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Phase III randomized trial of tislelizumab plus gemcitabine/capecitabine (GX) versus tislelizumab plus gemcitabine/cisplatin (GP) as first-line therapy for recurrent/metastatic nasopharyngeal carcinoma: A prospective multicenter study (PROGRESS).
TPS6125 Background: Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and Southern China. Around 10% of pts have distant metastasis at initial diagnosis, and ~30% of those initially without metastasis will develop distant metastasis after radical treatment. These recurrent/metastatic (R/M) NPC pts have poor prognosis with a 5-year survival rate of only 20–30%. The RATIONALE-309 study established tislelizumab plus GP as a standard first-line therapy for R/M NPC, but most pts still experience disease progression in 2 years. Furthermore, in real-world clinical practice, a lot of pts are either platinum-intolerant or platinum-refractory recurrent, underscoring the urgent need for novel treatments. Recent studies suggest that first-line treatment regimens incorporating capecitabine may provide longer progression-free survival (PFS) compared to the GP regimen with a more favorable safety profile. Additionally, a retrospective study demonstrated that tislelizumab plus GX achieved notable tumor responses and PFS benefits in R/M NPC pts who have relapsed immunotherapy. Methods: This is a prospective, multicenter, randomized, controlled Phase III trial evaluating the efficacy and safety of tislelizumab + GX vs. tislelizumab + GP as first-line therapy in R/M NPC. 266 pts will be randomly assigned to the experimental or the control group. The experimental group will receive tislelizumab plus GX (gemcitabine 1g/m² D1,8 + capecitabine 1000 mg/m² BID D1-14) for 4–6 cycles, followed by tislelizumab plus capecitabine maintenance. The control group will receive tislelizumab plus GP (gemcitabine 1 g/m² D1,8 + cisplatin 80mg/m² D1) for 4–6 cycles, followed by tislelizumab monotherapy. Treatment will continue until disease progression or intolerable toxicity. The primary endpoint is PFS. Secondary endpoints include objective response rate, duration of response, overall survival, etc. Adverse events will be monitored and graded according to NCI CTCAE v5.0. Patient enrollment began in December 2023 across 10 centers in China, with 168 pts enrolled by December 2025. Clinical trial information: NCT06177301 .
Trends and characteristics of clinical trials presented in ASCO plenary sessions (2011–2025).
11024 Background: Clinical trials presented during the ASCO Annual Meeting Plenary Session (PS) represent a curated subset with high scientific and clinical impact. However, characteristics associated with PS selection and their evolution have not been comprehensively described. This study evaluates trends and trial-, sponsor-, and presenter-related characteristics of trials in PS. Methods: Trials presented in PS from 2011–2025 were analyzed. Extracted variables included tumor type, therapeutic modality, disease setting, sponsorship, primary endpoint, effect size, geographic scope, and presenter sex and affiliation. Associations between variables were evaluated using chi-square, and multivariable logistic regression analyses. Temporal trends were assessed using Cochran-Armitage trend test. Results were considered significant at α = 0.05. Results: From 2011–2025, 60 trials were presented in ASCO PS. The majority evaluated therapies for solid tumors (90%). Most common therapeutic modalities were immune checkpoint inhibitors (18%), chemotherapy (16%), and hormone therapy (13%). Most trials were conducted in the palliative (46%), followed by adjuvant setting (25%). Only 9 trials (15%) included pediatric patients. Overall, 85% of trials met their primary endpoint. Overall survival (OS), progression-free, and disease-free survival were the most used primary endpoints, with surrogate endpoints increasingly represented over time compared with OS (p < 0.001). One trial used quality of life (QoL) as primary endpoint. Mean hazard ratio was 0.68 ± 0.24. Industry-sponsored (Ind) studies accounted for 52% of PS presentations, with four sponsors responsible for 61% of Ind trials. The proportion of Ind trials significantly increased over time (p = 0.03). Ind was significantly associated with meeting the primary (p = 0.048) and use of surrogate endpoints (p = 0.008), remaining an independent predictor of both in multivariable regression (p = 0.035, β = 0.318; p = 0.033, β = 0.333). Most studies were conducted globally (61%), 12% exclusively in the United States (US), followed by Europe (10%). Among presenters, 23% were female, with female representation not changing over time. Most presenters were affiliated with institutions in the US (62%), followed by the United Kingdom (7%). In multivariable regression analysis, Ind was associated with lower odds of a female presenter (p = 0.039; β = -0.342). Conclusions: Over the past 15 years, ASCO PS have predominantly featured global, Ind trials in solid tumors, with an increasing reliance on surrogate endpoints. Ind emerged as key factor associated with trial characteristics, including endpoint selection and trial success. Female presenter inclusion, pediatric trials, and QoL endpoints remain underrepresented. These findings provide an overview of evolving trial characteristics and inform discussions on research priorities, trial design, and representation.
Real-world comparison of anti-GPRC5D bispecific therapy versus anti-BCMA treatment in relapsed/refractory multiple myeloma after prior BCMA-directed therapy.
