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Patient-reported quality of life and mood in prolonged responders to immune checkpoint inhibitors for metastatic solid tumors.
e24138 Background: Immune checkpoint inhibitors (ICIs) have transformed metastatic cancer care by enabling prolonged tumor control, creating a novel survivorship population living years with advanced disease. While tumor response rates are well documented, patient-reported outcomes including health-related quality of life (HRQoL) and psychological adjustment remain underexplored, particularly among real-world responders from middle-income settings where access barriers persist. Methods: This cross-sectional study, conducted between November 2020 and November 2021, included 38 adults (≥18 years) with metastatic solid tumors receiving immune checkpoint inhibitor therapy for at least six months without disease progression at a single Brazilian cancer center. Participants were selected through convenience sampling. Health-related quality of life was assessed using the validated Portuguese version of the Functional Assessment of Cancer Therapy–General (FACT-G, version 4), a 27-item instrument with total scores ranging from 0 to 108 across physical, social/family, emotional, and functional well-being domains. Symptoms of anxiety and depression were screened using the Hospital Anxiety and Depression Scale (HADS), with subscale scores ≥8 indicating clinically relevant symptoms. Clinical and demographic data were extracted from medical records. Descriptive statistics, including means, standard deviations, and frequencies, were used, and results were compared with published normative data from oncology populations. Results: Participants (mean age 69 years; 61% male) showed preserved function (ECOG 0/1/2: 68/26/5%) across primaries (lung 26%, melanoma 24%, other 50%). Most received pembrolizumab monotherapy (66%); mean treatment duration 101 weeks (SD 63); immune-related adverse events (all grade 1-2) affected 37%. FACT-G scores aligned with norms: total 82 (SD 10); physical 22 (4), social/family 24 (4), emotional 19 (4), functional 18 (4). Differences versus references fell below minimal important differences (total <5 points, domains <2). HADS identified anxiety in 8% (n=3) and depression in 5% (n=2); no correlations observed between PROs, irAEs, or treatment duration. Conclusions: Metastatic cancer patients achieving durable ICI responses demonstrate normative HRQoL profiles with minimal psychological distress, suggesting favorable long-term tolerability. These findings support routine patient-reported outcome monitoring within comprehensive survivorship programs tailored to this population. FACT-G by domain. FACT-G Domain Mean (SD) Range Physical Well-Being 22 (4) 20-24 Social/Family 24 (4) 22-25 Emotional 19 (4) 18-21 Functional 18 (4) 17-20 Total Score 82 (10) 80-85
Geographic accessibility of recruiting clinical trials for rare and common gastrointestinal malignancies in the United States.
1540 Background: Gastrointestinal (GI) cancers account for substantial cancer mortality, with rare GI malignancies experiencing particularly poor outcomes and limited therapeutic options. Clinical trials are essential for treatment development; however, the geographic accessibility of disease-specific trials for rare GI cancers remains insufficiently characterized. Methods: We queried ClinicalTrials.gov to identify actively recruiting interventional disease-specific trials for GI cancers in the United States (accessed Jan 2026). Trials were classified as common (colorectal, pancreatic, hepatocellular, gastroesophageal) or rare (anal, appendiceal, small bowel adenocarcinoma, biliary tract) GI cancers. Trial sites were geocoded by ZIP code. Geographic accessibility was defined as the proportion of the U.S. population residing within 30 miles of a recruiting trial site; areas without a site within 30 miles were defined as clinical trial deserts. Urban–rural status and income quartiles were derived from census-based classifications. A 60-mile access definition was evaluated as a sensitivity analysis. Results: A total of 283 disease-specific GI cancer trials encompassing 1,322 unique U.S. trial site ZIP codes were included. More than 80% trials were early-phase (Phase I–II). Using a 30-mile access definition, overall population coverage was 83.6%, with lower coverage in rural versus urban populations (47.5% vs 90.9%) and in the lowest vs highest income quartiles (65.8% vs 98.0%). Common GI cancers had broad access, including colorectal cancer (80.2% population coverage) and pancreatic cancer (75.3%). In contrast, more than half of the population resided in a clinical trial desert for rare GI cancers (biliary tract = 55.2%, small bowel = 56.4, anal cancer= 80.8%, appendiceal 99.5%). Over 75% of rural residents resided in trial deserts for any rare GI cancer. Findings were consistent using a 60-mile access definition. Conclusions: Geographic accessibility remains a major barrier for disease-specific clinical trials of rare GI malignancies. This results in extensive clinical trial deserts and perpetuates existing disparities for rural and lower-income populations. These findings highlight structural gaps in trial availability and support the need for more geographically inclusive trial designs. Geographic access to disease-specific gastrointestinal cancer clinical trials. Cancer type Trials(N) Trial site ZIP (N) % Pop ≤30 mi %Pop in trial desert %Rural Pop in trial desert %Lowest income quartile in trial desert Common Colorectal 82 1,026 80.2 19.8 59.2 38.5 Pancreas 75 730 75.3 24.7 67.1 45.1 Gastroesophageal 46 684 71.9 28.1 69.1 49.8 Hepatocellular cancer 45 210 54.7 45.3 93.2 64.5 Rare Biliary tract cancer 28 109 44.8 55.2 95.1 70.3 Small bowel adenocarcinoma 2 419 43.6 56.4 77.5 67.2 Anal 5 19 19.2 80.8 99.1 86.6 Appendicular 1 1 0.5 99.5 99.9 99.7
KITE-753: A phase 2 study of an autologous anti-CD19/CD20 CAR T-cell therapy in CAR-naive patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL).
