Browse Articles

Endocrine stress phenotypes as drivers of extreme inpatient severity and resource utilization without increased mortality in cancer hospitalizations: National Inpatient Sample, 2018–2022.

e23201 Background: Endocrine complications during cancer hospitalization may reflect acute physiologic stress rather than chronic disease. Whether stress hyperglycemia and adrenal insufficiency function as high-acuity, resource-intensive inpatient phenotypes that amplify physiologic severity without increasing in-hospital mortality is incompletely characterized nationally. Methods: A serial cross-sectional, hospitalization-level analysis of the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample (NIS) was performed. Adult hospitalizations with a principal diagnosis of malignancy were identified using ICD-10-CM codes C00–C97 and D45–D47. Stress hyperglycemia was defined as hyperglycemia without diabetes, and adrenal insufficiency was identified via inpatient diagnosis proxies. Primary outcomes were All Patient Refined Diagnosis Related Group (APR-DRG) severity of illness subclass, an ordinal measure, and extreme severity defined as APR-DRG level 4. Secondary outcomes included mechanical ventilation as an ICU-level care proxy, length of stay (LOS), total hospitalization cost, and in-hospital mortality. Results: Stress hyperglycemia occurred in 2.09% of cancer hospitalizations and was associated with higher mean inpatient severity than the reference group (APR-DRG 3.02 vs 2.50). Extreme inpatient severity occurred in 30.97% of stress hyperglycemia hospitalizations compared with 15.64% in the reference group. After adjustment, stress hyperglycemia remained independently associated with higher inpatient severity (adjusted β 0.45, 95% CI 0.42–0.48) and increased odds of extreme severity (adjusted OR 2.25, 95% CI 2.06–2.45), and was associated with longer LOS (10.32 vs 6.64 days) and higher mean hospitalization cost ($48,257 vs $29,765). Adrenal insufficiency was similarly associated with increased inpatient severity (mean 2.98 vs 2.56) and greater odds of extreme severity (adjusted OR 2.04, 95% CI 1.47–2.85), along with increased mechanical ventilation utilization. Neither stress hyperglycemia (adjusted OR 1.05, p = 0.223) nor adrenal insufficiency (adjusted OR 1.23, p = 0.123) was independently associated with increased in-hospital mortality after adjustment. Conclusions: In U.S. cancer hospitalizations, endocrine stress phenotypes amplify physiologic severity and drive disproportionate resource use without increasing adjusted in-hospital mortality. This suggests stress hyperglycemia and adrenal insufficiency serve as administrative markers of acute inpatient vulnerability, with relevance to ICU capacity, LOS, and cost. Recognizing these phenotypes may improve inpatient risk stratification and guide earlier resource planning in oncology care.

Comorbidities and concomitant medication use in patients with TKI-naive, advanced, or metastatic ALK-positive NSCLC.

e20737 Background: Recommended therapies for anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) are ALK-tyrosine kinase inhibitors (TKI). We aimed to understand the challenges in patient management by evaluating comorbidities and medications observed before and after treatment initiation among TKI-naïve patients, receiving alectinib, brigatinib, or lorlatinib (i.e., 1L TKIs). Methods: Adult (≥18 years) patients treated with 1L alectinib, brigatinib or lorlatinib between 1/1/2020-12/3/2023 were identified in the Komodo Healthcare Map claims database. Patients had ≥6 months of continuous enrollment prior to and after the date of 1L initiation (i.e., index date [ID]). Comorbidities, concomitant medications and total medical costs were evaluated over the 6 months pre- and post-ID. Comorbidities and concomitant medications of interest were curated with clinician input. Comorbidities were identified by International Classification of Diseases, 10 th Revision codes and treatment. Concomitant medications were identified using the first 4 to 6 digits of the Generic Product Identifier. Analyses were descriptive. Results: 815 patients were included (mean age: 58.6 years) and median follow up days were 558, 577, and 480 for alectinib, brigatinib, and lorlatinib, respectively. The proportion of patients with evidence of hyperlipidemia slightly decreased post-ID in patients treated with alectinib (47.4% pre-ID; 41.7% post-ID) or brigatinib (34.0% pre-ID; 29.8% post-ID) and increased in patients treated with lorlatinib (47.3% pre-ID; 96.4% post-ID). Post-index changes in other select comorbidities, and use of concomitant medications are detailed in the table. Mean total medical costs decreased post-ID, from $11223 to $5090 for alectinib, $6997 to $3176 for brigatinib, and $7577 to $3421 for lorlatinib. Conclusions: Results showed a high burden of disease management prior to initiating 1L ALK-TKI therapy. Variability in changes to disease management burden were observed by 1L treatment choice, which may reflect differences in agent-specific tolerability profiles. These results highlight the importance of using a personalized approach to therapy. Comorbidities (all grade)/concomitant medications 1L AlectinibN=713 (87.5%) 1L BrigatinibN= 47 (5.8%) 1L LorlatinibN=55 (6.7%) Pre-ID, Post-ID% delta Pre-ID, Post-ID% delta Pre-ID, Post-ID% delta Elevated liver enzymes 4.2, 9.3 5.0 6.4, 19.1 12.8 7.3, 3.6 -3.6 Peripheral edema 8.3, 18.2 10.0 8.5, 12.8 4.3 5.5, 30.9 25.5 Peripheral neuropathy 15.7, 13.7 -2.0 23.4, 15.0 -8.5 16.4, 30.9 14.5 Anti-emetics 59.0, 32.8 -26.2 46.8, 44.7 -2.1 49.1, 20.0 -29.1 Benzodiazepines 24.8, 19.6 -5.2 38.3, 23.4 -14.9 18.2, 21.8 3.6 Antipsychotics/anti-manics 36.5, 18.9 -17.5 25.5, 34.0 8.5 32.7, 20.0 -12.7 Proton pump inhibitors 40.4, 27.6 -12.8 34.0, 36.2 2.1 49.1, 30.9 -18.2 Statins 29.6, 27.6 -2.0 21.3, 25.5 4.3 34.6, 78.2 43.6