e19509 Background: In relapsed/refractory multiple myeloma (RRMM), B-cell maturation antigen (BCMA)-directed therapies (BDT), such as CAR-T, antibody-drug conjugates, and bispecifics, have shown promising results. However, relapse is common, and optimal sequencing post-BCMA therapy remains uncertain. The immediate second BDT after relapse had shown lower response rates. GPRC5D-directed bispecific therapy (talquetamab) post-BDT had an overall response rate (ORR) of 67% in the MonumenTAL-1 trial. No direct head-to-head comparisons of talquetamab vs repeat BDT in BCMA-exposed RRMM patients are available so far. Methods: We conducted a retrospective cohort study using the TriNetX Global Health Network. MM patients aged ≥18 years who had received prior BDT (Ide-cel, Cilta-cel, Teclistamab, Elranatamab) were selected. Defined into two cohorts as those who received (1) talquetamab (n=368) and (2) sequential BDT (N= 1118) after prior BCMA therapy. Propensity score matching (1:1) was done to balance demographics, comorbidities, and prior therapies. Follow-up period was 1 year. Survival was assessed using Kaplan-Meier analysis. Hazard ratios (HR) and log-rank p-values were calculated. Results: After matching, each cohort had 282 patients. Mean age was 67 ± 10 years, with 56% male and 64% white in both groups. Treatment patterns showed a heavily pretreated population: proteasome inhibitors (bortezomib 44.7%), IMiDs (lenalidomide 65%, pomalidomide 56%), anti-CD38 therapy (daratumumab 49%), CAR T (20%), autologous stem cell transplant (44.3%), belantamab (5.7%), elranatamab (6%), and teclistamab (74%). Mean follow-up was 206 vs 239 days in talquetamab and sequential BDT groups, respectively. All-cause mortality was slightly higher in the talquetamab group (HR = 1.101, 95% CI: 0.8–1.5), with survival probabilities of 63.79% vs 66.92% in the BDT group, but this difference was not statistically significant (P = 0.548). ER visits (HR = 0.716), anemia (HR = 0.915), sepsis (HR = 0.803), and pneumonia (HR = 0.641) were numerically lower in the talquetamab group but were not statistically significant (p > 0.05). Neutropenia (HR = 1.082), thrombocytopenia (HR = 1.301), and CRS (HR = 1.617) did not differ significantly (p > 0.05). Hospitalization, MM relapse, and neurotoxicity were not analyzable due to low events. Conclusions: This real-world study showed no significant difference in mortality, toxicities, infectious or healthcare outcomes between talquetamab and BDT in RRMM patients with prior BCMA exposure. This suggests that antigen escape is less common than anticipated. While these results need to be further evaluated in prospective studies, future research should focus on outcomes based on timing or type of prior BCMA therapy, biomarker-driven treatment selection, and optimal sequencing based on resistance mechanisms.
Protonation‐Triggered Fluorescence Switching in COF Membranes for the Selective and Rapid Detection of New Psychoactive Substances
ABSTRACT New psychoactive substances (NPS) typically exhibit low saturated vapor concentrations and are susceptible to interference such as water vapor and carbon dioxide, making the realization of high‐performance gas‐phase detection a challenge in both scientific research and public safety. Herein, we presented a self‐standing covalent organic framework (COF) membrane formed between 1,3,5‐tris‐(4‐aminophenyl)triazine (TTPA) and 4,4',4''‐nitrilotribenzaldehyde (TFPA), TTPA–TFPA COF, which was fabricated via a two‐step synthesis involving interface‐confined polymerization followed by post‐processing. The sensor used the ozone‐treated COF membrane as the sensing layer exhibited rapid, highly selective, and visually observable fluorescence response toward the NPS simulant (S)‐ N , α ‐dimethylbenzylamine (DMBA), achieving a fast response time of less than 1 min and an ultra‐low detection limit of 2.1 ppb. Moreover, the sensor successfully discriminates seven structurally analogous NPS reference standards through kinetic response profiling. The infrared and XPS spectra, along with theoretical calculations, further reveal the sensing mechanism is driven by hydrogen bond interaction between the ozone‐treated COF membrane and the DMBA. These findings offer valuable insights for developing portable, real‐time chemical monitoring devices, providing an innovative solution for on‐site trace‐level NPS detection. This holds promising potential for addressing serious threats to human health, family harmony, and social stability.
Leveraging Lithium‐Bond Chemistry in a Tailored Electrolyte to Control Sulfur and Lithium Evolution in Li–S Batteries
ABSTRACT Rational regulation of lithium polysulfide reaction kinetics, coupled with strategies for stabilizing the Li anode, constitutes a cornerstone for lithium–sulfur (Li–S) chemistry. Herein, we propose phthalocyanine (Pc) as a homogeneously dispersed promoter in the electrolyte for Li–S batteries, based on its N 8 ‐cavity planar rigid structure featuring an electron‐rich macrocyclic core. Under the optimized concentration of Pc in electrolyte, we reveal that the Li─N coordination bonds between Li 2 S 8 and Pc in the catholyte of Li–S batteries, which significantly contribute to the catalytic conversion of sulfur species. Meanwhile, Pc molecules in the anolyte preferentially adsorb onto the Li anode surface, forming a dense molecular layer by virtue of Li─N bonding, which effectively enhances interfacial desolvation kinetics and thereby promotes uniform Li deposition. Enabled by the promoted Li–S chemistry through Li─N bonds, the battery with Pc enabler achieves a low decay rate of 0.0479% per cycle after 600 cycles at 1C. More remarkably, 1.07 Ah pouch cells deliver a high energy density of 325.5 Wh kg −1 , serving as a compelling design strategy for leveraging sustainable Li─N bond chemistry to achieve high‐rate and long‐life Li–S battery technology.
Accelerating OH <sup>−</sup> Transport for 5000‐Hour‐Stable Kilowatt‐Scale Alkaline Water Electrolysis
ABSTRACT Enhancing the continuous supply of OH − reactants to anode catalytic sites under high current density is critical for the development of alkaline water electrolyzer (AWE). Herein, a strategy for promoting OH − transport is demonstrated by using rare earth oxide clusters (REO x ) to reconfigure interfacial hydrogen bond networks. This structural modulation achieves a nearly threefold increase in the OH − transport rate. Mechanistic analysis reveals that the incorporation of rare earth weakens the charge‐dipole interaction between the oxygen in the * OH intermediate and interfacial H 2 O molecules, promoting the transition from a rigid, ordered interfacial water structure to a more isolated, loose configuration. A linear correlation among the proportions of isolated water species, OH − transport rates, and OER activity across a series of REO x /NiCo 2 S 4 catalysts supports this mechanism. A kilowatt‐scale AWE consisting of 17 cells with a total active area of 1334 cm 2 was assembled using a DyO x /NiCo 2 S 4 anode. For the first time, the system operated stably for over 5,000 h at a current of 39.25 A under industrial operating conditions, achieving a cumulative hydrogen output of 1,400 Nm 3 . This work highlights the potential of manipulating the electrode‐electrolyte interface to enhance catalyst performance in producing industrial‐scale green hydrogen.
