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YOCAS yoga, mood disturbance, and insomnia: A URCC NCORP RB nationwide, phase III, randomized, controlled trial with cancer survivors.
12004 Background: Mood disturbance (MoD) and insomnia are two of the most pervasive and troubling side effects experienced by cancer survivors for years after completing adjuvant treatments. MoD and insomnia significantly interfere with survivors’ ability to perform essential daily activities such as cleaning, grocery shopping, cooking, taking medications, driving, and communicating with others. We previously reported that Yoga for Cancer Survivors (YOCAS) is effective for treating insomnia. YOCAS may also alleviate MoD, and changes in MoD may mediate the influence of YOCAS on insomnia. Methods: We conducted a nationwide, multisite, phase III randomized, controlled trial to examine: 1) the effects of YOCAS on MoD (i.e., overall MoD, anxiety, and fatigue), and 2) whether changes in MoD mediate the association between YOCAS and changes in insomnia. Survivors were recruited via the University of Rochester Cancer Center NCI Community Oncology Research Program Research Base (URCC NCORP RB). Non-metastatic cancer survivors, between 2-24 months post adjuvant therapy, aged 21 or older, with moderate or greater sleep disruption, and with no participation in yoga during the prior 3 months, were randomized to two arms: 1) standard care and 2) standard care plus the 4-week YOCAS intervention (2x/week; 75 min/session). The YOCAS consists of breathing exercises, 18 gentle Hatha and Restorative yoga postures, and meditation. MoD and insomnia were assessed using the Profile of Mood States and Insomnia Severity Index, respectively, at pre- and post-intervention. Results: A total of 410 survivors, recruited from 12 community-based oncology practices across the USA, were randomized (mean age = 54 10.4 years; 96% female; 75% breast cancer survivors). ANCOVAs revealed YOCAS participants, compared to standard care participants, experienced significantly less overall MoD (Mean Difference [Standard Error] = -5.08 [1.36]), anxiety (MD [SE] = -0.72 [0.29]), and fatigue (MD [SE] = -1.49 [0.41]; all p < 0.05) at post-intervention. Additionally, YOCAS participants reported significant improvements from pre- to post-intervention on overall MoD, anxiety, and fatigue (all p < 0.05), whereas standard care participants did not. Causal mediation analyses revealed changes in overall MoD partially mediated (24.9%; 95% CI: 10.9%, 42.6%) the association between YOCAS and changes in insomnia. Changes in fatigue also partially mediated (24.6%; 95% CI: 11.3%, 43.9%) the association between YOCAS and changes in insomnia (all p < 0.05). Conclusions: YOCAS yoga is effective for treating overall MoD, anxiety, and fatigue among survivors. Additionally, improvements in insomnia stemming from YOCAS yoga may be mediated by changes in overall MoD and fatigue. Clinicians should consider recommending yoga for survivors who experience overall MoD, anxiety, fatigue, and insomnia. Clinical trial information: NCT00397930 .
Twenty-five years of the IMPACT men’s health study: Survivorship, health behaviors, and social determinants of health among uninsured and underrepresented prostate cancer patients.
e13586 Background: The UCLA Men’s Health Study (MHS) was initiated 25 years ago to address critical gaps in prostate cancer (PCa) survivorship, quality of life(QOL), and health outcomes among uninsured and underrepresented men. MHS has collected patient-reported data across sociodemographic, physical, emotional, behavioral, and cancer-specific domains, providing an unparalleled view of survivorship patterns in a diverse, low-income, multi-ethnic PCa population. We conducted a systematic review of MHS findings to characterize long-term survivorship trends, identify determinants of QOL, and inform health-equity–focused interventions. Methods: The cohort included 1,328 participants enrolled in a program providing free PCa-related care to uninsured men in California across three periods: 2000–2008, 2009–2018, and 2019–2025, reflecting evolving treatment practices, health policy (including the Affordable Care Act), and external influences such as the COVID-19 pandemic. We evaluated longitudinal trends in patient-reported physical health, emotional well-being, and cancer-specific outcomes by enrollment period. Results: Participants included 771 enrolled PCa patients in 2000–2008, 529 in 2009–2018, and 28 in 2019–2025. Participants were predominantly < 65 years (86%), Hispanic (60%), and married/partnered (59%), and had low educational attainment (46%). Daily alcohol use declined over time (25% to 10%, p < 0.0001), and comorbidity burden decreased, with the proportion of participants with Charlson Comorbidity Index = 0 increasing from 36% to > 60% (p < 0.0001). Disease characteristics shifted, with earlier cohorts having a higher proportion of T1 disease and later cohorts showing more T2 disease, (p = 0.0004), Gleason grade distribution (p = 0.026),in later cohorts reflecting a higher proportion of intermediate/high-grade disease (GG 2–4), and pretreatment PSA levels (p < 0.0001). In multivariable analyses, current smoking was associated with worse survivorship outcomes, including lower physical functioning (β = −7.7, p = 0.028), lower SF-12 physical component scores (β = −3.2, p = 0.009), and greater bowel bother (β = −6.8, p = 0.037). Comorbidity burden was associated with poorer physical functioning (β = −5.5, p < 0.05) and worse mental health outcomes (β = −3.1, p < 0.05). Mental health outcomes were less strongly associated with age but were consistently influenced by behavioral and comorbidity factors. Conclusions: Across 25 years of follow-up, modifiable health behaviors, particularly smoking and comorbidity burden emerged as the strongest drivers of survivorship disparities among uninsured and underrepresented PCa patients These findings highlight the importance of integrating behavioral risk reduction and comorbidity management into survivorship care models to advance health equity.
Achieving epidemiologically representative enrollment and social determinants of health in the phase III evERA Breast Cancer study (NCT05306340).