Treatment modalities among long-term survivors of primary pulmonary NUT carcinoma: A systematic review and meta-analysis.

e20782 Background: Primary pulmonary NUT carcinoma (NC) is a rare, highly aggressive malignancy with a reported median overall survival of approximately 6.8–9.2 months. There are no FDA-approved targeted therapies, no consistently effective chemotherapy regimens, and no established standard-of-care or first-line treatment. Long-term survival in this disease is exceptionally rare, and treatment characteristics associated with durable outcomes remain poorly defined. Methods: We performed a systematic review and meta-analysis of published case reports and case series describing adult patients with primary pulmonary NC who achieved long-term survival, defined as survival ≥5 years following diagnosis. A comprehensive literature search of PubMed, Scopus, Embase, and Web of Science was conducted for studies published between January 2014 and March 2025. Extracted variables included age at diagnosis, disease stage, metastatic status, surgical management, radiation therapy, systemic treatment regimens, and survival outcomes. Descriptive statistics were used to summarize treatment patterns among long-term survivors. Results: Thirty-two long-term survivors met inclusion criteria. Median age at diagnosis was 23 years (interquartile range [IQR], 18–44). All patients presented with localized, non-metastatic disease at diagnosis. Definitive surgical resection was performed in all cases, with tumors deemed operable and completely resectable. Adjuvant and/or neoadjuvant radiation therapy was administered in 21 patients (65.6%). Systemic therapy was utilized in 18 patients (56.3%), most commonly in the perioperative setting. Chemotherapy regimens were heterogeneous but predominantly included platinum-based agents (72.2%) and ifosfamide-based combinations (44.4%), reflecting variability in baseline clinical characteristics and institutional practice patterns. Two patients (6.3%) received pembrolizumab as part of systemic therapy and achieved durable long-term survival. No long-term survivor had metastatic disease at initial presentation. Conclusions: Long-term survival in primary pulmonary NUT carcinoma is rarely observed in patients with localized, non-metastatic disease managed with complete surgical resection. Younger age at diagnosis and aggressive local control appear to be common features among long-term survivors. Further research is needed to optimize multimodal treatment strategies and reinforce the necessity of a multidisciplinary approach incorporating surgery, radiation, and systemic therapy in the management of this devastating malignancy.

Liraglutide may be associated with increased skin cancer risk: A propensity score-matched analysis.

e21504 Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used for type 2 diabetes (T2DM) and obesity but long-term oncologic safety data remain limited. In the LEADER trial, liraglutide-treated participants had numerically higher skin cancer rates than placebo. Later studies have yielded mixed results and largely evaluated GLP-1 RAs as a class. In this study, we aimed to evaluate agent-specific associations between individual GLP-1 RAs and skin cancer risk. Methods: Using the TriNetX Global network, we conducted a retrospective cohort study of adults aged ≥18 years with T2DM who was started on an FDA-approved GLP-1 RA (dulaglutide, exenatide, liraglutide, or semaglutide) or a comparator therapy (DPP-4 inhibitor [DPP-4i], SGLT2 inhibitor [SGLT2i], sulfonylurea, or thiazolidinedione [TZD]) between 2015-2020. Patients with a prior history of cancer were excluded. Propensity score matching was performed to balance baseline demographics, comorbidities, and medications. Primary outcome was the incidence of any predefined skin cancer (melanoma, squamous cell carcinoma [SCC], or basal cell carcinoma [BCC]) within 5 years from treatment initiation. Secondary outcomes included the incidence of each individual skin cancer subtype. Results: After propensity score matching, cohort sizes ranged from 14,802 to 59,748. Liraglutide was associated with a modestly higher melanoma risk across multiple active comparators and a higher total skin cancer risk versus SGLT2i (Table 1). No consistent association was observed with BCC, and SCC risk was lower versus DPP4i (Table 1). Dulaglutide, exenatide, and semaglutide were otherwise not associated with a statistically significant change in total skin cancer risk or individual subtypes, except for dulaglutide versus SGLT2i, which showed higher total skin cancer risk (HR 1.19; 95% CI 1.06–1.34). Conclusions: In this study, most GLP-1 RAs were not uniformly associated with risk of total skin cancer or major skin cancer subtypes. However, liraglutide was associated with a higher risk of melanoma across multiple active comparators. These findings suggest agent-specific heterogeneity in skin cancer risk within the class. Further studies are needed to validate these findings. Hazard ratios with 95% confidence intervals for each liraglutide comparison after propensity score matching. Comparison Total skin cancer Melanoma BCC SCC Liraglutide vs DPP4i 1.09 (0.99–1.21) 1.38 (1.09–1.75) 1.11 (0.85–1.47) 0.68 (0.49–0.96) Liraglutide vs SGLT2i 1.15 (1.02–1.29) 1.50 (1.13–1.99) 1.12 (0.81–1.56) 1.08 (0.70–1.66) Liraglutide vs Sulfonylurea 1.07 (0.95–1.20) 1.36 (1.04–1.79) 0.96 (0.71–1.28) 0.82 (0.54–1.24) Liraglutide vs TZD 1.11 (1.00–1.23) 1.35 (1.04–1.76) 1.00 (0.75–1.34) 0.85 (0.59–1.21)

