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Evaluating the impact of the 2021 USPSTF age expansion (50–54 years) on racial disparities in early-stage lung cancer diagnosis.
10546 Background: In 2021, the USPSTF updated its guidelines to address known racial disparities in lung cancer outcomes. By lowering the screening age to 50 and reducing the pack-year threshold, one of the goals was to better identify Black individuals, who historically develop cancer at younger ages and with lower smoking intensity than their White counterparts. However, despite this expanded eligibility, screening uptake among the newly eligible 50–54 years cohort remains low. Our study evaluates whether these policy changes have translated into a tangible 'stage shift' toward earlier detection among the newly eligible age group and assesses if these benefits are being realized equitably across racial groups. Methods: We conducted a retrospective cohort study using SEER November 2024 sub data (21 Registries) for non-small cell lung cancer (NSCLC) cases. We compared the Pre-Guideline (2016–2019) period to the Post-Guideline (2022) period, excluding initial COVID-19 and transition years (2020–2021). A Difference-in-Differences (DiD) approach compared the newly eligible Target Group (50–54 years) against a Control Group (45–49 years) to control for secular staging trends. The primary outcome was the percentage of localized disease at diagnosis, stratified by race. Results: In the newly eligible 50–54 cohort, White patients demonstrated a robust stage shift, with localized disease increasing from 23.2% to 28.7% (p<0.001). Conversely, Black patients in the target age group experienced a decline in localized detection from 20.1% to 17.5%, with a concurrent rise in distant-stage diagnoses. Notably, Black patients in the younger control group (45–49) showed improved early detection (+3.3%), suggesting the disparity was specific to the guideline implementation in the target cohort. The DiD interaction was significant (p<0.05), confirming racially distinct outcomes. Hispanic patients saw a case volume surge without a significant rise in localized disease (22.3% to 22.6%). Conclusions: Initial data following the 2021 USPSTF expansion suggests an early stage shift for White patients aged 50–54, while a similar trend was not observed among Black patients in this first year of implementation. This divergence may reflect a temporary implementation lag, variability in provider adoption, or early access delays rather than a definitive failure of the policy. Continued longitudinal surveillance is required to determine whether this gap represents a transient uptake issue or a persistent disparity necessitating targeted structural interventions. Impact of age expansion on early detection (% localized disease). Group Race Pre-Guideline (2016-19) Post-Guideline (2022) Net Change Target (50-54 years) White 23.22% 28.65% +5.43% Black 20.14% 17.53% -2.61% Hispanic 22.33% 22.58% +0.25% Control (45-49 years) White 21.20% 22.44% +1.24% Black 17.79% 21.09% +3.30%
The inpatient cancer diagnostic service: An academic cancer center experience.
e23015 Background: Rapid inpatient cancer diagnosis may reduce time to treatment and improve outcomes, particularly among medically complex patients. The Ohio State University (OSU) Comprehensive Cancer Center established an Inpatient Cancer Diagnostic Service (ICDS) for hospitalized patients with suspected new malignancy to expedite diagnosis and treatment. We describe clinical outcomes associated with this inpatient diagnostic care model. Methods: We retrospectively reviewed hospitalized patients evaluated by ICDS between January 1, 2018 and June 30, 2021. Data included pathology, cancer type, time to oncology follow-up, time to treatment initiation, and overall survival (OS). OS was calculated from admission to death, censoring patients alive at last follow-up. Kaplan–Meier and log-rank tests were used. Results: A total of 1,281 patients met inclusion criteria; 252 did not undergo inpatient tissue sampling (192 deferred to outpatient evaluation, 56 declined further workup and enrolled in hospice, and 4 were diagnosed with hepatocellular carcinoma based on imaging and included in the analysis). Inpatient diagnostic evaluation was completed in 1,033 patients (median age 64 years; 57.6% male). Benign pathology was identified in 17.3%. Among patients with cancer (n = 854), gastrointestinal (30.0%) and thoracic (26.6%) malignancies were most common (Table). Hematologic malignancies comprised 7.4%, most commonly lymphoma (41.6%). A total of 552 patients (64.6%) established oncology follow-up at OSU; 474 (55.5%) received cancer-directed therapy at OSU and 201 received treatment outside OSU. Mean time from admission to diagnosis was 6.4 days; among those followed at OSU, mean time to first oncology visit and treatment initiation was 18.7 and 29.3 days. With median follow-up of 4.2 years, patients treated at OSU had improved OS compared with those treated elsewhere (P < 0.001), likely reflecting referral and selection bias at a tertiary cancer center. One-year survival was 59.1% for patients treated at OSU, 31.3% for those treated elsewhere, and 3.1% for patients referred to hospice. Median OS was 1.48, 0.33, and 0.06 years, respectively. Conclusions: The ICDS model facilitated timely diagnosis and oncologic follow-up and was associated with improved survival among patients receiving longitudinal care at OSU. This ICDS model may be scalable to other comprehensive cancer centers. Limitations include retrospective design and potential selection bias among patients receiving care at OSU. Cancer diagnoses. Cancer Type Number, (%) Median OS in Years, (95% CI) Gastrointestinal 260 (30%) 0.44 (0.31-0.60) Thoracic 228 (26.6%) 0.55 (0.40-0.77) Genitourinary 70 (8.2%) 1.04 (0.55-1.71) Head and neck 65 (7.6%) 1.00 (0.54-2.02) Hematologic 64 (7.4%) 3.82 (2.41-NR) Other 61 (7%) 0.87 (0.72-1.44) Unknown primary 53 (6%) 0.13 (0.09-0.21) Breast 37 (4.3%) 1.86 (0.81-3.06) Gynecologic 16 (1.8%) 2.02 (0.50-NR)
Trends in locoregional colorectal cancer incidence by socioeconomic factors in US adults aged 45-49 with updated screening guidelines (2013-2022).
