Browse Articles

Directional heat rectification in electronic logic circuits via near-field radiative heat transfer

Synaptic Functionality and Neuromorphic Information Processing in Membrane Ion Channel Junctions (Adv. Mater. 31/2026)

Upconversion detection of terahertz wave with nanosecond pulse duration using continuous-wave laser

Steroid receptor coactivators in immunity - From function to emerging translational opportunities

USP10 activity as sensitizer of lung adenocarcinoma to immune checkpoint inhibitors: Upregulating PD-L1 via the ANT3-mediated activation of the cGAS-STING pathway.

8542 Background: Although immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape for advanced lung adenocarcinoma (LUAD), response heterogeneity remains substantial. The cGAS–STING pathway plays a pivotal role in activating antitumor immune responses, yet its upstream regulatory mechanisms remain poorly defined. This study investigated the role of the deubiquitinating enzyme USP10 in remodeling the LUAD immune microenvironment and its mechanistic link to PD-L1 expression via the cGAS-STING axis to establish its potential as a predictive biomarker for ICIs efficacy. Methods: Interactions between USP10 and the mitochondrial protein ANT3 were characterized using Co-IP, LC-MS/MS, and in vitro deubiquitination assays. Mitochondrial DNA (mtDNA) leakage and cGAS-STING activation were assessed via immunofluorescence and qPCR. The therapeutic impact of USP10 on PD-1 blockade was evaluated in an orthotopic murine LUAD model. Furthermore, Furthermore, a clinical cohort of 228 patients with advanced driver-gene negative LUAD receiving first-line ICIs treatment was analyzed to correlate USP10 expression with objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: Mechanistically, USP10 directly interacts with mitochondrial adenine nucleotide translocase 3 (ANT3) and stabilizes its protein level by removing K48-linked ubiquitin chains. USP10-mediated ANT3 accumulation triggers mitochondrial stress and promotes mtDNA release into the cytosol, thereby activating the cGAS-STING-TBK1-IRF3 signaling pathway and ultimately driving transcriptional upregulation of PD-L1. In orthotopic LUAD models, USP10-overexpressing tumors exhibited an "inflamed" phenotype characterized by a significant increase in CD8+ T cell infiltration. USP10 expression levels sensitized tumors to immunotherapy; USP10-high tumors demonstrated dramatic regression upon anti-PD-1 treatment compared to controls. In the cohort of 228 patients, high USP10 expression was identified as a robust predictor of superior clinical benefit to first-line ICIs treatment . Patients in the USP10-high group achieved significantly prolonged PFS (p = 0.028), higher ORR (p = 0.037), and improved DCR (p = 0.041) compared to the USP10-low group. Conclusions: Our study identifies a novel USP10-ANT3-cGAS-STING-PD-L1 regulatory axis that converts "cold" tumors into "hot" tumors. By inducing a pro-inflammatory TIME, USP10 enhances the sensitivity of LUAD to ICIs. These findings establish USP10 as a promising predictive biomarker and a potential therapeutic target to optimize immunotherapy strategies in lung adenocarcinoma.

Empowering multidisciplinary teams in cancer survivorship: Results from the ASCO Project ECHO survivorship program in Brazil.

11096 Background: As the number of cancer survivors increases in Brazil, access to structured survivorship education for health professionals remains limited. ASCO Project ECHO Survivorship Program was implemented to strengthen survivorship knowledge and care coordination among multidisciplinary teams. Methods: This longitudinal, virtual, case-based education series was conducted from September to December 2025. Intended audience included oncologists, general physicians, nurses, psychologists, and other professionals involved in survivorship care. Program consisted of 08 distinct, self-contained sessions, beginning with an introductory session on core survivorship principles, followed by cancer-specific survivorship topics delivered through short didactics and case discussions. Participants were encouraged to attend all sessions; however, each session was designed to be independent. Attendance was tracked, and final post-program survey assessed satisfaction and self-reported impact on clinical practice. Analyses focused on participants attending ≥4 sessions (≥50%), which was the criterion for certification and a pragmatic threshold to ensure meaningful engagement. Results: 161 health professionals attended at least one session, and 65 (40.4%) participated in ≥4 sessions. Participants represented diverse disciplines, including physicians and oncologists (31%), psychologists (13.7%), nutritionists (8.7%), pharmacists (6.2%), nurses (11.2%), and other professionals. Subsequent analyses were limited to participants attending ≥4 sessions. Among these,final survey response rate was 66.2%. Reported practice changes and satisfaction outcomes were collected through the post-program survey. Respondents described increased confidence in identifying and managing late and long-term physical effects, addressing psychosocial and sexual health concerns, improving interdisciplinary collaboration, and supporting transitions to post-treatment care. Overall satisfaction was high, with 97.7% reporting being satisfied or very satisfied. Despite high satisfaction, attendance declined across sessions, highlighting the need to better understand factors influencing sustained participation in longitudinal virtual education programs. Conclusions: ASCO Project ECHO Survivorship Program in Brazil demonstrated strong engagement and meaningful self-reported integration of survivorship principles into clinical practice among a multidisciplinary workforce. This flexible, scalable educational model supports survivorship capacity-building across diverse professional roles in middle-income settings. Further evaluation is needed to better understand factors associated with decreased attendance over time and to inform strategies that optimize sustained engagement in longitudinal survivorship education programs.

