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Comprehensive genomic and clinicopathologic characterization of <i>KRAS</i> G12C– and other <i>KRAS</i> G12–mutated non-colorectal gastrointestinal malignancies.
e16486 Background: Allele-specific KRAS G12C inhibitors have revolutionized lung and colorectal cancer treatment, yet the biology of G12C in other gastrointestinal (GI) malignancies remains undefined. We aimed to elucidate the clinicopathologic and genomic landscape of KRAS G12C-mutated tumors compared to other G12 variants in a large non-colorectal GI cohort. Methods: We queried cBioPortal for pancreatic, esophagogastric, hepatobiliary, ampullary, and appendiceal adenocarcinomas. Following data quality control, the final cohort (n = 6,352) was stratified into KRAS wild-type (n = 3,293), G12C (n = 63), and other G12 variants (n = 2,996). Clinicopathologic features, tumor mutational burden (TMB), microsatellite instability status, and co-alteration in 96 key genes across 11 signaling pathways were compared. Statistical significance was assessed using Fisher’s exact or Chi-square tests for categorical variables and Kruskal-Wallis tests for continuous variables. The Benjamini-Hochberg method was applied to correct for multiple hypothesis testing. Results: KRAS G12C prevalence was 1.0% overall, with significant heterogeneity across cancer subtypes (p < 0.001). Appendiceal adenocarcinoma demonstrated the highest G12C prevalence at 5.71% (10/175), followed by ampullary (1.44%, 2/139), pancreatic (1.17%, 34/2906), hepatobiliary (0.88%, 12/1360), and esophagogastric cancers (0.28%, 5/1772). G12C patients were significantly older than wild-type patients (64.8±11.2 vs 62.5±12.9 years, mean±SD, p < 0.001) but younger than other G12 variant carriers (65.8±10.4 years). G12C tumors demonstrated intermediate genomic instability, with a TMB of 4.82±6.17 compared to 4.98±10.55 in wild-type tumors and 3.67±10.12 in other G12 variants (p < 0.001). Notably, G12C tumors were universally microsatellite stable (0% MSI-H vs 4.0% wild-type vs 0.9% other G12, p < 0.001). Genomic analysis revealed that AKT1 mutations were significantly enriched in the G12C cohort (6.3% vs 0.4%; q = 0.025) as compared to other G12 variants. A trend of increased mutation frequency in HRAS was observed specifically in pancreatic cancers in G12C tumors as compared to other variants (8.8% vs 0.7%; q = 0.083). In pancreatic adenocarcinoma, G12C tumors were enriched for chromatin modifiers, notably ARID1A (17.6% vs 7.7%, p = 0.045) and SETD2 / SETD26 (8.8% vs 1.1%, p = 0.006), though these did not reach FDR significance. Notably, the immunotherapy-resistance drivers STK11 and KEAP1 were absent (0%) in the whole G12C cohort. Conclusions: KRAS G12C represents a biologically distinct subgroup of exon 2 KRAS mutations compared to other KRAS G12 pathogenic variants. The absence of resistance markers and enrichment of actionable AKT1 and chromatin-modifier mutations suggest distinct therapeutic vulnerabilities in non-colorectal KRAS G12C-mutated GI cancers.
Real-world insights into bone marrow carcinomatosis in metastatic breast cancer: A retrospective analysis from two large university breast cancer centers.
1104 Background: Bone marrow carcinomatosis (BMC) is a rare but severe manifestation of metastatic breast cancer (mBC) characterized by diffuse bone marrow infiltration and hematologic dysfunction. Data on incidence, clinical presentation, and treatment outcomes remain limited. Methods: This bicentric retrospective real-world study included breast cancer patients diagnosed with BMC between 2010 and 2023 at two German university centers. BMC was diagnosed using bone marrow biopsy and/or leukoerythroblastic blood smear in the presence of cytopenia. Clinical characteristics, systemic treatments, and overall survival (OS) were analyzed descriptively. Survival was estimated using Kaplan–Meier method. Results: During the study period, 1,399 patients presented with mBC at one of two participating centers. Among these, 37 were diagnosed with BMC, corresponding to an incidence of 2.6% (0.5% of all breast cancer cases). Median age was 58 years (range 30 – 76). Most patients had hormone receptor (HR)–positive HER2-negative disease (89%). At BMC diagnosis, anemia occurred in 84%, thrombocytopenia in 76%, and pancytopenia in 57% of patients. Median OS after BMC diagnosis was 12.0 months (95% CI: 6.0, 38.0). Patients with bone-only metastases showed longer survival compared with those with additional visceral involvement (median OS not reached vs. 9 months). In HR-positive HER2-negative disease, patients receiving endocrine-based therapy including CDK4/6 inhibitors demonstrated numerically longer survival compared with chemotherapy-based approaches; however, subgroup sizes were small and analyses exploratory. Conclusions: BMC is an uncommon but clinically relevant manifestation of mBC associated with substantial morbidity and limited prognosis. This largest European real-world cohort highlights heterogeneous treatment approaches and outcomes. Endocrine-based strategies combined with targeted agents appear feasible in selected patients. Multicenter registries and prospective studies are needed to optimize diagnostic and therapeutic strategies in this patient group. Real-world data of the analyzed cohort of patients with BMC. No of patients IHC subtype n (%) Metastatic status at initial BC presentation n (%) Metastatic site at BMC diagnosisn (%) Diagnostic method n (%) Median time to BMC in months (range) Initial treatmentfor BMCn (%) a) HR pos/HER2negb) HER2 posc) TNBC a) M0b) M1 a) visceralb) brainc) bone +/- otherd) bone only a) BM biopsy / smearb) blood smear a) after mBC diagnosisb) after initial BC diagnosis a) combined CTb) mono CTc) ET+CDK4/6id) ET onlye) Anti HER2f) BSC 37 a) 33 (89)b) 4 (11)c) 0 (0) a) 16 (43)b) 21 (57) a) 22 (60)b) 1 (3)c) 37 (100)d) 11 (30) a) 26 (70)b) 11 (30) a) 28 (0-107)b) 58 (0-249) a) 3 (8)b) 20 (54)c) 6 (16)d) 1 (3)e) 1 (3)f) 1 (3)Other: 5 (14)
Molecular landscape of gynecological malignancies in India as associated with distinct MSI and histotype-specific genomic features with therapeutic implications.
