Browse Articles

Early integrated rehabilitation and risk of distant metastases in breast cancer patients: A prospective controlled study.

e12701 Background: Integrated rehabilitation improves quality of life in breast cancer patients, but its impact on long-term outcome of disease is unclear. The aim of our study was to find out whether early initiation of integrated rehabilitation is associated with a lower incidence of distant metastases. Methods: The subjects of our prospective study were 553 female non-metastatic invasive breast cancer patients (26-65 (mean 52) years of age), who participated in the pilot study on the individualized integrated rehabilitation of breast cancer patients in 2019-2022. The patients completed three questionnaires (EORTC QLQ - C30, B23 and NCCN): before, six and twelve months after the beginning of cancer treatment. The control group included 278 patients and the intervention group 275 patients. The control group obtained the same rehabilitation as was offered to all breast cancer patients in our hospital before the start of our study. The multidisciplinary rehabilitation team reviewed the documentation of all the patients from the intervention group before, six and twelve months after the beginning of treatment and recommended appropriate interventions according to the patient's problems. The integrated rehabilitation coordinator referred patients for additional treatments in compliance with the institute’s new clinical pathway (psychologist, general practitioner, nutritional treatment, physical rehabilitation, kinesiologist-guided online exercises, gynaecologist, analgesia, vocational rehabilitation). Data on the patients’ demographics, disease extent, cancer treatment, distant dissemination and distant disease-free survival were collected. This data were analysed using the chi-square and ANOVA test. Distant disease-free survival and disease-specific survival were estimated using the Kaplan–Meier method, and between-group differences were assessed using the Cox proportional hazards model. Adjustment for tumor subtype and type of systemic therapy was not performed. Results: There were no differences between the control and the intervention group of patients in terms of age, education, disease extent, surgical procedures, systemic cancer treatment, radiotherapy, or disease-specific survival. The follow-up period ranged from 1 to 72 (median 57) months. Distant metastases occurred in 3% of the intervention group and 7% of the control group. Distant disease-free survival was 97% in the intervention group and 94% in the control group (HR = 0.43, 95% CI 0.19-0.98; p = 0.04). Conclusions: Early integrated rehabilitation is associated with longer distant disease-free survival compared to the control group. These findings suggests that early individualised integrated rehabilitation may contribute not only to improved quality of life but also to favourable long-term oncological outcomes.

A phase 1/2 study of the next-generation nectin-4–targeting antibody-drug conjugate CRB-701 (SYS6002) in patients with recurrent or metastatic cervical cancer.

5508 Background: CRB-701 is a next-generation Nectin-4–targeted monomethyl auristatin E (MMAE)-based antibody–drug conjugate with differentiated safety, efficacy and pharmacokinetics compared with other agents in the same class. As previously reported, CRB-701 demonstrated antitumor responses independent of Nectin-4 expression levels in solid tumors, notably in patients with heavily pretreated head and neck squamous cell carcinoma (HNSCC) and cervical cancer, as well as those with urothelial carcinoma. Here, we provide data from this phase 1/2 trial in patients with cervical cancer enrolled in dose escalation (part A) and dose optimization (part B) (NCT06265727). Methods: Patients with recurrent or metastatic (R/M) cervical cancer who had received ≥ 1 line of therapy were enrolled. Part A employed a Bayesian Optimal Interval design with four doses (1.8, 2.7, 3.6 and 4.5 mg/kg; each every 3 weeks [Q3W]) to determine the maximum tolerated dose. In part B, the pharmacologically active dose range identified in part A was evaluated using a time-to-event Bayesian optimal phase 2 design. Patients were randomized 1:1 to receive CRB-701 at 2.7 or 3.6 mg/kg Q3W. The primary endpoints for parts A and B were dose-limiting toxicities and objective response rate (ORR), respectively. Safety, tolerability and pharmacokinetics were also assessed. Nectin-4 expression was evaluated retrospectively. Results: As of September 2025, 54 patients with cervical cancer had enrolled across parts A and B. At the time of data cut, most patients were awaiting a confirmatory scan. The unconfirmed ORR was 22.2% (4/18 evaluable patients) at the 2.7 mg/kg dose and 37.5% (6/16 evaluable patients) at the 3.6 mg/kg dose. Confirmed partial responses were observed in 1/18 participants at the 2.7 mg/kg dose and 3/16 patients at the 3.6 mg/kg dose. One patient had a confirmed complete response at the 2.7 mg/kg dose. The safety profile of CRB-701 was broadly consistent with earlier findings: keratitis, anemia, alopecia, fatigue and dysgeusia were the most frequently reported treatment-emergent adverse events (≥ 15% of overall solid tumor population [N = 167]). An expanded efficacy analysis reporting an additional 6 months of follow-up, including ORR, duration of response and progression-free survival, will be presented at the congress. Subgroup analyses by treatment history and disease extent will also be presented. Conclusions: CRB-701 has shown promising efficacy in patients with R/M cervical cancer, as well as a favorable safety profile compared with other MMAE-based therapies. Ongoing evaluation of CRB-701 will determine its potential as a new treatment option for this patient population. Clinical trial information: NCT06265727 .