e15686 Background: Colorectal cancer (CRC) screening guidelines from the American Cancer Society recommended lowering the starting age from 50 to 45 in 2018, and the US Preventive Services Task Force followed suit in 2021. We examined the impact of these guideline changes on locoregional CRC incidence overall and by county-level socioeconomic factors. Methods: We used the SEER Research Plus database to identify locoregional CRC cases diagnosed in 2013-2022 in adults aged 45-49. We calculated age-adjusted annual incidence rates (IRs) per 100,000 persons by county-level median household income, educational attainment, and urbanicity. We measured IRs for 2013-2022 and used NCI’s Joinpoint Regression Program v5.4.0 to estimate annual percent change (APC) trends. Results: We identified 14,123 locoregional CRC cases during the study period. Joinpoint regression detected an APC trend change in 2020. For overall incidence, the APC was 1.41% (95% CI -3.08-3.29) from 2013-2020 and increased to 23.07% (95% CI 10.47-30.25) from 2020-2022. The sharp rise in APC was observed across all income categories, but the magnitude of increase was larger with higher income, higher educational attainment ( < 20% adults with less than a high school education), and urban residence (Table 1). Conclusions: Following CRC screening guidelines updates, locoregional CRC incidence among adults aged 45–49 years rose across all groups, though the relative magnitude of increase differed by socioeconomic status. Counties with higher income, higher educational attainment, and located in urban areas saw greater relative increases in locoregional CRC, which have a more favorable prognosis. This may indicate higher screening uptake in areas with higher socioeconomic status. These findings underscore the need to improve access and address disparities in early CRC screening. Trends in locoregional CRC incidence by county-level socioeconomic factors. Socioeconomic Factor 2013-2020 APC (95% CI) 2020-2022 APC (95% CI) APC change (2020-2022) vs (2013-2020) Lowest income quintile 0.08 (-4.53-1.90) 17.87 (6.20-25.54) 17.79 Highest income quintile 2.19 (-4.25-4.69) 24.94 (9.93-35.26) 22.75 Low education -2.81 (-15.20-12.94) 13.61 (-5.19-29.61) 16.42 High education 1.77 (-1.88-3.49) 23.42 (11.52-30.16) 21.65 Rural -0.94 (-6.00-0.98) 16.82 (3.98-25.46) 17.76 Urban 1.83 (-1.83-3.54) 23.70 (11.83-30.60) 21.87
Risk stratification for prostate cancer screening using PSA and prostate volume.
e17000 Background: Prostate-specific antigen (PSA) testing is widely used for prostate cancer screening but is limited by low specificity, leading to unnecessary imaging and biopsies. In this retrospective study across seven Brazilian laboratories, we developed a logistic regression model incorporating total PSA, free PSA, age, and PSA density (PSA/Prostate Volume), and compared its performance with PSA alone. Methods: We analyzed PSA data from 2,978 men aged 45-75 years who underwent prostate magnetic resonance imaging (MRI) or biopsy within six months of blood collection, collected between September 2010 and October 2024 across seven Brazilian diagnostic laboratory networks (Fleury, Labs a+, Grupo Pardini, a+ Medicina Diagnóstica, Felippe Mattoso, Weinmann and LAFE). Cases (190) were defined by biopsy-confirmed prostate cancer, and controls (2,788) by benign MRI findings (PI-RADS 1-2) or negative biopsy. Prostate volume was extracted from MRI or ultrasound reports. Data were pooled into a single dataset, randomly split into training (70%) and test (30%) sets, and used to train a logistic regression model with bootstrap-based performance estimation. Results: Total PSA, free PSA, PSA density (p < 0.001), and age (p < 0.05) were significantly higher in men with prostate cancer. Incorporation of these variables into a logistic regression model yielded an average AUC of 0.77 ± 0.04, with sensitivity of 0.80 ± 0.06, specificity of 0.65 ± 0.02, accuracy of 0.66 ± 0.02, balanced accuracy of 0.72 ± 0.03, negative predictive value of 0.98 ± 0.01, and positive predictive value of 0.13 ± 0.02. Compared with PSA alone using a cutoff of 4 ng/mL, which yielded a sensitivity of 0.80 ± 0.06 and a specificity of 0.46 ± 0.02, the model was associated with a 35.1% relative reduction in false-positive classifications. Conclusions: Our machine learning model, integrating PSA-derived parameters and PSA density, demonstrates potential as a risk stratification tool to identify men at elevated risk for prostate cancer, potentially optimizing the use of MRI and biopsy resources, as prostate volume can be estimated using lower-cost ultrasound. This strategy may be particularly advantageous in resource-limited settings, where access to advanced imaging and invasive diagnostic procedures is limited. External validation across diverse populations is required to support clinical implementation and confirm model generalizability and effectiveness.
A phase III randomized trial of pembrolizumab in combination with sacituzumab govitecan vs standard of care in anti–PD-(L)1–resistant advanced urothelial cancer: ECOG-ACRIN EA8231.
TPS4641 Background: Patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) who progress after anti-PD-(L)1 therapy (CPI-R) and enfortumab vedotin (EV) have relatively limited treatment options and poor outcomes. SG, a TROP-2–directed antibody–drug conjugate (ADC), has meaningful efficacy in previously treated la/mUC, while SG plus pembro achieved 41% overall response rate (ORR; 20% complete response rate) in platinum-refractory la/mUC. With rapidly evolving treatment paradigms and earlier use of EV and anti-PD(L)1, the frequency of CPI-R la/mUC is expected to increase; therefore, newer combinations and the role of anti-PD(L)1 re-challenge should be prospectively evaluated in previously treated la/mUC. We hypothesized that SG/pembro combination would improve outcomes over standard chemotherapy (SOC) in pts previously treated with anti-PD(L)1. Methods: EA8231 is an open-label, multicenter, randomized phase III trial enrolling adults with unresectable la/mUC. Key eligibility criteria: a) ECOG PS 0-2 b) Prior anti-PD(L)1 given in any disease setting but no cancer progression within 12 weeks from starting prior anti-PD(L)1initiation c) Prior exposure to EV unless contraindicated d) ≥1 lines of systemic therapy for la/mUC [ FGFR3 altered tumors must have received prior FGFR inhibitor unless contraindicated] e) Bellmunt score 0-2 f) No prior exposure to SG or other TROP-2 directed therapies or drugs containing topo-isomerase I inhibitor. Treatment: Pts are randomized 1:1 to Arm A SOC (platinum-gemcitabine or taxane Q3 week cycle) OR Arm B pembro/SG (Pembro 200mg on day 1 + SG 10mg/kg on days 1, 8 of a 21-day cycle with G-CSF support). Pts are stratified by Bellmunt score (0-1 vs 2), prior lines of therapy (≤2 vs >2), prior exposure to platinum-based chemotherapy (yes vs no prior exposure and platinum-eligible vs no prior exposure and platinum-ineligible), duration of prior anti PD-(L)1 therapy (≤6 vs >6 months). G-CSF primary prophylaxis is strongly recommended, esp. with SG. Endpoints : Primary endpoint: overall survival (OS); secondary endpoints: progression-free survival, ORR, clinical benefit rate, duration of response, safety/tolerability, health related QOL (NFBlSI-18; FACIT-Fatigue; EQ-5D-5L). Statistical plan: Trial is designed to demonstrate 42.5% improvement in median OS [platinum-ineligible cohort: median OS increase from 9 to 12.8 months; platinum-eligible cohort: median OS increase from 10.3 to 14.7 months]; 80% power with 1-sided 0.025 type I error rate; HR (pembro+SG/SOC) 0.70, N=320. Trial Status: Activation date: 10/23/2025 (1 patient accrued as of Jan 6, 2026; 28 approved sites, additional sites pending). Clinical trial information: NCT06524544 .
