Browse Articles
Discover research articles across all indexed journals
Incidence and disability burden of pancreatic cancer in the United States compared with high socio-demographic index countries: A global analysis, 1990–2023.
e16390 Background: Pancreatic cancer remains one of the most lethal malignancies worldwide, with limited improvements in long-term survival. Although incidence has increased globally, whether trends in mortality and disability burden differ between the United States (US) and other high Socio-demographic Index (SDI) countries is unclear. We compared long-term trends in incidence, mortality, and disability-adjusted life years (DALYs) attributable to pancreatic cancer in the US versus high SDI countries. Methods: We extracted pancreatic cancer–related incidence, mortality, and DALY data from the Global Burden of Disease (GBD) 2023 study. Age-standardized rates (ASRs) per 100,000 population were analyzed from 1990 to 2023 for the US and high SDI countries, stratified by sex. Temporal trends were evaluated using Joinpoint regression to estimate annual percentage changes (APCs) and average annual percentage changes (AAPCs) with 95% confidence intervals (CIs). Statistical significance was defined as P < 0.05. Results: In the US, age-standardized incidence increased from 9.65 per 100,000 in 1990 to 10.53 in 2023, with a significant AAPC of 0.30% (95% CI: 0.25–0.36; P < 0.001). Mortality increased from 8.95 to 9.56 per 100,000 (AAPC: 0.22%; 95% CI: 0.14–0.30; P < 0.001), while DALY rates rose from 203.7 to 211.2 per 100,000 (AAPC: 0.12%; 95% CI: 0.03–0.21; P = 0.009). Sex-stratified analyses demonstrated consistently greater increases among females in the US, including incidence (AAPC: 0.33%; P < 0.001), mortality (AAPC: 0.28%; P < 0.001), and DALYs (AAPC: 0.20%; P < 0.001), whereas trends among males were smaller and frequently nonsignificant.Across high SDI countries, incidence increased from 8.38 to 9.25 per 100,000 (AAPC: 0.30%; 95% CI: 0.19–0.41; P < 0.001), and mortality rose modestly (AAPC: 0.21%; 95% CI: 0.02–0.40; P = 0.028). In contrast, DALY rates remained largely stable over time (AAPC: 0.03%; P = 0.79), despite similar female-predominant incidence increases. Conclusions: From 1990 to 2023, pancreatic cancer incidence and mortality increased in both the US and high SDI countries; however, only the US experienced a sustained rise in disability burden, particularly among women, suggesting increasing survivorship with persistent functional impairment. These findings highlight disparities in disease impact and underscore the need for improved prevention, early detection, and treatment strategies.
Post-operative neurologic outcomes in children with WNT-medulloblastoma.
e22005 Background: WNT-activated medulloblastoma (WNT-MB), the least common molecular subtype of medulloblastoma with a putative brainstem cell of origin, is associated with excellent survival outcomes. Recent clinical trials have focused on decreasing morbidity related to craniospinal irradiation and chemotherapy. Little is known about the role of surgery in contributing to long-term morbidity in this population. Objective: To describe the incidence and persistence of post-operative neurologic morbidity in patients with WNT-MB. Methods: We conducted a retrospective cohort study of pediatric patients with molecularly confirmed WNT-MB who underwent tumor resection and treatment at our institution between 2003–2024. Demographic, clinical, treatment, and neurologic outcome data were extracted. Neurologic findings were assessed pre-operatively, post-operatively prior to the initiation of radiation or chemotherapy, and at last follow-up. Changes in functional neurologic exam domains and posterior fossa syndrome symptoms were analyzed. Results: One hundred sixty-four patients with medulloblastoma who had available molecular subgroup data were identified; 16 (10%) had WNT-activated tumors of whom 13 met study inclusion criteria. The median age at diagnosis was 9 years (range 5-16). Median follow-up time was 8 years (range 0.6-16.1). One patient died early in their treatment course; the remaining 12 patients (92%) were alive at last follow-up. New post-operative neurologic deficits were seen in all 13 patients (100%), most commonly involving loss of independent ambulation (n=12, 92%), motor function (n = 11, 85%), language (n=10, 77%), and cranial nerve abnormalities (n= 8, 62%). Post-operative posterior fossa symptoms were frequent, including dysarthria (n=10, 77%) and ataxia (n=9, 69%). Ten patients (77%) exhibited persistent deficits at last follow-up. Conclusions: Despite excellent overall survival, patients with WNT-MB experience notable post-operative neurologic morbidity. More conservative resection strategies should be considered in future prospective studies for this population.
Discrimination and medical trust among breast cancer outpatients in an urban safety net setting.
e13726 Background: Discrimination in health care is prevalent and linked to poorer patient-reported experiences, including reduced trust and engagement. In breast oncology, trust is central to longitudinal, preference-sensitive care. Prior work has largely focused on health system distrust or conceptual frameworks, with fewer quantitative assessments of how experienced discrimination relates to trust in the treating clinician in outpatient care. We evaluated the association between perceived discrimination and trust in one’s clinician in a safety-net setting and examined whether patterns differed by age, race, and income. Methods: A cross-sectional survey was administered to 100 English- and Spanish-speaking patients receiving breast cancer care at Boston Medical Center. 98 had complete responses. Perceived discrimination was measured using the Everyday Discrimination Scale. Trust was assessed by the Trust in Physician Scale, measuring perceived fairness, communication, and confidence in care. The association between discrimination and trust was estimated by a linear regression with stratified models by age, race, and income. Results: Among 98 participants (mean age 64.5 years [SD 11.45]), Black (n=39) and White (n=39) patients were equally represented. Fifty patients reported annual income <$40,000 and 35 >$40,000. Most had early-stage disease (stage I: 56.1%; stage II: 32.7%). Overall trust scores were high (mean 4.51/5 (SD 0.67)). Reported discrimination levels were low (mean 1.57/5 (SD 0.61)). Higher discrimination was associated with lower trust (β=−0.33; p<0.001). The inverse association was significant among patients <65 but not ≥65. Associations persisted across income strata. Among Black patients, the association was significant whereas for White patients, the association was borderline (Table 1). Conclusions: Perceived discrimination was associated with lower trust in one’s provider. Subgroup patterns suggest discrimination may be particularly consequential for trust among Black and younger individuals, for whom trust erosion may increase vulnerability to disengagement during complex cancer care. Trust is a modifiable determinant of engagement across multimodality treatment. These findings underscore the importance of addressing discrimination and support equity-focused quality improvement efforts to reduce discrimination and strengthen trust, particularly in groups disproportionately affected. Association of discrimination and trust by subgroups. Participants (n) Association (β) p-value 95% confidence interval Overall 98 -0.33 <0.001* [-0.507, -0.163]* Black 39 -0.66 <0.001* [-0.928, -0.387]* White 39 -0.59 0.05* [-1.190, 0.002] Age <65 49 -0.60 <0.001* [-0.617, -0.193]* Age >65 45 -0.17 0.28 [-0.479, 0.141] Income <$40k 50 -0.37 <0.001* [-0.585, -0.146]* Income >$40k 35 -0.64 0.02** [-1.159, -0.121]*
CD40 agonist mitazalimab + mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Final efficacy analysis of the OPTIMIZE-1 study.