Safety and objective response of KRAS G12C inhibitors versus docetaxel in previously treated advanced NSCLC: Meta-analysis of randomized trials.

e20747 Background: Patients with previously treated KRAS G12C–mutated advanced non–small cell lung cancer (NSCLC) have limited standard options, with docetaxel remaining a commonly used therapy after progression on platinum-based chemotherapy and immunotherapy. KRAS G12C inhibitors have demonstrated antitumor activity in this setting, but their comparative efficacy and treatment tolerability versus docetaxel across randomized trials remain clinically relevant. We conducted a systematic review and meta-analysis to compare objective response rate (ORR) and treatment discontinuation due to treatment-related adverse events (TRAEs) between KRAS G12C inhibitors anddocetaxel. Methods: A systematic search was conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2025 to identify randomized controlled trials comparing KRAS G12C inhibitors versus docetaxel in patients with previously treated advanced or metastatic KRAS G12C–mutated non–small cell lung cancer. Three study reports/datasets were included, comprising a total of 912 patients. Eligible studies reported objective response rate (ORR) and/or treatment discontinuation due to treatment-related adverse events (TRAEs). Pooled analyses were performed using random-effects models, and results were expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Results: Three study reports/datasets were included. For objective response rate (ORR), KRAS G12C inhibitors were associated with significantly higher tumor response compared with docetaxel (RR 2.90; 95% CI 1.72–4.89; P < 0.0001; I² = 44%), with a total of 165 responses among 550 patients in the KRAS G12C inhibitor group versus 38 responses among 362 patients receiving docetaxel. Regarding treatment tolerability, discontinuation due to treatment-related adverse events (TRAEs) was significantly more frequent with KRAS G12C inhibitors compared with docetaxel (RR 1.78; 95% CI 1.02–3.13; P = 0.04; I² = 0%), corresponding to 45 discontinuations among 545 patients in the KRAS G12C inhibitor group versus 15 discontinuations among 327 patients in the docetaxel group. Conclusions: KRAS G12C inhibitors demonstrate significantly higher objective response rates compared with docetaxel in previously treated KRAS G12C–mutated advanced NSCLC, supporting superior antitumor activity in this setting. However, treatment discontinuation due to TRAEs was also significantly more frequent with KRAS G12C inhibitors, highlighting an important tolerability trade-off that may impact treatment delivery in clinical practice. These findings emphasize the need to balance response benefit with toxicity-related interruption, and underscore the importance of time-to-event outcomes and patient-centered endpoints to guide optimal sequencing strategies.

Association of Palmar-plantar erythrodysesthesia syndrome (PPES), hypothyroidism, and clinical outcomes in previously treated endometrial cancer (EMC) with pMMR status: A subgroup analysis of FRUSICA-1.