The neurotoxicity rating scale: A novel patient-reported outcome (PRO) measure for neuro-psycho-behavioral late effects in head and neck cancer (HNC) survivors.
12115 Background: Chronic fatigue, mood disorders and cognitive dysfunction are well recognized but understudied late toxicities experienced by HNC survivors. In addition to these well recognized central symptoms, patients also experience an array of less well recognized psycho-behavioral complaints (see table below). These symptoms may profoundly affect a patient’s ability to function within society. The neurotoxicity rating scale (NRS) was developed to assess the breadth of neuro-psycho-behavioral symptoms in cancer patients treated with interferon. We conducted a prospective cohort study in HNC survivors to assess the psychometric properties of this tool. Methods: Eligible patients included HNC survivors without evidence of disease ≥6 months after completion of therapy. The NRS was administered as part of a battery of patient reported outcome measures to assess pain and central symptoms. The NRS is a patient reported outcome measure which includes 36 items ranked from 0-4 (0 = no symptoms, 4 = severe). Hierarchical clustering was applied. Results: 243 patients were included with an average age of 72 years. Patients experienced clinically significant levels of neuro-psycho-behavioral symptoms; prevalence for selected items are shown in the table below. Preliminary analysis results in a group of six of clusters. The six-cluster solution was chosen as the most appropriate fit based on expert opinion. Clusters included: pain (α=0.89), sleep (α=0.83), general systemic symptoms (α=0.67), neuromotor-autonomic (α=0.73), cognitive (α=0.82), and psycho-behavioral (α=0.94). Conclusions: The NRS is a unique tool that comprehensively captures neuro-psycho-behavioral symptoms not assessed by existing instruments. The preliminary analysis amongst HNC survivors confirms the high prevalence of neuro-psycho-behavioral symptoms in this population. We identified six distinct symptom clusters: all demonstrated good internal constancy. This instrument allows for systematic study of neurotoxicity patterns, identification of high-risk patients, and evaluation of targeted interventions. Future directions include longitudinal validation and correlation with objective neuropsychiatric testing. Selected items from the NRS with prevalence. Item Prevalence (%) Tiredness/Fatigue 68% Difficulty staying asleep 58% Loss of interest in sex 41% Restlessness 44% Distractibility 41% Word-finding difficulty 41% No interest in activities 35% Memory problems 50% Decreased motivation 43%
Impact of GLP1 receptor agonists on survival of breast cancer patients.
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.
Evaluation of imiquimod treatment outcomes in vulvar melanoma.
5540 Background: Vulvar and vaginal melanomas account for approximately 10% of vulvar malignancies and less than 1% of all melanomas. Compared to cutaneous melanoma at other sites, vulvovaginal melanoma is associated with significantly worse outcomes. Wide local excision is the standard treatment for vulvar melanoma, but anatomical challenges and the “field effect” complicate complete resection. The field effect refers to a margin of pre-cancerous intraepithelial cells extending beyond the visible tumor and is thought to contribute to local recurrence. Imiquimod, an immune-modifying cream indicated for genital warts and some types of early keratinocyte carcinomas, is used off-label as an adjunct therapy to prevent marginal recurrence of vulvar melanoma in situ. Its benefit in this setting remains unclear due to limited outcome data, and it is associated with significant side effects. More research is needed to clarify the role of imiquimod and explore alternative therapies. This case series aims to evaluate recurrence and survival outcomes following imiquimod treatment and inform clinical management in this understudied cancer subtype. Methods: Patients were identified by two criteria: (1) confirmed vulvar melanoma and (2) treatment with imiquimod. Cases were drawn from a previously published institutional cohort focused on adjuvant radiation therapy in vulvovaginal melanoma and from MD Anderson’s electronic medical records. Regional progression-free survival and overall survival were defined as study endpoints. Data included demographics, clinical characteristics, and recurrence and mortality outcomes. Kaplan–Meier analysis compared progression-free and overall survival between patients treated with imiquimod and those who were not. Results: Among 124 patients, 19 received imiquimod. The imiquimod group showed a modest improvement in regional progression-free survival, but no significant difference in overall survival (p = 0.1753 and p = 0.2775, respectively). Imiquimod was associated with notable side effects, including burning, itching, and blistering. Conclusions: This case series highlights the limited evidence supporting imiquimod as an effective adjunct therapy for vulvar melanoma. Although there was a trend toward delayed regional progression, differences were not statistically significant, and side effects raise concerns about patient quality of life. These findings underscore the need for more effective and tolerable strategies. A systematic review is underway, and multi-institutional efforts aim to expand the dataset. Greater evidence is essential to guide treatment decisions, optimize outcomes, and ensure survivor-centered care in this rare and understudied cancer.
The prognostic and predictive role of FDG PET/CT in melanoma patients treated with immune checkpoint blockade: A meta-analysis.