Associations of race and obesity with mortality and cardiotoxicity in breast cancer.

e23304 Background: Racial disparities in mortality and cardiotoxicity among breast cancer patients remain insufficiently characterized. Prior studies have shown limited variation in overall cardiotoxicity, but the extent to which race and obesity independently influence specific cardiotoxic endpoints is still unclear. To address this gap, we evaluated the associations of race and obesity with mortality and cardiotoxicity outcomes in a large, diverse breast cancer cohort. Methods: We conducted a retrospective cohort study of 31,312 breast cancer patients diagnosed within Kaiser Permanente Southern California between 2007 and 2022. Mortality outcomes included all-cause, cancer-specific, and cardiovascular disease (CVD) mortality. Cardiotoxicity outcomes included congestive heart failure (CHF), cardiomyopathy, and major adverse cardiovascular events (MACE), with Percutaneous Transluminal Coronary Angioplasty and Coronary Artery Bypass Grafting procedures included. Associations of race and obesity with these outcomes were evaluated using Cox proportional hazards models adjusted for age, smoking status, tumor stage and grade, laterality, insurance type, and pre-existing cardiovascular comorbidities. Results: Asian (HR 0.66, 95% CI 0.59–0.73) and Hispanic patients (HR 0.85, 0.78–0.92) had lower all-cause mortality than Non-Hispanic White (NHW) patients, while underweight status increased risk (HR 2.06, 1.62–2.62) and overweight/Class I–II obesity had lower hazard. For cancer-specific mortality, Non-Hispanic Black (NHB) patients had higher risk (HR 1.21, 1.07–1.37), whereas Asian (HR 0.57, 0.49–0.68) and Hispanic patients (HR 0.80, 0.71–0.89) had lower risk. Asian (HR 0.52, 0.43–0.63) and Hispanic patients (HR 0.70, 0.62–0.80) also had lower CVD mortality. No racial differences were observed in CHF, but obesity showed a strong graded association, with Class III obesity conferring the highest CHF risk (HR 1.82, 1.51–2.20). For cardiomyopathy, NHB patients had higher risk (HR 1.40, 1.18–1.67) and Asian patients’ lower risk (HR 0.73, 0.58–0.93); obesity was not associated with cardiomyopathy. For MACE with procedures, Asian (HR 0.67, 0.61–0.74) and Hispanic patients (HR 0.86, 0.79–0.92) had lower hazards. Underweight status increased MACE risk (HR 2.03, 1.62–2.53), while overweight and Class I–II obesity had lower hazard (HRs 0.82–0.88). Conclusions: Mortality and cardiotoxicity risks vary meaningfully by race and body weight. NHB patients had higher cardiomyopathy and cancer-specific mortality, while Asian and Hispanic patients consistently demonstrated lower MACE and mortality risks. Clinicians should incorporate race-aware and weight-stratified risk assessment into survivorship care, with heightened vigilance for cardiomyopathy in Non-Hispanic Black patients and for CHF in patients with severe obesity.

Evolution of immune checkpoint inhibitor trials in oncology from 2011 to 2025: A cross-sectional study.

11048 Background: Immune checkpoint inhibitors (ICIs) have transformed the oncology therapeutic landscape since the first FDA approval in 2011. Over the past decade, ICIs have expanded rapidly across tumor types, disease settings, and therapeutic strategies. However, a comprehensive evaluation of the long-term evolution and key characteristics of global ICI clinical trials remains limited. We conducted a cross-sectional analysis to characterize temporal trends and fundamental features of ICI oncology trials registered on ClinicalTrials.gov from 2011 to 2025. Methods: All interventional oncology trials with a primary treatment purpose registered on ClinicalTrials.gov between January 1, 2011, and December 31, 2025, were included. ICI trials were defined as studies investigating agents targeting CTLA-4, PD-1, PD-L1, or next-generation immune checkpoints (e.g., LAG-3, TIGIT, TIM-3). Trials were categorized by phase, randomization, enrollment, funding source, geography, tumor type, treatment setting, and primary endpoints. Descriptive statistics summarized trial characteristics and temporal trends. Results: A total of 8,756 interventional treatment-purpose ICI trials were identified. Annual trial starts increased from 32 in 2011 to a peak of 955 in 2021, remaining consistently high thereafter (858 in 2022, 848 in 2023, and 817 in 2024), and reaching 940 in 2025. Most trials were Phase 2 (4,174/8,756; 47.7%), Phase 1 (1,756; 20.1%), or Phase 1/2 (1,374; 15.7%), while Phase 3 trials only accounted for 870 (9.9%) overall. The number of Phase 3 trials increased from 4 in 2011 to 100 in 2019, declined during 2020–2022, and subsequently rebounded to 101 in 2023, 110 in 2024, and a peak of 137 in 2025, reflecting ongoing maturation toward late-stage development. Funding was most frequently categorized as other (5,291; 60.4%), followed by industry (3,065; 35.0%) and US federal sources (400; 4.6%). The most common tumor groups were non–small cell lung cancer (NSCLC) (1,014; 11.6%), melanoma (579; 6.6%), breast cancer (498; 5.7%), and colorectal cancer (431; 4.9%). Among trials with available location data (n=8,152), the United States (4,173; 51.2%) and China (2,647; 32.5%) were the most frequent trial locations. Conclusions: Over the past 15 years, ICI clinical trials have expanded markedly in number and across tumor types; however, the majority remain early-phase, open-label, and small in scale, with Phase 3 studies comprising less than 10% of all trials. Encouragingly, the recent increase in late-phase trials suggests continued maturation of the immuno-oncology field and sustained progress toward regulatory approval. Persistent geographic concentration highlights the need to broaden global participation and strengthen the generation of confirmatory evidence to maximize the clinical impact of ICIs in cancer care.