e17612 Background: FRUSICA-1(NCT03903705) is an open label, single-arm, pivotal phase II study, demonstrated the promising efficacy and favorable safety of fruquintinib (F) + sintilimab (S) in previously treated advanced EMC patients (pts) with pMMR status, with objective response rate (ORR): 35.6%; median progression-free survival (mPFS): 9.5mo; median overall survival (mOS): 21.3mo (Wu X, et al; 2024 ASCO). PPES and hypothyroidism are two common adverse events in the combination therapy of angio-genesis tyrosine kinase inhibitors and PD-1 antibody. Researches have indicated patients with PPES may experience better treatment outcomes in various cancer types. Immune related adverse events (irAE) were also deemed as predictor of response in gynecologic cancers. Therefore, we launched a subgroup analysis of the treatment outcome in patients who developed PPES or hypothyroidism in FRUSICA-1. Methods: EMC pts with centrally confirmed pMMR status who progressed after ≤ 2 platinum-based systemic therapy were treated with F (5mg QD orally, 2w on/1w off) + S (200mg IV, Q3W), in a 3-week cycle until disease progression or unaccepted toxicity. Patients who developed PPES or hypothyroidism were extracted and the efficacy analysis was then conducted accordingly. Results: As of 15th May 2024, 98 eligible pts were enrolled and evaluated with a median follow-up of 22.0 mo (95%CI: 20.5, 23.7). In the full analysis set (FAS), 38 (38.8%) pts experienced PPES, 45 (45.9%) experienced hypothyroidism. Assessed by independent review committee (IRC), Patients who developed PPES showed numerically higher efficacy with an ORR 47.4% (95% CI: 31.0, 64.2), DCR 92.1% (95% CI: 78.6, 98.3), mPFS and mOS not reached (NR), 15-mo PFS rate 60.7% (95% CI: 39.3, 76.6), 24-mo OS rate 59.3% (95% CI: 40.5, 73.9). Patients who had irAE hypothyroidism, also showed a higher efficacy, with an ORR 44.4% (95% CI: 29.6, 60.0), DCR 93.3% (95% CI: 81.7, 98.6), mPFS 16.6 mo (95% CI: 6.9, 27.4), mOS 24.0 mo (95% CI: 17.7, NR), the maturity of PFS and OS were 53.3% (24/45) and 46.7% (21/45). Conclusions: In FRUSICA-1 study, PPES and irAE hypothyroidism may be associated with higher ORR, longer PFS and OS in advanced EMC patients. PPES and irAE hypothyroidism could potentially be predictive of clinical outcomes for pts with treatment with fruquintinib plus Sintilimab. Clinical trial information: NCT03903705 .

Pathologic response and surgical conversion after preoperative docetaxel, cisplatin, and oral 5-FU with or without PD-1 inhibitors in resectable HNSCC: A retrospective cohort study.

e18072 Background: Induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) has been widely used in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but its clinical utility is often limited by substantial toxicity. A modified regimen consisting of docetaxel, cisplatin, and oral tegafur–uracil (DCU) has been adopted as a more tolerable alternative. Immune checkpoint inhibitors have demonstrated a survival benefit in recurrent or metastatic HNSCC (KEYNOTE-048) and have shown promising efficacy in the perioperative setting (KEYNOTE-689), providing a rationale for exploring adding chemotherapy to perioperative pembrolizumab for resectable HNSCC, based on the KEYNOTE-689 study results. Methods: We conducted a retrospective cohort study of patients resectable HNSCC who received DCU-based induction chemotherapy at Linkou Chang Gung Memorial Hospital between August 2024 and December 2025. A total of 59 patients were included, of whom 37 received DCU alone and 22 received pembrolizumab plus DCU (PDCU). Outcomes included progression-free survival (PFS), overall survival (OS), pathological and clinical responses, conversion to definitive surgery, and treatment-related adverse events (AEs) graded according to CTCAE v5.0. Results: Patients treated with PDCU showed numerically longer PFS and OS compared with those receiving DCU alone; however, no statistically significant differences were observed. Pathologic complete response (pCR) was achieved in 33% in the PDCU group, whereas no pCR was observed in the DCU group. In addition, a higher proportion of patients treated with PDCU underwent definitive surgery compared with those receiving DCU alone (41% vs. 14%), with higher clinical response rates. Treatment-related AEs were generally manageable in both groups, and the addition of pembrolizumab did not result in a marked increase in severe toxicity. Those who did not accept surgery proceeded from concurrent chemoradiotherapy with the following maintenance therapy with pembrolizumab or oral tegafur-uracil for a one-year course (ongoing). Conclusions: In this real-world cohort of patients with resectable HNSCC, induction DCU demonstrated acceptable efficacy and tolerability. The addition of pembrolizumab was feasible and associated with higher pCR rates and increased conversion to surgery. These findings warrant further investigation of pembrolizumab-based induction strategies with longer follow-up and larger prospective studies.

See Her Screen Her: An opportunistic VIA screening and HPV vaccination among female patient attendants at a tertiary cancer care center in a low-resource setting.

