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Circulating tumor DNA (ctDNA) dynamics as early biomarkers of response to enfortumab vedotin plus pembrolizumab (EVP) in advanced urothelial carcinoma (aUC).
4582 Background: Radiographic assessment of treatment response remains challenging in aUC. ctDNA testing offers a sensitive, noninvasive measure of real-time treatment response. With EVP established as a frontline standard, we hypothesized that ctDNA dynamics correlate with radiographic response and survival. Methods: We retrospectively analyzed an institutional cohort of 302 patients (pts) with aUC treated with EVP at MD Anderson; 79 pts with baseline and serial ctDNA testing using a tumor-informed assay (Signatera) (08/23–01/26) were included. ctDNA dynamics were evaluated in two ways: (1) early on-treatment change (baseline vs. first on-treatment ctDNA) for association with radiographic response, and (2) time-dependent modeling as a covariate in Cox proportional hazards analyses of progression-free survival (PFS) and overall survival (OS) to account for immortal-time bias. Results: All pts had a median of 4 ctDNA tests (range: 1-9). Baseline ctDNA was obtained before or at EVP start in 67 (84.8%). Among these patients, first ctDNA clearance occurred in 46.3%, decrease in 26.9%, and increase in 19.4%; 6% had persistently undetectable ctDNA and 1.5% was lost to follow-up. Median time to first ctDNA reduction (clearance or decrease) was 48 days [IQR: 40–86]. Pts without baseline ctDNA prior to EVP (12, 15.2%) were non-evaluable. The best overall response rate to EVP was 53/79 (67.1%), including complete in 13.9% and partial responses in 53.2%. Objective responses were highest among pts with first ctDNA clearance (87.1%), lower with first ctDNA decrease (55.6%), and uncommon with first ctDNA increase (38.4%) (χ² test, p =0.003). In the overall cohort (n=79), median PFS from EVP start was 20.4 months (mo) [95% CI: 8–NE] and median OS from EVP start was 30.3 mo [95% CI: 26.3–34.3], with a median follow-up of 12.1 mo [95% CI: 9.1–14.9]. In time-dependent Cox models accounting for immortal-time bias, increasing ctDNA levels over time were associated with inferior PFS (HR 1.49 [95% CI: 1.11–2]; p =0.007) and OS (HR 1.41, [95% CI: 0.96–2.08], p =0.08). Conclusions: Early ctDNA dynamics provide a clinically meaningful measure of response to EVP in aUC and correlate with imaging outcomes. ctDNA clearance identifies pts with deep and durable benefit, while lack of clearance flags early resistance. Longer follow-up will evaluate ctDNA-guided monitoring to inform treatment de-escalation or maintenance approaches. Baseline characteristics of cohort (n=79). Variable Measure Age at aUC diagnosis, median [IQR] 71 [65 – 76] Sex, male, n (%) 56 (70.9%) Tumor Origin, n (%)BladderUpper Tract 61 (77.2%)18 (22.8%) Visceral mets, n (%) 34 (43%) Nodal-only mets, n (%) 40 (50.6%) Baseline ctDNA before/at EVP start (MTM/mL), median [IQR]All (n=67)Visceral mets (n=30)Nodal-only mets (n=33) 12.9 [1.1 – 105.5]12.8 [1.3 – 140.2]16.9 [1.4 – 96]
Larynx preservation via chemotherapy-free neoadjuvant sintilimab-cetuximab-SBRT and response-adapted treatment in locally advanced laryngeal cancer: A phase II, single-arm clinical trial (the NeoVOICE study).
6095 Background: The current standard of care for locally advanced laryngeal squamous cell carcinoma (LA-LSCC), including surgery and chemoradiotherapy, might cause long-term toxicities and laryngeal dysfunctions. The study aims to investigate the efficacy and safety of neoadjuvant cetuximab, sintilimab and stereotactic body radiation therapy (SBRT) treating patients with LA-LSCC for larynx preservation. Methods: In this phase II, single-arm trial, patients with LA-LSCC (cT2N1-3M0 or cT3-4aN0-3M0, AJCC 8.0 th ) were recruited. Eligible patients received SBRT (8 Gy × 3 fractions), followed by sintilimab (200mg, Q3W, 2 cycles) and cetuximab (a loading dose of 400 mg/m 2 , followed by 250 mg/m 2 , QW, 6 cycles). Further treatment was determined by a radiographic evaluation per RECIST 1.1: patients who reached CR or PR would receive intensity modulated radiation therapy (The initial IMRT dose to the primary tumor was 46 Gy in 23 fractions, with a pre-specified plan to reduce the dose to 37.8 Gy based on early tolerance data from the cohort.) or minimally invasive surgery, while ones with SD or PD would receive radical surgery. The primary endpoint was the larynx-preservation rate (LPR) at 1-year post-radiation. Results: Between July 1, 2024 and June 30, 2025, 20 patients were enrolled. 15 (75%) were clinical stage III and 5 were stage IVa. 19 finished neoadjuvant SBRT, sintilimab and cetuximab (one withdrawn due to personal reasons after SBRT), with the ORR of 100% (12 had CR and 7 had PR). Then 18 patients received sequential IMRT, with a median dose of 37.8 Gy (one refused and chose active surveillance). During the whole treatment, grade 3 TRAEs occurred in 5/20 patients (25%), including 3 cases of post-radiation pharyngitis, 1 myocarditis and 1 rash. All 3 cases of grade 3 pharyngitis occurred in the first 6 patients with 46 Gy IMRT. Following a protocol amendment, subsequent patients (n=12) received a reduced dose of 37.8 Gy. In the reduced-dose cohort, no further grade 3+ pharyngitis was observed, while the LPR remained high. After a median follow-up of 7.4 months, 3 patients failed to larynx preservation, including 2 cases with tracheotomies due to pharyngitis and 1 receiving total laryngectomy due to tumor recurrence. Based on results of EORTC QLQ-H&N35 questionnaires, compared to the baseline, most patients reported similar or improved symptoms, including pain, speech and dry mouth, at 6 months post-radiation. Conclusions: Neoadjuvant combination of immunotherapy, targeted therapy and SBRT showed excellent efficacy and tolerant toxicity for patients with LA-LSCC. Importantly, dose reduction of sequential IMRT appears to mitigate severe toxicity without compromising laryngeal preservation, outlining a promising de-escalation strategy for future practice. Clinical trial information: ChiCTR2500100185.
