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Efficacy and safety of second or further line KC1036 in patients with thymoma and thymic carcinoma: A multicenter, single-arm phase II trial.
8116 Background: Patients with advanced or recurrent thymoma or thymic carcinoma (T/TC) progressing after platinum-based chemotherapy have an unmet therapeutic need. This report assessed the clinical efficacy and safety of KC1036, a novel multi-kinase inhibitor of AXL, VEGFR2, and FLT3, in the treatment of T/TC. Methods: This open-label, multicenter, single-arm, phase II study enrolled patients with advanced or recurrent T/TC who had progressed on at least one prior line of chemotherapy. Eligible participants were required to have measurable disease according to RECIST v1.1 and an ECOG performance status of 0 or 1. KC1036 was administered orally at 60 mg QD, every 21 days as a cycle, until disease progression, death or intolerable toxicities. The primary endpoint was investigator-assessed objective response rate (ORR). Results: Between February 23, 2023 and January 4, 2024, 6 thymoma (T) and 25 thymic carcinoma (TC) patients were enrolled; all had distant metastases. Median age was 47.5 years (range, 34-71) for T and 57.0 years (37-73) for TC. Most patients had an ECOG PS of 1 (T: 100%; TC: 88.0%). While all T patients received one prior line of therapy, 48.0% of TC patients had received ≥2 prior lines. At the data cutoff of June 9, 2025, with a median follow-up of 19.3 months (95% CI, 13.4-NR), the T cohort achieved 100% SD with a median PFS of 13.6 months (95% CI, 4.1-NR). The TC cohort showed an ORR of 20.0% (n=5, PR) and a DCR of 80.0% (n=15, SD), with a median PFS of 8.2 months (95% CI: 4.1-15.1) and a median DOR of 15.3 months (95% CI: 1.5-NR). Median OS was not reached in either cohort; and the 18-month OS rates were 100% and 75.5% in the T and TC cohorts, respectively. The median duration of treatment exposure was 7.1 months. Treatment-related adverse events (TRAEs) were predominantly Grade 1 or 2. Grade 3 TRAEs occurring in ≥5% of subjects were hypertension (4 [12.9%]) and diarrhea (3 [9.7%]). No Grade 4 or 5 TRAEs were reported. TRAEs leading to dose reduction and treatment discontinuation occurred in 41.9% and 3.2% of patients, respectively. Conclusions: KC1036 demonstrated promising antitumor efficacy in patients with advanced or recurrent T/TC. Additionally, KC1036 exhibited a favorable safety profile and tolerability. These encouraging outcomes support further evaluation of KC1036 in a forthcoming phase III trial. Clinical trial information: NCT05683886 .
TroFuse-036/GOG-3123/ENGOT-cx22: A 2-part, phase 3, randomized study of sacituzumab tirumotecan (sac-TMT) + pembrolizumab (pembro) ± bevacizumab (bev) vs standard of care (SoC) as first-line maintenance therapy for PD-L1–positive cervical cancer.
TPS5628 Background: First-line pembro + platinum-doublet chemo ± bev is the preferred SoC for PD-L1-positive stage IVB, persistent, or recurrent cervical cancer. However, ~50% of patients experience progressive disease (PD) within 1 y, highlighting the need for first-line maintenance therapies that can extend clinical benefit. Sac-TMT is a TROP2-directed antibody-drug conjugate with a unique, bifunctional linker that maximizes payload delivery to tumor cells. In a prior phase 2 basket study, sac-TMT + pembro demonstrated promising antitumor activity (ORR, 58% [22/38]) with a manageable safety profile in participants (pts) with recurrent or metastatic cervical cancer that progressed on or after platinum-doublet chemo. TroFuse-036/GOG-3123/ENGOT-cx22 (NCT07216703) is evaluating first-line maintenance therapy with sac-TMT + pembro ± bev vs SoC in pts with cervical cancer. Methods: This 2-part, phase 3, randomized, open-label study is enrolling pts aged ≥18 y with persistent, recurrent, or newly diagnosed stage IVB squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment (surgery/radiation), ECOG PS of 0 or 1, and PD-L1 combined positive score ≥1. In part 1 (safety run-in), ~20 eligible pts who complete 6 cycles of induction therapy with pembro 200 mg Q3W + paclitaxel 175 mg/m 2 Q3W + cisplatin 50 mg/m 2 (or carboplatin AUC 5 mg/mL/min Q3W) + bev 15 mg/kg Q3W without PD per investigator will receive maintenance therapy with sac-TMT 4 mg/kg Q2W + pembro 400 mg Q6W for ≤14 6-wk cycles + bev 15 mg/kg Q3W until treatment discontinuation criteria are met. Enrollment in part 2 will start after enrollment in part 1 is complete. In part 2, ~1003 eligible pts will receive 6 cycles of induction therapy (same doses as in part 1) with pembro + platinum-doublet chemo ± bev at investigator discretion. For randomization to maintenance therapy, pts must complete induction therapy and have CR, PR, or SD per RECIST v1.1 by investigator as assessed by an evaluable tumor scan at week 18; evaluable TROP2 expression; and resolution of any AEs to grade ≤1. After part 1 safety data review is complete, ~802 eligible pts in part 2 maintenance part will be randomized 1:1 to receive sac-TMT 4 mg/kg Q2W + pembro 400 mg Q6W for ≤14 6-wk cycles ± bev 15 mg/kg Q3W or SoC with pembro 400 mg Q6W for ≤14 6-wk cycles ± bev 15 mg/kg Q3W; bev use is at investigator discretion and continues until treatment discontinuation criteria are met. The primary endpoint is safety in part 1 and PFS per RECIST v1.1 by blinded independent central review and OS with maintenance therapy in part 2. Secondary endpoints associated with maintenance therapy in part 2 are PFS2 per investigator, safety, and patient-reported outcomes. Enrollment began in Dec 2025. Clinical trial information: NCT07216703 .
