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Gut microbiota dynamics of antibiotic fecal microbiota transplantation in esophageal and gastric cancer patients treated with immune checkpoint inhibitors: Preliminary results from the Biorich2 study.
e16030 Background: Despite advances in immune checkpoint inhibitor (ICI)–based therapy, outcomes for patients with unresectable or recurrent esophageal and gastric cancers remain poor. The gut microbiome has emerged as a determinant of response to ICI, and modulation of the gut microbiome through fecal microbiota transplantation (FMT) has shown potential to improve ICI efficacy. We conducted a phase I/II study to evaluate the safety, feasibility, and efficacy of FMT with antibiotic pretreatment (A-FMT) combined with ICI-based regimens in patients with esophageal squamous cell carcinoma (ESCC) and gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Methods: The study consists of a safety part and an expansion part. Patients receive a 1-week course of oral antibiotics (amoxicillin, fosfomycin, and metronidazole), followed by a single donor-derived FMT via colonoscopy. ICI-based therapy is initiated the day after A-FMT. For ESCC, regimens included nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg), or fluorouracil (800 mg/m 2 ) plus cisplatin (80 mg/m 2 ) [CF] combined with pembrolizumab (200 mg/body). For G/GEJ cancer, the regimen consisted of oxaliplatin (130 mg/m 2 ) plus S-1 (40 mg/m 2 ) [SOX] combined with nivolumab (360 mg/body). The primary endpoint was the incidence of dose-limiting toxicities (DLTs) within 28 days after FMT. DLTs were defined as any grade 3 or higher non-hematological toxicity related to FMT. Secondary endpoints included efficacy outcomes and incidence of adverse events. Exploratory translational analyses using stool, blood, and tumor samples evaluated immune modulation and gut microbiome dynamics. Results: Since June 2024, seven patients have been enrolled in the safety part. Six patients received A-FMT; one patient with G/GEJ cancer discontinued the protocol prior to FMT due to rapid disease progression. The ICI-based regimens administered ipilimumab plus nivolumab (n = 3), CF plus pembrolizumab (n = 1), and SOX plus nivolumab (n = 2). Among these six patients, no DLTs were observed within 28 days. A grade 3 AST elevation (n = 1) and grade 3 pneumonitis (n = 1) were observed during the DLT evaluation period; however, these were considered unrelated to FMT. An objective response was achieved in 4 of 6 patients, including two patients with ESCC and two with G/GEJ cancer; stable disease was observed in two patients with ESCC. Notably, one patient with G/GEJ cancer achieved complete resolution of peritoneal metastasis and underwent conversion surgery. Longitudinal fecal microbiome analyses demonstrated decreased Bray–Curtis dissimilarity between recipient and donor microbiota after A-FMT. Conclusions: A-FMT demonstrated an acceptable safety profile and feasibility, allowing the study to proceed to the expansion part for further efficacy evaluation. Clinical trial information: jRCTs031240170.
Safety, efficacy, and pharmacokinetics of XNW28012, a tissue factor antibody-drug conjugate (ADC) with topoisomerase 1 inhibitor (TOP1i) payload, in patients with advanced solid tumors: Results from a phase I/II study.
3040 Background: Tissue factor (TF) is overexpressed in a broad range of solid tumors including pancreatic ductal adenocarcinoma (PDAC). XNW28012 is the first TF ADC with a novel TOP1i payload. Here we report the safety and PK of XNW28012 in patients (pts) with solid tumors, and the efficacy in PDAC from a Phase I/II study. Methods: Eligible pts who failed standard therapy received XNW28012 Q3W. TF expression was not required for enrollment. The primary endpoints for dose escalation and expansion were safety and ORR, respectively. BOIN design was used for dose escalation. Eligible pts with PDAC and other solid tumors were enrolled at 2.0 and 2.4 mg/kg for dose expansion. Results: As of Nov. 21, 2025, 313 pts were enrolled (escalation: 16; expansion: 297), with median age of 56.3 yrs; 77.0% of ECOG 1; and 56.9% received ≥2 lines of prior systemic therapy. TEAEs in ≥20% pts were anemia (62.0%), stomatitis (60.1%), nausea (49.5%), WBC count decreased (47.0%), appetite decreased (43.1%), neutrophil count decreased (39.9%), vomiting (39.6%), asthenia (35.5%), weight decreased (30.7%), conjunctivitis (29.4%), rash (28.1%), hypokalemia (23.3%), hyponatremia (21.4%), and hypoalbuminemia (21.1%). ≥Grade 3 TEAEs in ≥5% pts were stomatitis (17.6%), neutrophil count decreased (14.4%), WBC count decreased (12.8%), anemia (11.5%), and lymphocyte count decreased (8.3%). Dose interruption, reduction and discontinuation due to TEAE occurred in 60.7%, 22.0%, and 3.8% of the pts, respectively. Grade 3 conjunctivitis was reported in 2.9% pts across the doses. Most common bleeding AE was epistaxis (12.1%), all grade 1/2. 1 pt at 3.6 mg/kg experienced DLT (grade 4 neutropenia, grade 3 stomatitis). 16 pts were enrolled in dose escalation from 0.6 to 3.6 mg/kg. ORR and DCR were 46.7% and 100%, respectively in 15 evaluable pts including PDAC, ovarian cancer, cervical cancer, and head and neck squamous cell carcinoma. In dose expansion, 45 and 48 PDAC pts were efficacy evaluable at 2.0 and 2.4 mg/kg, with a median follow up of 4.4 m and 6.0 m, respectively. Efficacy data in PDAC pts in dose expansion were summarized in the Table. PK data showed dose proportionality and very low payload exposure in the system indicating stable linker. Conclusions: XNW28012 demonstrated a manageable safety profile in heavily treated advanced solid tumor pts and promising anti-tumor activity in PDAC patients. The data support further development of XNW28012 in a broad range of solid tumors including PDAC. Clinical trial information: NCT06799637 . Prior line 2.0 mg/kg, 1L(N=25) 2.0 mg/kg, 2L+(N=20) 2.4 mg/kg, 1L(N=21) 2.4 mg/kg, 2L+(N=27) ORR, n (%) 7 (28.0%) 3 (15.0%) 10 (47.6%) 7 (25.9%) DCR, n (%) 23(92.0%) 18(90.0%) 19 (90.5%) 23 (85.2%) mPFS, (months) 4.2 4.5 6.4 5.2 mOS, (months) NC 10.7 14.6 9.0 KM OS rate at 9m (%) 64.5% 51.6% 54.2% 50.5% KM OS rate at 12m (%) NC NC 54.2% 22.9% NC: Not Calculated.
A first-of-its-kind multi-omic assay using lipids and proteins to identify early-stage ovarian cancer in symptomatic individuals.