Long-term trends and demographic disparities in renal cell carcinoma mortality in the United States, 1968–2023.

e16541 Background: Accounting for 2% of cancer diagnoses and deaths globally, renal cell carcinoma (RCC) is regarded as the 9th most commonly occurring malignancy in the United States (U.S.). Over the past few decades, the epidemiology of RCC has evolved in response to changes in population demographics, diagnostic practices, and exposure to established risk factors. We aimed to characterize long-term trends in RCC mortality and to examine temporal patterns across sex, race, and age groups. Methods: Data were obtained from the CDC WONDER Underlying Cause of Death database. RCC deaths were identified using ICD codes: ICD-8 code 189, ICD-9 code 189, and ICD-10 code C64. Age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000 population were calculated for adults aged 25 years and older from 1968 to 2023. Annual Percent Changes (APCs) and Average Annual Percent Changes (AAPCs) were computed using Joinpoint regression. Results: Between 1968 and 2023, RCC accounted for 579,290 deaths. From 1968 to 1979, AAMR increased non-significantly (APC: 0.37%), followed by a significant rise from 1979 to 1991 (APC: 1.34%). A non-significant decline occurred between 1991 and 2002 (APC: −0.12%). Thereafter, AAMR declined significantly from 2002 to 2015 (APC: −0.86%), with a further significant decrease from 2015 to 2019 (APC: −2.41%). No significant change was observed from 2019 to 2023 (APC: −0.07%). Overall, a non- significant decline in AAMR was observed across the full study period (AAPC: −0.05%). Gender-based analysis revealed that males had a higher average AAMR (8.5) compared with females (3.8). From 1968 to 2023, AAMR declined significantly among females (AAPC: −0.22%), whereas a non-significant increase was observed among males (AAPC: 0.04%). Compared with the Black population (5.3), the White population had a higher average AAMR (6.0). Over the study period, AAMR increased significantly among the Black population (AAPC: 0.22%), whereas a non-significant decline was observed among the White population (AAPC: −0.03%). Age-group stratification using age-specific CMR revealed that CMR declined significantly among individuals aged 25–34 years (AAPC: −0.85%), 35–44 years (AAPC: −1.22%), 45–54 years (AAPC: −0.97%), 55–64 years (AAPC: −0.55%), and 65–74 years (AAPC: −0.22%). In contrast, CMR increased significantly among those aged 75–84 years (AAPC: 0.31%) and 85 years and older (AAPC: 1.43%). Conclusions: RCC mortality demonstrated substantial temporal heterogeneity across sex, race, and age strata. Declining trends were observed among females and younger individuals, whereas the Black population and adults aged ≥75 years experienced increasing mortality. Continued monitoring of RCC mortality is warranted to guide targeted prevention, improve treatment equity, and reduce persistent disparities.

Impact of postsurgical circulating tumor DNA (ctDNA) dynamics on eligibility of colorectal cancer (CRC) patients for randomized ALTAIR trial: Implications for treat-on-molecular-recurrence (TOMR) trials.

3628 Background: Postsurgical ctDNA positivity is strongly associated with recurrence risk and is driving the development of TOMR trials like the phase III ALTAIR trial (NCT04457297), which evaluated the benefit of trifluridine/tipiracil versus placebo in CRC patients (pts) with ctDNA positivity in the absence of clinical relapse. We evaluated the impact of longitudinal ctDNA dynamics during adjuvant chemotherapy (ACT) and surveillance on eligibility for enrollment into ALTAIR. Methods: CIRCULATE-Japan’s GALAXY (UMIN000039205) study screened clinical stage II-IV CRC pts receiving standard-of-care (SOC) perioperative chemotherapy for eligibility for interventional trials by ctDNA monitoring using the personalized, tumor-informed Signatera assay in plasma collected at 1, 3, 6, 9, 12, 18, and 24 months (mos) post-surgery. Pts with ctDNA positivity without clinical recurrence were eligible for ALTAIR within 3 months of detection. We analyzed ctDNA dynamics and eligibility across all GALAXY sites, extending prior analyses limited to ALTAIR-participating sites. Results: Of 5,355 pts enrolled by April 2023, 693 (12.9%) were ctDNA-positive 2–10 weeks post-surgery (MRD-positive). Of 378 MRD-positive pts who received ACT, 117 (31.0%) remained persistently positive, 76.1% of whom did not relapse within 3 mos. ctDNA cleared after ACT in 237 pts, but 122 (51.5%) reconverted to positive, 67.2% of whom remained relapse-free for ≥3 mos after reconversion. Among 1,341 MRD-negative pts receiving ACT, 183 (13.6%) converted to ctDNA-positive, 123 (67.2%) of whom remained relapse-free for ≥3 mos after molecular relapse. Overall, 17.1% of GALAXY pts met ALTAIR ctDNA-based criteria with stage-specific eligibility rates of 13.2% (II), 14.7 % (III), and 34.6 % (IV). Overall, 243 (4.5%) were enrolled in ALTAIR, including 18.6% of MRD-positive and 2.4% of MRD-negative pts. Conclusions: Approximately one-third (123/334) of ALTAIR-eligible pts were initially MRD-negative and later converted to ctDNA-positive without early clinical relapse, highlighting the importance of longitudinal ctDNA monitoring in TOMR trial design. When compared to the previous analysis limited to ALTAIR-participating sites, we observed higher eligibility yet lower enrollment rates in the full cohort at all GALAXY sites, underscoring the need for broader access and efficient enrollment networks to optimize TOMR trials. Clinical trial information: NCT04457297 . ctDNA dynamics MRD positive(N = 378) MRD negative(N = 1,341) Persistently positive, all 117 (31.0%) NA Persistently positive, eligible for ALTAIR 89 (23.5%) NA Transient clearance, all 122 (32.2%) NA Transient clearance, eligible for ALTAIR 82 (21.7%) NA Turned positive, All NA 183 (13.6%) Turned positive, eligible for ALTAIR NA 123 (9.2%)