Patterns of use and adherence to breast cancer clinical practice guidelines among Brazilian medical oncologists: The GUIDE-Breast survey (LACOG 0924-GBECAM|D9673N00006).
e23146 Background: Clinical practice guidelines are central to standardize breast cancer (BC) care and reduce disparities in outcomes. Understanding their integration into routine practice and the impact of access limitations is essential to guide strategies that improve equity and quality of care in Brazil. Methods: A national survey was conducted among clinical oncologists treating BC in Brazil. Domains included demographics, guideline utilization patterns, influence on clinical decision-making, and perceived barriers and facilitators to adherence. The primary endpoint was self-reported adherence to BC clinical practice guidelines. Results: Among 284 respondents, median age was 40 years (range 35.5-45.0), and 64% were female. Twelve percent treated exclusively BC, 48% mainly BC, and 40% multiple solid tumors including BC. Overall, 98% reported using guidelines to support clinical decisions, and 78% consulted them at least monthly. The SBOC guideline was most frequently considered to best reflect Brazilian clinical practice (42%), followed by ESMO (15%). Key facilitators included regularly updated evidence (24%), and ease of interpretation (22%). In contrast, the main barriers to guideline adherence were limited access to medications and/or procedures (22%), and difficulty applying guidelines to real-world clinical practice (12%). Only 19% reported full access to all guideline-recommended therapies, exams, and procedures; 38% had access to most resources, and 29% to only some resources (Table 1). Conclusions: Brazilian oncologists report high utilization of BC clinical practice guidelines. However, restrict access to guideline-recommended therapies remains a major barrier to full implementation, reinforcing persistent structural inequities in BC care and the need for system-level strategies to expand access. Guidelines utilization patterns. ASCO(American Society of Clinical Oncology) NCCN(National Comprehensive Cancer Network) ESMO(European Society for Medical Oncology) SBOC(Sociedade Brasileira de Oncologia Clínica) MOC(Manual de Oncologia Clínica) St Gallen International Consensus Guidelines for Early Breast Cancer Advanced Breast Cancer International Consensus Conference Institutional Guideline Other/None How frequently do you use this guideline in your clinical practice for breast cancer (% frequently or very frequently) 74% 89% 78% 56% 52% 27% 26% 46% - Which guideline(s) do you use to study / to keep up to date? (% checked) 60% 53% 57% 32% 34% 19% 12% 1% 5% Which guideline(s) generally influence your decisions Regarding the utilization of innovative agents? (% checked) 56% 53% 50% 31% 30% 12% 8% 8% 5%
Survival, fertility preservation, and pregnancy after treatment in young patients with BRCA-associated triple-negative breast cancer.
e23345 Background: As survival outcomes improve with novel systemic therapies, fertility preservation (FP) and post-treatment pregnancy have become increasingly important issues for young patients with triple-negative breast cancer (yTNBC) harboring BRCA1/2 pathogenic variants. However, real-world data on reproductive outcomes and survivorship issues in this population remain limited. Methods: We retrospectively analyzed patients younger than 40 years with yTNBC and confirmed germline BRCA1/2 pathogenic variants who underwent primary surgery between 2007 and 2022 at a single tertiary cancer center. Oncologic outcomes, FP practices, pregnancy outcomes, and the timing of risk-reducing salpingo-oophorectomy (RRSO) were evaluated. Results: Thirty-eight patients were included. The median age at surgery was 34 years. BRCA1 and BRCA2 pathogenic variants were identified in 80% and 20% of patients, respectively, and 65% had stage II disease. Chemotherapy was administered to 97.4% of patients, including neoadjuvant chemotherapy (53.8%), adjuvant capecitabine (7.9%), and PARP inhibitors (13.2%). With a median follow-up of 5.9 years, disease events included lung metastases (n=2), local recurrence (n=1), ipsilateral breast tumor recurrence (n=2), contralateral breast cancer (n=10), ovarian cancer (n=2), and ureteral cancer (n=1). The 5- and 10-year overall survival rates were 97.4% and 87.6%, respectively. Among 12 patients expressing a desire for future pregnancy, 7 attempted FP, and FP was successfully completed in 6 patients prior to chemotherapy. All patients received genetic counseling and underwent surveillance for breast and ovarian cancer at 6- and 3-month intervals, respectively. Six patients achieved a total of 11 pregnancies, including one ongoing pregnancy, resulting in 6 live births. All pregnancies occurred in patients without disease recurrence. Notably, three of the six patients who achieved pregnancy had a prior history of treatment with PARP inhibitors. The median interval from surgery to first pregnancy was 2.5 years. RRSO was performed in 13 patients at a median age of 41 years, with a median interval of 3.0 years from surgery. Conclusions: Despite the limited sample size, this study provides real-world insight into survivorship and reproductive outcomes in young patients with BRCA-associated yTNBC. Favorable survival and successful pregnancies were observed following individualized, multidisciplinary care. Importantly, these findings highlight the emerging and largely unexplored issue of pregnancy following PARP inhibitor exposure. The high incidence of contralateral breast cancer and variability in RRSO timing underscore the need for personalized survivorship planning integrating cancer risk management with reproductive decision-making in the era of novel systemic therapies.
A phase Ib/III randomized double-blinded placebo-controlled study of suvemcitug combined with trifluridine/tipiracil for refractory metastatic colorectal cancer.
