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The spectrum of bevacizumab-induced renal injury: A systematic review of published case reports.

e24143 Background: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is widely used across solid tumors. Despite its therapeutic benefit, renal toxicity remains an important and incompletely characterized adverse effect. Available evidence is limited to case reports and small series. We therefore performed a systematic review to clarify the clinical spectrum and outcomes of bevacizumab-induced renal injury. Methods: A systematic search of PubMed, Google Scholar, EMBASE, and Scopus was conducted from inception through November 2025 to identify case reports and case series describing renal injury attributed to bevacizumab. Extracted variables included demographics, malignancy type, bevacizumab exposure, clinical presentation, biochemical findings, renal pathology, management, and outcomes. Duplicate cases and reports lacking sufficient clinical detail were excluded. Descriptive statistics were used. Results: 31 patients from 21 publications were included. Mean age was 64 years, and 58.1% were women. Underlying malignancies included colorectal (25.8%), breast (22.6%), ovarian (16.1%), and lung cancers (12.9%), with most patients having advanced or metastatic disease. Clinical presentation was dominated by hypertension (71%), nephrotic-range proteinuria (48.4%), acute kidney injury (41.9%) and nephrotic syndrome (32.3%). Kidney biopsy was performed in 22 patients, with thrombotic microangiopathy (TMA) representing the predominant lesion (50% of biopsied cases; 35.5% overall). Other pathologies included immune-complex glomerulonephritis, membranoproliferative patterns, IgA nephropathy with superimposed TMA, endothelial injury, and acute interstitial nephritis. Bevacizumab was discontinued in 74.2% of cases, with dose reduction or interruption in the remainder. Management strategies varied and included supportive care, antihypertensives, corticosteroids, dialysis and complement inhibition with eculizumab in 5 cases. Full renal recovery occurred in 48.4% of patients, partial recovery in 38.7%, while 12.9% progressed to end-stage kidney disease or had no meaningful recovery. Overall mortality was 25.8%, mainly attributable to underlying malignancy progression rather than renal failure. Conclusions: Bevacizumab-induced renal injury encompasses a broad clinicopathologic spectrum, with hypertension and TMA emerging as the most frequent presentation and biopsy-proven pattern. Although most patients experience complete or partial renal recovery after drug withdrawal, a notable minority progress to severe or irreversible renal dysfunction. These findings highlight the importance of early recognition, blood pressure and proteinuria monitoring, and timely bevacizumab discontinuation to reduce renal morbidity. Prospective studies are needed to better define risk factors and optimal management strategies.

From eligibility to enrollment: Evaluating barriers to clinical trial participation for leiomyosarcoma (LMS) at MD Anderson Cancer Center (MDACC).

e23531 Background: LMS is a rare, aggressive malignant tumor of smooth muscle origin, and its clinical heterogeneity complicates diagnosis, treatment, and research. Clinical trial enrollment among adult sarcoma patients (pts) remains low, with many eligible pts not routinely identified or referred. Understanding enrollment barriers and improving screening are critical to increase trial access. This study evaluated a standardized manual pre-identification and referral process for LMS pts at MDACC and assessed its impact on screening, enrollment, and participation barriers. Methods: This prospective study implemented a systematic pre-identification and referral workflow for LMS pts (Sept-Dec 2025). Medical charts were reviewed 2-3 days before each outpatient sarcoma oncology visit in EPIC to document tumor site, histopathology, prior therapy, stage, and inclusion/exclusion criteria for 6 active LMS trials in pre- and post-intervention periods. Eligible pts were identified and referred to physicians and the trial team by email. Primary outcomes: % improvement in monthly screening and enrollment. Secondary outcomes: the average monthly pts screened and enrolled during pre-intervention (03/2025-08/2025: 6 months) vs post-intervention (09/2025-12/2025: 4 months) periods, and recording of reasons for non-inclusion. Results: A total of 13 pts were screened and 12 enrolled during the pre-intervention period, versus 15 screened and 12 enrolled during the post-intervention period. Implementation of the pre-identification and referral workflow led to 73% and 50% improvement in monthly screening and enrollment, respectively. The average monthly screening of pts increased from 2.2 (±1.2) to 3.8 (±1.9), and the enrollment from 2.0 (±1.4) to 3.0 (±1.4). Example from one LMS trial (protocol 2023-0710): no pts screened/enrolled pre-intervention; post-intervention: 25 pre-identified, 2 screened and enrolled. Reasons for non-enrollment across all trials: summarized in Table 1, with clinical/protocol ineligibility most common. Post-intervention data collection is ongoing; a full 6-month comparison to be included in the final presentation. Conclusions: The implementation of pre-identification and referral workflow showed a trend toward increased screening and enrollment in LMS trials, with trial-level examples suggesting improved pt identification. The study also identified LMS-specific barriers, defining targets for future interventions. Incorporating AI-assisted screening may further increase pt identification, reduce manual workload, and improve trial enrollment. Reasons for non-enrollment among screened pts (%). Reason for non-enrollment (%) Clinical/protocol ineligibility 58 Difficulty in traveling to MDACC 17 Patient preference 14 Alternative treatment selection 7 Communication/administrative barriers 4

Prognostic value of ultra-low PSA after 3 and 6 months of intensified androgen deprivation therapy in patients with metastatic castration-sensitive prostate cancer: Real-world data from a single healthcare center in Caracas, Venezuela.