9542 Background: Immune checkpoint blockade (ICB) is standard therapy for advanced melanoma, but many patients derive limited benefit. Biomarkers to guide treatment decisions are needed. FDG PET/CT (PET) shows promise for response assessment, but most studies are small or evaluate a single timepoint. Here, we conducted a meta-analysis to assess the prognostic value of metabolic response for overall survival (OS) and progression-free survival (PFS), and the diagnostic performance of PET-derived parameters. Methods: PubMed, Cochrane, and EMBASE were searched for studies including melanoma patients treated with ICB who underwent baseline and follow-up PET. Metabolic response was defined using PERCIST, PERCIST5, or EORTC criteria, dichotomizing patients as responders or non-responders. Random-effects meta-analyses estimated pooled hazard ratios (HRs) for OS and PFS, with subgroup analyses by PET timing (early ≤4 months vs late > 4 months). Univariate diagnostic meta-analyses evaluated the accuracy of changes in total lesion glycolysis (TLG) and metabolic tumor volume (MTV) for predicting death or OS, as well as the ability of PET-defined progressive metabolic disease (PMD) to identify clinical or RECIST-based disease progression. Results: Of the 15 studies included, 943 pts were included. Interval metabolic response was significantly associated with improved OS (HR 0.22; 95% CI 0.13-0.36; p = 0.02), with no significant difference according to the time of PET assessment early vs late (p for interaction = 0.75). Similarly, metabolic responders experienced significantly longer PFS (HR 0.21; 95% CI 0.11-0.39; p = 0.03). Although the association was statistically significant for late (HR 0.21; 95% CI 0.11-0.41), but not for early assessment (HR 0.13; 95% CI 0.01-1.91), no subgroup difference was observed (p for interaction = 0.73). In diagnostic analyses for OS prediction, changes in TLG demonstrated a pooled sensitivity of 0.70 (95% CI 0.54-0.82) and specificity of 0.79 (95% CI 0.52-0.93). Changes in MTV showed comparable performance, with a sensitivity of approximately 0.70 (95% CI 0.54-0.82) and a specificity of 0.83 (95% CI 0.42-0.97). PET-defined PMD showed good diagnostic accuracy for identifying clinical or RECIST-defined disease progression, with a pooled sensitivity of approximately 0.71 (95% CI 0.42-0.89) and specificity of 0.86 (95% CI 0.69-0.95). Conclusions: In our study, metabolic response by PET was associated with improved OS and PFS, irrespective of the timing of imaging. Quantitative changes in TLG and MTV provide moderate accuracy for predicting survival, while PET/CT-defined PMD reliably identified RECIST-based disease progression. These findings support future prospective studies investigating the role of PET dynamics as a minimally invasive prognostic and predictive biomarker for pts with advanced melanoma undergoing treatment with ICB.
A randomized, active-controlled phase 3 study of ivonescimab + FOLFOX versus bevacizumab + FOLFOX as first-line treatment of metastatic colorectal cancer (mCRC): HARMONi-GI3.
TPS3682 Background: Fluorouracil (5-FU)-based chemotherapy plus an anti–vascular endothelial growth factor (VEGF) or anti–epidermal growth factor receptor (EGFR) therapy is recommended as first-line treatment for many patients with mCRC; however, prognosis is still poor, with a 5-year survival rate of <30%. The investigational, anti–programmed cell death protein 1 (PD-1)- and VEGF-bispecific antibody ivonescimab is approved in China for non-small cell lung cancer (NSCLC) and is currently being evaluated as monotherapy or in combination with chemotherapy in global phase 3 clinical trials for NSCLC, and in other tumor types including colorectal cancer. Methods: HARMONi-GI3 (NCT07228832) is a randomized, active-controlled, double-blind, multiregional, phase 3 trial to compare the efficacy and safety of ivonescimab + 5-FU, oxaliplatin, and leucovorin (mFOLFOX6) versus bevacizumab + mFOLFOX6 in patients with mCRC who are not candidates for surgical resection, have not previously received systemic therapy for metastatic disease, and have an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients with microsatellite instability-high or mismatch repair deficient disease, and with BRAF V600E mutation or dihydropyrimidine dehydrogenase deficiency, will be excluded. Approximately 600 patients will be randomly assigned (1:1) to receive ivonescimab 20 mg/kg + mFOLFOX6 or bevacizumab + mFOLFOX6 every 2 weeks for up to 4 months, followed by maintenance with ivonescimab + 5-FU and leucovorin or bevacizumab + 5-FU and leucovorin until disease progression, intolerable toxicity, or initiation of new anti-tumor therapy. Randomization will be stratified according to geographic region (East Asia, Europe, North America), liver metastases at study entry (absence or presence), and rat sarcoma virus tumor mutational status (RAS; mutant or wild-type). The hypothesis of this study is that ivonescimab + mFOLFOX6 has superior efficacy to bevacizumab + mFOLFOX6 in patients with mCRC who have not previously received systemic therapy for metastatic disease, as determined by progression-free survival (PFS). The primary endpoint is PFS (assessed by independent radiology review committee per Response Evaluation Criteria in Solid Tumors, v1.1). Secondary endpoints are overall survival, objective response rate, duration of response, safety, pharmacokinetics of ivonescimab + mFOLFOX6, and immunogenicity. All patients will have regular tumor evaluations every 8 weeks until week 48, then every 12 weeks until disease progression, loss to follow-up, death, withdrawal, or study closure. HARMONi-GI3 is currently recruiting participants. Clinical trial information: NCT07228832 .
Health shocks and advance care planning among U.S. older adults: Evidence from HRS 2012-2022.
11093 Background: Advance care planning (ACP) allows individuals to discuss and document preferences for future medical care under serious illness, yet engagement among older adults remains limited. Experiences of a health shock, such as a diagnosis of cancer, major illnesses, or hospitalization, may prompt participation in ACP. This study aimed to examine the association between health shocks and subsequent ACP engagement and variation by key sociodemographic characteristics. Methods: We conducted a longitudinal cohort study using data from the Health and Retirement Study (HRS), a nationally representative survey of U.S. adults aged ≥65 years. Adults from 2012–2022 HRS with no baseline ACP who completed at least one follow-up wave were included. The exposure was a new health shock, defined as a new diagnosis of cancer, stroke, heart disease, or hospitalization. The outcome was new ACP engagement in subsequent waves. Generalized estimating equation models estimated adjusted odds ratios (ORs) of experiencing a health shock due to cancer diagnosis and due to other causes (vs. no health shock) on new ACP; and how such associations varied by respondents’ characteristics. Results: Among 8,553 person-wave observations (4,426 unique respondents), median age was 74 years (IQR 69–79); 52.9% were women, 24.3% lived alone, 27.6% experienced a health shock, and 3.11% reported a health shock from new cancer diagnosis. Health shocks were associated with higher odds of ACP engagement (OR = 1.41; 95% CI, 1.28–1.56). In the three-level shock model, both non-cancer shock (OR = 1.43; 95% CI, 1.28–1.59) and cancer shock (OR = 1.31; 95% CI, 1.01–1.70) were associated with higher odds of ACP compared with no shock. Older age, female gender, and higher education were associated with greater ACP engagement overall. Compared with non-Hispanic Whites, non-Hispanic Black (OR = 0.73; 95% CI, 0.64–0.84) and Hispanic (OR = 0.55; 95% CI, 0.47–0.65) had lower odds of ACP. Living alone was associated with higher ACP engagement (OR = 1.29; 95% CI, 1.14–1.45). However, when stratified by patient sociodemographic characteristics, the associations between health shock and ACP were similar across groups, except that for those living alone who showed larger odds of initiating a new ACP following health shock (OR = 1.76; 95% CI, 1.45-2.14) than those not living alone (OR = 1.31; 95% CI, 1.16-1.47). Conclusions: Health shocks were associated with new ACP engagement among older adults, with similar associations observed for cancer-specific and non-cancer health shocks. Alhtought disparities in ACP by sociodemographic characteristics persisted, health shocks were associated with similarly odds of initiating ACP across population subgroups. This highlights the importance of leveraging health shocks as clinical touchpoints for ACP discussions, and the need for targeted strategies to reduce inequities in ACP engagement outside of acute health events.