SATURN-STS: Phase II study of neoadjuvant atezolizumab with doxorubicin, concurrent atezolizumab with pre-operative radiation therapy and adjuvant atezolizumab in patients with high-risk surgically resectable extremity and truncal soft tissue sarcoma.
TPS11595 Background: High-risk, localized soft tissue sarcoma (STS) remains associated with high rates of distant relapse despite modern multimodality therapy. Immune checkpoint inhibition (ICI) has demonstrated activity in certain metastatic STS subtypes with signals of enhanced response when combined with doxorubicin in the advanced/metastatic setting, as well as improved disease-free survival when combined with radiotherapy (RT) in the neoadjuvant setting; however, the optimal integration of neoadjuvant chemotherapy, immunotherapy, and RT in resectable disease is unknown. This single-arm phase II trial evaluates whether neoadjuvant atezolizumab combined with doxorubicin, followed by concurrent atezolizumab with preoperative RT and adjuvant atezolizumab, can improve relapse outcomes in patients with resectable, high-risk STS of the extremity and trunk. Methods: SATURN-STS is an investigator-initiated phase II study enrolling 50 adults with treatment-naïve, localized, intermediate- to high-grade STS >5 cm, including undifferentiated pleomorphic sarcoma, myxofibrosarcoma, de-differentiated/pleomorphic liposarcoma, leiomyosarcoma, and unclassified sarcoma. Neoadjuvant treatment includes 4–6 cycles of doxorubicin (60–75 mg/m²) plus atezolizumab (1200 mg IV q3w), followed by atezolizumab with preoperative RT (50 Gy in 25 fractions or 42.75 Gy in 15 fractions), surgical resection, and up to 16 cycles of adjuvant atezolizumab. Radiographic imaging is performed at baseline, during neoadjuvant therapy, post-RT prior to surgery, and throughout follow-up. Longitudinal tissue is acquired for translational analyses with biopsy prior to initiation of chemoimmunotherapy and prior to RT/immunotherapy combination, followed by collection at the time of surgery. The primary endpoint is time-to-relapse (TTR), defined from time of surgical resection to the date of documented disease recurrence, compared to a historical control using a single-arm, time-to-event Bayesian monitoring approach. Secondary endpoints include objective response (RECIST 1.1), pathologic response, local recurrence-free survival, distant metastasis-free survival, progression-free survival, overall survival, and safety (CTCAE v5.0). Exploratory objectives include profiling immune microenvironment changes, genomic correlatives, circulating tumor DNA, and spatial analyses. As of January 2026, 6 patients have initiated treatment at an accrual rate of 1-2 patients per month. Clinical trial registration: NCT07049848. Support: The University of Texas MD Anderson Cancer Center and Genentech Strategic Alliance Grant. Clinical trial information: NCT07049848 .
Phase 2 study integrating early palliative care in advanced sarcoma patients for enhanced quality of life (SARQUALITY Trial: NCT06805669): An interim analysis.
11552 Background: Patients (pts) with advanced cancer may experience substantial symptom burden that adversely affects quality of life (QoL). Although early palliative care (EPC) integrated with standard oncologic care (SOC) has demonstrated clinical benefit, patients with sarcoma have been underrepresented in prior studies. This phase II trial evaluates whether EPC combined with SOC improves outcomes in pts with advanced sarcoma compared with SOC alone. Results from the first interim analysis are presented. Methods: Adult pts with advanced sarcoma who are systemic treatment naïve were randomized (1:1) to either SOC alone or with EPC. EPC intervention included palliative care (PC) review within 4 weeks of randomization, routine PC contact and access to 24-hour support. Pts receiving SOC alone are referred to PC at time of clinical need. Pts complete Edmonton Symptom Assessment System (ESAS) and EORTC QLQ-C30 questionnaires at baseline, weeks 6, 12 and 24. The primary endpoint is the change in ESAS score at week 12 compared to baseline. Secondary endpoints include EORTC QLQ-C30 score change, emergency department (ED) attendance and overall survival (OS). The aim is to accrue 136 pts, providing 80% power at one-sided 5% level of significance to detect standardised difference of 0.45 between-group in ESAS score from baseline to 12 weeks. Results: Enrollment commenced in July 2024. At data lock (November 2025), 44 pts were enrolled (SOC, n=21; EPC, n=23). The cohort was predominantly female (n=29, 66%), with a median age of 60 years (range 29–85). Soft tissue sarcoma accounted for 43 cases (one had osteosarcoma); 39 (89%) pts had metastatic disease and 5 (11%) had locally advanced disease. Age, gender, race, histologic subtype, and number and sites of metastases were balanced between arms. ESAS and EORTC scores for pts in EPC arm (Table 1) but ED attendances were similar (EPC-24, SOC-23). In SOC arm, symptom management interventions (radiation, surgery) occurred more frequently than the EPC arm (12 vs. 2 pts). Seven pts were referred to PC from the SOC arm (median of 3.2 months from randomization). OS data is immature. Conclusions: The interim results of SARQUALITY trial demonstrate EPC has an impact on ESAS and EORTC scores, however, further data required to demonstrate if there is a benefit on QoL. There was a reduction in number of symptom management interventions in EPC arm, suggesting EPC may reduce need for additional interventions. Trial accrual is ongoing. Clinical trial information: NCT06805669 . Mean score change at 6, 12 and 24 weeks compared with baseline. Week 6 12 24 Arm EPC N=20 SOC N=20 p-value EPC N=18 SOC N=18 p-value EPC N=14 SOC N=15 p-value ESAS (95% CI) -1.8 (-9.0 – 5.5 3.8 (-0.2 – 7.7) 0.172 -3.4 (-13.9 – 7.1) 3.2 (-2.8 – 9.1) 0.261 -1.8 (-11.4 – 7.9) 4.5 (0.0 – 8.9) 0.220 EORTC QLQ (95% CI) -0.6 (-6.7 – 5.6) 4.5 (1.2 – 7.7) 0.143 0.2 (-5.6 – 6.0) 3.8 -2.5 – 10.1) 0.379 0.0 (-6.4 – 6.4) 4.4 (-1.2 – 10.0) 0.274
Trends and disparities in mortality due to coexisting respiratory infections and multiple myeloma among middle-aged and older adults in the United States.