TPS3674 Background: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. For patients with metastatic CRC (mCRC) that has progressed on standard chemotherapies, available treatments offer limited benefit. Notably, the phase III SUNLIGHT trial demonstrated the efficacy and safety of trifluridine/tipiracil (FTD/TPI) in combination with bevacizumab in refractory mCRC. Suvemcitug is a new-generation recombinant humanized anti-VEGF rabbit monoclonal antibody. In the previous clinical trials, suvemcitug demonstrated its favorable safety profile and efficacy signals as a single agent or in combination with chemotherapy for the treatment of mCRC. This study aims to assess the efficacy and safety of the combination of suvemcitug and FTD/TPI in patients with refractory mCRC. Methods: This phase Ib/III, randomized, double-blinded, placebo-controlled, multi-cohort study (NCT07361003) consists of two parts, Part 1 (phase Ib) and Part 2 (phase III). Estimated total enrollment is approximately 464 participants: 30 for Part 1 and 434 for Part 2. Patients with mCRC are eligible for participation if they have received chemotherapy based on fluoropyrimidine, oxaliplatin and irinotecan, and have either previously received or are unsuitable for anti-VEGF therapy and anti-EGFR therapy (if RAS wild-type). Part 1: Phase Ib: Participants will be enrolled to receive suvemcitug combined with FTD/TPI. The dose of suvemcitug is 1.5 mg/kg administrated intravenously every two weeks. The primary endpoint is safety and tolerability of suvemcitug. The secondary endpoints include pharmacokinetic (PK) profile of suvemcitug; the incidence, duration, and titer of anti-drug antibodies (ADA); as well as objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Part 2: Phase III: Part 2 is designed as a Phase III to further evaluate the antitumor activity of suvemcitug in combination with FTD/TPI in refractory mCRC. Eligible participants will be randomized (1:1 ratio) to receive FTD/TPI in combination with suvemcitug or matching placebo at the dose identified in Part 1. Stratification criteria include primary tumor location, prior bevacizumab exposure, and time from initial metastasis to enrollment. The primary endpoint is OS. The secondary endpoints include PFS, ORR, DoR, DCR, safety, quality of life, PK and immunogenicity (ADA incidence, titer, duration). The exploratory endpoints are correlations among PK, pharmacodynamics, safety and clinical efficacy. Study treatment will continue until progressive disease, unacceptable toxicity, withdrawal of consent, or the investigator’s decision to discontinue. Clinical trial information: NCT07361003 .
A real-world study of triple-negative breast cancer patients with brain metastases: A multicenter retrospective analysis.
e13130 Background: Triple-negative breast cancer patients with brain metastasis (TNBC-BM) have extremely poor prognosis, posing significant clinical challenges. While immunotherapy combined with chemotherapy has improved the treatment of advanced triple-negative breast cancer, its efficacy and prognostic determinants in TNBC-BM patients require further elucidation. Methods: This retrospective study enrolled patients with TNBC-BM treated at the PLA General Hospital and the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) between January 2015 and October 2024. Clinicopathological characteristics and treatment regimens were collected. The primary endpoint was overall survival after brain metastasis (BMOS). Survival analysis was performed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards model to identify independent prognostic factors. To further evaluate the efficacy of immunotherapy, propensity score matching (PSM) was applied to balance baseline characteristics between patients who receive immunotherapy or not. Results: A total of 161 patients were included. By the final follow-up date (October 31, 2025), 134 patients (83.23%) died, with a median BMOS of 13 months (95% CI: 11–16). Univariate and multivariate Cox regression analyses identified the following as independent prognostic factors. ECOG performance status < 2 at BM diagnosis (HR = 4.12, 95% CI: 2.44–6.97, P < 0.001), hemoglobin level > 110 g/L (HR = 0.58, 95% CI: 0.38–0.90, P = 0.015), and receipt of immunotherapy after brain metastasis (HR = 0.39, 95% CI: 0.23–0.66, P < 0.001) were associated with a more favorable prognosis . Presence of liver metastasis (HR = 3.16, 95% CI: 1.95–5.13, P < 0.001), distant lymph node metastasis (HR = 1.47, 95% CI: 1.01–2.16, P = 0.047) were associated with a poorer prognosis. In the PSM-adjusted subgroup analysis, patients receiving immunotherapy had a median BMOS of 19 months (95% CI: 12–NA), compared to 10 months (95% CI: 5–16) for those not receiving immunotherapy. Immunotherapy was associated with a 48% reduction in the risk of death (HR: 0.52, P = 0.022). Conclusions: TNBC-BM patients with good performance status and absence of anemia at BM diagnosis have superior survival outcomes, while the presence of extracranial metastases, particularly liver metastasis, suggests a poorer prognosis. Therapeutically, TNBC-BM patients derived survival benefits from immunotherapy. Prospective studies are warranted to further define the precise patient population that benefits from this treatment approach.
Clinical implications of primary and metastatic tumor-informed clonal tracking for MRD assessment in oligometastatic colorectal cancer.
3601 Background: While minimal residual disease (MRD) assays informed by primary tumor sequencing have demonstrated prognostic value in locally advanced colorectal cancer (CRC), the additive clinical benefit of combined tracking of metastatic-specific private variants in oligometastatic CRC (mCRC) remains unclear. We aimed to evaluate whether a combined primary and metastatic tumor-informed approach improves MRD detection sensitivity and prognostic accuracy following curative resection. Methods: We enrolled 24 patients who underwent curative resection for liver and/or lung oligometastases between 2023 and 2025. A comprehensive tumor-informed panel was designed based on variants identified through whole-exome sequencing (WES) of both primary and metastatic tissues. Serial plasma ctDNA was analyzed at three time points: post-metastasectomy (P1), post-adjuvant chemotherapy (P2), and at the time of recurrence (P3). The clinical performance of a primary tumor-only (PT-only) assay was compared with a combined primary and metastatic tumor-informed (PT+MT) assay. Results: The median age was 65 years (range 33–83), and 18 (75%) were male. Primary tumor locations included the colon (83%) and rectum (17%). Fourteen (58%) patients presented with synchronous metastases. Metastatic sites involved the liver (n = 13), lung (n = 10), or both (n = 1). At P1, P2, and P3, MRD positivity rates using the PT-only assay were 54%, 47%, and 100%, respectively. The PT+MT assay identified only one additional patient as MRD-positive at P1 compared to the PT-only assay. At a median follow-up of 29.2 months (IQR 22.6–32.7), 16 patients (67%) experienced recurrence. The PT-only assay showed significant prognostic impact (HR for ctDNA positivity: 4.53; 95% CI, 1.41–14.57; P = 0.006), which was comparable to the PT+MT assay (HR: 4.46; 95% CI, 1.38–14.38; P = 0.007). While PT+MT tracking did not significantly improve detection sensitivity at P1, it effectively captured clonal dynamics, showing a significant enrichment of metastatic-specific private variants in plasma at recurrence (26%, P3) compared to P1 (17%) and P2 (13%). Conclusions: Integrating metastatic-specific private variants into MRD tracking revealed distinct clonal dynamics but did not significantly enhance clinical sensitivity or prognostic performance compared to a primary tumor-informed assay in patients with oligometastatic CRC. These findings suggest that current MRD assay designs based on primary tumor sequencing remain a robust standard, even in the metastatic setting after curative resection.