e17110 Background: Prostate cancer is the most frequent cause of cancer-related morbidity worldwide in men, with a national incidence of 50.49 cases per 100,000 men. The standard treatment for advanced castration-sensitive prostate cancer is intensified androgen deprivation therapy. Prostate-specific antigen (PSA) is crucial for monitoring. We aimed to evaluate the decrease in PSA at 3 and 6 months of treatment as a prognostic factor for biochemical recurrence-free survival (BRFS) in patients with metastatic castration-sensitive prostate cancer (mCSPC). Methods: This was a single center study conducted at the Medical & Educational Center La Trinidad, in Caracas (Venezuela). One hundred and eighteen (n = 118) patients with mCSPC who received intensified treatment and had recorded PSA levels at 3 and 6 months after starting treatment were included. Patients were stratified according to their PSA value into: group A (≤ 0.02 ng/mL), group B (≥ 0.02 ng/mL y < 0.2 ng/mL), group C (≥ 0.2 ng/mL and < 4 ng/mL), and group D (≥ 4 ng/mL). Kaplan-Meier plots were used to assess the BRFS, and forest plots with landmark analysis were used to interpret the risk of the variables. Results: The median BRFS was 72.96% at 2 years of follow-up for the general population. High-volume disease was identified as a risk factor with a hazard ratio (HR) of 3.42, while synchronous vs. metachronous disease and dual vs. triple therapy did not reach statistical significance. The variable with the greatest impact was ultra-low PSA with an HR of 0.07, acting as a protective factor, while PSA > 4 ng/mL acted as a strong predictor for biochemical recurrence with a HR of 13.52. Conclusions: A progressive and significant decrease in BRFS was observed as PSA levels increased. The median BRFS was not reached for groups A, B, and C; therefore, longer follow-up is required to draw definitive conclusions. A PSAt value < 0.02 ng/mL is a protective factor in terms of BRFS, while a PSAt > 4 ng/mL is a poor prognostic factor.

Immune microenvironment, MSI status, and tumor mutational burden as prognostic factors in colorectal cancer.

e14524 Background: Immune checkpoint inhibition has demonstrated meaningful clinical benefit in microsatellite instability–high (MSI-H) colorectal cancer (CRC); however, outcomes remain heterogeneous. The interaction between tumor immune microenvironment features, tumor mutational burden (TMB), and survival outcomes has not been fully characterized. We conducted an integrative analysis of publicly available genomic data to evaluate the prognostic impact of immune infiltration stratified by MSI status and TMB in CRC. Methods: Transcriptomic, somatic mutation, and clinical data for primary colorectal adenocarcinoma were obtained from TCGA-COAD and TCGA-READ. About 600 patients with overall survival data were analyzed. MSI status was taken from TCGA molecular subtype annotations. TMB was defined as the number of nonsynonymous somatic mutations per tumor and dichotomized at the median.Immune infiltration (CD8⁺ and CD4⁺ T cells, macrophages, neutrophils, dendritic cells) was estimated using TIMER. Patients were classified as high or low infiltration by the median. Overall survival was assessed using Kaplan–Meier analysis and Cox models adjusted for age, sex, and tumor stage., and tumor stage. Results: The cohort included approximately 15% MSI-H tumors, which demonstrated significantly higher TMB compared with microsatellite-stable (MSS) tumors. MSI-H tumors exhibited an inflamed immune phenotype, with approximately twofold higher CD8⁺ T-cell infiltration relative to MSS tumors. Across the overall cohort, high CD8⁺ T-cell infiltration was associated with improved OS compared with low infiltration (median OS not reached vs approximately 60–70 months). In contrast, increased macrophage infiltration was associated with inferior survival outcomes. When stratified by genomic features, the favorable prognostic association of CD8⁺ T-cell infiltration was most pronounced in MSI-H and TMB-high tumors, corresponding to an estimated 30–40% relative reduction in mortality risk compared with MSI-H/TMB-high tumors with low immune infiltration. Immune infiltration demonstrated weaker and less consistent associations with OS in MSS/TMB-low tumors. In multivariable analyses, CD8⁺ T-cell infiltration remained independently associated with improved OS after adjustment for clinical covariates, whereas macrophage infiltration remained independently associated with worse outcomes. Findings were consistent across colon and rectal cancer subgroups. Conclusions: In this integrative analysis of TCGA colorectal cancer datasets, features of the tumor immune microenvironment, together with MSI status and TMB, were associated with survival. These results support immune-genomic stratification and suggest that combining immune and molecular biomarkers may improve prognostic assessment and immunotherapy trial design in colorectal cancer.

Impact of time-to-surgery on survival outcomes in Korean breast cancer patients: A nationwide population-based cohort study.

