Browse Articles

Digital prehabilitation and functional performance signals in older adults undergoing hepatobiliary cancer surgery: A pilot study.

12039 Background: Older adults undergoing hepatobiliary cancer surgery often have limited functional reserve and face barriers to accessing structured preoperative conditioning. Technology-enabled, home-based prehabilitation may offer a scalable approach to support surgical readiness while generating early signals of functional change. Methods: Adults aged ≥65 years scheduled for hepatobiliary tumor resection with ≥4 weeks before surgery were enrolled in a multimodal, digitally supported prehabilitation program. The intervention combined wearable-monitored aerobic activity (≥90 minutes/week) with twice-weekly, live video–supervised progressive resistance training delivered by certified exercise trainers. Functional performance was assessed using the 30-second chair stand and arm curl tests, and health status was measured with the SF-12 survey at baseline and preoperative follow-up. Implementation and engagement metrics were captured to contextualize delivery in a geographically dispersed population. Analyses of functional outcomes were exploratory and intended to estimate effect sizes and inform future, adequately powered studies. Results: Twenty-one participants (median age 78 years; range 66–88) completed baseline and preoperative assessments over a median intervention duration of 4.5 weeks. Participants resided a median of 127 km from the cancer center, supporting remote delivery of the intervention. Improvements were observed in lower extremity function (30-second chair stand: 12.0 ± 3.2 to 13.8 ± 4.6 repetitions; p = 0.04) and upper extremity strength (30-second arm curl: 17.7 ± 5.4 to 22.2 ± 7.1 repetitions; p < 0.001). Patient-reported physical and mental health scores demonstrated favorable, though not statistically significant, trends. Engagement with wearable-monitored aerobic activity exceeded recommended weekly targets, and completion of tele-supervised resistance sessions remained high across the intervention period. Conclusions: In this pilot cohort of older adults preparing for hepatobiliary cancer surgery, a digitally supported, home-based prehabilitation model was associated with favorable short-term functional performance signals and high levels of engagement across a geographically dispersed population. These findings are hypothesis-generating and support further evaluation of tele-prehabilitation in trials powered to assess perioperative and clinical outcomes.

The impact of aspirin use on pathological outcomes in locally advanced rectal cancer patients undergoing total neoadjuvant therapy: Real-world data from the Ankara University Colorectal Cancer study group.

e15657 Background: Total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC) has become standard of care, but predictors of pCR and ideal patient selection are not well-defined. There is now increasing evidence that common cardiometabolic agents, including aspirin, may confer an oncological benefit; however, their impact in the TNT setting remains unclear. Methods: We performed a single-center retrospective cohort study of 117 patients with locally advanced rectal adenocarcinoma treated with TNT. Aspirin exposure was defined as continuous use of 100 mg aspirin throughout the treatment course. pCR was defined as ypT0N0 (absence of viable tumor cells in the resected specimen). Downstaging was defined as post-TNT clinical stage regression from stage III to stage II or from stage II to stage I. Associations were assessed using univariable analyses and multivariable logistic regression. Results: pCR was achieved in 40/117 (34.2%) patients. Those with pCR had a higher rate of aspirin use than those without (47.5% vs 22.1%, P = 0.006). Aspirin use remained an independent predictor of pCR in the final multivariable model (adjusted OR 3.25; 95% CI, 1.33–7.96; P = 0.010), and clinical T-stage was also retained (adjusted OR 3.12; 95% CI, 1.14–8.54; P = 0.027). Downstaging was observed in 96/117 patients (82.1%), and aspirin use was a correlate of downstaging on univariable analysis (35.4% vs 9.5%, p = 0.020). In the final multivariable model for downstaging, aspirin demonstrated a strong positive association that did not reach conventional statistical significance (adjusted OR 5.15; 95% CI, 0.92–28.92; P = 0.063). Conclusions: In this TNT-treated LARC cohort, continuous 100 mg aspirin use throughout therapy independently predicted pCR, supporting aspirin as a pragmatic adjunct candidate to intensify treatment response. These data warrant prospective confirmation of aspirin’s role as an adjunct to TNT, particularly for maximizing complete response.

Exploratory biomarker analysis of ociperlimab (OCI) plus tislelizumab (TIS) in patients (pts) with PD-L1–positive non–small cell lung cancer (NSCLC) in AdvanTIG-105.

2571 Background: OCI (anti-TIGIT) plus TIS (anti-PD-1) may enhance antitumor immune responses in advanced solid tumors. We present a retrospective biomarker analysis of pts in AdvanTIG-105 (NCT04047862), a phase 1/1b open-label study of OCI plus TIS for treatment-naïve metastatic non-squamous (NSQ) and squamous (SQ) PD-L1-positive (TC ≥1%) NSCLC. Methods: Pts in cohort 3 (n=46) were treated with 900 mg OCI plus 200 mg TIS. Pts in cohort 10 (n=68) were treated with 450 mg (Arm A), 900 mg (Arm B), or 1800 mg (Arm C) OCI plus 200 mg TIS. Baseline tumor tissue was used to measure PD-L1 and TIGIT expression (SP263 and SP410 IHC assays). Gene expression profiling (GEP) was performed using TrueSeq RNA Access (Illumina); gene signature scores were evaluated with ssGSEA. Progression-free survival (PFS) hazard ratio (HR) was calculated by Cox proportional hazards regression. Results: At Aug 2024 data cutoff, median follow-up was 19.7 months (range: 0.7-41.6 mo) for cohort 3 and 9.8 mo (range: 0.3-21.4 mo) for cohort 10. Baseline characteristics, overall response rate (ORR), and PFS were comparable across cohorts and between biomarker-evaluable and intent-to-treat (ITT) pts. PD-L1 ≥25% vs <25% and TIGIT ≥5% vs <5% subgroups were associated with a trend toward higher ORR and longer PFS, with greater increment in pts with NSQ- vs SQ-NSCLC (Table). PD-L1/TIGIT double high subgroup showed further enriched clinical efficacy in NSCLC (Table). Anti-TIGIT mechanism of action-related GEP signatures (NK cells, Treg, macrophages) were associated with a trend toward longer PFS primarily in pts with NSQ-NSCLC. Conclusions: Pts with NSCLC with PD-L1 ≥25%, TIGIT ≥5%, or PD-L1/TIGIT double high can achieve a trend toward longer PFS and higher ORR than PD-L1 low or TIGIT low subgroups when treated with OCI plus TIS. Longer PFS in PD-L1 ≥25% or TIGIT ≥5% subgroups in NSQ- vs SQ-NSCLC may be associated with biological differences in histology. Confirmation of these results will require prospective evaluation of OCI plus TIS in randomized studies. Clinical trial information: NCT04047862 . Subgroup mPFS (mo) ORR (%) NSCLC Evaluable pts (n=113) 5.5 34.5 PD-L1 ≥25% vs <25%(n=57 vs 56) 6.9 vs 4.2HR 0.58 (95% CI: 0.37-0.9) 47 vs 22 TIGIT ≥5% vs <5%(n=62 vs 48) 6.8 vs 4.1HR 0.64 (95% CI: 0.41-1) 45 vs 19 PD-L1/TIGIT double positive vs other(n=38 vs 72) 8.3 vs 4.2HR 0.53 (95% CI: 0.33-0.86) 55 vs 22 NSQ-NSCLC PD-L1 ≥25% vs <25%(n=35 vs 32) 8.3 vs 4.2HR 0.55 (95% CI: 0.32-0.98) 49 vs 19 TIGIT ≥5% vs <5%(n=36 vs 29) 6.5 vs 4.1HR 0.53 (95% CI: 0.3-0.94) 50 vs 14 SQ-NSCLC PD-L1 ≥25% vs <25%(n=22 vs 24) 5.5 vs 5.3HR 0.63 (95% CI: 0.35-1.29) 45 vs 25 TIGIT ≥5% vs <5%(n=26 vs 19) 5.5 vs 5.5HR 0.93 (95% CI: 0.46-1.87) 38 vs 26