Creating affordable and accessible cancer care at scale: History of extension from 12 to 750 districts, covering the whole of the nation—India.
e13599 Background: The principal challenges in cancer care are the affordability, accessibility, and availability of an adequately trained oncology workforce. In central India, a structured model of cancer care delivery was initiated in 2014 across 12 districts. This model is currently being scaled up to achieve nationwide coverage. We present how cancer care services achieved large-scale expansion through the optimization of existing health system infrastructure, systematic capacity building, task sharing, and the development of an alternative oncology workforce. Methods: Each district is served by a state-owned comprehensive district hospital, which provides free general medical services. An oncology capacity-building program targeting medical officers and nursing personnel was implemented, leading to the establishment of dedicated oncology units in each district hospital. In 2014, this program started with 12 districts. Now, it has grown to 200 districts in eight Indian states. The training methodology, documentation protocols, follow-up training procedures, and support mechanisms were standardized at all sites. A key feature of the program was the provision of continuous (24 × 7) professional backup to the entire oncology workforce. Simultaneously, the district-level essential medicines list was revised to include essential anticancer drugs. Results: In total, more than 200 districts participated, with over 296 physicians and 542 nurses trained (Table 1). The training program was complemented by on-site supervisory visits that included cancer-related service delivery activities in each district, short-term continuing medical education (CME) courses, and participation in scientific conferences. State-level WhatsApp groups facilitated routine communication and case-based discussions to support ongoing clinical decision-making. This implementation model contributed to health system strengthening through broad-based adoption, enhanced resilience during crises, and integration into governmental structures. Conclusions: The challenges of ensuring affordable and accessible cancer care have been substantially addressed through the district cancer care model. The Government of India has adopted it for national implementation. This model has the potential to alleviate financial toxicity and reduce the overall economic burden associated with cancer care and it addresses critical shortages in the oncology workforce. Thus, the district cancer care model may serve as a foundational framework for health systems worldwide. Training of oncology workforce. S.no Name of State Doctors Staff Nurse Year of Training 1 Madhya pradesh 90 240 2014 2 Odisha 28 56 2015 3 Rajasthan 33 66 2016 4 Gujarat 19 36 2017 5 Uttar Pradesh 15 30 2017 6 Himachal Pradesh 44 22 2017 7 Bihar 16 42 2017 8 Chattisgarh 45 44 2017 9 Haryana 6 6 2025 Total 296 542
Intensive chemotherapy versus venetoclax–hypomethylating agents therapy for acute myeloid leukemia: A large real-world propensity-matched study.
e18541 Background: Intensive induction chemotherapy (IC) with cytarabine and an anthracycline has been the frontline approach for acute myeloid leukemia in fit adults for decades. Despite its long use, long-term survival remains limited, and it has significant toxicities. In VIALE-A, venetoclax with azacitidine (Ven-Aza) improved survival and remission rates among patients who were not candidates for IC. The phase 2 PARADIGM trial compared Ven-Aza with standard IC in fit adults and reported higher response rates and better event-free survival with Ven-Aza. Using a large, real-world cohort with propensity-matched controls, we compared survival outcomes between patients treated with IC and those treated with Venetoclax combined with a hypomethylating agent (Ven-HMA). Methods: Using the TriNetX research network, adults with AML receiving either IC or Ven-HMA as initial therapy were identified; patients with acute promyelocytic leukemia were excluded. Cohorts were propensity score–matched 1:1 on age, sex, comorbidities, TP53 mutation, and the presence of another primary malignant neoplasm. The primary outcomes were mortality at 3, 6, and 12 months. Secondary outcomes included sepsis, acute kidney injury (AKI), tumor lysis syndrome (TLS), and acute myocardial infarction (AMI) or stroke. Results: After matching, 2,588 patients were included per cohort. At 3 months, mortality was lower with IC than with Ven-HMA 13.7% versus 18.1% (hazard ratio [HR] 0.75, 95% CI 0.65–0.86; log-rank p<0.0001). At 6 months, mortality remained lower with IC, 20.3% versus 29.6% (HR 0.66, 95% CI 0.59–0.74; log-rank p<0.0001), and at twelve months, 30.8% versus 44.9% (HR 0.63, 95% CI 0.58–0.69; log-rank p<0.0001), favoring IC across all intervals. Incidents of sepsis (35.2% vs 32.5%; p = 0.047) and AKI (40.7% vs 37.9%; p = 0.04) were modestly higher with IC, whereas TLS and stroke or AMI were similar between groups. Conclusions: IC was associated with significantly improved short-term survival compared with Ven-HMA therapy among patients with AML, despite slightly higher risks of sepsis and acute kidney injury. These findings suggest that while Ven-HMA remains an appropriate option for patients unfit for intensive therapy, IC continues to provide superior survival outcomes in appropriately selected patients. Further studies integrating molecular risk stratification and measurable residual disease are warranted to optimize treatment selection in AML.
Influence of neoadjuvant therapy on tumor-vascular-immune stromal networks in colorectal cancer liver metastases.