Associations between neighborhood disadvantage, cannabis use, and patient-reported outcomes among patients with cancer.
e13501 Background: Cannabis use is proliferating among oncological populations. However, research is limited on whether cannabis use, including route and source, is associated with neighborhood disadvantage and may elucidate differences in patient-reported outcomes (PROs). This analysis evaluates the relationship between neighborhood disadvantage and cannabis source and route, and their association with PROs. Methods: Analyses included 106 patients with cancer from varying levels of neighborhood disadvantage. Logistic regressions tested the association of neighborhood disadvantage with cannabis source (i.e., regulated vs. unregulated) and route (i.e., inhaled vs. consumed/other formulations). Multilevel regressions tested the association of neighborhood disadvantage with PROs (e.g., anxiety, depression, sleep quality, pain, quality of life) and moderation by cannabis source and route. Results: Controlling for covariates, neighborhood disadvantage did not uniquely predict cannabis source or route ( p ’s > .05) or PROs ( p ’s > .05). Conversely, household income predicted pain interference and severity, quality of life, and depression, indicating that lower household income was associated with worse outcomes ( p ’s < .05). Multilevel analyses including cannabis route as a moderator revealed that cannabis route significantly moderated the relationship between neighborhood disadvantage and anxiety ( b = 0.09, 95%CI [-0.01,0.2], p = .03). Inhaled formulations (vs consumed/other formulations) were associated with high levels of anxiety for patients from moderately disadvantaged neighborhoods. Conversely, inhaled formulations were associated with lower levels of anxiety for patients from the most disadvantaged neighborhoods. Conclusions: Although the composite index of neighborhood disadvantage was not associated with cannabis use or PROs, our data suggest that income and cannabis route may be key factors associated with health disparities among patients with cancer.
Improving hematology/oncology education for physician trainees through an interactive online platform.
e21008 Background: Internal Medicine residency education in Hematology/Oncology remains challenging due to the complexity and rapid advancement of the field, limited time for teaching, and other competing time interests such as direct patient care. Residents often struggle with keeping up to date on epidemiology, diagnosis and workup, prognosis, and treatment approaches. Online platforms offer a scalable solution to bridge this knowledge gap. This project focuses on the development of an interactive website designed to enhance the clinical knowledge and decision-making skills of internal medicine residents. Methods: A pre-survey was used to assess resident self-reported baseline knowledge and preparedness before Hematology/Oncology rotations. Descriptive statistics were employed to identify the areas in which residents needed the most support. The survey included 5-point Likert-scale questions, with a focus on clinical practice and decision-making skills. An interactive online platform was developed with modules covering key topics including signs and symptoms of disease, diagnosis and workup, treatment, emergency management, and complications of treatment. This website was then shared with residents when their Hematology/Oncology rotations began. Results: 48 out of 51 residents (94%) completed the baseline assessment in January 2026. Out of 46 respondents, 47.9% either disagreed or strongly disagreed that they are confident in formulating an initial management plan for Oncology patients. Additionally, 64.6% either disagreed or strongly disagreed that they were aware of current Hematology/Oncology practice guidelines, and 39.6% either disagreed or strongly disagreed that they know how to access these guidelines. 16.7% of residents either strongly agreed or agreed that they know how to find actively recruiting clinical trials relevant to their patients, and 18.7% strongly agreed or agreed that they are able to identify professional societies related to oncology. An internal intranet website was created to increase resident education and empowerment during their Hematology/Oncology rotations. Website topics included management of cancer patients, evaluation of patients with Hematologic malignancies, current treatment guidelines, and Hematology/Oncology literature. Conclusions: Pre-survey responses indicated that residents may benefit from increased emphasis in many domains within Hematology/Oncology. An online educational platform has been developed to address these gaps in knowledge and shared with residents who have begun their Hematology/Oncology rotation. Future steps include performing post-surveys to evaluate the impact of the website on resident education and refining the website as needed. This model of using online platforms to augment resident sub-specialty education could be expanded to other subspecialties to further improve residency training.
Inpatient mortality across gastrointestinal malignancies by hospital structural characteristics in the United States, 2018–2022.
e16353 Background: Inpatient mortality among gastrointestinal (GI) cancer hospitalizations is often attributed to tumor biology and disease severity. National data describing the relative contribution of hospital structural characteristics to acute inpatient outcomes across GI malignancies remain limited. Methods: A serial cross-sectional analysis was conducted using the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample. Adult hospitalizations with a principal diagnosis of esophageal, gastric, colorectal, hepatocellular, or pancreatic cancer were identified. Outcomes included in-hospital mortality (primary), length of stay (LOS), and hospitalization cost estimated using cost-to-charge ratios. Hospital structural characteristics examined included teaching status, bed size, geographic region, and urban–rural classification. National estimates accounted for survey weighting, clustering, and stratification. Survey-weighted multivariable logistic regression identified factors independently associated with in-hospital mortality, adjusting for cancer subtype, demographics, payer, neighborhood income quartile, hospital characteristics, and calendar year. Results: From 2018–2022, 214,740 unweighted GI cancer hospitalizations represented an estimated 1,073,700 hospitalizations nationally. Overall weighted in-hospital mortality was 4.03%. After adjustment, admission to a teaching hospital was associated with lower odds of in-hospital death compared with non-teaching hospitals (adjusted odds ratio [aOR] 0.56, 95% CI 0.51–0.63). Large hospitals also demonstrated lower mortality compared with small hospitals, while no significant difference was observed for medium hospitals. Geographic variation persisted, with lower adjusted mortality in the Midwest and South compared with the Northeast. By comparison, adjusted mortality differences across major GI cancer subtypes were smaller than those observed across hospital structural characteristics. Teaching hospitals demonstrated longer LOS but lower mortality following acute complications, consistent with differences in rescue capacity rather than complication incidence. Conclusions: Among GI cancer hospitalizations, inpatient mortality varied more by hospital structural characteristics than by cancer subtype. Teaching status, hospital size, region, and urban–rural context were associated with differences in survival independent of tumor site. These nationally representative findings provide benchmarking data on the institutional context of inpatient mortality in gastrointestinal oncology.
