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Diabetes risk reduction diet and mortality outcomes following breast cancer diagnosis in Black women.

10622 Background: Black women continue to experience a ~40% higher breast cancer mortality rate than White women. Type II diabetes (T2D) management-related factors have received increasing attention as contributors to this disparity. Emerging evidence, largely derived from studies conducted among White women, suggests that adherence to the diabetes risk reduction diet (DRRD) may be associated with improved breast cancer outcomes. Despite Black women having more than twice the risk of developing T2D compared with White women, no studies to date have examined the association between the DRRD and mortality among Black breast cancer survivors. Methods: We conducted a cohort analysis of 1,732 Black breast cancer survivors from the Women’s Circle of Health Follow-Up Study. Participants’ prediagnostic intake of DRRD components was calculated from validated food frequency questionnaires that included: cereal fiber, coffee, nuts, whole fruits, polyunsaturated/saturated fat ratio, glycemic index, trans fats, sugar-sweetened beverages, and red/processed meat. Consumption levels for each component were scored 1-5, summed to form a DRRD adherence score (higher scores signify greater adherence), and further categorized into tertiles. Death outcomes and causes were ascertained via linkage to the New Jersey State Cancer Registry. Associations with mortality were evaluated using multivariable-adjusted Cox proportional hazards regression models. Results: After a median of 10.8 years of follow-up since diagnosis, 422 total deaths (213 breast cancer-related) were identified. The mean DRRD score was 26 (std 5.5). In the multivariable–adjusted model, women with higher scores had a 34% lower risk of breast cancer-specific mortality (top vs. bottom tertile HR = 0.66; 95% CI = 0.46-0.93; p = 0.02) and a 23% lower risk of overall mortality (HR = 0.77; 95% CI = 0.59-1.00; p = 0.05). The associations were consistent across diabetes and menopausal status, and also across household income subgroups. However, the risk reduction appeared more pronounced among women with early-stage disease (HR = 0.54; 95% CI = 0.34-0.88), luminal tumor subtypes (HR = 0.49; 95% CI = 0.28-0.87), those with a BMI ≥30 kg/m 2 (HR = 0.55; 95% CI = 0.34-0.88), and those in the lower half of the neighborhood socioeconomic status distribution (HR = 0.57; 95% CI = 0.35-0.93), compared with their respective counterparts. Conclusions: This study represents the first and largest investigation of DRRD adherence and breast cancer outcomes among Black women. Our findings suggest that greater DRRD adherence may offer a protective effect on both breast cancer-specific and overall mortality in Black women, a population facing the highest breast cancer mortality in the US. More broadly, these results, together with prior evidence, suggest that adhering to dietary patterns consistent with T2D prevention may be important for both White and Black breast cancer survivors.

Effect of group community health worker–led advance care planning education on advance care planning documentation, satisfaction, palliative care, and hospice: Results from a randomized clinical trial.

1521 Background: Advance Care Planning (ACP) is recommended for all patients with cancer yet engagement remains low due to multilevel barriers including limited clinician time, lack of adequate reimbursement, and workforce shortages. Our team demonstrated that one-on-one community health worker (CHW)-led education interventions can improve ACP documentation, satisfaction, and hospice use. Group CHW-led interventions may improve scale and spread, however, the effectiveness of such approaches compared to usual cancer care remains unknown. Methods: This prospective randomized clinical trial compared a 1-month CHW-led group ACP education intervention plus usual cancer care (intervention group) with usual cancer care alone (control group). Veterans newly diagnosed with solid tumor malignancies, 18 years of age or older, and planned to receive cancer care at one VA facility were eligible. All who verbally consented were randomized 1:1 to the intervention group or the control group. The intervention consisted of two 90-minute group sessions over 1-month post-randomization with 8-10 participants per group led by trained CHWs. The sessions included tailored education regarding ACP, surrogate decision-maker designation, and communication strategies with cancer clinical teams. Usual care included access to nurse navigators, social workers, palliative care and hospice teams, and ancillary support services. The primary outcome was ACP documentation (comprised of the VA Life Sustaining Treatment, VA Advance Directive, and Goals of Care documentation by the oncology clinician) in the electronic health record within 6-months after randomization. Secondary outcomes included satisfaction with care decision, palliative care use, and hospice use. Results: 65 patients were screened with 60 (92.3%) eligible of whom all 60 (100%) participated with 30 in each group. There were no withdrawals or participants lost to followup; 55 (91%) were male; 5 (8.3%) were female; median age was 79 years (IQR 67-86); 53 (88.3%) had stage 3 or 4 cancer; 9 (15%) reported ethnicity as Hispanic or Latino; 39 (65%) reported race as White; 12 (20%) Black; 3 (5%) American Indian; and 6 (10%) multiple races. At 6-months followup, intervention group participants had greater ACP documentation (30 (100%) versus 12 (40%)), strongly agreed that they were satisfied that care matched their preferences (27 (90%) versus 18 (66.7%)); no differences in palliative care use (3 (10%) versus 3 (10%)) and greater hospice use (15 (55.6%) versus 3 (10.0%)) than control group participants. Conclusions: This group CHW-led ACP education intervention improved ACP documentation, satisfaction, and hospice use at one VA. Group CHW-led ACP approaches may be a potentially scalable approach to address workforce shortages and effectively improve ACP. Clinical trial information: NCT06646614 .