TPS7098 Background: CD19-directed CAR T-cell therapy has become the standard of care for R/R LBCL; however, some patients are refractory to CD19 CAR T-cell therapy and a subset of responders relapse (Eyre et al. Ann Oncol . 2025, Westin et al. N Engl J Med . 2023). KITE-753 is an investigational, bicistronic, CD19/CD20 CAR T-cell therapy with a parallel CAR design to optimally engage two tumor antigens, synergistic CD28/4-1BB costimulation to enhance T-cell function, and a rapid manufacturing process that preserves naive and stem cell memory T cells. It is designed to improve cure rates while limiting toxicity for patients with R/R LBCL. In vitro, KITE-753 demonstrated potent antitumor activity at a dose >25-fold lower than an identical product manufactured with a traditional ex vivo expansion period (Murakami et al. ASH 2024). Phase 1 assessment of KITE-753 showed very low rates of immune effector cell-associated neurotoxicity syndrome (ICANS) and no high-grade cytokine release syndrome or ICANS in patients with R/R LBCL at the intended pivotal dose level. Furthermore, high response rates were observed with 79% of patients achieving complete response (CR). CAR T-cell expansion was comparable to KITE-363 and axi-cel despite a 10-fold lower dose (Dahiya et al. ASH 2025, Dahiya et al. ASCO 2025). Based on Phase 1 outcomes, the Phase 2 dose was established as 2×10 5 CAR T cells/kg. This Phase 2 study will evaluate the safety and efficacy of KITE-753 in CAR-naive patients with R/R LBCL. Methods: In this open-label, multicenter, single-arm study, patients will undergo leukapheresis and receive optional bridging therapy, followed by lymphodepleting chemotherapy (cyclophosphamide [300 mg/m 2 /day] and fludarabine [30 mg/m 2 /day]) from Day -5 to Day -3, and infusion of KITE-753 at a target dose of 2×10 5 CAR T cells/kg on Day 0. The primary endpoint is objective response rate (CR rate + partial response rate) assessed by central review per Lugano Classification (Cheson et al. J Clin Oncol . 2014). Secondary outcomes include CR rate, duration of response, progression-free survival, overall survival, and safety. The target enrollment is 80 patients. Eligible adults have histologically confirmed R/R LBCL (including transformation of indolent lymphomas and primary mediastinal B cell lymphoma) after ≥2 prior lines of systemic therapy (including anti-CD20 mAb or bispecific antibody + anthracycline). Other key inclusion criteria are adequate bone marrow and organ function and ECOG performance status ≤2. Key exclusion criteria are prior CAR T-cell therapy or active central nervous system involvement from lymphoma. This study is currently open and actively accruing patients (NCT04989803). Clinical trial information: NCT04989803 .
An open-label, multicenter study of DPTX3186 to evaluate safety, tolerability, and pharmacokinetics in subjects with known Wnt pathway–activated solid tumors where no other treatments exist.
TPS3169 Background: Constitutive activation of the Wnt/β-catenin pathway drives malignancy in a wide range of cancers, where β-catenin has been notoriously difficult to drug due to its disordered nature, lack of defined drug-binding pockets, and associated toxicities. Biomolecular condensates are membraneless organelles that orchestrate cellular processes, biological pathways, and protein activity by compartmentalizing biomolecules. DPTX-3186 is a small molecule condensate modulator (c-mod) that acts via a novel mechanism of action, sequestering β-catenin into inactive condensate depots. This sequestration selectively inhibits β-catenin-driven transcription and induces robust cancer cell death. DPTX3186 is an orally bioavailable small molecule c-mod that demonstrates strong anti-tumor activity across multiple tumor types driven by various defects along the Wnt/β-catenin pathway. Studies in xenographs show that DPTX-3186 modulates Wnt pathway activity as evidenced by formation of inactive β-catenin condensates and modulation of β-catenin-driven gene transcription. Profound pharmacological efficacy, including regressions and complete responses, has been observed in murine models of gastric cancer as monotherapy. The molecule has been granted Fast Track and Orphan Drug Designations by the FDA. Methods: This first-in-human, phase 1/2, multicenter, open-label, dose-escalation (phase 1) and dose-expansion (phase 2) study evaluates the safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor effects of DPTX3186 monotherapy in patients with known Wnt pathway activated solid tumors. Eligible patients must have no other approved treatment options available. In Phase 1, DPTX3186 is administered orally in a 4 days on / three days off schedule, at escalating dose levels, evaluated sequentially in a BOIN design. Phase 2 dose expansion will utilize a TOP-BOIN design and will evaluate DPTX3186 monotherapy in patients with histologically or cytologically confirmed non-resectable gastric adenocarcinoma who are refractory to prior treatment. Primary endpoints are safety and tolerability of DPTX-3186, including dose-limiting toxicities (DLT) and the determination of the MTD and recommended dose for expansion. Secondary endpoints are PK, PD, and preliminary anti-tumor activity (e.g. overall response rate, duration of response, progression-free survival, disease control rate, and overall survival). 40 patients are planned to be enrolled in Part 1, which is currently enrolling in the USA. Clinical trial information: NCT07312903 .
Phase II study of ABSK061 (selective FGFR2/3 inhibitor) combined with ABSK043 (oral PD-L1 inhibitor) ± CAPOX in advanced FGFR2-positive gastric cancer and gastroesophageal junction cancer (GC/GEJC): Preliminary results from ABSK061-201.
e16036 Background: Aberrant FGFR2 signaling is a validated driver associated with poor prognosis in advanced GC/GEJC. FGFR2b overexpression is observed in 16%-30% of patients in this tumor type, while approximately 5%–10% of GC cases have FGFR2 gene amplification. ABSK061 is a highly selective oral FGFR2/3 inhibitor designed for treating GC/GEJC. Methods: This ongoing phase II study (NCT06632262) is to evaluate the safety and preliminary efficacy of ABSK061 plus ABSK043 with or without chemotherapy. In dose escalation cohort and expansion cohort 4, patients with solid tumors including pretreated (2L+) GC/GEJC with FGFR2b overexpression and/or FGFR2 amplification, were enrolled and received ABSK061 plus ABSK043. Expansion cohort 1 specifically enrolled treatment-naïve (1L) advanced HER2- GC/GEJC patients with FGFR2b overexpression and/or FGFR2 amplification, who received ABSK061 plus ABSK043 and CAPOX. Results: As of January 2026, a total of 37 patients (24 2L+, 13 1L) were enrolled with ABSK061 75mg BID and ABSK043 800mg BID ± CAPOX. No dose-limiting toxicities (DLTs) were observed. Treatment emergent adverse events (TEAEs) occurred in 97.3% of patients, of which 51.4% were Grade ≥3. The most common TEAEs included increased aspartate aminotransferase (54.1%), increased alanine aminotransferase (45.9%), and anaemia (43.2%). In expansion cohort 1, TEAEs occurred in 92.3% of patients, of which 53.8% were Grade ≥3. The most common ( > 10%) Grade ≥3 TEAEs included platelet count decreased (23.1%), hypokalaemia (15.4%) and neutrophil count decreased (15.4%), which were most likely attributable to chemotherapy. Across cohorts, all FGFR-related AEs including ocular events (2.7% grade 3), stomatitis (2.7% grade 3) and nail disorder ( all grade 1-2) were reversible and well managed through dose modifications without leading to permanent discontinuation. Among 10 treatment-naïve patients with GC/GEJC who received at least 1 cycle of treatment, all patients showed target-lesion shrinkage and remain on treatment, 9 achieved partial response (PR) per RECIST v1.1, yielding an objective response rate (ORR) of 90%. Among 16 evaluable pretreated (2L+) patients with GC/GEJC, 5 achieved PR (ORR: 31.3%), with the longest duration of treatment being 7.6 months. Conclusions: ABSK061 combined with ABSK043, with or without CAPOX, has demonstrated a manageable safety profile and encouraging anti-tumor activity in both 1L and 2L+ FGFR2-positive GC/GEJC. These promising results warrant further clinical development of the doublet and quadruplet regimens for GC/GEJC. Clinical trial information: NCT06632262 .