e16380 Background: With a 5-year overall survival (OS) rate <5%, PDAC is a major cause of cancer-related mortality. OPTIMIZE-1 is an open-label, single-arm, multicenter phase 1b/2 study to evaluate efficacy and safety of mitazalimab, a human CD40 agonistic IgG1 antibody, in combination with mFFX in untreated patients with mPDAC. The study met its primary endpoint with promising clinical efficacy vs. historical controls resulting in an overall response rate (ORR) of 54.4 % (unconfirmed; 42.1% confirmed) (Van Laethem 2024). We report the final efficacy analysis for patients treated with 450 and 900 µg/kg mitazalimab. Methods: Patients received mitazalimab on day 1 (priming dose), followed by a 2-week regimen starting with mFFX on day 8 and mitazalimab on day 10. The primary endpoint was ORR compared to 30% ORR for FFX alone. Secondary and exploratory endpoints include Duration of Response (DoR), Progression Free Survival (PFS), OS, safety, PK and PD biomarker assessments. Results: Between 2021 and 2025 94 patients with mPDAC were treated with mFFX + mitazalimab (29 at 450 µg/kg and 65 at 900 µg/kg). 22 patients at 450 µg/kg and 57 at 900 µg/kg received ≥2 treatment cycles and were efficacy evaluable. Efficacy outcomes for both dose levels are summarized in Table 1. The 900 µg/kg dose presented higher ORR, DoR, mPFS and mOS and has been selected for Phase 3 development. The primary efficacy analysis comprised 57 evaluable patients treated with 900 µg/kg mitazalimab + mFFX. Median follow up was 36 months and median exposure to treatment was 7 months. Eighteen patients remained treatment for more than 12 months, including seven who continued beyond 24 months. One patient remains on treatment. ORR was 54.4% (42.1% confirmed) and 22 patients achieved stable disease, for a disease control rate of 78.9%. Three patients achieved complete responses (CR) in target lesions, including one with CR in target and non-target lesions. Median DoR was 12.6 months, mPFS was 7.7 months and mOS was 14.9 months (12, 18, 24 and 30-mo OS rates of 58%, 37%, 26% and 21% respectively). Conclusions: Mitazalimab (900 µg/kg) in combination with mFFX continues to demonstrate clinically meaningful survival benefits compared with historical controls. The robust duration of response and encouraging long-term survival—six patients surviving >36 months—support continued development of mitazalimab in a confirmatory Phase 3 study. Clinical trial information: NCT04888312 . 450 µg/kg(N=22) 900 µg/kg(N=57) Median follow up (95% CI) 13.1 (12.1 - 13.9) 36.2 (30.9 - 36.7) ORR n % (90% CI) 5 (22.7) 24 (42.1) DoR (95% CI) NE (3.7 - NE) 12.6 (7.5 - 22.0) mPFS (95% CI) 5.3 (2.0 - 9.2) 7.8 (5.8 - 11.5) mOS (95% CI) 9.7 (5.9 - NE) 14.9 (10.0 - 17.3) 12-month OS, % (95% CI) 42.9 (21.9 - 62.3) 57.8 (43.9 - 69.4) 18-month OS, % (95% CI) 32.1 (11.1 – 55.7) 37.3 (24.8 - 49.9) 24-month OS, % (95% CI) - 26.1 (15.4 - 38.2) 30-month OS, % (95% CI) - 20.5 (11.0 - 32.1)
Burden of pancreatic cancer in the Asia–Pacific region: Incidence, mortality, and modifiable risk attribution across Southeast Asia, East Asia, and Oceania (2000–2023).
e16362 Background: Pancreatic cancer has the highest mortality-to-incidence ratio among gastrointestinal malignancies, with rapidly escalating burden across Asia–Pacific regions. We quantified long-term epidemiologic trends, risk factor attribution, and treatment disparities in Southeast Asia, East Asia, and Oceania. Methods: Using Global Burden of Disease 2023 data, we analyzed pancreatic cancer incidence, mortality, prevalence, and disability-adjusted life years (DALYs) from 2000–2023 across 48 countries and territories (Southeast Asia: 11; East Asia: 6; Oceania: 31). Age-standardized rates and annual percent change (APC) were estimated. Risk attribution was assessed for tobacco use, alcohol consumption, high body-mass index (BMI), diabetes, and dietary factors. Regional treatment access and healthcare expenditure were evaluated. Results: In 2023, pancreatic cancer accounted for 248,600 incident cases and 236,400 deaths across the three regions, yielding a mortality-to-incidence ratio of 0.95 and contributing 5.87 million DALYs. Southeast Asia alone reported 112,300 cases and 106,200 deaths. Total incident cases increased from 143,600 in 2000 to 248,600 in 2023 (APC: 2.1%; 95% CI: 1.8%–2.4%). Age-standardized incidence rates were highest in East Asia (12.6–18.4 per 100,000) compared with Southeast Asia (6.8–11.2 per 100,000), while Oceania demonstrated the highest regional incidence (22.3 per 100,000 in high-income Pacific nations). Mortality-to-incidence ratios exceeded 0.94 in all regions, substantially higher than reported in Western countries (~0.85). Modifiable risk factors accounted for 38.6% of DALYs, driven by tobacco use (14.2%), high BMI (11.8%), diabetes (8.4%), and alcohol consumption (4.2%). Countries with structured diabetes registries and early detection programs (Japan, South Korea) demonstrated a 3.8% higher 5-year survival compared with countries lacking systematic surveillance. Surgical resection rates ranged from 18% in lower-income Southeast Asian countries to 52% in Japan, while per-patient healthcare expenditure varied from $8,200 USD to $47,600 USD across regions. Conclusions: Pancreatic cancer burden in Asia–Pacific regions has risen sharply over the past two decades, with persistently high mortality reflecting late-stage diagnosis and unequal access to curative treatment. Strengthening diabetes surveillance and tobacco control alone could mitigate approximately 23.4% of attributable pancreatic cancer burden, highlighting actionable prevention opportunities in rapidly aging Asian populations.