A network meta-analysis of efficacy and safety of neoadjuvant anti-HER2 treatments in HER2-positive early breast cancer.

e12636 Background: Neoadjuvant treatment options for HER2-positive early breast cancer are continuously evolving, including chemotherapy combined with either single or dual HER2-targeted antibodies or HER2-targeted antibody–drug conjugate (ADC), leading to improved pCR rates and long-term survival outcomes. However, the relative efficacy and safety of these regimens still need to be further clarified. This study aims to compare the efficacy and safety of single versus dual HER2-targeted antibodies and ADCs, as well as to conduct comparative analysis across these regimens. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for phase III randomized controlled trials (RCTs). Eligible RCTs must include at least two of the following interventions as neoadjuvant therapy: TH, THP, TCbHP, AC-THP, T-DM1+P, or T-DXd-THP. Outcomes were pCR, event-free survival (EFS), and grade ≥3 or severe adverse events. Data were extracted independently by two reviewers; risk of bias was assessed using Cochrane RoB 2. A Bayesian network meta-analysis with fix-effects model estimated odds ratio (OR), hazard ratio (HR), and treatment rankings using SUCRA. Results: Six phase III RCTs comprised of 3,287 patients with HER2-positive early breast cancer were included in our study. The results showed a superior pCR rate of regimens incorporating dual HER2-targeted antibodies or ADCs, including T-DXd-THP (OR 3.07, 95% CI 1.42–6.75), THP (OR 2.34, 95% CI 1.39–4.05), and TCbHP (OR 2.05, 95% CI 1.16–3.70), comparing to TH in the overall population. The SUCRA analysis showed that T-DXd-THP ranked highest for pCR rate (0.95), indicating the greatest probability of being the most effective regimen, followed by THP (0.77), TCbHP (0.55). In HR-negative patients, T-DXd-THP (OR 5.17, 95% CI 1.13–24.09) and THP (OR 3.85, 95% CI 1.79–8.91) had a significant pCR rate benefit comparing to TH, with T-DXd-THP ranked highest in SUCRA (0.93). Additionally, T-DXd-THP (OR 3.52, 95% CI 1.13–11.29) demonstrated a significant pCR rate improvement compared to TCbHP. In terms of EFS, T-DXd-THP showed a consistent trend towards improved outcomes compared with other dual HER2-targeted therapies, in line with its highest SUCRA ranking (0.95). Compared to TH, both AC-THP and TCbHP showed a higher risk of grade≥3 anemia, grade≥3 neutropenia, and serious adverse events (SAEs). Notably, T-DXd-THP demonstrated a lower risk of grade≥3 anemia and grade≥3 neutropenia compared to TCbHP or AC-THP. TCbHP showed a higher risk of grade≥3 vomiting compared to THP (OR 7.69, 95% CI 2.88–27.09). Conclusions: Neoadjuvant therapies with dual HER2-targeted antibodies or ADCs provide superior pCR rates compared to single anti-HER2 antibodies for HER2-positive early breast cancer. T-DXd-THP demonstrated the greatest therapeutic effectiveness among all regimens while maintaining a well-balanced safety profile.

Antibiotics and immune-related toxicity during pembrolizumab therapy in NSCLC: Real-world analysis.

e20637 Background: Antibiotic exposure around immune checkpoint inhibitor (ICI) therapy has consistently been associated with inferior clinical outcomes, likely mediated by disruption of the gut microbiome and downstream immune dysregulation. While microbiome composition has been linked to ICI-related colitis, the impact of antibiotics on organ-specific immune-related toxicities remains incompletely characterized, particularly for renal and endocrine adverse events in non–small cell lung cancer (NSCLC). Methods: We conducted a retrospective cohort study using a large U.S. electronic health record network. Adults with NSCLC treated with pembrolizumab were identified. The primary exposure cohort included patients receiving any systemic antibiotic within ±2 weeks of a pembrolizumab dose; controls had no antibiotic exposure within 1 month of pembrolizumab and low ECOG performance status. Propensity score matching (1:1) adjusted for demographics, comorbidities, smoking-related diagnoses, chemotherapy exposure, concomitant medications (including proton pump inhibitors and corticosteroids), and available laboratory values. Outcomes were assessed after matching using Kaplan–Meier analyses and Cox proportional hazards models, reported as hazard ratios (HR) with 95% confidence intervals (CI). Results: Among 5,690 antibiotic-exposed and 7,371 control patients, 2,381 well-balanced matched pairs were analyzed. Median follow-up was shorter in the antibiotic cohort (329 vs 511 days). Despite shorter follow-up, increased hazards of early-onset toxicities were observed, including acute kidney injury (AKI; HR 1.45, 95% CI 1.20–1.75; log-rank p < 0.001) and adrenal insufficiency (HR 2.67, 95% CI 1.78–4.01; log-rank p < 0.001). Modest associations were observed for unspecified colitis (HR 1.47, 95% CI 1.09–1.97; log-rank p = 0.010), while toxic colitis showed a borderline increase (HR 1.37, 95% CI 1.00–1.89; log-rank p = 0.053). No significant differences were observed for thyroiditis, dermatitis, gastrointestinal bleeding, acute liver failure, or composite ICI-linked diagnoses. Findings were similar using a broader ±1-month antibiotic exposure window in sensitivity analyses. Conclusions: In matched NSCLC patients receiving pembrolizumab, antibiotic exposure near treatment was associated with increased hazards of renal and endocrine immune-related toxicity, with weaker associations for colitis. These results extend prior microbiome–ICI literature beyond efficacy and gastrointestinal toxicity, supporting a microbiome-mediated, organ-specific toxicity hypothesis and highlighting the importance of antibiotic stewardship and enhanced renal and endocrine monitoring during ICI therapy.