e14567 Background: Gynaecological malignancies, including ovarian, endometrial, cervical, uterine sarcoma, and vulvar/vaginal cancers, are a major cause of morbidity and mortality among women in India. Limited genomic data from Indian patients restrict insights into population-specific tumor biology. This study aimed to characterize the genomic landscape of gynaecological cancers in an Indian cohort and identify clinically actionable alterations. Methods: A total of 615 histologically confirmed gynecological tumors underwent targeted sequencing to identify somatic variants, copy-number alterations, and gene fusions, with MSI and PD-L1 assessed where available. Co-occurrence and mutual exclusivity were evaluated using Fisher’s exact test with Benjamini-Hochberg correction (q < 0.05), and genomic profiles were compared with TCGA and other international cohorts. Results: Recurrent and co-occurring genomic alterations across 615 gynecological cancers (385 ovarian, 143 endometrial, 68 cervical, 11 uterine sarcoma, and 8 vulvar/vaginal) are summarized in Table 1. Ovarian cancers showed histotype-specific patterns, with TP53 alterations in serous tumors, PI3K/PTEN in endometrioid and clear-cell subtypes, and KRAS in mucinous tumors. MSI-H frequency was higher in ovarian cancers (7.8%), enriched in endometrioid tumors, while endometrial cancers showed a lower MSI-H rate (17.8%) than TCGA. Our analysis revealed population-specific mutation patterns. PD-L1 positivity was generally low, highest in cervical cancer (~40%), and tumor mutational burden was predominantly low to intermediate. Conclusions: This comprehensive genomic analysis of Indian gynecologic malignancies reveals both shared oncogenic drivers and distinct, population-specific molecular features. Uterine sarcomas exhibited distinct ATRX and FGF-axis alterations, highlighting actionable FGF-axis vulnerabilities rarely discussed in gynecologic precision oncology. MSI-H was enriched in ovarian endometrioid tumors but was less frequent in Indian endometrial cancers, underscoring histology- and population-specific MSI patterns. Low-intermediate TMB and limited PD-L1 expression suggest MSI may better predict immunotherapy response in this cohort. Recurrently altered genes and co-occurring genomic events. Cancer Type Recurrent Gene Alterations Co-occurring Alterations Ovarian Cancer TP53 ( 59% ) , PIK3CA ( 24% ) , PTEN (15%), and KRAS (13%) TP53-CCNE1 (p-value<0.05), PIK3CA-ARID1A ( p-value <0.01) Endometrial Cancer TP53 ( 57% ) , PTEN (39%), PIK3CA (37 % ) , and KRAS (19%) PIK3CA-MYC ( p-value <0.01), PIK3CA-BCL9 ( p-value <0.05) Cervical Cancer PIK3CA (43 % ), TP53 (29 % ) , KRAS (13%) and PTEN (13%) BRAF-RB1 (p-value <0.05 ), PIK3CA-ATR (p-value <0.05 ) Uterine Sarcoma TP53 (45%), ATRX (36%) FGF19/3 (27%) - Vulva/Vagina Cancer TP53 (38%), PTEN (25%) -
Clinical efficacy and safety of tiragolumab plus atezolizumab across solid tumors: A meta-analysis of randomized controlled trials.
e14574 Background: Tiragolumab, a first-in-class anti-TIGIT antibody, has emerged as a novel immunotherapeutic strategy in combination with immune checkpoint inhibitors. While its combination with atezolizumab has been evaluated across multiple solid tumors; however, the overall clinical benefit remains uncertain. This systematic review aims to summarize the current clinical evidence evaluating the efficacy and safety of tiragolumab plus atezolizumab in patients with solid tumors. Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane databases to identify relevant randomized controlled trials (RCTs) published up to 15 January 2026. Outcomes were pooled using an inverse-variance random-effects meta-analysis. Relative risks (RRs) and hazard ratios (HRs) were used as effect measures (PROSPERO CRD420261285773). Results: Five RCTs comprising 1466 patients were analyzed. Compared to atezolizumab-based chemoimmunotherapy, tiragolumab/atezolizumab improved objective response rate (ORR: RR 1.49 [95%CI 1.33–1.68]), although it resulted in similar disease control rate (1.29 [0.92-1.81]), overall survival (OS: HR 0.75 [95%CI0.51–1.12]) and progression-free survival (PFS: 0.78 [0.52-1.16]). There were no significant differences in grade ≥3 adverse events (AEs) (RR0.89 [95%CI0.66–1.21]) or grade 5 AEs (0.79 [0.19–3.22]). In a subgroup of esophageal cancer patients, tiragolumab/atezolizumab resulted in better OS (HR 0.69 [95%CI 0.55-0.86]), PFS (HR 0.56 [95%CI 0.45-0.68]), and ORR (RR1.36 [95%CI1.15-1.61]), with similar rates of grade ≥3 AE (RR 1.12 [95%CI 0.98-1.29]) compared to chemotherapy alone. Conclusions: The addition of tiragolumab to atezolizumab-based chemoimmunotherapy regimen provides a modest improvement in ORR with limited survival benefit. Nonetheless, this regimen appears superior to chemotherapy alone. Interpretation of tumor-specific efficacy is constrained by the limited availability of data, and further high-quality, tumor-specific RCTs are needed to substantiate our findings. Meta-analysis on the efficacy and safety of tiragolumab/atezolizumab versus atezolizumab-based chemoimmunotherapy regimen in patients with solid tumor. Outcome No. of reports No. of patients Estimate 95%CI I2 P heterogeneity Efficacy OS 4 833 HR 0.75 0.51-1.12 71% 0.017 PFS 4 833 HR 0.78 0.52-1.16 71% 0.212 ORR 5 910 RR 1.49 1.33-1.66 7% 0.369 DCR 3 356 RR 1.29 0.92-1.81 47% 0.150 Safety Grade ≥1 AE 5 976 RR 1.03 0.98-1.08 40% 0.152 Grade ≥3 AE 5 976 RR 0.89 0.66-1.21 67% 0.016 Grade 5 AE 5 976 RR 0.79 0.19-3.22 34% 0.221 Abbreviation: AE, adverse event; DCR, disease control rate; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RR, relative risk.
Enhanced local and systemic efficacy in refractory solid tumors via integrated intra-tumoral injection and radiotherapy: A study of the ‘R-ISV-RO’ modality.