Differential risk patterns of secondary breast cancer in medullary versus papillary thyroid carcinoma survivors: A SEER-based analysis.
10585 Background: Prior studies suggest that thyroid cancer (TC) survivors may have an elevated risk of secondary malignancies. However, whether this risk differs by TC histology, specifically with breast cancer (BC), remains unclear. We aimed to investigate the association between TC subtype—papillary thyroid carcinoma (PTC) versus medullary thyroid carcinoma (MTC)—and subsequent BC risk, adjusting for demographic factors. Methods: We conducted a retrospective cohort study using the SEER (2000–2022), including adults with a primary, microscopically confirmed PTC or MTC. Subsequent BC occurrence was defined as a binary outcome (yes/no). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for MTC versus PTC, controlling for age (<50 vs ≥50 years), sex, and race. Stratified analyses by age and race were also performed. Stata 15 was used for statistical analyses. Results: 14,840 patients (14,563 PTC, 277 MTC) were included. MTC patients were older (mean 59.08±12.66 vs 56.16±12.98 years, p<0.001) and had a higher proportion of males (44.4% vs 29.4%, p<0.001). The overall incidence of secondary BC was lower in MTC patients (7.6% vs 22.5%, p<0.001). In unadjusted logistic regression, MTC was associated with significantly lower BC risk (OR=0.28, 95% CI: 0.18–0.44, p<0.001). After adjustment, MTC remained significantly protective (aOR=0.34, 95% CI: 0.22–0.55, p<0.001). Stratified analyses demonstrated consistent findings across age groups (<50: aOR=0.10, 95% CI: 0.03–0.42; ≥50: aOR=0.34, 95% CI: 0.21–0.54), , as well as white and Hispanic patients. Conclusions: Survivors of MTC have a substantially lower risk of developing secondary BC compared to PTC survivors. This association persists after adjustment for age, sex, and race, and is consistent across age and most racial subgroups. However, different BC types were not assessed due to limited number of BC patients among MTC survivors, and the small MTC sample size and potential survival differences between groups may affect the results. These findings highlight a possible effect of TC subtype on BC risk, suggesting the potential influence of underlying biological or genetic mechanisms. Baseline demographic characteristics of patients with papillary and medullary thyroid carcinoma. Characteristic Papillary Thyroid Carcinoma (PTC) (N=14,563) Medullary Thyroid Carcinoma (MTC) (N=277) P-value Age at Diagnosis 0.0002* Mean ± SD, years 56.16 ± 12.98 59.08 ± 12.66 Median, years 57 61 Sex, n (%) <0.001† Female 10,288 (70.6) 154 (55.6) Male 4,275 (29.4) 123 (44.4) Race, n (%) 0.015† White 10,263 (70.5) 197 (71.1) Black 921 (6.3) 15 (5.4) American Indian 77 (0.5) 1 (0.4) Asian 1,379 (9.5) 13 (4.7) Hispanic 1,903 (13.1) 50 (18.1) SD: Standard Deviation. *P-value from two-sample t-test (equal variances assumed). †P-value from chi-square test for the overall distribution across categories.
Re-sensitizing PD-1/PD-L1 relapsed/refractory solid tumors: Phase 1a results of IOS-1002, a LILRB1/2 and KIR3DL1 checkpoint inhibitor, in combination with pembrolizumab.
2501 Background: Despite anti-PD-1/PD-L1 therapy success, 60-70% of patients develop progression with limited options (ORR 6-8% to retreatment). Upregulation of inhibitory receptors LILRB1/2 and KIR3DL1 mediates immune escape in anti-PD-1/PD-L1-resistant tumors. IOS-1002, a novel LILRB1/2 and KIR3DL1 antagonist, restores anti-tumor immunity when combined with pembrolizumab. Methods: Open-label, multicenter, dose-escalation Phase 1a study (NCT05235308) evaluated IOS-1002 (300-1800mg, Q2W IV) plus pembrolizumab 400mg (Q6W IV) in advanced solid tumors progressing on prior anti-PD-1/PD-L1 therapy. Primary endpoints: safety, tolerability; secondary: ORR, DCR, duration of response (DOR). Comprehensive biomarker analysis included serial cytokine profiling, target receptor expression (LILRB1/2, KIR3DL1), and tumor immune score (TIS) by gene expression analysis. Responses were assessed by RECIST v1.1. Results: As of January 1st, 2026, 28 patients received combination treatment with 16 anti-PD-1/PD-L1-relapsed/refractory patients (median age 65, ECOG 0-1). 3 confirmed PRs (tumor reduction -35% to -58% from baseline) leading to an ORR of 20% (3/15 evaluable) were noted with a DCR of 54% at week 12 (7/13) and 40% at week 24 (4/10), respectively. Durable responses included: 1 metabolic CR (urothelial cancer), 1 pathological CR confirmed by repeat biopsy showing absence of viable tumor cells (cutanteous SqCC), and 1 cervical cancer patient achieving -29% tumor reduction with concomitant > 90% decline in CA-125 tumor marker. Median treatment DOR was 30+ weeks (range 12-46+); 8 patients remain on treatment. Biomarker analysis demonstrated strong predictive value for TIS and target receptor expression achieving 75% ORR (3/4) versus 0% in dual-low patients (0/5). Combined biomarker score significantly correlated with depth of response (R² = 0.72, p = 0.008) and progression-free survival (HR 0.31, 95% CI 0.11-0.88, p = 0.04). Safety profile was favorable with no increase in grade≥3 immune-related adverse events beyond pembrolizumab monotherapy. Conclusions: IOS-1002 plus pembrolizumab demonstrated clinically meaningful efficacy in pretreated anti-PD-1/PD-L1-relapsed/refractory patients. Biomarker-driven patient selection using dual-high TIS and target receptor expression enhanced ORR to 75% and strongly predicted response depth, durability, and survival benefit. The favorable safety profile with no incremental immune-related toxicity, coupled with durable responses and high disease control rates, provides compelling rationale for Phase 1b expansion in biomarker-selected PD-1/PD-L1-refractory solid tumors. Clinical trial information: NCT05235308 . Endpoint Result ORR (evaluable) 20% (3/15) DCR Week 12 54% (7/13) DCR Week 24 40% (4/10) Biomarker-selected ORR 75% (3/4) Ongoing treatment 8/16 (50%)
Light‐Modulated Xylan‐Reinforced Nanofluidic Memristor for Ionic Neural Network‐Based Robot Movement Modulation
ABSTRACT The balance between excitatory and inhibitory (E/I) signaling underpins complex neural functions in biological systems. However, replicating such ion‐mediated regulation with biobased materials in artificial systems remains challenging. Herein, we demonstrate two distinct light‐modulated 2D nanofluidic memristors based on paper‐mill waste (xylan) reinforced membranes that emulate complementary E/I synaptic signaling, enabling precise robotic motion control via ionic neural networks. The memristors were constructed using xylan‐reinforced MXene membranes with asymmetric electrolytes, leveraging the interfacial interactions between the functional groups of xylan derivatives and MXene to achieve nanofluidic membrane assembly and precise control over surface charge and ion selectivity. Upon illumination, the photothermal effect of MXene induces a uniform thermal field that enables thermally activated ion transport in the interlayer spacing, allowing these biomass‐based memristors to emulate key excitatory and inhibitory synaptic behaviors. These complementary memristors further implement reconfigurable Boolean logic operations and serve as foundational components for ionic circuits, as demonstrated in series and parallel configurations. As a proof‐of‐concept, an E/I‐integrated ionic neural network achieved precise control of ten robotic motion modes by tuning light pulses, concentration gradients, and ion selectivity. This work highlights the potential of biomass‐reinforced materials for nanofluidic memristors and explores new frontiers in the application of biomass materials.
