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Characterization of contemporary practice patterns in the management of <i>IDH</i> -mutant glioma: A multidisciplinary multi-institutional survey.
2058 Background: The management of isocitrate dehydrogenase (IDH) mutant glioma is rapidly evolving following the recent FDA approval of the mutant IDH inhibitor, vorasidenib. Optimal treatment decisions for many specific clinical scenarios remain undefined leading different neuro-oncology providers to recommend different treatment approaches. The aim of this study was to characterize how clinicians collectively approach different clinical scenarios and evaluate how demographic and professional backgrounds influence decision-making in IDH-mutant glioma. Methods: An online survey was developed by a team of neuro-oncologists and radiation oncologists and distributed via email and X to clinicians treating patients IDH-mutant glioma. The survey included demographic questions and multiple case-based clinical scenarios with standardized response options. We compared the responses of neuro/medical oncologists, radiation oncologists, and neurosurgeons, and performed univariable regression to identify predictors of treatment preference, as well as to understand familiarity and enthusiasm with the use of IDH inhibitors. Results: A total of 153 clinicians (58% neuro/medical-oncologists, 34% radiation oncologists, 8% neurosurgeons) completed the online survey. Five of ten scenarios reached consensus (>75% agreement on a treatment option), while the remainder demonstrated heterogeneity of treatment approaches. Compared to neuro/medical oncologists, radiation oncologists were less likely than neuro/medical oncologists to recommend IDH inhibitor therapy (IRR 0.57, p<0.001) and more likely to recommend radiotherapy (IRR 1.54, p<0.001) or chemo-radiotherapy (IRR 1.47, p<0.001). Neuro-oncologists and neurosurgeons reported the most and least familiarity, respectively, with the use of IDH inhibitors whereas medical oncologists and radiation oncologists reported the most and least enthusiasm for IDH inhibitor use, respectively. Conclusions: Our survey results evidence substantial variation in real-world management of IDH-mutant glioma across specialties and institutions. While several clinical scenarios demonstrated strong therapeutic consensus, others revealed diverse approaches, underscoring the need for ongoing multidisciplinary collaboration and further advancement of evidence-based consensus to guide clinical decisions.
Systemic third generation allosteric STING agonist CRD3874-SI, a novel immunotherapy, in patients with advanced solid tumors: Results from a single-agent phase I study.
2661 Background: CRD3874-SI is a first in class, systemically administered, allosteric STING agonist that blocks STING’s proton channel activity differentiating it from previously developed STING agonists. The drug has demonstrated pre-clinical anti-cancer activity in several murine tumor models and has pharmacological properties distinct from earlier generation STING agonists. Methods: This is a single institution, open-label, phase I study of CRD3874-SI in patients with advanced solid tumors. The dose escalation study follows a standard 3+3 design. CRD3874-SI is administered intravenously once per week for 2 cycles. Cycle duration is 28 days. From cycle 3 onwards, continuous weekly treatment +/- one week break (week 4) may be considered. The primary objective is to assess the safety of CRD3874-SI by determining the maximum tolerated dose, recommended phase 2 dose and schedule of administration. Secondary objectives include examining the pharmacokinetics and pharmacodynamics (IP10 analysis) of CRD3874-SI and evaluating the efficacy of CRD3874-SI as determined by best objective response rate per RECIST v 1.1. Clinical trial information: NCT06021626. Research sponsor: Curadev Pharma, Inc. Results: As of January 5th 2026, 21 patients (sarcoma n=20, adenoid cystic carcinoma n=1) received treatment at four escalating dose levels (0.1-1.8mg/kg). The median number of prior lines of treatment was 4 (1-11). The median duration of treatment was 7 weeks (range: 1-32 weeks). 2 patients continue treatment. Reasons for treatment discontinuation include: progression of disease (n=16), toxicity (n=2), patient withdrawal (n=1). Treatment emergent adverse events (TEAEs) were manageable and reversible. Only low-grade cytokine related symptoms were reported. TEAEs possibly related to study treatment reported in >20% of participants and were mostly low grade include: fatigue (43%), chills (38%), nausea (38%), diarrhea (33% (G3 (10%)), headache (29%) and flu-like symptoms (24%). Low grade colitis not typical of auto-immune mechanism, responding well to temporary treatment pause +/- oral budesonide, were reported in 4 patients. One DLT at dose level 4 (G3 dyspnea) was observed. 19 patients are evaluable for efficacy. The best objective response per RECIST v1.1: confirmed partial response, n=1 (malignant phyllodes tumor); stable disease, n=9; progressive disease, n=9. Dose level 3 (0.9mg/kg) represents a biologically active dose (one confirmed PR and a second case with -27% tumor regression was observed). Dose proportional increase in AUC with concomitant increase in plasma CXCL10 levels were observed. Conclusions: CRD-3874-SI has demonstrated clinical activity with manageable safety. Dose level 0.9mg/kg is biologically and clinically active. A dose expansion phase at this dose level in is planned in >5 histology specific cohorts. Clinical trial information: NCT06021626 .
Assessing grade 3 and grade 4 immunotherapy-induced dermatologic toxicities at a tertiary medical center.
e24192 Background: Immune checkpoint inhibitors (ICIs) are increasingly used across multiple malignancies but are associated with immune-related adverse events, including dermatologic toxicities that may necessitate treatment interruption or discontinuation. Data describing the prevalence, severity, and risk factors for high-grade dermatologic toxicities in real-world settings remain limited. Methods: We conducted a single-center retrospective cohort study of adult patients treated with ICIs at a tertiary medical center and affiliated oncology clinic between January 2021 and December 2024. Patients receiving PD-1, PD-L1, and/or CTLA-4 inhibitors were included. Dermatologic immune-related adverse events were identified and graded using CTCAE criteria. Demographics, comorbidities, tumor type, and treatment characteristics were compared between patients with and without dermatologic toxicity. Multivariate logistic regression was used to identify predictors of moderate-to-severe toxicity (Grade ≥2). Results: Among 273 patients receiving ICIs, 44 (16.1%) developed dermatologic toxicity. Grade 1 events occurred in 19 patients (43.2%), Grade 2 in 15 (34.1%), Grade 3 in 4 (9.1%), and Grade 4 in 6 (13.6%), resulting in an overall Grade 3–4 toxicity rate of 3.7%. Patients with dermatologic toxicity had a higher mean BMI compared to those without toxicity (28.26 vs. 26.61 kg/m², p = 0.0169) and were older on average (68.6 vs. 63.3 years, p = 0.0599). Race and alcohol use differed significantly between groups, while sex was not associated with toxicity. PD-1 inhibitors were the most commonly used agents (93.4%), while CTLA-4 inhibitors were used in 10.3% of patients. In multivariate analysis, skin cancer diagnosis was the only independent predictor of Grade ≥2 dermatologic toxicity compared with lung cancer (adjusted OR 5.88; 95% CI 1.19–30.18; p = 0.0306). CTLA-4 inhibitor exposure and diabetes mellitus showed numerically higher odds but were not statistically significant. Conclusions: In this real-world cohort, dermatologic toxicities associated with ICIs were relatively common, though severe Grade 3–4 events were rare. Higher BMI and skin cancer diagnosis were associated with increased risk, with skin cancer emerging as the sole independent predictor of moderate-to-severe toxicity. These findings underscore the importance of risk stratification and early dermatologic evaluation to optimize immunotherapy management.