Treatment outcomes with pembrolizumab and chemotherapy in metastatic metaplastic triple-negative breast cancer: Data from a central European cohort.

e13119 Background: Metaplastic triple-negative breast cancer (MpTNBC) is a rare and clinically aggressive subtype of breast cancer associated with poor prognosis. Although immunotherapy combined with chemotherapy has demonstrated clinical benefit in patients with metastatic triple-negative breast cancer (mTNBC), data specific to MpTNBC remain limited. This study aimed to evaluate the real-world efficacy and safety of pembrolizumab in combination with chemotherapy in patients with metastatic MpTNBC. Methods: Within the CEBCC-101 real-world evidence program, a multinational, multicenter retrospective study collecting data from 20 oncology centers across Central Europe, we performed a predefined subanalysis restricted to patients with histologically confirmed metaplastic MpTNBC treated with first-line pembrolizumab plus chemotherapy in routine practice (outside clinical trials). Among 178 women with mTNBC included in CEBCC-101, 14 MpTNBC cases (7.9%) were identified across 9 oncology centers and constituted the study population for the present analysis. Treatment was initiated in Poland, the Czech Republic and Slovakia between September 2022 and June 2025. Safety was assessed as the incidence and severity of treatment-emergent adverse events (AEs), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The median age at treatment initiation was 59.7 years (range, 33.1–81.0). The median follow-up was 14.0 months (range, 7.5–20.4). At data cutoff, 13 patients had discontinued treatment due to disease progression (n = 11) or treatment-related toxicity (n = 2), while one patient remained on therapy; 11 patients had died. Objective response rate (ORR) was observed in 7 of 14 patients (50.0%), and disease control rate (DCR) was achieved in 11 patients (78.6%). Median overall survival (mOS) was 14.1 months, with 6-, 12-, and 18-month OS rates of 100.0%, 64.3%, and 40.2%, respectively. Median progression-free survival (mPFS) was 6.0 months, with corresponding PFS rates of 50.0%, 14.3%, and 7.1%. Grade ≥2 AEs occurred in 12 patients (85.7%). Grade 3 toxicity was observed in 6 (42.9%), with no grade 4–5 events reported. The most frequent AEs were chemotherapy-related, predominantly neutropenia and peripheral neuropathy. Conclusions: This first international real-world series evaluates pembrolizumab in combination with chemotherapy in patients with metastatic MpTNBC. mPFS and mOS observed in this real-world cohort were markedly shorter than those reported in the phase III KEYNOTE-355 trial, most likely reflecting the exceptionally aggressive clinical course of MpTNBC. The safety profile of treatment was acceptable. These findings underscore the need for further prospective studies and international collaboration in rare breast cancer subtypes.

Efficacy and safety of cadonilimab (CD) in combination with disitamab vedotin (RC48) or nab-paclitaxel (NP) in the treatment of recurrent or metastatic cervical cancer (r/mCC): A prospective, double-cohort, multicenter, open-label, phase II clinical study.

5526 Background: The prognosis for patients(pts) with r/mCC is poor. The available second-line treatment regimens are limited, highlighting the need for more effective therapies. CD is a dual-target immune checkpoint inhibitor targeting PD-1 and CTLA-4 and RC48 is an antibody-drug conjugate targeting HER2. Here, we report updated results from a phase II study of CD plus RC48 or NP in r/mCC. Methods: This is a prospective, multicenter, open-label, phase II trial with two parallel cohorts(AK001). Eligible patients had r/mCC with progression after 1-3 prior lines of chemotherapy. Patients were assigned by HER2 immunohistochemistry (IHC): cohort I (HER2 IHC 1+ - 3+) received CD (6mg/kg) plus RC48 (2.5mg/kg) biweekly; cohort II (HER2 IHC 0) received CD (10mg/kg) plus NP (260mg/m 2 ) triweekly. The primary endpoint of the study was objective response rate (ORR). Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. A Simon's two-stage design was applied, with the ORR from the innovaTV 204 study as a historical control, which was 24%. Assuming the ORR for cohort I is 50% and for cohort II is 40%, with a power of 0.8 and a one-sided α of 0.05, and considering a dropout rate of 10%, the total sample size calculated was 32 for cohort I and 42 for cohort II. Results: As of the data cutoff (January 15, 2026), 62 pts were enrolled, including 53 evaluable pts (26 in cohort I and 27 in cohort II) across 5 large academic centers in China. Median follow-up was 12.03 months (range, 1.87 - 26.57). For cohort I, the ORR was 57.7% ( 95% CI, 36.9% - 76.6%) and median DOR was not reached (95% CI, 3.97 - NR). Median PFS was 8.23 (95% CI, 3.41 - 13.06) months and 12-month PFS rate was 45%. For cohort II, the ORR was 55.6% ( 95% CI, 35.3% - 74.5%) and median DOR was 4.57 (95% CI, 2.30 - 6.83) months. Median PFS was 5.87 (95% CI, 4.55 - 7.19) months and 12-month PFS rate was 38%. Toxicity was tolerable in both cohorts. Grade 3-4 treatment-related adverse events occurred in 15.4% of pts in cohort I and 21.4% of pts in cohort II. Conclusions: Our current results support a potential HER2 expression-guided option for second-line treatment of r/mCC. CD plus RC48 demonstrated favorable efficacy and a manageable safety profile, and may emerge as a novel effective combination for the treatment of HER2 positive cervical cancer. Long-term benefits and further analysis of the role of this combination therapy in r/mCC will be critical to advancing treatment strategies. Clinical trial information: ChiCTR2300076740. Antitumor activity assessed by RECIST version 1.1. Cohort I (n=26) Cohort II (n=27) ORR 15(57.7%) 15(55.6%) 95%CI 36.9 - 76.6 35.3 - 74.5 DCR 24(92.3%) 20(74.1%) 95%CI 74.9 - 99.1 53.7 - 88.9 Best Overall Response CR 3(11.5%) 0 PR 12(46.2%) 15(55.6%) SD 9(34.6%) 5(18.5%) PD 2(7.7%) 7(25.9%)