1572 Background: Clinical trials have historically under-enrolled patients (pts) from racial and ethnic minority groups, resulting in study populations that do not reflect the epidemiology of cancer in the United States (US), limiting generalizability of the findings. In parallel, social determinants of health (SDOH) are increasingly recognized as key drivers of cancer outcomes, yet are infrequently collected in oncology trials due to operational, ethical, and privacy concerns. The Phase III evERA breast cancer (BC) study (Mayer et al ESMO 2025) was intentionally designed to address both challenges through proactive enrollment strategies and prospective SDOH data collection. Methods: evERA BC is a global study in pts with ER+, HER2– advanced BC. In the US, a multi-pronged operational strategy was implemented to achieve epidemiologically representative enrollment, including expanded and pragmatic eligibility criteria, prioritization of community-based sites, real-time enrollment monitoring, patient navigation and financial support, and advocacy partnerships. A tailored survey assessing 5 key social determinants of health (education, income, employment status, marital status, insurance type) was offered to US pts to support a protocol-specified exploratory SDOH efficacy objective. Results: The multifaceted operational enrollment strategy used in the evERA BC study resulted in a US cohort (n=144 of total accrual 373) whose racial and ethnic composition exceeded SEER epidemiologic distributions for ER+, HER2− advanced BC for African American (AA) (12.5% vs 11.1%), Asian (9% vs 5.7%), and Hispanic (H) pts of any race (16% vs 8.9%). Enrollment for the aggregate White race (71.5%) and non-Hispanic (NH) ethnicity (83.3%) categories were slightly lower than SEER estimates for White race (82.9%) and NH ethnicity (91.1%). These enrollment patterns contrast with historic Phase III BC trials, in which AA pts typically comprise <5% and H pts <9% of enrolled populations. Of the 144 U.S. evERA BC pts, 128 (89%) completed the optional SDOH survey, demonstrating feasibility of SDOH data collection in a clinical trial setting and informing evaluation of potential trends and associations with outcomes. Conclusions: The evERA study demonstrates that key operational strategies can achieve epidemiologically representative enrollment while enabling robust and compliant SDOH data collection in oncology clinical trials. These findings provide a practical roadmap for industry sponsors seeking to improve recruitment of underrepresented populations and to generate more clinically meaningful and generalizable evidence by integrating social context into trial design and data interpretation. Clinical trial information: NCT05306340 .
Peak inflammatory stress versus baseline neutrophil-to-lymphocyte ratio (NLR) for prediction of in-hospital mortality in critically ill glioblastoma patients: MIMIC-IV cohort analysis.
e14103 Background: Systemic inflammation is a recognized driver of disease progression in Glioblastoma (GBM). While the Neutrophil-to-Lymphocyte Ratio (NLR) is an established oncologic biomarker. It is still ambiguous whether acute adverse outcomes are driven by a patient’s baseline inflammatory state or the magnitude of their physiological response to acute stress (surgery, clinical decline). We analyzed whether the "peak inflammatory surge" within the first 24 hours of ICU admission is a prognostic marker of in-hospital mortality compared to baseline values. Methods: we conducted a retrospective cohort study utilizing the MIMIC-IV(v3.1) database. Adult GBM patients admitted to the ICU were included. To capture the dynamic range of acute inflammation, we derived two distinct metrics from complete blood counts obtained within the first 24 hours of admission: "Baseline NLR" (minimum physiological stress: min neutrophils/max lymphocytes) and "Peak NLR" (maximum physiological stress: max neutrophils/min lymphocytes). The primary endpoint was in-hospital mortality. Due to the right-skewed distribution of inflammatory biomarkers, NLR values were natural log-transformed (ln[NLR]) for multivariate logistic regression analysis, adjusted for age. Results: A total of 242 patients met the inclusion-exclusion criteria. The overall in-hospital mortality rate was 9.9% (n=24). Baseline NLR did not differ significantly between survivors and non-survivors (median 7.71 vs 8.39; P=0.203), suggesting comparable initial physiological states. In contrast, Peak NLR was significantly high in nonsurvivors compared to survivors (median 10.28 vs 8.74; P=0.039). In univariate analysis, Peak NLR was significantly associated with mortality (OR 1.77; 95% CI 1.08–2.88; P=0.023). Upon multivariate adjustment for age, Peak NLR remained an independent predictor of mortality (OR 1.69; 95% CI 1.03–2.76; P=0.038). Conclusions: Mortality in critical GBM cases is independently associated with the magnitude of acute inflammatory surge rather than baseline status. Peak NLR may serve as a valuable prognostic and cost-effective marker for risk stratification in neuro-oncology critical care. Statistically significant clinical and laboratory predictors of in-hospital mortality. Predictor Variable Survivors (N=218) Non-Survivors (N=24) Adjusted / Unadjusted Odds Ratio (95% CI) P-value Age, median (IQR), years 61.0 (51.0–69.0) 71.5 (57.8–79.3) 1.04 (1.00–1.07) 0.018 Peak NLR, median (IQR) 8.74 (3.54–16.37) 10.28 (6.61–23.53) — 0.039 Log (Peak NLR), univariate — — 1.77 (1.08–2.88) 0.023 Log (Peak NLR), multivariate* — — 1.69 (1.03–2.76) 0.038 Age, multivariate* — — 1.03 (1.00–1.06) 0.055 Mortality rate by stress tier (%) 8.8 13.1 — 0.330 CI: Confidence Interval, IQR: Interquartile Range.
Longitudinal safety of lisocabtagene maraleucel (liso-cel) in patients (pt) with second-line or later (2L+) large B-cell lymphoma (LBCL).
7031 Background: Liso-cel has shown favorable efficacy and a manageable, consistent safety profile across B-cell malignancies, including R/R LBCL. Here, we present pooled longitudinal safety results in pts who received liso-cel as 2L+ treatment for LBCL in 3 pivotal clinical trials. Methods: Data from liso-cel–treated pts in the TRANSFORM (2L transplant-eligible LBCL, NCT03575351), PILOT (2L transplant-noneligible LBCL, NCT03483103), and TRANSCEND NHL 001 (third-line or later LBCL, NCT02631044) trials were pooled. Incidences of infections, laboratory parameters, and concomitant medication/procedure use were assessed from Day (D) 0–15, D16–30, Month (M) 2–3, M4–6, M7–9, M10–12, M13–18, M19–24, and M25 to end of study (EOS). Incidences were calculated as pts with ≥ 1 event divided by ongoing pts during that period. Results: A total of 420 pts were included. Incidence of grade (gr) ≥ 3 neutropenia was highest from D0–15 (Table), decreased sharply after M6, then remained low. Overall, 62% of pts received growth factors for neutropenia, with highest use from D0–15 and minimal use after M3. Rate of gr ≥ 3 anemia was highest from D0–15, declined by M9, then remained low. A total of 49% of pts received red blood cell (RBC) transfusions at any point with highest use from D0–15 and minimal use after M3. Incidence of gr ≥ 3 thrombocytopenia was highest from D0–M3, declined by M9, then remained low. Platelet transfusions were received by 31% of pts at any point with highest use from D0–M3 and minimal use after M3. Use of erythropoiesis- and thrombopoiesis-stimulating agents was rare (1% and 2% at any point, respectively). Incidence of gr ≥ 3 infections was 15% overall and remained low in all periods (Table). Hypogammaglobulinemia (serum immunoglobulin < 500 mg/dL) ranged from 43% to 63% across periods with IVIG use in 20% of pts at any point on study. B-cell aplasia declined over time from 99% from D0–15 to 73% by M12 and < 50% beyond M18. The overall incidence of second primary malignancies was 6%. Conclusions: In these longitudinal analyses in liso-cel–treated pts with 2L+ LBCL, gr ≥ 3 cytopenias and concomitant medication use decreased over time with minimal needs for growth factors or transfusions after M3. Gr ≥ 3 infections remained low in the short- and long-term periods despite persistent hypogammaglobulinemia and B-cell aplasia in most pts at M12. These data underscore the favorable long-term safety of liso-cel in pts with 2L+ LBCL, reinforcing the feasibility of outpatient management and the potential for low health care resource utilization in clinical practice. Clinical trial information: NCT03575351 , NCT03483103 , and NCT02631044 . Period Gr ≥ 3 neutropenia, % Growth factor for neutropenia, % Gr ≥ 3 anemia, % RBC transfusion,% Gr ≥ 3 thrombo-cytopenia, % Platelet transfusion, % Gr ≥ 3 infection, % D0–15D16–30M2–3M4–6M7–9M10–12M13–18M19–24M25–EOS 8736332612151046 421816512< 111 2912171242132 351920521< 1< 11 2335321691331 12221832< 1001 6252< 11< 121
Embedding germline genetic testing into African oncology care: Early results from the Genetic Cancer Families (GenCAF) program.