11558 Background: As for most refractory solid tumors, especially sarcoma, immunotherapy still lacks meaningful improvement in their outcomes. The novel 'R-ISV-RO' in situ vaccine, in which we merged radiotherapy, intratumoral delivery of R837 and OX-40 ligand, together with systemic use of immune-checkpoint blockades, may be clinically beneficial. Methods: This was an exploratory, single-center, single-arm clinical trial aimed at evaluating the efficacy and safety of the 'R-ISV-RO' in situ vaccine therapy for advanced solid tumors. Thirty patients aged 18 years or older with advanced solid tumors and at least one measurable lesion were enrolled. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), time to progression (TTP), and clinical benefit rate (CBR). The safety of the treatment and the injection procedures were also evaluated. Results: The ORR and DCR for injected lesions were 44.4% and 96.3%. Sarcoma patients exhibited superior outcomes, with a 100% DCR in injected lesions. The median PFS was 15.9 months for injected lesions and median OS was 23.6 months. The abscopal effect occurred in 12 patients. 'R-ISV-RO' treatment was well tolerated, with only 6.7% of patients experiencing grade 3 or higher adverse events. Improved clinical responses were associated with enhanced CD4⁺/CD8⁺ T-cell infiltration and peripheral expansion. Metabolomics analysis revealed therapy-induced metabolic remodeling. Conclusions: In this exploratory trial, 'R-ISV-RO' with concurrent immunotherapy demonstrated promising efficacy for both primary and distant tumors, especially for sarcomas. Systemic immune response and metabolic remodeling were also observed after the therapy. Clinical trial information: ChiCTR2100053870.
Ovarian cancer and hypertension: Changes in comorbidity-related mortality among U.S. women aged ≥45 years, 1999–2023.
e17591 Background: Ovarian cancer causes over 200,000 deaths globally each year, while diabetes mellitus affects more than 450 million adults worldwide and contributes substantially to mortality. Coexisting diabetes is associated with increased ovarian cancer risk, worse prognosis, and greater healthcare burden. Methods: This STROBE-adherent study analyzed diabetes mellitus (DM)–related mortality among U.S. adults aged 45–85 years with ovarian cancer (OC) from 1999 to 2023 using CDC WONDER multiple cause of death data. Deaths were identified using ICD-10 codes for OC (C56) and DM (E10–E14). Analyses were stratified by census region and race/ethnicity. Crude and age-adjusted mortality rates (AAMRs) per 100,000 population were calculated. Joinpoint regression was used to assess temporal trends, reporting annual percent changes (APCs) and average annual percent changes (AAPCs) with 95% confidence intervals. Results: From 1999 to 2023, DM-related mortality among patients with ovarian cancer demonstrated variable trends. Mortality declined from 1999 to 2018 (APC −1.13%, 95% CI −1.60 to −0.65, p<0.001), followed by a sharp increase from 2018 to 2021 (APC 10.59%, 95% CI 5.69 to 15.85, p<0.001), and a subsequent decline through 2023 (APC −4.81%, 95% CI −11.26 to 1.94, p=0.14). Annual deaths increased from approximately 360 in 1999 to a peak of about 740 in 2021. In the Southern U.S., mortality increased from 1999 to 2005 (APC 4.10%, 95% CI 0.71 to 7.62, p=0.02), declined from 2005 to 2015 (APC −2.66%, 95% CI −4.35 to −0.93, p=0.005), and rose again from 2015 to 2023 (APC 5.24%, 95% CI 3.12 to 7.40, p<0.001). The Midwest showed no significant change from 2021 to 2023 (APC −1.06%, 95% CI −11.77 to 10.96, p=0.85), while the West remained stable from 1999 to 2023 (APC 0.04%, 95% CI −0.26 to 0.35, p=0.78). Among racial groups, non-Hispanic White patients had stable mortality from 1999 to 2018 (APC −0.44%, 95% CI −0.65 to −0.23, p<0.001), followed by a significant increase from 2018 to 2023 (APC 6.94%, 95% CI 4.32 to 9.63, p<0.001). The sharp rise observed between 2018 and 2021 may partly reflect the impact of the COVID-19 pandemic on healthcare access and chronic disease management. Conclusions: DM-related mortality among patients with ovarian cancer has increased notably since 2018, with the greatest burden observed in the Southern United States and among non-Hispanic White populations. These findings indicate emerging regional and racial disparities and highlight the need for targeted strategies to improve diabetes management and integrate cardiometabolic care into oncology practice for vulnerable populations.
Systemic review and meta-analysis: Treatment-related adverse events of neoadjuvant immune checkpoint inhibitors.
e14581 Background: Immune checkpoint inhibitors (ICIs) are increasingly used in cancer treatment, with recent expansion into neoadjuvant settings. Treatment-related adverse events (TRAEs) in the neoadjuvant setting may differ from those in the adjuvant setting due to higher tumor burden, distinct tumor microenvironments, and shorter treatment duration. Methods: Major databases were systematically searched to identify clinical trials evaluating single-agent or combination ICIs as neoadjuvant regimen. Trials reporting tabulated TRAE data were included. Incidence of TRAEs and surgery delay were pooled using a random-effects model in RStudio (2024.09.1) Results: A total of 49 trials comprising 69 treatment arms and 3157 patients were included. Among them, TRAEs of any-grade occurred in 2212 (70.01%) patients; while grade ≥3 TRAEs were observed in 588 (18.9%) of 3,110 patients across 48 trials. Surgery was delayed in 42 patients (2.3%) among 1,855 patients from 29 trials. The 8 most common any-grade and grade ≥3 TRAEs are summarized in the table. Monotherapy was associated with lower incidences of both any-grade and grade ≥3 TRAEs compared with combination therapy. Regimen-specific TRAE profiles are presented in the table. Conclusions: TRAEs are common with neoadjuvant ICIs; despite that over 97% of patients proceeding to planned surgery without delay. Monotherapy shows a more favorable safety profile than combination therapy. This study complements prior data from the adjuvant setting and may facilitate early toxicity management and future trial design. Further investigation of TRAEs by therapy dose and tumor type is warranted as more trials become available. Top 8 All grade TRAEs Incidence (95% CI) Top 8 Grade ≥3 TRAEs Incidence (95% CI) Therapies Incidence (95% CI)of all grade TRAEs Incidence (95% CI)of grade≥3 TRAEs Fatigue 17.43% (13.19%, 22.68%) Elevated transaminase 6.8% (4.53%, 10.08%) Monotherapy 63.6% (52.55%, 73.38%) 13.66% (9.56%, 19.15%) Rash 15.3% (10.75%, 21.33%) Lipase elevation 5.28% (3.02%, 9.07%) Combination 78.96% (70.86%, 85.27%) 22.1% (65.1%, 28.94%) Elevated transaminase 14.04% (10.83%, 18.02%) Hyponatremia 4.93% (3.19%, 7.54%) Durvalumab 57.64% (11.37%, 93.25%) 19.84% (7.55%, 42.88%) Pruritus 13.38% (9.62%, 18.33%) Colitis 4.77% (2.43%, 9.16%) Nivolumab 58.25% (38.87%, 75.37%) 15.15% (9.82%, 22.65%) Hyperthyroidism 13.3% (10.7%, 16.43%) Rash 4.64% (1.94%, 10.68%) Pembrolizumab 58.65% (24.36%, 86.2%) 17.11% (5.77%, 41.03%) Hypothyroidism 12.13% (9.16%, 15.89%) Hypertension 4.08% (1.2%, 12.98%) Cemiplimab 89.71% (78.76%, 95.35%) 21.89% (6.28%, 53.96%) Nausea 11.95% (7.17%, 19.27%) Diabetes/hyperglycemia 3.84% (0.99%, 13.71%) Nivolumab + Ipilimumab 75.88% (60.12%, 86.78%) 25.2% (17.45%, 34.92%) Dry mouth 11.3% (7.74%, 16.21%) Adrenal insufficiency 3.7% (2.08%, 6.51%) Durvalumab + Tremelimumab 80.97% (36.85%, 96.88%) 23.21% (12%, 40.12%)
Neoadjuvant androgen receptor pathway inhibition for patients with high-risk localized prostate cancer: 5-year survival update and PSMA PET correlatives of the randomized NeoPRO trial.