Regional trends in esophageal cancer burden across Africa, 1990–2023: A Global Burden of Disease study.
e16042 Background: Esophageal cancer is a major contributor to cancer-related mortality in Africa, with marked regional disparities; this study assesses long-term trends in its burden using the Global Burden of Disease (GBD) 2023 study. Methods: Age-standardized death rates (ASDRs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and disability adjusted life years (DALYs) per 100,000 population were obtained for African regions based on GBD classifications, including Northern, Central, Eastern, Western, and Southern Africa, as well as the African Union aggregate.Trends were assessed using joinpoint regression with average annual percentage change (AAPC) used to quantify long-term trends. Statistical significance was determined p-value (< 0.05). Results: Between 1980 and 2023, ASDRs increased significantly in Central Africa (AAPC: 0.43; 95% CI 0.32–0.55; p < 0.00001), Northern Africa (AAPC: 0.43; 95% CI 0.27–0.59; p < 0.00001), and Western Africa (AAPC: 0.16; 95% CI 0.05–0.27; p = 0.003663), while Southern Africa experienced a significant decline (AAPC: −0.69; 95% CI −0.92 to −0.46; p < 0.00001). Eastern Africa and the African Union demonstrated stable trends with non-significant changes over time. A similar pattern was observed for ASPR, with significant increases in Central Africa (AAPC: 0.47; 95% CI 0.27–0.66; p = 0.000002), Northern Africa (AAPC: 0.44; 95% CI 0.22–0.66; p = 0.000095), and Western Africa (AAPC: 0.16; 95% CI 0.023–0.30; p = 0.0221), contrasted by a decline in Southern Africa (AAPC: −0.57; 95% CI −0.86 to −0.27; p = 0.000127). ASIR increased persistently in Central Africa (AAPC: 0.65; 95% CI 0.50–0.79; p < 0.000001), Eastern Africa (AAPC: 0.30; 95% CI 0.10–0.50; p = 0.0025), Northern Africa (AAPC: 0.37; 95% CI 0.062–0.69; p = 0.0186), and Western Africa (AAPC: 0.33; 95% CI 0.23–0.43; p < 0.000001), whereas Southern Africa showed a significant reduction (AAPC: −0.63; 95% CI −0.92 to −0.34; p = 0.000022). No significant change in ASIR was observed for the African Union. Trends in DALYs mirrored mortality patterns, with significant increases in Central Africa (AAPC: 0.55; 95% CI 0.42–0.69; p < 0.000001), Eastern Africa (AAPC: 0.22; 95% CI 0.0092–0.44; p = 0.0411), and Western Africa (AAPC: 0.27; 95% CI 0.17–0.37; p < 0.000001), alongside a marked decline in Southern Africa (AAPC: −0.64%; 95% CI −0.95 to −0.34; p = 0.000028). No significant DALY trends were observed in Northern Africa. Conclusions: Despite declines in Southern Africa, esophageal cancer incidence, mortality, and DALYs continue to rise in several African regions highlighting the need for geographically targeted prevention, early detection, and cancer control strategies. ↑ significant increase; ↓ significant decrease; NS non-significant trend (p>0.05). African Region ASDR ASIR ASPR DALYs Central ↑ ↑ ↑ ↑ Northern ↑ ↑ ↑ NS Western ↑ ↑ ↑ ↑ Eastern NS ↑ NS ↑ South ↓ ↓ ↓ ↓ African Union NS NS NS NS
Long term follow up of multiple myeloma patients achieving MRD negativity at 10 <sup>-6</sup> .
e19549 Background: Achievement of deep responses in multiple myeloma (MM) has been associated with improved outcome and the regular assessment of minimal residual disease (MRD) has become the new standard in patient care. With the improvement of molecular assays, the sensitivity of MRD assessment has deepened to levels of 10 -6 and the achievement of MRD negativity at such levels has shown to predict for excellent long-term outcome. Yet, follow up in most studies has been short and there is a lack of understanding if and how other factors could influence the prognostic impact of MRD negativity. This retrospective, single-center study investigates the long-term outcome of MM patients that achieved MRD negativity at 10 -6 and investigate the impact of other meaningful clinical parameters, such as age, high-risk (HR) disease and treatment lines. Methods: Negative test results from any MM patient who had at least one negative MRD test at 10 -6 by Clonoseq between 2018-2024 were included, yielding a total of 726 samples from 271 patients. HR status was defined according to the IMS/IMWG consensus. Time to progression (TTP) and overall survival (OS) were calculated with Kaplan Meier Curves; multivariate analysis (MVA) was performed using Cox regression with a counting-process model. Results: Median age of the patient cohort was 64 years with 136 (51%) being male and 84 patients (31.5%) had HR disease. For 222 patients (83.2%), the MRD test was done during first line therapy, while in 27 patients (10%) the test was performed during second line and in the remaining 18 (7%) patients, MRD was performed in 3 rd or later lines. Median TTP for the whole cohort from time point of initial negative MRD test was not reached, but the 5-year TTP was 72.8%. 5-year OS was 82.1%. Median time from MM diagnosis to initial MRD negative test was 43 months for the whole cohort and 37 months for patients in 1 st line. For patients that progressed, the median time from last negative MRD test to next treatment was 18.5 months. 5-year TTP was significantly worse for HR patients (60% vs 79%) compared to non-HR patient, p=0.01. Furthermore, in MVA, a higher age (>60 years) and more than one treatment line were significantly associated with shorter progression free survival. Conclusions: Here we show that MM patients who achieve MRD negativity at 10 -6 have an excellent long-term outcome, yet MRD negative results should always be interpreted in the context of other clinical factors. Even among patients that achieve MRD-negativity at 10 -6 , IMWG risk, age and number of prior lines continue to have prognostic impact.