The efficacy of adjuvant chemoendocrine versus endocrine therapy alone in hormone receptor-positive, HER2-negative early breast cancer: A meta-analysis of reconstructed individual patient data.
e12504 Background: The benefit of adding adjuvant chemotherapy to endocrine therapy for hormone receptor–positive (HR+), HER2-negative (HER2-) early breast cancer remains controversial, particularly in the era of genomic risk stratification. This meta-analysis evaluated long-term survival outcomes of chemoendocrine therapy (CET) versus endocrine therapy alone (ET) in this population. Methods: PubMed, EMBASE, and the Cochrane Library were searched for randomized controlled trials (RCTs) comparing CET with ET in HR+/HER2– early breast cancer. Individual patient time-to-event data were reconstructed from published Kaplan–Meier curves. Pooled hazard ratios (HRs) for overall survival (OS), invasive disease-free survival (IDFS), and distant disease-free survival (DDFS) were estimated using Cox frailty models. The proportional hazards assumption was tested, and restricted mean survival time (RMST) analyses quantified absolute survival differences. Results: Five RCTs including 13,866 patients met inclusion criteria. The addition of chemotherapy did not significantly improve OS (HR = 0.90; 95% CI 0.77–1.06; P = 0.221) or DDFS (HR = 0.92; 95% CI 0.74–1.15; P = 0.464). A statistically significant but clinically modest improvement was observed in IDFS (HR = 0.90; 95% CI 0.82–0.99; P = 0.035), corresponding to an RMST difference of only 0.07 years at 9 years. No violation of proportional hazards assumptions was detected. Conclusions: Among patients with HR+/HER2– early breast cancer, adjuvant chemotherapy added to endocrine therapy does not yield a significant overall survival benefit and offers only a minimal, clinically questionable improvement in invasive disease-free survival. These findings suggest that endocrine therapy alone is sufficient for most patients with low to intermediate genomic risk.
Beta-blockers and overall survival in men receiving ADT + systemic therapy for metastatic prostate cancer.
e17112 Background: Beta-adrenergic signaling has been implicated in prostate cancer progression. However, observational studies of beta-blocker (BB) use have shown inconsistent associations with survival. We evaluated whether BB use at systemic therapy initiation was associated with overall survival (OS) in men with metastatic prostate cancer treated with androgen deprivation therapy (ADT) plus systemic therapy. Methods: Using the TriNetX network, we identified men with metastatic prostate cancer who initiated ADT and subsequently started systemic therapy with an androgen receptor signaling inhibitor (ARSI) or docetaxel. The index date was systemic therapy initiation. Patients were classified as BB users or BB nonusers based on medication exposure at the index date. Propensity score matching (1:1) was performed to balance demographics, metastatic patterns, comorbidities, and baseline laboratory values. OS was analyzed using Kaplan-Meier methods and Cox regression. A 30-day landmark analysis was performed to address early nonproportional hazards. Subgroup and active-comparator analyses were conducted. Results: Among 8,634 eligible patients, 1,238 patients were included in each group after matching. Approximately 70% of patients received an ARSI, and 30% received docetaxel as index systemic therapy. The mean age in the matched cohort was 72 years (SD: 9). Racial and ethnic distributions were similar. The cardiovascular, metabolic, and renal comorbidity burden, as well as baseline lab values were well-balanced between groups (Table 1). BB use at systemic therapy initiation was not associated with improved OS compared with no BB use (HR 1.04, 95% CI 0.91–1.18; p = 0.56). Early hazards were non-proportional, with worse early survival among BB users; however, a 30-day landmark analysis yielded similar results (HR 1.01, 95% CI 0.88–1.15; p = 0.91). Findings were consistent in the ARSI-only subgroup (HR 1.10, 95% CI 0.93–1.30; p = 0.25) and in an active-comparator analysis versus calcium channel blockers (HR 1.00, 95% CI 0.80–1.24; p = 0.97). Conclusions: In this large real-world cohort of men receiving ADT plus systemic therapy for metastatic prostate cancer, BB use at the time of systemic therapy initiation was not associated with an overall survival benefit. Overall, these results reassure that BB use is not associated with inferior overall survival in this high-risk population. Baseline characteristics after propensity score matching. Variable Beta-Blocker No Beta-Blocker Age, mean ± SD (y) 72.0 ± 9.1 72.3 ± 8.9 Race/Ethnicity, % White 67.6 69.3 Black 16.7 15.3 Hispanic 5.9 5.4 Other 9.8 10.0 Comorbidities, % Hypertension 67.2 67.2 CAD 29.4 29.4 Heart failure 14.8 14.8 Atrial fibrillation 20.8 20.8 DM 28.3 28.3 CKD 18.0 18.0 Baseline laboratory values, mean ± SD Hemoglobin (g/dL) 11.7 ± 2.4 11.5 ± 2.4 Albumin (g/dL) 3.7 ± 0.6 3.7 ± 0.6 Sodium (mmol/L) 138 ± 3.5 138 ± 3.6 PSA (ng/mL) 280 ± 970 292 ± 963
AcTFirst: A phase 3 trial of <sup>225</sup> Ac-PSMA-617 plus ARPI versus standard of care in adults with PSMA-positive metastatic castration-resistant prostate cancer.