5552 Background: Ovarian cancer (OC) is often diagnosed at advanced stages, leading to one of the highest mortality rates for gynecologic malignancies. While 85% of patients are symptomatic even at early stages, symptoms are vague and overlap with benign conditions. Existing diagnostic tools such as CA125 and HE4 lack sufficient sensitivity and specificity to detect early-stage disease, even in symptomatic individuals. As a result, there is a critical unmet need for a highly sensitive diagnostic tool designed for patients presenting with vague abdominal symptoms. Methods: Here, we report the first large-scale, prospective U.S. clinical trial evaluating a targeted multi-omic assay of symptomatic women, its intended-use population. Assay performance was assessed in a subset of an independent, prospectively recruited, multi-site study enrolled across the United States, supplemented with samples from a commercial vendor (N=346). The cohort comprised patients diagnosed with OC across stages and subtypes (N=116: 50 early-stage I/II, 66 late-stage III/IV) and a symptomatic control group (N=230), comprising individuals with benign adnexal masses (BAN; N=116) and symptomatic individuals with vague abdominal symptoms who were followed longitudinally for 12 months to confirm absence of malignancy (symptomatic normal; N=114). Serum lipids including selected phospholipids, sphingolipids, and ceramides were quantified by mass spectrometry. Proteins were measured using clinically validated immunoassays. An ensemble machine learning modeling approach was applied using targeted feature subsets from a refined panel of 23 lipid and 5 protein markers, with outputs weighted to reflect anticipated disease prevalence in the intended-use population. Results: The assay demonstrates consistently high diagnostic performance, achieving 96.5% sensitivity with 80.6% specificity for OC vs. symptomatic control, and 92% sensitivity for early-stage OC in the same comparison. Integrating lipid and protein biomarkers into a targeted multi-omic model therefore results in a substantial improvement in OC detection, especially early-stage, over current standard-of-care biomarkers. Conclusions: In a large, prospectively collected cohort reflecting real-world symptomatic patients, this first-of-its-kind, targeted multi-omic assay accurately distinguishes OC from non-malignant conditions in symptomatic women with dramatic improvement in early-stage detection. These findings support the feasibility and clinical utility of a multi-omic assay in addressing a longstanding diagnostic gap for symptomatic women, clearing a path to earlier triage and diagnosis.
Personalized tumor-informed ctDNA monitoring for recurrence in high-risk locally advanced gastrointestinal stromal tumor.
e23514 Background: Gastrointestinal stromal tumor (GIST) is the most prevalent mesenchymal neoplasm of the gastrointestinal tract. While radical resection is the gold-standard treatment for localized GIST, the 5-year recurrence rate of high-risk GIST exceeds 50%, posing a major clinical challenge. Whether ctDNA-based detection of postoperative molecular residual disease (MRD) can reliably predict recurrence in high-risk locally advanced GIST patients remains a key question in translational oncology. Methods: This prospective study enrolled patients with high-risk locally advanced GIST who underwent R0 resection. Surgical tissue specimens were obtained for genomic profiling. Blood samples were collected at baseline (pre-surgery), at a landmark time point within one month after surgery, and serially thereafter at 3- to 6-month intervals during follow-up. Tumor-derived variants were identified through whole-exome sequencing of resected tumors. A personalized tumor-informed assay was designed by selecting up to 50 top-ranked variants with a variant allele frequency ≥3.0% to monitor MRD status. Results: As of Jan 2026 (cutoff), 44 eligible patients were enrolled. 44 tumor samples, 42 pre-surgical plasma samples, and 330 post-surgical blood samples were analyzed, with a median follow-up of 21 months. Tumor sequencing detected mutations in KIT and PDGFRA in 39 (88.6%) and 4 (9.1%) patients. Prior to surgery, MRD was detected in 57.1% (24/42) of plasma samples, and positivity correlated with larger tumor volume, higher Ki-67 index, mitotic count, and TMB (all P < 0.05). Multivariable logistic regression identified the Ki-67 index as an independent predictor of pre-surgical MRD positivity (OR, 1.20; 95% CI, 1.02 to 1.41; P = 0.024). In landmark analysis, ctDNA was detectable in 4 patients (4/41, 9.8%). These patients had worse DFS trend vs. MRD-negative patients (HR=3.48, 95% CI=0.70–17.35, P =0.11). To date, 8 patients had radiologically confirmed recurrence via CT. Among 4 patients with both MRD positivity and recurrence, one had longitudinal MRD positivity at 9 months post-op (3-month lead before CT relapse), and 2 had simultaneous detection by both methods. Notably, none of these 4 patients received regular adjuvant therapy. Additionally, multivariable Cox regression (adjusted for sex, age, TNM stage, and adjuvant therapy) showed longitudinal MRD positivity was associated with inferior DFS (HR=4.59, 95% CI=1.00–20.98, P =0.05). Patients with sustained negative MRD (n=29) had better survival than those with MRD conversion to negative (n=2), positive (n=8), or persistent positivity (n=2) (P=0.1). Conclusions: This study indicates that personalized tumor-informed ctDNA may predict recurrence in high-risk locally advanced GIST patients, particularly those not receiving regular adjuvant therapy. Clinical follow-up is ongoing. Clinical trial information: NCT05408897 .
Next-generation sequencing–based mutation profiling in solid tumors: A study from a north Indian tertiary care center.
e15077 Background: Tumor heterogeneity points to the need for accurate molecular biomarkers to enable early detection, prognostication, and personalized therapy. Conventional diagnoses often fail to address tumor heterogeneity. Next-generation sequencing (NGS) testing is very important in precision oncology because it helps find important genetic changes and predicts how well patients will respond to immune checkpoint inhibitors.We aim to assess the viability of NGS testing and scrutinize the mutation landscape, encompassing common driver mutations and co-mutations, in a tertiary care center located in North India. Methods: This observational study comprised 180 histologically verified cancer patients who received NGS testing at the Department of Medical Oncology and Hematology, Sarvodaya Hospital and Research Centre, Faridabad, Haryana, from February 2022 to July 2025. Demographic details, sample type, NGS panel utilized, tumor type, and detected genomic alterations were analyzed. Results: The majority of patients were aged 55–64 years (36.7%), with a male predominance (71.1%). Most samples were formalin-fixed paraffin-embedded (FFPE) tissue (94.4%), while 5.6% were liquid biopsy samples. The 20-gene panel was the most frequently used (45.6%), followed by the 161-gene panel (26.7%). Lung adenocarcinoma was the most common tumor subjected to NGS (40%), followed by lung squamous cell carcinoma (14.4%) and gallbladder carcinoma (6.1%).The mutation analysis showed that TP53 was the most common change found (25%), followed by EGFR (12.8%) and Other actionable or clinically relevant mutations included ERBB and NOTCH (5% each), MET and PTEN (3.9%), and ALK and CDKN2A (3.3%), along with several low-frequency variants. Conclusions: This study highlights the feasibility of NGS-based molecular profiling in identifying actionable and prognostically relevant mutations in Indian cancer patients. The predominance of TP53 co-mutations alongside targetable drivers such as EGFR and PIK3CA emphasizes the complexity of tumor biology. Integration of NGS in routine oncology practice can enhance personalized, biomarker-driven treatment strategies and support the advancement of precision oncology in India.
The Bermuda model: Achieving world-class, equitable, and efficient cancer care in a small island nation.