Adjuvant nivolumab in high-risk muscle-invasive urothelial carcinoma: Real-world evidence from the SOGUG-NIADY study of the Spanish Oncology Genitourinary Group (SOGUG).
4606 Background: Adjuvant nivolumab significantly improved disease-free survival (DFS) in patients (pts) with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical surgery in the phase III CheckMate-274 trial. Based on these results, since august 2023, the Spanish National Health System reimburses postoperative nivolumab in high-risk, positive programmed death ligand 1 (PDL1) MIUC. The aim of the PrInCIS-NIADY study was to assess the effectiveness and safety of adjuvant nivolumab in real-world clinical practice after its approval in Spain. Methods: PrInCIS is a nationwide multicentre, non-interventional epidemiological study with retrospective patient inclusion and prospective follow-up. The NIADY cohort included pts with high-risk PDL1+ MIUC treated with adjuvant nivolumab in routine practice, was conducted across 65 hospitals belonging to the Spanish Oncology Genitourinary Group (SOGUG) in 16 Spanish regions. Baseline characteristics, treatment patterns, safety, and outcomes were analysed and compared against CheckMate-274. Results: A total of 395 evaluable pts were included, 95.7% were PD-L1 positive. Median age was 69.5 years, (74.9% aged ≥65 years); 91.4% had bladder cancer and 8.6% had upper tract disease. Predominant histology was urothelial carcinoma (79.2%). 51.2% pts received neoadjuvant platinum-based chemotherapy (NAChT) (48.9% cisplatin vs. 2.3% carboplatin) (Table). With a median follow-up of 13 months, 27.3% of pts had disease recurrence. Treatment after recurrence was platinum-based ChT in 8.8% and enfortumab vedotin in 6.6% of pts. Median DFS and overall survival (OS) were not reached. The estimated 18-month DFS and OS probability were 65.6% and 78.3% respectively. Nivolumab was well-tolerated: Treatment delays or dose reductions occurred in 37.3% of pts. Most common (>10%) grade 1-2 immune-related adverse events were fatigue, pruritus and diarrhea, while grade 3–4 toxicity was infrequent (>1%), mainly consisting in hepatic enzyme and creatinine elevation. Conclusions: Outcomes and effectiveness of adjuvant nivolumab in this large Spanish real-world cohort were consistent with the Checkmate-274 results, with a manageable safety profile despite an older population. In spite of short-term follow-up, these findings externally validate the results of the pivotal trial reinforcing the role of adjuvant nivolumab in daily clinical practice for high-risk MIUC. Patient characteristics. Characteristics CHECKMATE-274 (N=353) NIADY (N=395) Age. Mean (range)-yr 65.3 (30-92) 69.5 (35-88) Sex. Male / Female 75.1 / 29.9 % 81.8 / 19.2 % ECOG 0-1 / >2 98 / 2 % 96.7 / 3.3 % Bladder/Upper tract 79 / 21% 91.4 / 8.6 % Pure urothelial / mixed histology 59.7 / 40.3 % 79.2 / 20.7 % NAChT cisplatin / carboplatin 43.3 / NA % 48.9 / 2.3 % pT2-4a N0 52.2 % 64.3 % pT4b o N+ 47.3 % 35.7 % PDL1+ >=1% 39.7 % 95.7 %
Early-onset colorectal cancer in a developing region: A five-year real-world analysis from Brazil.
e15704 Background: Numerous studies have reported a rising incidence of cancer among young adults worldwide, particularly colorectal cancer (CRC), raising concerns about shifts in epidemiological patterns traditionally associated with older populations. While most data originate from high-income countries, there is a paucity of real-world evidence from middle-income regions, including Brazil. Understanding regional trends in CRC among individuals younger than 50 years is essential to inform prevention strategies, screening policies, and health system planning. Methods: We conducted a retrospective, descriptive, population-based study evaluating all newly diagnosed cases of colorectal cancer between 2020 and 2024 in the southern region of Espírito Santo, Brazil. Data were obtained from institutional cancer registries and medical records. Variables analyzed included year of diagnosis, sex, and age at diagnosis. Early-onset colorectal cancer (EOCRC) was defined as diagnosis before 50 years of age. Absolute numbers and proportions of EOCRC cases were calculated for each year of the study period. Results: Between 2020 and 2024, a total of 708 patients were diagnosed with colorectal cancer. Of these, 128 patients (18.1%) were younger than 50 years at diagnosis. In 2020, 142 cases were identified (61 men, 81 women), with 26 patients (18.3%) under 50 years. In 2021, 155 cases were diagnosed (77 men, 78 women), including 24 patients (15.5%) younger than 50 years. In 2022, 156 cases were recorded (70 men, 86 women), with a notable increase to 41 early-onset cases (26.3%). In 2023, 124 cases were diagnosed (72 men, 52 women), of which 15 patients (12.1%) were under 50 years. In 2024, 131 cases were identified, including 22 patients (16.8%) younger than 50 years. Across the study period, EOCRC represented a consistent and clinically significant proportion of all CRC diagnoses, with a peak observed in 2022. Conclusions: Colorectal cancer in individuals younger than 50 years represents a substantial and persistent burden in the southern region of Espírito Santo, Brazil. The sustained proportion of early-onset cases highlights an urgent need for public health policies specifically targeting colorectal cancer in younger populations, including earlier screening strategies, risk factor modification, and improved awareness among healthcare professionals and the general population. These findings reinforce the importance of adapting national cancer control policies in Brazil to emerging epidemiological trends, aiming to reduce morbidity and mortality associated with early-onset colorectal cancer.