A phase I, multi-center study of KIVU-107, a novel PTK7-targeting antibody-drug conjugate (ADC), in participants with advanced solid tumors.

TPS3158 Background: Protein tyrosine kinase 7 (PTK7) is a transmembrane pseudokinase involved in normal embryonic development and has been associated with tumor initiation, metastasis and therapeutic resistance in cancer. PTK7 is over-expressed in multiple solid tumors, including lung, head and neck, breast, ovarian and endometrial cancers. KIVU-107 is an antibody-drug conjugate (ADC) comprised of a PTK7-targeting antibody conjugated to the SYNtecan E linker-payload via the GlycoConnect/Hydraspace (GC/HS) site-specific conjugation technology with a drug-to-antibody ratio of 4. 1,2 The GC/HS platform abolishes Fcγ receptor-mediated effector activity and utilizes a highly polar spacer to reduce hydrophobicity and aggregation of the ADC, translating into improved safety and pharmacokinetic profiles. 1,2 KIVU-107 has demonstrated potent anti-tumor efficacy as a single agent and in combination across multiple preclinical tumor models, including regression in tumors refractory to chemotherapy or ADCs. 1,2 Moreover, KIVU-107 is highly stable and well tolerated in non-human primates. 1,2 Methods: This Phase 1, multi-center, open-label, dose-finding and dose-expansion study is designed to investigate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of KIVU-107 in patients with select advanced solid tumors. The Dose Finding stage will employ Backfill Bayesian Optimal Interval (BF-BOIN) design to establish the maximum tolerated dose (MTD) and recommended dose for expansion (RDE). Eligible participants for the Dose Finding stage include those with advanced solid tumors known to be enriched for PTK7 overexpression and that have exhausted available standard-of-care (SOC) treatments including non-small cell lung, small cell lung, head and neck squamous cell carcinoma, breast, endometrial, ovarian and others. The Dose Expansion stage will further explore the safety, tolerability and preliminary efficacy in disease-specific cohorts relapsed or refractory to SOC therapies. The primary endpoints include safety, tolerability, and determination of MTD and RDE for KIVU-107. Secondary and exploratory endpoints include PK, immunogenicity, preliminary clinical activity and biomarker assessments. Enrollment for Dose Finding has initiated. Clinical trial information: NCT07229313. 1) Trikha M. Striving for Kinder and Gentler ADCs: Spotlight on Solid Tumor Target and Preclinical Development of KIVU-107. Presented at: 16 th World ADC San Diego; November 4, 2025; San Diego, CA. 2) Viller V, Zhang L, Jiang X, et al. Preclinical Efficacy and Safety of KIVU-107, a Novel PTK7-Targeting Antibody-Drug Conjugate (ADC). Poster presented at: 16 th World ADC San Diego; November 5, 2025; San Diego, CA. Clinical trial information: NCT07229313 .

3D object detection for vehicle-mounted LiDAR based on deep learning and euclidean clustering algorithm

Object Detection (OD) stands as a fundamental task in the area of autonomous driving environment perception. This study introduces a 3D OD method grounded in deep learning and an improved Euclidean clustering algorithm, aiming to improve the accuracy and efficiency of point cloud segmentation and OD. The core methodological innovations include: (1) the integration of the Cloth Simulation Filter (CSF) for accurate ground and non-ground point separation, combined with a K-Dimensional Tree (KD-Tree) structure and an adaptive parameter mechanism to enhance clustering robustness and efficiency; and (2) an enhanced PointNet architecture incorporating multi-scale grouping (MSG), multi-resolution grouping (MRG), and skip connections to improve local feature extraction and multi-level feature fusion. This method is differentiated from prior works by its holistic integration of density-aware segmentation and hierarchical feature aggregation, addressing key bottlenecks in handling sparse and uneven LiDAR data. The proposed method is rigorously evaluated on the KITTI and NuScenes benchmarks. It achieves segmentation accuracies of 94.96% and 93.12%, with single-frame processing times of 15.63 ms and 17.24 ms, respectively, demonstrating a superior balance of speed and precision compared to traditional Euclidean clustering and other baseline methods. For the 3D OD task, the model attains average detection accuracies of 94.36% and 92.68% on the respective datasets, representing statistically significant improvements ( p  < 0.001) over the standard PointNet. The detection speed reaches 34 fps and 31 fps, meeting real-time requirements while outperforming existing frameworks in challenging scenarios involving occluded and multi-scale objects. The findings confirm that the proposed framework provides a robust, efficient, and generalizable solution for 3D environmental perception in autonomous driving systems.