10572 Background: Breast cancer outcomes in sub-Saharan Africa are marked by early onset, advanced stage at diagnosis, and high mortality. Although prior studies demonstrate a high burden of inherited cancer susceptibility variants in African populations, access to ancestry-informed genetic counseling and testing remains limited due to infrastructure constraints and poor integration into routine oncology care. The GenCAF program was developed to translate prior genomic evidence from Nigeria into a scalable, clinically embedded cancer genomics implementation model in African settings. Methods: Consecutive breast cancer patients were prospectively enrolled and offered genetic counseling and testing regardless of age or family history. Germline testing was performed using the Color Hereditary Cancer Test (Color Health Inc). Counseling and result disclosure were delivered by locally trained oncology nurses or breast health specialists using a structured protocol. Clinical and tumor characteristics were correlated with genetic findings. The program was designed for scalability across English- and French-speaking sites. Results: Among 263 participants, 235 unrelated index breast cancer cases underwent germline testing. Overall, 43.0% (101/235) had a reportable germline finding, including 21.7% (51/235) with pathogenic or likely pathogenic (P/LP) variants and 21.3% (50/235) with variants of uncertain significance (VUS). Among genes present in ≥5% of cases with variant calls, VUS were most frequent in APC, ATM, PALB2, PMS2 , and BRCA2 , with several moderate-penetrance DNA repair genes exhibiting disproportionately high VUS burden, representing key candidates for future reclassification as African-ancestry reference data and gene–environment context expand. P/LP variants were most common in BRCA1 (n = 22), BRCA2 (n = 13), ATM (n = 4), and PALB2 (n = 4). P/LP carriers tended to be diagnosed before age 30 (13.7% vs 7.6%) and were more frequently diagnosed with advanced-stage disease (stage III–IV, 30.6%). Mean age did not differ overall; however, BRCA1 P/LP carriers had an earlier onset (mean age 40.1 years). Conclusions: These findings support integrating germline cancer genetics into routine breast cancer care in Africa through a scalable, nurse-led counseling model. The substantial VUS burden underscores the need for ancestry-informed interpretation and future reclassification efforts incorporating population-specific and environmental data. Planned implementation of point-of-care next-generation and long-read sequencing will further strengthen local diagnostic capacity and enable sustainable, locally driven precision prevention and oncology through risk-informed care. Age Group (yrs) P/LP (%) VUS (%) <30 13.7 7.6 30–39 15.7 23.9 40–49 23.5 23.4 50–59 27.5 26.6 ≥60 15.6 19.0
Clinical validation of ultra-sensitive WGS-based MRD detection in head and neck squamous cell carcinoma: Results from MONSTAR-SCREEN-3.
6066 Background: Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection has shown promise across various malignancies, yet limited data exist for Head and Neck Squamous Cell Carcinoma (HNSCC). The prospective, multicenter MONSTAR-SCREEN-3 study evaluates an ultra-sensitive whole-genome sequencing (WGS)-based MRD assay in patients with resectable solid tumors undergoing curative-intent therapy. Here, we report preliminary results from patients with resectable HNSCC enrolled in the definitive cohort (target n=1,100). Methods: Personalized ctDNA panels were generated using a WGS-based tumor-informed platform (Myriad Genetics), incorporating up to 1,000 tumor-specific variants identified through WGS of matched tumor tissue. Serial plasma samples were collected at baseline, 1 month post-surgery, quarterly during the first year, and biannually thereafter for up to two years. Results: As of November 2025, 44 patients with resectable HNSCC were enrolled; MRD results were available for 139 samples from 34 patients. Median age was 65 years (range: 39-87), with male predominance (65.7%). Clinical staging included Stage III (15.6%), IVA (75.0%), and IVB (9.4%). All patients underwent upfront radical surgery. Personalized panel creation succeeded in 100% of patients (34/34), identifying a median of 6,119 highly confident tumor-specific alterations per patient (range: 1,288-15,418) and yielding bespoke panels containing 717-1,000 alterations. Customized panels were created with 97.7% SNVs and 2.3% indels. The assay demonstrated 100% baseline ctDNA detection (34/34), with 5.9% detected at ultra-sensitive levels (tumor fraction <100 parts per million [ppm]; minimum detection: 83.3 ppm). MRD positivity at 1 month, 3 months, and 6 months was at ultrasensitive levels in 10/14 (71.4%), 6/16 (37.5%), and 4/5 (80%) patients, respectively. Among 10 patients who developed radiological recurrence, median lead time was 2.7 months (range: 0-4.6 months). MRD-positive patients at 1 month after surgery had poorer disease-free survival than MRD-negative patients (HR 18.9, 95% CI 2.4–148.9; log-rank P<0.0001). Nine of the 13 patients who were ctDNA-positive at 1 month experienced recurrence, whereas only 1 of the 20 ctDNA-negative patients recurred. Conclusions: The WGS-based personalized ctDNA assay achieved high technical feasibility in HNSCC, with comprehensive customized variant panels highlighting the critical importance of ultra-sensitive platforms. These results suggest potential clinical utility for recurrence surveillance in HNSCC. Updated results will be presented. Clinical trial information: UMIN000053975.
Safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activities of FL115, a novel IL-15 superagonist, from the first-in-human study in patients with locally advanced/metastatic solid tumors.