The bladder cancer journey: Using a social media campaign to uncover educational needs of patients' caregivers.

e21017 Background: After a cancer diagnosis, many patients and their family members/friends turn to social media for information and support. Despite the prevalence of bladder cancer, social media resources are lacking compared to those for other cancers and contain moderate- to poor-quality information. To address these gaps, we designed a nationwide educational campaign using social media to raise awareness about bladder cancer symptoms, diagnosis, and treatments, as well as empower patients and caregivers to voice their concerns to their cancer care team. Methods: The educational campaign began with a live session on Instagram with a urologist content creator and oncologist to provide opportunities for real-time learning and dialogue about bladder cancer symptoms, diagnosis, and treatments. Next, 4 content creators with connections to bladder cancer or to those who may have an increased risk disseminated educational content about bladder cancer symptoms, diagnosis, and treatments. A survey evaluated the awareness and experiences of caregivers (family members or friends) of people with bladder cancer. Results: The live session and social media campaign garnered almost 170,000 total views. Among the comments posted (n = 30), the top themes included personal experience with bladder cancer (83%), appreciation for education (57%), early detection/positive outcomes (33%), and frustration with treatment (30%). In the survey, 67% of caregivers (n = 79) were able to correctly identify blood in the urine as the most common symptom of bladder cancer, but 65% (n = 79) said they were not at all familiar with symptoms before their family member/friend was diagnosed. Regarding their experiences with the cancer care team, 62% (n = 77) said they were extremely or moderately satisfied with the communication between their family member/friend and their cancer care team. Notably, only 41% (n = 76) said their family member/friend felt extremely or moderately included when making decisions with their cancer care team about their treatment. Additionally, 48% (n = 75) said they wished their family member’s/friend’s healthcare team talked more about their overall well-being. When asked to describe the most common difficulties their family member/friend experienced in receiving cancer treatment, caregivers (n = 48) most frequently reported access to care (25%), side effects from treatment (21%), and death (21%). Caregivers (n = 45) identified critical gaps in information that they felt should have been addressed before treatment began, specifically regarding symptoms/early signs of bladder cancer (27%), education in general (24%), treatment options (18%), and support needs (16%). Conclusions: Family members and friends feel underprepared to support patients with bladder cancer, primarily due to insufficient early education about symptoms and inadequate resources for ongoing reference and support.

Delayed serplulimab combined with nab-paclitaxel and epirubicin in high-risk, early HR+/HER2− breast cancer (HELEN-B 018): A multicenter, single-arm, phase 2 trial.

609 Background: Novel treatment options are needed to improve long-term outcome of high-risk early HR+/HER2− breast cancer. Evidence shows a programmed death 1 inhibitor combined with chemotherapy increases pCR rates in this subtype. We aimed to evaluate the efficacy and safety of serplulimab combined with nab-paclitaxel and epirubicin in high-risk, early HR+/HER2− breast cancer. Methods: This multicentre, single-arm, phase 2 trial was conducted in China at 6 hospitals. Patients were eligible if they were 18 years or older, with previously untreated early HR+/HER2- breast cancer, and Ki-67 greater than or equal to 20%, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. Participants were allocated to intravenous nab-paclitaxel (260 mg/m 2 ) and intravenous epirubicin (75 mg/m 2 ) on the first day and intravenous serplulimab (4.5mg/kg) on the third day of the treatment cycle. 6 cycles of neoadjuvant treatment were administered. The primary outcome was pCR (defined as ypN0 or ypT0/is), assessed in the full analysis set, which included all patients who had started the trial treatment. We estimated that with enrollment of 109 participants, this trial would have 80% power to detect a true difference in the percentage of patients with a pCR of 10% at a one-sided alpha level of 0.025, with a dropout rate of 10%. This study is registered with ClinicalTrials.gov (NCT06394661). Results: Between Apr 28, 2024, and May 24, 2025, 136 patients were assessed for eligibility; 27 were ineligible and 109 participants were enrolled in this study, of whom 101 participants started trial treatment. Median age of the participants was 49 [range, 30 to 72] years at the time of enrolment, and 45 (44.6%) were PD-L1 positive (CPS ≥1). pCR was achieved in 23 patients (22.8%, 95%CI 15.3%-32.4%). PCR rate was numerically higher in patients with PD-L1 positive tumors (44.4%, 95%CI 30.0%-59.9%). During the neoadjuvant phase, 30 (29.7%) patients experienced grade 3 or higher treatment-related adverse events. The most common grade 3–4 adverse events were increased alanine aminotransferase (ALT; six [5.9%]), increased aspartate aminotransferase (AST; five [5.0%]), and diarrhea (four [4.0%]), There were no treatment-related deaths. Conclusions: Delayed serplulimab combined with nab-paclitaxel and epirubicin showed promising anti-tumour activity and manageable safety in patients with HR+/HER2− breast cancer; the pCR rate was higher in PD-L1 expression tumor. These findings support further evaluation of this regimen in randomized controlled trials. Clinical trial information: NCT06394661 .

Disparities in inpatient treatment delivery for gynecologic cancers: A national analysis using machine learning.

e13694 Background: Patients with gynecologic malignancies are frequently hospitalized for cancer-related and unrelated indications. Treatment varies by cancer type: endometrial and ovarian cancers are managed with surgery and adjuvant chemotherapy; early cervical cancer requires surgery while locally advanced disease requires chemoradiation; vulvar and vaginal cancers require surgical resection with or without radiation. We used machine learning to identify factors associated with treatment receipt among hospitalized patients. Methods: We queried the National Inpatient Sample (2016-2021) for hospitalizations with cervical, ovarian, endometrial, vulvar, or vaginal cancer. Treatment was defined as gynecologic surgery, staging/debulking, lymphadenectomy, chemotherapy, or radiotherapy during admission. A gradient boosting classifier predicted treatment receipt with SHAP analysis for feature importance. Results: Among 188,709 admissions (mean age 62; 66% White, 15% Black, 11% Hispanic), 34% included treatment. Among treated patients, 67% received gynecologic surgery, 47% oophorectomy/salpingectomy, 17% lymphadenectomy, 9% omentectomy, 4% chemotherapy, and 1% radiotherapy. Treatment rates by cancer: endometrial 38%, ovarian 33%, cervical 26%, vulvar 17%. Elective admissions were more likely to include treatment than non-elective (77% vs 13%). Treatment was more frequent at urban teaching vs rural hospitals (37% vs 16%) and among privately insured vs Medicare patients (44% vs 28%). Model AUC: 0.906. Top predictors: admission type, teaching status, age, cancer type, payer. Conclusions: Treatment delivery varies substantially by admission context and hospital setting. These system-level factors may represent targets for improving care coordination and access.

Long-term oncologic outcomes of PSMA PET–guided salvage radiotherapy for biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis.