5119 Background: Patients with high-risk prostate cancer remain at elevated risk of recurrence after local therapy. Ongoing trials are investigating neoadjuvant strategies using androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPI). Methods: This phase II trial randomized patients with Gleason ≥ 8 and/or cT3N0-1 and/or PSA ≥ 20 ng/mL to receive either goserelin (ADT) plus abiraterone acetate and prednisone (AAP arm) or AAP plus apalutamide (A-APA arm) prior to radical prostatectomy. The primary endpoint was the rate of pathological complete response (pCR) or minimal residual disease (tumor ≤ 0.5 cm). Here we present updated survival data after a median follow-up of 59 months. Biochemical-free survival (BFS) was defined as the time from randomization to PSA > 0.1 ng/mL, metastasis, or death. Metastasis-free survival (MFS) was defined as the time from randomization to metastasis or death. Kaplan-Meier method and log-rank tests were used for time-to-event analyses. Results: Sixty-two patients were randomized (AAP = 31; A-APA = 31). Previous results showed no significant difference in the primary endpoint (Bastos D, et al. ASCO 2022). A total of 35 patients experienced biochemical recurrence. No significant difference was observed between the AAP and A-APA arms in 5-year BFS (48% vs 35%, p = 0.55) or MFS (83% vs 84%, p = 0.88). Achieving complete PSMA response on PSMA PET prior to surgery was a significant prognostic factor for improved 5-year BFS (28% vs 66%, p = 0.003) and MFS (74% vs 100%, p = 0.009). A trend toward higher 5-year overall survival (OS) was also observed among those with complete PSMA response (87% vs 100%, p = 0.09). Residual cancer burden ≤ 0.25 cm³ was associated with better 5-year BFS (32% vs 77%, p = 0.008), but not with MFS (79% vs 100%, p = 0.06) or OS (89% vs 100%, p = 0.22). Conclusions: No difference in 5-year BFS or MFS was observed between AAP and A-APA. Complete PSMA response on PSMA PET is a promising prognostic marker and may serve as a surrogate for BFS and MFS after neoadjuvant treatment in high-risk prostate cancer. Clinical trial information: NCT02789878 .
Real-world survival outcomes with pembrolizumab plus chemotherapy in advanced triple-negative breast cancer: Multicenter evidence from Poland, the Czech Republic, and Slovakia.
e13118 Background: In KEYNOTE-355, pembrolizumab plus chemotherapy improved efficacy versus chemotherapy alone in first-line advanced triple-negative breast cancer (TNBC) with programmed death-ligand 1 (PD-L1) combined positive score (CPS)≥10 (median progression-free survival [mPFS] 9.7 vs 5.6 months [mo]; median overall survival [mOS] 23.0 vs 16.1 mo). Given limited real-world evidence we evaluated survival outcomes of pembrolizumab-chemotherapy across 20 oncology centers in Poland, the Czech Republic and Slovakia. Methods: This multicenter observational study, CEBCC-101, included patients with advanced TNBC and CPS≥10 treated with first-line pembrolizumab plus chemotherapy in routine practice. Primary endpoints were OS and PFS. Survival functions were estimated by Kaplan–Meier methodology. Associations between selected clinicopathologic variables and OS/PFS were explored using univariable and multivariable Cox proportional hazards models. Patients initiated treatment through June 2025; the data cutoff was November 2025. Results: The cohort included 178 female patients with median age 58.1 years (IQR 49–67, range 28–86). Median follow-up was 13.2 months (IQR: 8.6-19.5; range 0.7-38.5). In Kaplan-Meier analysis, 73 OS events occurred; estimated OS rates at 3, 6, 9, 12, 15, 18, 21, and 24 months were 97.2%, 89.9%, 83.1%, 72.9%, 66.0%, 61.2%, 48.8% and 45.1%, respectively, with mOS of 20.4 months. For PFS, 120 events occurred; estimated PFS rates at 3, 6, 9, 12, 15, 18, 21, and 24 months were 91.6%, 68.9%, 48.4%, 36.7%, 32.7%, 28.7%, 27.3% and 23.5%, respectively, with mPFS of 8.5 months. The objective response rate was 55.1% (97/176) and the disease control rate was 87.5% (154/176). In multivariable analysis for OS, presence of visceral metastases was associated with higher mortality risk (HR 2.024; 95% CI 1.162–3.525; p = 0.013). In multivariable analysis for PFS, longer time to metastatic diagnosis (HR 0.934 per year; 95% CI 0.881–0.990; p = 0.022) and de novo metastatic disease (HR 0.572; 95% CI 0.369–0.885; p = 0.012) were associated with lower risk of progression/death. Conclusions: In this Central European cohort, the observed real-world survival outcomes are consistent with those reported in the registration trial. To our knowledge, this is the first real-world evidence including mature OS estimates for pembrolizumab-chemotherapy in this setting. Visceral metastases were independently associated with worse OS. Longer time from initial diagnosis to metastatic disease and de novo metastatic presentation were independently associated with improved PFS. These findings support the effectiveness of pembrolizumab-chemotherapy in routine practice and suggest the prognostic relevance of metastatic pattern and disease-free interval in patients with advanced TNBC.