Tough Hydrogels with Robust Wet Adhesion via Entropy‐Driven Hydrogen Bond Reorganization
ABSTRACT High‐performance hydrogels for tissue repair should provide both mechanical reinforcement and interfacial adhesion. However, conventional strengthening strategies typically rely on hydrogen bonding within the network, whose inherent bonding energy and restricted configurational freedom intrinsically limit chain mobility at the interface, ultimately weakening wet adhesion. To overcome the strength‐adhesion trade‐off caused by hydrogen bond distribution, this study proposes an entropy‐driven strategy that decouples the spatial distribution of hydrogen bonds to simultaneously achieve high bulk strength and robust wet adhesion. Starting from a conformationally disordered and high‐entropy mixture, the hydrogen bonds then concentrate in the bulk through entropy‐favored reconfiguration to strengthen the network. The bulk‐interface energetic and conformational mismatch in turn triggers a localized phase separation, which reduces interfacial entropy to form a hydrogen bond‐depleted nanoconfined water layer. This layer permits dynamic polymer‐tissue hydrogen bonding, enabling robust wet adhesion without loss of bulk strength. The resulting hydrogel can rapidly conform to tissue surfaces, forming a high modulus structure (∼13 MPa) that withstands hydrostatic pressures up to 368 mmHg. It achieves sealing beyond physiological limits and maintains stable adhesion, demonstrating effective repair in models of skin injury, oral mucosal ulceration, and cardiac bleeding.
Selective bladder-sparing trial with sasanlimab as maintenance treatment based on clinical response to neoadjuvant treatment in molecularly categorized muscle invasive bladder cancer patients: SASAN-SPARING trial.
TPS4644 Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease with a high risk of progression, for which radical cystectomy (RC) remains the standard of care. Adaptive bladder-sparing strategies based on post-neoadjuvant clinical restaging are increasingly explored to maintain oncologic control while preserving quality of life. SASAN-SPARING evaluates sasanlimab, a PD-1 inhibitor, as maintenance therapy in patients achieving a clinical response after neoadjuvant cisplatin-based chemotherapy. Methods: SASAN-SPARING (HM-8788561; NCT06623162) is an ongoing, single-arm, multicenter, phase II trial enrolling patients aged ≥18 years with treatment-naïve, localized MIBC (pT2–T4a, N0, M0) eligible for neoadjuvant chemotherapy. All patients receive four cycles of cisplatin (70 mg/m² on day 1) plus gemcitabine (1000 mg/m² on days 1 and 8) every 3 weeks, followed by comprehensive clinical restaging. Patients achieving a clinical response (cT0/Ta/T1/Tis, negative cytology, and negative imaging) are eligible for bladder preservation with sasanlimab 300 mg administered subcutaneously every 4 weeks for up to 12 cycles. Non-responders (≥cT2) undergo RC. During maintenance, restaging is performed every 12 weeks, and RC may be considered upon loss of response or disease progression. The primary endpoint is bladder-intact overall survival at 12 months after the first dose of sasanlimab. Secondary endpoints include disease-free survival, metastasis-free survival, overall survival, safety, and health-related quality of life. The study incorporates an ambitious biomarker analysis, including whole-genome sequencing of tumour tissue and plasma, the use of ctDNA in plasma and urine for tumour assessment and molecular dynamics, and the study of the gut microbiome in stool. Biomarker-correlative studies will provide a valuable tool for personalized treatments and inform treatment decisions in adaptive strategies such as SASAN-SPARING. The Expected sample size is 70 patients, assuming a 12-month biOS of 81% (H0) and an increase with sasanlimab up to 93% (H1) (one-arm survival test; α=0.05 β=0.8).Recruitment began in December 2024. As of January 2026, 62 patients have been enrolled across 10 centers, and 21 started sasanlimab maintenance therapy. Enrollment is ongoing.SASAN-SPARING explores an adaptive, biomarker-integrated bladder-sparing strategy which aims to generate prospective evidence to support organ-preservation strategies in MIBC. Clinical trial information: NCT06623162 .
Safety and 5-year survival following treatment with leronlimab plus physician’s choice combination therapy in patients with metastatic triple-negative breast cancer.