11080 Background: Bermuda is a small island nation that historically faced significant challenges in provision of local cancer care. Between 2000-2017, 100% of patients requiring radiation therapy (RT) had to travel abroad, causing prohibitive financial toxicity. In 2017, Bermuda Cancer and Health Centre (BCHC) evolved to deliver an integrated and comprehensive national cancer solution, including RT. The "Bermuda Model" represents a national approach to address critical gaps in cancer care by leveraging innovative partnership models to enable access, efficiency, health equity and international quality standards. Methods: We conducted a retrospective descriptive cohort study. Data for cancer incidence/outcomes were collected from the Bermuda National Tumour Registry; treatment/quality data and patient satisfaction surveys were collected from BCHC clinical records. Timeframes for travel reduction data were between 2015-2020. Outcomes measures included percentage of overseas referrals for RT and chemotherapy, international quality assurance, patient satisfaction scores from 2025, access measures such as interval from diagnosis to treatment, cancer-specific overseas insurance claims, and selected clinical outcomes, including early breast cancer detection and survival rates. Results: The Bermuda Model has eliminated the need for overseas RT, ensuring access for the 70-90% who previously went abroad and the remainder who went without. Through an international strategic partnership with Brigham and Women’s Hospital, high quality and consistent peer-review of radiation treatment plans by Harvard faculty specialists was ensured for 100% of all patients receiving RT at BCHC. Patient satisfaction rates for RT were 100% positive for multiple months in 2025. Between 2017-2019, Bermuda achieved excellent clinical outcomes including an 87% early detection rate for localized (Stage 1-2) breast cancer and a lower breast cancer mortality rate than either the USA or Europe. Care timelines were efficient; average time from diagnosis to first treatment was as low as 16 days in 2025. The model was associated with an approximately 24% reduction in cancer-specific overseas insurance claims between 2017-2020 ($6.2 million and $4.7 million respectively). Conclusions: The "Bermuda Model" demonstrates that with strategic investment and international partnerships, a small island nation can locally establish world-class, equitable, and efficient cancer care services. Eliminating overseas treatment, high satisfaction, and excellent outcomes evidence its success. The reduction in claims has been particularly impactful for Bermudian residents with government-level insurance, helping to advance, access-to-all cancer care. This model serves as a valuable blueprint for other small nations or isolated regions seeking to improve their delivery of cancer care.
Efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib vs TACE alone in the treatment of non-resectable hepatocellular carcinoma: A systematic review and meta-analysis.
e16213 Background: Hepatocellular carcinoma (HCC) poses a significant global health challenge, with limited treatment options for non-resectable cases. This meta-analysis aims to evaluate the safety and efficacy of combining transarterial chemoembolization (TACE) with sorafenib compared to TACE alone in treating non-resectable HCC. Methods: A systematic literature search following PRISMA guidelines identified 10 studies (n = 1818 patients) meeting inclusion criteria. The quality of the studies was assessed using the Jadad and Newcastle-Ottawa scales. Data extraction included baseline characteristics, overall survival, adverse events, and treatment specifics. Statistical analyses were performed using Review Manager 5.4. We used a random-effects model to pool risk ratio (RR) along with their 95% confidence intervals (CI). Results: TACE plus sorafenib demonstrated a significantly higher objective response rate (ORR) (RR = 1.18, 95% CI: 1.04–1.33, p = 0.010) and disease control rate (DCR) (RR = 1.12, 95% CI: 1.02-1.24, p = 0.02) compared to TACE alone. Adverse events such as diarrhea, fatigue, weight loss, hand-foot skin reactions, rash, alopecia, and fever were more prevalent in the combination therapy group. Conclusions: TACE plus sorafenib demonstrated superior efficacy in terms of ORR and DCR compared to TACE alone in non-resectable HCC. However, the higher incidence of adverse events emphasizes the need for careful consideration of risk-benefit profiles in clinical decision-making.
The landscape of oncology clinical trials in Africa over the last three decades (1995-2025).
e23236 Background: Africa is home not only to 20% of the world’s population but also to the highest human genetic diversity. Genomics increasingly drives cancer drug discovery, biomarker development, and dose optimization. This study reviews Africa’s representation in high-impact oncology clinical trials. Methods: We identified all oncology clinical trials published in The Lancet and The New England Journal of Medicine (NEJM) between 1995 and 2025, and retrieved full-text PDFs from the journals' websites. Using an LLM (Gemini-2.5-Flash), structured variables, including trial phase, cancer type, enrollment countries, and participant race and/or ethnicity, were automatically extracted from texts, tables, and figures. Trials were stratified by decade (1995–2005, 2006–2015, and 2016–2025) to evaluate temporal trends. Results: Among the 1,385 global oncology trials reviewed, only 66 (4.8%) were conducted in African countries: 16 in 1995–2005, 30 in 2006–2015, and 20 in 2016–2025. The trials occurred in just 11 African countries, with South Africa alone accounting for 56 (84.8%) of these 66 trials. Egypt contributed 6 trials (9.1%), and Mauritius 5 trials (7.6%). Early-phase trials were rare: only 1 Phase 0 (1.5%) and 1 Phase 2 (1.5%) trial were identified, while the majority were Phase 3 (64 trials, 97.0%). Across all periods, Phase 3 studies dominated. The trials covered 58 distinct cancer types, but the most frequent were squamous cell carcinoma of the head and neck (n = 3), non-small cell lung cancer (n = 2), colorectal adenomas (n = 2), and chronic lymphocytic leukemia (n = 2). The number of African trials increased from 16 (24.2%) in 1995–2005 to 30 (45.5%) in 2006–2015, before declining to 20 (30.3%) in 2016–2025. Geographic diversity improved modestly: 5 countries participated in the first two periods, compared with 7 in the most recent period. Conclusions: This study shows that cancer research continues to overlook Africa and its genetic diversity. This omission demands deliberate investment in clinical trial infrastructure, regulatory harmonization, diaspora-academic partnerships, and early-phase trial capacity in Africa to ensure the development of globally representative, biologically robust cancer therapeutics. Characteristic Overall (N=66) 1995–2005 (n=16) 2006–2015 (n=30) 2016–2025 (n=20) Global trials, n 1,385 – – – Trials with African sites, n (%) 66 (4.8) 16 (24) 30 (46) 20 (30) African countries, n 11 5 5 7 Trial phases 0, 2, 3 3 2, 3 0, 3 0, n (%) 1 (1.5) 0 0 1 (5.0) 2, n (%) 1 (1.5) 0 1 (3.3) 0 3, n (%) 64 (97.0) 16 (100) 29 (96.7) 19 (95.0) Cancer types, n 58 14 29 18 Most frequent cancers HNSCC, NSCLC, CLL, CRC, Prostate NSCLC, CLL HNSCC, CRC, Breast NSCLC, Prostate, TNBC Trials by country, n (%) South Africa 56 (84.8) 14 (87.5) 28 (93.3) 14 (70.0) Egypt 6 (9.1) 2 (12.5) 4 (13.3) 0 Mauritius 5 (7.6) 0 1 (3.3) 4 (20.0) CAR 3 (4.5) 0 1 (3.3) 2 (10.0) Tunisia 2 (3.0) 1 (6.2) 1 (3.3) 0 Algeria 2 (3.0) 2 (12.5) 0 0 Other countries ≤1 each – – –
Metronomic adjuvant chemotherapy (MACE) in locally advanced oral cavity squamous cell carcinoma post-surgery and adjuvant treatment (MACE postop): A phase III randomized controlled trial.