Final results of the phase III OCTAVA trial: Clinical benefit of low-dose anti–CTLA-4 plus anti–PD-1 combination vs anti–PD-1 monotherapy in unresectable or metastatic melanoma.

9544 Background: BCD-217-2/OCTAVA is an international, multi-center, randomized, double-blind, placebo-controlled phase III study conducted to assess the efficacy and safety of nurulimab +prolgolimab (nuru + prolgo ) combination therapy with continued prolgolimab therapy compared to prolgolimab monotherapy at the 1st line treatment of patients (pts) with unresectable or metastatic melanoma (un/mM). BCD-217 is a fixed-dose combination of nurulimab (aCTLA-4, 5 mg/ml) and prolgolimab (aPD-1, 15 mg/ml) which was recently approved for this indication in Russia and Belarus. Here we present efficacy results based on 24 mos of therapy. Methods: Treatment-naïve pts with un/mM (stage IIIC–IV) were randomized 1:1 to two arms. The nuru+prolgo arm received a combo of nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) at 0.2 ml/kg Q3W for the first four infusions. The prolgo arm received prolgolimab monotherapy (3 mg/kg Q3W) for the first four infusions. Both arms then received prolgolimab maintenance therapy for up to two years. The primary endpoint of the study was PFS. Results: 271 pts were randomized to nuru+prolgo (n=135) or prolgo monotherapy (n=136) arms. After a median follow-up of 24.7 mos the mPFS was 15.4 (95% CI 8.4; NA) mos in the nuru+prolgo arm and 8.3 (95% CI 4.2; 14.8) mos in the prolgo monotherapy arm (HR 0.696, 95% CI 0.502; 0.965), iRECIST, ITT population). The PFS benefit was consistent per RECIST 1.1 (HR 0.717, 95% CI 0.533; 0.964). ORR, DCR and TTR were also higher in nuru+prolgo arm. mOS was not reached in both groups (HR 0.836, 95% CI 0.495; 1.41). 24-mos OS was 76.1% in nuru+prolgo arm and 71.7% in prolgo arm respectively. The mDOR was also not reached in any arm, meaning that more than half of the pts who responded to therapy maintained their response until the end of the FU period. Grade ≥3 treatment-related AEs occurred in 17.8% of pts (nuru+prolgo) vs 13.2% (prolgo). Gr ≥3 irAEs were 14.1% vs 5.1%, respectively (p=0.0126). Any-grade irAEs were reported in 51.9% vs 33.8% of cases (p=0.0027). Treatment discontinuation due to AEs was 11.1% vs 5.1%. Conclusions: The OCTAVA trial results demonstrated a statistically significant and clinically meaningful improvement in PFS for the 1st line low-dose nuru + prolgo combination followed by prolgo maintenance, compared to prolgo monotherapy, in patients with unresectable or metastatic melanoma. This efficacy benefit was accompanied by manageable rate of immune-related AE, consistent with the known profile of CTLA-4/PD-1 combinations. These results support the use of the nuru + prolgo regimen as a valuable 1st line treatment option for this population. Clinical trial information: NCT05732805 .

An intervention in disguise: An immersive care model for families where a parent has a brain tumor.

e13551 Background: Having a parent with brain cancer deeply impacts the family unit, leading to increased isolation and long-term adverse psychiatric effects, particularly in children. Milton Marks Neuro-Oncology Family Camp (MMFC) is a free, immersive retreat, offered in collaboration with the UCSF Gordon Murray Neuro-Oncology Caregiver Program, for families where a parent has a primary brain tumor and children living at home. Camp aims to reduce isolation by strengthening community within and among families and their medical care teams. Methods: MMFC integrates UCSF medical providers and volunteer psychologists, camp counselors, musicians, bodyworkers, portrait photographers, and art therapists. Camp includes family and separate child/parent activities. Outcomes were evaluated using longitudinal surveys collected pre-camp, post-camp, and at one-year follow-up. Measures include validated measures and study-designed questions assessing isolation, trust in medical teams, family communication, and psychosocial coping. The 2025 cohort incorporated clinical screening tools (PHQ-4 and PROMIS) to better assess psychiatric symptom burden. Results: From 2014-2025, an average of 11 families (25 children) participated annually, with 63% having fathers and 37% having mothers diagnosed with primary brain tumors. Children’s ages ranged from 0-23 years, with most between 4-17 years. In the 2025 cohort (n = 45), inclusion of PHQ-4 and PROMIS revealed clinically significant symptoms of depression, anxiety, and social isolation, with several participants meeting criteria for moderate to severe symptom burden. 53% of first-time attendees in 2025 had clinically elevated anxiety (GAD-2 ≥3) before camp compared to 18% of returning attendees (p = 0.0235). Prior camp outcomes showed that 93% of attendees (2016-2025, n = 135) reported decreased loneliness and isolation after camp, and 88% reported increased trust and openness with their UCSF medical team. Overall, findings support that creating community through immersive, family-centered interventions is an effective approach to addressing loneliness, isolation, and emotional distress in families affected by brain tumors. Conclusions: Immersive, wraparound models of care such as MMFC are a novel approach to addressing the psychosocial needs of families affected by primary brain tumors. The integration of clinical assessments demonstrates the extent of psychiatric symptom burden and the potential role of community-based interventions in mitigating isolation and enhancing engagement with medical care. Limitations include the relatively small sample size of new families, which is inherent to the scope and immersive design of camp. Further research with expanded cohorts is warranted to quantify long-term mental health outcomes and define best practices for integrating immersive, family-centered models into comprehensive cancer care.