TPS5134 Background: In the VISION and PSMAfore trials, β-emitting radioligand therapy (RLT) with [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) shows superior efficacy and tolerable safety compared with standard of care (SoC) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). [ 225 Ac]Ac-PSMA-617 ( 225 Ac-PSMA-617), an α-emitting agent, may offer an alternative treatment option to SoC in mCRPC because its higher linear energy transfer increases the likelihood of higher cytotoxicity in tumor cells. Methods: AcTFirst (NCT06855277) is a phase 3, open-label, multicenter, randomized study to evaluate the efficacy and safety of 225 Ac-PSMA-617 plus androgen receptor pathway inhibitor (ARPI) in patients with PSMA-positive mCRPC. Eligible participants are adults with PSMA positron emission tomography-positive mCRPC and progressive disease on androgen deprivation therapy plus one ARPI as their last treatment in the metastatic hormone-sensitive prostate cancer (mHSPC) or earlier setting. ARPI treatment received in the mHSPC setting can be continued until cycle 1. Key exclusion criteria include previous treatment with RLT or systemic anti-cancer therapy for mCRPC. Participants with homologous recombination repair gene-mutated mCRPC who had prior exposure to poly-adenosine diphosphate ribose polymerase inhibitors (PARPi) for HSPC can be included. Participants with inadequate bone marrow, hepatic or renal function are excluded. Participants will be randomized to three treatment arms: 1) a combination of 225 Ac-PSMA-617 (up to six cycles) plus ARPI change (enzalutamide or abiraterone); 2) 225 Ac-PSMA-617 monotherapy (up to six cycles); or 3) investigator’s choice of SoC (ARPI change, taxane chemotherapy or 177 Lu-PSMA-617). Efficacy will be assessed using a hierarchical group sequential testing strategy for the primary and key secondary objectives. The primary endpoint is radiographic progression-free survival (rPFS) by conventional imaging for the combination and SoC arms. Key secondary endpoints are overall survival (OS) for the combination and SoC arms, rPFS by conventional imaging for the monotherapy and SoC arms, OS for the monotherapy and SoC arms, and rPFS by PSMA positron emission tomography/computed tomography imaging for the combination and SoC arms. Other outcomes of interest include safety, health-related quality of life and other patient-reported outcomes. As of January 2026, patient enrollment is ongoing. Clinical trial information: NCT06855277 .
Complementary liquid and tissue NGS testing to identify actionable therapeutic targets missed by single-modality profiling: Insights from a blood-tissue pilot cohort analysis.
e15081 Background: Comprehensive genomic profiling (CGP) is standard-of-care for identifying actionable mutations in advanced cancers. However, whether liquid biopsy (LBx) or tissue biopsy (TBx) alone captures all therapeutically relevant alterations remains unclear. We evaluated blood-tissue concordance and clinical impact of complementary NGS testing. Methods: We analyzed 10 patients with advanced solid tumors (colon n = 4, lung n = 3, breast/gastric/pancreas n = 1 each; median age 64 years, range 48-78) who underwent tissue and blood testing using Caris comprehensive genomic profiling. Specimens were collected at different timepoints (median 7 days apart, tissue performed first in 70%). Thirty-three variant observations across 8 evaluable cases were classified as concordant (detected in both), blood-only, or tissue-only. Actionable variants were defined as alterations with FDA-approved targeted therapies. Gene Ontology enrichment was also performed on concordant gene sets using clusterProfiler with org.Hs.eg.db. Results: Blood-tissue concordance was 87.9% (29/33 variants). ctDNA captured all tissue-detected variants plus 4 blood-only findings in 4 patients (12.1%), including one FDA-actionable alteration. One of the cases harbored an EML4::ALK fusion detected exclusively by LBx, missed by TBx. The patient initiated alectinib therapy 2 weeks prior to data cutoff on the 05 Jan 2026 (response assessment pending). Without complementary LBx, this actionable driver would have been missed, precluding access to an ALK inhibitor with expected PFS of 25-34 months. Concordant genes (n = 12: TP53, APC, KRAS, EGFR, CTNNB1, PIK3CA, others) were significantly enriched for canonical Wnt signaling (p.adj = 0.002), cell cycle G1/S transition (p.adj = 0.004), and regulation of apoptosis (p.adj = 0.004), representing core carcinogenic drivers. Conclusions: Liquid biopsy demonstrates high concordance with tissue-based testing for core driver mutations but uniquely captures actionable therapeutic targets (ALK fusions) missed by single-site tissue sampling. Liquid biopsy captured spatial/temporal tumor heterogeneity not represented in the single tissue sample. Complementary blood-tissue NGS testing identified actionable therapeutic targets in 10% of patients that would have been missed by single-modality profiling. These findings support dual modality testing to maximize detection of actionable alterations and optimize treatment selection. Validation in a larger prospective cohort is needed to establish clinical utility and inform testing guidelines.
Decline in credit score and excess mortality risk among cancer patients: Evidence from Washington State.
11037 Background: Patients experiencing bankruptcy following a cancer diagnosis have been shown to have increased mortality, but few studies have evaluated the impact of other types of financial hardships on mortality risk. We conducted an analysis to understand the relationship between a drop in credit score, a marker of less severe types of financial strain, and mortality among cancer patients in Washington State. Methods: We linked records from cancer patients (age 18+) diagnosed with any cancer (except in situ) between 2010 - 2023 from the Western Washington SEER cancer registry to credit report data from a national credit reporting agency. We excluded patients without a valid credit score near diagnosis (±100 days). In a Cox proportional hazards model using a landmark approach, we examined the relationship between a drop in credit score (25-49, 50-99, or 100+ points) in the first year of diagnosis and subsequent mortality after year 1, using no- or low-drop (<25 points) as the reference. Hazard ratios (HRs) and 95% confidence intervals were derived. Model covariates included age, gender, race/ethnicity, marital status, Area Deprivation Index, urban/rural residence, diagnosis year, cancer type, stage, and credit score at diagnosis. Results: Among 212,898 evaluable patients [49% male, 84% white, median age 65 (IQR 56 - 73)], credit scores at diagnosis were: 42% excellent (800-850), 25% very good (740-799), 15% good (670-739), 12% fair (580-669), and 6% poor (300-579). In the year following diagnosis, 40,078 patients’ credit scores fell ≥25 points (18.8%), including 21,716 falling 25-49 points (10.2%), 12,954 falling 50-99 points (6.1%), and 5,408 falling ≥100 points (2.5%). Among all cancers combined, patients experiencing 50-99 point and ≥100 point reductions (but not 25-49 point reductions) in credit scores had excess mortality (Table). Excess risk of death was observed for nearly all individual cancer types at the ≥100-point reduction level except kidney. Conclusions: In this retrospective study, a substantial reduction in credit scores, typically reflecting the experience of adverse financial events, was associated excess mortality compared to those with stable credit scores. Future studies are needed to understand the mechanisms of the relationship. Excess risk of death following a post-diagnosis fall in credit score (vs no/low reduction). 25-49 points 50-99 points ≥100 points Cancer Type HR CI HR CI HR CI All 0.96 0.94 - 0.99 1.06 1.02 - 1.10 1.33 1.27 - 1.39 Breast 1.00 0.92 - 1.08 1.07 0.97 - 1.18 1.39 1.23 - 1.59 Colorectal 1.02 0.93 - 1.11 1.11 0.99 - 1.23 1.31 1.14 - 1.51 Kidney 0.85 0.73 - 1.00 0.86 0.70 - 1.05 1.23 0.95 - 1.59 Leukemia/lymphoma 0.87 0.79 - 0.96 0.94 0.82 - 1.07 1.29 1.09 - 1.54 Lung 1.00 0.93 - 1.08 1.13 1.04 - 1.24 1.15 1.02 - 1.30 Melanoma 0.90 0.78 - 1.04 1.01 0.85 - 1.20 1.60 1.23 - 2.09 Prostate 0.95 0.87 - 1.03 1.06 0.96 - 1.17 1.39 1.20 - 1.61 Other 0.97 0.92 - 1.01 1.05 1.00 - 1.11 1.31 1.22 - 1.42
InDuRanS: A randomized phase II trial on induction immunochemotherapy followed by surgery or chemoradiotherapy and consolidation durvalumab in stage III NSCLC.