6002 Background: The role of maintenance systemic therapy following definitive surgery and adjuvant treatment in locally advanced oral cavity squamous cell carcinoma (OCSCC) remains undefined. This phase III trial evaluated whether oral metronomic adjuvant chemotherapy (MACE) improves survival compared with observation. Methods: This multicenter, open-label, phase III superiority trial conducted in India enrolled patients with stage II–IV OCSCC (AJCC 7th edition) who were clinico-radiologically disease-free 1–2 months after completion of definitive surgery with adjuvant treatment. Patients were randomly assigned (1:1) to observation (OBS) or oral MACE for up to 18 cycles. MACE comprised methotrexate 15 mg/m² once weekly (four doses per 28-day cycle) plus celecoxib 200 mg twice daily. Adherence to MACE was monitored at 3-monthly follow-up visits using patient-reported medication logs, supplemented by objective verification through review of returned empty drug containers. The primary endpoint was 2-year overall survival (OS). The planned sample size was 712; accrual was stopped early following emerging external evidence, with ethics committee approval. Results: Between February 2017 and April 2025, 410 patients were enrolled (OBS, n=208; MACE, n=202); approximately three-quarters had stage IV disease in both arms. The median number of MACE cycles delivered was 15; 92 patients discontinued treatment, most commonly because of noncompliance (n=55) or disease progression (n=27). At a median follow-up of 42.5 months, 129 deaths were observed (70 in OBS and 59 in MACE). Two-year OS was 70.2% (95% CI, 63.0–76.2) in the OBS arm and 79.2% (95% CI, 72.5–84.4) in the MACE arm (hazard ratio [HR], 0.76; p=0.13). Two-year progression-free survival was 68.0% (95% CI, 61.0–74.1) with OBS and 77.0% (95% CI, 70.2–82.4) with MACE (HR, 0.72; p=0.044). Distant recurrences occurred in 30 patients (14.4%) in the OBS arm and 17 patients (8.4%) in the MACE arm, while second primary malignancies were observed in 8 (3.8%) and 3 (1.5%) patients, respectively. Grade 3–4 toxicity with MACE was observed in 6.9%. Exploratory subgroup analyses suggested greater benefit in patients with extranodal extension and stage IV disease. The average cost of MACE per cycle, including toxicity management, was approximately USD 10. Conclusions: MACE following definitive local therapy did not significantly improve overall survival in locally advanced OCSCC. However, a statistically significant improvement in progression-free survival was observed, driven by a reduction in distant metastases and second primary malignancies. These findings suggest that selected high-risk subgroups—particularly patients with extranodal extension and advanced-stage disease—may derive benefit from this low-cost and well-tolerated strategy. Clinical trial information: CTRI/2017/02/007777.
Trends in utilization and inpatient outcomes of minimally invasive colectomy for colorectal cancer in the United States, 2018–2023.
e23195 Background: Use of minimally invasive surgery (MIS) for colorectal cancer (CRC) resection has expanded rapidly, with increasing adoption of robotic platforms. Contemporary national data describing inpatient utilization trends, outcomes, and costs across surgical approaches remain limited. Methods: A retrospective, serial cross-sectional analysis was performed using the 2018–2023 Healthcare Cost and Utilization Project National Inpatient Sample. Adult hospitalizations with a principal diagnosis of CRC undergoing colorectal resection were identified using ICD-10-CM and ICD-10-PCS codes. Surgical approach was classified as open, laparoscopic, or robotic-assisted. Outcomes included in-hospital mortality, a composite of in-hospital complications, length of stay (LOS), and hospitalization cost estimated using cost-to-charge ratios. National estimates accounted for survey weighting, clustering, and stratification. Survey-weighted regression models adjusted for demographics, payer, income quartile, elective status, APR-DRG severity and risk of mortality, calendar year, and hospital characteristics. Sensitivity analyses were performed in elective-only and non-metastatic cohorts. Results: From 2018–2023, an estimated 348,390 CRC resection hospitalizations were identified nationally. Robotic-assisted surgery increased from 16.5% in 2018 to 33.3% in 2023, while open surgery declined from 61.9% to 47.7% (design-based p < 0.001). Unadjusted in-hospital mortality was highest following open surgery (2.58%) compared with laparoscopic (0.70%) and robotic-assisted (0.65%) approaches. Mean LOS was 9.76 days for open colectomy versus 6.35 days for laparoscopic and 5.76 days for robotic-assisted colectomy; mean costs were $37,744, $27,468, and $35,558, respectively. In adjusted analyses using laparoscopy as the reference, open surgery was associated with higher odds of in-hospital complications (OR 1.25, 95% CI 1.09–1.44) and longer LOS (+1.58 days), while robotic-assisted surgery was associated with longer LOS (+0.63 days) and higher costs, including approximately 28% higher adjusted costs compared with laparoscopy. Sensitivity analyses demonstrated similar patterns across elective-only and non-metastatic subgroups. Conclusions: Between 2018 and 2023, inpatient CRC resections in the United States demonstrated rapid growth in robotic-assisted surgery with a concurrent decline in open surgery. Across analyses, open colectomy was associated with higher mortality, complications, LOS, and costs compared with MIS approaches, while robotic-assisted colectomy was associated with higher inpatient costs relative to laparoscopy. These findings provide contemporary national benchmarking data on surgical utilization patterns, inpatient outcomes, and costs for CRC resection.
Adjuvant (Ad) and neoadjuvant (NAd) strategies in higher risk hormone receptor–positive (HR+)/HER2-negative (HER2−) early breast cancer (EBC): Moroccan real-world outcomes.