3154 Background: FL115 is an engineered IL-15/IL15Rα-Fbody fusion protein, in which Fbody is a single-chain Fc designed to eliminate classical Fc effects including ADCC/CDC/ADCP while retaining FcRn engagement. It aims to enhance anti-tumor immunity via IL-15-mediated signaling on NK and CD8+ T cells while minimizing complexity from Fc. Methods: The first-in-human, dose-escalation study of FL115 (NCT06130722) evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of FL115 in adult patients with advanced solid tumors. FL115 monotherapy was administered intravenously once weekly. Results: 11 patients (7F, 4M) were enrolled, median age 64, who had progressed on prior systemic therapies across four dose cohorts (3–60 μg/kg). MTD was not reached. No SAEs related to FL115 or DLT were observed. Most TRAEs were Grade 1–2 and aligned with the known safety profile of cytokine-based therapies and underlying conditions of patients. Only three reversible TRAEs occurred, including transient Grade 3 alanine aminotransferase elevation, Grade 3 headache, and Grade 4 neutropenia. PK was dose-dependent, with half-life at 2.1-3.1 hours. Four patients had Stable Disease per imaging (DCR 36.3%). Dose-dependent expansion of lymphocytes was observed, with average absolute lymphocyte count (ALC) of 1257 cells/μl at baseline, and peak ALC count of 2371 cells/μl post treatment, mainly from increase in NK cells and CD8+T cells. One patient (Cervical Cancer) had Stable Disease from 1st dose at July 2024 (ALC of 1100 cells/μl) to study completion (ALC of 1900 cells/μl in August 2025). FL115 treatment led to significant transient cytokine release in peripheral blood: at 3 μg/kg, peak interferon-γ level reached 3730 pg/ml with IL-6 at 0.8 pg/ml, suggesting specific targeting of NK and T cells. An essentially identical Phase 1 study of FL115 was conducted in China, in which similar trends were observed; two patients remained on treatment with confirmed partial responses lasting 32 and 24 weeks, respectively. Conclusions: FL115 is the first IL-15 superagonist as monotherapy has shown a favorable safety profile and promising signs of durable antitumor activities in heavily pretreated patients, along with significant and sustained expansion of NK and T cell population and unique robust transient induction of interferon-γ. A Phase II study of FL115 with Bacillus Calmette-Guérin in patients with nonmuscle invasive bladder cancer (NCT07122414) and a Phase Ib study of FL115 (IV) in combination with an anti-PD-1 antibody in solid tumor patients (NCT07131202) are ongoing, and a Phase I study of FL115 subcutaneous injection will be initiated soon (IND submitted). Clinical trial information: NCT # 06130722 .
Social determinants of health and long-term outcomes in prostate cancer: Mortality, survival, and comorbidity risks in a propensity score–matched federated database analysis.
12119 Background: Social determinants of health (SDOH) such as housing instability, food insecurity, and low income are known to influence health outcomes, but their long-term effects on prostate cancer (PCa) patients remain underexplored. To compare long-term outcomes, including mortality, sepsis, sexual dysfunction, and comorbidities across major organ systems, between prostate cancer patients with and without adverse SDOH. Methods: Retrospective cohort study using the TriNetX federated database (deprecated COVID-19 Research Network, 88 healthcare organizations). Cohort 1 included adults (≥18 years) with PCa (ICD-10-CM C61) and at least one adverse SDOH code (n = 14,595). Cohort 2 included PCa patients without SDOH codes (n = 875,545). Propensity score matching (1:1) balanced cohorts on demographics, external morbidity causes, ECOG status, and BMI (final n = 12,626 per cohort). The index event was the first prostate cancer diagnosis (with SDOH for Cohort 1). Outcomes assessed from 1-day post-index onward (up to 20 years prior exclusion). Risk ratios (RR), hazard ratios (HR) from Kaplan-Meier survival, and mean instances via t-tests for mortality, severe sepsis, sexual dysfunction, and diseases of genitourinary, circulatory, endocrine/metabolic, respiratory, digestive, and infectious systems. Results: After matching, cohorts were balanced (mean age ~72 years, ~56% White, ~25% Black). PCa with adverse SDOH had higher mortality risk (22.0% vs 17.3%; RR 1.272 [95% CI, 1.209-1.338]; p < 0.001) and worse survival (median 2821 vs 5246 days; HR 2.018 [95% CI, 1.906-2.137]; p < 0.001). Severe sepsis risk was elevated (5.6% vs 4.7%; RR 1.199 [95% CI, 1.074-1.339]; p < 0.001; HR 1.824 [95% CI, 1.626-2.047]; p < 0.001). Sexual dysfunction risk was lower (0.2% vs 0.4%; RR 0.493 [95% CI, 0.305-0.794]; p = 0.003). For comorbidities, PCa with adverse SDOH showed mixed risks—genitourinary diseases had a lower risk but poorer survival (HR 1.113, 95% CI 1.017-1.218, p = 0.020); circulatory diseases showed equivalent risk but worse survival (HR 1.223, 95% CI 1.089-1.374, p = 0.001); endocrine/nutritional/metabolic conditions had similar risk but reduced survival (HR 1.277, 95% CI 1.151-1.418, p < 0.001); respiratory diseases had equivalent risk but poorer survival (HR 1.531, 95% CI 1.416-1.656, p < 0.001); digestive diseases demonstrated lower risk with worse survival (HR 1.308, 95% CI 1.200-1.425, p < 0.001). Conclusions: Adverse SDOH are associated with increased mortality and poorer survival in prostate cancer, alongside heightened sepsis risk and differential comorbidity patterns. Interventions targeting SDOH may improve long-term outcomes.
Comparative outcomes of leukapheresis and pharmacologic cytoreduction in hyperleukocytosis.
e18554 Background: Hyperleukocytosis, defined as a white blood cell (WBC) count ≥100 × 10⁹/L, is a hematologic emergency in acute and chronic leukemias, with morbidity and mortality driven primarily by complications such as leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC). Despite widespread use, retrospective studies and meta-analyses show no consistent survival benefit with leukapheresis over pharmacologic cytoreduction alone, yet practice patterns remain variable. We performed a large real-world analysis to compare short-term mortality and complication rates among patients treated with hydroxyurea alone, leukapheresis alone, or combination therapy. Methods: We conducted a retrospective cohort study using the TriNetX Research Network, comprising electronic health records from 111 healthcare organizations. Adult patients (≥18 years) with acute or chronic leukemia and hyperleukocytosis (WBC ≥100 × 10⁹/L) between January 2010 and December 2025 were identified. Patients were categorized into hydroxyurea alone, leukapheresis alone, or combination therapy groups, with index date defined as treatment initiation within 7 days of hyperleukocytosis diagnosis. Propensity score matching (1:1) balanced demographics, leukemia subtype, comorbidities, and baseline laboratory values, including leukocyte count. Thirty-day outcomes included mortality, TLS, neurologic complications, respiratory failure requiring mechanical ventilation, major bleeding, and DIC. Results: After matching, 976 patients were included (488 per group: hydroxyurea alone vs hydroxyurea plus leukapheresis). At 30 days, mortality was comparable (21.3% vs 20.0%; HR 1.06, 95% CI 0.80–1.40; p=0.83). Leukapheresis was associated with higher rates of neurologic events (17.8% vs 11.5%; RR 1.55; p=0.005) and respiratory failure or mechanical ventilation (35.2% vs 24.0%; RR 1.47; p<0.001), likely reflecting confounding by indication and greater baseline disease severity. TLS rates were numerically higher (28.5% vs 23.2%; p=0.057), while major bleeding/DIC rates were similar (17.8% vs 15.6%; p=0.35). Conclusions: In this large real-world analysis, leukapheresis provided no overall survival benefit over pharmacologic cytoreduction alone. Given its high cost, resource intensity, and limited accessibility, these findings support selective rather than routine use, prioritizing prompt medical cytoreduction and supportive care.