e19541 Background: Patients with multiple myeloma (MM) are highly susceptible to respiratory infections due to disease- and treatment-related immunosuppression. Mortality due to coexisting respiratory infections and MM remains understudied, and national trends and sociodemographic disparities among middle-aged and older adults in the United States (US) are poorly characterized. Methods: We analyzed CDC WONDER mortality data (1999–2020) to identify deaths among U.S. middle-aged (55–74 years) and older adults (≥75 years) in which both respiratory infections and multiple myeloma were listed as causes of death on death certificates. Causes of death were identified using ICD-10 codes. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated overall and stratified by sex, age group, race/ethnicity, and state. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC), with statistical significance defined as p ≤0.05. Results: From 1999 to 2020, 21,930 deaths due to coexisting respiratory infections and MM were identified. Mortality declined significantly from 1999 to 2012 (APC −4.14%, p <0.05) but increased thereafter, peaking in 2020 (AAMR: 1.40). Males accounted for 58.9% of deaths and had nearly two-fold higher mortality than females (AAMR: 1.94 vs. 0.98), with a significant rise from 2015 to 2020 (APC +4.53%, p =0.045), while female trends remained stable. Older adults (≥75 years) had higher mortality than those aged 55–74 years, despite long-term declines in both groups. Black or African American individuals experienced persistently higher mortality with a significant increase after 2012 (APC +4.10%, p =0.02), and Hispanic individuals showed a sharp rise from 2018 to 2020 (APC +29.9%, p =0.003), whereas mortality among White and Asian or Pacific Islander populations remained stable or declined. State-level analyses demonstrated over two-fold variation, with the highest absolute burden in California, Texas, New York, and Florida. Conclusions: Mortality due to coexisting respiratory infections and MM among middle-aged and older adults declined over the past two decades but showed concerning recent increases, particularly among males, Black, and Hispanic populations. Persistent racial and geographic disparities underscore the need for targeted infection prevention strategies and equitable supportive care for high-risk MM populations.
End-of-life anti-cancer treatment (Rx) patterns in patients (pts) with the six most common cancers in the USA.
12034 Background: Pts with ≤ 6 months of life expectancy qualify for hospice. However, most pts with advanced/metastatic (a/m) cancer continue to receive Rx up to weeks prior to death. Data describing end-of-life Rx patterns in these pts remain limited but are essential to improve clinical care delivery. Herein, we evaluated real-world Rx patterns in relation to the time of death across 6 most common a/m solid tumors: advanced non-small cell lung cancer (aNSCLC), metastatic breast cancer (mBC), metastatic prostate cancer (mPC), advanced colorectal cancer (aCRC), metastatic pancreatic cancer (mPanC), and advanced urothelial carcinoma (aUC). Methods: This study used the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility: diagnosis of aNSCLC, mBC, mPC, aCRC, mPanC and aUC, had a recorded date of death, and information on initiation of first-line (1L) Rx. The data cutoff date was 6/30/2025. Pts were categorized as treatment-free if no systemic Rx was administered within the final 1 or 3 months of life, or on-treatment if systemic Rx was received within 1 or 3 months before death. Demographic and clinical variables at the last line of Rx initiation, including age, race, socioeconomic status, practice type, and insurance, were summarized using medians (IQR) or proportions. Results: Of 111,337 pts with aNSCLC, 82,339 had a recorded date of death, of whom 59,777 initiated 1L Rx. Of 43,218 pts with mBC, 26,572 had a recorded date of death, of whom 23,055 initiated 1L Rx. Of 27,979 pts with mPC, 14,793 had a recorded date of death, of whom 9,667 initiated 1L Rx. Of 45,013 pts with aCRC, 29,749 had a recorded date of death, of whom 24,219 initiated 1L Rx. Of 18,942 pts with mPanC, 15,690 had a recorded date of death, of whom 11,528 initiated 1L Rx. Of 15,236 pts with aUC, 10,872 had a recorded date of death, of whom 7,815 initiated 1L Rx. The proportion of pts receiving systemic Rx within 1 month or 3 months before death for each cancer type is summarized in Table. Baseline characteristics, Rx patterns and trends by cancer type will be presented at the meeting. Conclusions: Across six most common cancers in the US, systemic Rx use remained common near the end of life, with up to one-third of pts treated in the final month. These findings suggest the need for greater emphasis on early involvement of palliative care teams and timely transition of pts with terminal cancers to comfort care. Proportion of pts with a/m cancer receiving systemic Rx within 1 month or 3 months before death. Cancer type Eligible pts Rx within 1 month of death, n (%) Rx within 3 months of death, n (%) aNSCLC 59,777 19,268 (32.2) 38,227 (63.9) mBC 23,055 8,416 (36.5) 15,972 (69.3) mPC 9,667 2,438 (25.2) 5,762 (59.6) aCRC 24,219 7,172 (29.6) 15,386 (63.5) mPanC 11,528 4,191 (36.3) 9,184 (79.7) aUC 7,815 2,358 (30.2) 5,170 (66.1)
Dual HER2 blockade with or without taxane induction in HR+/HER2+ metastatic breast cancer: A comparative analysis of clinical outcomes.