Trends and disparities in stroke mortality among gastric cancer patients in the United States, 1999–2023.
e16023 Background: Stroke is an underrecognized cause of death among patients with gastric cancer. While overall cancer mortality has improved, less is known about long-term trends and disparities in stroke-related deaths. We examined national patterns in stroke mortality among gastric cancer patients from 1999 to 2023. Methods: U.S. national mortality data were used to calculate age-adjusted mortality rates (AAMR) per 100,000. Joinpoint regression identified temporal changes and estimated annual percent change (APC) and average annual percent change (AAPC). Analyses were stratified by age, sex, race and ethnicity, census region, and urbanization. Results: Between 1999 and 2023, an overall decline in stroke-related mortality was noted with AAMR falling from 167.29 to 111.35 per 100,000 people (AAPC −1.70%, 95% CI −1.9 to −1.5). The decline was greatest between 2002 and 2009 (−5.28% per year) after which it began to plateau until it rose significantly between 2018 and 2021 (APC 6.56%) followed by a decline after 2021 (−3.63%). Older adults had the highest level of stroke related mortality, and therefore the greatest reduction over time (from 756.36 to 479.63) with a total reduction of −36.6% yet they saw a significant increase in mortality between 2018 and 2021. Middle aged patients had little overall improvement and demonstrated the steepest recent increase (APC 8.46%). Younger patients concluded the study period at rates similar to those seen in 1999. Men demonstrated a greater incidence of stroke related mortality compared to women (118.67 vs 104.15 in 2023) with similar trends over time. Racial disparities were present with Black patients showing the highest stroke related mortality in all years (from 242.47 to 156.26) and the largest recent increase (APC 7.37%). Regionally, the South and rural areas carried the highest mortality burden; however, all geographic areas demonstrated an identical increase between 2018 and 2021. Conclusions: Although stroke-related mortality among gastric cancer patients has declined over two decades, recent nationwide increases highlight ongoing vulnerability and persistent disparities. Targeted integration of cardiovascular risk assessment and stroke prevention into gastric cancer care may help sustain progress and reduce inequities. Group (Category A / Category B) AAMR 1999 (A / B) AAMR 2023 (A / B) Recent Surge Trend 2018–2021 (APC) Overall 167.3 111.4 +6.6%* Sex (Male / Female) 181.5 / 156.2 118.7 / 104.2 +6.8%* / +6.2%* Race (NH White / NH Black) 160.4 / 242.5 108.2 / 158.4 +6.3%* / +7.4%* Race (Hispanic / Asian) 140.3 / 153.6 97.7 / 80.0 +6.9%* / +5.2%* Age (Young / Middle) 6.7 / 47.7 6.7 / 42.3 +7.8%* / +8.5%* Age (Old 65+) 756.4 479.6 +6.2%* Region (Northeast / Midwest) 141.5 / 172.0 82.7 / 115.3 +4.4%* / +6.7%* Region (South / West) 177.5 / 171.4 125.7 / 107.2 +6.9%* / +6.2%* An asterisk (*) indicates that the APC is statistically significant (p < 0.05).
Contrast-free virtual enhancement: Multi-modal deep learning synthesis of CECT from pCT and MRI.
e17533 Background: Contrast-enhanced CT (CECT) is routinely used in radiotherapy planning to improve visualization of tumors, lymph nodes, and vascular anatomy for accurate target delineation. However, contrast administration is contraindicated in a subset of patients (e.g., iodine allergy, renal insufficiency), and reliance on non-contrast planning CT (pCT) alone may compromise soft-tissue contrast and introduce contouring uncertainty. We propose a Multi-Modal Generative Synthesis Network (MMGSN) to generate synthetic CECT (sCECT) from pCT and T2-weighted MRI, aiming to provide a non-invasive “virtual enhancement” tool for contouring support without physical contrast injection. Methods: We retrospectively collected 47 pelvic tumor patients treated with radiotherapy, each with paired non-contrast pCT, T2-weighted MRI, and ground-truth CECT. For each patient, the CECT volume used in this study consisted of 40 axial slices (used as the reference for training/evaluation). MMGSN adopts a dual-stream encoder to fuse the geometric fidelity of pCT with the soft-tissue characterization of MRI, followed by a decoder to reconstruct high-fidelity sCECT. Training employed a compound objective combining adversarial loss, weighted L1 loss, and SSIM loss. Performance was evaluated on a held-out test set using PSNR, SSIM, and MSE, and compared against the baseline similarity between pCT and CECT. Results: MMGSN generated sCECT with high quantitative fidelity to ground-truth CECT, achieving a mean PSNR of 43.36 dB and mean SSIM of 0.979 on the test set. Compared with the baseline (pCT vs CECT), MMGSN demonstrated a clear improvement in perceptual/structural similarity (e.g., representative case: SSIM 0.978 vs 0.966 and PSNR 43.088 vs 39.757, respectively). As illustrated in the tri-planar views (axial/coronal/sagittal), sCECT better reproduced contrast-related appearance and improved delineation cues for pelvic vasculature and soft-tissue boundaries relative to pCT, while maintaining geometric consistency required for radiotherapy planning. Conclusions: MMGSN enables high-quality generation of contrast-free sCECT from pCT and MRI in pelvic radiotherapy patients. This approach has the potential to provide clinically useful “virtual enhancement” for target/OAR contouring in patients with contrast contraindications, improving visualization without exposing patients to contrast-related risks and potentially streamlining radiotherapy workflows. Quantitative evaluation: similarity between MMGSN-generated sCECT and ground-truth CECT. MSE SSIM PSNR MMGSN 0.001 0.978 43.088 PCT 0.001 0.966 39.757
The SPIN Score, a simple clinical score to predict pain response following celiac plexus radiosurgery for retroperitoneal cancer pain.
4211 Background: Celiac plexus radiosurgery is a novel non-invasive palliative treatment for pancreatic cancer pain that was recently added to NCCN guidelines. In the pivotal phase 2 trial (NCT03323489; Lancet Oncol 2024;25:1070-79), pain response was 53% (95% CI 42-64%). Prespecified exploratory analysis identified age and BMI as predictors; however, no clinically actionable patient selection tool was developed. We sought to identify additional predictors and create a practical risk stratification score. Methods: Post-hoc analysis of 90 evaluable patients from the phase 2 trial. Pain response was defined per protocol (≥2-point reduction in average pain from baseline to three weeks, on Brief Pain Inventory–Short Form). Candidate baseline predictors were examined by univariate and multivariate logistic regression. Only variables remaining significant in multivariate analysis were included in the final score to ensure independence and avoid overfitting. Internal validation used bootstrap resampling (500 iterations with replacement) to calculate optimism-corrected AUC. Analysis performed using Stata IC/16.1. Results: Univariate analysis identified 4 significant predictors: neurotoxic chemotherapy exposure (OR 5.33, 95% CI 2.13-13.4, p<0.001), baseline pain intensity (OR 1.73, p=0.003), age (OR 1.06, p=0.014), and therapy line (OR 0.65, p=0.04). On multivariate analysis, only neurotoxic exposure (OR 5.1, p=0.009) and baseline pain (OR 1.8, p=0.003) remained independently significant predictors. Age and therapy line lost significance due to collinearity. Dose-response analysis confirmed pain threshold optimization: >5 (61.5% response), >6 (65.8%), >7 (83.3%), >8 (85.7%), with >6 providing optimal discrimination. We created the SPIN (Severe Pain + Intact Nerves) score (0-2 points): baseline Pain >6 (+1), No prior Neurotoxic chemotherapy (+1). Response rates by score: 0 points: 32% (n=31); 1 point: 53% (n=40); 2 points: 89% (n=19). The 2-variable model achieved an apparent AUC=0.716. Following bootstrapping, the optimism-corrected AUC was=0.714. Conclusions: The simple score allows identification of distinct patient subgroups with markedly different probabilities of pain response following celiac plexus radiosurgery. This suggests the intervention should be considered earlier in the disease course, before exposure to neurotoxic agents. External validation is needed prior to clinical implementation. Financial support: Gateway for Cancer Research, The Israel Cancer Association. Clinical trial information: NCT03323489 .