3586 Background: Neoadjuvant therapy's effect on vascular, tumor, and immune compartments, and their co-regulation, in colorectal liver metastases (CRLMs) remains poorly understood. We performed multiplex-based tissue profiling to quantify how treatment reshapes stromal compartment and co-occurrence networks, defined by inside-case correlations between features. Methods: We analyzed 76 CRLM cases (27 untreated, 49 neoadjuvant-treated [43 chemotherapy, 6 chemo + VEGF-/EGFR-targeted]). Tissue microarrays (1-3 1-mm cores/tumor) underwent multiplex immunofluorescence to quantify immune/tumor subsets (CD3/CD4/CD8/PD-1/FOXP3/TIM-3/Ki67/CDX2), vessels (claudin-5), and stromal perivascular compartments (αSMA/PDGFRβ). Statistical analysis included Mann-Whitney U tests and Spearman correlations. Results: Neoadjuvant-treated CRLMs had 42% fewer proliferating tumor cells (CDX2⁺KI67⁺density, p=0.006) and 33% lower CDX2⁺ density (p=0.031) compared with untreated CRLMs. This was accompanied by a 32% reduction in proliferating cytotoxic T-cells (CD3⁺CD8⁺Ki67⁺ density, p=0.029). A reduction in vessel size was also observed in treated CRLMs (vessel size, -12%, p=0.077). Analyses suggested different effects by type of neoadjuvant treatment. Chemotherapy alone reduced proliferating tumor cells (CDX2⁺KI67⁺ density, -37%, p=0.016) and suppressed cytotoxic T-cell proliferation (CD3⁺CD8⁺Ki67⁺ density, -40%, p=0.017). The addition of VEGF/EGFR-targeted agents produced the most pronounced reduction in tumor burden (CDX2⁺ density, -73%, p=0.012; CDX2⁺KI67⁺ density, -76%, p=0.010) vs. untreated. CRLM co-occurrence networks were also affected by treatment. Treatment abolished positive correlations between tumor cells (CDX2⁺ and CDX2⁺KI67⁺ densities) and αSMA⁺PDGFRβ⁺ perivascular fraction/vessel size (r=+0.42 – +0.60, p<0.05), and negative correlations between tumor cells and αSMA⁺PDGFRβ⁻ perivascular fraction/vessel density (r=-0.47 – -0.40, p<0.05) in untreated (vs +0.05 – +0.27 and +0.09 – +0.21, p=n.s., in treated). Treatment also eliminated positive correlations between vessel size and exhausted (CD8⁺PD-1⁺) and regulatory (CD4⁺FOXP3⁺) T-cell densities (untreated r=+0.40 – +0.47, p<0.05). In parallel, new positive links emerged between αSMA⁻PDGFRβ⁺ perivascular fraction and CD4⁺ and CD8⁺ T cells (r=+0.41 – +0.42, p<0.05). Conclusions: This exploratory study indicates that neoadjuvant treatment alters the CRLM microenvironment, affecting tumor, vascular, and immune compartments. Additionally, analyses suggest that treatment induces a restructuring of their interdependence networks, defined by the loss of specific tumor-stromal-vascular links seen in untreated CRLMs, while establishing new ones. These findings motivate continued mechanistic studies and analyses on how these changes are related to benefits of treatment.
Influence of socioeconomic factors on patient-reported provider communication among patients with cancer.
12091 Background: Patient-provider communication is central to patient’s understanding and overall experience, particularly in multi-disciplinary cancer care. Socioeconomic disadvantages may amplify downstream consequences of poor communication by eroding trust and exacerbating structural and access-related barriers. Using nationally representative survey data, we examined the association between socioeconomic factors and patient-reported communication experiences among adult cancer survivors. Methods: We analyzed pooled 2011-2023 data from the US Medical Expenditure Panel Survey (MEPS) to identify adults (≥18 years) with a history of cancer. Patient-provider communication was assessed by how often providers (1) treated patients with respect, (2) listened carefully, (3) explained things in a way they understood, and (4) spent enough time. Survey-weighted estimates compared communication scores across income and insurance groups. Multivariable ordinal logistic regression (MVA) models including survey year, race/ethnicity, education, region, sex, marital status and age estimated adjusted odds ratios (aORs) for the association of income level and insurance with patient-provider communication. Results: Among 9,535 cancer survivors, those in the lowest income quintile (family income < federal poverty line (FPL)) reported the lowest rates of effective provider communication across all domains (57% listened, 53% time, 61% respect, and 57% explained). Survivors who reported being uninsured similarly reported the lowest rates of provider communication (50% listened, 43% time, 49% respect, and 51% explained). In adjusted analyses, lowest-income survivors were less likely than the highest income quintile survivors ( > 4×FPL) to report being listened to (aOR 0.76, 95% CI 0.63–0.91), respected (aOR 0.76, 95% CI 0.63–0.93), or receiving clear explanations (aOR 0.75, 95% CI 0.63–0.91). Compared with privately insured patients, uninsured survivors were less likely to report clear explanations (aOR 0.57, 95% CI 0.39–0.85), or feeling listened to (aOR 0.56, 95% CI 0.38–0.82). Both uninsured and Medicaid-insured survivors were less likely to report adequate time (uninsured: aOR 0.54, 95% CI 0.36–0.82; Medicaid: aOR 0.89, 95% CI 0.79–0.99), or feeling respected (uninsured: aOR 0.51, 95% CI 0.35–0.73; Medicaid: aOR 0.86, 95% CI 0.76–0.98). Conclusions: Lower income and lack of insurance were associated with worse communication among US cancer survivors. Given substantial financial, logistical, and personal burdens of cancer care, these communication gaps may weaken trust and undermine patients’ ability to understand and engage with recommended treatments. Targeted provider interventions aimed at improving clinician communication and care coordination will be essential to advancing equitable cancer care and rebuilding trust in an increasingly fractured healthcare system.
Uniportal versus multiportal video-assisted thoracic surgery (VATS) in esophageal cancer: A systematic review and meta-analysis.
e16114 Background: Minimally invasive approaches are increasingly used in esophageal cancer surgery, but the relative benefits of uniportal versus multiportal video-assisted thoracic surgery (VATS) remain unclear. This study aimed to compare perioperative outcomes, complications, and survival between the two approaches.To compare the perioperative outcomes, postoperative complications, and survival of uniportal versus multiportal VATS in patients undergoing esophagectomy for esophageal cancer.To evaluate whether uniportal VATS offers clinical advantages in pain reduction, hospital stay, and complication rates. Methods: A systematic review and meta-analysis was performed including studies comparing uniportal and multiportal VATS in patients undergoing esophagectomy. Primary outcomes were postoperative pain (POD1, VAS), overall postoperative complications (Clavien–Dindo grade I–II), length of hospital stay, mortality, and overall survival. Secondary outcomes included postoperative pneumonia, anastomotic leakage, and operative time. Effect sizes were pooled using a random-effects model and reported as mean difference (MD), odds ratio (OR), or hazard ratio (HR) with 95% confidence intervals (CI). Heterogeneity was assessed using I². Results: Uniportal VATS was associated with significantly lower postoperative pain on POD1 compared with multiportal VATS (MD −1.89, 95% CI −3.47 to −0.31, p = 0.019; I² = 99.1%). A trend toward fewer overall postoperative complications was observed (OR 0.51, 95% CI 0.24–1.10, p = 0.088; I² = 54.6%), while length of hospital stay was significantly shorter in the uniportal group (MD −1.22 days, 95% CI −2.15 to −0.29, p = 0.010; I² = 96.3%). No significant differences were found in mortality (OR 1.63, 95% CI 0.20–13.34, p = 0.65; I² = 0%) or overall survival (HR 1.07, 95% CI 0.51–2.24, p = 0.87; I² = 0%). Among secondary outcomes, uniportal VATS significantly reduced postoperative pneumonia (OR 0.48, 95% CI 0.26–0.88, p = 0.017; I² = 35.4%), while anastomotic leakage rates were comparable (OR 0.56, 95% CI 0.22–1.40, p = 0.21; I² = 0%). Conclusions: Uniportal VATS for esophageal cancer is associated with lower early postoperative pain, reduced length of hospital stay, and fewer postoperative pneumonias, with comparable mortality, anastomotic leakage, and long-term survival relative to multiportal VATS. These findings support the safety and potential perioperative benefits of the uniportal approach.