Evaluating the cost per month of response for olutasidenib (OLU) versus ivosidenib (IVO) for patients with relapsed/refractory (R/R) mutant <i>IDH1</i> (m <i>IDH1</i> ) acute myeloid leukemia (AML).

e18504 Background: In the United States (US), the incidence of AML has steadily increased over the past decade and is associated with substantial clinical and economic burden. Evaluating the cost effectiveness of treatment strategies can demonstrate the value of healthcare expenditure and support evidence-based clinical and payer decision-making. Methods: An economic model was developed to compare the cost per month of response for OLU and IVO for patients with R/R m IDH1 AML. Total costs per patient (regardless of response) were calculated for each therapy, including drug acquisition based on monthly drug prices and median treatment duration (4.7 mo OLU vs 4.1 mo IVO), monitoring, and adverse event (AE) management. US payer costs were sourced from public databases (e.g. HCUP). Clinical inputs were sourced from a previously conducted matching-adjusted indirect comparison and included complete remission (CR; 27% OLU vs 25% IVO), CR + CR with partial hematologic recovery (CRh; 29% OLU vs 33% IVO), duration of CR (21.3 mo OLU vs 10.1 mo IVO), duration of CR + CRh (17.5 mo OLU vs 8.2 mo IVO), and restricted mean survival time (15.6 mo OLU vs 12.2 mo IVO). AE frequencies, monitoring requirements, and treatment duration were taken from the FDA labels for each therapy. Sensitivity analyses were conducted to test assumptions regarding the AEs included and the treatment duration for each therapy. Results: Table 1 summarizes the results of the cost per month of response analysis. Monthly drug costs were comparable between therapies; however, median treatment duration was longer for OLU resulting in higher total costs for OLU than for IVO ($172,501 vs $150,680), with drug costs accounting for &gt;96% of the total costs for each treatment. Due to the longer duration of response for OLU, the cost per month of CR was 50% lower for OLU than IVO ($29,995 vs $59,675). Similarly, cost per month of CR + CRh and cost per month of survival were lower for OLU than IVO. The analysis demonstrated that treating one patient with OLU yields an expected 3.23 months of CR benefit versus IVO. The results of the sensitivity analyses were consistent with the base case. Conclusions: This analysis demonstrated that OLU is associated with a lower cost per month of CR and CR + CRh compared with IVO. To further assess the economic value, a full cost-effectiveness analysis capturing all costs and outcomes over a lifetime horizon is warranted. Results of the cost per month of response analysis for OLU vs. IVO for m IDH1 R/R AML. Analysis results per patient OLU (USD) IVO (USD) Total cost per month of CR $29,995 $59,675 Total cost per month of CR + CRh $33,990 $55,684 Total cost per month of survival $11,044 $12,321 Total costs $172,501 $150,680  Total drug costs $168,589 $145,051  Total monitoring costs $206 $872  Total AE costs $3,706 $4,757

PAXG versus (m)FOLFIRINOX as first-Line therapy for unresectable locally advanced or metastatic pancreatic cancer: A real-world, propensity-weighted analysis.