5121 Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging has demonstrated superior diagnostic accuracy over conventional imaging in localizing recurrent prostate cancer after radical prostatectomy. Previous meta-analyses have established its value in detection and treatment planning; however, whether PSMA-guided salvage radiotherapy (SRT) translates into improved long-term oncologic outcomes remains uncertain. We conducted a systematic review and meta-analysis to assess the impact of PSMA PET-guided SRT on survival outcomes in patients with biochemical recurrence after radical prostatectomy. Methods: A comprehensive search of PubMed, Embase, and Cochrane Library was performed on January 16, 2025. Studies comparing PSMA PET–guided SRT with conventional SRT in post-radical prostatectomy patients with biochemical recurrence were included. Long-term oncologic outcomes including failure-free survival (FFS), biochemical progression-free survival (bPFS) and metastasis-free survival (MFS), were pooled using hazard ratios (HRs). Results: Nine studies comprising 4,278 patients met the inclusion criteria, including 1,418 patients treated with PSMA PET–guided salvage radiotherapy and 2,860 who received conventional salvage radiotherapy. Compared with conventional SRT, PSMA PET–guided SRT was associated with significantly improved FFS (HR, 0.46; 95% CI, 0.28–0.75). However, the PSMA PET-guided SRT group had a significantly higher risk of biochemical progression; bPFS (HR, 1.40; 95% CI, 1.16–1.69) and metastasis; MFS (HR, 3.16; 95% CI, 2.08–4.80). Conclusions: PSMA PET–guided salvage radiotherapy was associated with reduced early treatment failure, as reflected by improved failure-free survival, but a higher risk of biochemical progression and metastatic events. These findings indicate that while PSMA PET-guided intervention may reduce early treatment failure, its impact on long-term disease control remains uncertain and requires further prospective validation.

Operationalizing yoga as a quantifiable component of guideline-aligned multimodal exercise oncology care using RE-AIM.

e13589 Background: Exercise oncology guidelines (ACSM/ACS) recommend ≥150 minutes/week of moderate-intensity aerobic activity plus resistance training; however, yoga remains inconsistently integrated into formal exercise prescriptions due to challenges defining frequency, intensity, time, and type (FITT), quantifying delivered dose, and standardizing safety and documentation. This gap limits inclusion of yoga within scalable, guideline-aligned multimodal exercise care, particularly for patients deconditioned during treatment. The CHALLENGE trial demonstrated survival benefits from structured exercise in colon cancer survivors, underscoring the importance of accurate exercise dose attribution. Methods: Guided by the RE-AIM framework, we developed an implementation-ready approach to operationalize yoga as a quantifiable, safe component of guideline-aligned multimodal exercise oncology care. To support Reach, relative intensity measures (rating of perceived exertion [RPE] and talk test) were used to accommodate treatment-related variability. To support Implementation, yoga sessions were decomposed using a predefined movement taxonomy (restorative/breathing, mobility, standing balance/strength, dynamic standing flow) to enable consistent dose attribution across instructors and sites, informed by the Compendium of Physical Activities metabolic equivalent of task (MET) values. Dose was operationalized through standardized estimated metrics, including moderate-intensity minutes, MET-minutes, and muscle-strengthening exposure defined by time-under-tension during loaded postures performed at ≥moderate relative effort. Safety was operationalized through standardized pre-exercise screening, symptom-guided modification, and explicit escalation pathways. Results: Dose Prescription (FITT): Frequency targeted 3–5 sessions/week. Intensity targeted moderate effort during flow-based segments (approximately 3–5 METs; RPE 3–4/10). Time was prescribed as 45–60 minutes/session, with ≥20–30 minutes of continuous standing flow. Type included standing flow for aerobic exposure, effort-qualified standing postures ≥2 days/week, and restorative components to support symptom management and exercise initiation. This structure was designed to yield approximately 60–150 minutes/week of moderate-intensity activity (180–600 MET-minutes) and was integrated with additional aerobic modalities as needed to meet guideline-based targets. Conclusions: This RE-AIM–aligned methods framework provides an implementation-ready care-delivery approach to standardize the integration, documentation, and safety of yoga within guideline-aligned multimodal exercise oncology care, enabling yoga to function as an entry point and complementary modality alongside traditional aerobic and resistance exercise.

Drivers of early readmission and mortality after metastatic spinal cord compression in cervical cancer: Real-world evidence on disease progression, infection, and palliative gaps.

e17523 Background: Metastatic spinal cord compression (MSCC) is a catastrophic complication of cervical cancer, yet real-world patterns of local therapy, short-term outcomes, and drivers of early readmission are poorly defined. We evaluated treatment selection, mortality, and causes of 30-day readmission in a nationally representative cohort. Methods: We performed a retrospective cohort study using the Nationwide Readmissions Database 2022. Adult index hospitalizations for cervical cancer with MSCC were identified using ICD-10 codes. Receipt of local therapy (surgery and/or radiation) and no therapy were the exposures. Survey-weighted analyses compared demographics, hospital characteristics, discharge disposition, comorbidities, metastatic burden, and goals of care. Multivariable Cox regression evaluated predictors of 30-day readmission and mortality. Primary readmission diagnoses were categorized to identify dominant drivers of early utilization. Results: Among 2,382 weighted index admissions, only 8.4% received local therapy. Treated patients were younger (50.5 vs 53.9 years) and were more often managed at large, urban hospitals. Neurologic deficit (OR 8.51, 95% CI 2.60–27.82) and visceral metastases (OR 11.71, 95% CI 2.65–51.79) strongly predicted receipt of surgery or radiation. Length of stay (16.0 vs 8.3 days, p=0.002) and total charges ($311,661 vs $107,270, p<0.001) were substantially higher in the local therapy group. The overall 30-day readmission rate did not differ by treatment (36.2% vs 33.3%; OR 1.14, 95% CI 0.42–3.08). The most common primary readmission diagnoses were recurrent or progressive cervical cancer, sepsis, cancer-related pain, brain metastases, and bone metastases, indicating that early readmissions were driven primarily by disease progression, infection, and symptom crises rather than procedural complications. In adjusted models, palliative or hospice care was associated with lower 30-day readmission (HR 0.66, p<0.001) but higher 30-day mortality (HR 4.25, p<0.001), reflecting advanced disease and treatment limitation. Acute kidney injury, respiratory failure, ICU admission, and sepsis independently predicted early mortality. Conclusions: In cervical cancer–associated MSCC, definitive local therapy is uncommon and concentrated among patients with severe neurologic compromise and extensive metastatic burden. Early readmissions are driven predominantly by tumor progression, infection, and uncontrolled symptoms rather than treatment toxicity. Short-term outcomes are strongly influenced by acute organ failure and goals of care. These findings highlight the need for rapid neurologic triage, early palliative care integration, and post-discharge pathways targeting infection prevention and symptom control to reduce avoidable readmissions.