581 Background: The increasing incidence of breast cancer and the resulting surgical workload in South Korea have led to concerns regarding surgical delays. While the clinical impact of time-to-surgery (TTS) remains debated, defining an optimal threshold is crucial for health policy and patient outcomes. This study aimed to investigate the impact of TTS on overall survival (OS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) using nationwide claims data. Methods: This study utilized a merged dataset from the National Health Insurance Service and Korean Statistical Information Service database. We identified 11,683 women newly diagnosed with Stage I-III primary breast cancer in 2016, excluding prior history or concurrent malignancies. TTS was defined as the interval from breast cancer diagnosis to the definitive surgical procedure. To determine the optimal clinical cutoff, the Contal and O’Quigley method was applied. Multivariable Cox proportional hazards models were used for OS. To account for competing risks, the Fine-Gray subdistribution hazard model was employed for DFS and BCSS, with non-breast cancer death treated as a competing event. Covariates included physical activity, type and region of institution, systemic treatments, income decile, and Charlson Comorbidity Index (CCI) score. Results: Initial analysis using 30-day and 60-day thresholds showed significant differences in survival outcomes. The Contal and O’Quigley method identified 68 days as the optimal cutoff for TTS. Patients with TTS > 68 days exhibited significantly worse OS compared to those with TTS ≤ 68 days (adjusted Hazard Ratio [HR], 3.396; 95% CI, 2.402-4.802; p < 0.001). In the competing risk regression, TTS > 68 days was associated with inferior DFS (adjusted subdistribution HR [sHR], 1.496; p = 0.001) and BCSS (adjusted sHR, 5.868; p < 0.001). The negative impact of delayed surgery remained consistent across various subgroups regardless of income level or comorbid status. Conclusions: Delays in surgery exceeding 68 days are significantly associated with poorer survival outcomes in Korean breast cancer patients. These findings suggest that every effort should be made to perform surgery within 68 days of diagnosis to optimize long-term prognosis. Clinicians should prioritize streamlining the diagnostic-to-treatment pathway to minimize surgical wait times.

Liquid-based methylation profiling of molecular breast cancer subtypes (MBS) in hormone receptor positive (HR+) metastatic breast cancer (MBC) treated with CDK4/6 inhibitor (CDK4/6i).

1095 Background: MBC remains incurable due to the invariable development of resistance, with most deaths resulting from HR+ MBC that acquires resistance to endocrine therapy (ET) combinations. HR and HER2 remain the most important biomarkers in MBC but, while it is known that receptor status and expression based molecular subtypes (e.g. PAM50) can vary over an individual patient’s (pts) disease course, serial evaluation is currently limited in routine clinical care by tissue requirements. Methods: The EMBRACE cohort study collects biospecimens with matched clinical annotations from pts with MBC at Dana-Farber Cancer Institute. A subset of 510 plasma samples collected around CDK4/6i treatment (tx; pre-tx: -90 to +30 days from start; on-tx; post-tx: -30 to +90 days from end) from 323 pts with HR+ MBC were assessed with Guardant360 Liquid. MBS calls were generated using a previously described cell-free DNA methylation-based deconvolution model that classifies HR and HER2 status in cases with tumor fraction (TF) ≥0.5% with accuracy >85%, and compared with tissue-based HR and HER2 status by immunohistochemistry (IHC). Results: Of 510 samples profiled, 308 (60.4%) were evaluable for MBS with TF ≥0.5%. The evaluable rate was lowest in on-tx samples at 48.7%, in line with lower median TF in this set. Of evaluable samples, 285 (92.5%) aligned with sufficient confidence to report a subtype: 273 (88.6%) of evaluable samples were classified as HR+, 23 (7.5%) undetermined, and only 12 (4.9%) HR-, all of which were either from on- or post-tx timepoints. MBS calls on pre-tx samples showed high concordance with clinical IHC, with higher concordance at metastatic diagnosis (91%) than primary diagnosis (86%). Notably, all discordances were cases abstracted as HR+/HER2- at metastatic diagnosis by IHC where MBS yielded HR+/HER2+. Overall, samples from 28 pts were assigned a HER2+ MBS and, in 9 (32%) of these, a concordant genomic alteration in ERBB2 (copy number gain, gain-of-function mutation and/or fusion) was detected on Guardant360 Liquid. Out of 48 pts with multiple classifiable samples, 11 (22.9%) showed differences in MBS across serial samples including 9 with changes in HER2 (5 gaining and 4 losing HER2 MBS), and 2 with changes in HR (both with an on-tx sample classified as HR- but the subsequent post-tx sample HR+). Conclusions: A methylation-based liquid biopsy assay can classify MBS with high correlation to clinical pathology in pre-tx samples and facilitate identification of discordant, or perhaps heterogenous, subtype while capturing the dynamics of MBS over disease course and treatment. Future studies are indicated to investigate the clinical utility of this assay as a biomarker for therapy selection.

Infection burden with BCMA versus GPRC5D-targeted bispecific antibodies in multiple myeloma: A systematic review and meta-analysis.