TPS8125 Background: The optimal local treatment strategy for patients with resectable or borderline resectable stage IIIA/B (N2) non-small-cell lung cancer (NSCLC) remains controversial. Earlier randomized trials comparing surgery with definitive chemoradiotherapy (CRT) failed to demonstrate a survival advantage for either modality; however, these studies predated routine PET staging, modern radiotherapy techniques, and standard-of-care immunotherapy. Consolidation durvalumab after definitive CRT has significantly improved survival in unresectable stage III NSCLC, while neoadjuvant immunochemotherapy has shown promising pathologic and survival outcomes in resectable disease. Whether surgery or definitive CRT provides superior outcomes following induction immunochemotherapy in stage III NSCLC is unknown. The InDuRanS trial aims to address this question in a randomized setting. Methods: InDuRanS (ARO-2024-12; NCT06810609) is a prospective, multicenter, open-label, randomized phase II trial conducted across approximately 10 centers in Germany. Eligible patients have (borderline) resectable stage IIIA/B (N2) NSCLC without targetable EGFR or ALK alterations. All patients receive three cycles of induction immunochemotherapy consisting of durvalumab (1,500 mg every 3 weeks) combined with platinum-paclitaxel. Following PET-based restaging, patients with persistent resectable disease are randomized 1:1 to surgery (Arm A) or definitive CRT (Arm B). CRT consists of 60–70 Gy in conventional fractionation with two cycles of concurrent platinum-vinorelbine. Both treatment arms subsequently receive consolidation durvalumab (1,500 mg every 4 weeks) for up to 13 cycles. The primary endpoint is 2-year event-free survival (EFS). Secondary endpoints include overall survival, progression-free survival, treatment-related toxicity, surgical outcomes, and quality of life. Exploratory analyses include radiomics, plasma proteomics, circulating tumor DNA, and immune profiling. A total of 176 patients will be enrolled, with 158 evaluable patients planned for randomization. Interim safety analyses are scheduled after treatment completion in the first 10 randomized patients. The trial is currently open and recruiting.
Discharge trajectories and 30-day readmission risk in hospitalized breast cancer patients with malignant pleural effusion: A National Readmissions study.
e13104 Background: Malignant pleural effusion (MPE) is a common complication of advanced breast cancer and a frequent cause of hospitalization, yet national data on early unplanned readmission after pleural drainage are limited. We examined patterns and predictors of 30-day readmission among hospitalized breast cancer patients with MPE. Methods: We performed a retrospective cohort study using the 2016–2017 Nationwide Readmissions Database. Adult hospitalizations with breast cancer and MPE were identified using ICD-10-CM codes; index admissions were defined as the first qualifying hospitalization per patient, excluding in-hospital deaths. The primary outcome was 30-day all-cause readmission; secondary outcomes included time to readmission and primary readmission diagnosis. Discharge disposition was classified as home without services, home with services, post-acute care, or other. Survey-weighted multivariable logistic regression was used, adjusting for demographics, payer, income quartile, length of stay, acute illness severity (APR-DRG), mortality risk, Charlson comorbidity index, and hospital characteristics. Results: Among 6,550 index hospitalizations, 8.9% resulted in 30-day readmission. Median time to readmission was 16 days (IQR 10–22). Discharge disposition was home without services (43.5%), home with services (39.7%), and post-acute care (15.5%). Cancer progression or metastases accounted for most readmissions (75%), followed by respiratory/pleural complications (7%) and infection/sepsis (4%). Readmission rates were highest among patients discharged home without services (12.2%) and lowest among those discharged to post-acute care (3.2%). In adjusted analyses, discharge to home with services (aOR 0.75, 95% CI 0.60–0.93) and post-acute care (aOR 0.39, 95% CI 0.26–0.59) were associated with lower readmission risk versus home without services. Older age (aOR 0.98/year, 95% CI 0.98–0.99) and longer index length of stay (aOR 0.92/day, 95% CI 0.90–0.95) were independently associated with reduced readmission risk. Conclusions: Nearly one in eleven hospitalized breast cancer patients with MPE experienced early readmission, typically within two weeks of discharge. Discharge disposition defined distinct inpatient trajectory phenotypes with markedly different readmission risks, highest among patients discharged home without services. These findings suggest that discharge destination reflects more than illness severity and represents an actionable transition point, while post-acute care and home services are protective. Older age and longer hospitalization were independently associated with lower readmission risk, noting the importance of discharge readiness and care transitions. Targeted discharge planning and post-acute support may reduce avoidable readmissions in this high-risk population.