e16401 Background: The PACT-21 (CASSANDRA) study recently demonstrated an event-free survival benefit with PAXG (cisplatin, nab-paclitaxel, capecitabine and gemcitabine) over modified FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) as neoadjuvant regimen in patients (pts) with early-stage pancreatic cancer (PDAC). A head-to-head comparison between these two intensive regimens in pts with unresectable, locally advanced (LAPC) or metastatic (m) PDAC has not yet been reported. Methods: We performed a retrospective analysis comparing consecutive pts with LAPC/mPDAC treated with FOLFIRINOX (or mFOLFIRINOX) or PAXG as first-line therapy between 2020 - 2024 at the Veneto Institute of Oncology (IOV), Padua, Italy. The primary endpoints were progression free survival (PFS) and overall survival (OS), as evaluated from the start of first line, according to the chosen regimen. To account for selection bias, clinical differences between the treatment arms were balanced through inverse probability of treatment weighting (IPTW). Results: A total of 138 patients were included, of whom 62 (45%) treated with mFOLFIRINOX and 76 (55%) with PAXG. Baseline characteristics [age, ECOG performance status, BMI, stage (LAPC vs mPDAC) and Ca19-9 levels] were balanced between the two arms after IPTW (n= 101, Table 1). No significant difference was observed in PFS [median 5.5 (mFOLFIRINOX) vs 7.6 (PAXG) months, adjusted HR 1.02, 95%CI 0.67 - 1.8, p = 0.71) or OS (median 16.0 vs. 12.0 months, adjusted HR 1.12, 95%CI 0.28 - 2.27, p = 0.24). Conclusions: In this real-world cohort, mFOLFIRINOX and PAXG showed comparable efficacy as first-line regimens in pts with LAPC and mPDAC, but larger matched cohorts are needed for validation. To this aim, a multicenter, observational, Italian study using target trial emulation (APOLLO) is currently ongoing. pts characteristics balanced after IPTW. Characteristic Overall N = 101 FOLFIRINOX N = 26 PAXG N = 75 p-value Adjusted standardized mean differences Age (median, IQR) 60 (55.7, 65.2) 61 (56.1, 66.5) 60 (53.1, 64.7) 0.200 -0.15 Stage 0.017 LAPC 22.0 (21.8) 10.0 (38.5) 12.0 (16.0) metastatic 79.0 (78.2) 16.0 (61.5) 63.0 (84.0) 0.09 BMI 0.040 normal 47.0 (46.5) 13.0 (50.0) 34.0 (45.3) -0.06 overweight 29.0 (28.7) 11.0 (42.3) 18.0 (24.0) -0.01 underweight 25.0 (24.8) 2.0 (7.7) 23.0 (30.7) 0.08 CA19-9 (kU/L) 11.0 (7.6, 13.4) 8.8 (5.9, 11.9) 11.5 (8.5, 13.7) 0.006 0.08 Missing 6 2 4 0.00 ECOG PS 0.600 0 63.0 (62.4) 15.0 (57.7) 48.0 (64.0) -0.04 ≥1 38.0 (37.6) 11.0 (42.3) 27.0 (36.0) Abbreviations: BMI: body mass index; ECOG PS: Eastern Cooperative Oncology Group Performance Status; LAPC locally advanced pancreatic disease;

A phase I study of [225Ac]Ac-PSMA-XT, a novel alpha-particle–emitting radioligand therapy, in patients with metastatic castration-resistant prostate cancer.

5063 Background: Targeted alpha therapy (TAT) is an emerging modality for metastatic castration-resistant prostate cancer (mCRPC), offering the potential for precise tumor cell eradication with limited off-target exposure. [225Ac]Ac-PSMA-XT (XT381) is a PSMA-targeted alpha-emitting radiopharmaceutical designed to deliver high linear energy transfer radiation. This single-center, open-label Phase I study (NCT07135102) in China aims to assess the safety, tolerability, and preliminary efficacy of [225Ac]Ac-PSMA-XT in heavily pretreated mCRPC. Methods: Patients with PSMA-positive mCRPC (confirmed by THERP trial criteria, ≥1 lesion with SUV max &gt; 20 on PSMA PET/CT imaging, and all measurable lesions with SUV max &gt; liver SUV mean ) who progressed after ≥1 line of androgen receptor pathway inhibitor were enrolled. A standard "3 + 3" design was used across five dose levels (25, 50, 75, 100 and 125 kBq/kg), with up to 6 cycles administered every 6 weeks. Primary endpoints were safety/tolerability (CTCAE v5.0). Key secondary endpoints inclued PSA50 response (≥50% decline), radiographic progression-free survival (rPFS), objective response rate (ORR) by RECIST 1.1, and disease control rate (DCR). Enrollment has completed through the 75 kBq/kg cohort, the 100 kBq/kg cohort is ongoing. Results: As of December 12, 2025, 12 paitents were dosed (cohorts 25-100 kBq/kg, n = 3 each). All patients received at least one dose of [225Ac]Ac-PSMA-XT. No dose-limiting toxicities have been observed. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 2 patients. The most common TRAEs were xerostomia and grade 1-2 hematologic toxicities, including anemia (55.6%, 5/9), leukopenia (44.4%, 4/9), lymphopenia (22.2%, 2/9), neutropenia (11.1%, 1/9), and thrombocytopenia (11.1%, 1/9). Among 9 evaluable patients (≥6 weeks follow-up), 7 (77.8%) achieved a PSA50 response, and 4 (44.4%) achieved a PSA90 response. The 6-month progression-free survival (PFS) rate was 71.4 (5/7). In 5 patients with RECIST-measurable disease, ORR was 60% (3 partial responses). Overall DCR was 67%. Conclusions: [225Ac]Ac-PSMA-XT shows a favorable and manageable safety profile with no DLTs observed up to 100 kBq/kg. Early efficacy signals are highly encouraging, with deep PSA declines and durable disease control observed in this heavily pretreated mCRPC population. These data support continued dose escalation and further development of this alpha-emitting PSMA-targeted therapy. Clinical trial information: NCT07135102 .

High mortality following unplanned breast cancer hospitalizations.

e23408 Background: The majority of breast cancer care occurs in outpatient settings, and data derived from hospital admissions remain scarce. Methods: A retrospective analysis was perfomed of unplanned admissions to a dedicated breast cancer unit at the National Cancer Institute, Brazil, over 18 months period. Demographic, clinical, and hospitalization characteristics were examined. Causes of admission were classified as disease progression, treatment-related toxicity, or non-oncologic complications. The primary outcome was in-hospital mortality, evaluated using multivariable logistic regression. Results: A total of 731 patients were included, accounting for 1053 unplanned admissions. Self-reported race was Black, White, and Asian in 62.1%, 37.5%, and 0.4% of patients, respectively. Median age at diagnosis was 54 years (IQR, 45.0–63.5). Most patients had advanced disease (stage III: 44.7%; stage IV: 27.3%). Tumor subtypes were hormone receptor–positive/HER2-negative in 59.4%, HER2-positive in 21.6%, and triple-negative in 14.8%. Most patients experienced one unplanned hospitalization (71.7%); 19.7% had two, and 8.6% had three or more. The median length of stay was 8 days (IQR, 5–13.0), and the median time to death was 8 days (IQR, 4–17). Readmissions occurred in 28.3% of patients, including 14.1% within 30 days. Admissions were mainly due to disease progression (63.0%); followed by non-oncologic complications (22.7%), and treatment-related toxicity (14.2%). In-hospital mortality was 39.1% and independent predictors of death were age (OR 1.02, 95% CI 1.00–1.03; p = 0.019), number of hospitalizations (OR 1.51, 95% CI 1.21–1.92; p = 0.001), poor performance status at the last admission (ECOG ≥2; OR 4.92, 95% CI 2.64–9.89; p &lt; 0.001), last admission due to disease progression (OR 2.90, 95% CI 1.88–4.53; p &lt; 0.001). These variables were adjusted by tumor subtype, and ongoing treatment during the last hospitalization. Conclusions: Unplanned admissions to a dedicated breast cancer unit were associated with high in-hospital mortality, particularly among patients with advanced disease, poor performance status, and repeated admissions. Early identification of high-risk patients may facilitate timely integration of palliative care strategies.