e13109 Background: There is a significant unmet need among patients with PD-L1 low/negative metastatic triple-negative breast cancer (mTNBC). >95% of TNBCs are positive for C-C chemokine receptor 5 (CCR5). Leronlimab (LRM) is a humanized monoclonal antibody given subcutaneously which blocks CCR5 and in a preclinical model reduced TNBC metastasis by more than 98%. Methods: In this post hoc analysis LRM safety and efficacy data were pooled from 28 mTNBC patients from 3 clinical trials (NCT03838367; NCT04313075; NCT04504942). LRM was given weekly at a dose of 350 mg (N=10), 525 mg (N=15), or 700 mg (N=3) in combination with various chemotherapies ± immune checkpoint inhibitors (ICI). PD-L1 staining (LifetracDx) was measured on cancer-associated macrophage-like cells (CAMLs) and circulating tumor cells (CTCs) prior to and after (≈40 days) LRM treatment. Results: Median age was 48.5 years (range 32-83) with a median of 2 prior metastatic therapies (range 0 to 5). Ten patients (35.7%) had non-visceral metastases; 18 (64.3%) had visceral metastases, including 7 (25.0%) with brain metastases. The most common treatment-emergent adverse events (TEAEs), at a rate of ≥10%, were fatigue (21.4%), headache (21.4%), anemia (10.7%), constipation (10.7%), nausea (10.7%), and decreased neutrophil count (10.7%) but with no febrile neutropenia events. Overall, 21.4% (6/28) patients reported any LRM treatment-related TEAE; of these none were classified as CTCAE grade >2. No patients discontinued treatment due to a LRM treatment-related TEAE. Overall, 35.7% (10/28) reported any serious TEAE; none of the serious TEAEs were considered related to LRM treatment. The median overall survival (OS) was 7.1 months. Survival at 1, 2, 3, 4, and 5 years was 35.7%, 21.4%, 17.9%, and 17.9%, 17.9%, respectively. OS among the 7 patients treated with LRM with an ICI, or followed by an ICI, was longer than among the remaining 21 patients (HR 4.14, 95% CI: 1.7–10.2; P=0.0041). For patients with available data, upregulation from baseline of PD-L1 was observed on CAMLs/CTCs in 76% (16/21) of patients. All five patients treated with LRM [525 mg (N=4), or 700 mg (N=1)] with an ICI, or followed by an ICI, and who significantly upregulated PD-L1, remained alive at 5 years. Conclusions: In this post hoc analysis LRM was well tolerated with no LRM treatment-related TEAEs leading to treatment discontinuation and no LRM treatment-related TEAEs graded as CTCAE >2. A 5-year OS rate of 17.9% (5/28) in this advanced population is encouraging. All 5 patients with PD-L1 upregulation treated with LRM with an ICI, or followed by an ICI, remained alive at 5 years suggesting a correlation with durable responses. These findings support the hypothesis that LRM may enhance PD-L1 expression on CAMLs/CTCs, potentially priming tumors for improved responses to ICIs. Confirmatory phase 2 studies in mTNBC are planned. Clinical trial information: NCT03838367 (N=10); NCT04313075 (N=16); and NCT04504942 (N=2).
Molecular differences between early- and later-onset colorectal cancer in a Chilean cohort: A retrospective MSI and NGS-based analysis.
3670 Background: The incidence of early-onset colorectal cancer (EOC) is increasing worldwide; however, molecular data from Latin American populations remain scarce. We compared molecular alterations, including microsatellite instability (MSI) status and selected next-generation sequencing (NGS)–derived gene alterations, between EOC and later-onset colorectal cancer (LOC) in a Chilean cohort. Methods: We conducted a retrospective analysis of patients diagnosed with colorectal cancer with MSI assessment and/or NGS testing available between March 2017 and September 2025 at a private hospital in Chile. MSI status was determined by immunohistochemistry and/or PCR. In-house NGS panels were analyzed. Clinical variables included age at diagnosis, sex, and tumor location. EOC was defined as diagnosis <50 years and LOC as ≥50 years. Molecular alterations were compared using Fisher exact test, reporting odds ratios (OR) with Benjamini–Hochberg false discovery rate (FDR) correction. Results: A total of 324 patients were included (EOC n=66; LOC n=258). Median age was 42.6 years in EOC and 66.5 years in LOC. Tumor sidedness was comparable between groups, with a predominance of left-sided tumors in both EOC (54.5%) and LOC (61.2%). MSI status was available in 310 patients; MSI-H prevalence was 10.8% in EOC and 15.1% in LOC (OR 0.68, 95% CI 0.29–1.59; p=0.43). NGS denominators varied by gene according to panel coverage. No individual gene showed statistically significant differences after FDR correction. Pathway-level trends were observed (Table 1). In the WNT pathway, APC alterations were more frequent in EOC (83.3% vs 52.2%; OR 4.60; p=0.059). In the MAPK pathway, KRAS alterations were numerically higher in LOC (55.2% vs 37.5%; OR 0.49; p=0.13), while BRAF alterations were more frequent in EOC (16.7% vs 8.3%; OR 2.20; p=0.29). In the PI3K pathway, PIK3CA (29.2% vs 15.6%; OR 2.22; p=0.12) and PTEN (8.3% vs 2.1%; OR 4.27; p=0.15) alterations trended higher in EOC. TP53 alterations were highly prevalent and similar across groups. Conclusions: In this Chilean cohort, EOC and LOC showed similar MSI prevalence and largely overlapping molecular profiles. Although no gene-level differences remained significant after multiple-testing correction, pathway-specific trends suggest increased WNT and PI3K alterations in EOC and higher MAPK signaling in LOC. These findings highlight the need for larger, uniformly sequenced studies in Latin American populations. Selected pathway-specific molecular alterations. Category Gene EOC n/N (%) LOC n/N (%) OR p WNT APC 10/12 (83,3) 36/69 (52,2) 4,60 0,059 MAPK KRAS 9/24 (37,5) 53/96 (55,2) 0,49 0,13 BRAF 4/24 (16,7) 8/96 (8,3) 2,20 0,29 PI3K PIK3CA 7/24 (29,2) 15/96 (15,6) 2,22 0,12 PTEN 2/24 (8,3) 2/96 (2,1) 4,27 0,15 DDR ATM 1/24 (4,2) 5/96 (5,2) 0,80 1,00 TGF-β SMAD4 3/24 (12,5) 7/96 (7,3) 1,81 0,47 Cell cycle TP53 15/24 (62,5) 62/96 (64,6) 0,91 1,00
Identifying optimized dosage for zelenectide pevedotin in locally advanced/metastatic urothelial carcinoma (la/mUC) using quantitative analyses.
