIST v1.1. Secondary objectives include examining safety and tolerability, residual cancer burden, and PEPI score. Correlative analyses include examining effect of treatment on select tumor and plasma biomarkers. Clinical trial information: NCT05607004 .

TPS3184 Background: Replication stress (RS) creates cancer cell vulnerability to which the critical DNA damage response kinase, ATR (Ataxia-Telangiectasia and Rad3-related) responds. ATR senses the stress, halts the cell cycle, and promotes DNA repair to allow proliferation. Alnodesertib is an ATR inhibitor developed to prevent cancer cells from successfully repairing RS and proliferating further. In earlier stages of alnodesertib development, preclinical and translational research demonstrated that tumor cells experience three combined biological insults: irinotecan-induced RS, endogenous RS via ataxia-telangiectasia mutated (ATM) loss, and RS rescue prevention by ATR inhibition. Data from the dose escalation and initial dose expansion cohorts of this trial in a tumor agnostic population showed encouraging results in ATM-negative cancers (confirmed Overall Response Rate of 50% in 20 patients with ATM negative cancers and responses across 8 cancer types including complete responses, Ulahannan et al, AACR 2025). Tumor-specific dose expansion cohorts are now enrolling, including colorectal cancer (CRC) and pancreas ductal adenocarcinoma (PDAC). Methods: Two tumor-specific cohorts are now open, each enrolling approximately 50 patients (pts): ATM-negative CRC and ATM-negative PDAC. Pts will receive the recommended dose of alnodesertib 200mg orally on days 1-3 and 8-10 combined with low-dose irinotecan 60mg/m 2 IV on days 1 and 8, of each 21-day cycle. Tumor tissue is prescreened by immunohistochemistry for ATM protein loss (H score 0) for enrollment eligibility. Pts with CRC must have received a maximum of 2 prior chemotherapies excluding prior trifluridine/tipiracil, fruquintinib, or regorafenib, and pts with PDAC must have received a maximum of 1 prior chemotherapy for advanced disease. Prior targeted agents are allowed and do not count as prior lines of therapy. Key objectives include safety, tolerability, and preliminary efficacy. Clinical trial information: NCT04657068 .

e23223 Background: Early-stage lung cancer is potentially curable with surgery, yet emergency or nonelective presentation represents a care-delivery phenotype reflecting failures in early diagnosis or access to care rather than tumor biology alone. The national impact of emergency presentation among surgically treated, presumed early-stage lung cancer patients is poorly defined. This study evaluates emergency versus elective presentation as a care-delivery phenotype and its association with perioperative morbidity, failure-to-rescue, and inpatient outcomes. Methods: A survey-weighted analysis of the National Inpatient Sample (2016–2023) was conducted. Adult lung cancer hospitalizations were identified using ICD-10-CM C34* in any diagnosis position. A presumed early-stage surgical cohort was defined by curative-intent lung resection without metastatic disease, malignant pleural effusion, or palliative care coding. The primary exposure was nonelective versus elective admission. Outcomes included in-hospital mortality; ICU-level care, defined by invasive mechanical ventilation, shock, or respiratory failure; major complications; failure-to-rescue; length of stay; and hospitalization cost and charges. Multivariable survey-weighted models adjusted for patient demographics, payer, neighborhood income, hospital characteristics, and year. Results: In the weighted cohort of 422,925 hospitalizations, nonelective admission occurred in 27.3%. After multivariable adjustment, nonelective admission was independently associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.59, 95% CI 2.22–3.03), ICU-level care (aOR 4.53, 95% CI 4.32–4.76), and major complications (aOR 5.00, 95% CI 4.78–5.23), as well as longer length of stay (+2.42 days). Notably, failure-to-rescue among patients with major complications did not differ by admission type (aOR 0.90, 95% CI 0.77–1.05), indicating that excess mortality associated with nonelective presentation is driven by presentation severity and care pathway rather than differences in rescue quality. In unadjusted analyses, nonelective presentation was associated with higher mortality (2.21% vs 0.68%), greater ICU-level care use (33.8% vs 8.9%), more frequent major complications (45.0% vs 12.4%), and longer length of stay (7.84 vs 4.99 days) compared with elective admissions. Conclusions: In a procedure-defined, presumed early-stage lung cancer surgical cohort, nonelective admission identifies a common care-delivery failure phenotype associated with higher perioperative morbidity, ICU-level care, in-hospital mortality, and longer hospitalization. Emergency presentation represents a systems-level vulnerability in curative-intent lung cancer care and serves as a scalable and actionable marker for quality improvement and disparity-focused analyses.