Clinical significance of <i>EGFR</i> amplification in patients with <i>EGFR</i> -mutated metastatic non–small cell lung cancer receiving first-line osimertinib.

8643 Background: With rapidly expanding first-line options for patients (pts) with EGFR -mutated non-small cell lung cancer (NSCLC), identifying biomarkers that may assist treatment selection is critical. The impact of EGFR amplification ( EGFR AMP ) on osimertinib outcomes is unclear. Methods: Pts with stage IV NSCLC and EGFR exon 19 deletions (ex19del) or the L858R mutation who received first-line osimertinib monotherapy at 5 centres across Italy and the United States and had undergone baseline next-generation sequencing (NGS) that included EGFR AMP assessment were included in this analysis. EGFR AMP was defined as an EGFR copy number (CN) ≥6. The predominantly amplified allele was inferred by INCOMMON, a biostatistical classifier, as previously described. Results: Among 473 pts, 81 (17.1%) had EGFR AMP . Compared to pts with non-amplified EGFR ( EGFR Non-AMP , n = 392), pts with EGFR AMP more frequently had TP53 co-mutations (80% vs 55%, p &lt; 0.001) and baseline brain (51% vs 34%, p = 0.008), liver (26% vs 13%, p = 0.009), and bone metastasis (65% vs 51%, p = 0.03). When treated with osimertinib, pts with EGFR AMP achieved similar objective response rate (ORR) (88% vs 83%, p = 0.23), but shorter median progression-free survival (mPFS) (11.6 vs 19.0 months, HR 1.77, p &lt; 0.0001) and overall survival (mOS) (34.0 vs 40.1 months, HR 1.40; p = 0.040). In a multivariable Cox-regression model, EGFR AMP retained its association with worse PFS (HR 1.36, p = 0.04), but not OS. EGFR AMP correlated with shorter PFS in both TP53 co-mutated (n = 269) (11.7 vs 15.0 months, HR 1.43, p = 0.02) and TP53 wild-type (n = 181) (10.4 vs 21.9 months, HR 2.38, p &lt; 0.001) cases, despite similar ORR and mOS. Among pts with ex19del, EGFR AMP (n = 44) showed similar ORR compared to EGFR Non-AMP (n = 241), but shorter mPFS (14.2 vs 20.2 months, HR 2.01, p &lt; 0.001) and mOS (35.4 vs 44.9 months, HR 1.62, p = 0.04). In contrast, no difference was observed in the L858R-mutated subgroup between EGFR AMP (n = 39) and EGFR Non-AMP (n = 150) cases (ORR 86% vs 75%, p = 0.14; mPFS 11.4 vs 14.3 months, HR 1.47, p = 0.06; mOS 33.2 vs 36.0 months, HR 1.19, p = 0.5). Within EGFR AMP cases, increasing EGFR CN ( EGFR Non-AMP vs CN≥6 &lt; 15 vs CN 15-30 vs CN &gt; 30) correlated with a stepwise reduction of mPFS (19.0, 16.7, 10.3, and 8.7 months, respectively; log-rank p &lt; 0.001) and mOS (40.1, 37.5, 38.8, and 15.3 months, respectively; log-rank p = 0.02). Moreover, amplification of the mutant allele, as opposed to wild-type amplification, correlated with inferior mPFS (8.3 vs 12.1 months, HR 2.72, p = 0.002) and mOS (17.3 vs 39.7 months, HR 2.08, p = 0.046). Among pts with paired NGS before and after acquired osimertinib resistance (n = 113), those with baseline EGFR AMP more frequently showed acquired MET alterations (29% vs 12%, p = 0.04). Conclusions: EGFR AMP is associated with distinctive characteristics and worse outcomes to osimertinib among pts with stage IV EGFR -mutated NSCLC.

"Who even talks to her anymore?" Misalignment between cervical cancer care landscape and community awareness in Rwanda.

1601 Background: Cervical cancer remains the most common female cancer in Rwanda. Despite the significant advancement in early detection and treatment of cervical cancer in the country, many patients do not seek care or experience significant delays in seeking and getting care. Historically, elements of stigma have contributed to care non-engagement and patient delays. With ongoing growth and expansion of care services over the past decade, we sought to explore the current state of Rwandan patients’ perspectives on and experience with cervical cancer stigma. Methods: We conducted an exploratory qualitative study using semi-structured interviews of a purposeful sample of 25 patients with cervical cancer, including 12 living with HIV, who were treated at a tertiary cancer facility in Northern Rwanda. Interviews were conducted in Kinyarwanda, audio-recorded, transcribed verbatim, and translated into English. Guided by the Health Stigma and Discrimination Framework, the team conducted thematic analysis supported by NVivo (LUMIVERO). Results: Our analysis revealed that cancer stigma remains prevalent in participants’ communities, and this stigma has multifaceted impacts on their cancer care journey. Despite the national expansion in the availability of screening, early detection, and curative cervical cancer care services, patients continue to report limited community awareness of cervical cancer, with prevailing beliefs of fatalism and care scarcity. Knowledge gaps in cervical cancer diagnosis, treatment, and side effects contribute to stigmatizing behaviors by family members and neighbors, including rumors and social isolation. Participants also described perceptions of cancer incurability as contributing factors to social isolation. However, illness acceptance and religious engagement were identified as helpful coping mechanisms to mitigate stigma and promote care-seeking. Finally, participants’ lived experiences with cervical cancer and survivorship motivated them to encourage others in their community to participate in screening and seek medical care. Conclusions: Our findings highlight the influence of community beliefs about cervical cancer on medical care-seeking behavior and community reception of patients. Some beliefs were misaligned with patients’ current lived experiences with recent advances in the national cancer care environment. For Rwanda to achieve its cervical cancer elimination goals, these findings reinforce the need for continued community awareness of cervical cancer symptoms and treatment as well as sensitization to the available community assets for early detection and treatment.