e19511 Background: The approved B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted bispecific antibodies (BsAbs) have demonstrated efficacy in relapsed/refractory multiple myeloma. However, infectious complications remain a major concern, and comparative class-level infection data remain incomplete. Methods: We searched PubMed/MEDLINE, EMBASE, and Scopus from inception through January 10, 2026, using predefined eligibility criteria to include clinical trials only of approved BsAbs (teclistamab, elranatamab, linvoseltamab, and talquetamab). Arm-level safety data were grouped by target class and regimen (monotherapy or combination). Monotherapy arms were pooled using random-effects meta-analysis of proportions. Endpoints were infections (any-grade, grade ≥3, opportunistic) and infection-related deaths. Heterogeneity was assessed using I² and τ². Indirect class comparisons used arm-level random-effects meta-regression on the logit scale. PROSPERO ID CRD420261288395. Results: Ten monotherapy arms were included (BCMA k=5, n=500; GPRC5D k=5, n=375). Any-grade infections were higher in BCMA monotherapy, showing 74.3% (95% CI 70.2–77.9; I²=0%) vs 62.1% (50.5–72.5; I²=57.7%) for GPRC5D. Grade ≥3 infections were 41.0% (32.3–50.4; I²=71.5%) vs 23.5% (14.1–36.6; I²=73.7%), respectively. Infection-related deaths were 8.6% (6.1–11.8; I²=22.9%) vs 2.0% (0.9–4.0; I²=0.0%), representing a 4-fold higher pooled estimate. Opportunistic infections were reported in 8 monotherapy arms (BCMA k=3; GPRC5D k=5); GPRC5D pooled incidence was 5.0% (3.2–7.9; I²=0%), whereas BCMA was summarized descriptively (9.1–11.1%). In arm-level meta-regression, GPRC5D was associated with lower odds of any-grade infections (β=−0.531, p=0.0038), grade ≥3 infections (β=−0.798, p=0.0248), opportunistic infections (β=−0.783, p=0.0092), and infection-related deaths (β=−1.526, p=0.00064). Exploratory analysis of combination-regimen arms (n=540) showed high infection rates, with any-grade infections of 84.5% (68.1–93.3; I²=89.5%), grade ≥3 infections of 41.8% (27.4–57.8; I²=87.4%), and infection-related deaths of 6.0% (3.3–10.5; I²=47.3%). Given the limited number of arms and substantial heterogeneity, these estimates should be interpreted as descriptive. Conclusions: Infections were frequent with severe and fatal events. Across pooled monotherapy estimates and arm-level meta-regression, BCMA vs GPRC5D-directed therapy showed higher infection burden. Separation was most consistent for infection-related deaths, while grade ≥3 infections showed greater heterogeneity. Despite heterogeneity, cross-trial limitations, and incomplete opportunistic infection reporting, these findings reinforce the need for careful monitoring and optimized supportive care and prophylaxis during treatment.

Urinary tumor DNA–guided de-escalation of systemic immunotherapy in extensive very high risk non–muscle-invasive bladder cancer.

4593 Background: Non-muscle-invasive bladder cancer (NMIBC) has entered the era of systemic immunotherapy. Large randomized trials, including CREST, POTOMAC, and ALBAN, have explored long-term systemic immunotherapy in NMIBC, yet the clinical benefit remains heterogeneous and is often accompanied by substantial toxicity. Urinary tumor DNA (utDNA) has emerged as a promising biomarker for molecular response assessment, yet its role in guiding treatment de-escalation has not been established. We evaluated whether utDNA negativity after complete response (CR) could support safe early treatment cessation of systemic therapy in patients with extensive very-high-risk NMIBC (VHR-NMIBC). Methods: Patients with extensive VHR-NMIBC who achieved CR after initial systemic therapy with the PD-1 inhibitor tislelizumab plus low-dose paclitaxel were included from a prospective cohort. After CR assessment, some patients underwent low-coverage utDNA testing as part of routine clinical decision-making following clinician–patient discussion. Patients with negative utDNA completed three additional cycles and subsequently stopped systemic therapy (utDNA-guided de-escalation group), whereas those who continued treatment beyond this point were categorized as the longer treatment-exposure group. Efficacy and safety outcomes included survival endpoints and adverse events (AEs) with exposure-adjusted incidence rates. Results: With a median follow-up of 42.8 months, 54 patients achieving CR were evaluable. Among them, 21 with negative utDNA status completed three additional cycles and underwent planned treatment cessation, while 33 continued systemic therapy with longer treatment exposure. Across key efficacy endpoints, outcomes were comparable between the utDNA-guided de-escalation and longer treatment–exposure groups, with no significant differences in recurrence-free survival (RFS; HR 1.37, 95% CI 0.21–8.87, P = 0.73), overall survival (OS; HR 2.48, 95% CI 0.12–53.7, P = 0.51), or duration of response (DOR; HR 1.33, 95% CI 0.21–8.50, P = 0.76). A difference in radical-cystectomy–free survival was observed (short vs long: HR 4.97, 95% CI 1.03–23.9, P = 0.03). Long-course treatment was associated with a higher cumulative incidence of any-grade AEs (88.1% vs 72.5%) and more AE types (median 5 vs 2, P < 0.001). Exposure-adjusted AE rates per cycle were lower in the long-course group (IRR 0.50, 95% CI 0.42–0.60, P < 0.001), while grade ≥3 AEs occurred in 2.9% and 9.5% of patients in the short- and long-course groups, respectively, predominantly during later treatment phases. Conclusions: UtDNA negativity after complete response may provide a molecular basis for individualized treatment duration, highlighting the potential role of liquid biopsy in guiding precision treatment tailoring and warranting prospective validation in larger biomarker-driven studies. Clinical trial information: NCT04730232 .

Phase II study of cemiplimab ± fianlimab following SBRT for oligometastatic clear-cell RCC (LAG-BOOST).