Disrupting the microbiome, disrupting immunity: Antibiotic exposure and survival outcomes with immune checkpoint inhibitors—A systematic review.
e23430 Background: The gut microbiome plays a critical role in shaping antitumor immunity and response to immune checkpoint inhibitors (ICIs). Antibiotic exposure may disrupt microbial diversity, potentially impairing immunotherapy efficacy. However, the consistency and magnitude of this association across solid tumors remain unclear. Methods: We conducted a systematic review of PubMed to identify studies evaluating the association between antibiotic exposure and clinical outcomes in adult patients with solid tumors treated with ICIs. The search was limited to human studies published in English within the last 10 years using the following MeSH-based strategy: (antibiotics OR antimicrobial OR antibacterial) AND (immune checkpoint inhibitors OR ICI) AND (cancer OR neoplasms OR tumors) AND (treatment outcome OR survival). Of 576 records identified, 175 studies were screened in detail after application of filters and removal of duplicates. Eligible studies reported survival outcomes stratified by antibiotic exposure occurring before or during immunotherapy. Results: A total of 25 studies comprising approximately 73,567 patients with solid tumors treated with ICIs were included. Antibiotic exposure within 30–60 days before or during ICI therapy was associated with inferior overall survival (OS) in the majority of studies. 22 of 25 studies demonstrated worse OS among antibiotic-exposed patients 2 studies showed no significant association 1 study in hepatocellular carcinoma (HCC) demonstrated a variable association dependent on hepatitis infection status Across all solid tumors except HCC, antibiotic exposure was consistently associated with worse OS, with reported hazard ratios ranging from 1.08 to 2.55, and one study reporting a markedly elevated risk (HR 7.4). A large melanoma cohort did not demonstrate a significant association, representing a notable exception. Several studies suggested that outcomes varied by antibiotic class, with fluoroquinolones associated with worse survival compared with other antibiotic classes in select analyses, indicating potential class-specific effects rather than a uniform antibiotic risk. Conclusions: Antibiotic exposure surrounding immune checkpoint inhibitor initiation is associated with worse overall survival across most solid tumors, with notable exceptions in melanoma and hepatitis-dependent HCC. These findings emphasize the importance of antibiotic stewardship in patients receiving immunotherapy. When clinically appropriate, clinicians should consider delaying ICI initiation for a short duration following recent antibiotic exposure (30–60 days) and avoid unnecessary concomitant antibiotic therapy, balancing infection severity against oncologic risk. Further prospective studies are needed to define class-specific antibiotic effects.
Risk stratification in systemic AL amyloidosis with cardiac involvement using a multiparametric echocardiography score.
e24024 Background: Mortality in AL amyloidosis is chiefly driven by the degree of cardiac involvement, known as light chain cardiomyopathy (AL-CM). Several echocardiographic parameters including relative wall thickness (RWT), E/e' ratio, global longitudinal strain (GLS), and tricuspid annular plane systolic excursion (TAPSE) have established diagnostic utility, yet the prognostic value of this constellation of values is not well-characterized. We evaluated the impact of a composite echocardiographic score, adapted from a previously validated diagnostic criteria shown to correlate with extracellular volume (ECV) on cardiac MRI in AL-CM patients, which would risk stratify patients with AL amyloidosis in terms of their overall survival (Boldrini et. al., 2020). Methods: We performed a retrospective analysis of 62 patients diagnosed with AL amyloidosis between March 2011 and July 2025 at the John Theurer Cancer Center on an IRB-approved protocol. Patients with endomyocardial biopsy-proven AL-CM or characteristic cardiac MRI/echocardiographic findings with extracardiac tissue confirmation, along with complete echocardiography including strain imaging were included in the study. A composite score was calculated based on parameters previously reported by Boldrini et al. for diagnostic purposes: RWT > 0.6 (3 points), E/e' > 11 (1 point), TAPSE ≥19 (2 points), and GLS < 13% (1 point). Patients were stratified by total score (≤4 vs > 4). OS was estimated using Kaplan-Meier methods; groups were compared using log-rank and Wilcoxon tests. Cox proportional hazards regression assessed the association between composite score and mortality. Results: Median age at diagnosis was 65 years; 40/62 patients were male (64.5%). Induction therapy consisted of daratumumab-bortezomib-cyclophosphamide-dexamethasone (Dara-VCD) in 31/62 of patients (50%). Concurrent renal involvement was present in 24/62 (38.7%) at the time of diagnosis. At a median follow-up of 46.3 months, 14 deaths (22.6%) occurred. Patients with composite scores > 4 demonstrated significantly inferior OS compared to those with scores ≤4. Median OS was 75 months in the low-risk group and was not reached in the high-risk group due to early mortality. (log-rank p = 0.0025, Wilcoxon p = 0.0006). At 27 months, 90.4% of patients were alive in the low-risk group as opposed to 57.7% in the high-risk group. The hazard ratio was 4.7 with a p value of 0.0072. Conclusions: A composite echocardiographic score incorporating RWT, E/e', GLS, and TAPSE (previously developed for diagnostic purposes) demonstrates significant prognostic utility in AL amyloidosis. Patients with scores exceeding 4 experienced inferior survival outcomes. This easily obtainable risk stratification tool may help identify patients requiring intensified monitoring and earlier therapeutic intervention. Prospective validation in larger cohorts should be considered.
Sotorasib vs adagrasib in the 2L+ setting: Outcomes in a large, multi-institutional, real-world database of KRAS-G12C mutated mNSCLC.