4567 Background: Zelenectide pevedotin (zele; BT8009) is a Bicycle Drug Conjugate (BDC) comprising a highly selective bicyclic peptide targeting Nectin-4 linked to the cytotoxin monomethyl auristatin E (MMAE) via a cleavable linker. Zele demonstrated preliminary antitumor activity and a generally tolerable safety profile in patients (pts) with la/mUC in the Phase 1/2 Duravelo-1 trial (NCT04561362) [Reig, 2024; Giannatempo, 2025]. Zele is being evaluated in a randomized Phase 2/3 study at 2 dosages, 5 mg/m 2 on Days (D)1/8/15 and 6 mg/m 2 on D1/8 of a 21-D cycle, each as monotherapy or combined with pembrolizumab (P) in pts with la/mUC (NCT06225596, Duravelo-2) [Loriot, 2025]. After 30 pts in each dosage arm had 27 weeks follow-up (N=120 total), an interim analysis was conducted to select the optimized dosage for further development. Methods: Pharmacometric (PMx) and utility score analyses were conducted to quantify the benefit-risk comprehensively. For the PMx analysis, all pharmacokinetic (PK), overall response rate [ORR, assessed by investigator (INV) and/or blinded independent central reviewer (BICR)], and adverse event (AE) data [zele-related and treatment-emergent (TE) Gr ≥3 AE, Gr ≥3 neutropenia, Gr ≥2 gastrointestinal disorders, Gr ≥2 peripheral neuropathy, any Gr skin reactions, dose modifications] from Duravelo-1 and -2 were pooled and analyzed using population PK (PopPK) and exposure-response (ORR, AE) modeling. Simulations for ORR and AE probabilities were then generated for comparing dosages with balance of relevant pt characteristics. The utility score analysis was mainly based on Gr ≥3 zele-related TEAEs and ORR by BICR regardless of confirmation in Duravelo-2, with sensitivity analyses based on alternative safety and/or efficacy endpoints (TEAEs, confirmed ORR by BICR). Results: The datasets for PopPK, ORR, and AE analysis included 434, 203 (203 INV assessed, 114 BICR assessed), and 394 pts, respectively, mostly treated at the 5 or 6 mg/m 2 dosages. Modeling of ORR did not detect a significant difference between the dosages studied. ORR was impacted positively by P combination, negatively by baseline tumor size, but not by the assessor (INV vs BICR). The AE rates were significantly correlated with exposures of zele and/or MMAE. Between 5 mg/m 2 D1/8/15 and 6 mg/m 2 D1/8, ORR did not differentiate them; safety favored 6 mg/m 2 D1/8 as its predicted AE probabilities were mostly lower. For AEs favoring 6 mg/m 2 D1/8, predicted probabilities were lower by 0.1% – 15.5% as monotherapy and by 0.1% – 19.1% in combination. The utility score analysis favored 6 mg/m 2 D1/8 consistently for zele combined with P and remained neutral between the dosages for monotherapy. Conclusions: 6 mg/m 2 D1/8 was identified as the optimized zele dosage for monotherapy and in combination with P based on the overall benefit-risk informed by the comprehensive quantitative analyses. Clinical trial information: NCT06225596 .
Comparative outcomes of continuous infusion versus intravenous push followed by infusion 5-fluorouracil in patients with pancreatic and colon cancer: A propensity-matched analysis.
e15735 Background: 5-Fluorouracil (5-FU) is a cornerstone of therapy for gastrointestinal malignancies and is commonly administered as continuous infusion or as intravenous (IV) push followed by infusion. Despite widespread use of bolus-containing regimens, real-world comparative data evaluating clinical outcomes between these administration strategies in pancreatic and colon cancer remain limited. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, including adults (≥18 years) with pancreatic or colon cancer who received injectable 5-FU between January 2000 and January 2026. Patients were categorized into continuous infusion 5-FU versus IV push followed by infusion 5-FU. Capecitabine exposure was excluded. Outcomes assessed from 1 to 365 days after the index event included all-cause mortality, hospitalization, granulocyte colony-stimulating factor (G-CSF) use, blood transfusion, platelet count < 50×10³/µL, and platelet count < 10×10³/µL. Propensity score matching (1:1) was performed to balance demographics, comorbidities, procedures, concomitant therapies, and genomic variables. Time-to-event outcomes were analyzed using Kaplan–Meier methods with log-rank testing, with Cox proportional hazards models used for effect estimation. Results: After propensity score matching, 8,256 patients were included (4,138 per cohort) with well-balanced baseline characteristics. At 1 year, mortality occurred more frequently in the continuous infusion group compared with the IV push followed by infusion group (8.6% vs 7.5%; risk difference 1.1%, p = 0.068). Kaplan–Meier analysis demonstrated a trend toward improved survival with IV push followed by infusion (log-rank p = 0.053). The hazard ratio did not reach statistical significance (HR 1.16, 95% CI 1.00–1.35, p = 0.074), suggesting a modest and potentially time-dependent difference in survival. No statistically significant differences were observed between groups for hospitalization (log-rank p = 0.349), G-CSF use (log-rank p = 0.303), blood transfusion (log-rank p = 0.527), platelet count < 50×10³/µL (log-rank p = 0.286), or platelet count < 10×10³/µL (log-rank p = 0.525). Conclusions: In this large real-world analysis of patients with pancreatic and colon cancer, IV push followed by infusion 5-FU demonstrated comparable safety outcomes and a trend toward improved survival compared with continuous infusion alone. While differences did not reach statistical significance, Kaplan–Meier analyses suggest potential time-dependent survival differences that warrant further investigation. Prospective studies are needed to clarify the optimal 5-FU administration strategy.
Real-world phlebotomy (PHL) burden and treatment gaps in US patients with polycythemia vera: A chart review across physician practice settings.
e18588 Background: Guideline-aligned PV management targets hematocrit (HCT) <45% using PHL and/or cytoreductive therapy, whereas PHL is often used as first-line treatment. Given implementation and PHL burden may vary by clinical setting, this study assessed PHL utilization, interruptions/discontinuations, tolerability, and iron deficiency (ID), overall and by practice setting. Methods: A retrospective chart review abstracted de-identified records of PV patients (≥ 18 years) first diagnosed between 8/2020-7/2023, with ≥ 24 months of follow-up unless deceased. Hematologists/oncologists completed structured case report forms and reported clinical practice setting (community [C], academic [A], mixed [M]). PHL-related burden outcomes included utilization, interruptions/discontinuations with reasons, tolerability, and ID. Poor PHL response/tolerance was defined as physician-documented failure to meet disease/hematologic criteria, procedure-related intolerance, or lack of symptomatic benefit. Hematologic reasons for PHL interruptions/discontinuations include anemia, ID, leukocytosis, thrombocytosis, inadequate HCT control. Results were summarized overall and by practice setting. Results: Among 128 patients with PV (median age 62 years; C: n=60, A: n=50, M: n=18; mean follow-up of 2.7 years), PHL was used in 71% (n=91), alone or with cytoreductive therapy. The most common planned administration frequency for PHL was every 4 weeks (45%; n=41) and planned HCT<45% target in 79% (n=72) (C: 86%, A: 76%). Mean PHL rate was 7.3 per patient-year during non-cytoreductive therapy period (C: 7.5, A: 8.1). PHL interruptions occurred in 18% (n=16) with the first one most often for hematologic reasons (56%). Among 34% (n=44) who discontinued PHL, reasons included hematologic reasons (41%), patient-centered factors (18%), and tolerability/limitations (18%). Poor PHL response/tolerance occurred in 29% (n=26) of PHL-treated patients; mean PHL duration before discontinuation among these patients was 294 days (C: 262, A: 296). After PHL discontinuation for poor response/tolerance, 50% started cytoreductive treatment (hydroxyurea 19%, ruxolitinib 19%, ropeginterferon alfa-2b 12%), and 50% had no further treatment observed. PHL-related ID occurred in 17% of PHL patients (C: 14%, A: 13%). Fatigue was noted in 93% of ID patients during the first ID episode. First ID episode management included pausing PHL (60%) and iron supplementation (40%). Conclusions: PHL remains widely used in routine PV care across clinical practice settings, with high reliance despite available cytoreductive therapy options. Substantial PHL burden and HCT control challenges were observed. These findings highlight a need for more effective, better-tolerated treatments that reduce PHL reliance, achieve and maintain HCT control and support consistent care across settings.