Efficacy and safety of third-line treatments in metastatic colorectal cancer: A meta-analysis.

e15623 Background: Metastatic colorectal cancer (mCRC) in the third-line setting has limited options after progression on standard therapies. This systematic review and meta-analysis compares efficacy and safety of trifluridine-tipiracil monotherapy, trifluridine-tipiracil plus bevacizumab, regorafenib, and fruquintinib versus placebo in refractory mCRC. Methods: We conducted a PRISMA-compliant systematic review of phase II/III and phase III randomized trials evaluating third-line treatments for mCRC. Databases included PubMed, Embase, Scopus, and others (up to 2025). Individual patient data (IPD) were reconstructed from digitized Kaplan-Meier curves for pooled estimates of overall survival (OS; primary), progression-free survival (PFS), and grade ≥3 adverse events (AEs). Random-effects models generated hazard ratios (HRs), median survivals (with 95% CIs), and heterogeneity (I²). Results: Data from 3,338 patients across key trials were included: trifluridine-tipiracil (n = 780), trifluridine-tipiracil plus bevacizumab (n = 246), regorafenib (n = 650), fruquintinib (n = 739), placebo (n = 923). Pooled median PFS (95% CI) were: trifluridine-tipiracil 2.09 months (2.00-2.27); trifluridine-tipiracil plus bevacizumab 5.51 months (4.48-5.89); regorafenib 2.11 months (1.92-2.88); fruquintinib 3.71 months (3.67-3.78); placebo 1.83 months (1.78-1.85). Versus placebo, all active arms significantly improved PFS (HRs 0.19-0.43, p &lt; 0.001). Combined TKI arm (regorafenib/fruquintinib) had median PFS 3.53 months (3.35-3.67; HR 0.34, 95% CI 0.30-0.37, p &lt; 0.001). Fruquintinib demonstrated superior PFS versus regorafenib (HR 0.72, 95% CI 0.63-0.82). Pooled median OS (95% CI) were: trifluridine-tipiracil 7.20 months (6.74-7.86); trifluridine-tipiracil plus bevacizumab 10.89 months (9.77-12.06); regorafenib 6.99 months (6.08-8.29); fruquintinib 7.96 months (7.40-8.77); placebo 5.58 months (5.10-6.04). Versus placebo, all active arms significantly improved OS (HRs 0.42-0.72, p &lt; 0.001). Trifluridine-tipiracil plus bevacizumab showed the greatest benefits. Combined TKI arm had median OS 7.66 months (7.22-8.27; HR 0.67, 95% CI 0.60-0.74, p &lt; 0.001). Grade ≥3 AEs included neutropenia/anemia (prominent with trifluridine-tipiracil plus bevacizumab), hypertension (fruquintinib), and hand-foot syndrome (regorafenib). Conclusions: All third-line regimens significantly improve PFS and OS over placebo in refractory mCRC. Trifluridine-tipiracil plus bevacizumab provides the most substantial survival benefit, followed by fruquintinib and regorafenib, with distinct toxicity profiles. These findings, derived from IPD-reconstructed meta-analysis, support trifluridine-tipiracil plus bevacizumab as a preferred option in suitable patients, while highlighting the need for direct head-to-head trials and biomarker-guided selection.

Synthesis methods, network selection, catalytic mechanism, and stability challenges of silver, gold, palladium, nickel, and cobalt nanoparticles: A review

[ ¹⁸ F] Fluoroestradiol PET/CT to guide second-line treatment decision-making in patients with estrogen receptor–positive, HER2-negative advanced breast cancer after progression on first-line aromatase inhibitor and CDK4/6 inhibitor: Primary results of ESTROTIMP.

1077 Background: Despite availability of novel endocrine treatment (ET) options for patients with ER+ HER2- ABC, many patients experience early disease progression under 2 nd line ET-based regimen after AI+CDK4/6i, underscoring a significant rate of endocrine resistance. Timely identification of endocrine-refractory disease at progression under 1 st line is critical to optimize treatment selection and consider non-ET strategies, such as antibody-drug conjugates or chemotherapy. FES PET/CT enables a non-invasive, whole-body assessment of ER expression; absent or heterogeneous FES uptake may indicate ER loss or downregulation, key mechanisms of resistance. Our objective was to evaluate the impact of FES PET/CT on 2 nd line treatment decisions. Methods: In this non-randomized prospective multicenter trial (NCT05486182), patients with ER+ HER2- ABC progressing on 1 st line AI+CDK4/6i underwent standard-of-care FDG PET/CT followed by FES PET/CT. Oncologists prospectively documented therapeutic management plans, before and after FES PET/CT. Patients rated pain and apprehension for FES PET/CT vs. biopsy on a Visual Analogue Scale. Primary endpoint was the proportion of patients with a therapeutic management change after FES PET/CT, and primary objective was to demonstrate that at least 10% of patients had their therapeutic management changed after FES PET/CT (Wald test). Results: Of 153 patients enrolled, 129 were evaluable for the primary endpoint. When compared with FDG PET/CT, FES uptake was classified as “all lesions ER+” in 65 (50%), “mixed ER+/- lesions” in 38 (30%), and “all lesions ER-” in 25 (19%) patients. Therapeutic management was changed based on incorporation of FES PET/CT results in 46/129 patients (35.7%; 96% CI [27.0-44.3], p&lt;0.0001), including treatment type (n=38), diagnostic modalities (n=8), and planned follow-up (n=12). Treatment changes mostly consisted of using chemotherapy instead of ET (n=16), ET instead of chemotherapy (n=3), adding targeted therapy to single agent ET (n=2), changing the targeted therapy paired with ET (n=8), adding radiation therapy to disease sites (n=4), and performing surgery (n=2). Oncologist confidence in FES PET/CT was on average 7.8/10 (Q1-Q3: 7-9). Patients reported significantly lower pain and apprehension for FES PET/CT vs. biopsy (Pain: Mean 0.8 vs 4.5; Apprehension: Mean 1.8 vs 5.2; both p&lt;0.0001). Conclusions: ESTROTIMP shows that, at progression under AI+CDK4/6i, ER expression is completely or partially lost in about half of patients with ER+ HER2- ABC. The trial reached its primary endpoint, demonstrating a clinically meaningful impact on therapeutic management, and supporting the use of FES PET/CT as a standard workup at time of progression under 1 st line AI+CDK4/6i. Clinical trial information: NCT05486182 .