e12735 Background: In low- and middle-income countries, many higher-risk HR+/HER2- EBC patients (pts) often undergo primary surgery followed by adjuvant anthracyclines (ATC) and taxanes (TX)-based chemotherapy (CT) and endocrine therapy (ET), while a smaller proportion receive NAdj CT-based ATC and TX followed by postoperative ET, frequently with deviations from established guidelines. The benefits derived from these two approaches and the incremented benefit attributable to specific CT combinations remain unclear. Methods: In this unicentric, retrospective cohort, we included stage I-III higher-risk HR+/HER2- EBC patients, aged > = 18 years, treated between January 1 st , 2020, and June 30 th , 2024, who received either Ad or NAd ATC +/- TX, followed by radiotherapy when indicated, and ET-based tamoxifen for premenopausal or fulvestrant/aromatase inhibitor for postmenopausal pts for up to 5-7 years or until local/regional/distant relapse or progression precluding surgery. Overall survival (OS) was the primary endpoint. Disease-free survival (DFS), event-free survival (EFS), and safety were the secondary endpoints. Results: At the data cutoff, 424 pts received Ad, and 236 pts received NAd, CT-based doxorubicin-cyclophosphamide (AC) monotherapy, AC with docetaxel (AC-D), AC with paclitaxel (AC-P), epirubicin-cyclophosphamide monotherapy (EC), EC with docetaxel (EC-D), EC with paclitaxel (EC-P), or TX (P or D) followed by ET. The median follow-up was 42 months (m) (IQR: 35, 48). There was no statistical difference in OS between the Ad and NAd groups (adjusted hazard ratio [aHR], 0.87; 95% CI, 0.58 to 1.3; p = 0.5). In the Ad group, the median DFS was 44m (95% CI, 26-Not Estimable [NE]) with EC-D, 36m (95% CI, 33-NE) with EC-P, 32m (95% CI, 24-NE) with AC-D, 28m (95% CI, 19-NE) with AC-P, 29m (95% CI, 16-NE) with ATC, and 20m (95% CI, 13-NE) with TX (aHR, 0.61; 95% CI, 0.38, 1.07; p = 0.06). In the NAd group, the median EFS was NE with EC-D, 22m (95% CI, 17-NE) with EC-P, 35m (95% CI, 27-NE) with AC-D, 29m (95% CI, 21-NE) with AC-P, 37m (95% CI, 30-NE) with ATC, and 28m (95% CI, 18-NE) with TX (aHR, 1.36; 95% CI, 0.82, 2.53; p = 0.56). Safety findings were consistent with expected profiles, predominantly grade 1-2 hematologic events; EC-D showed a lower incidence, and no treatment discontinuations occurred. Conclusions: The findings suggest that both strategies were similarly effective for treating higher-risk HR+/HER2- EBC, with a potential advantage favouring EC-D in both approaches; however, as these results remain early and exploratory, longer follow-up and larger, more inclusive cohorts are needed to confirm this observation, all with fewer adverse events, supporting its use in low-resource settings without compromising patient-reported quality of life.
Population-level trends in breast cancer incidence, staging, and mortality in Armenia.
e22581 Background: Armenia, an Upper-Middle Income Country in the South Caucasus, has one of the highest breast cancer mortality rates in the world, with a mortality-to-incidence ratio (MIR) substantially exceeding that of peer countries. However, longitudinal data on incidence, stage at diagnosis, and mortality are limited. We analyzed national population data to evaluate trends in breast cancer epidemiology in Armenia. Methods: We conducted a retrospective, population-level analysis using publicly available statistical yearbooks from Armenia’s National Institute of Health from 2010–2024. Data were extracted on breast cancer incidence (2010-2024), stage at diagnosis (2016-2024), and mortality (2019-2024). Descriptive and regression analyses were performed to evaluate temporal trends across the study period. The study was reviewed by the UMass Chan institutional review board and deemed exempt from human subjects research. Results: Breast cancer incidence rates increased over the study period, rising from approximately 32 per 100,000 in 2010 to 54 per 100,000 in 2024. In contrast, breast cancer mortality rates did not change meaningfully from 2019-2024 (Table 1). Consequently, the MIR has declined over time, from 33.2 in 2019 to 26.4 in 2024. In 2020, a transient decrease in reported incidence led to a peak in the calculated MIR. Analysis of stage distribution demonstrated a shift toward more advanced disease, with a statistically significant decline in the proportion of Stage I/II diagnoses and a corresponding significant increase in the proportion of Stage III diagnoses (Table 1). Changes in the proportion of Stage IV diagnoses were insignificant. Conclusions: Breast cancer incidence in Armenia has increased over time, while mortality has remained stable, resulting in a declining MIR ratio. However, the observed shift toward later-stage diagnosis, particularly stage III disease, highlights persistent challenges in early detection and timely diagnosis. Epidemiology of breast cancer in Armenia over 6 years. Year 2019 2020 2021 2022 2023 2024 Incidence Rate 1 44.7 37.7 44.8 47.9 51.0 53.9 Mortality Rate 1 14.9 14.8 14.7 14.5 14.9 14.2 Mortality-to-Incidence Ratio 0.33 0.39 0.33 0.30 0.29 0.26 Stage I/II (%) 76.8 65.8 56.4 66.3 56.1 63.1 Stage III (%) 6.9 15.8 25.1 18.4 22.5 21.4 Stage IV (%) 16.3 18.5 18.5 15.3 21.5 15.5 1 Per 100,000 people. Calculated using population data published by the World Bank.
Using artificial intelligence (AI) and retrieval-augmented generation (RAG) to identify patient-reported symptoms post-ambulatory surgery for cancer.
e18003 Background: As ambulatory procedures become commonplace in oncology, post-surgical remote symptom monitoring (RSM) is important for timely responses to emergent problems. Patient-reported outcomes (PROs) are the gold standard for the capture of the patient symptomatic experience; however, existing electronic PRO (ePRO) assessments that include free text reporting are not well-equipped to capture emergent symptoms or nuanced concerns due to resource constraints. Recent significant advances in AI modeling may allow for a minimally burdensome opportunity to monitor patients’ recovery. As a proof of concept, we aimed to determine whether large language models (LLMs) could efficiently classify verbatim free text patient-reported symptoms post-ambulatory surgery. Methods: Secure enterprise cloud-based versions of GPT-5.2 and Claude Sonnet 4.5, licensed to our institution, were used to identify symptoms from verbatim free-text responses collected from a retrospective sample of N = 1,070 cancer patients post-ambulatory surgical procedures for up to 10 days. Responses from thyroidectomy patients (n = 147) were coded and verified by a surgeon into 161 unique symptoms (e.g., ‘headache’, ‘dizziness’, ‘swollen incision’) and used as the gold standard. Coded responses were incorporated into RAG for postulated performance boost. The fine-tuned model was then used to analyze responses from mastectomy (n = 252) and prostatectomy (n = 671) patients. Results: GPT-5.2 with RAG identified 360 symptoms post-thyroidectomy, including (ordered by prevalence) ‘headache’ (area under the receiver operating characteristic curve [AUC]=0.89, 95% Confidence Interval [CI]: 0.83, 0.94), ‘dizziness’ (AUC=0.72, 95% CI: 0.72), ‘cough’ (AUC=0.81, 95% CI: 0.73, 0.90), ‘cough’ (AUC=0.99, 95% CI: 0.99, 1.00), and ‘sore throat’ (AUC=0.78, 95% CI: 0.65, 0.88). Patients differed in words chosen (e.g., ‘pain on swallowing’, ‘burning with swallowing’, and ‘difficulty swallowing’). Semantic similarity incorporated into modeling yielded a taxonomy of 98 symptom categories and an overall performance at 0.93 precision, 0.92 recall, and 0.93 F1 score. Claude Sonnet 4.5 had comparable results. Removing RAG resulted in a negligible reduction in model performance. In mastectomy and prostatectomy respectively, the most prevalent symptoms were ‘swelling’, ‘pain’, ‘drainage’, and ‘numbness’; and ‘swelling’, ‘pain’, ‘hematuria’, and ‘bleeding.’ Conclusions: Real-time processing of patient-reported free text post-ambulatory surgical concerns may be feasible using AI. RAG did not confer an advantage, due in part to the limited number of human-annotated symptoms. If further validated, AI-assisted RSM can offer patients an efficient and unfiltered pathway for reporting their post-surgical experiences in a way that can be integrated into clinical decision-making.