Distinct biological and immune microenvironment features of MSI-H BRAF <sup>V600E</sup> colorectal cancer: Potential for combined PD-1, BRAF, and EGFR inhibition.
e14598 Background: Immune checkpoint inhibitors (ICIs) have shown remarkable efficacy in microsatellite instability-high (MSI-H) colorectal cancer (CRC). However, a substantial subset of patients fails to achieve durable clinical benefit. BRAF mutations—particularly BRAF V600E —are associated with aggressive tumor behavior and poor clinical outcomes, and targeted therapies provide effective treatment options. Epidemiological studies reveal that BRAF mutations frequently coexist with MSI-H status. Nevertheless, the optimal treatment strategy for MSI-H BRAF V600E CRC remains unclear, including whether these patients benefit most from ICIs alone, targeted therapy alone, or combined ICIs and targeted therapy therapy. This study aims to comprehensively characterize the biological properties and tumor immune microenvironment (TME) in MSI-H BRAF V600E CRC, with the goal of improving therapeutic strategies for MSI-H BRAF V600E CRC. Methods: MSI-H BRAF WT and MSI-H BRAF V600E cell lines were generated from the MC38 background. The biological behaviors of cells were evaluated using colony formation, CCK-8, transwell, and Western bloting. Flow cytometry and multiplex immunofluorescence were performed to evaluate immune cell infiltration. RNA sequencing was conducted to explore underlying molecular mechanisms. Therapeutic efficacy was assessed in vivo across four groups: vehicle, anti-PD-1, BRAFi+EGFRi, and anti-PD-1+BRAFi+EGFRi. Results: MSI-H BRAF V600E cells exhibited significantly enhanced malignancy. In vivo, MSI-H BRAF V600E tumors displayed profound alterations in the immune microenvironment, including reduced infiltration of CD8⁺ T cells, along with decreased IFN-γ and GZMB levels. Conversely, M2 macrophages were significantly increased. Multiplex immunofluorescence confirmed reduced CD8⁺ T cell infiltration, and elevated PD-1⁺ cell frequencies. Notably, MSI-H BRAF V600E tumors exhibited an increased proportion of PD-1⁺CD8⁺ T cells and greater spatial separation between CD8⁺ T cells and PD-L1⁺ tumor cells. In vivo, combined PD-1, BRAF, and EGFR inhibition resulted in the strongest tumor suppression in MSI-H BRAF V600E tumors, demonstrating a marked therapeutic advantage, including decreased infiltration of CD8⁺ T cells, along with decreased IL-2 and GZMB levels. Conclusions: MSI-H BRAFV600E CRC exhibits distinct molecular and immunological characteristics. Our findings demonstrate that triple-combination therapy targeting PD-1, BRAF, and EGFR substantially enhances antitumor activity in MSI-H BRAFV600E tumors, outperforming ICIs alone or targeted therapy alone. Collectively, these results support a refined molecular subclassification of MSI-H CRC and provide valuable insights for optimizing personalized immunotherapeutic strategies for CRC patients with MSI-H BRAFV600E.
Phase I study of BL-M14D1, a novel DLL3-directed antibody-drug conjugate (ADC), in patients with locally advanced or metastatic small-cell lung cancer (SCLC), neuroendocrine carcinoma (NEC), and other solid tumors.
3001 Background: BL-M14D1 is a novel DLL3-directed ADC with a potent topoisomerase I inhibitor Ed-04. Results for safety and efficacy from a phase I study on BL-M14D1 in patients with locally advanced or metastatic (LA/M) SCLC and NEC are presented. Methods: Patients who had LA/M solid tumors were enrolled in dose escalation and dose expansion phase and treated with BL-M14D1 at 0.66, 2.0, 3.5, 4.0, 4.5, 5.0, and 6.0mg/kg on Day 1 every 3 weeks (D1 Q3W). SCLC and NEC patients enrolled in dose expansion phase were treated at 4.0 and 4.5mg/kg D1 Q3W. Results: As of Nov 30, 2025, a total of 127 patients were enrolled, including 87 SCLC and 40 NEC. Median prior line of therapy was 2 (range 1-5). Treatment-related AEs (TRAEs) rate was 98.4% and grade≥3 TRAEs rate was 74.0%. The most frequent grade≥3 TRAEs were hematologic, including thrombocytopenia (54.3%), neutropenia (53.5%), leukopenia (46.5%) and anemia (32.3%), which were able to be effectively managed with standard supportive measures including dose reductions, as demonstrated by a low rate (1.6%) of TRAEs leading to discontinuation. One grade 3 ILD and one treatment-related death was reported. Efficacy data at 4.0 and 4.5mg/kg was presented below. BL-M14D1 has demonstrated a promising efficacy with an ORR/cORR of 71.1%/57.8% and mPFS of 7.2 months in heavily pre-treated SCLC. Furthermore, BL-M14D1 has shown encouraging activity in other gastrointestinal and gynecological NECs. Conclusions: BL-M14D1 has demonstrated promising antitumor activity with a tolerable safety profile at dose levels of 4.0mg/kg and 4.5mg/kg D1 Q3W in heavily pretreated patients with SCLC and NEC, supporting further clinical development of BL-M14D1 in SCLC and other less common NECs. Phase III studies assessing BL-M14D1 in SCLC and NEC are in preparation. Clinical trial information: NCT06505824 . SCLC Total * (N=83) SCLC 4.0mg/kg (N=34) SCLC 4.5mg/kg (N=37) NEC † Total * (N=22) NEC † 4.0mg/kg (N=3) NEC † 4.5mg/kg (N=19) Median prior LoT (range) 2 (1-5) 2 (1-3) 2 (1-5) 2 (1-3) 2 (1-2) 2 (1-3) ORR, % (95% CI) 71.1 (60.1, 80.5) 73.5 (55.6, 87.1) 70.3 (53.0, 84.1) 40.9 (20.7, 63.6) 33.3 (0.8, 90.6) 42.1 (20.3, 66.5) cORR, % (95% CI) 57.8 (46.5, 68.6) 61.8 (43.6, 77.8) 56.8 (39.5, 72.9) 27.3 (10.7, 50.2) 33.3 (0.8, 90.6) 26.3 (9.1, 51.2) DCR, % (95% CI) 94.0 (86.5, 98.0) 97.1 (84.7, 99.9) 91.9 (78.1, 98.3) 90.9 (70.8, 98.9) 100 (29.2, 100) 89.5 (66.9, 98.7) mFU for PFS (mo) (95% CI) 6.8 (5.5, 7.2) 7.7 (5.6, 8.2) 4.4 (4.1, 5.5) 3.0 (1.6, 4.3) NR (1.8, NR) 3.0 (1.4, 3.9) mPFS (mo) (95% CI) 7.2 (5.6, 12.7) 7.2 (5.6, NR) 6.9 (4.2, NR) 5.3 (3.9, NR) 4.6 (3.9, 5.3) NR (2.6, NR) † Sites of NEC included cervix, esophagus, stomach and others. * Efficacy analysis included pts at 4.0 and 4.5 mg/kg who received BL-M14D1 and had at least one post-baseline scan.