Risk factors associated with early-onset versus later-onset pancreatic cancer: A systematic review and meta-analysis.

e16487 Background: The incidence of early-onset pancreatic cancer (EOPC), predominantly pancreatic ductal adenocarcinoma, is increasing worldwide, yet its risk factor profile remains incompletely understood. While established pancreatic cancer risk factors are well characterized in older populations, it is unclear whether these exposures differentially characterize early-onset versus later-onset disease. We conducted a systematic review and meta-analysis to synthesize available evidence on factors associated with EOPC. Methods: We systematically searched MEDLINE, PubMed, Embase, Scopus, and Cochrane CENTRAL from inception to January 2026 for studies evaluating associations between established pancreatic cancer risk factors and EOPC. Eligible studies included adult patients with pancreatic cancer and compared early-onset disease, as defined by individual studies, with later-onset pancreatic cancer (LOPC). Random-effects meta-analyses pooled odds ratios (ORs) with 95% confidence intervals (CIs); heterogeneity was assessed using I². Results: Nineteen retrospective studies conducted between 1975 and 2022 across 11 countries were included, comprised of 1,486,388 participants. Definitions of EOPC varied across studies, with age thresholds ranging from &lt; 40 to &lt; 60 years, while LOPC was defined using thresholds from &gt; 40 to &gt; 70 years. In pooled case–case analyses comparing EOPC with LOPC, several established risk factors were associated with higher odds of early-onset disease. Alcohol exposure was associated with higher odds of EOPC (5 studies; n = 5,853; pooled OR = 1.40, 95% CI 1.08–1.81; p = 0.011; I² = 0.0%). Diabetes mellitus was similarly associated with lower odds of EOPC (5 studies; n = 4,476; pooled OR = 0.29, 95% CI 0.10–0.80; p = 0.016), with substantial heterogeneity (I² = 90.4%). Male sex was associated with higher odds of EOPC (11 studies; n = 1,461,133; pooled OR = 1.33, 95% CI 1.27–1.39; p &lt; 0.0001; I² = 79.3%), with no evidence of small-study effects (Egger’s test p = 0.065). Smoking was associated with higher odds of EOPC (8 studies; n = 7,932; pooled OR = 1.79, 95% CI 1.32–2.42; p = 0.0209; I² = 57.6%). No statistically significant differences in age at diagnosis were observed for family history of pancreatic cancer, obesity, or pancreatitis. Genetic risk factors were not pooled due to insufficient data. Conclusions: Alcohol use, male sex, and smoking were associated with higher odds of EOPC, while diabetes mellitus was inversely associated with EOPC. These findings suggest that EOPC may represent a distinct etiologic subtype characterized by earlier exposure to certain lifestyle-related risk factors, alongside reduced contribution from cumulative metabolic comorbidity.

Shallow whole-genome sequencing genomic instability score across endometrial cancer subtypes.

e17632 Background: Genomic instability (GI) is a hallmark of cancer. In endometrial cancer (EC) the TCGA molecular classification is prognostic. GI scores (GIS) are widely studied and clinically validated in high grade serous ovarian cancer (HGSOC). The distribution and biological significance of GIS scores in EC remain unclear. We aimed to characterize and explore GI across EC subtypes using shallow whole-genome sequencing. Methods: Up to 96 prospective FFPE EC samples were included, mainly presenting endometrioid (72 %), and serous histologies (14.5 %). The remaining 13.5 % include clear cell and mixed histologies. Stage was categorized as follows: I/II (66.7 %) and III/IV (33.3 %). Cases without primary surgery were excluded from survival analysis. Molecular classification frequencies were CNH (22.9%), CNL (39.6 %), MSI-H (30.2 %) and POLE (7.3 %). Libraries were constructed using HyperPlus kit (Roche diagnostics) and sequenced in a NextSeq 2000 (2x100 paired-end) (Illumina) to achieve a 0.5x coverage. Copy-number (CN) calling and GIS were obtained using QDNA and ShallowHRD. Data were further compared with our own GIS in 60 HGSOC (Romero, I ASCO 2025). All the analyses were performed in Python v3.8 and R v.4.3.11. Results: Basic clinical characteristics and sequencing performance parameters are detailed in table 1. In EC, GIS decreasingly ranged from CNH, CNL, MSI-H to POLE (Table 1) showed statistically significant differences between CNH and the rest of molecular subtypes (p=0.00027). Higher GIS also correlated with serous histology (p=4.6*10 -5 ) and worse PFS (P=0.0062). GIS showed consistently lower values in EC than HGSOC (table 1, p&lt;2*10 -16 ). Among CNH group, highest GIS values (q4) had worse PFS and OS (both p=0.05). CN at chromosomic level were evaluated: amplifications in chromosome 1 and 10 were enriched in MSI-H (p=0.0002) and CNL (p=0.0277) groups respectively. Chromosome 1 CN was correlated with endometrioid histology (p=0.007851). Conclusions: Shallow whole-genome sequencing is a valuable approach to characterize GI across EC populations. However, additional GI parameters should be explored to better understand the nature and possible biological sources of GI in EC. Main clinical and sequencing performance parameters of the EC series. Parameter Median [range] Age at diagnosis (years) 62 [40-89] Progression-Free Survival (PFS, months) 17.33 [0-158.367] Overall Survival (PFS, months) 19.55 [0-186.667] Follow-up (months) 19.55 [0-186.667] Total reads 21740865.5 [1169173-347460678] Whole-genome coverage 0.642 [0.024-10.366] Targeted-sequence coverage 2.111 [1.814-208.054] Genome covered (%) 30.519 [0.012-89.132] Genomic Instability Score (GIS) CNH 5 [0-42] CNL 0 [0-14] MSI-H 0 [0-5] POLE 0 [0-2] CE-GIS 1 [0-42] HGSOC-GIS 20 [1-43]

Comparative survival and long-term gastrointestinal outcomes of ipilimumab/nivolumab vs durvalumab/tremelimumab in unresectable hepatocellular carcinoma: A propensity-matched real-world analysis.