8608 Background: KRAS-G12C mutations are found in ~12% of mNSCLC. KRAS-G12C inhibitors sotorasib and adagrasib are approved treatments but have never been compared head-to-head. We report the first large, multi-institutional database analysis comparing efficacy and safety of sotarasib vs adagrasib. Methods: Flatiron Health's de-identified electronic health record US database was used to identify patients with KRAS G12C-mutated NSCLC who started treatment 12/2022-10/2025 with either sotorasib or adagrasib in 2L+. Baseline characteristics were abstracted and evaluated using chi-square tests, Wilcoxon rank-sum tests, and a multivariable logistic regression adjusting for practice type, sex, ECOG performance status, age, line of therapy, prior immunotherapy, and brain metastases. Overall survival (OS), progression-free survival (PFS), and time to treatment discontinuation (TTD) were estimated using Kaplan-Meier curves and compared using the log-rank test and Cox regression. Multivariable Cox regression model included sex, age, ECOG, line of therapy, prior immunotherapy, brain metastases, and PD-L1 expression to control for possible confounding. Results: Of the 1133 patients identified, 768 (69%) received sotorasib, and 345 (31%) received adagrasib. Sex, age, PD-L1 status and prior immunotherapy exposure did not affect choice of treatment (Table 1). In a multivariable logistic regression analysis, patients with brain metastases were more likely to be treated with adagrasib (HR =0.64; p=0.003), while patients with higher ECOG PS (2+) were more likely to be treated with sotorasib (HR =1.18; p=0.047). There was no difference in OS between sotorasib and adagrasib (HR = 1.01; p = 0.87), and there was no difference in OS on multivariable regression (adjusted HR = 0.96; p=0.02). There was no difference in PFS between sotorasib and adagrasib (HR = 0.91; p=0.15). Sotorasib had longer TTD than adagrasib (mTTD 3.8 vs 3.3m; HR = 0.82; p =0.005); this association persisted in the adjusted model (adjusted HR = 0.80; p=0.006). Conclusions: Sotorasib was associated with slightly longer TTD compared with adagrasib, which may suggest better tolerability, but no difference in PFS or OS. Sotorasib was more likely to be used in patients with poor PS while adagrasib was more likely to be used in patients with CNS metastases. Sotorasib (n = 768) Adagrasib (n = 345) p-value 2L (vs 3+) 68.6% 73.0% 0.15 ECOG PS 0-1 (vs 2-4) 64.6% 69.9% 0.13 PDL1 <1% 31.2% 38.3% 0.10 1-49% 36.4% 32.4% >=50% 32.4% 29.3% Prior immunotherapy 85.9% 89.0% 0.18 Brain metastases 28.1% 35.1% 0.02 mPFS 3.5 3.3 0.15*0.25 mTTD 3.8 3.3 0.005 *0.006 mOS 9.6 8.7 0.87*0.70 All survival data in months. Significant values in bold.
Quantifying equol-producing and beta-glucuronidating gut bacteria in breast cancer using 16S rDNA sequencing methods.
10601 Background: Gut bacteria with hormone-modulating potential may influence breast cancer (BC) risk: Equol-producing bacteria convert dietary isoflavones into equol, a phytoestrogen that binds estrogen receptors, while beta-glucosidating bacteria affect glycosides of dietary phytoestrogens, and beta-glucuronidating bacteria regulate the deconjugation and reabsorption of endogenous estrogens. We aimed to investigate whether gut bacterial species that have the potential to affect phytoestrogens or endogenous estrogens can be detected using 16S rDNA sequencing methods, and to what extent this detection may be influenced by the choice of 16S hypervariable region targeted for sequencing. Methods: DNA extracted from stool samples of women with BC (n = 112) and healthy controls (n = 171) was subjected to PCR amplification and high-throughput sequencing of the V1-V3 and V3-V4 16S rRNA hypervariable regions, commonly used regions in microbiome research. Data was processed using QIIME, and taxonomy assignment was performed with the SILVA database to the species level. Relative abundance and detection of taxa in cases vs controls were evaluated using Wilcoxon and McNemar’s tests in R. Taxa were classified as equol-producing based on Setchell and Clerici (2010) or beta-glucuronidating and beta-glucosidating based on Dabek et al (2008). Results: The relative abundance of equol-producing bacteria was significantly higher in the BC group vs controls in the V1–V3 (p = 0.0007); V3–V4 (p = 0.0089) regions, and when both regions were summed (p = 0.0011). Adlercreutzia equolifaciens was detected 29.6% more often in a presence/absence analysis of the V1-V3 region (V1-V3 presence: 93.0%, V3-V4 presence: 63.4%, p < 0.001), while Finegoldia magna was detected 21.1% more often in the V3-V4 region (V1-V3 presence: 18.0%, V3-V4 presence: 39.1%, p < 0.001). The relative abundance of beta-glucuronidating and beta-glucosidating bacteria was significantly higher in the BC group vs controls in the V1-V3 region (p = 0.0094) and when both regions were summed (p = 0.0254), and approached significance in the V3-V4 region (p = 0.0534) . Presence of Bifidobacterium adolescentis was detected 21.8% more often in the V1-V3 region (V1-V3 presence: 21.8%, V3-V4 presence: 0.00%, p < 0.001), and Roseburia inulinivorans was detected 21.1% more often in the V3-V4 region (V1-V3 presence: 63.0%, V3-V4 presence: 83.1%, p < 0.001). Conclusions: Equol-producing and beta-glucuronidating and beta-glucosidating bacteria appear enriched at the species-level analysis in BC subjects, but detection of specific organisms is sensitive to the 16S region sequenced. Accurate identification of hormone-modulating taxa requires both the V1-V3 and V3-V4 regions, as either alone is insufficient to capture the full range of taxa. Additional analyses with absolute quantification such as qPCR are needed to validate the results.
Spatial immune architecture as a predictor of response to neoadjuvant chemoradiotherapy in rectal cancer.
e15739 Background: Response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer is highly variable, and predictive biomarkers are lacking. While immune infiltration influences treatment response, the spatial organisation and functional state of immune cells within the tumour microenvironment remain poorly understood. Methods: re-treatment rectal cancer biopsies from patients treated with nCRT (n = 20; 12 complete responders, 4 intermediate responders, 4 non-responders) were analysed using NanoString GeoMx digital spatial proteomics. Regions of interest (ROIs) were selected based on immune architecture, including tertiary lymphoid structures (TLSs) and tumour regions without TLSs, and segmented into CD19⁺, CD3⁺, PanCK⁺, and full ROIs. Protein expression across immune, checkpoint, cell death, and innate immune pathways was quantified. Unsupervised clustering and differential expression analyses used linear mixed-effects models accounting for repeated measures. Results: Spatial proteomic profiling revealed distinct immune patterns associated with response to nCRT. Complete responders formed discrete clusters across multiple ROI types and exhibited reduced expression of immune checkpoint proteins (PD-1, PD-L1, CTLA-4) alongside increased expression of cell death–associated proteins, including cleaved caspase-9. TLSs were more frequently observed in complete responders and displayed response-associated protein signatures. In tumour regions lacking TLSs, complete responders showed reduced ARG1, CTLA-4, and CD68 expression, with increased STING expression, consistent with a less immunosuppressive and more innate immune–activated tumour microenvironment. Conclusions: Distinct spatial immune architectures characterise response to nCRT in rectal cancer. Complete response is associated with reduced immune suppression, enhanced apoptotic signalling, and spatially organised immune features, including TLSs and STING activation in non-TLS tumour regions. These findings support spatial proteomic biomarkers as tools for predicting treatment response and guiding precision therapy in rectal cancer.