Study on the mechanisms of alpha-linolenic acid in influencing the efficacy of immunotherapy for lung squamous cell carcinoma.
e20639 Background: Alpha Linolenic acid (ALA) has been shown to correlate with gut microbiota and plays a significant role in tumorigenesis, progression, and treatment. It also exhibits potential in modulating immune responses and promoting anti-tumor immunity. Lung squamous cell carcinoma (LUSC), a subtype of lung cancer, often faces limited immunotherapy efficacy due to an immunosuppressive microenvironment. Therefore, investigating the impact of ALA on the efficacy of LUSC immunotherapy and its underlying mechanisms holds significant clinical importance. Methods: This study begins with clinical samples, categorizing LUSC patients based on their progression-free survival (PFS) post-immunotherapy into a responder group (PFS > 6 months) R group (15 cases) and a non-responder group (PFS ≤ 6 months) NR group (8 cases). Pre-treatment fecal samples were collected for untargeted metabolomic analysis to identify differential gut metabolites affecting the efficacy of immunotherapy in LUSC. A mouse lung cancer model was employed, divided into a solvent control group, an ALA intervention group, a programmed death receptor 1 inhibitor (anti-PD-1) treatment group, and a combination therapy group (ALA + anti-PD-1), to observe changes in tumor volume across different treatment groups. Flow cytometry and immunohistochemistry were used to detect changes in CD8 + T cells within the tumors of different treatment groups. ELISA was utilized to measure the expression levels of interferon-gamma (IFN-γ) in the plasma of mice across different treatment groups. Results: Untargeted metabolomics analysis revealed that the abundance of ALA was significantly increased in the R group compared to the NR group in LUSC patients following immunotherapy. In vivo studies using a mouse model demonstrated that the combination therapy group (ALA + anti-PD-1) exhibited a markedly slower tumor growth rate compared to the anti-PD-1 monotherapy group. Flow cytometry and immunohistochemistry results indicated an increased infiltration of CD8 + T cells in the tumor tissues of the combination therapy group (ALA + anti-PD-1) relative to the anti-PD-1 monotherapy group. Concurrently, ELISA results showed an elevated proportion of IFN-γ in the peripheral blood, suggesting a systemic immunomodulatory effect of the gut metabolite ALA. Conclusions: Our findings suggest that the efficacy of immunotherapy in LUSC may be associated with the intestinal levels of ALA. ALA enhances the function of CD8 + T cells by increasing their tumor infiltration and elevating the levels of the cytokine IFN-γ, thereby demonstrating a synergistic effect when combined with anti-PD-1 therapy in improving the efficacy of LUSC immunotherapy.
A phase 2 study to assess the safety and efficacy of bomedemstat (IMG-7289) in combination with momelotinib in patients with myelofibrosis.
TPS6605 Background: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, cytopenias, inflammatory symptoms, and progressive marrow fibrosis. Momelotinib, a JAK1/JAK2 and ACVR1 inhibitor, improves splenomegaly and anemia; however, a substantial proportion of patients experience inadequate spleen, symptom, or hematologic responses. Bomedemstat (IMG-7289), an oral irreversible inhibitor of lysine-specific demethylase 1 (LSD1), has demonstrated disease-modifying activity in MF, including effects on megakaryopoiesis, inflammatory signaling, and fibrosis. Preclinical and clinical data support complementary mechanisms between JAK inhibition and LSD1 inhibition. Methods: This is an open-label, single-arm, multicenter phase 2 study enrolling approximately 50–60 adults with primary or secondary MF (post–polycythemia vera or post–essential thrombocythemia) with intermediate-2 or high-risk disease. All patients receive momelotinib 200 mg orally once daily. After 12 weeks of momelotinib monotherapy, patients with protocol-defined suboptimal response—based on spleen volume reduction, symptom improvement, hematologic parameters, or transfusion requirements—initiate combination therapy with bomedemstat 50 mg orally once daily, with dose titration per MF-specific guidelines, through week 24. Two cohorts are included: (1) patients previously treated with momelotinib who demonstrate suboptimal response after ≥12 weeks of therapy, and (2) patients with baseline cytopenias initiating momelotinib within the study who demonstrate suboptimal response at week 12. The primary endpoint is the proportion of patients achieving ≥35% spleen volume reduction at week 24 by MRI or CT. Secondary endpoints include ≥50% reduction in total symptom score, changes in symptom burden, transfusion independence, hematologic responses, overall response rate, duration of response, progression-free survival, overall survival, and safety and tolerability. Exploratory endpoints include molecular and biomarker analyses assessing changes in driver mutation allele burden, inflammatory cytokines, and markers of differentiation and fibrosis. The study will run in 5 Countries (UK, France, Spain, Dubai, USA), for a total of 20 Sites. Enrollment expected to start in September 2026. Clinical trial information: ISRCTN98283910.