e16221 Background: The FDA approval of Nivolumab plus Ipilimumab (Ipi/Nivo) as a first-line (1L) therapy for unresectable hepatocellular carcinoma (HCC), following the CheckMate 9DW trial, has expanded the dual-immunotherapy landscape alongside Durvalumab plus Tremelimumab (Durva/Trem). However, direct comparative data regarding long-term gastrointestinal (GI) complications in a real-world setting remain scarce. This real-world analysis provides the first comparative assessment of survival and GI outcomes between these two treatment regimens. Methods: Using the TriNetX Global Federated Database, we identified patients aged 18-90 years with unresectable HCC who were treated with 1L Ipi/Nivo (Cohort A) or Durva/Trem (Cohort B). Cohorts were propensity score-matched (1:1) using the nearest-neighbor algorithm for demographics, hepatic comorbidities, and Child's Pugh Score. The primary endpoint was all-cause mortality. Secondary endpoints were the incidence of GI complications, including GI bleed, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), colitis, portal vein thrombosis (PVT), ascites, and jaundice. Outcomes were assessed at 1-, 2-, and 3-year post-index. Kaplan–Meier curves assessed cumulative incidence, while Cox proportional hazards models estimated adjusted hazard ratios (HRs, 95% CI). Results: After matching, 580 patients were included per cohort. Median follow-up was 3 years for Ipi/Nivo and Durva/Trem. Demographics were similar between cohorts (mean age 64, 22% Female, 78% Male, 59% White, 13% Black). There was no significant difference in all-cause mortality between Ipi/Nivo vs Durva/Trem at 1 year [114/574 (19.9%) vs 124/566 (21.9%); HR: 0.807 (0.625-1.041)], 2 years [188/574 (32.7%) vs 164/566 (28.9%); HR: 0.937 (0.760-1.156)], and 3 years [235/574 (40.9%) vs 181/566 (31.9%); HR: 1.025 (0.844-1.245)]. Long term GI outcomes at 3 years showed a 68% reduction in HE [HR: 0.321 (0.222-0.465)], a 34% reduction in PVT [0.661 (0.496-0.880)], and a 32% reduction in ascites [HR: 0.678 (0.550-0.835)], all favoring Ipi/Nivo. No significant differences were observed between Ipi/Nivo and Durva/Trem for GIB, SBP, colitis, and jaundice. Conclusions: In this multicenter, real-world analysis, 1L treatment with Ipi/Nivo and Durva/Trem demonstrated similar survival benefits at 1, 2, and 3 years. However, Ipi/Nivo demonstrated a significantly superior GI safety profile, showing reductions in HE, PVT, and ascites compared to Durva/Trem at 3 years. These results suggest that while both dual-immunotherapy regimens offer similar survival benefits, Ipi/Nivo appear to be associated with a more favorable long-term GI safety profile. Future prospective head-to-head comparisons are warranted to better understand these associations.

Phase angle and urea-to-creatinine ratio in hospitalized cancer patients.

e24056 Background: Malnutrition, impaired cellular integrity, and hypercatabolic states are common in hospitalized cancer patients and are associated with adverse clinical outcomes. Phase angle (PhA), derived from bioelectrical impedance analysis, reflects cellular membrane integrity and physiological resilience, while the urea-to-creatinine ratio (UCR) serves as a surrogate marker of protein catabolism. This study evaluated the association of PhA and UCR measured at hospital admission with length of stay (LOS) and in-hospital mortality in oncology patients. Methods: This prospective observational study included 104 adult oncology inpatients. PhA and body composition parameters were assessed at admission using bioelectrical impedance analysis. Laboratory data were used to calculate UCR. Patients were stratified by median PhA (4.5°) and by elevated UCR. LOS was analyzed as a continuous variable and dichotomized at the 75th percentile. Associations were evaluated using nonparametric tests, correlation analyses, and multivariable logistic regression. Results: Median LOS was 3 days (interquartile range [IQR], 2–7). UCR showed a moderate positive correlation with LOS (r = 0.449; p &lt; 0.001), whereas PhA was not linearly correlated with LOS (r = −0.124; p = 0.226). Patients with lower PhA had reduced muscle mass, lower appendicular muscle index, and higher UCR, indicating poorer nutritional and functional status, although LOS did not differ significantly between PhA strata (p = 0.336). Elevated UCR was associated with prolonged LOS (44.8% vs 15.4%; p = 0.002) and remained the only independent predictor in multivariable analysis (odds ratio [OR], 1.057 per unit increase; p = 0.015). In mortality analyses (8 deaths; 7.8%), PhA as a continuous variable was associated with in-hospital mortality in the initial multivariable model (OR, 0.20 per degree increase; p = 0.031). This association was attenuated after stepwise adjustment, likely due to the limited number of events. Conclusions: UCR measured at hospital admission is independently associated with prolonged hospitalization, reflecting an underlying hypercatabolic phenotype. PhA demonstrates a clinically relevant association with in-hospital mortality, capturing loss of cellular integrity and physiological resilience. The combined assessment of PhA and UCR may provide complementary prognostic information and support early risk stratification in hospitalized cancer patients.

Financial toxicity and head and neck cancer: A systematic review and meta-analysis.

e13629 Background: Patients with head and neck cancer (HNC) may be particularly vulnerable to Financial Toxicity (FT) due to intensive multimodal treatments, new high cost technologies, prolonged recovery, and impaired return to work. We conducted a systematic review and meta-analysis to quantify FT in HNC patients and to examine associated factors across healthcare settings. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Searches were performed in MEDLINE/PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, and LILACS through June 4, 2025. Eligible studies assessing FT in adult patients with HNC using validated patient-reported outcome measures were included. Random-effects meta-analyses were conducted using RStudio software to estimate pooled FT levels, with subgroup analyses. Results: Thirteen studies were included in the systematic review, of which nine were eligible for meta-analysis, comprising a total of 833 patients. Financial toxicity (FT) was most commonly assessed using the FACIT-COST instrument, and 10 of the 13 studies were conducted in High-income countries. The oropharynx was the most frequently reported subsite. The pooled mean COST score was 21.12 (95% CI, 17.78–24.47), which, although classified as mild, indicates a clinically meaningful financial burden. FT may show partial recovery over time and varied across economic and demographic contexts: patients aged &lt; 60 years had worse toxicity (COST 17.93) than older patients, and those from upper-middle and low-income countries experienced greater toxicity (COST 16.03) compared with patients from high-income settings. No consistent differences were observed by sex. Conclusions: FT in HNC is a dynamic and context-dependent phenomenon shaped by individual characteristics and structural conditions. Further studies are needed to clarify the role of gender in FT. Analyses stratified by tumor subsite and type of treatment would be particularly valuable, given the heterogeneity of treatment pathways and functional outcomes across HNC subsites. Longitudinal and context-sensitive FT assessment is essential to inform equitable cancer care and prevent financial burden from undermining treatment benefits.