Uncovering prostate cancer and sepsis-related mortality shifts in the USA (1999-2020).
e17104 Background: Prostate cancer is a commonly diagnosed malignancy among men. Sepsis continues to pose a significant threat to outcomes. Patients with are particularly vulnerable to sepsis due to immunosuppression from the malignancy itself, advanced age, and treatment-related factors including catheter use. Sepsis is associated with high short-term mortality, and worsened overall outcomes, underscoring the need for epidemiological and clinical evaluation. Methods: We analyzed death certificates from 1990-2023 from CDC Wonder Database. We used ICD-10 codes, C61 for malignant neoplasm of prostate and C56 for sepsis to identify related deaths. Mortality rates were compared by urbanization, sex and census region. Joinpoint Regression Program V5.4.0 computed Annual Percent Change with 95% CIs. p value < 0.05 was considered statistically significant. Results: Between 1999 and 2023, 39,801 deaths were recorded. Overall age-adjusted mortality rates (AAMRs) changed little over time, remaining near 2 deaths per 100,000 population (2.02 in 1999 and 2.00 in the most recent year). Clear differences were seen across demographic groups.In 1999, AAMRs among Black or African American was highest with value of 6.80 compared to white and hispanic or latino individual with AAMR vales 1.67 and 1.89 respectively.In 2023, mortality among Black individuals fell to 5.06; however, rates were still higher than those seen among White (1.76) and Hispanic/Latino (1.92) populations. Geographic differences were also evident.The mortality rate in the South, decreasing from 2.43 in 1999 to 2.16 in 2023, was highest among all the other census regions.Mortality rates declined across both metropolitan and nonmetropolitan areas, falling from 2.02 to 1.84 in metropolitan regions and from 2.05 to 1.73 in nonmetropolitan regions in year 2020. Conclusions: Overall sepsis-related mortality has remained relatively unchanged over the two decades, with significant racial and geographic disparities. Black individuals continue to experience disproportionately higher mortality, and Southern region showed consistently elevated rates. Both metropolitan and non-metropolitan areas saw modest declines. These findings highlight the continued need for targeted preventive measures and management strategies to reduce mortality and improve outcomes. Prostate cancer with sepsis AAMRs. variable AAMR 1999 AAMR 2023 Overall / Male 2.02 (1.91-2.14) 2.00 (1.92-2.09) Race Black or African American 6.80 (6.04-7.56) 5.06 (4.60-5.53) White 1.67 (1.56-1.78) 1.76 (1.67-1.85) Hispanic or Latino 1.89 (1.39-2.50) 1.92 (1.65-2.20) Census Region Northeast 2.25 (2.00-2.51) 1.99 (1.80-2.18) Midwest 1.71 (1.50-1.92) 1.65 (1.49-1.81) South 2.43 (2.22-2.63) 2.16 (2.02-2.30) West 1.54 (1.33-1.76) 2.12 (1.94-2.30) Urbanization AAMR 2020 Metro 2.02 (1.90-2.15) 1.84 (1.75-1.93) Non-metro 2.05 (1.79-2.30) 1.73 (1.54-1.92)
Evaluating AFP–liver reserve discordance and microvascular invasion in resected and transplanted hepatocellular carcinoma.
e16262 Background: The prognosis of hepatocellular carcinoma (HCC) is influenced by tumor biology and liver function. Mismatch between tumor aggressiveness and liver function can obscure the accuracy of current risk stratification models especially when tumors occur in patients with preserved liver function. Alpha-fetoprotein (AFP) reflects aggressive tumor biology through association with larger tumor size, vascular invasion, and higher grading. MELD score reflects liver function and reserve in HCC patients by quantifying the liver dysfunction through various laboratory and liver function parameters. Despite the recognized importance of tumor characteristics and liver function, existing HCC staging systems have not defined the combined prognostic significance using AFP and MELD score. Methods: Among 366 patients (199 transplant, 167 resection), we evaluated whether preoperative AFP in relation to liver reserve was associated with microvascular invasion (MVI). Multivariable logistic regression included 276 patients (90 excluded due to missing data), adjusting for age, tumor diameter, multifocality, and locoregional therapy. Patients were stratified into four discordance phenotypes based on AFP ( > 40 ng/mL) and liver reserve (above or below median MELD). Interaction terms evaluated effect modification by surgery type. Secondary analyses addressed capsular/lymphatic invasion and tumor differentiation (proportional odds ordinal regression). Statistical analyses were performed in Python (statsmodels) with significance set at a two-sided p < 0.05. Results: Larger tumor diameter was independently associated with higher odds of MVI (OR 1.14 per cm; 95% CI 1.04–1.25; p = 0.005). Patients with a high-AFP/low-reserve phenotype showed higher odds of MVI (OR 1.96), though not statistically significant (p = 0.378), warranting further validation. There was no significant interaction between discordance phenotype and surgery type (all p > 0.30), indicating that the association between discordance phenotypes and MVI was similar in both resection and transplant cohorts. Surgery type showed a trend toward lower odds of MVI in transplant recipients (OR 0.41; p = 0.089). Conclusions: AFP–liver reserve discordance may refine risk stratification for microvascular invasion in HCC, as the association between these phenotypes and MVI risk was not significantly modified by surgery type. These findings support incorporating AFP-liver reserve phenotypes into a unified staging or risk framework to enhance prognostic accuracy in HCC beyond current AFP or MELD based models.