Real-world experience of a pediatric precision oncology protocol utilizing paired somatic and germline sequencing at a single institution: Interim analysis.

10008 Background: While most pediatric oncology patients are cured with upfront therapy, outcomes for patients with metastatic and relapsed/refractory disease remain poor. Salvage therapy is toxic and has marginal success rates, necessitating novel, personalized approaches. We established our pediatric precision oncology program based on integrative clinical sequencing (ICS) in 2012 and present an interim outcomes analysis of this single institution cohort. Methods: Pediatric and AYA oncology patients (age 0-25 years) underwent paired somatic and germline sequencing, including whole exome and transcriptomic analysis. Results were annotated with longitudinal clinical data extracted from the medical record using the NCI-supported tool EMERSE, which has been enhanced by the addition of a beta version of a large language models (LLM) integrated “Chatbot” to implement more efficient data abstraction from clinical notes. Results: Of the 1000 patients enrolled, 925 (92.5%) were sequenced successfully. We present interim analysis of the first 435 patients. Within this interim cohort, 233 (53.56%) of patients were male and 79.8% were non-Hispanic white. Hematologic malignancies accounted for 110 (25.3%) diagnoses, brain tumors 75 (17.2%), and non-brain solid tumors 250 (57.5%). ICS succeeded for 400/435 (92.0%) patients. Overall, 471 actionable alterations (AA) were discovered in 266 (66.5%) patients (mean 1.77 AA/patient). These included 62 actionable germline alterations in 60 patients (15%). There were 195 single nucleotide variants (SNV) in 142 patients, 69 gene fusions in 62 patients, and 145 copy number alterations (CNA) in 92 patients. Actionable findings guided the use of targeted therapies (TT) supported by NCI-MATCH criteria in 116 patients (29.0%) with a total of 209 targeted therapies given (mean 1.80 /patient). Thirty-two patients (8.0%) enrolled on therapeutic clinical trials featuring an identified targeted therapy. Sixteen (4.0%) patients without AAs received 22 TTs based on clinician preference. Additionally, 166 patients (41.5%) did not receive TT despite at least one AA due to lack of availability of a suitable formulation, pursuit of alternative therapy, or death prior to therapy initiation. Repeat ICS (range 1-4) was completed for 115 patients (28.8%), among which 8 (7.0%) had additional AAs identified and 5 (4.4%) received TT based on repeat ICS. Conclusions: This study highlights the importance of ICS based precision oncology with 67% of patients having AAs and 29% receiving TTs. Analyses are ongoing to study the most frequently altered signaling pathways, frequency of targeted agents used, impact of ICS and TT on the clinical outcomes for these patients, barriers in receiving TT despite having AAs, role of longitudinal sequencing, and the impact of LLM based “Chatbot” on data extraction efficiency.

Landscape of the immune microenvironment in malignant pleural effusion from EGFR-TKI-resistant NSCLC.