Investigating transcriptional regulation of cisplatin sensitivity in small cell lung cancer using a functional overexpression screen.

e20162 Background: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy characterized by initial sensitivity to platinum-etoposide chemotherapy, yet patients commonly experience early relapse and the development of drug resistance. In the absence of recurrent actionable genomic alterations, accumulating evidence points to epigenetic dysregulation as a central driver of progression and therapy resistance. SCLC exhibits remarkable molecular heterogeneity and phenotypic plasticity, with recent classification systems defining distinct molecular subtypes based on differential expression of lineage-defining transcription factors. Dynamic changes in subtype identity during treatment have emerged as a potential mechanism of acquired resistance and differential responses to platinum-based chemotherapy. Defining the transcriptional programs that govern these patterns of chemoresistance therefore represents a critical unmet need in SCLC. Methods: To identify transcriptional regulators that confer cisplatin resistance, we performed a pooled, barcoded open reading frame (ORF) overexpression screen in an SCLC cell line model under prolonged cisplatin treatment. This unbiased functional genomics approach revealed selective enrichment of members of the Forkhead box (FOX) family of transcription factors. FOX proteins are an evolutionarily conserved family defined by a characteristic winged helix DNA binding domain that regulate diverse cellular processes, including stress responses, cell cycle control, DNA damage repair, and cell fate determination. Across cancer types, FOX factor dysregulation has been linked to drug resistance through regulation of DNA repair pathways, apoptotic signaling, and pro-survival pathways. Results: We have confirmed that FOX transcription factors emerging from the ORF overexpression screen are mediators of cisplatin resistance. We are systematically characterizing resistance phenotypes across major SCLC molecular subtypes using a comprehensive panel of cell line models. Integrating transcriptomic analysis with functional assays, we will delineate the FOX-driven transcriptional programs and assess whether resistance is mediated through shared or subtype-specific mechanisms, including validation in patient-derived datasets. Conclusions: The impact of these findings could inform SCLC management by identifying transcriptional biomarkers predictive of cisplatin response and early drug resistance. Mechanistic insights into FOX-mediated resistance programs may also support rational combination strategies that pair platinum chemotherapy with targeted inhibition of key resistance pathways.

A phase 1/2 study of BDC-4182, a Claudin 18.2–targeting next-generation immune-stimulating antibody conjugate (ISAC), in patients with advanced gastric and gastroesophageal cancer.

TPS4242 Background: Claudin 18.2 (CLDN18.2) is a transmembrane tight junction protein with expression restricted to the gastric mucosal epithelia where CLDN18.2 protects against paracellular acid leakage and associated gastritis. 1 CLDN18.2 overexpression has been observed in several tumor types, including gastric, esophageal, and pancreatic cancer. 2,3 Loss of cell polarity in these tumors results in CLDN18.2 localization to surfaces that are more readily accessible to biologics and effector cells. This expression pattern makes CLDN18.2 a compelling target for immune-stimulating antibody conjugates (ISACs) that combine the specificity of tumor-targeting antibodies with the potency and durability of immune activation. BDC-4182 is a next-generation ISAC consisting of a CLDN18.2-targeting antibody covalently attached to a novel toll-like receptor (TLR)7/8 agonist via a non-cleavable linker. In preclinical models, systemic delivery of ISACs has been shown to broadly activate the innate and adaptive immune system, leading to complete tumor regression. A BDC-4182 surrogate induced immunologic memory and epitope spreading as evidenced by rejection of tumor cells that no longer express the target antigen (CLDN18.2) following re-challenge. 4,5 Methods: This is a first-in-human Phase 1 dose escalation and Phase 2 expansion study of BDC-4182. Up to 122 patients with advanced gastric and gastroesophageal cancer will be enrolled. To optimize tolerability, BDC-4182 is administered via an intra-patient step-up dosing regimen wherein subjects receive lower initial priming doses prior to the target dose. Primary objectives are to define safety and tolerability and to determine the recommended phase 2 dose (RP2D) of BDC-4182 as a single agent. Secondary objectives will evaluate the preliminary anti-tumor activity of BDC-4182, analyze PK characteristics of BDC-4182, and evaluate the immunogenicity of BDC-4182 as a single agent. Exploratory analyses will also be conducted to explore potential biomarkers in blood and tumor tissue associated with exposure, efficacy, or safety of BDC-4182, and to define CLDN18 expression in tumor tissue. This study is being conducted in Australia, South Korea, and Taiwan. References: 1. Suzuki K, Sentani K, Tanaka H, et al. Cell Mol Gastroenterol Hepatol. 2019;8:119-142. 2. Hong JY, An JY, Lee J, et al. Transl Cancer Res. 2020;9:3367-3374. 3. Chen J, Xu Z, Hu C, et al. Front Oncol. 2023;13:1132319.4. Fu C, Luo A, Liu J, et al. J Immunother Cancer. 2024;12(Suppl 2):Abstract 1052. 5. Kim HK, Monnier J, Fu C, et al. J Immunother Cancer. 2023;11(Suppl 1):Abstract 1147-D. Clinical trial information: NCT06921837 .