Development of a composite risk score for chemotherapy toxicity and unplanned hospitalization in older adults with cancer: A prospective cohort study.
1659 Background: Older adults receiving chemotherapy are at high risk for severe treatment-related toxicities, which may compromise treatment completion and lead to unplanned hospitalizations. We developed a composite risk score integrating the components of Cancer and Aging Research Group (CARG) chemotherapy toxicity score and proved clinical predictors to enhance prediction of grade 3–5 (G3–5) chemotherapy-related toxicities, treatment tolerance, and unplanned hospitalization. Methods: Patients aged ≥70 years with solid tumors initiating chemotherapy were enrolled between December 2024 and August 2025 at a tertiary hospital in Shanghai, China. The primary endpoint was the occurrence of any G3–5 chemotherapy-related toxicity; secondary endpoints included chemotherapy incompletion and unplanned hospitalization. Baseline characteristics included the CARG score, tumor- and treatment-related characteristics, and laboratory parameters. Toxicities (graded using CTCAE v5.0 ), treatment completion, and unplanned hospitalizations were assessed at each cycle for up to 6 months or until completion of the planned treatment course. Predictors of G3–5 toxicities were screened by LASSO-penalized multivariable logistic regression, and model discrimination was evaluated by receiver operating characteristic curve. Results: Among 242 patients (median age 74 years; range 70–88), 71.9% were male, 64.5% had gastrointestinal malignancies, and 73.1% had stage IV disease. Overall, 164 patients (67.8%) experienced G3–5 toxicities, and 63 (26.0%) had unplanned hospitalizations. The score system included cancer type, hemoglobin, estimated glomerular filtration rate, falls within 6 months, medication management ability, C-reactive protein/albumin, MAX2 index, walking ability, and social activity level. The median score was 10 (range 6–14). Each one-point increase in score was associated with higher risk of any G3–5 toxicity (OR 1.21, 95% CI 1.14–1.30; AUC 0.75) and non-hematologic G3–5 toxicity (OR 1.19, 95% CI 1.12–1.27; AUC 0.73).The score was also positively associated with unplanned hospitalization (OR 1.07, 95% CI 1.01–1.13; AUC 0.62), but was inversely associated with chemotherapy incompletion (OR 0.93, p=0.019), suggesting more proactive treatment modifications in high-risk patients. In this cohort, the new score showed superior discrimination for any G3–5 toxicity, with a higher AUC than the CARG score (0.75 vs. 0.63). The optimal cutoff point of any G3–5 toxicity was 7.5 with relatively good specificity (72%) and sensitivity (65%). Conclusions: The composite score may help predict G3–5 toxicity, non-hematologic G3-5 toxicities, and unplanned hospitalization, potentially outperforming the CARG score. External validation and evaluation of clinical utility are warranted.
HPV-enriched oropharyngeal head and neck cancer and inpatient outcomes: A national analysis of U.S. hospitalizations, 2016 to 2023.
e23173 Background: HPV-associated oropharyngeal cancer has favorable oncologic prognosis, but its inpatient risk profile is poorly defined. The HPV paradox hypothesis proposes lower inpatient mortality despite similar or higher acute complication burden. Methods: A retrospective, survey-weighted analysis of the National Inpatient Sample (NIS), 2016 to 2023, was performed including adults hospitalized with head and neck cancer (HNC) identified by ICD-10-CM codes C00 to C14 and C30 to C32 across any diagnosis field. Tumor site was assigned by first-hit anatomic code, and palliative encounters (Z51.5) were excluded. HPV-enriched status was defined by oropharyngeal site (C09 to C10). Outcomes included in-hospital mortality, mechanical ventilation, tracheostomy creation, shock, any airway intervention, length of stay (LOS), and hospitalization cost. Survey-weighted models used subpopulation methods and adjusted for demographics, year, payer, income quartile, admission characteristics, hospital factors, comorbidity burden when available, and site. In models including site, the oropharynx category was collinear with HPV-enriched status and served as the reference. Results: The cohort included 117,198 unweighted HNC hospitalizations (weighted national estimate 585,990). HPV-enriched oropharynx represented 16.85% (95% CI 16.61 to 17.10). HPV-enriched admissions involved younger patients (mean 63.18 vs 64.97 years) and fewer females (19.61% vs 29.57%). Crude inpatient mortality was similar between HPV-enriched and non enriched admissions (3.25% vs 3.29%). HPV-enriched admissions had lower rates of mechanical ventilation (5.84% vs 7.40%), tracheostomy (7.63% vs 16.89%), shorter LOS (6.19 vs 7.07 days), and lower mean costs ($23,855 vs $29,753). After adjustment, HPV-enriched status was not associated with inpatient mortality (OR 1.04, 95% CI 0.92 to 1.17) or shock (OR 1.02, 95% CI 0.88 to 1.19). HPV-enriched status was associated with lower odds of mechanical ventilation (OR 0.78, 95% CI 0.72 to 0.85), tracheostomy (OR 0.39, 95% CI 0.36 to 0.42), shorter LOS (−0.68 days, 95% CI −0.83 to −0.52), and lower costs (gamma-log coefficient −0.163, 95% CI −0.194 to −0.132), corresponding to 15% lower adjusted costs. Adjusted absolute risk differences were consistent. In stratified analyses restricted to patients requiring airway intervention, HPV-enriched status was associated with higher mortality (OR 1.45, 95% CI 1.19 to 1.77). A similar association was observed among patients with shock (OR 1.66, 95% CI 1.13 to 2.43). Conclusions: HPV-enriched oropharyngeal HNC admissions had lower airway intervention rates, shorter LOS, and lower costs without reduced inpatient mortality. Among patients with severe complications, HPV-enriched status was associated with higher mortality, identifying a high risk subgroup requiring targeted inpatient risk stratification.