e22518 Background: Cervical cancer remains one of the major causes of cancer mortality in low- and middle-income countries (LMICs) like Bangladesh, largely due to advanced stage at presentation, which is the result of low uptake of screening and HPV vaccination. This low uptake of screening is not only due to lack of access, but also due to fear, time constraints, inertia, and low risk perception. Female patient attendants at tertiary hospitals represent a large population with frequent hospital visits. Their hospital waiting time can be a natural setting for contextual nudges that reduce friction and increase preventive care uptake. We incorporated behavioral nudged-based strategies into an opportunistic visual inspection by acetic acid(VIA) screening, which is a very cost-effective option for cervical cancer screening in low resource setting, and HPV vaccination for female patient attendants visiting the oncology outpatients department, converting their waiting time into cervical cancer prevention time. Methods: We conducted a prospective, single-arm implementation study among female patient attendants aged 30-60 years attending outpatient departments, including chemotherapy day-care and radiotherapy waiting room at Ahsania Mission Cancer and General Hospital, from January,2025 to December,2025. Eligible female attendants were counseled and offered to do on-site VIA screening, which is free of cost. VIA-positive women navigated to colposcopy and biopsy accordingly. HPV vaccination was offered to eligible VIA-negative women, and they were encouraged to bring their other female relatives to do the same. The primary outcome was screening uptake, and the secondary outcomes were VIA positivity rate, detection of cervical intraepithelial neoplasia (CIN), invasive cervical cancer diagnosis, and HPV vaccination rate. Results: Over 12 months,2100 female attendants were approached, of whom 1680(80%) underwent VIA screening. VIA positivity was found in 420 women (25%).355 (85%) VIA-positive women completed their colposcopic evaluation. Among them, 60 women were found to have CIN I and CIN II. 10 patients were diagnosed with invasive cervical carcinoma. Among the VIA-negative women eligible for vaccination, 612 received at least 1 dose of HPV vaccine. This intervention substantially increased screening and vaccination coverage compared to the previous years. Conclusions: Opportunistic VIA screening with further navigation and HPV vaccination among female patient attendants is a feasible, effective, and scalable cervical cancer prevention strategy in low resource setting like Bangladesh. Implementing this novel strategy in other centers can meaningfully improve cervical cancer early detection and elimination efforts without additional infrastructure, stuffing and financial burden.

Impact of baseline severe cytopenia on post–BCMA CAR T-cell therapy outcomes in multiple myeloma: A propensity-matched multicenter study.

e19527 Background: Severe cytopenias are common in relapsed/refractory multiple myeloma (MM) and may influence outcomes after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy. However, comparative real-world data describing subsequent cytopenias and acute toxicities among patients with pre-index severe cytopenia remain limited. This study is one of the first real-world attempts to evaluate the association between baseline severe cytopenia and post–BCMA CAR-T cytopenia and toxicity outcomes in a propensity score–matched (PSM) MM cohort. Methods: We conducted a retrospective, propensity score–matched, multicenter cohort study using the US Collaborative Network (TriNetX). Adults with MM who received BCMA-directed CAR T-cell therapy (idecabtagene vicleucel or ciltacabtagene autoleucel) between January 1, 2021 and January 1, 2025 were included. Patients were stratified by presence versus absence of severe cytopenia within 3 months on or before MM diagnosis (Hb≤8 g/dL, absolute neutrophil count ≤0.50×10^3/µL, or platelets ≤50×10^3/µL). The index date was defined as first fulfillment of cohort eligibility. Outcomes were assessed beginning 30 days post-index without a prespecified end date. PSM (1:1, nearest neighbor) balanced prior transplant, chemotherapy exposure, and baseline laboratory parameters. Outcomes included post–CAR T cytopenias (individual and prolonged), hospitalization, and cytokine release syndrome, hemophagocytic lymphohistiocytosis, and immune effector cell–associated neurotoxicity syndrome. Risks were compared using measures of association, and time-to-event outcomes were analyzed using Kaplan-Meier methods with log-rank testing and hazard ratios with 95%CI. Results: After matching (n = 81 per cohort), mean age was 67.7±9.7 vs 66.8±8.8 years, with 60.5% vs 63.0% male patients. Median follow-up was 312 days (severe cytopenia) vs 191 days (no severe cytopenia). The severe cytopenia cohort had higher risk of anemia (29.6% vs 13.6%; RD 16.0%, p = 0.013) and prolonged cytopenia (40.7% vs 23.5%; RD 17.3%, p = 0.018). Time-to-event analyses showed increased hazard for anemia (HR 2.15, 95% CI 1.05–4.41; log-rank p = 0.032) and for prolonged cytopenia (HR 1.83, 95% CI 1.04–3.22; log-rank p = 0.032). Risks of neutropenia, thrombocytopenia, hospitalization, and CRS/HLH/ICANS were not significantly different (all RD p > 0.05; log-rank p > 0.15). Conclusions: In this propensity-matched real-world MM cohort receiving BCMA CAR-T, pre-index severe cytopenia was associated with higher subsequent rates and earlier onset of anemia and prolonged cytopenia beginning 30 days post-index, without a detectable increase in hospitalization or CRS/HLH/ICANS. These data support enhanced cytopenia monitoring and proactive supportive care strategies in patients presenting with severe cytopenia prior to CAR-T.