Genomic determinants of metastatic burden and survival in metastatic urothelial carcinoma.

4572 Background: Metastatic urothelial carcinoma (mUC) has variable outcomes. Metastatic site count (MSC) correlates with prognosis; the genomic landscape underlying metastatic burden and survival is poorly characterized. We investigated associations among somatic alterations, metastatic patterns, and survival in a large clinical-genomic cohort. Methods: We analyzed 1,157 patients with metastatic bladder cancer by integrating genomic data from the AACR Project GENIE Cohort v18.0-public with clinical annotations and metastatic site information from the MSK-MET database. Associations between 428 genomic alterations and MSC were assessed using Mann-Whitney tests. Survival analyses (n=1,153; 364 events) used Kaplan-Meier estimation, log-rank tests, and Cox regression. Models were adjusted for age, MSC (stratified), and location (lymph, liver, lung). FDR correction was applied, and proportional hazards assumptions verified. Results: Median age was 68.7 years; median OS was 15.8 months. MSC stratification revealed survival differences: 0-1 sites (n=515, median OS not reached), 2-4 sites (n=415, median OS 62.8 months), and &gt;=5 sites (n=223, median OS 13.1 months; log-rank p &lt; 2.5 x 10 -19 ). Each increase in MSC category was associated with worse OS (FDR p &lt; 0.001). MSC predicted 2-year survival with an AUC of 0.78 (95% CI: 0.75–0.82). Six alterations were significantly associated with lower MSC (FDR &lt; 0.05): ERCC2 (n=122; d=0.50, FDR p=5.6 x 10 -6 ), STAG2 (n=128; d=0.40, FDR p=1.9 x 10 -4 ), FBXW7 (n=96; d=0.36, FDR p=7.1 x 10 -3 ), FGFR3 (n=291; d=0.17, FDR p=8.1 x 10 -3 ), TP53BP1 (n=35; d=0.59, FDR p=4.3 x 10 -2 ), and ARID2 (n=70; d=0.41, FDR p=4.6 x 10 -2 ). ERCC2 mutation frequency was 15.7% in 0-1 sites and 4.0% in &gt;=5 sites. Conversely, CDKN2A/B deletions were enriched in patients with &gt;=5 sites (28.3%/27.9%) compared with 0-1 sites (16.5%/15.9%; FDR p &lt; 0.01). Five alterations were independently associated with OS in univariable analysis (FDR &lt; 0.05): CDKN2B deletion (HR 1.81, 95% CI: 1.43–2.28, FDR p=1.7 x 10 -4 ), CDKN2A deletion (HR 1.79, 95% CI: 1.42–2.26, FDR p=1.7 x 10 -4 ), ERCC2 mutation (HR 0.39, 95% CI: 0.24–0.62, FDR p=1.1 x 10 -2 ), CREBBP mutation (HR 0.53, 95% CI: 0.37–0.75, FDR p=3.1 x 10 -2 ), and KDM6A mutation (HR 0.66, 95% CI: 0.52–0.84, FDR p=4.4 x 10 -2 . In multivariable analysis adjusting for age, MSC, and location, no genomic alterations retained independent significance, suggesting MSC mediates these prognostic effects. Penalized regression confirmed MSC as the dominant prognostic variable (HR 1.39 per site increase). Conclusions: DNA damage repair and chromatin modifier mutations are associated with oligometastatic phenotypes and favorable survival, whereas CDKN2A/B deletions correlate with polymetastatic disease. The attenuation of genomic effects after MSC adjustment suggests that metastatic burden is a key mediator. These findings support using genomic profiling to guide mUC prognosis.

Evaluation of adnexal features and histological response to intralesional SP-002 in nodular basal cell carcinoma.

2596 Background: No FDA approved nonsurgical therapies exist for primary nBCC at high-risk sites, e.g., H-zone, representing a significant unmet medical need. Recombinant IFN-alfa-2b previously achieved ∼85% complete histologic clearance in superficial and nBCC, but required multiple (9-12) injections and was associated with systemic toxicity. SP-002 encodes human IFN-γ and enables sustained, localized cytokine expression with anti tumor activity, achieved with a once weekly, three dose regimen that demonstrates a superior therapeutic index. Methods: Two early phase clinical studies of SP-002 in nBCC were completed: a single lesion study (ASN-002-001, NCT02550678, n=16), and a combination multilesion study with 4 weeks of vismodegib (ASN-002-003, NCT04416516, n=21, 46 lesions). Pretreatment biopsies from ASN-002-001 served as discovery specimens, while pretreatment biopsies from ASN-002-003 were prospectively assessed by central review for adnexal features (AdnF; follicular or eccrine differentiation) using standardized criteria. Post-treatement excision specimens were evaluated by local histopathology laboratories for CHC per protocol-defined criteria. CHC rates were calculated by AdnF. Results: ASN-002-001: sporadic low frequency/risk BCC, AdnF(+) rate was 20%. CHC rates were 33% (5e10vp), 83% (1.5 and 3.0e11vp). ASN-002-003: high-frequency multilesion BCC, AdnF(+) rate was ∼50%. CHC rates were 75% (1 nBCC)/52.9% (3 nBCC) (1.0e11vp) and 52.4% (3 nBCC) (1.5e11vp)-ITT. When analyzed by AdnF status, CHC rates were 97% in AdnF(-) lesions and 11.5% in AdnF(+) lesions. Baseline biopsies in non-responders demonstrated follicular/eccrine structures especially papillary mesenchymal bodies, harboring CKT15(+) stem cells (SC) and nuclear β-catenin, indicating active WNT signaling. Dual repression of programmed cell death effectors, CASP8/RIPK3, was also observed at baseline in lesions with residual disease with focal loss or widespread loss across tumor islands in β-catenin active regions. Either or both CASP8/RIPK3 were present in all complete responders at baseline and their absence may indicate risk for incomplete response to SP-002. Conclusions: SP-002 achieved high CHC rates at doses of 1.5e11vp/3.0e11vp and AdnF(-) lesions (most nBCC) had clearance rates comparable to surgical excision (&gt;90%).Adnexal differentiation identifies a biologically distinct, treatment-resistant subset with WNT pathway activation, adnexal niches harboring CKT15(+) SC, and impaired IFN-γ cell death. These findings support AdnF as a predictive biomarker and position SP-002 as a promising non-surgical option for selected patients with nBCC. Clinical trial information: NCT02550678 , NCT04416516 . CHC rate AdnF(-)n/N lesions (%) CHC rate AdnF(+)n/N lesions (%) ASN-002-001 (n=15, 15 lesions) 11/12 (91.6%) 0/3 (0%) ASN-002-003 (n=21, 46 lesions) 23/23 (100%) 3/23 (13%) 34/35 (97.1%) 3/26 (11.5%)