Chidamide in combination with CHOP in previously untreated peripheral T-cell lymphoma with T follicular helper phenotype: Results of the phase II SWIFT trial.
7082 Background: Peripheral T-Cell Lymphoma with T-follicular helper phenotype (PTCL-TFH), which mainly includes angioimmunoblastic T-cell lymphoma (AITL), is a biologically distinct subtype characterized by frequent epigenetic alterations. Chidamide is an oral, histone deacetylase (HDAC) inhibitor that targets HDAC subtypes 1, 2, 3, and 10, has shown encouraging activity in R/R PTCL-TFH. This study aimed to evaluate the efficacy and safety of chidamide in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated PTCL-TFH patients. Methods: This is a multicenter, open-label, single-arm phase II study (NCT05572983). Patients with previously untreated PTCL-TFH were enrolled and received chidamide (20 mg, oral, biweekly) combined with CHOP regimen for up to six induction cycles. Patients achieving complete response (CR) after induction entered a maintenance phase with chidamide for up to two years. The primary endpoint was CR rate. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between May 2023 and July 2025, a total of 47 patients were enrolled, and enrollment was completed. All patients had the AITL subtype. The median age was 62 years (IQR, 54–67), and 25.5% were female. Advanced-stage disease (stage III–IV) was present in 85.0% of patients, and 48.9% had extranodal involvement. The median number of induction cycles was 5 (range, 1–6), with 33 patients completing six cycles of induction therapy. Among 35 patients who underwent post-treatment PET/CT evaluation, the best CR rate during the induction phase was 85.2% (30/35), with an ORR of 100%. At the end of induction therapy, the CR rate was 87.9% (29/33), and the ORR remained 100%. As of October 2025, disease progression was observed in 10 patients. The most common grade 3–4 adverse events were neutropenia (42.6%), thrombocytopenia (19.1%), infections (17.0%), anemia (6.4%), and elevated transaminases (2.1%). Conclusions: Chidamide in combination with CHOP demonstrated promising efficacy with a manageable safety profile in previously untreated PTCL-TFH patients. A randomized controlled trial is currently ongoing to further validate these findings (NCT06947967). Clinical trial information: NCT05572983 . Baseline characteristics. Characteristics Patients(n=47) Age, years (median [IQR]) 62 (54-67) Sex Male 35 (74.4%) Female 12 (25.5%) IPI score 0-2 25 (53.1%) ≥3 22 (46.9%) Ann Arbor Stage I-II 7 (14.8%) III-IV 40 (75.2%) Extranodal involvement No 24 (51.1%) Yes 23 (48.9%) Data are shown as number (%).
Spatial immune architecture as used to define progression and treatment response in penile squamous cell carcinoma.
5035 Background: Penile squamous cell carcinoma (PSCC) is a rare, aggressive malignancy with limited treatment options and poor outcomes. Although immunotherapy has shown activity in a subset of patients, the spatial immune mechanisms underlying disease progression and treatment resistance remain unknown. We hypothesized that clinical behavior in PSCC is driven by spatial organization of the tumor microenvironment (TME), rather than immune cell abundance alone. Methods: We conducted the first and largest longitudinal, multi-omics study of PSCC, integrating spatial transcriptomics (NanoString CosMx 6K panel) and single-cell RNA sequencing across 81 patients spanning all disease stages. Spatial profiling was performed on a tissue microarray of 35 primary tumors from 31 patients, capturing >390,000 spatially resolved cells. Patients were stratified by progression status, HPV, stage, and chemotherapy response (n=12) per RECIST 1.1. Spatial architecture was quantified using neighborhood Enrichment Analyses, Spatial cell–cell proximity and Ripley K AUC analyses. Results: Two distinct and clinically divergent TME architectures were identified. Tumors with favorable clinical behavior exhibited organized, antigen-driven immune surveillance. HPV-positive (n=18) and non-progressed tumors (n=17) showed coordinated neighborhoods involving myeloid cells, dendritic cells, T cells, and endothelium. Proliferative tumor programs were spatially proximal to DCs, and effector CD8 T cells maintained close coupling to tumor states, with preserved CD8–DC interactions. In contrast, HPV-negative (n=17), progressed (n=18), and chemotherapy non-responders (n=4) converged on a dysregulated inflammatory state characterized by B cell–macrophage and CAF-associated neighborhoods, EMT–hypoxia tumor programs, and immune–stromal self-clustering. These tumors showed reduced tumor-directed immune engagement and loss of organized immune domains. Notably, chemotherapy non-responders were not immune-depleted but instead exhibited dense innate and antigen-presenting cell infiltrates that were spatially confined to stromal and vascular compartments, with limited tumor-directed immune engagement. Conclusions: This study establishes the first spatially resolved atlas of PSCC, integrating spatial and single-cell multi-omics to uncover distinct immune and stromal architectures linked to progression and therapy resistance. Distinct TME architectures define progression and treatment resistance, supporting spatial biomarkers for patient stratification and therapeutic optimization.
Access-related disparities and survival in high-grade glioma: A social vulnerability analysis at a Texas tertiary cancer center.
e14043 Background: Glioblastoma (GBM) and astrocytoma, IDH-mutant grade 4, are aggressive brain tumors requiring timely access to care. While social vulnerability has been linked to cancer outcomes at the population level, its relevance among patients treated at tertiary referral centers remains unclear. Methods: We conducted a retrospective cohort study of adults with GBM (N=400) and astrocytoma, IDH-mutant grade 4 (N=84) treated at a comprehensive cancer center from 2020–2025. OS was defined from diagnosis to death or last follow-up. Social vulnerability was measured using the CDC Social Vulnerability Index (SVI), assigned at the county level for all patients and at the census tract level for Houston metropolitan patients. SVI was analyzed continuously and by quartiles. Kaplan–Meier and multivariable Cox models evaluated associations with OS, adjusting for age, sex, Karnofsky Performance Status (KPS), extent of resection, MGMT promoter methylation, insurance type, and distance to center. Results: SVI was not independently associated with OS after adjustment (GBM county-level HR per 0.1 increase 1.02, 95% CI 0.97–1.08; tract-level HR 1.05, 95% CI 0.97–1.12; astrocytoma grade 4 county-level HR 1.04, 95% CI 0.95–1.14). Higher SVI was associated with non-private insurance, lower KPS, and reduced likelihood of gross total resection (all p<0.05). Distance to the tertiary cancer center was not independently associated with OS. Houston metropolitan and non-Houston patients had similar outcomes once treated (GBM median OS 28.8 vs 28.3 months; 24-month OS 48.7% vs 47.9%; astrocytoma grade 4 median OS not reached; 24-month OS 84.0% vs 86.5%). In contrast, a county-based comparison across Texas showed a modest survival difference (log-rank χ²=4.704, p=0.030), with one region experiencing ~24% lower hazard of death (HR 0.76, 95% CI 0.58–0.99) despite a small absolute median OS difference (23.36 vs 21.16 months). Conclusions: Among patients with high-grade glioma treated at a tertiary referral cancer center, neighborhood-level social vulnerability was not independently associated with survival after adjustment, whereas clinical and tumor-related factors predominated. Although regional survival differences were observed across Texas, these differences attenuated after tertiary referral, indicating that disparities primarily arise upstream—at diagnosis, referral, and access to definitive treatment—rather than during specialty neuro-oncologic care. Together, these findings suggest that improving timely access to tertiary neuro-oncologic care at diagnosis represents a critical opportunity to reduce survival disparities and supports further investigation of interventions that expedite referral and treatment initiation.