e23193 Background: Small cell lung cancer (SCLC) is typically treated with outpatient systemic therapy; inpatient chemotherapy during acute hospitalization represents a high-risk care-delivery phenotype driven by delayed diagnosis, access barriers, or acute clinical decompensation rather than tumor biology alone. National data describing this care pathway and its inpatient outcomes remain limited. Methods: The U.S. National Inpatient Sample (2016–2023) was analyzed using survey weights. Adult hospitalizations meeting an ICD-10–based proxy definition for small cell lung cancer, defined by lung cancer diagnoses combined with neuroendocrine malignancy codes and excluding palliative care admissions, were identified. Inpatient chemotherapy was defined using ICD-10-PCS administration codes with prespecified sensitivity definitions. Outcomes included in-hospital mortality (primary), ICU-level care, sepsis, acute kidney injury, length of stay, hospitalization costs, and routine discharge. Multivariable survey-weighted logistic regression adjusted for patient demographics, payer, admission characteristics, and hospital factors. Results: The analytic cohort included 2,507 unweighted hospitalizations, representing 12,535 nationally weighted admissions. In multivariable analyses adjusting for demographics, payer, admission characteristics, and hospital factors, inpatient chemotherapy was independently associated with higher in-hospital mortality (adjusted odds ratio [aOR] 2.31, 95% CI 1.48–3.60) and greater ICU-level care (aOR 2.80, 95% CI 1.86–4.23). These associations were consistent across prespecified sensitivity analyses. In unadjusted analyses, inpatient chemotherapy occurred in 12.3%–19.3% of admissions annually from 2016–2023 and was associated with higher mortality (8.7% vs 5.2%), greater ICU-level care (11.8% vs 4.9%), longer length of stay (11.6 vs 7.0 days), higher costs ($38,446 vs $23,746), and lower routine discharge rates (42.8% vs 48.4%). Among 400 admissions with procedure-day data, chemotherapy was administered a mean of 3–5 days after admission. Late inpatient chemotherapy (day ≥2) was associated with higher mortality (10.6% vs 5.6%), greater ICU-level care (14.8% vs 9.2%), longer hospitalization (14.1 vs 8.0 days), and higher costs ($46,203 vs $28,025) compared with early chemotherapy (day 0–1), supporting inpatient chemotherapy as a marker of late care escalation rather than planned inpatient treatment. Conclusions: Inpatient chemotherapy identifies a high-risk care-delivery phenotype in hospitalized small cell lung cancer, with higher mortality, greater ICU-level care, and increased resource use, supporting its role as a marker of late care escalation or system-level barriers and a scalable quality indicator.