Clinico-genomic landscape and prognostic impact of APC/CTNNB1 oncogenic alterations in non–small cell lung cancer.
8552 Background: Genomic activation of the WNT/β-catenin pathway via APC loss-of-function or activating CTNNB1 mutations is well established across multiple cancer types, but its prevalence and genomic context in non–small cell lung cancer (NSCLC) remain poorly characterized. We systematically characterized the prevalence of APC and CTNNB1 alterations in NSCLC, and defined their mutational landscape and prognostic impact. Methods: We conducted a multicenter cohort study including patients with NSCLC whose tumors underwent targeted exon sequencing at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC). Tumors were classified as APC-mutated, CTNNB1-mutated, or WNT-mutated (APC and/or CTNNB1 mutated). Pathogenic alterations were defined as oncogenic or likely oncogenic per OncoKB, or as missense variants with a REVEL score > 0.5. Gene enrichment analyses used gene-wise logistic regression adjusted for tumor mutational burden (TMB), testing genes meeting a predefined prevalence threshold, with Bonferroni correction within each analysis. Results: In the DFCI cohort (N = 4,717), APC or CTNNB1 alterations were identified in 4.5% of NSCLC (212/4,717), including APC in 1.7% (79/4,717) and CTNNB1 in 2.8% (133/4,717), and were mutually exclusive. APC alterations were predominantly loss-of-function events (85.3% of qualifying APC variants) and splice-region/site variants (14.8%). CTNNB1 alterations were all missense mutations (100%), clustering in exon 3, consistent with β-catenin stabilization and gain-of-function. Relative to WNT–wild-type tumors, WNT-mutated NSCLC occurred more frequently in never-smokers (32% vs 24%, p = 0.03), patients of Asian race (11.8% vs 4.2%, p < 0.001), and non-squamous histology (99.5% vs 88.6%, p < 0.001). These tumors exhibited lower median PD-L1 expression (p < 0.001) and TMB (p = 0.03). Similarly, in the MSK cohort (N = 4710), the prevalence of APC and CTNNB1 alterations was 0.7% and 2.7%, respectively. Relative to WNT–wild-type tumors, WNT-altered NSCLC was significantly enriched for EGFR mutations (19.3% vs 10.5%; OR 2.18; p < 0.01) and SMAD4 mutations (7.1% vs 2.1%; OR 3.47; p = 0.0026), with relative depletion of KRAS alterations (20.8% vs 32.1%; OR 0.55; p = 0.027). External validation reproduced these findings, with WNT-altered tumors enriched for EGFR (42% vs 21.7%; OR 3.21: p < 0.001) alterations and depleted for KRAS (16.7% vs 29.4%; OR 0.47; p = 0.011). In the DFCI cohort, APC/CTNNB1 alterations were not associated with overall survival [HR 1.05 (0.88-1.25 95% CI; p = 0.57)]. Conclusions: Genomic activation of the WNT/β-catenin pathway is characterized by EGFR and SMAD4 co-alterations, relative KRAS depletion, and lower PD-L1 and TMB. These results suggest that WNT pathway alterations contribute to molecular heterogeneity in NSCLC with potential relevance for future biomarker and therapeutic studies.
Liposomal irinotecan plus cisplatin/carboplatin as second-line therapy for platinum-sensitive relapsed extensive-stage small cell lung cancer: Interim results of a phase II trial.
e20128 Background: Platinum-sensitive relapsed extensive-stage SCLC represents an unmet medical need, with limited second-line options offering modest efficacy and significant toxicity. Liposomal irinotecan, a topoisomerase I inhibitor with enhanced tumor targeting, may improve outcomes in this setting. This phase II study evaluated the efficacy and safety of liposomal irinotecan combined with cisplatin or carboplatin in patients with platinum-sensitive relapsed extensive-stage SCLC. Methods: This prospective, multicenter, single-arm, exploratory phase II trial enrolled patients with pathologically confirmed extensive-stage SCLC who had progressed ≥6 months after first-line platinum-based chemoradiotherapy (with or without immunotherapy). The study was planned to enroll a total of 24 patients, with an interim analysis scheduled to be conducted following efficacy evaluation of 12 patients. Patients received liposomal irinotecan (70 mg/m 2 IV on days 1 and 15) plus cisplatin (60 mg/m 2 IV on day 1) or carboplatin (AUC=5 IV on day 1) every 4 weeks until disease progression, intolerable toxicity, withdrawal, or investigator decision. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety (incidence and severity of treatment-related adverse events [TRAEs]). Results: Enrollment began in June 2024, and as of December 30, 2025, 15 patients had been enrolled (median age 58 years, 86.7% male, 73.3% with stage IV disease). Most patients (80.0%) had received prior platinum-based therapy combined with immunotherapy or targeted agents. Among 12 efficacy-evaluable patients, the ORR was 41.7% (95% CI: 19.3–68.0%), with 5 partial responses; DCR was 75.0% (95% CI: 46.8–91.1%). Median treatment cycles were 2 months(range: 1–9), and median follow-up was 3.45 months. PFS, OS, and DoR data are immature due to short follow-up. Safety analysis (n=15) showed any-grade TRAEs in 66.7% of patients, with grade 3–4 TRAEs in 46.7%. Common TRAEs included neutropenia (46.7%), diarrhea (26.7%), thrombocytopenia (26.7%), and leukopenia (46.7%). Most TRAEs were manageable with supportive care or dose adjustments (only one dose adjustment due to AE). No treatment-related deaths occurred. Conclusions: Liposomal irinotecan combined with cisplatin/carboplatin demonstrates promising antitumor activity (ORR 41.7%) and a manageable safety profile in platinum-sensitive relapsed extensive-stage SCLC. These interim results support further investigation of this regimen as a potential second-line option. Longer follow-up is needed to assess survival endpoints and durability of response. Clinical trial information: NCT06467786 .
Azenosertib plus paclitaxel for platinum-resistant ovarian cancer: Results from a phase 1b study.