A phase 3 study of ateganosine (THIO; 6-thio-2'-deoxyguanosine) sequenced with immune checkpoint inhibitor (ICI) versus standard-of-care chemotherapy in ICI-resistant advanced NSCLC: THIO-104 trial in progress.
TPS8672 Background: Despite progress in the treatment of advanced non-small cell lung cancer (NSCLC), therapeutic options remain scarce for patients who have developed resistance to immune checkpoint inhibitors (ICIs). Ateganosine (THIO; 6-thio-2'-deoxyguanosine), a telomere-targeting agent, is selectively recognized by telomerase and integrated into the telomeres of cancer cells. Once incorporated, Ateganosine compromises the telomere structure and function, leading to ‘uncapping’ of the chromosome ends and thus resulting in rapid tumor cell apoptosis. Methods: THIO-104 is a multicenter, open-label, randomized Phase 3 study enrolling approximately 300 subjects with histologically confirmed advanced/metastatic NSCLC. Eligible participants must have received two prior lines of systemic treatment, including at least one line of ICIs and platinum-based chemotherapy. Participants will be randomized 1:1 to receive either THIO 180 mg per cycle (60 mg IV on Days 1-3 of a 3-week cycle) followed by cemiplimab 350 mg IV on Day 5, or single-agent chemotherapy (vinorelbine, gemcitabine, or docetaxel). The primary endpoint is overall survival (OS). Secondary endpoints include objective response rate (ORR), progression-free survival (PFS) and duration of response (DoR). Current Status: Enrollment is ongoing , preliminary safety data and efficacy outcomes will be assessed through scheduled interim analyses. Conclusion: THIO-104 will provide critical insights into the potential role of telomere-targeting agents in restoring tumor sensitivity to ICIs in NSCLC. The study will also explore key biomarkers to further characterize Ateganosine’s mechanism of action and its potential to predict patient response to therapy. Clinical trial information: 2024-520164-33-00.
Proton pump inhibitor use and overall survival in patients with gastric adenocarcinoma treated with first-line immunotherapy: A real-world pharmacoepidemiologic study.
e15693 Background: Proton pump inhibitors (PPIs) are frequently prescribed to patients with gastric cancer for gastroesophageal reflux disease (GERD), ulcer prophylaxis, and symptom control. Emerging evidence suggests that PPIs may adversely affect immune checkpoint inhibitor (ICI) efficacy by disrupting gut microbiota composition, a factor increasingly recognized as a determinant of the antitumor immune response. We evaluated the association between concomitant PPI use and overall survival (OS) in a real-world cohort of patients receiving first-line ICI therapy. Methods: We performed a retrospective study using TriNetX. Adult patients with gastric adenocarcinoma who initiated nivolumab- or pembrolizumab-based first-line treatment between 2016 and 2024 were identified. Patients were classified as active PPI users if they had documented PPI prescription/administration (omeprazole, pantoprazole, esomeprazole, lansoprazole) within 30 days before or after ICI initiation, and non-users otherwise. Cohorts were 1:1 propensity score-matched for age, sex, PPI indication, comorbidities, baseline corticosteroid use, and prior Helicobacter pylori infection. OS was analyzed using Kaplan–Meier and Cox proportional hazards models. Sensitivity analyses exclude patients with recent GI bleeding and restricted exposure to sustained PPI use (> 60 days). Results: Following propensity score matching, 4,372 patients were included (2,186 PPI users and 2,186 non-users). Baseline characteristics were well balanced between cohorts (mean age 64.1 years; 38% female; GERD prevalence 41%; peptic ulcer disease 18%). At a median follow-up of 20.3 months, active PPI use was associated with significantly worse overall survival compared with non-use. Median OS was 11.2 months in PPI users versus 14.9 months in non-users (log-rank p < 0.001). Concomitant PPI exposure was independently associated with inferior OS (HR 1.27, 95% CI 1.16–1.39). Subgroup analyses demonstrated consistent findings across: ICI agents such as nivolumab (HR 1.25) and pembrolizumab (HR 1.29), presence of GERD, HR 1.22 in documented GERD, and absence of ulcer disease: HR 1.31 in patients without prior peptic ulcer disease. Sensitivity analyses yielded similar effect estimates, supporting the robustness of the findings. Conclusions: In this large real-world cohort of patients with gastric adenocarcinoma treated with first-line immunotherapy, concomitant PPI use was associated with significantly worse overall survival, even after rigorous adjustment for PPI indications and comorbidity burden. These findings support the microbiome hypothesis, suggesting that acid-suppressive therapy may impair the effectiveness of immunotherapy. Careful evaluation of the need for PPIs and prospective studies incorporating microbiome-directed interventions are warranted.
Liquid biopsy with peripheral blood mononuclear cells: Deciphering systemic immunity to predict PARPi-immunotherapy efficacy in early HER2-negative breast cancer.