e19046 Background: While outcomes in pts with R/R FL have improved with current SOC treatments (Tx), there remains a need for safe, efficacious, and convenient Tx options. GOLCA is a potential, first-in-class, oral CELMoD designed for Tx of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA induces rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing and immunomodulatory activity. GOLCA + R was well tolerated and effective in heavily pretreated pts in the two-part Ph 1/2 study, CC-99282-NHL-001. Here, we provide longer f/u in pts with R/R FL from Part B of the study. Methods: Pts with R/R FL with ≥2 prior lines of Tx (≥1 if prior anti-CD20 Tx) received GOLCA orally, once daily at 0.2 mg (n=22) or 0.4 mg (n=38) ± R for up to 2 y or until progressive disease (PD)/unacceptable toxicity. Primary endpoints included safety and RP2D determination; secondary endpoints are preliminary efficacy and PK. Results: As of September 15, 2025, 60 pts were enrolled. In 0.2 and 0.4 mg groups, median prior Tx lines were 3 and 3, 32% and 32% had prior lenalidomide (LEN), 27% and 29% had prior T-cell–redirecting Tx (CAR T and/or bispecific antibody) and 32% and 32% were refractory to last regimen. Tx is ongoing in 6 (27%) and 17 (45%) pts at 0.2 and 0.4 mg, respectively; discontinuations (d/c) were mostly due to PD. Neutropenia, an on-target side effect of GOLCA, was the most common grade 3/4 Tx-emergent adverse event (TEAE) occurring in 59% and 68% of pts at 0.2 and 0.4 mg, followed by anemia (9% and 16%) and febrile neutropenia (9% and 8%). Median time to resolution of neutropenia was 8 days. Dose reductions occurred in 14% and 37% of pts at 0.2 and 0.4 mg, most commonly due to neutropenia (5% and 21%) and febrile neutropenia (5% and 5%). No d/c or deaths were from GOLCA-related TEAEs. Non-hematologic TEAEs were infrequent and mostly low grade. In efficacy-evaluable pts (GOLCA 0.2 and 0.4 mg + R, n=22 and n=36), median f/u was 14.03 months (mo), overall response rate (ORR) was 77% (complete response rate [CRR], 41%) at 0.2 mg, and 97% (CRR, 78%) at 0.4 mg. In the 0.4 mg group, responses were consistent in high-risk subsets including pts with prior LEN (ORR, 100%; CRR, 75%) and/or T-cell–redirecting Tx (ORR, 91%; CRR, 64%). GOLCA 0.4 mg + R demonstrated durable responses (median DOR, 9.17 mo; 91% of pts who achieved a CR remained in CR at cutoff). Conclusions: With longer f/u, GOLCA + R demonstrated promising efficacy with durable responses and no new safety signals. The 0.4 mg group had higher ORR and CRR than 0.2 mg, including in pts with prior LEN-based and/or T-cell–redirecting Tx, with a manageable safety profile at both doses. The results support the development of GOLCA + R as a fixed-duration, chemotherapy-free outpatient Tx in the Ph 3 GOLSEEK-4 study in 2L+ FL (NCT06911502). Clinical trial information: NCT03930953 .

e16435 Background: Peritoneal metastasis in pancreatic ductal adenocarcinoma (PDAC) is historically associated with a dismal prognosis and limited response to systemic therapy alone. The role of locoregional therapy remains controversial. This study evaluated the survival impact and safety of HIPEC, with or without cytoreductive surgery (CRS), compared to standard-of-care systemic therapy in patients with peritoneal metastatic PDAC. Methods: We conducted a comparative analysis of 130 patients with peritoneal metastatic PDAC, comprising a study cohort treated with HIPEC (n = 33) and a control group treated with systemic chemotherapy alone (Non-HIPEC, n = 97). HIPEC patients received induction chemotherapy (predominantly FOLFIRINOX) followed by HIPEC ± CRS. Co-primary endpoints included 12 months survival, and 6 months progression free survival (PFS). Secondary endpoints evaluated Overall Survival (OS ), safety of CRS, and impact of germline mutation status on survival. Study was approved under IRB protocol 25-008762. Results: The 12-month OS rate was significantly higher in the HIPEC group compared to the chemotherapy-only control group (100% vs. 52.6%, P < 0.001). The 6-month PFS rate in the HIPEC group was 63.0% vs. 47.94 in-only control group (P < 0.001). For secondary endpoints, the HIPEC group demonstrated a significantly longer median OS of 33.0 months vs. 17.0 months for controls (P < 0.001). Within the HIPEC cohort, the addition of CRS (n = 25) significantly improved outcomes compared to HIPEC alone (n = 8): median OS improved from 21.5 to 36.0 months (P = 0.03). Germline testing was performed in 61% of HIPEC patients and 48% of controls, identifying pathogenic mutations in 25% and 17%, respectively. Identified pathogenic mutations in both groups included ATM (n = 4), MUTYH (n = 2), BRCA2 (n = 1), CHEK2 (n = 1), PALB2 (n = 1), and KIT (n = 1). In the control group, specific mutations drove divergent outcomes; ATM median OS: 23.5 months vs. MUTYH : 8.0 months (P = 0.04). Conversely, in the HIPEC+CRS cohort, survival was excellent regardless of genetic profile: mutation carriers achieved a median OS of 33.0 months compared to 31.0 months in wild-type patients (P = 0.85). Despite a 34.8% postoperative complication rate in the HIPEC group, there was no perioperative mortality. Conclusions: In selected patients with peritoneal metastatic PDAC, HIPEC provides a substantial survival advantage over systemic therapy alone, achieving a 100% 12-month survival rate and more than doubling the median overall survival. Importantly, germline mutation status did not preclude survival benefit, with mutation carriers deriving equal efficacy from the multimodal approach. These findings support HIPEC+CRS as a highly effective strategy that may overcome adverse biologic drivers.