TPS4637 Background: Oligometastatic clear-cell renal cell carcinoma (ccRCC) is a biologically distinct, often indolent state where metastasis-directed therapy, including metastasectomy or SBRT, provides durable local control and delays systemic therapy. Randomized prospective trial evidence demonstrates a survival benefit with adjuvant programmed cell death-1 (PD-1) inhibition following surgical metastasectomy in oligometastatic ccRCC. However, the role of adjuvant PD-1 inhibition following stereotactic body radiation therapy (SBRT) has not been prospectively evaluated. SBRT induces immunogenic tumor cell death, enhances tumor antigen presentation, and promotes T-cell priming, providing a strong biologic rationale for evaluating PD-1 inhibition following SBRT. Beyond PD-1 blockade alone, lymphocyte activation gene-3 (LAG-3) is an inhibitory immune checkpoint expressed on tumor-infiltrating lymphocytes in ccRCC and contributes to T-cell exhaustion and immune evasion. Dual PD-1 and LAG-3 blockade has demonstrated promising antitumor activity with acceptable tolerability in early-phase studies, supporting investigation of strategies to enhance the efficacy of adjuvant PD-1 inhibition following SBRT in oligometastatic disease. Methods: LAG-BOOST is a 1:1 randomized, prospective, multicenter, investigator-initiated phase II trial. Eligible patients have histologically confirmed oligometastatic ccRCC, defined as ≤5 metastatic lesions by RECIST v1.1, all amenable to SBRT. Following SBRT to all visible lesions, patients are randomized to receive one year of adjuvant PD-1 inhibition (cemiplimab) alone or combined PD-1 and LAG-3 inhibition (cemiplimab and fianlimab). Treatment continues for up to one year or until disease progression, unacceptable toxicity, or withdrawal of consent. Patients must be naïve to systemic therapy for metastatic RCC; prior adjuvant therapy for non-metastatic RCC is permitted in the absence of radiographic disease progression within 12 months of treatment completion. Stratification is based on International Metastatic RCC Database Consortium (IMDC) risk and metastatic burden: (1) favorable or intermediate IMDC risk with 3 or fewer metastatic lesions and no brain metastases versus (2) poor IMDC risk or 4–5 metastatic lesions or the presence of brain metastases. The primary endpoint is 1-year progression-free survival (PFS). Secondary endpoints include safety and tolerability (treatment-related adverse events per CTCAE v5.0), objective response rate by RECIST v1.1, duration of response, disease control rate, and overall survival. As of submission, 2 of the planned 72 patients have been enrolled. The study is powered for H₀: 65% versus H a : 85% 1-year PFS, with α = 0.05 and power = 0.8. ClinicalTrials.gov identifier: NCT07223541. Clinical trial information: NCT07223541 .

Breast cancer survivor perspectives on nutrition: Results of a comprehensive survey.

e22674 Background: The majority of patients gain weight during breast cancer (BC) treatment. Weight gain is often distressing to patients and weight gain after diagnosis has been associated with worse outcomes. Previous studies have found nutrition is of interest to BC patients but there is a paucity of recent U.S. research. Therefore, we conducted an online survey of BC survivors to characterize the level of interest in and perceived importance of nutrition, current dietary habits, and perspectives on body weight. Methods: Between May 2024 and May 2025 patients diagnosed with BC in the past 10 years were recruited via the electronic medical record (EMR) at University of Rochester, flyers at the BC clinic, and email lists and social media posts of multiple BC advocacy organizations. The one-time survey was administered via REDCap. Eligibility criteria included age ≥18 years, initial diagnosis or recurrence of BC in ≤10 years, and living in the U.S. Descriptive statistics were performed to characterize respondents and their responses and chi-square tests were performed to determine if there were differences by respondent characteristics. Results: 1007 participants completed the survey. The majority were female sex (98.1%), white (92.7%), non-Hispanic (96.6%), and had early-stage BC (61.8%). Mean age was 60.2±11.6 years. Mean BMI based on self-reported weight and height was 28.7±7.0 kg/m2. 47.6% were currently receiving cancer treatment. 89.7% were recruited from the EMR and clinic flyers and 10.3% were recruited from advocacy organizations and referrals. Interest in and perceived importance of nutrition were high, with 73.1% interested or very interested since diagnosis and mean rating of importance of nutrition for those with a BC diagnosis was 8.4±1.9 out of 10. 57.4% reported dietary changes since diagnosis. A greater proportion of younger participants reported changing their diets compared to older participants (68.0% < 45, 60.6% age 45-65, and 49.7% > 65 years; p < 0.001). Despite a high proportion reporting dietary change, vegetables were consumed less than twice daily by 78.6% and fruits were consumed less than twice daily by 76.8% of respondents. 78.3% of respondents said they would like to lose weight and 52.7% reported working to lose weight in the last 30 days. 78.4% reported that their weight had not been addressed by their oncology team. Conclusions: Level of interest in and perceived importance of nutrition were high among those with a BC diagnosis. Most participants reported dietary change since diagnosis, with an even greater proportion among younger participants. Despite reporting dietary changes, fruit and vegetable intakes were largely suboptimal. Weight loss was desired, but weight was largely not addressed in the oncology setting. These findings suggest that increased emphasis on nutrition and access to nutrition services would be welcomed by BC survivors and fill a clinical need.

Role of trilaciclib against chemotherapy-induced myelosuppression: An updated systematic review and meta-analysis.