Preferential enhancement of high-rate performance in LiNi0.5Mn1.5O4 cathodes via improved ion transport kinetics and structural stability

Spinel LiNi0.5Mn1.5O4 (LNMO) cathodes offer significant potential for grid-scale energy storage, combining the merits of low cost and a high voltage plateau (∼4.7 V vs Li+/Li). However, they still suffer from rapid capacity decay, especially at high C-rates, due to confined ion transport kinetics and severe structural instability upon cycling. Herein, we incorporated fluorine into LNMO and found that F− incorporation induces an increase in the Mn3+ ratio and disorder degree in the lattice, promoting the expansion of interplanar spacing for fast ion transport and the optimization of structural stability for performance improvement. The as-obtained F− incorporated cathodes exhibit preferential enhancement of high-rate performance at 2C and 5C compared to low-rate performance at 0.5C and 1C. Moreover, this work clarifies the importance of the Mn3+ coordination environment for the structural stability of LNMO and highlights the potential of LNMO cathodes for fast-charging applications.

Green synthesis of ZnO nanoparticles using semi- conductor biosolid for ammonium removal from synthetic municipal wastewater

A Kinetic‐Thermodynamic Synergy to Enhance {110} Texture for Stable Lithium Metal Anodes

ABSTRACT Lithium metal anodes (LMAs) are critical for developing next‐generation high‐energy‐density batteries, while uncontrolled dendrite growth and low Coulombic efficiency hinder their practical application. Engineering the crystallographic texture during lithium (Li) deposition to favor the {110} orientation is a promising strategy to suppress dendrite formation and improve performance. Here, we present a synergistic approach that combines deposition thermodynamics and kinetics to achieve a dominant {110} texture. By depositing Li on a lithiophilic tin (Sn)‐modified copper substrate at a high current density, the alloying reaction between Li and Sn yields a deposition interlayer composed of Sn and Li─Sn intermetallics that regulates both Li diffusivity and adsorption during initial deposition. Two‐dimensional Li nucleation and planar growth in larger grain sizes are achieved, thereby minimizing the total surface energy and promoting {110} texture formation. This effect, coupled with the kinetic selection of fast‐growing {110} planes, triples the volume fraction of the desired {110} texture while suppressing the competing {111} counterpart. When paired with a LiFePO 4 cathode, the resulting full cell exhibits stable cycling under practical conditions of a low negative‐to‐positive ratio and a lean electrolyte loading. This co‐regulation of deposition thermodynamics and kinetics offers a novel and effective strategy for fabricating high‐performance, dendrite‐free LMAs.

Thermal efficiency of a ferrofluid in a horizontal channel with non-uniform magnetic fields and curved heat sources: a computational study

Phosphorylation of RBM39 by CDK13 stabilizes RAD50 mRNA to drive cisplatin resistance in endometrial cancer

The investigator-initiated trial (IIT) of GO306 injection, a recombinant oncolytic vaccinia virus, in patients with advanced soft tissue sarcomas.

11564 Background: Oncolytic vaccinia viruses exert anti-tumor effects via direct lysis and systemic immunity induction. Advanced soft tissue sarcomas (STS) are heterogeneous malignancies with limited post-standard therapy options. GO306 is a oncolytic virus expressing PD-1/TGFβ inhibitors for tumor-selective replication and enhanced immunity. We report GO306’s preliminary safety and tolerance in pretreated advanced STS. Methods: This open-label, single-arm IIT enrolled histologically confirmed advanced STS refractory to standard therapy. A 3+3 dose-escalation design was used, with intratumoral GO306 at 3×10 7 PFU, 3×10 8 PFU and 1×10 9 PFU. A 21-day DLT assessment period was set. Tumor assessment was done on day 28 per RECIST v1.1. Primary endpoints: MTD, DLTs, safety; secondary endpoints: OS, ORR, PFS, immunogenicity, viral shedding. Results: As of Dec 5 th , 2025, 10 participants were enrolled across 3 dose cohorts, 9 completed the 21-day DLT assessment (1 non-DLT withdrawal). Demographics: median age 52.4 years, 80% male, ECOG 1-2. No DLTs were observed; MTD not reached. A total of 110 AEs were reported, including 52 treatment-related adverse events (TRAEs), 98.8% (51/52) were grade 1-2, with 1 grade 3 pulmonary infection (SAE due to prolonged hospitalization). No grade 4-5 TRAEs occurred. Most common AEs: pyrexia (60%, grade 1-2), followed by hypokalemia, hypocalcemia and hypoalbuminemia (40% each, grade 1-2). Efficacy was evaluable in 8 participants: 87.5% (7/8) SD and 12.5% (1/8) PD. Survival data: 2 participants with OS＞5 months, 1 alive at 260 days (all received subsequent anti-tumor therapies), 2 with 90-day survival documented. Viral shedding: GO306 was below the limit of quantification (BLQ) in feces, urine, throat swabs, and plasma on day 3/7, undetectable on day 30 (some samples pending). PD-1 inhibitor was detectable in 6/10 participants (29.91~19073.64 ng/mL); TGFβ inhibitor in 7/10 participants (80.39 to 460.31 ng/ml). Conclusions: Intratumoral GO306 showed favorable safety profile and manageable TRAEs in pretreated advanced STS. Preliminary efficacy support phase I/II expansion and combination studies with other immunotherapies or targeted therapies. Clinical Trial Registration Number: ChiCTR2400088508. Xianhai Zhu and Hu Liu contributed equally as corresponding author. Clinical trial information: ChiCTR2400088508. Demographic and overall response of participants. Screen No. Age Gender ECOG Malignancy Diagnosis Overall Response* S002 60 M 1 Retroperitoneal Liposarcoma SD S003 59 F 2 Liposarcoma SD S006 70 M 1 Leiomyosarcoma SD S007 60 M 2 Retroperitoneal Liposarcoma PD S010 48 M 1 Retroperitoneal Leiomyosarcoma SD S011 48 M 1 Retroperitoneal Leiomyosarcoma SD S012 56 M 1 Chondrosarcoma SD S013 30 M 1 Synovial Sarcoma SD Abbreviations: *Per RECIST V1.1; 8/10 enrolled participants had evaluable day-28 tumor assessments and are included.