e14531 Background: Neoadjuvant immunotherapy shows promising efficacy in early HER2-negative breast cancer, predictive biomarkers for treatment response remain limited. Peripheral blood mononuclear cells (PBMCs) provide a noninvasive approach to assess systemic immune responses during neoadjuvant therapy (NAT). We investigated whether PBMC-based immune profiling could predict pathological complete response (pCR) in patients with HER2-negative early breast cancer treated with the combination regimen of Nab-Paclitaxel, Camrelizumab (PD-1 inhibitor) and Fuzuloparib (PARP inhibitor). Methods: PBMC samples (n = 48) were collected from 16 patients with stage II–III HER2-negative breast cancer harboring BRCA1/2 or PLAB2 germline pathogenic/likely pathogenic variants, who received the neoadjuvant combination therapy of Nab-Paclitaxel, Camrelizumab and Fuzuloparib. The samples were obtained at baseline (C1D1), during neoadjuvant treatment (C2D1, C4D1), and preoperatively. RNA sequencing was performed on PBMC-derived RNA. Gene sets from the GO and KEGG databases were used for enrichment analyses. Additionally, CIBERSORT, Xcell, MCPcounter and TIMER in-house established algorithm were applied to estimate immune cell populations from PBMC-derived gene expression profiles. Results: Sixteen patients completed NAT and underwent surgery, 12 with the luminal subtype and 4 with triple-negative breast cancer (TNBC). The overall pCR rate was 56.25% (9/16)with pCR rates of 50% (6/12) in the luminal tumors and 75% (3/4) in TNBC. At baseline, higher levels of CD4⁺ T cells (p = 0.021), CD4⁺ memory T cells (p = 0.009) and CD4⁺ Tem cells (p = 0.009) correlated with improved treatment response. Baseline PBMCs from patients achieving pCR showed enrichment of gene signatures related to positive thymic T cell selection (p.adjust = 0.086) and αβ-TCR complex (p.adjust = 0.028). During NAT, macrophage counts increased significantly in the pCR group at C2D1 (p = 0.029) and preoperatively (p = 0.011) vs baseline. Additionally, myeloid DCs (p = 0.033) and neutrophils (p = 0.013) were progressively elevated from C1D1 to preoperative time points during NAT. Immune activation-related features (leukocyte activation in inflammatory response, C2D1 vs C1D1, p.adjust = 0.028; macrophage activation, C2D1 vs C1D1, p.adjust = 0.0008) were also enriched in the pCR group, while energy metabolism-related features (ATP synthesis coupled electron transport, p.adjust = 0.021) were enriched in the non-pCR group. Conclusions: PBMC-based transcriptional profiling at baseline and during NAT is associated with response to neoadjuvant PARP inhibitor–immunotherapy and may provide a noninvasive approach to predict pCR in early HER2-negative breast cancer.
A phase Ib/II study of mirdametinib in combination with palbociclib in patients with advanced dedifferentiated liposarcoma.
TPS11594 Background: Dedifferentiated liposarcoma (DDLPS) is a rare adipocytic malignancy characterized by frequent amplification of MDM2 and CDK4 and associated with poor outcomes, with a median overall survival of approximately 15 months. A phase II trial at Memorial Sloan Kettering Cancer Center demonstrated activity of the CDK4/6 inhibitor palbociclib in advanced WD/DDLPS, with a 12-week progression-free survival (PFS) rate of 57%, exceeding historical chemotherapy benchmarks (<35%) and leading to its inclusion in the NCCN Guidelines. Despite this, durability of benefit remains limited, and outcomes following progression are poor. Preclinical work from our group demonstrated that CDK4/6 inhibition in DDLPS induces cellular geroconversion from quiescence to irreversible senescence, accompanied by MDM2 downregulation. This process requires suppression of HRAS signaling and inhibition of the MAPK pathway and is associated with activation of the senescence-associated secretory phenotype (SASP). Preclinical models further suggest that dual CDK4/6 and MEK inhibition enhances SASP activation, providing a mechanistic rationale for combination therapy. Based on these findings, we initiated a phase Ib/II clinical trial of mirdametinib, a MEK1/2 inhibitor, in combination with palbociclib in patients with DDLPS (NCT06843967). Methods: This is an ongoing phase Ib/II, single-arm, open-label, single-center study evaluating the safety, tolerability, and efficacy of mirdametinib plus palbociclib in patients with unresectable, recurrent, or metastatic DDLPS (NCT06843967). Patients may enroll at any line of therapy, including first line, consistent with contemporary palbociclib use; patients with prior CDK4/6 inhibitor exposure are eligible for the phase Ib portion. Key eligibility criteria include ECOG performance status 0–2 and RECIST v1.1–measurable disease. Phase Ib uses a Bayesian optimal interval (BOIN) design with three dose levels to determine dose-limiting toxicities, maximum tolerated dose, and recommended phase II dose (RP2D), enrolling up to 24 patients. Phase II will assess efficacy at the RP2D, with the primary endpoint of PFS at 18 weeks by RECIST v1.1 in 30 patients. Enrollment began February 19, 2025. As of January 2026, accrual is ongoing at dose level 2. Enrollment to dose level 3 is anticipated in February 2026. Clinical trial information: NCT06843967 .
Genomic landscape of <i>TP53</i> Y220C–mutated clinically advanced prostate carcinoma (CAPC).
5044 Background: The TP53 Y220C base substitution mutation has become a significant therapeutic target with the development of reactivator drugs that restore TP53 function with a regulatory function in the cell cycle. However, its real-world prevalence and associated genomic landscape is not established in CAPC. Data on concurrent genomic alterations (GA) may guide the development of combinatorial therapeutic strategies. Methods: 26,156 cases of CAPC underwent hybrid capture-based comprehensive genomic profiling (CGP) to study all classes of GA including base substitutions, short insertions, deletions, copy number changes, rearrangements and fusions. Microsatellite instability (MSI) status and tumor mutation burden (TMB) were determined from the sequencing data; comparisons utilized the Fisher Exact method. Results: 144 CAPC (0.6%) of CAPC cases featured TP53 Y220C mutation ( TP53 Y220C+). Patients with TP53 Y220C+ CAPC had slightly higher median age (70.0 vs 68.2; p = 0.020) and numerically lower frequency of TMPRSS2 GA (33.0% vs 39.4%; Not significant (NS)). GA potentially associated with CAPC primary hormonal-based therapy response more frequently found in TP53 Y220C+ cases included SPOP (10.5% vs 1.4%; p < 0.0001) with AR GA (13.6% vs 11.3%; NS) being similar in both groups. GA linked to PARP inhibitor response slightly more frequent in TP53 Y220C+ cases included BRCA2 GA (8.7% vs 3.5%; p = 0.0003) and ATM GA (5.9% vs 4.2%; NS). GA in RAD21 were slightly higher in TP53 Y220C- CAPC (14.8% vs 8.3%; p = 0.029). GA in PIK3CA (6.6% vs 7.0%) and PTEN (32.4% vs 34.5%) were similar in the two groups. Biomarkers likely associated with benefit with anti-PD1/L1 agents were very low in both groups, included higher frequency of CDK12 GA (5.4% vs 0.7%; p < 0.0001) in TP53 Y220C+ cases and higher frequencies of MSI-High status (2.7% vs 0.0%; p = 0.045), mean TMB (3.8 vs 2.1 mutations/Mb; p < 0.0001) and TMB > 10 mutations/MB (4.4% vs 0.0%; p = 0.010) in TP53 Y220C- cases. Conclusions: TP53 Y220C is a rare finding in CAPC, but it may offer a potential therapeutic avenue for these patients whose tumors feature such a mutation. In addition, TP53 Y220C+ cases appear to be genomically relatively distinct from TP53 Y220C- CAPC cases and may feature genomic signatures that could influence treatment selection and trial design. Study limitations include a retrospective, descriptive design, a lack of clinical data annotation, and selection and confounding biases, so our findings are hypothesis-generating. Selective GA in TP53 Y220C+ vs TP53 Y220C- in patients with CAPC. TP53 Y220C+ CAPC (144 cases) TP53 Y220C- CAPC (26,012 cases) P Value Median Age (yrs) 70 (46-89+) 68 (35-89+) TP53 (all) 100.0% 39.7% <0.0001 TP53 (non-Y220C) 7.6% 39.7% <0.0001 SPOP 10.5% 1.4% <0.0001 BRCA2 8.7% 3.5% 0.0003 CDK12 5.4% 0.7% <0.0001 APC 9.1% 4.2% 0.0004 MSI-High 0.0% 2.7% 0.045 Mean TMB 2.1 3.8 <0.0001
Preliminary results of a single-arm, muti-center, prospective clinical study of disitamab vedotin combined with toripalimab and pelvic lymph node dissection for bladder preservation in patients with cT2-4aN0M0 bladder urothelial carcinoma and HER2 expression ≥ 2+ after maximal TURBT.