1059 Background: In the era of modern dual HER2 blockade, the necessity of taxane induction for ER+/HER2+ metastatic breast cancer (MBC) remains debated. While CLEOPATRA established pertuzumab/trastuzumab plus taxane as a standard backbone, emerging de-escalation strategies suggest that endocrine therapy (ET) combined with HER2 blockade may provide durable disease control in this favorable-prognosis subgroup (SYSUCC002, PERTAIN). Robust real-world comparative data addressing the survival–toxicity trade-off between chemotherapy-free versus taxane-induction approaches are limited. Methods: The TriNetX Global Collaborative Network (168 healthcare organizations; data updated Dec 2025) was queried for adults (≥18 years) with incident HR+/HER2+ MBC treated with dual HER2 blockade (trastuzumab + pertuzumab) plus ET. Patients receiving induction taxane (paclitaxel or docetaxel) comprised the induction cohort (IND); those treated with dual blockade + ET without induction comprised the chemotherapy-free cohort (Chemo-Free). 1:1 propensity-score matching (greedy nearest-neighbor; caliper 0.10) on demographics and comorbidities yielded 137 well-balanced pairs (N=274) with all post-match standardized mean differences <0.10. The primary endpoint was 3-year overall survival (OS; 1095-day window). Secondary outcomes included neutropenia, sepsis, heart failure, emergency department (ED) visits, and ICU admission. Results: Among 957 eligible patients, 153 received Chemo-Free and 804 received IND; 137 matched pairs were analyzed. Three-year OS was similar between cohorts with no statistically significant separation of survival curves (3-year OS 89.1% Chemo-Free vs 82.0% IND; HR 0.65 [0.32–1.31]; p=0.219). Deaths within 3 years were 13/137 (9.5%) in Chemo-Free versus 19/137 (13.9%) in IND, corresponding to an absolute death risk difference of −4.4% (95% CI −12.0% to +3.2%). Omitting induction was associated with reduced neutropenia (12.4% vs 21.9%; absolute risk reduction 9.5%; OR 0.51 [0.26–0.97] and a lower time-to-neutropenia hazard (HR 0.50 [0.28–0.91]; p=0.020). Serious adverse events and acute care utilization were not increased with Chemo-Free: heart failure 16.1% vs 16.1%; sepsis 10.9% vs 13.1%; ICU admission 11.7% vs 13.9%; ED visits 40.9% vs 45.3%. Conclusions: In a propensity-matched real-world cohort receiving contemporary dual HER2 blockade plus ET, a chemotherapy-free strategy demonstrated similar 3-year OS compared with taxane induction, with a clinically meaningful reduction in neutropenia (number needed to treat ≈11 to prevent one event) and no signal for higher sepsis, heart failure, or acute care utilization. These data support the feasibility of chemotherapy de-escalation in selected HR+/HER2+ MBC patients and motivate prospective validation to refine patient selection and minimize treatment-related toxicity.
Neoadjuvant pyrotinib vs pertuzumab therapy for HER2-positive early breast cancer: The HELEN HER-013 randomized clinical trial.
509 Background: Docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) is a standard neoadjuvant regimen for stage II–III human epidermal growth factor receptor 2 (HER2)–positive breast cancer; however, its use is associated with substantial treatment burden, particularly hematologic toxicity, highlighting the need for alternative strategies that maintain efficacy with different toxicity profiles.This study to determine whether a chemotherapy-de-escalated regimen of nanoparticle albumin–bound paclitaxel, trastuzumab, and the tyrosine kinase inhibitor pyrotinib (nab-PHPy) is noninferior to standard TCHP with respect to pathological complete response (pCR). Methods: The HELEN HER-013 trial was a multicenter, randomized, open-label, phase 3 noninferiority trial conducted at 15 centers in China. Women with previously untreated, operable stage II–III HER2-positive breast cancer were enrolled between May 2023 and May 2025.Participants were randomly assigned (1:1) to receive six 21-day cycles of either nab-paclitaxel, trastuzumab, and oral pyrotinib (nab-PHPy group) or TCHP group.The primary end point was pCR (ypT0/Tis ypN0), assessed in the modified intention-to-treat (mITT) population (patients who received ≥1 dose of study treatment). The prespecified noninferiority margin was −5.5%( ClinicalTrials.gov Identifier: NCT05918328 ). Results: Among 709 screened individuals, 610 were randomized, and 589 were included in the mITT population (295 in the nab-PHPy group and 294 in the TCHP group; all female). Median age was 51 years (interquartile range [IQR], 43–56) in the nab-PHPy group and 52 years (IQR, 45–57) in the TCHP group. The primary end point of pCR was achieved in 186 patients (63.1%; 95% CI, 57.4%–68.4%) in the nab-PHPy group and 174 patients (59.2%; 95% CI, 53.4%–64.8%) in the TCHP group. The between-group difference was 3.9% (95% CI, -4.2% to 11.9%), which met the prespecified criterion for noninferiority (noninferiority P = .01). Grade 3 or higher treatment-emergent adverse events occurred in 113 patients (38.3%) receiving nab-PHPy and 107 patients (36.4%) receiving TCHP. The most common grade 3 or higher adverse events were diarrhea (31.5% vs 17.0%), anemia (1.7% vs 10.2%), and nausea (0% vs 5.8%). No treatment-related deaths were reported. Conclusions: Among women with operable stage II–III HER2-positive breast cancer, neoadjuvant treatment with nab-PHPy was noninferior to TCHP with respect to pCR and was associated with a distinct toxicity profile, supporting its role as an alternative neoadjuvant strategy. Clinical trial information: NCT05918328 .