e20532 Background: Malignant pleural effusion (MPE) is a poor prognostic factor in non-small cell lung cancer (NSCLC), which often develops resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Depicting the TKI-resistant MPE landscape is key for clarifying resistance mechanisms and finding therapeutic strategies. Methods: We used single-cell RNA sequencing and GO/KEGG/Reactome enrichment analysis to examine the immune microenvironment of fresh MPE samples (n=7), and compared the 3 rd -genration TKI-resistant subgroup (3 rd -GR, n=4) with the 1 st -genration TKI-resistant subgroup (1 st -GR, n=2). Results: 63,843 cells were isolated, with minimal epithelial cells (3.45%) and most being immune cells. T lymphocytes made up the largest proportion (49.72%), followed by macrophages (13.87%, mainly M1 phenotype), monocytes (8.27%), dendritic cells (7.23%), B cells (7.20%), neutrophils (3.01%), natural killer T (NKT) cells (3.00%), natural killer (NK) cells (2.30%), fibroblasts (0.88%), plasma cells (0.59%), mast cells (0.31%) and endothelial cells (0.16%). CD4+ T cells were dominated by Th1-type central memory T (TCM) cells, though few in low/recent activation states. Regulatory T cells (Tregs) were identified as natural central Tregs rather than peripherally induced Tregs. Cell proportions in 3 rd -GR MPE did not differ significantly from those in 1 st -GR MPE. However, cancer cells in 3 rd -GR MPE showed stronger aerobic metabolism and protein synthesis, with reduced adhesion and antigen presentation abilities, and more strongly inhibited apoptotic pathways. Functional differences in immune cells were also seen in 3 rd -GR MPE, showing a more markedly suppressed immune microenvironment. There was a trend toward higher Treg proportions, with significantly enhanced survival/ immunosuppressive capacity, and higher exhausted cytotoxic T lymphocyte (CTL) proportions, with more complete functional collapse. Despite enhanced protein synthesis and direct cytotoxic potential in mucosal-associated invariant T (MAIT) cells, NKT and NK cells, their aerobic metabolism was significantly reduced, insufficient to sustain their functions. Macrophages had weaker adhesion ability; M1 subtypes showed stronger aerobic metabolism and phagocytic/pro-inflammatory activities, but weaker antigen-presenting capacity, while M2 subtypes shifted from aerobic to lipid metabolism, with enhanced anti-inflammatory activity. These findings matched sequential MPE samples from a single patient after developing resistance to 1 st -G and then 3 rd -G TKIs. Conclusions: This study is the first to depict the immune microenvironment of EGFR-TKI resistant MPE. We found far more severe immune suppression in 3rd-GR MPE. These findings may offer a theoretical basis for creating local immunomodulatory strategies to overcome TKI-resistant MPE.

Platinum-based chemotherapy in early-stage, high-risk, triple-negative breast cancer: A systematic review and meta-analysis of randomized trials.

529 Background: The clinical benefit of adding platinum agents to adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) remains uncertain. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the impact of carboplatin-based adjuvant chemotherapy on survival outcomes in patients with early-stage, high-risk TNBC. Methods: RCTs comparing carboplatin plus standard adjuvant chemotherapy versus chemotherapy alone in early-stage, high-risk TNBC were identified through systematic searches of PubMed, Embase, Cochrane CENTRAL, and major oncology meeting proceedings. The primary endpoint was disease-free survival (DFS). Secondary endpoints included recurrence-free survival (RFS), distant disease–free survival (DDFS), and overall survival (OS). Hazard ratios (HRs) were pooled using random-effects models. Absolute survival differences at fixed timepoints were estimated using reconstructed individual patient–level data derived from published Kaplan–Meier curves. Results: Five randomized trials enrolling 3,153 patients were included; 1,576 (49.9%) received carboplatin-based chemotherapy. Median age ranged from 47 to 56 years, and most patients had grade 3 tumors and node-positive disease. Carboplatin-based chemotherapy significantly improved DFS compared with chemotherapy alone (HR 0.66, 95% CI 0.62–0.71; p < 0.001). Consistent proportional benefits were observed for RFS (HR 0.66, 95% CI 0.62–0.71; p < 0.001), DDFS (HR 0.66, 95% CI 0.62–0.71; p < 0.001) and OS (HR 0.66, 95% CI 0.62–0.71; p < 0.001), with no substantial between-trial heterogeneity (I² < 25% for all endpoints). Reconstructed survival analyses demonstrated increasing absolute benefit over time. At 3 years, carboplatin-based chemotherapy was associated with absolute improvements of approximately 4–6% in DFS and 3–5% in OS. At 5 years, absolute differences favored carboplatin by approximately 7–9% for DFS, 6–9% for RFS, 6–8% for DDFS, and 6–8% for OS (log-rank p < 0.001 for all comparisons). DFS benefit was observed across clinically relevant subgroups, including node-negative (HR 0.69, 95% CI 0.53–0.90) and node-positive disease (HR 0.57, 95% CI 0.37–0.86), as well as among patients with and without germline BRCA1/2 mutations. Greater proportional benefit was observed in patients with grade III tumors and pT2–T3 disease. Conclusions: Across RCTs, the addition of carboplatin to standard adjuvant chemotherapy was associated with significant and durable improvements in DFS and OS in patients with early-stage, high-risk TNBC. Absolute survival gains increased with longer follow-up, supporting the clinical relevance of platinum-based adjuvant strategies in selected high-risk populations.

Updated efficacy and safety of olverembatinib (HQP1351) as second-line therapy in patients with chronic-phase chronic myeloid leukemia (CP-CML).