Outcomes of frailty among hospitalized patients with acute myeloid leukemia: A National Inpatient Sample analysis (2017–2022).
e18520 Background: Frailty is increasingly recognized as an important determinant of outcomes in patients with hematologic malignancies. However, population-level data evaluating the burden of frailty and its impact on inpatient outcomes among patients hospitalized with acute myeloid leukemia (AML) remain limited. We aimed to assess the prevalence of frailty and its association with in-hospital mortality and healthcare utilization among hospitalized AML patients in the United States. Methods: We conducted a retrospective study using the National Inpatient Sample (NIS) from 2017 to 2022. Adult hospitalizations with a diagnosis of AML were identified using ICD-10 codes. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. Multivariate and univariate survey-adjusted regressions were employed to assess the association between frailty and in-hospital mortality, length of stay (LOS), and total hospital charges. Year-stratified analyses were conducted to evaluate temporal trends. Results: Among an estimated 376,755 hospitalized patients with AML nationwide, 17.5% (95% CI 17.1–17.9%) met criteria for frailty. The mean age of frail patients was 63.5 years, compared to 58.8 years in non-frail patients, with a male predominance. Frailty prevalence varied significantly by race, with higher proportions observed among Black patients and lower proportions among Hispanic patients (p<0.001). Patients with frailty had significantly higher odds of in-hospital mortality compared with non-frail patients (OR 2.12, 95% CI 2.00–2.26; p<0.001). Frail patients experienced longer hospitalizations, with a mean increase of 6.0 days (95% CI 5.6–6.4; p <0.001), and substantially higher healthcare utilization, incurring $104,391 more in total hospital charges per admission (95% CI $94,783–$113,998; p <0.001). These associations were consistent across all study years (2017–2022), with frailty conferring an approximately twofold increase in mortality risk annually. Conclusions: Frailty is present in nearly one in six hospitalized patients with AML and is linked to higher in-hospital mortality, longer hospital stays, and substantially increased healthcare costs. Baseline functional impairment and geriatric syndromes increase vulnerability to infections, treatment-related complications, and delayed recovery, likely explaining our observed findings and highlighting the need for systematic frailty assessment and targeted interventions to improve outcomes in this vulnerable population.
RAISIC-1: A phase 1/2 clinical trial of the GPR65 inhibitor PTT-4256—Preliminary safety, tolerability, pharmacokinetic, and pharmacodynamic results.
2608 Background: The acidic tumor micro-environment is linked to immune suppression and insensitivity to immunotherapy. The G protein-coupled receptor, GPR65, is activated in this low pH environment, driving the increased transcription of myeloid immune-suppressive genes and reduced transcription of T- and NK-cell functional and effector genes. Against the backdrop of this target validation, PTT-4256, a first-in-class, potent, orally-bioavailable, allosteric, small molecule inhibitor of GPR65, is being developed as a potential treatment of solid tumors. In mouse syngeneic cancer models, oral administration of PTT-4256 as monotherapy delivers pronounced efficacy, which is enhanced in combination with an anti-PD-1 antibody. Transcriptomic analysis shows that PTT-4256 effectively reverses the acidic immune suppression in mice tumors. Methods: RAISIC-1 is a multi-modular Phase 1/2 clinical trial in adults with histologically confirmed advanced/metastatic solid malignancies who have previously received standard of care therapies. Phase 1 (Module A) is aimed to evaluate safety (treatment emergent and related adverse events – TEAE/TRAE; dose limiting toxicity – DLT; maximum tolerated dose-MTD), pharmacokinetics, pharmacodynamics, preliminary efficacy (as per RECIST 1.1) and estimate the optimal biological dose (OBD) / recommended Phase 2 dose (RP2D). PTT-4256 is administered orally in 21-day cycles until disease progression or unacceptable toxicity. A comprehensive biomarker program is included to detect immune-related changes in blood/plasma. Results: As of 7 January 2026, 14 participants (3 ongoing) have been treated with one of 5 dose-levels (10, 20, 40, 80 and 160 mg/day). PTT-4256 was well-tolerated with no DLTs. TRAEs were reported in ten participants, with fatigue (n = 8), nausea (n = 4), rash (n = 4), reduced appetite (n = 4), vomiting (n = 2) reported in more than 1 participant. All were grade 1 or 2 except one transient episode ( < 1 day) of grade 3 hypertension. Tumor shrinkage and stable disease have been observed at doses 40mg and above in six participants, of which two (nasopharyngeal cancer and renal cell cancer (RCC)) are ongoing in treatment > 5 months. Transcriptomics and proteomics analyses show dose-dependent changes in immune-related markers in blood/plasma following PTT-4256 treatment that are consistent with preclinical data and the mode of action. Conclusions: Enrollment at dose levels ≥ 300 mg is ongoing. Phase 2 (Module B) as PTT-4256 monotherapy or in combination with anti-PD1 in RCC and head & neck squamous cell cancer (HNSCC) will commence upon identification of RP2D. Clinical trial information: NCT06634849 .
Triple-negative oligometastatic breast cancer: A retrospective cohort.
e13000 Background: The optimal management of oligometastatic breast cancer (OMBC) remains undefined. Given its biological heterogeneity, subgroup-specific analyses are warranted. Data focusing on triple-negative (TN) OMBC are lacking. We aimed to describe the clinical characteristics, initial metastatic patterns, treatments, outcomes, and pattern of progression of a consecutive de novo TN OMBC and oligorecurrent TN metastatic breast cancer (MBC) cohort. Methods: We retrospectively identified all consecutive patients treated for de novo or recurrent MBC between 2012 and 2020 at a single institution. Among them, TN OMBC was defined as breast cancer with 1–5 metastatic lesions without hormone receptor or HER2 expression. Metastatic presentation, treatments including standard systemic therapy (SOC) and local ablative treatment (LAT), and patterns of progression at first relapse were analyzed. Survival outcomes were analyzed using the Kaplan–Meier method, log-rank tests and Cox proportional hazards models. Results: TN OMBC accounted for 49 cases, corresponding to 2.5% (49/1,980) of all metastatic breast cancers. 33% were de novo, while the remainder were metachronous, occurring before (29.2%) or after 24 months (37.5%). A single organ was involved in 81.6% of patients, and 1–3 metastases were observed in 87.8%. Distant lymph nodes were the most frequent metastatic site (38%), exceeding lung, liver, brain, and bone involvement. Overall, 28.6% of patients received local ablative treatment (LAT), either alone or combined with systemic therapy. No patients received immunotherapy during the study period. With a median follow-up of 75.9 months (95%CI [54.4; 82.0]), median progression-free survival was 6.7 months (95%CI [4.8; 9.8]) and median overall survival was 23.1 months (95%CI [17.2; 29.5]). At 36 months, PFS was 10.4% (95% CI [3.8–20.9]) and OS was 31.8% (95% CI [19.3–45.0]). No prognostic factor was identified in univariable analyses including treatment, metastatic distribution, and metastatic chronology. After first-line treatment, 43 patients (87.7%) experienced disease progression. Local control was achieved in 47.9% of cases. Among patients with disease progression, 65.9% presented with oligoprogression. LAT targeting progressive lesions was administered in 23.3% of progressing patients. Conclusions: This study provides the first dedicated description of TN OMBC. TN OMBC is a rare clinical entity. The metastatic pattern showed a frequent involvement of distant lymph nodes. At three years, nearly one-third of patients are still alive. Following first-line systemic therapy, oligoprogression represented the predominant pattern of disease progression. Within the limitations of this retrospective study, these findings suggest that TN OMBC may represent a distinct clinical presentation compared with unselected TN metastatic breast cancer, and support further dedicated investigation.