Clinical utility analysis of a computational reasoning system on large-scale tumor genomic data.
1625 Background: Comprehensive tumor molecular testing has become routine in clinical oncology. However, interpretation of complex molecular profiles in clinical practice can be challenging and subjective. The Digital Drug Assignment (DDA) system is a knowledge-graph-based computational method that automates reasoning at the patient level and scores molecularly targeted agents (MTAs) based on the full tumor genome. This approach was predictive of relative benefit of the agents as used in the SHIVA01 trial (NPJ Precis Oncol. 2021 5:59) and in real-world setting (NPJ Precis Oncol. 2025 9:159). Here, we assessed the potential clinical utility of DDA by analyzing large-scale tumor genomic data. Methods: Tumor molecular profiles of 20,923 patients of the MSK-CHORD real-world clinicogenomic dataset (Nature. 2024 636:728-36) were processed by DDA. DDA classified all alterations and scored all associated MTAs based on a functional and pharmacological evidence network. Previous research evidenced that high-score MTAs (1000 ≦ DDA score) predict increased clinical benefit. Utility of DDA was assessed by the proportion of patients with at least one high-score MTA option associated with their molecular profiles. Results: Tumor molecular complexity is evidenced by the number of driver alterations, with an average of 4.6 (range: 1 – 45) drivers per tumor (Table). 75% of all tumors were associated with high-score MTAs, 55% had on-label options. Availability of high-score options was high in all tumor types, with the exception of prostate tumors (24%). Only 3% of pancreatic cancer patients were associated with on-label high-score MTA options. Of the patients with known MTA treatments (n = 14,168), only 37% were administered a high-score MTA during their treatment course (Table). Conclusions: Our analysis recapitulates the presence of multiple driver alterations, highlighting the need for methods like DDA that consider the totality of molecular profiles for assigning MTAs, rather than relying on identifying single ‘actionable biomarkers’. The substantial gap between the proportion of patients who did receive and those whose tumor genomes were associated with high-score MTAs indicates a strong potential for improving outcomes in precision oncology. Moreover, the proportion of high-score off-label (i.e., approved in other oncological indications) MTAs highlights the potential of DDA in drug repurposing. Tumor site Mean no. of alterations (±SD) Mean no. of drivers (±SD) HS MTAs associated* HS MTA administered* HS developmental MTAs associated* HS off-label MTAs associated* HS on-label MTAs associated* All (20,923) 9.9 (11.8) 4.6 (3.9) 75 37 74 71 55 Breast (5,164) 8.1 (8.1) 4.3 (3.4) 90 57 90 89 86 Colorectal (4,565) 13.2 (18.0) 6.0 (5.5) 69 18 67 60 46 Lung (5,932) 11.6 (10.2) 4.6 (3.2) 85 57 83 84 79 Pancreas (2,619) 6.2 (6.0) 3.6 (2.3) 86 2.5 86 86 3 Prostate (2,643) 7.4 (9.5) 3.6 (3.3) 24 6.6 21 11 7 HS: high-score. *% of patients.
Risk and protective factors for acral, mucosal, and uveal melanoma in a multi-institutional cohort of veterans and civilians.
9555 Background: Melanoma is the 4th most common cancer among US Veterans. Non-acral cutaneous melanoma has well-established risk factors including history of sunburn, ultraviolet (UV) exposure, fair skin and features. Risk factors for acral (AM), mucosal (MM), or uveal melanoma (UM), are less understood. Methods: We conducted a nested case-control study (2000-2024) identifying cases of acral (N=1,292, Veterans only), mucosal (N=520, combined Veteran and civilian cohort), and uveal (N=2,010, combined Veteran and civilian cohort) melanoma using the Veterans Affairs (VA) Cancer Registry, natural language processing applied to pathology reports, and Mass General Brigham Research Patient Data Repository. Results: For AM, current smoking was associated with reduced odds, while Agent Orange Exposure (AOE) was associated with increased odds compared to both control populations. Compared to non-melanoma controls, prior nevus, keratinocyte carcinoma (KC), and actinic keratosis (AK) were associated with increased odds of AM. For MM, prior KC was associated with higher odds of MM compared to non-melanoma controls, consistent across anogenital, sinonasal, and upper aerodigestive tract sites. Smoking status was associated with reduced MM odds in the sinonasal cohort. For UM, we conducted a case-control study using data from 3 academic medical centers and the VA. Prior cutaneous and systemic immune disease were protective of UM development compared to CM. Smoking status and prior nevi had higher odds of UM compared to CM and non-cancer controls. Conclusions: To our knowledge, this is the largest cohort of AM, MM, and UM cases to date. Our study identified unique factors associated with risk of, or protection from, AM, MM, or UM, compared to CM or non-cancer controls. These findings provide novel insights into potential risks for rare melanomas and can help guide future biologically driven studies. Risk and protective factor associations across rare melanomas. Melanoma type Factor type Both cohorts CM only Non-cancer only Acral High risk association factors Younger age, female sex, Black race, Hispanic ethnicity, AOE Asian race Prior nevus, prior KC, prior AK Protective factors Current smoking ≥2 comorbidities, AUDIT-C positive, prior KC, prior AK Former smoking No associations BMI Mucosal High risk association factors Younger age, female sex Black race, Hispanic ethnicity Prior KC Protective factors Former smoking Current smoking, ≥2 comorbidities No associations Prior nevus, BMI Uveal High risk association factors Older age, former smoking, current smoking, prior nevus Black race, American Indian/Alaska Native race, obesity Protective factors ≥1 comorbidities, prior photosensitizing medication use, prior cutaneous autoimmune disease, prior systemic autoimmune disease Prior non-melanoma skin cancer Hispanic ethnicity, normal or underweight BMI No associations Sex
Remote, scalable weight-loss interventions after early-stage breast cancer: A systematic review and meta-analysis of randomized controlled trials.