Prevalence and fracture burden of osteoporosis among patients with colorectal cancer: A real-world analysis.
11170 Background: Osteoporosis is a common age-related skeletal disorder that may be underrecognized among patients with colorectal cancer (CRC), despite shared risk factors including advanced age, systemic inflammation, nutritional deficiencies, and cancer-related treatments. Population-level data describing the prevalence, demographic distribution, and fracture burden of osteoporosis in CRC remain limited, particularly in real-world clinical settings. Methods: We conducted a retrospective, cross-sectional cohort study using the TriNetX Global Collaborative Network comprising over 180 million patients across 165 healthcare organizations using R. Adult patients aged 18–85 years with colorectal cancer were identified using ICD-10-CM codes C18–C20. Two cohorts were constructed: CRC patients with osteoporosis (defined by ICD-10-CM codes M80–M81) and CRC patients without osteoporosis. Osteoporosis subtypes were further categorized into osteoporosis with current pathological fracture (M80) and osteoporosis without current pathological fracture (M81). Cohorts were compared using aggregate-level demographic data, including age, sex, race, ethnicity, and fracture status. Results: Among 696,434 patients with colorectal cancer, 40,051 (5.7%) had a documented diagnosis of osteoporosis. CRC patients with osteoporosis were significantly older than those without osteoporosis (mean age 74 vs 68 years) and were predominantly female (79.2% vs 43.9%). Racial distribution among CRC patients with osteoporosis included White (56.7%), Black or African American (6.0%), Asian (6.8%), and other or unknown race (30.5%). Age-stratified analyses demonstrated a marked increase in osteoporosis prevalence with advancing age, particularly among patients aged ≥75 years. Among the CRC with osteoporosis cohort, 13% had documented osteoporosis with current pathological fracture (M80), while 87% had osteoporosis without fracture (M81), indicating a substantial fracture burden in this population. Age-related osteoporosis accounted for the majority of cases, with multiple fracture-related subcodes reflecting clinically significant skeletal fragility. Patient arrival rate analyses demonstrated sustained real-world healthcare utilization across participating institutions. Conclusions: In this large real-world cohort, osteoporosis was prevalent among patients with colorectal cancer and was strongly associated with advanced age and female sex. A clinically meaningful proportion of CRC patients with osteoporosis had documented pathological fractures, highlighting an underappreciated source of morbidity. These findings underscore the importance of routine bone health assessment and fracture risk evaluation in colorectal cancer care, particularly among older adults.
Trends in mortality involving esophageal cancer and alcohol-related behavioral disorders in the United States, 1999–2023.
e16071 Background: Esophageal cancer carries one of the highest mortality rates among solid tumors, while alcohol-related behavioral disorders (ARBD) represent a growing public health concern. Alcohol exposure is a known risk factor for esophageal cancer, yet national trends in mortality involving both conditions remain poorly defined. We evaluated long-term mortality patterns and disparities among U.S. deaths involving esophageal cancer and ARBD. Methods: Mortality data from the CDC WONDER Multiple Cause of Death database (1999–2023) were analyzed. Deaths involving esophageal cancer and ARBD were identified using ICD-10 codes. Age-adjusted mortality rates (AAMR) per 100,000 population were calculated overall and stratified by sex, age, race/ethnicity, U.S. census region, and urbanization. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals. Results: A total of 74,832 deaths involving both esophageal cancer and ARBD were identified. Overall AAMR increased from 0.12 in 1999 to 1.37 in 2023, representing a significant upward trend (AAPC 6.1%, p < 0.001). Mortality rose sharply between 2003 and 2018 (APC 9.4%, p < 0.001), followed by a modest decline after 2019. Males consistently had higher mortality than females (peak AAMR 2.54 vs 0.47). Older adults accounted for the highest absolute mortality, while middle-aged adults experienced the fastest relative increases (AAPC 7.3%, p < 0.001). Mortality rates were highest among White individuals, residents of the Midwest, and non-metropolitan populations. Conclusions: Mortality involving esophageal cancer and alcohol-related behavioral disorders has increased substantially in the United States over the past two decades, with pronounced disparities by sex, age, geography, and urbanization. These findings highlight a growing high-risk population and underscore the need for integrated cancer prevention, alcohol-use screening, and behavioral health interventions alongside oncologic care. Average annual percent change (AAPC) in mortality involving esophageal cancer and alcohol-related behavioral disorders, United States. Subgroup AAPC (%) 95% CI P value Overall 12.8 10.2–15.5 <0.001 Male 12.7 10.0–15.6 <0.001 Female 11.0 8.3–13.6 <0.001 Age ≥65 years 13.0 10.0–16.1 <0.001 White 14.2 11.8–16.8 <0.001 Black 6.5 3.9–9.2 <0.001 Midwest 12.6 3.6–22.5 0.005 Northeast 16.0 11.0–21.3 <0.001 Non-metropolitan 16.2 12.6–20.0 <0.001
Bone marrow metastasis in prostate cancer: Treatment feasibility and survival in a real-world cohort.