Real-world outcomes of biomarker-intended pembrolizumab use in soft tissue sarcomas.
e23574 Background: Pembrolizumab has a tissue-agnostic FDA indication for metastatic or unresectable solid tumors with high tumor mutational burden (TMB-H; ≥10 mut/Mb) or microsatellite instability–high (MSI-H), after exhausting standard treatment options. This is supported by pan-tumor trials including KEYNOTE-158. However, soft tissue sarcomas (STS) had limited representation in pan-tumor trials. Therefore, the real-world effectiveness of pembrolizumab in biomarker-intended advanced STS remains incompletely characterized. Methods: In January 2026, the TriNetX database (171 global healthcare organizations) was queried to identify patients with STS who received pembrolizumab for this diagnosis. ICD-O-3 codes that corresponded to the histological subtype listed in the NCCN Soft Tissue Sarcoma Guidelines (v1.2026) were used to build the cohort. Undifferentiated sarcoma, pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma, and alveolar soft part sarcoma were excluded to reduce inclusion of histologies where pembrolizumab may be used outside tissue-agnostic biomarker-induced indications. We extracted demographics, biomarker data, overall survival (OS), and pembrolizumab treatment duration using TriNetX Treatment Pathways. Outcomes were measured from index event (first recorded pembrolizumab administration for STS). Results: A total of 145 patients met initial criteria of selected STS histology and pembrolizumab initiation. Median age was 62 with IQR span of 19. There was a slight female predominance at 57.9%. The most common histologies were leiomyosarcoma (37%), sarcoma, NOS (14%), and lipomatous neoplasms (12%). Prior neoplastic agents were documented in 99 (68%) patients. Common prior treatments included gemcitabine (30%), doxorubicin (27%), and pazopanib (14%). Unfortunately, MSI status was reported only in 7% of the cohort and TMB was not reported. One- and two- year OS were 53.6 and 42.6%, respectively, with median OS of 15.9 months from index. Among the 145 patients, 115 received pembrolizumab without concurrent administration of other antineoplastic agents and also had treatment duration data available. Among patients who received concurrent antineoplastic therapy, doxorubicin, lenvatinib, and cabozantinib were among the most commonly used agents. Median pembrolizumab treatment duration in the 115 patients was 4.1 months. Conclusions: Our findings are broadly consistent with KEYNOTE-158 data, thereby supporting the application of biomarker-intended pembrolizumab use in advanced STS. Limitations of our study include retrospective design, potential confounders, and incomplete biomarker evaluation. Prospective studies are needed to validate outcomes in biomarker-confirmed STS.
Impact of liquid biopsy training on real-world testing practices for advanced NSCLC across Latin America: The OMEGA (LACOG 0424/GBOT) survey.
9029 Background: The therapeutic landscape of non-small cell lung cancer (NSCLC) has evolved with advances in genomic profiling and the integration of next-generation sequencing (NGS) platforms. Liquid biopsy (LB) enables minimally invasive biomarker-guided treatment across solid tumors, including NSCLC. However, disparities in physicians' familiarity with these tests and limited access to continuing education can affect their optimal implementation. Despite the potential benefits, access to and utilization of LB testing across LATAM remains unexplored. In this LATAM survey, we evaluated oncologist’s attitudes and practices related to LB. Methods: A cross-sectional survey was conducted to evaluate oncologists’ attitudes, practices, and expectations regarding LB use in NSCLC across LATAM. A 33-item questionnaire was distributed between August and December 2024 through the Brazilian Thoracic Oncology Group (GBOT), the Brazilian Society of Clinical Oncology (SBOC), and the Latin American Consortium for Lung Cancer Research (CLICaP). Descriptive statistics summarized the data, and associations were assessed using chi-square or Fisher’s exact tests for categorical variables and Student’s t-test or Wilcoxon rank-sum test for continuous variables. Results: Among the 178 respondents, 84.8% were from Brazil. Most of the oncologists had completed their oncology training between 5 and 20 years prior (61.2%). In terms of clinical exposure, 43.3% reported treating 10 to 30 new patients with lung cancer annually. While 72.5% reported prior use of LB, only 30.0% expressed confidence in interpreting the results. In addition, 50% of respondents (n = 89) reported no formal training in LB over the past three years. Among those reporting educational updates, the most prevalent source of educational updates was ASCO-affiliated platforms (43.8%). Respondents who had received dedicated training during this period were significantly more likely to request LB testing (87.2% vs 60.7%; p<0.0001) and to report confidence in interpreting ctDNA results (86.0% vs 53.9%; p<0.0001). The most frequently used techniques were DNA-based NGS (38.8%) and reverse transcription polymerase chain reaction (RT-PCR) (43.5%). Most respondents (96.1%) anticipated an increase in the use of LB over the next five years. Conclusions: The OMEGA survey indicates that while LB use is common among LATAM oncologists, formal training remains limited. Educational exposure significantly increased both the likelihood of requesting NSCLC testing and confidence in molecular report interpretation. Thus, future efforts implementing structured educational programs are very needed to support the equitable and effective adoption of liquid biopsy throughout LATAM.
Comprehensive characterization of HIF-2α and carbonic anhydrase IX expression and the genomic landscape in clear cell and <i>VHL</i> -altered renal cell carcinoma.
4543 Background: Clear cell renal cell carcinoma (ccRCC) is commonly driven by VHL loss, resulting in HIF-2α stabilization and upregulation of targets such as carbonic anhydrase IX (CA9). Clarifying the relationship between CA9 and HIF-2α expression is critical to guide rational therapeutic strategies. Methods: DNA (592-gene panel or whole exome) and RNA (whole transcriptome) sequencing was performed on ccRCC and RCC–not otherwise specified, (NOS) tumors with VHL alterations via Caris Life Sciences for integrated genomic and transcriptomic profiling. The primary objective was to characterize the expression patterns of HIF-2α and CA9 across RCC tumors and co-occurring genomic alterations. Overall survival (OS) as measured from initial diagnosis. Results: A total of 1,935 RCC tumors were analyzed, including 967 (50%) ccRCC and the remainder RCC–NOS with VHL alterations; 49% were derived from the primary site. Expression of HIF-2α and CA9 were similar across racial and ethnic subgroups. Compared to primary kidney tumors, lower HIF-2α expression was observed in lymph node and liver metastases (both p <0.0001) and lower CA9 expressions were observed in CNS and bone metastases (both p <0.0001). Increased either HIF-2α or CA9 expressions were associated with high angiogenic and T-effector gene signatures as defined in IMmotion150 (all p < 0.001). HIF-2α expression positively correlated with CA9 expression (r=0.43, p <0.001). Tumors with highest quartile HIF-2α expression (Q4) had increased PBRM1 and decreased BAP1, TP53, and TERT mutation frequencies (Table). High CA9 expression (Q4) had increased PBRM1 and decreased TP53 mutations. High HIF-2α (Q4) and CA9 (Q4) expressions were associated with improved OS compared with Q1 (HIF-2α: median OS 97 vs 64.7 months, HR 0.56, p < 0.0001; CA9: median OS 90 vs 49 months, HR 0.63, p = 0.002). Conclusions: High expression of HIF-2α and CA9 identifies a canonical VHL/HIF-driven RCC subtype marked by enrichment of PBRM1 mutations, depletion of aggressive genomic alterations ( BAP1 , TP53 , TERT ), and improved OS. Strong associations with angiogenic and immune-related gene signatures further support a coherent HIF-dependent phenotype. Key gene mutation frequency by HIF-2 α/CA9 expression. HIF-2α (Q1) HIF-2α (Q4) P value CA9 (Q1) CA9 (Q4) P value PBRM1 33% 48% <0.001 22% 46% <0.001 BAP1 29% 8% <0.001 22% 19% 0.43 TP53 13% 7% 0.012 16% 8% 0.04 TERT 13% 6% 0.005 12% 8% 0.37
Development and validation of a National Database–derived nomogram for predicting postoperative survival in colorectal cancer.