e16323 Background: Advanced EP-NEC are typically treated with the combination of platinum plus etoposide. Despite therapy, outcomes remain poor, with reported median overall survival (OS) of 12-13 months. Early initiation of systemic therapy is commonly practiced given the aggressiveness; however, recent data from small cell lung carcinoma (SCLC) suggest that shorter TTI does not necessarily improve OS. The impact of TTI on outcomes in EP-NEC has not been well studied. Methods: We conducted a multicenter retrospective cohort study across three Mayo Clinic sites including adults with biopsy-confirmed stage IV EP-NEC diagnosed between 2005 and 2025. TTI was defined as days from pathologic diagnosis to initiation of first-line systemic therapy. A binary cutoff (≤14 vs > 14 days) was determined using receiver operating characteristic (ROC) analysis, and TTI was also analyzed as a continuous variable. OS and progression-free survival (PFS) were estimated using the Kaplan–Meier method and evaluated using Cox proportional hazards models. Multivariable analyses adjusted for age, sex, ECOG performance status, presence of liver metastases, and first-line treatment strategy (chemotherapy alone vs chemotherapy plus immunotherapy). Results: Among 248 pts, median age was 61 years. Median OS for the cohort was 13.9 months (95% CI, 11.7–16.7), and median PFS was 5.7 months (95% CI, 5.3–6.3). Pts with TTI > 14 days had longer median OS compared with those treated within ≤14 days (16.4 vs 10.1 months), with improved OS on unadjusted analysis (HR 0.69, 95% CI 0.50–0.96; p = 0.028), though this association was not statistically significant after multivariable adjustment (HR 0.74, 95% CI 0.53–1.05; p = 0.097). Pts with TTI > 14 days also had longer median PFS compared with ≤14 days (6.5 vs 4.8 months), with improved PFS on unadjusted analysis (HR 0.67, 95% CI 0.51–0.88; p = 0.0038). On multivariable analysis, TTI > 14 days remained independently associated with improved PFS (HR 0.75, 95% CI 0.56–1.00; p = 0.047). However, when analyzed as a continuous variable, TTI was not independently associated with OS (HR 0.99, 95% CI 0.98–1.00; p = 0.173) or PFS (HR 0.99, 95% CI 0.98–1.00; p = 0.089). Conclusions: In this multicenter cohort of pts with metastatic EP-NEC, earlier initiation of systemic therapy (≤14 days) was not associated with improved overall survival, and longer time-to-treatment was independently associated with improved PFS. However, when TTI was analyzed as a continuous variable, no statistically significant associations were observed, suggesting that the observed benefit with delayed treatment may reflect pt selection or clinical context rather than a direct biological effect. These findings may provide reassurance in scenarios where short delays are necessary—for biomarker testing or clinical trial enrollment—and highlight the need for further investigation in the era of precision oncology.