6510 Background: Olverembatinib is a third-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) approved in China for chronic myeloid leukemia (CML) resistant/intolerant to ≥ 2 TKIs or with the T315I mutation. This study assessed olverembatinib as second-line treatment in patients with CP-CML resistant/intolerant to first-line TKIs without the T315I mutation. Methods: This single-arm, multicenter, open-label study enrolled patients (ECOG PS 0-2, adequate hepatic/renal function) who receive olverembatinib 40 mg orally every other day in 28-day cycles. Efficacy and safety were assessed every 3 cycles. The primary endpoint was complete cytogenetic response (CCyR) rate. Results: From August 4, 2022, through January 14, 2026, 47 patients were enrolled (91.5% first-line TKI resistant, 8.5% intolerant). The median age was 42.0 (19-70) years; 66.0% were male. Twelve (25.5%) received first-line imatinib, and 35 (74.5%) received first-line second-generation TKIs. Thirty-six (76.6%) had no baseline BCR::ABL1 kinase domain mutations, and 11 (23.4%) had non-T315I mutations. At data cutoff, 33 (70.2%) continued treatment, while 14 (29.8%) discontinued because of adverse events (n = 3), treatment failure (n = 4), progression (n = 2), or other reasons (n = 5). Among 42 evaluable patients, 76.2% achieved CCyR and 47.6% major molecular response (MMR). CCyR/MMR rates increased progressively: cycle 6 (57.5%/25.0%), cycle 9 (60.4%/33.3%), cycle 12 (75.0%/37.5%), cycle 15 (83.3%/46.7%), cycle 18 (89.3%/50.0%), cycle 21 (92.0%/64.0%), and cycle 24 (91.3%/60.9%). Complete hematologic response was achieved in 83.3% (15/18) and major cytogenetic response in 83.3% (35/42). Among 32 patients pretreated with first-line second-generation TKIs, 81.3% achieved CCyR and 50% MMR. The median treatment duration was 16.0 (6-38) cycles. Any-grade treatment-related adverse events (TRAEs) occurred in 42 (89.4%) patients; 21 (44.7%) had grade ≥ 3 TRAEs; and 6 (12.8%) had serious adverse events (SAEs). Nonhematologic TRAEs (mainly grade 1-2) included skin hyperpigmentation (51.1%), hyperuricemia (31.9%), and creatine phosphokinase increased (27.7%). Grade ≥ 3 hematologic toxicities included platelet count decreased (42.6%), neutropenia (25.5%), and anemia (8.5%). Olverembatinib-related SAEs included platelet count decreased (6.4%), anemia, myelosuppression, and pyrexia (2.1% each). Most hematologic TRAEs were manageable with supportive care. Two cardiovascular events (grade 1 hypertension) were possibly treatment-related. No deaths occurred. Conclusions: Olverembatinib shows good tolerability and leads to high MMR and CCyR in patients with CP-CML without T315I mutation that is resistant/intolerant to first-line TKIs. Clinical trial information: ChiCTR2200061655.

Effect of neoadjuvant radiotherapy combined with surgery on long-term prognosis of patients with centrally located hepatocellular carcinoma: A machine learning and propensity score weighting analysis.

e16259 Background: Primary liver cancer is the sixth most common malignancy globally and the third leading cause of cancer-related deaths. Centrally located hepatocellular carcinoma (HCC) is a distinct subtype of liver cancer, typically arising in the central liver segments. It is further defined as tumors adherent to or within 1 cm of major intrahepatic vascular or biliary structures. This anatomical location makes surgical resection technically challenging, with a higher risk of recurrence. Neoadjuvant radiotherapy (NeoRT) has been increasingly applied in the treatment of HCC; however, its therapeutic efficacy remains uncertain. Methods: This study retrospectively collected data on HCC patients who underwent liver resection (LR) from January 2018 to June 2024. The inclusion criteria as follows: (1) age ≥18 years; (2) diagnosed with centrally located HCC; (3) Child-Pugh A; (4) BCLC stage 0 or A. The exclusion criteria as follows: (1) portal venous tumor thrombus; (2) undergoing other forms of radiation therapy; (3) multiple liver tumors. Patients were divided into two groups based on whether they received NeoRT. Directed acyclic graph (DAG) was constructed to identify potential confounders. Propensity scores (PS) were calculated using seven machine learning algorithms, including decision tree, KNN, LDA, logistic regression, random forest, SVM and xgboost. The best algorithm was selected according to standardized mean difference. Subsequently, the optimal weighting method of four propensity score weighting was used to balance confounders, including entropy, inverse probability, matching and overlap weighting. Weighted Kaplan-Meier, Cox regression, E-value calculation, and landmark analysis were performed to evaluate the association between NeoRT and recurrence-free survival (RFS). Registration number: ChiCTR2300072378. Results: This study included 480 patients, comprising 430 in the LR group and 50 in the NeoRT group. 22 potential confounders were identified using DAG. PS were estimated via an optimal logistic regression based machine learning. Group imbalances were addressed using overlap weighting. Before weighting, the 1-year, 3-year, and 5-year RFS rates were 80%, 63%, and 47% in the NeoRT group versus 60%, 36%, and 24% in the LR group. Weighted Kaplan-Meier analysis showed that the NeoRT group had significantly better RFS (P < 0.01). Weighted Cox regression indicated that NeoRT was an independent protective factor for RFS (HR = 0.42, 95% CI: 0.23-0.76, P = 0.005). The E-value for unmeasured confounding was 3.06, supporting the robustness of findings. Landmark analysis further confirmed the superior RFS in the NeoRT group (P < 0.05). Conclusions: NeoRT combined with surgery is a safe and effective strategy for the treatment of centrally located HCC, contributing to improved RFS.