3669 Background: Prognosis after curative-intent surgery for colorectal cancer remains heterogeneous and incompletely explained by TNM staging alone. Existing prognostic tools often exclude important demographic, clinical, and biologic factors. Improved risk stratification is needed to support individualized postoperative prognostication. Methods: Using the National Cancer Database (NCDB), data from 88,696 patients diagnosed between 2018–2019 were used to develop and internally validate five prognostic models. All models were extensions of the MSK colon cancer nomogram and were fit using the full cohort. The full model incorporated all MSK predictors plus additional demographic, tumor, and treatment variables including perineural invasion and microsatellite instability status. Reduced models included MSK predictors and select variable subsets. Cox proportional hazards regression was used to estimate 5-year (5y) overall survival. Calibration was assessed by comparing deciles of predicted vs observed 5y Kaplan–Meier survival probabilities (expected-to-observed (E/O) ratios). Discrimination was evaluated using 5y area under the time-dependent receiver operating characteristic curve (AUC). Bias-corrected calibration curves and AUCs were generated to assess model generalizability to external populations. Model performance was compared directly with the MSK nomogram by comparing 5y AUCs calculated using a random sample of 1,000 NCDB-cohort patients. Category-free net reclassification improvement (NRI) was also calculated for patients with known vital status at 5y. Results: Calibration and discrimination were similar across all models. In the full model, E/O ratios demonstrated excellent calibration, with median E/O = 1.01 (range = 0.82-1.08). Full model discrimination was excellent with 5y AUC = 0.787 (95% CI, 0.782–0.793). Bias-corrected calibration curves and AUCs indicated stable performance supporting generalizability. In our 1,000 patient random sample, the full model 5y AUC was 0.822 (95% CI, 0.779–0.866), compared with 0.799 (95% CI, 0.753–0.844) for the MSK nomogram, with no statistically significant difference (p = 0.13). In our 1,000 patient NCDB sample, 397 patients had known 5y vital status (258 deaths, 139 alive, 603 censored prior to 5y) with the full model showing improved overall, event and nonevent discrimination compared with the MSK nomogram (overall 5y NRI = 0.35, event NRI = 0.12, and nonevent NRI = 0.24). Conclusions: We developed a postoperative survival nomogram for colorectal cancer that demonstrated good calibration and discrimination and meaningfully improved risk classification compared with the MSK model. Integration of additional routinely available variables enables more individualized postoperative prognostication.
Emotional health concerns due to kidney cancer (KC) and unmet needs in patient support: Results from the International Kidney Cancer Coalition (IKCC) Global Patient Survey (GPS).
4532 Background: KC negatively impacts the emotional well-being of patients, and patient support services are a critical component of care to improve emotional health and patient outcomes. Since 2018, the IKCC and its network have conducted a biennial GPS to assess patient/caregiver experiences on KC burden, diagnosis, and management, determine unmet needs and country variances, and identify opportunities to close gaps. We present global data from the 2025 GPS on emotional well-being and use of patient support resources. Methods: An IKCC steering committee of patient advocates, medical experts and the Picker Institute (UK) designed the 2025 GPS targeting KC patients and caregivers. It was cognitively tested, translated into 16 languages, and hosted online and on paper. Data were independently analyzed using cross-tabulations. Results: Between Sept 24 and Nov 15, 2024, 2677 responses were received from patients (n=2049) and caregivers (n=628) from 46 countries. Globally, 85% of respondents were impacted emotionally due to KC, with impacts observed across all disease stages. The most common were disease-related anxiety (50%), fear of recurrence (49%), sadness/depression (36%), and fear of dying (35%). Respondents aged 80+ and 66–80 years reported fewer emotional concerns than younger respondents. Globally, only 40%–66% of respondents discussed emotional concerns with a healthcare provider (HCP). Respondents from India and Mexico were more likely to discuss concerns with an HCP, while those from the Republic of Korea were least likely to discuss concerns. Many conversations with HCPs were considered unhelpful; notably, 33% indicated discussions about difficulties navigating the healthcare system were unhelpful. Globally, 50% of respondents accessed a patient support group, either in person or online. Respondents from Japan (19%), Türkiye (24%), France (25%), and Italy (27%) were least likely to access a patient support group, while those from India (90%) and the Republic of Korea (88%) were most likely to access a group. Overall, 47% said support groups were helpful. Patient organization websites (28%) and online support groups (27%) were considered most helpful, with variations observed across countries. Respondents indicated a desire for more counselling and/or psychological support, in-person support, peer-to-peer support, and online support. Conclusions: Most respondents experienced an impact on their emotional well-being due to KC; however, many did not discuss their emotional concerns with an HCP or access a patient support group either in person or online. Improved communication is needed between patients/caregivers and HCPs to address emotional concerns. HCPs can improve patient well-being through referrals to counselling/psychological support, and patient organizations in their country.
First-in-human study of cavitation-enhanced drug delivery (CEeDD) by sonosensitive particles and focused ultrasound applied to colorectal metastases in the liver.