e24158 Background: Trilaciclib, a reversible CDK4/6 inhibitor, is used before chemotherapy to reduce myelosuppression. We conducted an updated systematic review and meta-analysis to quantify its myeloprotective benefits and safety. Methods: We systematically reviewed double-blind, placebo-controlled randomized trials of adults receiving cytotoxic chemotherapy with Trilaciclib administered prior to treatment. Primary outcomes were severe neutropenia (SN), febrile neutropenia (FN), duration of severe neutropenia (DSN), G-CSF Administration, ESA Administration, RBC Transfusion and Platelet Transfusion. Secondary outcomes included Anemia, grade 3/4 anemia, grade 3/4 leukopenia and all cause chemotherapy dose reduction, MAHE, Thrombocytopenia, grade 3/4 thrombocytopenia, leukopenia, neutropenia and grade 3/4 neutropenia, overall safety (TEAEs/SAEs), and antitumor efficacy (PFS, OS, ORR). Pooled effects were summarized with RRs/HRs/MDs and 95% CIs using fixed or random effects as appropriate. Results: Five RCTs (n=642; 322 Trilaciclib, 320 control) were included. Trilaciclib reduced SN (RR 0.18, 95% CI 0.07–0.45) and FN (RR 0.24, 0.09–0.60) and shortened DSN (MD −2.78 days, −4.05 to −1.51). Supportive-care use was lower with Trilaciclib: G-CSF (RR 0.59, 0.42–0.82) and ESAs (RR 0.38, 0.18–0.81). Red-blood-cell transfusions trended lower (RR 0.60, 0.34–1.04), while platelet transfusions were similar (RR 0.86, 0.41–1.80). Overall safety was comparable between groups. We found no clear differences in PFS (HR 0.97, 0.67–1.40), OS (HR 0.97, 0.73–1.28), or ORR (RR 0.92, 0.76–1.12). Sensitivity analyses were broadly consistent; excluding the colorectal-cancer trial suggested a modest PFS benefit (HR 0.80, 0.66–0.97). Conclusions: Trilaciclib consistently eases the hematologic burden of chemotherapy and reduces supportive care needs, without an apparent trade-off in survival or response. Benefits are most robust in extensive-stage small-cell lung cancer; tumor-type heterogeneity warrants cautious extrapolation elsewhere.

Machine learning model for lung cancer risk stratification using routine complete blood count exams.

e20005 Background: Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis. Although low-dose computed tomography (LDCT) enables early detection, its widespread implementation is limited by cost, resource availability, and access disparities. This retrospective study aimed to develop a machine learning model using complete blood count (CBC) tests as a low-cost tool for lung cancer risk stratification. Methods: We analyzed CBC tests from 53,093 individuals (30,313 females, 57.10%; 22,780 males, 42.90%) 50 years and older who underwent chest CT or biopsy within six months of blood testing in Grupo Fleury laboratory, Brazil. The study population was retrospectively assembled from real-world clinical data. Low-risk CT findings were used as controls (36,243 for training and 15,535 for validation). High-risk CT findings (n = 1,178), identified from radiology reports describing features highly suggestive of lung cancer and corresponding to an estimated malignancy probability ≥85%, were used exclusively as cases for model training, while biopsy-confirmed lung cancer cases (n = 141) were reserved as the only positive cases in the independent test set for final model evaluation. A ridge regression model was trained using selected CBC-derived features. Model performance was additionally evaluated in a predefined subgroup of 1,267 individuals with documented smoking status to assess performance in a high-risk population. Results: Several CBC parameters showed significant differences between high-risk CT cases and low-risk controls, including neutrophil count and RDW (p < 0.001 for both). Following feature selection, MCV, neutrophil count, and RDW were retained in the final model, which achieved an AUC of 0.71 (95% CI: 0.70–0.71). Model discrimination remained stable across bootstrap resampling. In the subgroup analysis restricted to smokers, model performance remained comparable to that observed in the overall population with an AUC of 0.68 (95% CI: 0.67-0.68) , indicating consistent discrimination in this high-risk group. Conclusions: A machine learning model based on routinely available CBC parameters demonstrated potential as a scalable and low-cost lung cancer risk stratification tool. This approach may help prioritize individuals for CT-based screening, particularly in settings with limited access to LDCT or when smoking history is unavailable. External validation is required to confirm generalizability and clinical utility.

CXCL9:SPP1 ratio: Macrophage polarization and outcomes with pembrolizumab or enfortumab vedotin plus pembrolizumab in metastatic urothelial cancer.