Comparison of cardiovascular outcomes among solid tumor ADCs: A tumor-agnostic observational study.
e15208 Background: Antibody-drug conjugates (ADCs) combine monoclonal antibodies with cytotoxic payloads to selectively deliver chemotherapy to tumor cells. Despite their targeted design, cardiovascular toxicity remains a significant concern. Cardiac adverse events include heart failure, left ventricular dysfunction, arrhythmias, and QT prolongation. Our study aims to assess the comparative cardiovascular toxicity profile of seven FDA-approved ADCs. Methods: We utilized data from the Global Collaborative Network-TriNetX to assess cardiovascular outcomes associated with seven ADCs: trastuzumab deruxtecan, sacituzumab govitecan, enfortumab vedotin, ado-trastuzumab emtansine, tisotumab vedotin, mirvetuximab soravtansine, and datopotamab deruxtecan. Using ICD-10 codes, we evaluated cardiomyopathy, congestive heart failure (CHF), heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), arrhythmias, myocarditis, and mean QT interval prolongation. Incidence was calculated as the proportion of patients experiencing each outcome among all patients exposed to each ADC. Results: Ado-trastuzumab emtansine demonstrated the highest cardiomyopathy incidence at 7.204% (n = 287, N = 3,984), followed by enfortumab vedotin at 6.36% (n = 249, N = 3,915) and sacituzumab govitecan at 5.338% (n = 170, N = 3,185). Trastuzumab deruxtecan showed 2.541% (n = 157, N = 6,179). For CHF, enfortumab vedotin and sacituzumab govitecan showed the highest rates at 2.406% and 2.231%, respectively. HFrEF occurred most frequently with enfortumab vedotin (3.184%) and ado-trastuzumab emtansine (3.122%). Arrhythmias were most common with enfortumab vedotin (7.628%) and sacituzumab govitecan (6.753%). Myocarditis was rare, with enfortumab vedotin reporting 0.464%. Tisotumab vedotin demonstrated the longest mean QT interval at 450ms (Std Dev 51ms), followed by mirvetuximab soravtansine at 435ms and enfortumab vedotin at 430ms. Conclusions: Our study demonstrates significant variability in cardiovascular toxicity among ADCs. Ado-trastuzumab emtansine, enfortumab vedotin, and sacituzumab govitecan showed the highest cardiomyopathy and heart failure rates, while trastuzumab deruxtecan demonstrated a favorable profile. These findings highlight the importance of cardiovascular risk stratification and monitoring in patients receiving ADC therapy. Given this is a retrospective observational study, prospective trials with standardized cardiovascular monitoring are warranted.
Scaling deep learning for neuro-oncology: Knowledge-distilled EfficientNetB0 powered MRI classification of brain tumors with international expert validation.
2018 Background: Accurate classification of brain tumors on magnetic resonance imaging (MRI) is critical for timely diagnosis, treatment planning, and referral in neuro-oncology. However, radiologic interpretation is challenged by tumor heterogeneity, overlapping imaging features, and growing imaging volumes, particularly in settings with limited subspecialty expertise. Although deep learning models have demonstrated high diagnostic accuracy, their computational complexity often limits real-world adoption. Scalable, resource-efficient AI systems capable of maintaining diagnostic performance are needed to enable global clinical translation. Methods: We retrospectively assembled a multicontinental dataset of 5,000 brain MRI studies from six continents, including pituitary tumors (n=1,200), meningiomas (n=1,300), gliomas (n=1,400), and non-tumor controls (n=1,100). Ground-truth diagnoses were established through independent review by at least two expert neuroradiologists. A high-capacity EfficientNetB4 model served as the reference architecture. A lightweight EfficientNetB0 model was trained using structured knowledge distillation with soft probabilistic supervision to preserve diagnostic fidelity while reducing computational cost. Model performance was evaluated on internal test data and independent external datasets using accuracy, class-specific sensitivity and specificity, F1-score, and area under the receiver operating characteristic curve (AUROC). Results: The distilled EfficientNetB0 model achieved an overall test accuracy of 94.8%, with balanced sensitivity across tumor classes (pituitary 93.1%, meningioma 95.2%, glioma 94.1%, non-tumor 96.4%). The overall F1-score was 0.946, and AUROC exceeded 0.92 on external validation datasets. Performance remained consistent across geographic regions and heterogeneous MRI acquisition protocols, with accuracy ranging from 93% to 96%. Mean inference time was 0.18 seconds per study on standard hardware, enabling real-time clinical integration. Clinician evaluators reported improved diagnostic confidence and utility for triage and workflow support. Conclusions: Knowledge-distilled EfficientNet models enable accurate, rapid, and computationally efficient classification of brain tumors on MRI without sacrificing clinically relevant performance. This scalable framework directly addresses key barriers to AI deployment in neuro-oncology and supports global implementation across resource-diverse settings. Prospective studies are planned to evaluate impact on diagnostic turnaround time, subspecialty access, and treatment decision-making.
Cadonilimab in combination with ivonescimab and chemotherapy as first-line (1L) therapy in patients with advanced gastric (G) or gastroesophageal junction adenocarcinoma (GEJA): Updated results from an open-label phase II trial.