ASCEND: A phase 1/2, dose-escalation, optimization, and dose-expansion study to evaluate the safety and antitumor activity of CR-001 in adults with locally advanced or metastatic solid tumors.
TPS2693 Background: CR-001 is a tetravalent bispecific antibody targeting anti-programmed cell death-1 (PD-1) and vascular endothelial growth factor (VEGF), designed to enhance antitumor activity through combined immune modulation and antiangiogenic effects. Its proposed mechanism of action involves dual binding and blockade of both PD-1/programmed death ligand-1 (PD-L1) and VEGF/vascular endothelial growth factor receptor 2 (VEGFR2) signaling. The blockade of VEGF signaling is aimed at inhibiting tumor angiogenesis and reversing immunosuppressive effects in the tumor microenvironment, while PD-1 binding is aimed at preventing T-cell suppression, thereby promoting the immune recognition and elimination of tumor cells. The established benefit/risk profiles and regulatory precedents for PD-1-, VEGF-, and dual-pathway-directed antibodies support evaluation of CR-001 in solid tumors. Methods: ASCEND (NCT07335497) is a global, first-in-human, open-label, phase 1/2 study assessing CR-001 monotherapy in adults with advanced solid tumors. The purpose of this study is to determine the safety and tolerability of CR-001 and identify the maximum tolerated dose, and/or recommended phase 2 dose. The study will initially involve three parts: dose escalation, backfill, and dose optimization. Key eligibility criteria include: age ≥18 years; locally advanced (nonresectable) or metastatic hepatocellular carcinoma, biliary tract cancer, gastric or gastroesophageal junction cancer, colorectal cancer, endometrial cancer, cervical cancer, ovarian cancer, or non-small-cell lung cancer; and progression on, intolerance to, or ineligibility for local standard-of-care anticancer therapies. Additional criteria include ≥1 measurable lesion and ECOG performance status 0–1. As part of a standard 3+3 dose-escalation design, CR-001 is planned to be administered at 4 dose levels as an intravenous infusion every 2 or 3 weeks. Tumor-specific backfill cohorts will enroll concurrently with dose escalation. Earlier-line participants, including those untreated in the advanced or metastatic setting, may also be eligible to participate in backfill cohorts. The recommended phase 2 dose will be determined based on review of pharmacokinetics/pharmacodynamics, safety, tolerability, and preliminary signs of antitumor activity. Up to 290 patients are planned to be enrolled across the dose-escalation, tumor-specific backfill, and dose-optimization cohorts. This global trial is currently enrolling. Clinical trial information: NCT07335497 .
Predictors of in-hospital mortality in chemotherapy-associated cardiomyopathy: A national inpatient sample analysis (2018-2022).
e24025 Background: Chemotherapy-associated cardiomyopathy (CAC) is a recognized complication of cancer treatment, yet predictors of in-hospital mortality remain poorly characterized at the national level. We aimed to identify baseline clinical factors associated with mortality in hospitalized CAC patients. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (2018-2022). Adults with cardiomyopathy (ICD-10: I420, I427, I428, I429) and chemotherapy exposure or cancer history (Z5111, Z5112, Z85) were included. Patients with ischemic, hypertensive, alcoholic, or postpartum cardiomyopathy were excluded. Survey-weighted multivariate logistic regression identified independent predictors of in-hospital mortality. Model discrimination was assessed using area under the receiver operating characteristic curve (AUC). Results: We identified 14,896 hospitalizations (weighted national estimate: 74,480). Mean age was 70.7 years and in-hospital mortality was 0.74% (n = 110). On multivariate analysis, independent predictors of mortality included metastatic cancer (aOR 4.01, 95% CI 2.31-6.96, p < 0.001), weight loss (aOR 3.74, 95% CI 2.28-6.14, p < 0.001), renal disease (aOR 2.51, 95% CI 1.67-3.76, p < 0.001), liver disease (aOR 2.26, 95% CI 1.12-4.56, p = 0.024), and increasing age (aOR 1.04 per year, 95% CI 1.02-1.07, p < 0.001). Female sex, coagulopathy, fluid/electrolyte disorders, complicated diabetes, and hypertension were not significantly associated with mortality. The prediction model demonstrated fair discrimination (AUC 0.746, 95% CI 0.700-0.792). Conclusions: In this nationally representative analysis of CAC hospitalizations, metastatic cancer, weight loss, renal disease, liver disease, and older age were independent predictors of in-hospital mortality. These findings may help identify high-risk patients requiring closer monitoring during hospitalization. Independent predictors of mortality. Predictor aOR (95% CI) P-value Significance AGE 1.04 (1.02-1.07) <0.001 *** female 0.90 (0.61-1.33) 0.611 Metastasis 4.01 (2.31-6.96) <0.001 *** renal composite 2.51 (1.67-3.76) <0.001 *** weight loss 3.74 (2.28-6.14) <0.001 *** coagulopathy 1.02 (0.51-2.05) 0.963 liver disease 2.26 (1.12-4.56) 0.024 * fluid electrolyte 1.07 (0.72-1.60) 0.724 diabetes 0.94 (0.53-1.67) 0.828 hypertension 0.67 (0.44-1.03) 0.069