5529 Background: Most patients (pts) with ovarian cancer develop platinum-resistant disease following surgery and platinum-based chemotherapy and have a poor prognosis. Paclitaxel (PAC) monotherapy is the most efficacious chemotherapy for platinum-resistant ovarian cancer (PROC) but clinical benefits require further improvement. Azenosertib (Azeno) is a potentially best-in-class, novel, selective and orally bioavailable small molecule inhibitor of the WEE1 tyrosine kinase. Herein we report results from a Phase 1b study of Azeno plus PAC for PROC. Methods: MUIR (NCT04516447) is an open-label Phase 1b study evaluating the safety, efficacy and preliminary clinical activity of Azeno plus chemotherapy (Part 1 dose escalation) for PROC. Eligible pts were aged ≥18 years, had ECOG PS score ≤2, histologically/cytologically confirmed high-grade serous epithelial ovarian, fallopian tube, or peritoneal carcinoma, and measurable disease per RECIST v1.1; pts had received 1‒4 prior lines of systemic therapy and had platinum-resistant disease. Pts were assigned to 1 of 4 cohorts: carboplatin, gemcitabine, pegylated liposomal doxorubicin, or PAC (80 mg/m 2 IV on Days 1, 8 and 15 of 28-day cycles). Azeno plus PAC is the focus of this analysis where Azeno was orally administered 200 mg (continuously) or 200, 250 and 300 mg (intermittently 5 days on, 2 days off [5:2]) for 28-day cycles. Primary objectives were safety and tolerability. Clinical activity was a key secondary objective assessed by objective response rate (ORR) and duration of response (DOR) per RECIST v1.1, and progression-free survival. Exploratory objectives included analysis of baseline tumor and plasma biomarkers with optional biopsies/blood plasma. Results: As of December 1, 2025, 46 pts received Azeno (continuously 200 mg, n=7 and intermittently 5:2: 200 mg, n=15; 250 mg, n=12; 300 mg, n=12) plus PAC. Median age was 66 years (range 45‒83), median number of prior lines of therapy was 2 (range, 1‒4), and all pts received prior PAC. Most common treatment related adverse events (TRAEs) were fatigue (61%), anemia (59%), nausea (52%), and neutropenia (50%); most frequent grade ≥3 TRAEs were neutropenia (30%) and anemia (20%). Serious TRAEs occurred in 20% of pts. Overall, confirmed ORR was 39.1% (95% CI, 25.1‒54.6) with a median DOR of 5.6 months (95% CI, 5.6‒9.2) (Table). Conclusions: Azeno plus PAC showed promising clinical activity and tolerability in pts with PROC. ORR and median DOR were improved when compared historically with PAC monotherapy supporting the continued evaluation of this regimen in PROC and other indications. Clinical trial information: NCT04516447 . OR and median DOR. Azeno 5:2 Azeno 5:2 Azeno 5:2 Azeno 200 mg + PAC (n=7) 200 mg + PAC (n=15) 250 mg + PAC (n=12) 300 mg + PAC (n=12) All(N=46) ORR, %(95% CI) 57.1(18.4‒90.1) 20.0(4.3‒48.1) 50.0 (21.1‒78.9) 41.7 (15.2‒72.3) 39.1 (25.1‒54.6) Median DOR, months(95% CI) 7.8(5.6‒NE) 5.6(3.7‒NE) 9.2 (3.8‒NE) 5.6 (5.2‒NE) 5.6(5.6‒9.2) NE, not evaluable.
Integrated spatial transcriptomics, single-nucleus RNA sequencing, and histopathology to reveal immune-suppressive niches in colorectal cancer liver metastases.
e15544 Background: Progression of colorectal cancer (CRC) is shaped by interactions between tumor, immune, and stromal cells, particularly within the liver metastases (LM) microenvironment. Spatial transcriptomics enables in situ dissection of these interactions within intact tissue architecture. We analyzed matched primary and LM CRC samples to identify liver-specific spatial programs associated with immune suppression and clinical outcome. Methods: Patients (pts) undergoing resection of primary CRC and LM were retrospectively selected and profiled with the spatial transcriptomic (ST) platform CosMx Spatial Molecular Imager with a 1k plex panel (Bruker Spatial) and single-nucleus RNA sequencing (snRNA-seq) with the Flex kit (10x Genomics) within a partner-of-choice framework. Tissue sections were annotated to define reference mucosa, premalignant lesions, and tumor regions. Rigorous QC removed low-quality cells, segmentation artifacts, retaining high-confidence spatially resolved cells. Spatial domains and neighbourhood interactions were defined using graph-based approaches and analyzed by cell-type enrichment, molecular status, and clinical prognosis (px) (classified as good or bad based on OS ( > or < 3 years), and PFS from primary or LM surgery to progression ( > 6 months). Results: Eighteen pts were included; 14 pts had stage IV disease (77.8%); 11 pts (61.1%) were classified as good px (Table). Cohort-level snRNA-seq analysis identified site-specific transcriptional programs, with LM enriched for IFN-low states and EMT, squamous, and fetal progenitor programs. Bad px pts clustered exclusively within IFN-low groups, whereas IFN-high profiles, characterized by higher CD74 expression, were restricted to good px pts. ST profiling revealed macrophage-rich, perivascular immunosuppressive niches in LM, preferentially localized at tumor borders in bad px pts. Increased MAPK pathway activity was observed in RAS-mut metastatic tumor cells, with spatial immune and stromal organization varying by px and treatment. Conclusions: Integrated snRNA-seq and ST analyses show that CRC LM are characterized by IFN-low, EMT/fetal-like transcriptional programs and spatially organized, macrophage-rich perivascular immune suppressive niches associated with bad prognosis and RAS status, providing biological insight into immune evasion mechanisms in CRC pts. Pt characteristics (n=18). Good Prognostic 11 (61) Bad Prognostic7 (39) Sex Fem 4 (36) 4 (57) Male 7 (64) 3 (43) Stage I 1 (9) 0 II 1 (9) 1 (14) III 1 (9) 0 IV 8 (73) 6 (86) Age Median (range) 61 (30-74) 60 (52-75) Molecular Status RAS mut 2 (18) 3 (43) BRAF mut 1 (9) 1 (14) wt 8 (73) 3 (43) MMR MSS 11 6 (86) MSI 0 1 (14) Site Right 2 (18) 4 (57) Left 9 (82) 3 (43) Treatment before surgery LM CT 2 (18) 1 (14) CT + EGFR inhibitor 7 (64) 0 CT+ Bevacizumab 2 (18) 5 (71) No treatment 0 1 (14) Values are shown as n (%).
Does BMA improve outcomes in mHSPC with bone metastases?: Landmark propensity-matched analysis and nested zoledronic acid vs denosumab.