4573 Background: Enfortumab vedotin plus pembrolizumab (EV+P) is standard first-line treatment for metastatic urothelial cancer (mUC), yet responses vary considerably. Identifying resistance mechanisms may guide patient selection and inform novel therapeutic strategies. Single-cell RNA sequencing (RNA-Seq) across tumor types has revealed dichotomous tumor-associated macrophage (TAM) populations: SPP1+ TAMs exhibit tumor-promoting programs while CXCL9+ TAMs express programs associated with anti-tumor immunity. The CXCL9:SPP1 gene expression ratio (CS ratio) from bulk RNA-Seq captures this balance and correlates with outcomes across solid tumors (Bill et al, Science, 2023). We explored the CS ratio's association with outcomes in mUC patients receiving pembrolizumab monotherapy or EV+P. Methods: We retrospectively analyzed mUC patients who underwent molecular profiling at Caris Life Sciences using NGS (592-gene panel, DNA WES, or RNA WTS). CS ratios were calculated and patients stratified into quartiles (Q1–Q4; Q4=highest ratio). PD-L1 expression was assessed by IHC (22c3, positive (+) CPS ≥ 10%) while TMB-High was defined as ≥ 10 Mut/Mb. TME composition was inferred using quanTIseq. Real-world overall survival (rwOS) was derived from insurance claims and calculated from biopsy to last contact or time on treatment (TOT) using Kaplan-Meier analysis while Hazard ratio (HR) was calculated by Cox proportional hazard method. Mann-Whitney U and χ²/Fisher exact tests were applied with adjustment for multiple comparisons. Results: Among 6,708 mUC patients, 1,299 received pembrolizumab and 561 received EV+P. Lower CS ratios (SPP1+ TAM predominance) were associated with shorter time on treatment and rwOS (Table 1). Low CS ratio was also associated with reduced PD-L1 expression (15.5% vs 66.7%, p < 0.001) and TMB-H prevalence (34.6% vs 52.3%, p = 0.006). Low CS ratio tumors demonstrated reduced immune infiltration except for neutrophil enrichment. Conclusions: Lower CS ratios associate with shorter time on treatment and rwOS with both pembrolizumab and EV+P. To our knowledge, this is the first analysis linking macrophage transcriptional states with EV+P resistance. Further validation of the CS ratio in patients treated with EV + P or P is warranted. CS ratio and associated outcomes with pembrolizumab monotherapy and EV+P. Pembrolizumab Monotherapy EV + P CS Ratio TOT (months) OS (months) TOT (months) OS (months) CS-Q1 2.7 (2.1-3.0) 5.7 (4.4-8.2) 7.6 (6.2-8.8) 17.8 (13.8-19.8) CS-Q2 3.1 (2.2-4.1) 7.2 (5.4-8.8) 6.9 (6.0-8.0) 16.4 (13.2-19.4) CS-Q3 4.5 (3.9-5.6) 13.5 (10.7-16.8) 9.2 (8.1-10.8) 17.2 (14.4-20.3) CS-Q4 6.9 (4.9-8.7) 18.7 (13.1-23.7) 10.6 (9.3-12.2) 21.8 (16.5-28.1) CS-Q4 vs. CS-Q1 HR 0.56, 95% CI 0.47-0.67,p < 0.001 HR 0.53, 95% CI 0.44-0.64,p < 0.001 HR 0.69, 95% CI 0.54-0.87, p = 0.00189 HR 0.62, 95% CI 0.46-0.83, p = 0.00148

Impactof <i>MET</i> amplification (amp) on telisotuzumab vedotin (Teliso-V) efficacy and safety in 2L+ non-squamous (NSQ) <i>EGFR</i> wild-type (WT) NSCLC with c-Met protein overexpression (OE).

8524 Background: Teliso-V is a c-Met–directed antibody-drug conjugate comprising telisotuzumab and the microtubule polymerization inhibitor monomethyl auristatin E (MMAE) payload. In the Ph2 LUMINOSITY study (NCT03539536), Teliso-V showed durable responses and manageable safety (Camidge et al, JCO 2024;42:3000-11) resulting in its accelerated approval in locally advanced/metastatic NSQ NSCLC with high c-Met protein OE (3+, ≥50%), as determined by an FDA-approved test. MET amp is a negative prognostic risk factor in advanced NSCLC, frequently associated with recurrent disease. High levels of MET amp and c-Met OE are hallmarks of MET -addicted tumors. Here, we analyzed the effects of MET amp on clinical responses to Teliso-V in LUMINOSITY. Methods: MET amp was evaluated by FISH and ctDNA in baseline samples from 108 NSQ EGFR WT NSCLC pts with c-Met OE (3+, ≥25%). MET amp by FISH was defined as having focal MET amp (MET/CEP7 ≥2.0) with MET gene copy number (GCN) ≥4. MET amp (focal) by ctDNA was defined as having plasma MET GCN ≥4 with no co-amplification in CDK6 and EGFR. c-Met OE by Immunohistochemistry (IHC; SP44) was defined as 3+ tissue staining intensity in ≥25% tumor cells (high c-Met OE: 3+, ≥50%; intermediate [int] c-Met OE: 3+, 25% to 49%). Exploratory analysis of tumor response was assessed in 76 efficacy evaluable pts with c-Met OE and MET amp assay results. Results: MET amp was detected in 34% (37/108) of pts with c-Met OE (3+, ≥25%) and was enriched by c-Met levels: 22% (11/50) in pts with Int c-Met OE (3+, 25% to 49%) and 45% (26/58) in pts with high c-Met OE (3+, ≥50%). The effects of MET amp on tumor response in LUMINOSITY are shown in Table 1. The majority of c-Met OE pts (79%) with PFS ≥10 mo (n=14) had GCN ≥10 and/or c-Met IHC 3+ ≥50%. No new safety signals were reported in pts with c-Met OE and MET amp. Conclusions: MET amp is more common in pts with high c-Met OE in this retrospective subgroup analysis. Tumor activity with Teliso-V was observed regardless of MET amp status. The impact of MET amp in pts with c-Met OE will be further evaluated in ongoing Phase 3 study (NCT04928846). Teliso-V efficacy in NSQ EGFR -WT NSCLC pts with c-Met OE with or without MET amp in LUMINOSITY. Total c-Met OE(3+, ≥25%) Total c-Met OE(3+, ≥25%) Intermediate c-Met OE(3+, ≥25%-49%) Intermediate c-Met OE(3+, ≥25%-49%) High c-Met OE(3+, ≥50%) High c-Met OE(3+, ≥50%) MET amp(N) No (N=53) Yes (N=23) No (N=30) Yes (N=7) No (N=23) Yes (N=16) ORR %(95% CI) 28 (18.0, 41.6) 39 (22.2, 59.2) 23 (11.8, 40.9) 57 (25, 84.2) 35 (18.8, 55.1) 31 (14.2, 55.6) PFS,median, mo(95% CI) 5.26 (3.71, 8.11) 8.02 (4.47, 14.65) 5.32 (2.69, 8.11) 7.52 (4.47, NA) 4.17 (3.25, 8.87) 8.02 (3.06, 25.92) OS,median, mo(95% CI) 14.5 (8.18, 17.38) 13.86 (6.54, 22.24) 14.03 (3.65, 17.02) 9.79 (6.54, NA) 16.26 (5.59, 36.44) 13.86 (3.06, 30.29)