Genetic biomarkers predicting sensitivity to atezolizumab plus bevacizumab in resected hepatocellular carcinoma (HCC): A SNP prediction signature for HCC.
e16014 Background: Current prognostic scoring systems based on clinicopathologic variables are inadequate for identifying patients with hepatocellular carcinoma (HCC) who would benefit from adjuvant therapy with atezolizumab plus bevacizumab following surgery. We developed a single-nucleotide polymorphisms (SNP)-based classifier to improve postoperative risk stratification and prediction of adjuvant therapy benefit for these patients. Methods: In this multicentre study, we developed a 12-SNP classifier derived from blood-based SNP profiles correlated with recurrence-free survival from 453 patients with resected HCC in training set. We assessed intratumour heterogeneity by analysing two regions of paraffin-embedded specimens from the same tumours in the training set. We validated the classifier’s prognostic and predictive performance in an internal testing set (n = 195), two independent external validation sets (n = 238 and n = 308), and TCGA dataset (n = 278). we conducted a nested case-control dataset (n = 388) to evaluate classifier’s ability for identifying patients likely to benefit from atezolizumab plus bevacizumab adjuvant therapy. Additionally, we performed in vitro analyses of the functional relevance of the twelve SNPs. Results: The twelve-SNP-based classifier demonstrated consistent predictive accuracy in blood samples and two different regions of the training set. The twelve-SNP-based classifier precisely predicted recurrence-free survival of patients in training and four validation sets. In the nested case-control analysis, atezolizumab-bevacizumab adjuvant therapy was associated with improved recurrence-free survival (HR 2.120, 1.246-3.599; p = 0.0054) and overall survival (HR 2.870, 1.194-6.900; p = 0.0184) in the high-risk subgroup as defined by the twelve-SNP-based classifier. In vitro analyses showed that the high-risk group, defined by a twelve-SNP classifier, exhibited upregulation of pathways involved in angiogenesis, tumor invasion, metastasis, and tumor immunosuppression compared to low-risk patients. Conclusions: The twelve-SNP classifier is a practical and reliable predictor that can complement the current classification system for identifying patients most likely to benefit from atezolizumab-bevacizumab adjuvant therapy.
Onsite serial monitoring of high grade serous ovarian cancer (HGSOC) mutations in circulating tumor DNA (ctDNA) via droplet digital PCR.
5603 Background: Comprehensive Genomic Profiling (CGP) of tumor and blood samples is increasingly employed for ovarian cancer diagnosis. We used diagnostic CGP sequencing results (523 genes) to identify mutations in HGSOC patients for surveillance of tumor treatment response by an onsite ddPCR assay (Bio-Rad, Hercules, CA). We compared ctDNA mutations to imaging (computed tomography & MRI) and CA125 values across a cohort of HGSOC patients undergoing surgery followed by platinum-based therapy with diverse outcomes. Methods: CGP mutations from matched index tumor, plasma and buffy coat cell samples (TSO-500, Illumina) were used to identify tumor- and patient-specific, coding mutations for interrogation of serial blood samples. Concordance was high for tumor and blood (MED = 97.1%, Q1: 93.3%, Q3: 98.8%) and 15 patients with inclusive longitudinal samples were selected for retrospective analysis of ctDNA samples versus CA-125, imaging and outcomes. Mutation variant allele frequency (VAF) suitable for primer construction ranged in variant allele frequency (VAF) from 0.5 to 24.4% (MED = 2.5%, Q1: 1.2; Q3: 3.8%) in cfDNA. A lower limit of detection (LLOD) of 1 to 2 copies/nanogram cell free DNA (cfDNA) was established using synthetic gene Block targets and FFPE tumor dilutions. Results: There was a significant correlation (r 2 = 0.85, p<0.0001) of initial target cfDNA VAF and numbers of mutation copies detected per nanogram cfDNA. There was no significant correlation of mutation copies with index or serial CA125 values (r 2 =0.11, p=0.38) over the wide range of CA125 values across the patient cohort. However, all patients displayed parallel dynamic changes in multiplex ctDNA mutations and CA125 values with variations in disease status and outcome over 1-3 years. Platinum-sensitive patients with a sustained response to therapy (n=3) based on imaging and CA 125 values displayed rapid elimination of tumor mutations via ddPCR prior to stabilization of “normal” CA125 values. Absence of mutations was further validated by interrogating 5X concentrated patient cfDNA aliqouts. Three patients (platinum-resistant) that initially responded to treatment by imaging and declining CA 125 values never achieved ctDNA mutation levels below the LLOD. These patients subsequently displayed tumor escalation with correlative increases in ctDNA mutation levels and CA125 values. Conclusions: Patient mutation monitoring via ddPCR of blood samples collected and processed onsite, provided rapid, iterative and quantitative results consistent with radiographic imaging and CA 125 assays. In addition, durable remission cases were characterized by rapid loss of mutations detected by ctDNA ddPCR assays prior to imaging and diminution of CA125 values. Low levels of ctDNA mutations above LLOD persisted in responders who otherwise achieved normal CA125 values but later developed disease progression.