4592 Background: With the evolution of different treatment eras, the clinical complete response (cCR) rate of bladder cancer has been progressively increasing, while the lymph node metastasis rate has still not improved significantly. Particularly, patients with HER2 overexpression are at a higher risk of lymph node metastasis, which poses a major challenge to bladder-sparing therapy for patients with muscle-invasive bladder cancer (MIBC). This study aims to establish a novel bladder-preserving treatment model by combining local therapy enhanced with pelvic lymph node dissection (PLND) and systemic therapy with Disitamab Vedotin and Toripalimab. Methods: Patients with cT2-4aN0M0 MIBC and HER2 expression ≥2+ were enrolled, The primary endpoint was 2-year bladder-intact disease-free survival rate. After maximal transurethral resection of bladder tumor (TURBT), patients received Toripalimab (3mg/kg, Q2W) combined with Disitamab Vedotin (2mg/kg, Q2W) for 6 cycles, followed by TURBT and PLND. Those with cCR or partial response (PR) continued the combined therapy for another 6 cycles. Patients achieving cCR after 12 cycles of combined therapy received maintenance Toripalimab (240mg, Q3W) for 1 year. Non-cCR patients received comprehensive treatment or salvage radical cystectomy(RC). Results: As of December 2025, 21 patients were enrolled, with a median age of 66 years (range: 37–82). The primary endpoint was not yet reached. Efficacy assessment was performed in 14 patients at Week 12: 10/12 (85.8%) achieved cCR, while 1 patient had stable disease (SD) and 1 had progressive disease (PD). Among 10 patients who underwent TURBT and PLND, pathological complete response (pT0N0M0) was achieved in 90.0%, and 1 patient was postoperatively staged as pT0N1M0. Patients with SD or PD underwent RC. All patients experienced treatment-related adverse events (TRAEs) of any grade. The most common TRAEs were pruritus (75.00%), paresthesia (68.75%), and elevated ALT (43.75%), all of which were Grade 1–2. One patient developed a Grade 3 adverse event (AE), which was severe urinary tract infection. No TRAEs of Grade ≥4 were observed. Conclusions: The novel bladder-sparing modality of Disitamab Vedotin combined with Toripalimab plus PLND after maximal TURBT currently demonstrates favorable efficacy and safety. Long-term outcomes warrant further investigation. Clinical trial information: ChiCTR2400081555.
Epidemiological trends and burden of Burkitt lymphoma mortality in South Asia: A retrospective analysis from 1990 to 2023 with advanced machine learning forecasting to 2050.
e19083 Background: Burkitt lymphoma (BL), an aggressive B-cell non-Hodgkin lymphoma, shows marked geographic variation, with highest incidence in sub-Saharan Africa but rising recognition in South Asia linked to improved diagnostics and possible infectious or immune triggers. Methods: This study utilized age-standardized mortality rates (ASMR per 100,000) for Burkitt lymphoma from the IHME Global Burden of Disease 2023 database, covering South Asia and its key countries (Bangladesh, Bhutan, India, Nepal, Pakistan) from 1990 to 2023, stratified by sex. Historical trends were quantified using estimated annual percentage change (EAPC) derived from log-linear regression of ASMR. Future mortality projections to 2050 were generated using autoregressive integrated moving average (ARIMA) time-series models fitted to historical data, yielding point forecasts and 95% prediction intervals (PI). Results: In South Asia (Both sexes), ASMR increased from 0.03 (1990) to 0.04 (2023), EAPC +0.71% (95% CI +0.62 to +0.81); males +0.53% (+0.44 to +0.62), females +0.94% (+0.80 to +1.09). Country-level variation was pronounced: Bangladesh Both stable at EAPC -0.19% (-0.45 to +0.08), ASMR 0.03 (1990) to 0.04 (2023), projected to 0.03 (0.02–0.04) by 2050; Bhutan Both sharply rising EAPC +0.97% (+0.71 to +1.23), ASMR 0.03 (1990) to 0.04 (2023), forecast 0.06 (0.04–0.07) in 2050; India Both modest decline EAPC -0.15% (-0.27 to -0.03), ASMR 0.02 (1990) to 0.02 (2023), forecast 0.02 (0.02–0.02) in 2050; Nepal Both increase EAPC +0.22% (+0.04 to +0.39), ASMR 0.03 (1990) to 0.03 (2023), forecast 0.03 (0.03–0.04) in 2050; Pakistan Both rapid rise EAPC +1.02% (+0.91 to +1.13), ASMR 0.10 (1990) to 0.13 (2023), forecast 0.16 (0.14–0.18) in 2050. Sex-specific trends showed pronounced female increases in Pakistan EAPC +1.78% (+1.61 to +1.96) and Bhutan +1.76% (+1.54 to +1.97). ARIMA projections forecast continued South Asia rise to 0.05 (0.04–0.06) by 2050, with Pakistan reaching 0.16, Bhutan 0.06, while India and Bangladesh stabilize near 0.02–0.03. Conclusions: BL mortality in South Asia rose modestly overall from 1990–2023, driven by rapid increases in Pakistan, Bhutan, and Nepal while India and Bangladesh remained stable or declined slightly. Projections to 2050 indicate further rise in high-burden areas. Location Sex EAPC Lower 95%CI Upper 95%CI Bangladesh Both -0.19 -0.45 0.08 Bangladesh Female -0.32 -0.69 0.05 Bangladesh Male -0.06 -0.24 0.12 Bhutan Both 0.97 0.71 1.23 Bhutan Female 1.76 1.54 1.97 Bhutan Male 0.51 0.20 0.82 India Both -0.15 -0.27 -0.03 India Female -0.23 -0.36 -0.11 India Male -0.07 -0.21 0.07 Nepal Both 0.22 0.04 0.39 Nepal Female -0.24 -0.54 0.06 Nepal Male 0.52 0.40 0.64 Pakistan Both 1.02 0.91 1.13 Pakistan Female 1.78 1.61 1.96 Pakistan Male 0.32 0.23 0.42 South Asia Both 0.71 0.62 0.81 South Asia Female 0.94 0.80 1.09 South Asia Male 0.53 0.44 0.62
Convergent PI3K pathway activation and SWI/SNF dysfunction as characteristics of bone-metastatic endometrial cancer.