Menopausal hormone therapy use and counseling patterns among surgically menopausal BRCA mutation carriers.

e12736 Background: Risk-reducing salpingo-oophorectomy (RRSO) for BRCA mutation carriers (BRCAm) is recommended by age 35–40, resulting in premature iatrogenic surgical menopause. Menopausal hormone therapy (MHT) is safe and effective in BRCAm without a personal history of breast cancer, but use remains variable despite clear recommendations. We aim to assess the prevalence of systemic MHT, provider counseling patterns, patient attitudes, and patient-reported outcomes among BRCAm following surgical menopause. Methods: We conducted a cross-sectional, web-based survey of patients recruited through a national BRCA network. Eligible participants were BRCAm and underwent RRSO to prevent or treat ovarian cancer before age 60. Individuals with a personal history of breast cancer were excluded. Menopausal symptom severity was assessed using the Menopause Rating Scale (MRS), and psychosocial distress was measured using the NCCN Distress Thermometer. Univariate and bivariate analyses (Chi-square for categorical variables; t-test/ANOVA for continuous) assessed the relationships between MHT and outcomes of interest. Results: Of 396 completed surveys, 259 respondents met eligibility criteria. The median age at surgical menopause was 41.6 years. Seven (2.7%) reported having their ovaries removed to treat ovarian cancer. Most identified as white (94.21%) and non-Hispanic (88%) and most were insured (94.2%), at least college-educated (71.43%), earning &gt; 100,000 per year (65.64%), and receiving medical care in urban or suburban areas (91.12%). Most were married (79.5%), followed by single (8.1%), divorced (5.0%), long-term partner (3.1%), and widowed (1.9%). 197 (73.78%) reported using some type of local or systemic hormone therapy, with 64.4% reporting systemic use. The majority (59.2%) also reported using non-hormonal alternative treatment. Reasons for MHT non-use included concern for cancer risk (70%), personal cancer history (2.8%), and other health problems (2.8%). Participants receiving systemic MHT had significantly lower MRS scores compared with non-users, while distress scores were similar between groups; 20.85% percent of women reported that menopausal symptoms were not discussed prior to RRSO. Conclusions: Among surgically menopausal BRCAm, 35.6% are not using MHT, and guideline-concordant counseling is inconsistently delivered. These findings highlight the need for improved provider and patient education and development of evidence-based, patient-facing interventions to reduce inappropriate non-use of systemic MHT and mitigate the long-term health consequences of estrogen deprivation.

Real-world conversion surgery, survival outcomes, and safety of atezolizumab plus bevacizumab with TACE in unresectable hepatocellular carcinoma.

e16223 Background: Hepatocellular carcinoma (HCC) remains challenging to manage once unresectable. Although atezolizumab plus bevacizumab is standard first-line therapy, its potential to enable conversion to curative resection is not well defined. We evaluated the efficacy and safety of atezolizumab plus bevacizumab combined with on-demand transarterial chemoembolization (TACE) in a real-world cohort, with a focus on surgical conversion. Methods: We conducted a multicenter real-world study of 121 patients with unresectable HCC treated with atezolizumab plus bevacizumab ± TACE. The primary endpoint was the objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate, surgical conversion rates and safety. Results: Patients treated in the first-line setting achieved better outcomes than those receiving second-line therapy (ORR 47.3%, 53/112, vs 22.2%, 2/9), with longer median PFS (19.0 vs 8.8 months) and OS (35.3 vs 13.0 months). In the first-line cohort, patients receiving atezolizumab plus bevacizumab with TACE showed higher ORR (50.5%, 48/95, vs 29.4%, 5/17), longer median PFS (20.9 vs 8.0 months) and OS (35.3 vs 25.6 months) compared with those without TACE, with outcomes numerically exceeding historical GO30140 and IMbrave150 benchmarks. Successful R0 resection was achieved in 33.7% (32/95) of patients in the with-TACE group versus 5.9% (1/17) in the without-TACE group. Among resected patients, pCR occurred in 34.4% (11/32) and MPR in 68.8% (22/32; MPR, &lt; 50% viable tumor cells). Among patients achieving MPR, RECIST responses included CR (n = 3), PR (n = 10), and SD (n = 9), indicating incomplete concordance between pathological and radiological assessments. A single tumor and higher CD8 + T-cell infiltration in baseline biopsy specimens were associated with a more favourable ORR. We further identified ECOG performance status, lower tumor burden, and pathological features of baseline biopsy specimens (higher CD4 + and CD8 + T-cell infiltration) as key factors associated with successful conversion to surgery. Treatment-related adverse events (TRAEs) occurred in 91.6% and 88.2% of patients in the with- and without-TACE groups, with grade 3/4 events in 54.7% and 52.9%, respectively; no grade 5 events or postoperative complications were observed. Conclusions: In this multicenter real-world cohort, on-demand TACE combined with atezolizumab plus bevacizumab enabled deep tumor responses and curative-intent resection in one-third of initially unresectable HCC patients. Baseline immune infiltration identified candidates most likely to benefit from conversion. These findings support a conversion-oriented strategy integrating locoregional and systemic therapy to bridge unresectable HCC toward surgical cure.