e12748 Background: Obesity is associated with worse breast cancer outcomes, but whether intentional weight loss improves recurrence or survival remains uncertain. Remote, scalable lifestyle interventions may broaden access to weight management after early-stage breast cancer. We conducted a systematic review and meta-analysis of randomized trials evaluating remote weight-loss interventions and their effects on weight and breast cancer outcomes. Methods: We searched PubMed and ScienceDirect for randomized controlled trials published through January 2026 evaluating telehealth/remote weight-loss interventions in patients with breast cancer and reporting weight-related outcomes and/or breast cancer endpoints. We followed PRISMA guidance and pooled outcomes using random-effects models in RevMan 5.4.1. Results: Of 638 records identified, 6 randomized controlled trials (n = 1,594) met inclusion criteria. Participants received weight-control interventions delivered via telehealth (48.9%), usual care (48.9%), or in-person programs (2.2%). In pooled analysis, telehealth interventions resulted in significantly greater weight reduction than usual care at 6 months (MD −3.17 kg; 95% CI −4.12 to −2.22; p < 0.0001; I² = 57%), 12 months (MD −3.94 kg; 95% CI −4.80 to −3.09; p < 0.00001; I² = 0%), and 18 months (MD −3.51 kg; 95% CI −4.50 to −2.53; p < 0.0001; I² = 0%). Waist circumference reduction was also significantly greater with telehealth at 6 months (MD −4.36 cm; 95% CI −7.09 to −1.63; p = 0.002; I² = 0%). Only one of the included trials had a follow-up period long enough to assess the impact of weight loss on survival outcomes and to evaluate oncologic outcomes; disease-free survival was not significantly different (HR 0.71; 95% CI 0.41–1.24; p = 0.23). A 5% weight reduction was associated with a non-significant improvement in overall survival (HR 0.72; 95% CI 0.47–1.12; p = 0.15). Conclusions: Remote/telehealth interventions produce clinically meaningful weight loss and reductions in waist circumference after early-stage breast cancer, underscoring their potential in patient management. Findings from the initial RCT to determine the impact of this weight loss on breast cancer survival suggest a possible benefit, though evidence remains limited. Larger RCTs with adequate follow-up are essential to confirm whether these interventions can improve breast cancer outcomes and inform clinical practice.
Gastric cancer incidence, prevalence, and mortality burden in the United States: Retrospective epidemiological trends and burden (1990–2023) with machine learning–based projections to 2050.
e16063 Background: Gastric cancer continues to represent a major global health challenge, though incidence and mortality have declined markedly in high-income countries including the United States, largely due to reductions in Helicobacter pylori prevalence, dietary improvements, and advances in early detection and treatment. This study evaluated age-standardized rates (ASRs) of DALYs, deaths, incidence, and prevalence from 1990 to 2023 using IHME GBD 2023 data, calculated estimated annual percentage changes (EAPC), and generated projections to 2050 via ARIMA time-series modeling. Methods: Age-standardized rates per 100,000 population were retrieved from the Global Burden of Disease 2023 database for the United States, stratified by sex (Both, Female, Male). Historical trends (1990–2023) were quantified using EAPC from linear regression on log-transformed ASRs. Future projections (2024–2050) were produced with ARIMA models fitted to historical data, yielding point estimates and 95% prediction intervals. Results: From 1990 to 2023, age-standardized DALYs (Both sexes) decreased from 125.34 (95% UI: 116.60–135.49) to 68.51 (95% UI: 61.82–75.62), with an EAPC of -1.88% (95% CI: -1.98 to -1.77); males exhibited a steeper decline (EAPC -2.22%, 95% CI: -2.32 to -2.11) than females (EAPC -1.49%, 95% CI: -1.59 to -1.38). Age-standardized death rates fell from 5.39 to 2.77 (EAPC -2.08%, 95% CI: -2.17 to -2.00), again with greater reductions in males (EAPC -2.39%) than females (EAPC -1.85%). Incidence declined from 8.02 to 4.94 (EAPC -1.59%, 95% CI: -1.66 to -1.52), and prevalence from 18.42 to 14.18 (EAPC -0.99%, 95% CI: -1.12 to -0.85), reflecting successful risk factor control and improved survival. ARIMA forecasts indicate accelerated ongoing declines in age-standardized DALYs (Both: from 67.56 in 2024 toward ~42.84 by 2050), deaths (to ~1.51), and incidence (to ~2.42), while prevalence continues to erode gradually. Conclusions: Age-standardized burden of gastric cancer in the US declined sharply from 1990–2023 across all metrics, with particularly strong reductions in males for DALYs, mortality, and incidence. Projections to 2050 suggest continued substantial decreases in key indicators, approaching very low levels, underscoring the success of primary and secondary prevention efforts, though vigilance remains warranted for high-risk subgroups and potential emerging risk factors. Measure Sex EAPC Lower 95%CI Upper 95%CI DALYs Both -1.88 -1.98 -1.77 DALYs Female -1.49 -1.59 -1.38 DALYs Male -2.22 -2.32 -2.11 Deaths Both -2.08 -2.17 -2 Deaths Female -1.85 -1.94 -1.75 Deaths Male -2.39 -2.47 -2.3 Incidence Both -1.59 -1.66 -1.52 Incidence Female -1.36 -1.44 -1.27 Incidence Male -1.88 -1.94 -1.81 Prevalence Both -0.99 -1.12 -0.85 Prevalence Female -0.76 -0.89 -0.63 Prevalence Male -1.23 -1.37 -1.09
Automatic pharmacogenomic testing provided on liquid biopsy: Access, prevalence, and integration in a safety net population.