e17636 Background: Bone metastasis from primary endometrial cancer is rare, reported in fewer than 1% of cases. Despite this, an increasing number of bone-metastatic cases has recently been observed at our institution. The molecular drivers underlying this uncommon metastatic pattern remain poorly defined. Methods: We performed whole-exome sequencing on tumor samples from 12 patients with endometrial cancer and confirmed bone metastases identified at our institution between October 2023 and August 2025. Pathogenic variants were analyzed with a focus on recurrently altered signaling and chromatin regulatory pathways. Histologic subtypes were reviewed and correlated with molecular findings. Results: Pathogenic alterations in genes involved in the PI3K–AKT–mTOR signaling pathway (PTEN, PIK3CA, PIK3R1) were identified in 8 of 12 cases (67%). Mutations in ARID1A, a core component of the SWI/SNF chromatin remodeling complex, were present in 7 of 12 cases (58%). Notably, 6 of the 8 tumors harboring PI3K pathway alterations also demonstrated concurrent ARID1A mutations, indicating a high degree of overlap between these pathways. All six tumors with combined PI3K pathway and SWI/SNF complex alterations were histologically aggressive, comprising either uterine papillary serous carcinoma or grade 3 endometrioid adenocarcinoma. Conclusions: Bone-metastatic endometrial cancers in this cohort are characterized by frequent co-alteration of PI3K–AKT–mTOR signaling components and SWI/SNF chromatin remodeling machinery. This pattern supports a synergistic biological model in which constitutive proliferative and survival signaling driven by PI3K pathway activation cooperates with epigenetic instability resulting from ARID1A loss to enable metastatic progression to bone. These findings suggest potential therapeutic vulnerabilities, including pharmacologic inhibition of the PI3K–AKT–mTOR axis using PI3K inhibitors, AKT inhibitors, or mTOR inhibitors, as well as emerging epigenetic strategies targeting ARID1A-deficient tumors, such as EZH2 inhibition and synthetic lethal approaches exploiting SWI/SNF dysfunction. Combined pathway targeting may represent a rational treatment strategy for patients with aggressive, bone-metastatic endometrial cancer and warrants further investigation.
Neoadjuvant pegylated liposomal doxorubicin plus anlotinib in locally advanced soft tissue sarcoma: Clinical outcomes and multi-omics analysis from a phase II study.
11561 Background: Neoadjuvant therapy may improve the R0 resection and limb salvage rates in locally advanced soft tissue sarcomas (STS). This phase II trial was designed to evaluate the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD) combined with anlotinib in the treatment of locally advanced STS. Methods: This single-center, single-arm phase II trial (NCT04765228) enrolled treatment-naïve patients with stage II/III. Patients received PLD (50 mg/m² intravenously on day 1) combined with anlotinib (12 mg orally daily on days 8-21) every 3 weeks for 2-4 cycles. Based on a one-proportion test, with α=0.05 (two-sided) and 80% power, to detect an increase in the objective response rate (ORR) from 10% to 26%, 45 patients were planned, accounting for a 20% dropout rate. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. The exploratory endpoint was biomarker analyses. The corresponding two-sided 95% CIs were estimated using the Clopper-Pearson method. The PFS and OS were estimated using the Kaplan-Meier method. Results: A total of 40 eligible patients were treated between November 2020 and November 2022, of whom 34 (85.0%) underwent surgery. The median age was 46.5 years (range: 15-74 years), and 23 (57.5%) of the patients were male. Histologically, the 40 patients included 9 cases of liposarcoma (LPS), 6 cases of malignant peripheral nerve sheath tumor (MPNST), 6 cases of synovial sarcoma (SS), 3 cases of low-grade fibromyxoid sarcoma (LGFMS), 3 cases of myxofibrosarcoma (MFS), 3 cases of spindle cell sarcoma (SCS), 3 cases of undifferentiated pleomorphic sarcoma (UPS), 2 cases of leiomyosarcoma (LMS), and 5 cases of other STS. The most common sites of primary tumor were lower extremities (42.5%), waist/hip region (17.5%) and other regions. The ORR based on RECIST 1.1 was 15.0% (95% CI: 3.4%-26.6%), and the ORR of 36 patients based on Choi's criteria was 58.3%. The median PFS was 14 months (95% CI: 4.22 - 23.79 months), and the median OS was not reached. Pathological response was evaluable in 24 patients, with pathological complete response (pCR) and pathological partial response (pPR) observed in 4.2% (1/24) and 50.0% (12/24) of cases, respectively. Among 34 patients who underwent surgical resection, 30 (88.2%) achieved R0 resection, while 3 (8.8%) had R1 resection. Common treatment-related adverse events (TRAEs) of any grade included mucositis oral (52.5%), neutrophil count decreased (25.0%). Fifteen (37.5%) patients experienced at least one grade 3-4 AE. Conclusions: Neoadjuvant PLD combined with anlotinib exhibits promising efficacy and acceptable toxicity in patients with locally advanced STS. Results from multi-omics analyses will facilitate the screening of suitable patients in future clinical practice. Clinical trial information: NCT04765228 .