When disaster strikes: A scoping review of climate-resilience toolkits relevant to cancer care delivery.

e23198 Background: External disruptions, such as extreme weather and infrastructure failures,are increasingly undermining timely, access to cancer care, while guidance onmaintaining treatment continuity during such events remains scattered and may not fully address the urgent, resource-intensive needs of oncology patients. This review examined whether existing resilience toolkits adequately address the unique needs of oncology care delivery. Methods: We conducted a scoping review of peer-reviewed and grey literature toidentify healthcare resilience toolkits and guidelines relevant to external disruptions. Sources were identified through PubMed, Google Scholar, and targeted web searches between October and December 2025. Resources were included if they offered practical strategies to support healthcare system resilience and were deemed relevant to cancer care delivery. Key characteristics of each resource, including the target audience, healthcare setting, and content focus, were summarized, and themes were identified. Results: Ten resilience-focused resources met the inclusion criteria, including five formaltoolkits. None were tailored specifically to oncology care. Most resources (75%) focused on emergency preparedness and infrastructure protection, with limited attention to outpatient cancer services, treatment continuity, or patient-level access barriers. Few addressed workforce constraints, scheduling flexibility, or the needs of clinically vulnerable populations. Oncology-specific challenges—such as frequent treatment visits, narrow therapeutic windows, and coordinated multidisciplinary care—were largely absent. Conclusions: Existing resilience toolkits insufficiently address operational cancer careduring external disruptions. These results suggest the need for resilience guidelines tailored specifically for oncology, considering urgent treatments, care coordination, and equity considerations. Developing and implementing such guidance is crucial to ensuring cancer care remains effective amid growing system-level challenges.

Early versus delayed biologic therapy for immune checkpoint inhibitor–associated colitis: A propensity-matched real-world analysis.

e24204 Background: Immune checkpoint inhibitor (ICI)–associated colitis is a clinically significant immune-related adverse event that may require biologic therapy when refractory to corticosteroids. Although infliximab and vedolizumab are commonly used, the impact of timing of biologic initiation on clinical outcomes remains uncertain. We compared outcomes associated with early versus delayed biologic therapy in patients with ICI-associated colitis using a large real-world database. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Adult patients treated with ICIs (pembrolizumab, nivolumab, or ipilimumab) who subsequently developed colitis were identified. Patients were categorized based on timing of biologic initiation (infliximab or vedolizumab): early initiation (within 3 days of colitis diagnosis) versus delayed initiation (between days 3 and 14). Propensity score matching (1:1) was performed to balance demographics, malignancy type, comorbidities, corticosteroid exposure, and baseline laboratory parameters. Outcomes assessed over 12 months included all-cause mortality, hospitalization, immune checkpoint inhibitor reinitiation, colonic perforation, and long-term corticosteroid therapy. Time-to-event and risk-based analyses were performed. Results: After propensity matching, 588 patients were included in each cohort with well-balanced baseline characteristics. At 12 months, no statistically significant differences were observed between early and delayed biologic therapy in all-cause mortality (21.7% vs 23.7%; hazard ratio [HR] 0.90, 95% CI 0.71–1.15; p = 0.69) or hospitalization (46.0% vs 49.2%; HR 0.91, 95% CI 0.71–1.16; p = 0.78). Rates of immune checkpoint inhibitor reinitiation were similar between cohorts (33.0% vs 29.6%; HR 1.13, 95% CI 0.92–1.39; p = 0.66). The incidence of colonic perforation was low and comparable (2.2% vs 2.6%). There was no significant difference in the requirement for long-term corticosteroid therapy (26.3% vs 27.9%). Conclusions: In this study, the timing of biologic therapy initiation for immune checkpoint inhibitor–associated colitis was not associated with statistically significant differences in mortality, hospitalization, immune checkpoint inhibitor reinitiation, colonic perforation, or long-term corticosteroid therapy. Although early biologic initiation was associated with numerically favorable outcomes across several endpoints, the study may have been underpowered to detect modest but clinically meaningful differences between treatment strategies. As such, these findings should be interpreted as hypothesis-generating. Prospective, adequately powered studies are warranted to determine whether earlier biologic escalation confers a true clinical benefit and to better define optimal treatment sequencing in this population.

Sequential use of antibody-drug conjugates in advanced breast cancer: A real-world study based on HER2 status.

e13020 Background: The optimal sequencing strategy for antibody-drug conjugates (ADCs) following progression on prior ADC therapy in advanced breast cancer remains uncertain. However, most pivotal trials excluded patients previously exposed to another ADC, leaving real-world evidence as the primary source to inform sequencing strategies, particularly across different HER2 expression levels. Methods: This single-center retrospective study included 82 patients with advanced breast cancer who received at least two different anti-HER2 ADCs sequentially between January 2019 and December 2023. Patients were stratified by HER2 status (HER2-positive, n = 51; HER2-low, n = 31). The second ADC (ADC2) treatments included trastuzumab deruxtecan (T-DXd, n = 43), trastuzumab emtansine (T-DM1, n = 9), disitamab vedotin (RC48, n = 26), and other agents including sacituzumab govitecan (n = 4). The primary endpoint was progression-free survival (PFS), analyzed as PFS on the first ADC (PFS1), PFS on the second ADC (PFS2), and total PFS from the initiation of the first ADC. Results: In the overall cohort, the median total PFS was 15.12 months for patients receiving T-DXd as ADC2, compared with 11.11 months for T-DM1 (P = 0.697) and 11.01 months for RC48 (P = 0.887), although these differences were not statistically significant. Analysis of sequential patterns revealed that the T-DM1 → T-DXd sequence (T-D pattern) was associated with the longest median total PFS (24.07 months). In the HER2-positive subgroup, T-DXd as ADC2 resulted in a median PFS2 of 15.98 months. Conversely, patients with HER2-low disease derived limited benefit from sequential ADC therapy, with a median PFS2 of 3–4 months and an objective response rate (ORR2) below 10%. Conclusions: In real-world clinical practice, sequential ADC therapy demonstrated clinically meaningful activity, particularly in HER2-positive advanced breast cancer. The T-DM1 → T-DXd sequence appears to be a promising approach. However, efficacy is significantly limited in the heavily pretreated HER2-low population, underscoring a "diminishing returns" phenomenon and the need for novel therapeutic strategies and a deeper understanding of cross-resistance mechanisms.