3549 Background: Effective treatment of colorectal liver metastases is limited by poor drug delivery, particularly for monoclonal antibodies, the large molecular weight of which, together with abnormal tumor vasculature, elevated interstitial pressure and dense stromal architecture, restricts penetration and distribution into solid tumors. This first-in-human study evaluated a novel platform combining intravenously infused sub-micron gas-stabilizing sonosensitive particles with novel handheld ultrasound probe to cause cavitation that enhances the transport of systemically co-administered therapeutics (i.e. cetuximab/irinotecan) from the vasculature into tumors, without the need to modify these therapeutics. Methods: The study comprised 3 patient cohorts. Cohort 1 evaluated the safety of ultrasound activation of intravenously infused sonosensitive particles alone, without drug. With safety confirmed, Cohort 2 assessed intratumoural drug concentration in patients undergoing surgical resection after receiving subtherapeutic irinotecan and cetuximab, with or without ultrasound-activated particles. Cohort 3 evaluated early efficacy in patients receiving standard of care FOLFIRI and cetuximab, with or without cavitation in repeated treatment cycles. Primary endpoints were grade 3 or higher adverse events in Cohort 1, intratumoural drug concentrations in Cohort 2, and radiological tumor response in Cohort 3. Results: In Cohort 2, seven evaluable patients underwent resection, with 4 in the control arm and 3 in the ultrasound-mediated-cavitation arm. Mean cetuximab concentrations were modestly higher in the tumour centre (3.6 vs 3.2 ng/mL) and mid radius (4.1 vs 3.7 ng/mL), and substantially higher at the tumour periphery (7.1 vs 3.7 ng/mL) in the ultrasound-mediated-cavitation arm, while liver margin levels were comparable. There was no appreciable beneficial difference in the mean tumour concentrations of irinotecan and its metabolites between the two arms. In Cohort 3, 10 evaluable participants completed at least 3 treatment cycles (control n=3; cavitation n=7). Objective response rate was 66.7% in the control arm versus 85.7 % with cavitation. Conclusions: Cavitation with sonosensitive particle infusion demonstrated a favourable safety profile, increased intratumoural antibody delivery, and showed early signals of enhanced anti-tumour activity, supporting further clinical development. Clinical trial information: ISRCTN17598292. Cohort Number treated Primary endpoint Key findings 1 9 Safety No grade 3 or higher events; sustained cavitation in the target region. 2 7 Drug levels Increased cetuximab concentrations in the tumours treated with cavitation (7.1 vs 3.7 ng/mL) 3 10 Radiological response Enhanced radiological response (ORR of 85.7% in patients treated with cavitation) ORR = objective response rate based on FDG PET-CT.
Infection-associated transitions to critical care–level interventions in adult cancer hospitalizations: A National Inpatient Sample analysis.
e23214 Background: Infectious diagnoses and complications during cancer hospitalizations are commonly evaluated using static outcomes such as mortality or organ-specific failure. Whether infection precipitates discrete shifts from routine inpatient management to critical care–level interventions remains poorly defined. This study examined the infection-associated transition to intensive care in hospitalized adults with cancer. Methods: A serial cross-sectional analysis of adult hospitalizations with a principal diagnosis of malignancy in the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample was conducted. We identified infection using validated any-diagnosis ICD-10-CM phenotypes for sepsis, infection-associated shock, or infection-associated acute organ dysfunction. The primary outcome was a composite escalation-anchored transition to critical care defined by initiation of mechanical ventilation, dialysis-requiring acute kidney injury, or shock during hospitalization. Secondary outcomes included in-hospital mortality, length of stay, and hospitalization cost derived using cost-to-charge ratios. National estimates were generated using survey-weighted analyses accounting for discharge weights, hospital-level clustering, and stratification, with multivariable adjustment for demographics, cancer lineage, APR-DRG severity, and hospital characteristics. Results: Among an estimated 4.81 million cancer hospitalizations nationally, 12.9% were complicated by infection. Critical care transitions occurred in 25.0% of infected admissions compared with 0.7% of non-infected hospitalizations. Infected admissions demonstrated substantially higher rates of mechanical ventilation (17.0% vs 0.5%), dialysis-requiring acute kidney injury (2.9% vs 0.3%), and shock (10.8% vs 0%). In-hospital mortality increased markedly following escalation, from 3.2% among admissions without transition to 34.4% among those requiring critical care–level intervention. Transitions to critical care were associated with significantly longer length of stay (16.5 vs 6.4 days) and higher mean hospitalization cost ($84,849 vs $27,964). After multivariable adjustment, infection remained independently associated with transition to critical care (adjusted OR 12.51; 95% CI 11.48–13.63). Conclusions: Infection in hospitalized adults with cancer is associated with discrete threshold crossings to critical care–level interventions rather than functioning solely as a static diagnostic category. Framing infection as a driver of inpatient escalation highlights opportunities for earlier risk identification, triage prioritization, and proactive escalation planning in high-risk oncology admissions.
Feasibility assessment of a global, anonymized, human-in-the-loop AI decision-support platform for oncology second opinions following a live demo at an international symposium.
e13672 Background: There are widespread disparities in access to rapid, expert-level second opinions worldwide. We assessed the feasibility and early adoption of an anonymized, human-in-the-loop AI decision-support platform (PrecisCa.AI) that analyzes cases in 2-3 minutes and offers optional expert faculty over-read on request. Methods: After a real-time demonstration during international breast cancer tumor boards (December 2025), we collected provider-submitted, de-identified cases. Feasibility measures included successful case processing and measured time to response. Secondary measures included clinician uptake, location of submitted cases, tumor of origin, referral sources, and in-app feedback. AI consults are undergoing expert review and scoring from 1-5 (5 being the highest) on 6 attributes: clarity, completeness, menu of options, recency, reasoning, and relevance. An in-app survey asked if the response was helpful. Results: Across the observation window, from 12/10/2025-1/23/2026, 256 cases were submitted by 89 unique active providers (mean 2.9 cases/provider) after 125 new sign-ups (100% registration completion). Processing success was 100% (0/256 failed), with mean turnaround time of 149 seconds. Submissions originated from North and South America, Europe, Middle East, Africa, and Asia. Breast cancer cases (58%) were most common followed by thoracic 13%, hematologic 9%, GI 8%, GU 5%, gynecologic 3%, head & neck 2%, and skin 1%. Referrals were most commonly from a colleague (45%) followed by referrals from a conference 32%, email 7%, social media 6%, Google 3%, and other 7%. In-app survey response rate was 16.8% (43/256) with mean score 3.7/5. 33% of survey responses contained free-text comments. Multiple adjudicator large language models were available and used (most commonly recent Gemini and ChatGPT). Conclusions: An anonymized, clinician-submitted, human-in-the-loop AI platform achieved feasible global use shortly after a public demonstration, with 100% processing success and short mean turnaround time across diverse tumor types and referral channels. Optional expert faculty over-read was available, and AI consults will now be expert-rated (1-5) on clarity, completeness, menu of options, recency, reasoning, and relevance. Detailed analyses of expert ratings and comparative model performance will be presented.