Controlling an altermagnetic spin density wave in the kagome magnet CsCr3Sb5
Abstract The interplay of charge and spin orders lies at the heart of correlated electron physics and plays a critical role in the emergence of unconventional quantum phases. Kagome magnets provide a particularly promising platform to investigate these phenomena, owing to their geometrically frustrated lattice structure. However, resolving spin and charge orders microscopically and establishing ways to control them remain fundamental challenges. Here, we demonstrate magnetic-field control of an altermagnetic spin density wave order intertwined with charge density wave order in kagome magnet CsCr 3 Sb 5 . Scanning tunneling microscopy down to deep cryogenic temperature of 50 mK reveals two previously unreported charge density wave orders. Density functional theory confirms that one of them, a 4 $${a}_{0}\times \sqrt{3}{a}_{0}$$ a 0 × 3 a 0 charge order, is coupled to a spin density wave with an altermagnetic ground state. The charge density waves can be tuned in both amplitude and phase by an external magnetic field, reflected in domain switching and stripe sliding of the charge density wave. Our findings deepen the understanding of symmetry-breaking in kagome systems, providing a tunable platform to explore the interplay of electronic correlation with emergent quantum magnetism.
EA6232: A phase II double-blind trial of sulforaphane for therapeutic prevention of melanoma in patients with multiple atypical nevi and a prior history of melanoma.
TPS9611 Background: A significant risk factor for melanoma is presence of atypical/dysplastic nevi (A/DN), and evidence suggests a 10-fold increased risk of new primary melanoma with A/DN. 1 Patients with prior melanoma and multiple A/DN are thus reasonable targets for therapeutic prevention due to high risk of additional melanoma. Currently, no preventative systemic agent for melanoma is approved. Sulforaphane, an isothiocyanate of cruciferous vegetables, demonstrates therapeutic prevention potential in multiple clinical trials. 2 3 Topical sulforaphane mitigates effects of UV radiation, a primary driver of melanoma development, in mouse and human skin. 4 The proposed mechanism involves alterations of transcription factor Nrf2, an antioxidant modulator, and IL-6/STAT-3 pathways in A/DN and melanoma. 5 6 7 Our team conducted a phase I trial of oral sulforaphane for 28 days in 17 patients with prior melanoma and ≥ 2 A/DN. 8 Statistically significant decreases in several serum pro-inflammatory cytokines were reported with no dose-limiting toxicities. This phase II trial aims to elucidate effects of daily sulforaphane on A/DN lesions and compare pigmentation change to placebo over one year. We hypothesize sulforaphane will demonstrate a greater decrease in total area of pigmented nevocellular nevi (both A/DN and banal nevi) vs. placebo as documented by serial digital photography. Methods: This phase II trial (NCT07040280) will assess impact of daily sulforaphane for 12 months vs. placebo on total area, quantity, and features of A/DN. Patients with ≥ 3 clinical A/DN (≥ 5 mm diameter with macular component, and ≥2 features of ill-defined borders, color variegation, uneven contour, or erythema) and a history of early stage-melanoma are eligible. Enrolled patients will undergo a baseline clinical skin exam and scheduled follow-up exams every 3 months. Photography of index A/DN and a standardized area of the posterior trunk, excisional biopsy of an A/DN, and peripheral blood sampling will be performed at baseline, 3 months, and 12 months. The primary endpoint is effect of sulforaphane vs. placebo on change in total area of pigmented nevocellular nevi on the posterior trunk at 12 months, calculated by Derma-AI image analysis software. 9 Secondary endpoints are number of posterior truncal nevi with moderate to significant changes in area, changes in A/DN features/area, and assessment of the safety/tolerability of sulforaphane. Exploratory endpoints include effects on circulating cytokine and chemokine levels assessed by multiplex technology, impact on A/DN immune cell infiltration by histopathology and immunochemistry, and evaluation of prespecified A/DN features at each timepoint. Outcome measures will be compared between arms over serial timepoints by Wilcoxon rank sum test. The study is open for enrollment with accrual goal of 120 patients.
Characterization of patients with head and neck cancer in Argentina.
e23396 Background: Head and neck squamous cell carcinomas (HNSCC) arise from epithelial cells of the lip/oral cavity (OC), oropharynx (OP), nasopharynx (NP), hypopharynx (HP), and larynx (LX). In Argentina, an estimated 3,000 new head and neck cancer (HNC) cases and 1,600 deaths occurred in 2022. Robust, locally relevant epidemiologic profiles for HNC can strengthen clinical practice and policy planning. We conducted a sector-wide assessment of tumor site, TNM stage, and patient characteristics in Argentina to detail evidence-based care and guide future research. Methods: observational, retrospective, cross-sectional study (2017–2020) conducted at two Buenos Aires referral hospitals (public and private). Adult new cases of HNSCC (excluding NP carcinoma) were included. Data were collected via chart review; descriptive statistics summarized demographics and clinical factors. Results: The sample consisted of 300 incident cases (150 per site), of which 68% (205) were male, mean age was 59 (SD = 11), with 65% aged 50–69. Patients were 34%, 39% and 27% never, former and current smokers, respectively; 89% reported no alcohol use. Patients were most often first identified by otolaryngologists (35%) or general surgeons (32%). Oncologists were rarely the first contact (4%). Staging at diagnosis was 23% I, 16% II, 26% III, and 35% IV (18% IVA, 11% IVB, 5% IVC). Primary tumor locations were OP (37%), lip/OC (33%), LX (24%), and HP (6%). ECOG at first visit was 0 in 49%, 1 in 19%, 2 in > 3% and 3 in > 1%, with 28% being unknown. 104 (mostly oropharynx) had HPV testing: 82% (n = 86) were HPV positive. Among oropharyngeal tumors, 75% (n = 111) were HPV-positive, 17% (n = 19) were negative, and 8% (n = 9) unknownThe private center (Alexander Fleming) had more lip/OC cancers (43% vs 23%), more stage I diagnoses (31% vs 15%), higher HPV positivity in OP tumors (95% vs 73%), faster access (53% seen within ≤1 month vs 39% at public center; 6% > 2 years at the latter), and more first identification by general surgeons (59% vs 5%). The public center (Instituto Ángel Roffo) had more OP (41% vs 33%) and laryngeal cancers (29% vs 20%), roughly twice the HP tumors (7% vs 4%), higher stage III–IV (30% vs 22% for stage III; 39% vs 31% for stage IV; IVB 15% vs 7%), greater current smoking (37% vs 17%) and alcohol use (16% vs 7%), more first identification by otolaryngologists (43% vs 25%) and clinicians (27% vs 2%), and far more second-opinion referrals (89% vs 17%). Conclusions: This two-center analysis reveals distinct sectoral profiles: the private center exhibited faster access and more early-stage and HPV-positive oropharyngeal cancers, whereas the public center had longer delays, more advanced-stage disease, higher tobacco and alcohol use, and more laryngeal/hypopharyngeal tumors. Targeted interventions to accelerate diagnosis, harmonize HPV testing, and mitigate modifiable risks may help reduce late-stage presentations and access inequities in Argentina and comparable health systems contexts.