Impact of fermi level engineering on the conductive behavior of MLGNR for nano-scale interconnects

1 nm‐Level Solid Electrolyte Interphase on Coal‐Based Hard Carbon Enables Superior Sodium Storage

ABSTRACT Solid electrolyte interphase (SEI) stands as a pivotal determinant of battery performance, governing ion transport and storage behavior, yet precise control over its thickness remains a formidable challenge. Here, we construct a 1 nm‐level SEI on coal‐based hard carbon through developing a synergistic regulation strategy toward surface chemistry and microstructure. Oxygen‐lean surface chemistry and typical micropore structure are created via phosphate‐directed oxygen and carbon etching in a confined microenvironment established by pitch light component surface coating. The surface oxygen content is remarkably reduced from 6.80 to 1.73 at.%, while the pore volume is enlarged by four times. The surface chemistry and structure properties of hard carbon contribute to the construction of 1 nm‐level SEI featured by an organic outer layer and an inner layer rich in Na 2 O and Na 2 CO 3 , which represents the lowest value in current hard carbon anodes of sodium‐ion batteries. Consequently, the as‐designed coal‐based hard carbon achieves superior initial coulombic efficiency (92.18%), reversible capacity (363 mAh g −1 ) and rate capability (231.2 mAh g −1 at 3 A g −1 ). This study provides a new material design approach to precise SEI thickness control, promising to inspire extensive research across diverse battery chemistries.

Modified monobenzone supercarriers as targeted therapies for metastatic melanoma.

e21530 Background: Melanoma is the deadliest form of skin cancer, with a five-year survival rate of ~35% once metastasis occurs. Despite advances in targeted and immunotherapeutic approaches, metastatic melanoma remains difficult to fully eradicate. Targeting the melanogenic pathway offers a complementary and selective strategy, as melanin biosynthesis occurs exclusively in melanocytes and melanoma cells via oxidation of L-tyrosine by tyrosinase and TRP-1 within melanosomes. Monobenzyl ether of hydroquinone (MBEH) is a phenolic compound used as a topical depigmenting agent that causes melanocyte destruction via tyrosinase-mediated toxic quinone generation inducing necrotic cell death and subsequent immune activation. MBEH has demonstrated anti-tumor effects in vivo when applied topically to tumors, yet the drug is not suited for systemic application to attack metastatic tumors. Methods: To reduce MBEH toxicity and improve solubility and selectivity, we developed a modified derivative formulated into ~100–150 nm liposomal nanoparticles (TOnc-LNP). Melanoma cells were treated in vitro with TOnc-LNP for 24 hours, and viability was assessed by IncuCyte imaging and LDH assays. In vivo , NSG and C57BL/6 mice received systemic TOnc-LNP every three days for two weeks, followed by lung, serum, and spleen collection for tumor burden and immunophenotypic analyses. Results: Treatment with TOnc-LNP resulted in pronounced, concentration-dependent killing of B16-F10 murine cutaneous melanoma cells and primary human uveal melanoma cells in vitro, reducing viable cell populations by more than 90% within 24 hours. In contrast, unencapsulated MBEH exerted only growth-inhibitory effects. Time-resolved live-cell imaging revealed extensive nanoparticle-induced membrane disruption, culminating in widespread cell death and lysis. In a murine pulmonary metastasis model using immunodeficient mice, systemic administration of TOnc-LNPs markedly reduced metastatic burden, with treated animals exhibiting over 50% fewer grossly visible lung metastases and more than a 40% reduction in gp100-positive tumor coverage relative to control mice, indicating substantial decreases in both metastatic nodule number and tumor-occupied lung area. Consistent with these findings, in an immunocompetent murine pulmonary metastasis model, TOnc-LNP treatment resulted in a greater than 70% reduction in metastatic lung nodules compared with controls. Conclusions: These results demonstrate that nanoparticle-mediated delivery significantly enhances the therapeutic efficacy of our lead candidate, achieving potent suppression of metastatic melanoma. Collectively, these findings support the further development of TOnc-LNP as a promising systemic strategy for melanoma therapy, with potential translational relevance for improving clinical outcomes in patients with metastatic disease.

Linperlisib plus CHOP for newly diagnosed peripheral T-cell lymphoma: A single-arm, phase Ib/II study (LINCH trial).

7004 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous type of aggressive non-Hodgkin lymphoma with poor prognosis. CHOP-based regimens are most widely used for PTCL yet response rates and long-term survival remain unsatisfactory. Linperlisib, a selective PI3Kδ inhibitor, has shown encouraging antitumor activity with manageable safety profile in relapsed or refractory PTCL. This study aimed to evaluate the efficacy and safety of linperlisib plus CHOP (L-CHOP) as first-line treatment for newly diagnosed PTCL. Methods: The LINCH trial (NCT05949944), a multi-center, single-arm phase Ib/II study, enrolled patients aged ≥ 18 years with newly diagnosed PTCL. In phase Ib, 6 patients received 6 cycles of L-CHOP to determine the recommended phase II dose (RP2D). In phase II, patients received L-CHOP at the RP2D. Following 6 cycles, patients achieving complete response (CR) or partial response (PR) continued linperlisib maintenance until progression or intolerable toxicity or up to 24 months. The primary endpoints were the DLTs incidence (phase Ib) and the CR rate after 6 cycles of L-CHOP (phase II). Preliminary results were reported. Results: From August 15, 2023 to November 15, 2025, 44 patients were enrolled, including 6 patients in phase Ib. The median age was 57 years (range 18–77); 28 patients were males (63.6%). Most patients (n = 35, 79.5%) had stage III-IV disease, and 17 (38.6%) had an IPI score of 3–5. In phase Ib, one DLT (grade 3 febrile neutropenia) occurred in cycle 1, confirming linperlisib 80 mg once daily as RP2D. At the data cutoff on December 30, 2025, efficacy was evaluable in 34 patients (26 completed six cycles; 8 discontinued early), with 10 still receiving induction therapy. After six cycles of combination therapy, 19 patients (55.9%) achieved CR and four achieved PR, resulting in an objective response rate (ORR) of 67.6%. Treatment-emergent adverse events (TEAEs) occurred in 32 patients (94.1%); hematologic toxicity were common: neutropenia (n = 24, 70.6%), leukopenia (n = 21, 61.8%), anemia (n =14, 41.2%). Grade ≥ 3 TEAEs occurred in 19 patients (55.9%), most frequently neutropenia (n = 13, 38.2%), leukopenia (n = 10, 29.4%) and pneumonia (n = 4, 11.8%). Conclusions: Preliminary results from LINCH study suggest that linperlisib combined with CHOP as first-line treatment for PTCL achieved promising efficacy and manageable safety. A randomized controlled trial evaluating linperlisib plus CHOP versus CHOP in patients with newly diagnosed PTCL has been initiated (NCT06548347). Clinical trial information: NCT05949944 . Baseline characteristics. Characteristics Patients (n=44) Age, years (median [IQR]) 57 (18-77)  Sex  MaleFemale 28 (63.6%)16 (36.4%) ECOG PS  0-12 39 (88.6%)5 (11.4%) Lugano stage  I-II III-IV 9 (20.5%)35 (79.5%) Pathological types  AITLPTCL-NOSALCLTFHL-NOSMEITLSPTCL 23 (52.3%)14 (31.8%)3 (6.8%)2 (4.5%)1 (2.3%)1 (2.3%)