Refined temporal-to-frontal horn shunting for trapped temporal horn syndrome: Long-term outcomes and complication management in a two-center series of 53 patients.
e14037 Background: Trapped temporal horn syndrome (TTH) is a rare form of obstructive hydrocephalus that frequently occurs after intraventricular tumor resection. Effective long-term management remains challenging. This study evaluated the long-term outcomes and complication management of refined temporal-to-frontal horn shunting (RTFHS) in patients with TTH. Methods: This retrospective case series included 53 consecutive patients with imaging-confirmed TTH treated at Beijing Tiantan Hospital of Capital Medical University and Beijing Fengtai Hospital between January 2018 and January 2025. Patients presented with symptoms such as headache, cognitive decline, or motor deficits and had a history of brain tumor surgery. All underwent RTFHS, with follow-up durations ranging from 1 month to 6 years. Of the 53 patients, 28 had follow-up over 6 months and 18 over 1 year. All patients received RTFHS with ipsilateral, contralateral, or bilateral shunting approaches. Primary outcomes included symptom improvement and temporal horn volume reduction. Secondary outcomes included management of complications such as high-protein CSF, infection, or suspected shunt catheter intolerance. Results: The initial shunt patency rate was 86.8%, and overall success rate reached 98.1%. Average temporal horn volume reduction was 30.0% on the day of surgery and 60.3% at 3 months. Locally weighted scatterplot smoothing (LOWESS) regression revealed a rapid decrease in the 1st week, a slower decline from 1 week to 3 months, and stabilization thereafter. Long-term follow-up showed no recurrence or re-enlargement in most patients. Complications were effectively managed in nearly all cases. Conclusions: RTFHS is a safe, adaptable, and effective surgical option for managing TTH. It offers favorable long-term outcomes and may be a valuable alternative to a ventriculoperitoneal shunt in selected patients. This study provides useful insights into the prevention and management of perioperative issues.
ctDNA as a complement to gene-expression–based site prediction to guide therapy in cancer of unknown primary: Results from Fudan CUP-001.
e15049 Background: Cancer of unknown primary (CUP) remains a clinical challenge with poor outcomes under empiric chemotherapy. Fudan CUP-001 trial showed site specific therapy (SST) guided by tissue origin gene expression profiling can improve progression free survival (PFS), while CUPSICO trial showed molecularly guided therapy based on comprehensive genomic profiling also provides PFS benefit. We hypothesized that the combined therapeutic approach would yield superior therapeutic efficacy. Methods: We analyzed 170 CUP patients enrolled in the Fudan CUP-001 trial with available ctDNA results, 129 of whom underwent 90-gene expression testing. Somatic alterations were profiled, and actionable variants were classified per Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer. Actionable variants were reclassified after integrating the predicted tissue of origin with ctDNA results. Prognostic factors were assessed using Cox regression models, and potential prognostic models were developed and validated for predictive performance. Results: Among 170 patients (median age 59 years), 148 (87.1%) harbored ≥1 genomic alteration, most commonly TP53 (51%), followed by ARID1A , APC , RB1 , PIK3CA , NFE2L 2 , and KRAS . Forty-eight patients (28.2%) carried actionable alterations (13 tier 1, 35 tier 2); 22.9% harbored > 1 targetable mutation. Integration with tissue prediction reclassified 10 patients from tier 2 and 2 from tier 4 into tier 1, providing treatment options to higher-level targeted therapies (e.g., BRCA1/2 , PTEN , KRAS , MSH6 , ALK , ERBB2 , MET , EGFR ). SST improved PFS (HR 0.66, 95% CI 0.47–0.93) and OS (HR 0.62, 95% CI 0.42–0.92). Independent adverse factors included elevated LDH, bone metastasis, male gender, and CDKN2A or KRAS mutation. The Cox proportional hazards model achieved the most robust prognostic performance, with a C-index of 0.751 and time-dependent AUCs > 0.70 at 1-, 2-, and 3-year follow-up. Conclusions: Integration of ctDNA with tissue origin prediction can escalate high level targeted treatment and may provide a practical framework for precision oncology in CUP, warranting further exploration in randomized clinical trials.
Baseline predictors of treatment response in the bounce back mind-body resiliency trial for AYA cancer survivors.
12101 Background: Mind-body interventions hold promise for improving coping and reducing psychological distress among adolescent and young adult (AYA) cancer survivors, yet benefits vary across participants. Little research has identified which survivors stand to benefit most from these programs. This secondary analysis of a randomized controlled trial of a mind-body group intervention tested whether baseline emotion regulation-related factors (worry and intolerance of uncertainty) moderated intervention effects on coping and distress (anxiety and depression). Methods: AYA cancer survivors (N = 72; ages 18–39) were randomized 1:1 to an 8-week virtual mind-body resiliency program (Bounce Back) or waitlist control. Primary outcomes were PROMIS anxiety and depression scores and total Measure of Current Status (MOCS) coping score at post-intervention (approximately 3-month follow-up), along with coping self-efficacy. Linear regression models, adjusted for baseline levels of each outcome, tested Randomization Group × Moderator interaction terms for two baseline moderators examined separately: Penn State Worry Questionnaire (PSWQ) and Intolerance of Uncertainty Scale (IUS). Interactions with p < 0.05 were considered evidence of moderation. Results: Compared to waitlist, participants assigned to Bounce Back showed greater improvements in anxiety and coping outcomes but similar depression outcomes overall. Randomization group differences in post-intervention anxiety were significantly moderated by both worry and intolerance of uncertainty. The intervention–control difference in anxiety (adjusted for baseline) was larger among participants reporting higher baseline worry (interaction β = −0.39, p = 0.033) and higher baseline intolerance of uncertainty (β = −0.48, p = 0.033). Neither moderator significantly altered randomization group differences in depression. For coping-related outcomes, higher baseline intolerance of uncertainty strengthened the intervention effect on coping self-efficacy (interaction β = 1.92, p = 0.047), and there was a trend for greater total MOCS improvement among participants with higher baseline worry (interaction β = 0.33, p = 0.086). Conclusions: In this secondary analysis of a randomized trial, the Bounce Back mind-body resiliency program produced the largest anxiety and coping benefits for AYA cancer survivors with relatively higher baseline worry and intolerance of uncertainty, whereas depression outcomes did not vary by these baseline characteristics. These findings suggest that emotion regulation vulnerabilities such as worry and uncertainty intolerance may help identify higher-risk AYAs who are most likely to benefit from group-based mind-body stress-management interventions. Future trials should confirm these moderators and test whether triaging higher-risk AYAs to mind-body programs improves psychological outcomes.