e17051 Background: Bone marrow metastasis (BMm) in prostate cancer (PCa) is a rare and life-threatening condition, typically presenting with severe cytopenias and limited therapeutic options. Owing to its rarity, real-world data on clinical presentation, treatment feasibility, and outcomes remain scarce. Methods: We retrospectively evaluated PCa patients with histopathologically confirmed BMm across four tertiary centers in Türkiye. Clinicopathological characteristics, laboratory findings, treatments administered after BMm diagnosis, and overall survival (OS) were analyzed. OS was calculated from the time of BMm diagnosis. Results: Among 3,129 screened patients with PCa, 36 (1.2%) had BMm. Most patients developed BMm during the castration-resistant phase (mCRPC; 77.8%), while 22.2% were in the hormone-sensitive phase (mHSPC). All cases were prostate adenocarcinoma, with no evidence of neuroendocrine differentiation. At BMm diagnosis, cytopenias were highly prevalent, including anemia in 91.4% (median hemoglobin 8.4 g/dL, IQR 7.7–9.4), thrombocytopenia in 83.3% (median platelet count 87×10³/µL, IQR 58–120.5), and leukopenia in 47.2% (median leukocyte count 4.0×10³/µL, IQR 3.0–4.75). Hemoglobin decline was the earliest laboratory abnormality in 69.4% of patients, whereas leukocyte counts were the last to decline in 77.7%. Following BMm diagnosis, 25 patients received systemic treatment, including chemotherapy (n = 16), ARPI (n = 8), or androgen deprivation therapy alone (n = 1), while 11 patients received best supportive care alone. Median overall survival (OS) for the entire cohort was 4.1 months (95% CI 2.4–5.7). Treated patients had significantly longer OS than untreated patients (9.1 vs 0.7 months, p < 0.001). OS was significantly longer in patients who developed BMm during the mHSPC phase compared with the mCRPC phase (10.2 vs 3.8 months, p = 0.038). At the time of BMm diagnosis, concomitant visceral metastases included lung metastases in 10 patients, liver metastases in 5, brain metastases in 4, and adrenal metastases in 2. On univariate analysis, the presence of brain metastasis at the time of BMm diagnosis was associated with a markedly inferior OS (HR 9.5, 95 %CI; 2.7-33.9, p < 0.001), while other visceral sites did not show a similar impact. No survival difference was observed according to the type of systemic therapy administered after BMm diagnosis. Conclusions: BMm defines an extremely high-risk disease state in PCa, characterized by early marrow failure and very limited survival. Although overall prognosis is poor, the marked survival difference between treated and untreated patients suggests that BMm does not uniformly preclude meaningful survival. Early recognition and individualized treatment decisions, particularly in the hormone-sensitive setting, may meaningfully influence outcomes in selected patients.
Quantifying the macroeconomic burden of cancer: Global disparities in value-of-lost-welfare (VLW).
10580 Background: Cancer (CA) remains a leading global driver of disability and premature death, yet its full macroeconomic toll is rarely quantified. In this study, we estimated the global economic welfare loss attributable to all cancers in 2023 across 183 countries using a standardized Value of Lost Welfare (VLW) framework. Methods: We obtained country-level disability-adjusted life years (DALYs) for CA from the Global Burden of Disease Study 2023. Corresponding GDP (PPP, current international dollars) and population data were sourced from the World Bank. We calculated VLW by multiplying DALYs by a fixed monetary value of USD 14,403.29 per DALY, yielding estimates of total VLW, per-capita VLW, and VLW/GDP (%). CA-specific estimates were derived using cause-wise DALY distributions across global and regional levels. Results: In 2023, CA caused 268.9 million DALYs globally, resulting in a global VLW of USD 3.87 trillion—equivalent to 2.12% of global GDP, with an average per-capita economic loss of 522 billion. The largest absolute economic losses were reported in China (915.5 billion), India (458.7 billion), and the United States, followed by Japan (126.7 billion) and Brazil (108.6 billion). When adjusted for national GDP, the highest VLW-to-GDP ratios were observed in Zimbabwe (4.24%), Cambodia (4.00%), Mongolia (3.45%), India (3.09%), and Egypt (1.63%), reflecting intense economic vulnerability. Across SDI strata, high-SDI countries bore the greatest economic burden, incurring a VLW of 1.80 trillion, followed by high-middle SDI (808.7 billion), low SDI (568.0 billion), low-middle SDI (406.5 billion), and middle SDI (384.9 billion). While absolute losses were highest in high-SDI settings, VLW/GDP ratios were notably elevated in low- and low-middle SDI regions, signaling disproportionate economic strain in resource-limited contexts. By CA type, lung CA led the global burden with 672 billion in welfare losses, followed by colorectal CA (377 billion), breast CA (355 billion), stomach CA (324 billion), and esophageal CA (202 billion). Conclusions: The global macroeconomic cost of CA surpassed USD 3.6 trillion in 2023, with marked disparities across countries and regions. High-burden nations such as China, India, and the U.S. faced the steepest absolute losses, while several low-income countries suffered disproportionately high economic strain relative to GDP. The concentration of losses in five major CA types signals an urgent need for enhanced global investments in CA prevention, early detection, and control. Regional cancer burden and economic losses in 2023. Region DALYs (Millions) VLW ($ Billion) VLW/GDP (%) Sub-Saharan Africa 28.82 415.14 6.64 South Asia 43.72 629.68 3.48 Southeast Asia, East Asia & Oceania 89.19 1284.6 2.76 North Africa & Middle East 14.34 206.6 2.50 Latin America & Caribbean 18.39 264.91 2.36 Central/Eastern Europe & Central Asia 20.89 300.85 2.20 High Income 60.37 869.53 1.25
Clinical outcomes of sequential androgen receptor pathway inhibitors (ARPIs) versus novel therapies in metastatic castration-resistant prostate cancer after progression on second-generation ARPIs: A systematic review and meta-analysis.