Clinical outcomes and resource utilization of sepsis in hospitalized patients with hematologic malignancies: A National Inpatient Sample study.
e18628 Background: Sepsis is a major cause of morbidity and mortality among patients with hematologic malignancies, yet outcome differences across major cancer subtypes remain incompletely characterized. We evaluated clinical outcomes and healthcare utilization among hospitalized sepsis patients with myeloma, leukemia, and lymphoma in the United States. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (2016–2021). Adult hospitalizations with sepsis were identified using ICD-10 diagnosis codes. Hematologic malignancies were classified as myeloma, leukemia, or lymphoma. Outcomes included in-hospital mortality, ICU-level care, mechanical ventilation, dialysis, acute kidney injury, respiratory failure, septic shock, disseminated intravascular coagulation, venous thromboembolism, gastrointestinal bleeding, encephalopathy/delirium, length of stay, and hospitalization charges. Survey-weighted multivariable logistic regression was used for binary outcomes and linear regression for log-transformed length of stay and charges. Models adjusted for age, sex, race, payer, income quartile, hospital region, bed size, teaching status, and year. Results are reported as odds ratios (OR) with 95% confidence intervals (CI) and p values. Results: Among 108,807 sepsis hospitalizations with hematologic malignancy, mortality was 18.7%. Compared with myeloma, leukemia was associated with higher mortality (OR 1.28, 95% CI 1.23–1.34, p<0.001) and lymphoma (OR 1.24, 95% CI 1.19–1.30, p<0.001). For ICU-level care, leukemia (OR 0.85, 95% CI 0.83–0.89, p<0.001) and lymphoma (OR 0.93, 95% CI 0.90–0.97, p<0.001) had lower odds compared with myeloma. For mechanical ventilation, lymphoma had higher odds (OR 1.06, 95% CI 1.01–1.11, p=0.01) while leukemia did not differ significantly. For dialysis, leukemia (OR 0.45, 95% CI 0.42–0.47, p<0.001) and lymphoma (OR 0.46, 95% CI 0.43–0.49, p<0.001) had markedly lower odds compared with myeloma. For complications, leukemia and lymphoma were associated with higher odds of AKI (p<0.001), septic shock (p<0.001), respiratory failure (p<0.001), DIC (p<0.001), VTE (p<0.001), and encephalopathy (p<0.001), while GI bleeding did not differ significantly across subtypes (p=0.85). Increasing age, male sex, larger hospital size, and teaching status were independently associated with worse outcomes. Conclusions: Sepsis outcomes differ substantially by hematologic malignancy subtype. Leukemia and lymphoma carry significantly higher mortality, while myeloma is characterized by a markedly higher burden of dialysis. These malignancy-specific patterns highlight the need for tailored sepsis risk stratification and management strategies.
Prospective evaluation of the psychological impact of multicancer early detection (MCED) blood testing: A smartphone-based patient-reported outcomes study.
10542 Background: Earlier detection may reduce cancer mortality by reducing the number of cancers diagnosed at advanced stages. Prospective data evaluating the emotional impact of MCED testing are limited, particularly when paired with digital engagement tools. Smartphone-based applications offer an opportunity to monitor patient-reported distress in real time and provide scalable support throughout the testing journey. The Falcon registry is a large prospective study evaluating the Exact Sciences MCED test in clinically cancer-free individuals that included evaluation of patient reported outcomes (PRO) using digital tools. Methods: Falcon (NCT06589310) is a multi-site registry enrolling up to 25,000 participants, 50-80 years of age. Participants receive the MCED test annually for 3 years and complete PRO measures, including the Generalized Anxiety Disorder-7 (GAD-7) assessment. The assessment is administered via the myBSWHealth digital platform at baseline (T0), ≤14 days of receiving test results (T1), and at approximately 6 months (T2). Reminders encouraged timely survey completion, and adaptive content was delivered based on distress scores. GAD-7 scores are categorized for clinical interpretation of anxiety: 0-4 minimal, 5-9 mild, 10-14 moderate, 15-21 severe. Clinically meaningful changes (+/->4) in anxiety severity at T0-T1 and T0-T2 were assessed. Results: 8,977/9,204 (97.5%) enrolled participants from 08/2024-01/2026 across the Baylor Scott & White Health System have an activated MyBSWHealth account. 4125 had the potential for 6-month follow-up at data analysis; 2729 (66.1%) completed ≥1 GAD-7 and 2161 (52.4%) had a T0 score. Most participants (94.9%) had minimal to mild anxiety at T0; however, a subset of participants (5.1%) demonstrated moderate to severe anxiety prior to testing. Overall, GAD-7 scores stayed within the minimal anxiety range over time with medians (interquartile ranges) of 1.00 (4.00), 0.00 (3.00) and 1.00 (4.00) at T0, T1 and T2, respectively. Among the 1219 participants who completed the GAD-7 at both T0 and T1, 86% had no clinically meaningful change in anxiety severity, 7% had a decrease, and 6% had an increase. Among the 989 participants who completed the GAD-7 at both T0 and T2, 85% had no change, 7% had a decrease, and 8% had an increase. Conclusions: Digital assessment of anxiety during MCED blood testing gives real-time data on the effects of cancer screening in an average risk population. Despite concerns about the potential for population-based cancer screening to increase anxiety, our preliminary findings suggest low levels of anxiety that remain stable in the majority of participants who completed follow-up assessments after receiving an MCED test result. Additional data for anxiety and distress using the Post-Traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5) will be presented. Clinical trial information: NCT06589310 .
Extracapsular dissection vs superficial parotidectomy for pleomorphic adenomas of parotid gland: An updated systematic review and meta-analysis.
e18086 Background: The optimal surgical approach for small pleomorphic adenomas of the parotid gland is disputed. Extracapsular dissection (ED) is considered less invasive than superficial parotidectomy, but concerns exist regarding oncologic safety and postoperative complication. Methods: A meta-analysis and systematic review were conducted according to PRISMA guidelines. We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, Scopus, and Ovid MEDLINE from 1950 until 2025. We reported comparative studies which included ED and SP. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for recurrence, facial nerve dysfunction, Frey's syndrome, salivary fistula, seroma, and hematoma were calculated using random-effects meta-analyses. Results: Across 8 studies including approximately 1492 patients, no significant difference in recurrence was observed between ED and SP (RR 0.45, 95% CI 0.12–1.72; I² = 35.2%). Extracapsular dissection was associated with a significantly lower risk of transient facial nerve palsy (RR 0.12, 95% CI 0.07–0.20; I² = 0%), while rates of permanent facial nerve palsy were comparable between techniques (RR 0.79, 95% CI 0.40–1.58; I² = 0%). Frey’s syndrome occurred significantly less frequently after ED (RR 0.33, 95% CI 0.15–0.71; I² = 72.2%), as did salivary fistula (RR 0.29, 95% CI 0.10–0.87; I² = 0%). No statistically significant differences were observed for seroma or hematoma. Conclusions: Extracapsular dissection considerably lowers surgical morbidity, especially temporary facial nerve dysfunction and Frey's syndrome, while offering recurrence rates similar to superficial parotidectomy. ED is a safe and efficient surgical substitute for SP in carefully chosen individuals with small, mobile pleomorphic adenomas limited to the superficial lobe. However, the high heterogeneity across studies necessitates more extensive, well-designed trials before definitive conclusions can be drawn.