Early-onset colorectal cancer hospitalizations in the United States: Metastatic burden, comorbidity, and mortality.

e15567 Background: The incidence of early-onset colorectal cancer (CRC) is increasing in the United States; however, national data on disease stage, comorbidity burden, and outcomes among hospitalized patients are limited. This study examined age-stratified trends in hospitalized CRC, focusing on metastatic burden, comorbidities, and in-hospital outcomes. It was hypothesized that younger patients present with more advanced disease despite lower medical comorbidity, and that benign gastrointestinal diagnoses and lifestyle-related risk factors may contribute to diagnostic delay. Methods: A retrospective analysis of the Nationwide Inpatient Sample (2018–2022) identified adult hospitalizations with CRC. Survey weighting, stratification, and clustering were used. Patients were grouped by age ( &lt; 45 versus 45–75 years). Metastatic disease, comorbidities, lifestyle-related factors (obesity, smoking, alcohol), and benign gastrointestinal diagnoses (IBS, hemorrhoids, abdominal pain) were identified by ICD codes. Outcomes included in-hospital mortality, length of stay, and hospital charges. Multivariable logistic regression was used to assess factors associated with mortality. Results: Among an estimated 2.0 million CRC hospitalizations, patients younger than 45 years represented a minority but exhibited a higher prevalence of metastatic disease compared to those aged 45–75 years (57.7% versus 47.6%). The younger cohort had a markedly lower prevalence of diabetes, hypertension, chronic kidney disease, coronary artery disease, chronic obstructive pulmonary disease, and cirrhosis. Obesity prevalence was similar across age groups, while smoking and alcohol use remained similar among younger patients. Benign gastrointestinal diagnoses associated with symptom misattribution were more prevalent among younger patients, including IBS, hemorrhoids, and chronic abdominal pain. Early-onset CRC hospitalizations were associated with lower in-hospital mortality (2.7% versus 4.0%) and similar length of stay and charges. Adjusted analyses indicated that mortality was primarily associated with age, acute organ dysfunction, severe illness, and cardiovascular comorbidities. Conclusions: Early-onset CRC hospitalizations show advanced metastatic disease despite lower comorbidity and mortality. High rates of benign gastrointestinal diagnoses and modifiable lifestyle factors may cause symptoms to be mistaken for noncancerous conditions, leading to delayed diagnosis. Prompt, vigilant diagnosis and targeted prevention are essential to improve outcomes.

TBCRC 058: A randomized phase II study of enzalutamide, enzalutamide with mifepristone, and treatment of physician’s choice in patients with androgen receptor-positive metastatic triple-negative or estrogen receptor-low breast cancer (NCT06099769).

TPS1162 Background: Triple-negative breast cancer (TNBC) refers to a heterogenous group of breast cancers that lack expression of ER, PR, and HER2. Despite recent advances with immunotherapy (IO) and antibody-drug conjugates (ADCs), TNBC remains the most aggressive subtype, with short overall survival in the metastatic setting. Breast tumors with low levels of ER and PR expression (1-10%) clinically behave like TNBC, and clinical management follows the TNBC treatment (tx) paradigm. We and others have identified a subset of ER/PR/HER2-negative breast cancers (BCs) that express the androgen receptor (AR). Enzalutamide (enza), an AR-antagonist, has demonstrated activity in AR-positive metastatic TNBC (Traina et al, JCO 2018). Activation of the glucocorticoid receptor (GR) has been implicated as a mechanism of resistance to AR inhibition in prostate and BCs (Kach et al, Sci Transl Med 2015). Effective therapies for advanced TNBC remain an unmet need, particularly in patients who are ineligible for or progress following a checkpoint inhibitor. This randomized study evaluates the efficacy of enzalutamide or enzalutamide plus the GR antagonist mifepristone (mif) as compared to physician’s choice chemotherapy (TPC). Methods: This is a randomized phase II trial; 201 patients (pts) will be randomized in a 1:1:1 fashion to enza, enza with mif, or TPC (carboplatin, paclitaxel, eribulin, or capecitabine). The primary endpoint (endpt) is progression-free survival (PFS), and the trial is designed to test the hypothesis that PFS in the pooled enza arms is superior to TPC; there is 80% power to detect a hazard ratio (HR) of 0.70, corresponding to an increase in median PFS from 3.5 months (mos) with TPC to 5.0 mos with enza-based tx. Secondary endpts include comparisons of PFS among the 3 arms and evaluation of response rate, clinical benefit rate, duration of response, overall survival, safety, and patient-reported outcomes by arm. Exploratory endpts include correlation of tumor and circulating markers (constitutively active AR variants in circulating tumor cells and cfDNA) with tx response. Eligible pts must have: ECOG 0-2, metastatic measurable or evaluable disease (dz), normal organ function, no history of brain mets, &lt; prior lines of chemotx, any # of prior endocrine txs, no prior anti-AR tx, no prior mif, no concurrent CYP17 inhibitor use. Tumors must test ER/PR low or negative, HER2 negative, AR &gt;10%. Pts with PD-L1+ BC must have received prior IO if not contraindicated. As of December 28, 2025, 32 of 201 pts have been enrolled on study. Clinical trial information: NCT06099769 .