A trial to evaluate CSF ctDNA and safety of plixorafenib alone or with retifanlimab in patients with BRAF-altered glioma.
TPS2100 Background: BRAF V600E mutant gliomas are difficult to treat in the recurrent setting due to adaptive resistance to FDA-approved targeted therapies. Emerging therapeutic approaches include novel BRAF inhibitors or combination therapies, but evaluating treatment response is limited by radiographic techniques and the infeasibility of serial tissue sampling. This two-arm study will evaluate the feasibility of using CSF and plasma circulating tumor DNA (ctDNA) as biomarkers for response to a novel-BRAF inhibitor, plixorafenib alone or in combination with PD-1 inhibitor, retifanlimab. Plixorafenib is a small-molecule selective inhibitor of BRAF-V600E and BRAF-fusion alterations without inducing paradoxical reactivation of MAPK signaling. Methods: This single institution trial of plixorafenib alone (Arm A) or combined with retifanlimab (Arm B) is enrolling patients (18+ years of age) with BRAF-V600E mutant glioma following progression on prior BRAF-targeted therapy who are recommended for a clinically-indicated diagnostic or debulking surgery. Eligible patients have recurrent BRAF-V600E mutant glioma (any grade) with measurable disease (by RANO 2.0), and a Karnofsky performance status ≥ 70. Leptomeningeal disease is allowed. All enrolled patients will undergo clinically-indicated resection or biopsy for confirmation of disease progression and characterization of putative resistance alterations with a ventricular reservoir placed at time of surgery for CSF sampling. In both arms, patients will initiate oral plixorafenib once clinically recovered from surgery. Patients will take the plixorafenib daily with food. In Arm B, enrolled patients will receive one dose of retifanlimab three weeks prior to surgery, then resume monthly retifanlimab infusions after surgery in combination with oral plixorafenib. MRI, CSF, and plasma assessments will occur approximately every two months to evaluate disease status. The primary trial endpoint is detectable ctDNA at baseline and after one month of treatment with plixorafenib. Secondary endpoints include safety of plixorafenib alone or in combination with retifanlimab, response rate in each arm, and the correlation of ctDNA with disease status over time. The trial is IRB approved and enrollment is ongoing (10 patients per arm). Clinical trial identifier NCT06610682. Clinical trial information: NCT06610682 .
Data-driven precision prognostic stratification in breast cancer leptomeningeal metastasis: The BC-LGPA model and treatment refinement.
1114 Background: Breast cancer leptomeningeal metastasis (BCLM) lacks data-driven prognostic models integrating diagnostic certainty with molecular features, resulting in empirical treatment limitations. Methods: We analyzed 403 BCLM patients (Nov 2013-Nov 2025) from four centers, constructing the Breast Cancer Leptomeningeal Graded Prognostic Assessment (BC-LGPA) based on diagnostic criteria (CSF cytology, symptoms, MRI patterns) and molecular subtype, validated externally. Results: The median overall survival (OS) was 7.5 months. As the first data-driven prognostic classification for BCLM, the BC-LGPA integrates diagnostic certainty scores (0–2) and molecular scores (0–1). ECOG performance status and extracranial metastases were excluded owing to collinearity with neurological symptoms and because leptomeningeal metastasis itself constitutes the primary survival-limiting factor. The model stratifies patients into high-risk (0 points, 4.7 months), intermediate-risk (1–2 points, 8.0 months), and low-risk (3 points, 16.6 months) groups (training p=0.001; validation: 4.1 vs. 7.9 vs. 16.0 months, p=0.003). Key innovations include: (1) Granular diagnostic stratification into Class A (cytology-proven), B (clinical-radiological), and C (incidental-radiological), with subclasses A1/A2/A3, B1/B2, and C1/C2/C-special; (2) Ultra-indolent entity identification: Class C-special (localized calvarial-meningeal disease without diffuse LM) shows exceptional median OS of 68.0 months, representing a distinct clinical entity unsuitable for conventional prognostic models; (3) Treatment refinement: Intrathecal therapy improved survival in Class A and Class B-Linear subgroups, whereas focal radiotherapy demonstrated no independent benefit, including in Class C2 (31 patients, p =0.794), challenging empirical RT practices. Conclusions: BC-LGPA establishes the first data-driven BCLM prognostic framework, correcting treatment recommendations through subgroup efficacy analyses to guide precision management and clinical trial design. The scoring criteria of the BC-LGPA. Prognostic Factor Score Criteria Definition Diagnostic Certainty CSF cytology Neurological symptoms MRI Class A(Cytology- proven) 0 + + / - + / - Class B(Clinico-radiological) 1 - / NA + + Class C*(Incidental radiological) 2 - / NA - + Molecular Subtype TNBC 0 ER - PR - HER2 - non-TNBC 1 ER/PR + and/or HER2 + Total score = Diagnostic Certainty score + Molecular Subtype score NA: Not Available; * Localized calvarial-meningeal disease were excluded.
Dissimilar Electrolyte Decouples Zn and MnO <sub>2</sub> Redox Chemistry Enabling Dual‐Electrode‐Free Lean‐Electrolyte Batteries
ABSTRACT Dual‐electrode‐free Zn–MnO 2 batteries offer exceptionally high theoretical energy density (616 mAh g −1 at 2 V) and simplified manufacturing, yet their practical use is hampered by low Coulombic efficiency (CE) and unstable cycling, arising from the intrinsic incompatibility of Zn and MnO 2 redox chemistries. Previous studies employing preloaded Zn and excess electrolyte obscure this incompatibility. Herein, we design a dissimilar electrolyte architecture to decouple Zn plating‐stripping from MnO 2 deposition‐dissolution, fundamentally addressing their incompatibility. The architecture integrates two distinct gels, wherein a self‐assembled nanometer‐thin water layer functions as a “soft wall” for selective ion transport due to binding energy differences at the gel/water interface. Further, the screening effect induced by the discrepancy in ionic conductivity across the junction is investigated for the first time, offering new insights into ion transport in heterogeneous electrolytes. This strategy enables a dual‐electrode‐free lean‐electrolyte Zn–MnO 2 cell with areal and volumetric energy densities of 3.1 mWh cm −2 and 25.8 Wh L −1 , and a power density of 24.1 mW cm −2 at 2 mAh cm −2 . The cell also achieves an average CE of 91% at 1mAh cm −2 cycling. Moreover, the dual‐electrode‐free configuration readily integrates with diverse current collectors, extending the concept to flexible and stretchable batteries for wearable electronics, soft robotics, and beyond.