Pharmacologic prevention of radiotherapy-induced nausea and vomiting: Network meta-analysis including olanzapine-based regimens.

e24087 Background: Radiotherapy-induced nausea and vomiting (RINV) negatively impacts adherence and quality of life. Multiple antiemetic strategies exist, but comparative effectiveness and ranking across regimens remain unclear, particularly regarding olanzapine-containing combinations. Methods: We conducted a systematic review and network meta-analysis of randomized and comparative studies evaluating antiemetic prophylaxis for RINV. Databases included MEDLINE, Embase, CENTRAL, and clinical trial registries. Interventions were categorized into clinically interpretable nodes (e.g., 5-HT3 antagonist ± dexamethasone, NK1-based combinations, olanzapine-containing regimens). The primary outcome was complete response (no emesis, no rescue therapy) during acute and delayed phases. Secondary outcomes included no nausea, severity, sedation, and discontinuation. Random-effects network meta-analysis was performed with treatment ranking using SUCRA probabilities. Results: Twenty-two studies encompassing 3,145 patients were included. Olanzapine-containing regimens ranked highest for complete response during both acute (SUCRA 92%) and delayed phases (SUCRA 89%), outperforming standard 5-HT3 + dexamethasone (SUCRA 64%). NK1-based triple therapy showed intermediate efficacy (SUCRA 78%). Olanzapine regimens had modest increases in sedation (RR 1.14, 95% CI 1.01–1.29) but no significant differences in discontinuation rates. Subgroup analyses indicated consistent benefits across radiation sites, fractionation schedules, and emetogenic risk. Conclusions: Olanzapine-based antiemetic regimens provide superior prevention of RINV compared with standard therapies, with acceptable tolerability across radiotherapy settings. Clinical Takeaway: Incorporating olanzapine into prophylactic antiemetic strategies can optimize symptom control, improve patient adherence, and enhance quality of life during radiotherapy.

Impact of adjuvant immunotherapy after pathologic complete response to neoadjuvant chemo-immunotherapy in resected stage II–III non–small cell lung cancer.

8062 Background: Perioperative chemo-immunotherapy has recently emerged as a new standard of care for patients with resectable non–small cell lung cancer (NSCLC) following positive results from the CheckMate-77T (NCT04025879) and KEYNOTE-671 (NCT03425643) trials. However, whether patients who achieve a complete pathologic response (pCR) after neoadjuvant chemo-immunotherapy derive additional benefit from subsequent adjuvant immunotherapy remains uncertain due to limited available data (only 58 patients achieved pCR in CheckMate-77T and 72 patients in KEYNOTE-671). The INSIGHT clinical trial (NCT06498635) is an ongoing phase III study designed to address this question; however, the trial is expected to be completed in 2039. Therefore, generating additional data in this area is critically important. We performed a retrospective analysis to assess whether the addition of adjuvant immunotherapy improves overall survival (OS) among patients with stage II–III NSCLC who achieve pCR following neoadjuvant chemo-immunotherapy. Methods: We conducted a retrospective cohort study using the National Cancer Database (NCDB) and included patients with complete follow-up data who were diagnosed between 2018 and 2023 with clinically staged IIA–IIIB NSCLC (cT1–cT4, cN0–cN2, cM0), underwent definitive surgical resection with pCR (ypT0N0M0), and received either neoadjuvant chemo-immunotherapy alone or neoadjuvant chemo-immunotherapy followed by adjuvant immunotherapy (perioperative chemo-immunotherapy). Survival outcomes were analyzed using Kaplan–Meier methods. Results: A total of 1,816 patients were included, of whom 967 (53.2%) were male, with a median age of 65 years (IQR, 60–71). Among these patients, 1,186 (65.3%) received neoadjuvant chemo-immunotherapy alone, and 630 (34.7%) received perioperative therapy. No significant difference in overall survival was observed between the two treatment groups. Median OS was not reached in either group, with a hazard ratio of 1.235 (95% CI, 0.602–2.533; p = 0.565). Conclusions: Among patients with stage II–III NSCLC who achieve pCR following neoadjuvant chemo-immunotherapy and undergo surgical resection, we observed no significant difference in overall survival between those treated with neoadjuvant therapy alone versus perioperative chemo-immunotherapy. These findings suggest that neoadjuvant chemo-immunotherapy alone may be sufficient for patients who achieve pCR, and that adjuvant immunotherapy in this setting may not provide additional survival benefit.

Artificial intelligence vs human-based frameworks for breast cancer molecular biomarker status assessment: A benchmarking analysis from 2500 patients.

e12568 Background: Accurate assessment of breast cancer biomarkers (HR-ER/PR, HER2, Ki-67 index) is essential for prognostication and treatment selection but is limited by inter-observer variability and subjective interpretation. The emergence of HER2-low disease and quantitative thresholds has highlighted limitations in conventional pathology. Artificial Intelligence (AI) has potential to improve consistency and infer molecular phenotypes, however performance relative to human pathologists remains unclear. We conducted a meta-analysis to compare AI and human performance in biomarker assessment. Methods: 670 MEDLINE records evaluating AI-based diagnostic frameworks in breast cancer pathology were identified (PROSPERO ID: CRD420251161868). 9/52 studies directly comparing AI with human pathologists in biomarker assessment were included. Data extracted included study characteristics, biomarkers assessed, AI methodology, comparator performance, and diagnostic metrics, including accuracy, sensitivity, specificity, and area under the curve (AUC). Results: Analysis of nine studies encompassing 2,575 patients reveals that AI-driven biomarker assessment significantly enhances diagnostic precision in breast oncology. Evaluating Hormone Receptors, HER2, and Ki-67, AI frameworks achieved a mean diagnostic accuracy of 92.0% (range: 85.0%–97.8%), consistently outperforming human benchmarks, which yielded a mean accuracy of 82.2% (range: 60.0%–85.3%). Head-to-head comparisons underscored AI's capacity to mitigate inter-observer variability, particularly in HER2 scoring. In this domain, AI achieved 92.1% accuracy against consensus standards, exceeding manual reads (85.3%) and demonstrating superior inter-rater reliability (Cohen's κ = 0.84) compared to human evaluators (0.675). In Ki-67 quantification, AI demonstrated high expert concordance (Spearman's ρ = 0.745-0.861), providing crucial standardisation at clinical thresholds. The relationship between sample size (n = 12 to 1,341) and performance remained remarkably robust; mean accuracy varied by only ±3.5% across heterogeneous cohorts. While AUC reporting was limited to 0.71-0.72, the data confirm that AI frameworks reliably resolve "borderline" cases, such as the HER2 0 vs. 1+ distinction, effectively matching or exceeding traditional pathology standards. Conclusions: AI-based pathology frameworks demonstrate consistently high diagnostic performance for breast cancer molecular biomarker assessment compared with human pathologists. However, heterogeneity in reported metrics and limited use of molecular reference standards highlight the need for standardised validation and reporting frameworks to support clinical translation.