e15137 Background: Pharmacogenomics (PGx) is a rapidly growing tool for precision oncology however remains underutilized in routine oncologic practices, particularly amongst under-insured and minority populations due to the cost and access barriers. Circulating tumor DNA (ctDNA) assays, such as Guardant360, now report on PGx variants alongside somatic alterations, expanding access without requiring separate testing, but it is not clear how and if PGx results are implemented in practice. Methods: We performed a retrospective review of 79 unique oncology patients who underwent Guardant360 testing at a safety-net cancer center. Genes assessed included UGT1A1, CYP2D6, DPYD, TPMT and HLA-B. Metabolizer phenotypes were characterized as normal, intermediate, or poor. Potentially actionable PGx was identified as intermediate or poor metabolizer status. Demographic data along with insurance status was also collected. Under-insured status was defined as Medical Access Program (MAP), Sendero, or uninsured. PGx integration was defined conservatively as documentation acknowledging the PGx result within 3 months of testing. Results: The median age of the cohort was 57 years, and 24 (30.0%) were ≤50 years at testing. Most patients were under-insured (71.2%). At the patient level, 57 of 79 patients (72.2%) had at least one potentially actionable PGx phenotype, and 32 patients had GI malignancies. One actionable phenotype was present in 33 (56%) of patients and two in 13 (17%). The most frequently flagged actionable genes were UGT1A1 (40/79, 51%) and CYP2D6 (24/77, 31%), with fewer actionable variants in TPMT (5/79, 6%) and DPYD (2/79, 3%); no actionable HLA-B variants were observed. Actionable PGx prevalence did not differ by ethnicity (p = 0.793). Despite potentially actionable PGx results, clinical integration and acknowledgment of PGx findings within 3 months was rare. We did not identify documented PGx-guided changes in systemic therapy within the observation window. Conclusions: In this safety-net population of cancer patients, automatic PGx reporting through routine liquid biopsy showed a high prevalence of potentially actionable PGx phenotypes, affecting nearly 3 of 4 patients. The low documentation rate points to an under-recognition of PGx data provided in liquid biopsy testing, even in the 40% of patients with GI malignancies, for whom PGx is most relevant. These findings show that automatic PGx is an under-recognized resource in safety-net oncology.
Virtual AI-informed immunocyte profiling (VAIP) from H&E as a predictor of multi-cancer prognosis.
3118 Background: Improved risk stratification is critically needed across multiple cancers to guide treatment decisions. This includes reducing overtreatment in Ductal Carcinoma in Situ (DCIS), addressing late recurrence risk in estrogen receptor-positive/lymph node-negative (ER+/LN-) breast cancer (BC), and refining prognosis in head & neck squamous cell carcinomas (HNSCC), and high-grade serous ovarian carcinoma (HGSOC). Tumor-infiltrating lymphocytes (TILs) reflect anti-tumor immunity, whereas tumor-associated macrophages (TAMs) polarize toward anti-tumor M1-like (CD68+) or immunosuppressive M2-like (CD163+) phenotypes. Integrating TILs with TAM polarization markers may better capture inflammatory balance and improve outcome prediction. We developed a hematoxylin and eosin (H&E)-only AI method (VAIP) to quantify TILs and virtual CD68/CD163 TAMs to develop multi-cancer based potential prognostic models. Methods: TILs were detected on H&E with HoVer-UNet, and virtual CD68 and CD163 macrophages were inferred with VISTA. In cancer regions, we computed cell densities and immune-balance ratios and trained cancer-specific Cox models with compact feature sets (DCIS 6; HGSOC 7; ER+ 4; HNSCC 4). Prognostic stratification used disease-free survival (DFS) for DCIS (N=273), HGSOC (training N=165, independent test N=220), and ER+ BC (training N=144, test N=622), and overall survival (OS) for HNSCC (N=77), reflecting clinical endpoints. Evaluation used cross-validation for cohorts without an external test set (DCIS, HNSCC) and independent training and testing when independent cohort was available (HGSOC, ER+). Results: Risk stratification performance across cancer types is in Table 1. The DCIS model used 6 features, largely TIL-macrophage contrast ratios (TIL/M2, TIL/M1). HGSOC used 7 features with a similar ratio-heavy immune-balance signature, plus macrophage-normalized density and polarization metrics (e.g., M1/N, M/N). In contrast, ER+ BC and HNSCC achieved best performance with 4 features dominated by macrophage measures, particularly M2 density and the M1/M2 ratio. Across sites, CD163-related macrophage metrics and immune-balance ratios were consistently informative. Conclusions: Integrating H&E-visible TILs with virtual CD68/CD163 TAMs enables fully automated, H&E-only prognostic biomarkers that stratify OS and DFS across multiple cancers, demonstrating consistent prognostic value in DCIS, ER+ BC, HGSOC, and HNSCC. These findings support further study of this histomorphometric risk classifier through broader external and prospective validation. Performance across cancer types. Cancer Type Cohort C-index HR [95% CI] p-value DCIS All 0.616 1.76 [1.20-2.59] <0.001 DCIS RT/No-treatment 0.624 1.94 [1.15-3.26] 0.003 HGSOC Test 0.553 1.38 [1.02-1.87] 0.030 ER+ BC Test 0.577 1.51 [1.00-2.28] 0.004 HNSCC All 0.603 1.92 [1.03-3.36] 0.012
A functional precision medicine strategy to guide patient selection for oncolytic vaccination in <i>NRAS</i> -mutant melanoma.