e17100 Background: Bone Marrow Agent (BMA) reduces skeletal-related events in bone-metastatic mCRPC, but their role in metastatic hormone-sensitive prostate cancer (mHSPC) disease remains uncertain; a LATITUDE post hoc analysis suggested longer time to skeletal-related events (SRE) with BMA use in patients with high-risk mHSPC but inconsistent OS. Methods: Retrospective cohort study using TriNetX database of mHSPC patients with bone metastases initiating first-line ADT (index). Primary analysis: early BMA (denosumab/zoledronic acid, 0–90d) vs no BMA; 90d landmark to limit immortal-time bias (exposure 0–90d; follow-up from day 90 in those alive/at risk). 1:1 PSM balanced demographics, comorbidities, tumor severity (PSA, Gleason, T/N stage), and prior therapies. Outcomes (code-defined) were OS, SREs (fracture, spinal cord compression, palliative RT), hypocalcemia, and acute kidney failure; Kaplan–Meier/Cox estimated HRs (95% CI), and risks/episode counts were summarized. Nested within early-BMA users, zoledronic acid vs denosumab was compared via 1:1 PSM using the same landmark. Results: Primary analysis: After 1:1 PSM, 505 matched pairs were analyzed. Deaths occurred in 163 (32.9%) in the BMA group vs 129 (26.0%) in the non-BMA group (p = 0.018); however, Kaplan–Meier time-to-event analysis was not significant (HR 1.06 [0.84–1.34]; p = 0.609). Pathologic fracture occurred in 23 (4.6%) vs 22 (4.4%) (p = 0.879; HR 0.91 [0.51–1.64]); spinal cord compression in 22 (4.4%) vs 15 (3.0%) (p = 0.241; HR 1.31 [0.68–2.52]); and palliative radiotherapy in 43 (8.5%) vs 46 (9.1%) (p = 0.739; HR 0.82 [0.54–1.25]). Acute kidney failure occurred in 97 (19.2%) in both groups (p = 1.000). Mean SRE episode counts were similar between groups (all p > 0.30). Nested analysis (ZOL vs DENO): After 1:1 PSM, 169 matched pairs were analyzed; only OS and AKI were reportable (other endpoints < 10 per group). Post-PSM deaths were 57 (34.3%) vs 56 (33.7%) (p = 0.908; HR 1.01 [0.70–1.46]). AKI occurred in 31 (18.3%) vs 35 (20.7%) (p = 0.583; HR 0.91 [0.56–1.48]); mean AKI episodes differed (2.45±2.10 vs 3.91±3.31, p = 0.039). Because fracture/SCC/RT/hypocalcemia were non-reportable post-PSM due to low case counts, crude estimates showed SCC 17/318 (5.35%) vs ≤10/287 (3.48%) (p = 0.268; HR 1.46 [0.67–3.19]), lower palliative radiotherapy (7.6% vs 12.5%; p = 0.040; HR 0.57 [0.34–0.96]), and lower hypocalcemia (3.5% vs 13.6%; p < 0.0001; HR 0.24 [0.12–0.46]) with zoledronic acid. P-value in negative controls > 0.1 both. Conclusions: In a landmark propensity-matched analysis, initiating BMAs early after ADT in mHSPC with bone metastases does not improve time-to-event survival or reduce skeletal-related events. In a nested comparative-effectiveness analysis, zoledronic acid and denosumab demonstrated similar survival and AKI risk, informing agent selection in routine practice.
The diagnostic delay signature in rare gynecologic cancers: Assessment of emergency presentation, acute organ failure, and failure-to-rescue.
e23143 Background: Rare gynecologic cancers lack standardized diagnostic pathways and are underrepresented in trials. Rarity may generate a reproducible inpatient “diagnostic delay signature,” reflected by altered admission pathways, acute organ failure at presentation, and adverse rescue outcomes. Methods: A survey-weighted analysis of the National Inpatient Sample (NIS), 2016–2023, evaluated adult hospitalizations for rare gynecologic cancers (vulvar C51, vaginal C52, gestational trophoblastic neoplasia [GTN] proxy O01/O02/C58/D39.2) versus common gynecologic cancers (endometrial C54–C55, cervical C53, ovarian C56). Overlap admissions and palliative encounters (Z51.5) were excluded. The diagnostic delay signature included nonelective admission and acute organ failure at presentation (sepsis A40/A41 or R65.2/R57.2, shock R57, respiratory failure J96/J80, acute kidney injury [AKI] N17). Outcomes included in-hospital mortality, ICU escalation (mechanical ventilation or shock), complication burden, failure-to-rescue, length of stay (LOS), cost, routine discharge, and hospital dependence. Results: The cohort included 215,343 unweighted admissions, representing 1,076,715 hospitalizations nationally. Rare gynecologic cancers accounted for 14.1% (95% CI 13.9%–14.3%) and common cancers for 85.9% (95% CI 85.7%–86.1%). Rare-cancer distribution was GTN 8.6%, vulvar 4.4%, and vaginal 1.2%. Rare cancers had lower nonelective admission rates than common cancers (61.5% vs 67.2%; 95% CI 60.8%–62.1% vs 66.7%–67.6%) and lower acute organ failure at presentation (13.2%, 95% CI 12.8%–13.6% vs 29.7%, 95% CI 29.4%–30.0%), including lower rates of sepsis (5.6% vs 10.2%), shock (0.6% vs 1.4%), respiratory failure (3.7% vs 8.4%), and AKI (7.3% vs 19.6%). ICU escalation was less frequent (1.4% vs 3.0%), with shorter LOS (3.14 vs 5.30 days) and lower costs ($12,036 vs $20,108). In-hospital mortality was 0.56% (95% CI 0.48%–0.65%) for rare cancers versus 1.97% (95% CI 1.90%–2.04%) for common cancers. Complication burden (23.4% vs 47.4%) and failure-to-rescue mortality (2.18%, 95% CI 1.86%–2.56% vs 3.78%, 95% CI 3.65%–3.92%) were lower in rare cancers. Routine discharge was more frequent (80.1%, 95% CI 79.6%–80.7%), highest in GTN (96.9%, 95% CI 96.6%–97.2%). Among rare cancers, acute organ failure increased from 10.2% in 2016 to 16.3% in 2023, while mortality remained low. Adjusted analyses showed lower odds of inpatient mortality (aOR 0.37, 95% CI 0.31–0.45) and failure-to-rescue (aOR 0.65, 95% CI 0.54–0.77). Conclusions: Rare gynecologic cancers comprised 14% of inpatient gynecologic cancer hospitalizations and showed rising acute organ failure at presentation over time. Despite increasing acuity, rare cancers were associated with lower inpatient mortality, ICU escalation, complication burden, and failure-to-rescue.
The impact of malaria-induced neutrophil subset shift and a link to Burkitt lymphoma
Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that remains a leading cause of childhood cancer mortality in sub-Saharan Africa. Although the epidemiological link between Plasmodium falciparum (Pf) malaria and BL has been established, our understanding of the underlying immunological mechanisms conducive to tumorigenesis is incomplete. To address a noted gap in our knowledge of the immune landscape, we conducted a prospective study to profile neutrophil subsets from children with different exposure histories to Pf -malaria and children diagnosed with BL from Western Kenya, along with healthy malaria low-exposed Kenyan adults. Using multiparameter flow cytometry, we characterized neutrophils by expression of CD15, CD16, CD10, CD11b, CD182, CD184, and CD62L and found that malaria-exposed children exhibited increased frequencies of aged neutrophil subsets, accompanied by a reduction in the mature active subset frequencies compared to malaria low-exposed children. Notably, a positive correlation (rs = 0.7; p < 0.0001) was observed in immature neutrophils between malaria-exposed healthy and BL children, revealing a possible similar expansion of this subset in both groups. These findings suggest a malaria-associated expansion of the immature neutrophil subset. While functional assays were not performed in this study, previous reports indicate that immature neutrophils can exhibit tumor-promoting functions. Therefore, the observed shift in neutrophil profiles may reflect phenotypic changes associated with malaria exposure that could contribute to a permissive environment for BL.