5075 Background: Most recent pivotal, randomized controlled trials (RCTs) testing novel therapies in ARPI pretreated mCRPC patients have incorporated sequential ARPI as the comparator. Given that sequential ARPI could be an inferior control arm based on CARD data, we conducted a meta-analysis to quantify the treatment effect of novel agents vs sequential ARPI and to evaluate whether sequential ARPI constitutes an appropriate control arm for future trials. Methods: A systematic search of PubMed, Europe PMC, and ClinicalTrials.gov up to August 14, 2025, identified 2,904 records. After removal of duplicates and exclusions, 17 RCTs met the inclusion criteria. Eligible studies enrolled patients with mCRPC who had progressed after prior exposure to second-generation ARPIs, comparing a novel agent (chemotherapy, targeted therapy, Immunotherapy and radioligands) with sequential ARPI treatment. Three independent reviewers screened the studies and extracted data in accordance with PRISMA guidelines. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the hazard ratios (HRs) were pooled using a random-effects model. Results: We included a total of 6,725 patients in this meta-analysis, with 3,579 (53.2%) receiving novel agents and 3,146 (46.8%) receiving ARPIs. Analysis revealed the pooled HR for OS was 0.86 (95% CI: 0.76–0.96; p<0.01). Substantial heterogeneity was observed (I2= 64.05%). This heterogeneity reflects the inclusion of trials with different novel agents and molecular selection criteria, with some highly selective trials (e.g., PROfound HR 0.58) showing greater benefit than others (e.g., ERA 223 HR 1.22). In addition, the pooled PFS analysis demonstrated a highly significant clinical advantage for novel therapies, resulting in a pooled HR of 0.72 (95% CI: 0.61–0.86; p<0.01). This PFS analysis exhibited very high heterogeneity (I2= 84.44%), driven by exceptional outcomes observed in trials targeting specific biomarkers. Conclusions: Across RCTs, novel therapies consistently outperform sequential ARPI for both OS and PFS in post-ARPI mCRPC. These pooled effects, and their amplification in biomarker-selected populations, suggest that sequential ARPI is a suboptimal control arm in this setting. Future trials should consider more appropriate, biomarker-driven or guideline-concordant active comparators, enabling fairer tests of clinical benefit and more generalizable results
A first-in-human phase I/II study evaluating CTS3497, an MTA-cooperative PRMT5 inhibitor, in advanced or metastatic <i>MTAP</i> -deficient solid tumors.
3115 Background: Protein arginine methyltransferase 5 (PRMT5) methylates multiple protein substrates with a variety of biological functions known to be dysregulated in cancer. CTS3497 is an orally available, brain-penetrable, MTA (methylthioadenosine) -cooperative PRMT5 inhibitor that preferentially targets the MTA-bound PRMT5 in MTAP (MTA phosphorylase) -deficient tumors and potently inhibits tumor growth in various preclinical models. Here we present clinical data from an ongoing Phase I/II study of CTS3497 in solid tumors (NCT06971523). Methods: Eligible pts with homozygous MTAP deletion (by next generation sequencing), or MTAP protein loss (by immunohistochemistry [IHC]) and advanced solid tumors in the dose-escalation stage received 50, 200, 300, 400 mg BID of CTS3497 orally, while pts in the dose-expansion stage were treated with 200, 300 or 400 mg BID until disease progression or intolerable toxicity. Efficacy, safety, PK, PD and biomarker profiles were evaluated. Results: As of 22 Jan 2026, 41 patients received ≥1 dose of CTS3497 treatment. No DLT was observed, and MTD was not reached; CTS3497 was well-tolerated. Most common (≥20%) treatment-related adverse events (TRAEs) were anemia (34%), white blood cell count decreased (32%), platelet count decreased (27%) and neutrophil count decreased (22%). The most common Grade ≥3 TRAE (occurring in ≥5% of patients) was platelet count decreased. No central nervous system (CNS) effects were reported. Among 21 centrally-confirmed MTAP-deficient, efficacy-evaluable patients, including 9 gastrointestinal (GI) cancers (ampullary cancer, biliary tract carcinoma, esophageal squamous cell carcinoma, gastric cancer and pancreatic ductal adenocarcinoma), 5 non-small cell lung cancer (NSCLC), 1 urothelial carcinoma and 6 rare cancers, the objective response rate (ORR) was 43%, and the disease control rate (DCR) was 91%. In GI cancers, the ORR and DCR were 56% and 89%. In NSCLC, the ORR and DCR were 60% and 80%. The exposures (Cmax, AUC0-24h) of CTS3497 increased in a linear, dose-proportional manner. The pharmacodynamic (PD) marker, plasma symmetric dimethylarginine (SDMA) level, showed a significant decrease. Conclusions: CTS3497 demonstrated a favorable safety profile and promising efficacy in heavily pretreated pts with MTAP-deficient advanced solid tumors, including GI cancers, NSCLC. Clinical trial information: NCT06971523 .
Association of expression of m6A-modified ACLY immunotherapy resistance and poor survival in head and neck cancer.
e18094 Background: N6-methyladenosine (m6A) is the most common internal RNA modification and plays a significant role in post-transcriptional gene regulation in cancer. Although metabolic reprogramming and m6A dysregulation are major characteristics of head and neck squamous cell carcinoma (HNSCC), the effects of m6A modification on metabolic enzyme–encoding genes, particularly on their function and immune responses, remain unexplored. Therefore, this study aimed to focus on the expression, prognostic significance, and m6A modification of ATP citrate lyase (ACLY), particularly their relationship to immunotherapy efficacy. Methods: The evaluation of ACLY expression, clinicopathological associations, and survival outcomes used transcriptomic and clinical data from the TCGA-HNSCC cohort. In silico MeRIP-seq data were used to assess m6A modification sites on ACLY mRNA and their correlation with m6A regulatory proteins. Independent HNSCC cohorts and experimental expression analyses were employed for validation. Functional enrichment, pathway analysis, immune cell infiltration profiling, and analyses of immune checkpoint–related gene signatures were performed to explore the biological and immunological roles of ACLY. Predictive immunotherapy response analyses were conducted to assess sensitivity to immune checkpoint blockade. Results: Compared with normal tissues, ACLY expression was significantly higher in HNSCC tumor tissues and correlated with advanced clinicopathological features and reduced overall survival. Conserved m6A modification sites in the ACLY transcript and a strong positive association with m6A regulators indicated m6A-dependent regulation. Altered ACLY expression was associated with changes in lipid and glucose metabolism, activation of oncogenic immune-related pathways, the presence of an immunosuppressive tumor microenvironment, and low predicted responsiveness to immune checkpoint inhibitor therapy. Conclusions: In conclusion, the present study demonstrates that m6A-modified ACLY is a key metabolic regulator associated with poor prognosis and resistance to immunotherapy in HNSCC, making it a candidate for both a prognostic biomarker and a therapeutic target.