The impact of different formulations and dosing intervals of goserelin on testosterone suppression in patients with prostate cancer: A real-world observational study.
e17093 Background: The purpose of androgen deprivation therapy (ADT) is to reduce and stabilise serum testosterone. However, dosing nonadherence for various reasons may lead to insufficient testosterone suppression, thus affecting the outcome of patients with prostate cancer. The present study evaluated the differences in testosterone control by different dosage forms and dosing intervals of goserelin. Methods: This analysis was conducted in real-world clinics, focusing on patients diagnosed with prostate cancer who had initiated goserelin acetate extended-release microspheres for injection dosed every 4 weeks (dosing intervals of 28, 56, and 84 days) and goserelin acetate sustained-release depot dosed every 12 weeks (dosing intervals of 84, 168, and 252 days). We retrospectively analysed the testosterone testing intervals and results from a minimum of three testosterone tests collected within six months following the initial goserelin dosage. Results: The present study comprised a total of 60 prostate cancer patients, with 30 patients in each group. The study found no statistically significant difference in the efficacy of the two goserelin drugs in terms of testosterone control (≤50ng/dl and ≤20ng/dl). However, in real-world clinical settings, there are unavoidable delays in medication administration, the rate of delayed injections was lower in patients applying the 4-week dosage form than the 12-week dosage form (P = 0.035, χ2 = 4.444). The mean and dispersion of delayed injection days were found to be greater in patients in the implant 12-week dosage form group. The proportion of delayed medication for a period exceeding one week is even higher (56% vs. 10%). Additionally, within the same group, a trend towards a correlation between the level of testosterone de-escalation and delayed injection days was identified. The chi-square test revealed a statistically significant difference in the proportion of punctual or delayed injections for profound testosterone lowering (≤20ng/dl) (P = 0.004, χ2 = 10.060). The baseline patient profile and key findings can be found in Table 1. Conclusions: The study investigated the impact of varying formulation types and delayed goserelin injection on testosterone control. It is imperative to allocate greater resources to the development of effective follow-up strategies and to enhance the compliance of prostate cancer patients with androgen deprivation therapy. Goserelin acetate extended-release microspheres for injection dosed every 4 weeks Goserelin acetate sustained-release depot dosed every 12 weeks N 30 30 Median age (years) 72.5(50-91) 73.0(50-90) Median treatment cycles 7(3-12) 4(3-5) Median days of delayed injections 4(2-9) 14(7-35) Delayed injection rate %(n) 46.7%(14/30) 73.3%(22/30) testosterone ≤50ng/dl % 100% 100% testosterone ≤20ng/dl %(n) 66.7%(20/30) 60.0%(18/30)
AI-derived CD8⁺ cytotoxic T-cell immune signatures from baseline H&E images to predict immunotherapy benefit over chemotherapy in non–small cell lung cancer: Blinded validation in CheckMate-227 (CM227).
8534 Background: Immunotherapy (IO) has transformed treatment for non–small cell lung cancer (NSCLC), but not all patients (pts) benefit, underscoring the need for predictive biomarkers to guide IO versus chemotherapy (Ch). CheckMate 227 (CM227; NCT02477826) showed a survival benefit of first-line nivolumab plus ipilimumab (nivo+ipi) over Ch in stage IV NSCLC. CD8⁺ T cells are key mediators of antitumor immunity and are associated with IO benefit. We developed an artificial intelligence (AI)–based pipeline (VIGOR-CD8) that predicts spatial CD8⁺ immune signatures from routine baseline H&E whole-slide images using histopathology foundation model embeddings (H-Optimus-0) and virtual gene expression modeling (HE2Gene), and evaluated its ability to identify pts who do and do not derive IO benefit over Ch in CM227. Methods: 1,598 pts with advanced NSCLC were analyzed, including multi-institutional retrospective cohorts (n = 487; 65 for patch-level CD8⁺ prediction and overall survival (OS), 422 for patient-level OS) and a blinded CM227 validation subset (n = 1,111). For orthogonal validation, 86,470 H&E patches were co-registered with quantitative CD8⁺ immunofluorescence. H-Optimus-0 and HE2Gene immune-related embeddings were used to train a random forest classifier to predict patch-level CD8⁺ probability. Patch-level probabilities were aggregated into a patient-level CD8⁺ signature and dichotomized into biomarker-positive (B⁺) and biomarker-negative (B⁻) groups by the training-set median. Cox models assessed the impact of VIGOR-CD8 on OS. In CM227, prognostic and predictive utility were evaluated using treatment-specific analyses; investigators were blinded to outcomes, and models were trained on independent, non-overlapping cohorts. Results: VIGOR-CD8 was associated with longer OS in the testing cohort (n = 422; HR 0.68, 95% CI 0.53–0.87, p = 0.00163) and CM227 (n = 1,111; HR 0.8, 95% CI 0.67–0.96, p = 0.016), irrespective of treatment type and PD-L1 expression. Among pts with evaluable PD-L1, B⁺ pts treated with nivo+ipi had superior OS versus Ch (n = 617; HR 0.72, 95% CI 0.58–0.90, p = 0.003), while in B⁻ pts there was no significant OS difference between treatment arms (n = 130; HR 1.18, 95% CI 0.79–1.75, p = 0.436), supporting a predictive rather than purely prognostic role for VIGOR-CD8. Conclusions: An AI-derived CD8⁺ immune signature from routine baseline H&E slides was associated with favorable OS in CM227 and predicted differential benefit from nivo+ipi versus Ch. VIGOR-CD8 may help identify advanced NSCLC pts most likely to benefit from first-line dual IO, but further validation in independent and prospective trials is warranted.
Interventions to improve hope and psychosocial outcomes in patients with advanced solid tumor cancer: A systematic review and meta-analysis.
e24100 Background: Hope is critical for individuals facing cancer, impacting quality of life, emotional well-being, and engagement with treatment. Interventions aimed at fostering hope may buffer against negative experiences and improve coping. Although a growing body of research has investigated psychological and spiritual approaches to support hope, the strength and consistency of evidence across diverse cancer populations remains unexplored. This systematic review synthesizes data on interventions designed to improve hope among adults with malignancy and evaluates their effects compared with standard care. Methods: Major databases including Scopus, PubMed, Embase, and CENTRAL were searched through July 17, 2025. Inclusion criteria were adults with any solid-tumor malignancy undergoing an intervention designed to improve hope. Outcomes included hope measured by a validated hope-scale, anxiety, depression, and perceptions of treatment. English language randomized controlled trials, prospective or retrospective comparative studies, single-arm pre–post intervention studies were included. Abstracts and full texts were doubly screened; included manuscripts were doubly extracted and data extracted and summarized. Risk of bias assessment was performed using ROB2 and ROBINS-I. A random-effects meta-analysis was conducted to pool standardized mean differences comparing pre- and post- intervention HHI scores across studies. Results: 42,111 abstracts screened, 46 full texts screened, and 21 studies included representing 1,659 patients with various types of solid-tumor cancer, including breast, pancreatic, lung, colorectal, stomach, head/neck, urologic, gynecologic, prostate, hepatic and other non-specified advanced malignancy. Hope interventions included psychosocial interventions, nursing interventions, and mindfulness/spiritual interventions. Participants in the intervention groups demonstrated a significantly higher mean increase of 0.51 [0.22, 0.80] (p = 0.0) on the Herth Hope Index compared with a non-significant increase of 0.06 [-0.07, 0.19] in the control groups. Across studies, outcomes consistently demonstrated improvements in hope levels for patients undergoing hope-based interventions. Conclusions: This systematic review and meta-analysis illustrate that hope-focused interventions are associated with consistent improvement in hope and psychosocial outcomes for patients with malignancy compared with routine care.