4048 Background: Cadonilimab (AK104), an anti-PD-1/CTLA-4 bispecific antibody, plus chemotherapy significantly improved OS versus chemotherapy and had a tolerable safety profile in first-line (1L) treatment of advanced G/GEJA patients (pts), including those with low PD-L1 expression. Currently, it has been approved by NMPA. Ivonescimab (AK112), also approved in China, is a novel bispecific antibody against PD-1 and VEGF and has shown a clinically significant improvement in efficacy with favorable safety for advanced NSCLC in two phase 3 studies (HARMONi-2 and HARMONi-A). Here, we presented the updated data for the safety and efficacy of AK104 combined with AK112 and chemotherapy as 1L treatment in advanced G/GEJA. Methods: Pts with previously untreated advanced G/GEJA were enrolled. The phase II trial consisted of a dose-escalation part (part 1) and a dose expansion part (part 2). Eligible pts were firstly enrolled into sequential part1 including 10mg/kg and 15mg/kg AK104 (Q6W, D8) combined with AK112 (20mg/kg, Q3W, D1) and chemotherapy (SOX or XELOX) following the conventional 3+3 design. If the starting dose of 10mg/kg AK104 led to ≥2 dose-limiting toxicities (DLTs), 6mg/kg AK104 would be administered. After the part 1 completed, eligible pts were enrolled into the part 2 and received AK104 (the recommended dose, Q6W, D8) combined with AK112 (20 mg/kg, Q3W, D1) and chemotherapy (SOX or XELOX). The primary outcomes were safety and ORR. Secondary endpoints included DCR, PFS, OS, biomarkers of drug activity and pharmacokinetics. Results: As of 19 January 2026, 54 pts were enrolled with a median age of 60 years (range: 39-75). 55.6% were PD-L1 CPS＜5, 42.6% had liver metastases and 40.7% had peritoneal metastases. Among efficacy evaluable pts, the ORR was 71.7% and DCR was 95.7%. The median PFS (mPFS) was 8.4 months (mo) (95%Cl: 6.0-13.1) and OS analysis was immature. In the pts with liver metastases, the ORR was 81.8%, DCR was 90.9% and mPFS was 10.7 mo (95%Cl: 5.7-13.1). In the pts with peritoneal metastases, the ORR was 72.2%, DCR was 100.0% and mPFS was 6.4 mo (95%Cl: 5.45-NR). Grade 3-4 treatment-related adverse events (TRAEs) were reported in 18.5% pts, mainly including hypokalemia (5.6%), decreased neutrophil count (3.7%), decreased platelet count (3.7%) and hyperbilirubinemia (3.7%). There were no grade 4/5 TRAEs or treatment-related deaths. Conclusions: Updated results demonstrated that AK104 combined with AK112 and chemotherapy as 1L treatment continued to show highly encouraging anti-tumor activity with a manageable safety profile in pts with advanced G/GEJA, including those with liver or peritoneal metastases. Clinical trial information: NCT06196697 .
PD-L1 CPS ≥10 population subgroup analysis of KEYNOTE-412: Pembrolizumab plus chemoradiotherapy versus placebo plus chemoradiotherapy for unresected locally advanced head and neck squamous cell carcinoma.
6063 Background: At the end-of-trial analysis of the randomized, double-blind, phase 3 KEYNOTE-412 trial (NCT03040999) in participants with unresected locally advanced (LA) head and neck squamous cell carcinoma (HNSCC), pembrolizumab plus chemoradiotherapy (CRT) was associated with a clinically meaningful event-free survival (EFS) benefit over placebo plus CRT (HR 0.79; 95% CI, 0.65-0.96) in the total population, and in participants whose tumors expressed PD-L1 CPS ≥1 (HR 0.80; 95% CI 0.64-0.98) and CPS ≥20 (HR 0.70; 95% CI, 0.49-1.00). We conducted a post hoc analysis of outcomes in the PD-L1 CPS ≥10 population. Methods: Adults with high-risk unresected LA HNSCC (T3-4 N0-3 or T1-4 N2a-3 laryngeal/hypopharyngeal/oral cavity/p16-negative oropharyngeal SCC, or T4 or N3 p16-positive oropharyngeal SCC) were randomly assigned to receive definitive CRT plus 17 cycles of pembrolizumab 200 mg or placebo intravenously every 3 weeks concurrently and after CRT. This exploratory analysis evaluated EFS and overall survival (OS) in the PD-L1 CPS ≥10 population. Results: Of 804 total participants, 382 had tumors expressing PD-L1 CPS ≥10 (n = 194, pembrolizumab group; n = 188, placebo group). As of data cutoff date (August 21, 2024), median study follow-up in the PD-L1 CPS ≥10 population was 74.1 months (range, 63.8-88.1). Median EFS was not reached (NR) in the pembrolizumab group and 61.4 months in the placebo group (HR 0.71; 95% CI, 0.53-0.97). The 60-month EFS rates were 62.4% and 50.3%, respectively. Median OS was not reached in either the pembrolizumab or the placebo group; the 60-month OS rates were 70.7% and 60.9%, respectively (HR 0.75 [95% CI, 0.53-1.04]). Conclusions: Results from this post hoc analysis of the KEYNOTE-412 trial with over 2 years of additional follow-up were consistent with those of the end-of-trial analysis in the overall population. For participants whose tumors expressed PD-L1 with a CPS ≥10, we observed a clinically meaningful EFS and OS benefit for pembrolizumab plus CRT over placebo plus CRT, with a numerically lower HR than reported for the overall population. Clinical trial information: NCT03040999 .
Clinicopathological characteristics and prognostic predictors in cervical clear cell adenocarcinoma: A multicenter cohort study.
e17505 Background: The clinicopathological profile and prognostic factors of cervical clear cell adenocarcinoma unrelated to diethylstilbestrol exposure are not well characterized in Chinese population. Methods: This multicenter retrospective study was conducted to analyze the characteristics of cervical clear cell adenocarcinoma patients from 10 medical centers. 97 patients surgically diagnosed with primary cervical clear cell adenocarcinoma were collected from 2010 to 2022. A comprehensive clinicopathological profile of cervical clear cell adenocarcinoma patients was depicted. The association between clinicopathological characteristics and prognostic factors was also assessed. Results: The peak age prevalence occurred in the 46-55 years group (n = 97), with the human papillomavirus (HPV)-negative rate of 85.1%. All surgically treated patients had FIGO stages IA-IIA or IIIC and received adjuvant radiotherapy and/or chemotherapy. With a median follow-up of 52 months (interquartile range, 36-70 months), multivariable analysis identified ovarian metastasis (HR = 3.89, P = 0.027 ) and lymph node metastasis (HR = 4.26, P = 0.004 ) as independent risk factors for overall survival. Multivariable analysis also demonstrated that lymph node metastasis (HR = 3.15, P = 0.005 ) remained a significant predictor for progression-free survival. Conclusions: This retrospective multicenter study characterized clinicopathological features of cervical clear cell adenocarcinoma and identified prognostic factors. Univariate and multivariate analysis of factors associated with overall survival. Variables Univariate HR (95%CI) P-value Multivariable HR (95%CI) P-value Tumor size >4 cm 3.85 (1.15–12.91) 0.029 3.13 (0.80–12.24) 0.102 DSI >2/3 8.30 (1.81–38.02) 0.006 3.36 (0.62–18.22) 0.161 Ovarian metastasis (Yes) 3.09 (1.03–9.39) 0.047 3.89 (1.17–12.98) 0.027 LVSI (Yes) 4.47 (1.80–11.07) 0.001 0.49 (0.26–3.58) 0.481 LNM (Yes) 4.80 (1.94–11.86) 0.001 4.26 (1.58–11.45) 0.004 Surgical approach (ARH) 1.57 (0.36–6.79) 0.548 - - HR, hazard ratio; 95%CI, 95% confidence interval; DSI, depth of stromal invasion; LVSI, lymphovascular space invasion; LNM, lymph node metastasis; ARH, abdominal radical hysterectomy; LRH, laparoscopic radical hysterectomy.