Cardiac safety of L-annamycin at high cumulative anthracycline exposure: Pooled analysis.

12025 Background: Anthracyclines are widely used chemotherapeutic agents but limited by dose-dependent cardiotoxicity and lifetime cumulative dose restrictions. L-Annamycin is a next-generation anthracycline designed to eliminate cardiotoxicity and overcome multidrug resistance. In a Phase 1b/2 study in patients with acute myeloid leukemia (AML), L-Annamycin administered in combination with cytarabine as second-line therapy achieved a 50% complete remission (CR) rate and a 60% composite CR (CRc) rate with a median overall survival of 12.39 months (95% CI, 2.07–13.96) in the intent-to-treat population. We evaluated the cardiac safety of L-Annamycin in multiple clinical trials to assess its ability to support sustained anthracycline exposure in patients with AML and soft tissue sarcoma. Methods: Cardiac safety was evaluated across sponsor- and investigator-initiated clinical trials of L-Annamycin. Assessments included serial 12-lead electrocardiograms (ECGs), cardiac biomarkers (troponin I and T), and transthoracic echocardiography with centralized evaluation of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), where available. Cardiac data were reviewed independently by a reviewer in the Division of Cardiovascular Medicine at the Cleveland Clinic. Changes in LVEF from baseline to final assessment were analyzed in relation to cumulative L-Annamycin dose and patient age. Results: An independent cardiac safety review was conducted for 90 patients who were treated with L-Annamycin across five completed clinical trials; 78 of these patients now have source-verified pre- and post-treatment left ventricular ejection fraction (LVEF) assessments. The median cumulative L-Annamycin dose among these patients was 660 mg/m² (95% CI, 645–690; range, 210–2,970 mg/m²), with most of the cumulative doses exceeding conventional lifetime anthracycline limits. Analysis of the change in LVEF from baseline to final assessment demonstrated no statistically significant difference (mean difference, −0.12%; 95% CI, −1.34 to 1.09; p = 0.84). Linear regression analysis documented no correlation between cumulative L-Annamycin dose and change in LVEF (p = 0.12), nor between patient age and change in LVEF (p = 0.73). Independent review of serial ECGs, cardiac biomarkers, cardiac adverse events, and available global longitudinal strain measurements also demonstrated no evidence of drug-induced cardiotoxicity. Conclusions: L-Annamycin was not associated with any detectable cardiotoxicity despite high cumulative anthracycline exposure. These findings suggest that L-Annamycin represents a next-generation anthracycline capable of delivering effective anthracycline therapy without traditional cumulative dose limitations, thus further supporting its ongoing pivotal Phase 2b/3 trial in AML patients.

The complementary anti-cancer and analgesic properties of the natural product barettin.

e15129 Background: Chemotherapy induced peripheral neuropathy (CIPN) is one of the most common side effects of chemotherapy and a leading cause of chemotherapy dose reduction and treatment cessation. This means that CIPN is not only a source of significant patient morbidity but also increases patient mortality. Despite this importance, the available treatments for CIPN remain limited. The marine natural product Barettin has previously been described to have anti-inflammatory effects and cytotoxicity only at doses above 100 mg/mL or 238 µM. We thus chose to investigate Barettin to determine if it could be used as a novel treatment for CIPN. Methods: Von Frey filaments were used to measure if Barettin had antinociceptive effects in a mouse model of CIPN. To assess the anti-cancer properties of Barettin, a growth inhibition assay using PanC-1 cells was utilized. To investigate the underlying mechanism of Barettin, the PRESTO-Tango assay was used to determine activity at the mu opioid (MOR) and Serotonin 2A (5HT2AR) receptors, while a decatenation assay was used to assess effects on Topoisomerase 2a activity. Results: Barettin presented dose dependent antinociceptive properties in a mouse model of CIPN when administered via intraperitoneal injection over a dose range of 32-178 mg/kg. Interestingly, this effect was seen specifically in adult male mice, with female mice having no response at all tested doses. Over a 48-hour treatment durations, 1 µM Barettin significantly decreased PanC-1 cell proliferation by approximately 50%. When investigating the underlying mechanism of these effects, Barettin was determined to act as an inverse agonist at the 5HT2AR and an inhibitor of Topoisomerase 2a, while having no activity at the MOR across all tested concentrations. Conclusions: Barettin acts as inverse agonist at the 5HT2AR, which mediates its antinociceptive properties in male mice with CIPN. Interestingly, Barettin also acts as an inhibitor of Topoisomerase 2a which mediates its ability to inhibit PanC-1 cell proliferation while having no cytotoxicity in normal cells at similar dosing. The dual anti-cancer and antinociceptive activities of Barettin suggest it could be utilized in the future as a chemotherapeutic agent that also simultaneously treats CIPN, ultimately leading to increased treatment efficacy and improved patient quality of life.