e21508 Background: The NRAS-mutant melanoma subtype represents one of the major challenges in melanoma treatment, as it is associated with aggressive disease biology, reduced overall survival (OS), heterogeneous responses to immune checkpoint inhibitors (ICIs), and the absence of approved targeted therapies. Methods: This is a single-center, prospective translational study enrolling metastatic NRAS-mutant melanoma patients (pts) undergone to standard clinical practice treatment with ICIs. Blood samples, longitudinally collected at baseline and during treatment, were employed with the aim to develop a patient-specific, functional 3D based platform capable of stratifying pts as potential responders or non-responders, ultimately improving selection for oncolytic cancer vaccination and personalizing therapy. The investigational vaccine leverages an oncolytic adenovirus (Ad5/3-D24-ICOSL-CD40L) designed to selectively replicate in tumor cells and enhance antitumor immunity via costimulatory molecules expression. To further strengthen immune activation, the viral vector was combined with melanoma-associated antigens targeting NRAS-mutant melanoma. Results: The preliminary analysis included 7 pts, 100% male, with ECOG 0 PS and a median age of 65 years. Most pts had poor prognostic features, including visceral disease, multiple metastatic sites (≥3) or elevated lactate dehydrogenase levels. Three pts were ICI-naïve, while 4 had primary resistance. Best overall response included stable disease in 2 pts, while 5 experienced progressive disease. Median progression-free survival was 3.1 months; mOS was not reached. To functionally assess vaccine activity and patient-specific immune responsiveness, we established a 3D co-culture system using patient-derived NRAS-mutant melanoma spheroids and autologous, HLA-matched peripheral blood mononuclear cells. This platform recapitulates key features of the tumor microenvironment and enables dynamic evaluation of immune-mediated antitumor effects, including tumor growth control and regrowth kinetics. Treatment of patient-derived melanoma spheroids with the oncolytic vaccine resulted in enhanced antitumor activity compared to relative control conditions, with a significant reduction in spheroid area and attenuation of tumor regrowth over time. Notably, under control co-culture conditions, spheroid growth dynamics qualitatively reflected the aggressive clinical course observed in pts with poor response to standard immunotherapy, whereas vaccine treatment promoted effective immune-mediated tumor control in vitro . Conclusions: These findings support the feasibility of a functional 3D model to capture differential therapeutic responsiveness and to inform future strategies for early stratification and personalized immunotherapeutic interventions in NRAS-mutant melanoma pts.
SVTRv2X: Enhanced scene text recognition via self-distilled mixture-of-experts
Scene Text Recognition (STR) is a fundamental component of intelligent perception systems and plays a crucial role in a wide range of real-world applications such as autonomous driving, document understanding, and human–computer interaction. STR still faces several challenges in practical applications, including high sensitivity to spatial perturbations, limited representational capacity of lightweight Connectionist Temporal Classification(CTC)-based models, and the difficulty of handling diverse text styles within a single unified architecture. Although SVTRv2 enhances the recognition ability of CTC models through a combination of local and global mixing mechanisms, its robustness and generalization capability remain insufficient when dealing with geometric distortions, complex backgrounds, or text with large stylistic variations. To address these issues, we propose SVTRv2X, an enhanced STR framework built upon SVTRv2 that integrates three complementary improvement modules. The Jumble Module strategically rearranges input patches before the patch embedding stage, fundamentally reducing the model’s reliance on fixed spatial structures and significantly improving robustness to rotated, misaligned, and irregular text. The Self-Distillation Module transfers deep-layer knowledge to shallow features, effectively strengthening early-stage representations while maintaining lightweight inference. The Mixture-of-Experts (MoE) Module expands model capacity through sparsely activated expert networks, allowing specialized processing of different text styles without introducing substantial computational overhead. Extensive experiments demonstrate that SVTRv2X achieves state-of-the-art performance on multiple STR benchmarks, substantially advancing the model’s recognition capability in real-world scene text scenarios.
Solar‐Driven Photocatalytic C─S Coupling for Organosulfur Synthesis Via Upcycling SO <sub>2</sub> and Plastic Waste
ABSTRACT Hydroxymethylsulfonate (HMS) is an important cleaning agent in the electronics industry and serves as a crucial intermediate in the synthesis of surfactants and pharmaceuticals. Conventional industrial production of HMS relies on toxic and volatile formaldehyde, presenting considerable safety and environmental risks. Herein, we report a solar‐driven photocatalytic route for the synthesis of HMS from waste SO 2 and polyethylene terephthalate (PET)‐derived ethylene glycol (EG) under ambient conditions, using a Cu single‐atom‐decorated TiO 2 catalyst (Cu 1 /TiO 2 ). The optimized Cu 1 /TiO 2 catalyst achieves an HMS yield rate of ∼ 2.31 mmol g cat −1 h −1 with a 77.5% carbon selectivity, along with a H 2 evolution rate of ∼ 4.36 mmol g cat −1 h −1 . Mechanistic studies reveal that the atomically dispersed Cu sites act as electron sinks, which enhance charge separation and induce electronic modulation of TiO 2 . This modulation facilitates the adsorption and activation of reactants while lowering the energy barrier for the formation of a key *CHOH─CH 2 OH intermediate via EG dehydrogenation. This resulting intermediate then undergoes nucleophilic attack by hole‐generated •SO 3 − , triggering C─C cleavage to form HMS. This work establishes a sustainable and waste‐valorizing route for organosulfur synthesis.