Development of an exploratory prediction model for preoperative CK19 expression in esophageal cancer driven by radiomics and machine learning

Background Esophageal cancer ranks among the most lethal malignancies worldwide, particularly prevalent in the Guangdong–Chaoshan region of China due to regional dietary habits. Cytokeratin 19 (CK19) is an important immunohistochemical marker reflecting tumor invasiveness and metastatic potential; however, noninvasive preoperative prediction of CK19 expression remains unavailable. This study aimed to develop a CT-based radiomics model combined with machine learning to predict CK19 expression preoperatively. Methods This study included 134 patients with primary esophageal cancer. All patients underwent enhanced CT scans before surgery, and CK19 expression was evaluated by pathological analysis after surgery. Radiomics technology was used to extract multidimensional image features including shape, texture, and first-order features from CT images. A prediction model was established by combining machine learning models such as gradient boosted decision tree (GBDT), random forest (RF), extreme gradient boosting (XGB), and lightweight gradient boosting machine (LGBM), and the interpretability of the model was analyzed by SHAP value. Results The random forest model showed relatively higher accuracy and precision among the compared models, with an AUC value of 0.6765 and an accuracy of 0.8293. GBDT demonstrated a more balanced performance (AUC: 0.6597), while XGB (AUC: 0.6744) and LGBM (AUC: 0.6807) showed comparable but overall slightly lower discriminative ability. Feature importance analysis showed that the features after wavelet transformation made a significant contribution to the prediction results. The results verified the potential of radiomics combined with machine learning technology in the preoperative prediction of CK19 expression. Conclusion This study developed a preoperative noninvasive prediction model based on radiomics and machine learning, which showed modest predictive performance in an exploratory setting in the evaluation of CK19 markers in patients with esophageal cancer, may provide preliminary support for further exploration in precision medicine. In the future, the clinical applicability of this model needs to be further verified and its promotion and application in a larger population needs to be optimized.

Bio‐Propelled Stomatocyte Nanomotors with Glutathione‐Responsiveness for Osteoarthritis Treatment

ABSTRACT Pharmacological intervention is a primary therapeutic strategy for Osteoarthritis (OA), however, improving the bioavailability of therapeutic agents remains a significant challenge. In this study, we developed oxygen‐propelled, glutathione (GSH)‐responsive stomatocyte nanomotors (MTX/MnO 2 ‐GSH‐stomatocytes) for osteoarthritis (OA) treatment. First, polymersomes were assembled composed of block copolymers containing a GSH‐cleavable disulfide linker, which were loaded with the therapeutic agent methotrexate (MTX) into their hydrophilic domain. Upon dialysis‐induced shape change bowl shaped stomatocytes were formed with manganese dioxide (MnO 2 ) particles encapsulated into the nanocavity with high loading efficiency. Within the OA microenvironment, MnO 2 decomposed the inflammatory hydrogen peroxide (H 2 O 2 ), generating an O 2 gradient that propelled the nanomotors and enabled chemotactic movement for targeted cargo delivery. Meanwhile, after cellular uptake elevated GSH levels cleaved the disulfide linkers, inducing the collapse of the stomatocyte structure and the rapid release of MTX. The motility and targeted release behavior of the nanomotors were systematically evaluated both in vitro and in vivo. Experimental results demonstrated that these nanomotors effectively alleviated oxidative stress, inflammation, and cartilage degradation, while exhibiting negligible adverse effects. Overall, this study presents a promising GSH‐responsive, nanomotor‐based strategy for enhanced osteoarthritis therapy.

Cold sintering opens the door to drug-eluting bioceramics for oral antifungal care: Opportunities and a development roadmap

Active Learning Identifies Sulfur‐Based Enhancers for Fe(III)‐Protoporphyrin Catalysis: Recapitulating Features of Natural Oxidase and Beyond

ABSTRACT Sequence‐controlled polymers, such as polypeptides, offer a versatile platform for tuning the microenvironment of catalytic centers, drawing inspiration from enzymes while enabling a larger design space, structural flexibility, automated synthesis, and compatibility with closed‐loop optimization. Here, we designed an artificial oxidase system by immobilizing Fe(III)‐protoporphyrin IX onto a lysine residue in synthetic decapeptides via amide linkage. Using hydrogen peroxide as the oxidant and acetophenone as a model substrate, we used an active‐learning‐guided closed‐loop workflow to prioritize peptide sequences across 233 variants over 20 rounds. Statistical analysis revealed that sulfur‐containing residues—cysteine and methionine—consistently enhanced activity when positioned adjacent to the coordination site. Notably, although sequence optimization began from random inputs, the algorithm quickly converged on cysteine‐containing motifs, consistent with features found in natural oxidases. Thioether‐containing methionine was also found to promote catalysis, extending the relevance of sulfur‐based coordination beyond naturally occurring systems. These findings demonstrate the application of data‐driven sequence design for developing tunable, enzyme‐inspired catalysts with simplified architectures.

Vicariant establishment of Dactylopterus in the western Atlantic linked to shallowing of Central American Seaway (CAS)

Correction: GPR39-mediated molecular signaling by bile acids