The impact of human papillomavirus (HPV) vaccination on cervical cancer risk reduction in the US.
e22531 Background: High-risk human papillomavirus (HPV) causes most cervical cancers. Both HPV vaccination and cancer screening reduce cervical cancer risk. However, screening rates by HPV vaccination status are not reported in the US, reducing the ability to assess population-level protection against cervical cancer. Using nationally representative data, we modeled how population-level cervical cancer risk changes as screening rates vary among vaccinated and unvaccinated females. Methods: Female respondents aged 21-39 years who self-reported cervical screening and HPV vaccination status in the 2019 National Health Interview Survey (NHIS) were included. Those aged 40 years or over in 2019 were excluded due to eligibility guidelines based on HPV vaccine introduction in 2006. Up-to-date cervical screening was defined as a Pap test within the past three years for ages 21-39 years or any HPV testing within five years for ages 30-39 years. Individuals receiving at least one dose of the HPV vaccine were considered vaccinated. Using estimates from US-focused modeling studies for the reduction in cervical cancer risk from vaccination (85%) and screening (70%), we calculated case scenarios to demonstrate how vaccination status changes the effect of cervical screening on population-level risk reduction of cervical cancer. Results: In the 2019 NHIS survey, 4,000 female respondents aged 21-39 years reported cervical screening attendance and HPV vaccination status. Up-to-date screening in ages 21-25 (63.9%) was lower compared to other age groups (26-29 years: 81.5%; 30-34 years: 85.6%; 35-39 years: 82.1%). However, reduction in cervical cancer risk in ages 21-25 was 68.6% relative to an unvaccinated and unscreened population, which was similar to risk reductions in all other age groups (26-29 years: 73.1%; 30-34 years: 67.7%; 35-39 years: 62.1%), a benefit likely due to their higher level of vaccination (56.7% vs. 26-29 years: 49.9%; 30-34 years: 26.4%; 35-39 years: 14%). Conclusions: This study demonstrates the importance of considering vaccination status when evaluating the population-level impact of cervical screening uptake on cervical cancer risk. Efforts to reduce the burden of cervical cancer should continue to include both vaccination and screening. Including vaccination status in national surveillance datasets would help identify and target interventions within communities at higher risk.
Comparative analysis of tirzepatide versus metformin and insulin in type 2 diabetes patients across the 13 most common cancers.
10508 Background: Emerging glucose-lowering therapies may influence cancer risk in patients with type 2 diabetes mellitus (T2DM). While several GLP-1 receptor agonists have been evaluated, data on tirzepatide, a dual GLP-1/GIP agonist with established cardiometabolic benefits, remain limited. We assessed the comparative risk of incident cancers and all-cause mortality among T2DM patients treated with tirzepatide versus metformin or insulin. Methods: We conducted a retrospective cohort study using TriNetX, a U.S.-based federated electronic health record network. Adults with T2DM initiating tirzepatide, metformin, or insulin between February 28, 2020 and February 28, 2025, without prior cancer, were included. Propensity score matching (1:1, greedy nearest-neighbor) balanced demographics, BMI, HbA1c, diabetes duration, and comorbidities. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the 13 most common incident cancers and all-cause mortality. Results: After 1:1 propensity score matching, baseline demographic, metabolic, diabetes-related, psychosocial, and medication characteristics were well balanced between groups, with minimal residual differences across age, sex, race/ethnicity, HbA1c, obesity severity, diabetes complications, and concomitant glucose-lowering therapies. In the tirzepatide versus insulin comparison, tirzepatide use was associated with significantly lower risks of multiple solid and hematologic malignancies, including lung, pancreatic, liver, colorectal, kidney, and endometrial cancers, as well as non-Hodgkin lymphoma (all log-rank p < 0.01), with no significant differences observed for prostate, thyroid, melanoma, bladder cancer, or leukemia. In the tirzepatide versus metformin comparison, tirzepatide was associated with significantly lower risks of lung cancer (HR 0.086, 95% CI 0.020-0.373; p < 0.001), pancreatic cancer (HR 0.124, 95% CI 0.015-1.039; p = 0.022), and breast cancer (HR 0.462, 95% CI 0.254-0.840; p = 0.009), while risks of other malignancies were not significantly different between groups. Across both matched cohorts, tirzepatide was consistently associated with markedly lower all-cause mortality compared with insulin and metformin, with absolute risk reductions of 4.8% and 0.6%, respectively (both p < 0.001). Conclusions: Among patients with type 2 diabetes, tirzepatide was associated with consistently lower all-cause mortality and reduced incidence of multiple cancers compared with insulin and metformin in a large, propensity-matched real-world analysis. These findings highlight tirzepatide as a glucose-lowering therapy with a potentially favorable oncologic risk profile, warranting prospective validation and mechanistic investigation.
Incremental prognostic value of an AI-derived histology signature beyond the 21-gene recurrence score: A prospective-retrospective validation in TAILORx.