Phase 3 study (APROMISS) of catequentinib hydrochloride (AL3818) monotherapy in patients with advanced alveolar soft part sarcoma (ASPS).

11502 Background: To report results from the open-label alveolar soft part sarcoma (ASPS) cohort of the phase III APROMISS trial (NCT03016819) evaluating Catequentinib hydrochloride (AL3818), an oral multitargeted receptor tyrosine kinase inhibitor, in adults with advanced or metastatic ASPS. Methods: Adult patients with pathologic and molecularly confirmed advanced ASPS, either treatment-naive or previously treated (excluding cediranib), were enrolled in the open-label, non-randomized ASPS cohort of the phase III APROMISS trial conducted across the United States, Asia, and Europe. Catequentinib hydrochloride was administered orally at 12 mg once daily in 21-day cycles (14 days on/7 days off) until disease progression, toxicity, or death. The primary endpoint was objective response rate (ORR) assessed per RECIST by Blinded Independent Central Review (BICR) (predefined threshold: 31%). Secondary endpoints included duration of response (DOR) with a predefined target of =/>6 months, progression free survival (PFS) and overall survival (OS). Results: From July 2017 to August 2022, a total of 56 patients entered the trial; 56 patients were evaluable for the primary endpoint. Median (m-) age was 29.5 years (range: 18 – 66), with 24 female and 32 male. Best overall response included 1/56 complete response (1.8%), 14/56 partial responses (25.0%), 36/56 stable disease (64.3%), and 3/56 (5.4%) progressive disease. RECIST ORR by BICR was 26.8% (95% CI, 15.8–40.3); m-DOR was 22.57 months (95%CI: 10.38-NE). The study data was collected close to 8 years for all patients. mPFS was 18.33 months (95% CI, 14.19–23.13), with 6- and 12-month progression-free rates of 88.77% (95% CI, 76.68–94.79) and 65.54% (95% CI, 50.42–77.06), respectively. mOS was 59.27 months (95% CI, 44.09–NE), with 6- and 12-month overall survival rates of 94.64% (95% CI, 84.30–98.24) and 90.81% (95% CI, 79.30–96.08), respectively. Overall, 27/56 (48.2%) patients experienced grade ≥3 treatment-related adverse events, most commonly diarrhea (50.0%), hypertension (44.6%), fatigue (37.5%), nausea (35.7%), and palmar-plantar erythrodysesthesia syndrome (30.4%); one patient (1.8%) had a grade 5 event (respiratory failure). Conclusions: Catequentinib hydrochloride demonstrated meaningful antitumor activity and durable responses in adults with advanced ASPS. Despite the ORR of 26.8% slightly below the predefined 31% threshold, disease control was prolonged, with a m-DOR exceeding 22 months. Favorable PFS and OS outcomes, together with a manageable safety profile, support its clinical benefit in this ultra-rare sarcoma. Clinical trial information: NCT03016819 .

Nodal station–mapped recurrence patterns after neoadjuvant immunochemotherapy and R0 esophagectomy for esophageal squamous cell carcinoma.

e16121 Background: Neoadjuvant immunochemotherapy (nICT) followed by R0 esophagectomy is increasingly used for resectable esophageal squamous cell carcinoma (ESCC), yet nodal-station–level lymph node (LN) failure patterns are unclear and total harvested LNs (TLN) may not reflect lymphadenectomy adequacy. We applied AJCC 8th-edition station mapping and an in-field/out-of-field framework to characterize LN relapse and assess associations with tumor regression grade (TRG) and nodal burden. Methods: Multicenter retrospective cohort from a prospectively maintained database (six centers). Consecutive ESCC patients underwent nICT and R0 esophagectomy (Jan 2022–Dec 2024). Response: Mandard TRG good (1–2) vs poor (3–5). LN metrics included dissection extent (TLN; regional and station counts), metastatic burden (positive LNs [PLN]; positive regions/stations), and relapse localization (LN recurrences mapped to region/station and labeled in-field vs out-of-field). DFS was time from surgery to first recurrence or death; OS from surgery to death. Survival was assessed using Kaplan–Meier/log-rank and Cox models. Results: Among 259 patients (median follow-up 26 months), 85 (33.0%) developed recurrence; 79 were localizable. Local recurrence occurred in 45/79 (57.0%) and distant metastasis in 45/79 (57.0%), including 11/79 (13.9%) with concomitant local and distant events. Out-of-field relapse occurred in 51/79 (64.6%) and in-field relapse in 37/79 (46.8%); 9/79 (11.4%) had both. Poor responders had higher recurrence (42.7% vs 17.8%, P = 0.0002) and mortality (25.6% vs 11.0%, P = 0.0042) than good responders. TLN (continuous) was not associated with DFS or OS. Each additional PLN increased the risk of DFS events (HR 1.05, 95% CI 1.01–1.08; P = 0.0082) and death (HR 1.05, 95% CI 1.01–1.09; P = 0.0132). Exploratory station-level analyses suggested heterogeneous signals (e.g., station 16 protective; 2R/2L, 8M/8Lo, and station 20 unfavorable), likely confounded by tumor burden, location, and surgical strategy. Conclusions: After nICT and R0 esophagectomy for ESCC, relapse was predominantly out-of-field. TLN did not predict outcomes, whereas TRG and nodal burden—and hypothesis-generating station patterns—better stratified risk, supporting station-informed, response-adapted postoperative surveillance and adjuvant decision-making.