554 Background: The 21-gene recurrence score (RS) is a foundational tool for risk-stratifying HR+/HER2- early breast cancer (EBC). However, clinical outcomes vary within RS categories. RlapsRisk BC (RR), an AI pathology-based test, integrates features from H&E-stained whole-slide images with clinical data (age, tumor size, nodal status) and was developed using 7 retrospective cohorts totaling 6,039 patients. We evaluated the clinical validity of RR and its histology-only component (RR-H) beyond RS and standard clinicopathologic factors. Methods: The clinical validity of RR was established through a validation program of 4 cohorts and over 8,521 patients across diverse geographic regions and laboratory settings. This included 3 international cohorts (n=933) and a prospective-retrospective analysis of the TAILORx trial, where RR-H was evaluable in 7,585 (97.5% of analyzable patients). The primary endpoint was distant recurrence-free interval (DRFI). In TAILORX, we assessed the additive value of the RR-H score to a base model (composed of age, tumor size, histological grade and RS) using Cox proportional hazards models and C-index comparison. Results: Across international validation cohorts (median follow-up 7.5 years, 9,8% DRFI events), RR successfully stratified patients (HR=4.91; 95% CI: 3.13-7.71; p < 0.00001), and identified a low-risk population with a 97.5% (95% CI: 95.8%-98.5%) 5-year DRFI rate. In the TAILORx population (n=7,584), the RR-H score was a highly significant independent predictor of DRFI. Incorporating RR-H as a continuous variable to the base model (including RS) significantly increased the C-index from 0.6730 to 0.7007 (p < 0.0001). The estimated HR for a 1-point difference in RR-H was 1.108 (95% CI: 1.078-1.138; p < 0.0001). When analyzed by quartiles, patients in the highest risk group (Q4) exhibited a significantly higher risk of distant recurrence compared to the lowest risk group (Q1) HR= 2.656 (95% CI: 2.003-3.522). Concordance analysis revealed that RR-H is independent of stromal TILs (R 2 =0.01). While RR-H correlated with increasing histological grade, substantial distribution overlap confirms intra-grade prognostic granularity. Furthermore, RR-H distributions were consistent across ILC and non-NLC. Conclusions: RR demonstrated robust and reproducible prognostic value across 8520 patients from diverse populations and settings establishing its clinical validity. Additional findings on TAILORx demonstrate that RR-H provides significant, independent prognostic value that complements existing prognostic tools (including genomic assays and clinicopathological factors), suggesting that integrating AI-pathology can refine precision risk assessment, and thus optimize adjuvant treatment in HR+ HER2- EBC.
Circulating tumor DNA monitoring for early detection of disease recurrence in bone/soft tissue sarcoma.
11540 Background: Circulating tumor DNA (ctDNA) is a powerful, minimally invasive biomarker of treatment response and patient prognosis in many tumors. Here, we assessed the clinical performance of the Signatera assay in patients with bone and soft tissue sarcomas in assessing molecular residual disease (MRD). Methods: We performed a retrospective analysis of patients at our institution who underwent commercial ctDNA testing using the Signatera mPCR-NGS assays after curative intent resection of their primary tumor. Patients with oligometastatic disease were included if they also underwent resection of oligometastatic sites and did not have any evidence of residual disease. Additional inclusion criteria included three or more ctDNA draws in the MRD setting with at least one ctDNA blood collection within one of year of completing curative intent procedures and at least 6 months of clinical follow up after surgery. ctDNA positivity was defined as any detectable level of ctDNA at any time point in the patient’s treatment course after surgery. Results: We reviewed 305 patients who underwent Signatera ctDNA collection; 107 patients met the inclusion criteria for this study. The most common reason for not meeting inclusion criteria was advanced/unresectable disease (n = 168). The included 107 patients underwent over 1300 plasma ctDNA assessments in the MRD setting (average 12 ctDNA assessments per patient) between September 2019 and November 2025. For the overall cohort, sensitivity was 75% (36/48); specificity was 100% (36/36). One patient with angiosarcoma had ctDNA detected one month prior to data cut-off and was awaiting re-staging imaging. The largest represented histologies were leiomyosarcoma (n = 42) and undifferentiated pleomorphic sarcoma and related tumors (n = 22); sensitivity were 85% (22/26) and 57% (4/7), respectively. The median duration of follow-up after surgery was 41 months (range 1.6 to 79 months). Of the 48 patients with disease recurrence, 27 (60%) developed local disease recurrence only, 17 (38%) developed distant recurrence only, and 4 (9%) developed local and distant disease recurrence. The most common site of distant disease recurrence was in the lungs (n = 16). Sensitivity was lowest in the patients who developed disease recurrence isolated to the lungs (42%, 5 out of 12) compared to patients who developed disease recurrence not confined to the lungs (89%, 32 out of 36). Of the patients who had ctDNA detected at time of recurrence, 47% (17/36) demonstrated ctDNA positivity before detection of recurrence on imaging with an average lead time of 20 days. Conclusions: In a cohort of over 100 sarcoma patients with over 1300 plasma samples collected in the MRD setting, Signatera ctDNA assay demonstrated a clinical sensitivity of 75% and specificity of 100% for relapse detection with the highest sensitivity in leiomyosarcoma (85%) and when disease recurrence was not confined to the lungs (89%).
Maintenance therapy and treatment holiday in patients with unresectable/locally advanced/metastatic pancreatic cancer who did not progress after at least 2 months of first-line chemotherapy.
e16372 Background: Although the overall prognosis of metastatic pancreatic cancer remains poor, according to SEER database there has been a gradual improvement in 5-year survival rate over the past decade plus, from 5% in 2000 to 13% as of 2016. This gradual yet significant improvement in long-term survival is in part attributable to improved efficacy of first line systemic therapy in the metastatic setting. With continued advances in systemic therapy, there will likely be an increasing number of long-term survivors who will be eligible for maintenance therapy or treatment holiday. Currently, there is limited data regarding efficacy and safety of maintenance therapy and treatment holiday in pancreatic cancer compared to other solid malignancies. Therefore, there is a growing area of unmet need in devising an optimal, safe treatment strategy for patients with advanced pancreatic cancer who had an initial favorable response to first line therapy. Methods: This study is a retrospective review of 274 patients with unresectable or metastatic pancreatic cancer (including de novo metastatic disease and progression from localized disease to metastatic disease) who did not undergo curative resection or had recurrence after resection. Patients received systemic therapy in the advanced setting for at least 2 months within Tufts Medicine network from 1/2014 to 5/2025. The data collected included demographic data (age, sex, BMI, ECOG), stage at diagnosis, number and location of metastatic sites, chemotherapy regimens, and disease outcomes (PFS1, OS, PFS2, DDC, adverse effects) which were compared across 3 different treatment strategy groups after at least 2 months of 1 st line chemo (group 1: continuation of 1 st line; group 2: maintenance; group 3: treatment holiday). Results: A total of 59 patients met the inclusion criteria (group 1: n = 36, group 2: n = 17, group 3: n = 6). Median age was 65 and there were 64% males. Median duration of 1 st line therapy was 5.3, 5.1, and 3 months, respectively. Group 2 led to statistically significant improvement in OS (18 mo vs 13.1 mo, HR 0.31), PFS1 (12.2 mo vs 6.5 mo, HR 0.16), and DDC (13.9 mo vs 9.5 mo, HR 0.20) compared to group 1, adjusted for age, sex, and BMI, but there was no statistically significant difference in PFS2. There was no statistically significant difference between group 1 and group 3 in terms of survival outcomes. Safety data showed diarrhea and fatigue were the most common adverse events during maintenance therapy, and all but 1 were grade 1-2. Conclusions: Maintenance therapy led to statistically significant improvement in PFS1 and OS compared to continuation of 1 st line therapy after at least 2 months, while having a favorable safety profile. Limitations include small sample size especially in treatment holiday group. Maintenance therapy should be studied in prospective trials.