Efficacy and safety of durvalumab with or without tremelimumab in metastatic NSCLC: A meta-analysis of randomized controlled trials.

e20568 Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Non–small cell lung cancer (NSCLC) comprises 80–85% of cases, and despite therapeutic advances, stage IV disease carries a poor 5-year survival rate below 10%. While immune checkpoint inhibitors have improved outcomes, the benefit of combining PD-L1 and CTLA-4 blockade remains uncertain. This meta-analysis aimed to evaluate the safety and efficacy of combined therapy in metastatic NSCLC. Methods: A comprehensive search of PubMed, Embase, and Cochrane Central was performed through May 2025 for randomized controlled studies (RCTs) assessing durvalumab alone or in combination with tremelimumab in advanced NSCLC. Outcomes of interest included overall survival (OS), analyzed using hazard ratios (HRs), and immune-related adverse events (irAEs), analyzed using odds ratios (ORs). Effect estimates were pooled using random-effects models and heterogeneity was assessed using Cochrane Q and I². When no direct comparisons were available, individual patient data were reconstructed from the original study Kaplan–Meier survival curves using the IPDfromKM method, with log-rank testing and Cox regression applied. Statistical analyses were performed in R version 4.5.0 with the meta package. Results: Three RCTs enrolling 2,726 patients met inclusion criteria. Of these, 891 (32%) were allocated to the durvalumab group and 884 (34%) to the durvalumab + tremelimumab group, whereas 891 (32%) were allocated to chemotherapy. Combined analysis showed no significant OS benefit with durvalumab plus tremelimumab compared to durvalumab alone (HR 0.97; 95% CI, 0.74–1.27). Pooled analysis of irAEs demonstrated significantly higher risks in the tremelimumab-containing arms: enterocolitis (OR 3.95; 95% CI, 1.71–9.11), pneumonitis (OR 2.25; 95% CI, 1.02–4.98), rash (OR 2.31; 95% CI, 1.28–4.16), thyroid disorders (OR 1.48; 95% CI, 1.02–2.16), and adrenal insufficiency (OR 2.97; 95% CI, 1.10–8.02). Conclusions: In metastatic NSCLC, the addition of tremelimumab does not confer a statistically significant OS advantage in unselected populations and is associated with a toxicity increase. Benefits may be restricted to biomarker-defined subgroups, but these findings remain exploratory. Further prospective studies are needed to clarify the optimal role of CTLA-4 blockade in combination immunotherapy. Characteristics of included studies. Trial Patients, No. Females, No. (%) Age ≥ 65, No. (%) ECOG, % 0/1 SCC, No. (%) ARCTIC a 126 36 (28.57) 56 (44.44) 40.5/59.5 32 (25.4) ARCTIC b 469 161 (34.32) 221 (47.12) 32.3/67.6 114 (24.31) MYSTIC 1118 346 (30.95) 248 (50.82)d 40.9/58.8 320 (28.62) POSEIDON 1013 243 (23.99) 477 (47.09) 33.4/66.5 374 (36.92) ECOG=Eastern Cooperative Oncology Group; SCC=Squamous cell carcinoma. a = PD-L1 ≥ 25%. b = PD-L1 <25%.

An immune-related pathologic response score as a predictor of survival after immune checkpoint inhibitor–based conversion therapy in hepatocellular carcinoma.

4162 Background: Immune checkpoint inhibitor (ICI) based conversion therapy is increasingly utilized in the management of initially unresectable hepatocellular carcinoma (HCC). However, the clinical significance of immune-related pathologic response (irPR) features remain poorly understood in HCC. Methods: We enrolled 217 HCC patients undergoing ICI-based conversion therapy followed by curative-intent resection and assigned them to discovery and validation cohorts (2:1). Thirteen immune-related pathological response (irPR) features—tumor-infiltrating lymphocytes, tertiary lymphoid structures, lymphoid aggregates, plasma cell infiltration, granulomas, neutrophils, foamy macrophages, cholesterol clefts, hemosiderin-laden macrophages, giant cells, neovascularization, necrosis, and mature fibrosis—were assessed on H&E-stained tumor bed sections. To explore differences in the tumor microenvironment, bulk mRNA sequencing was performed on FFPE samples from patients in the discovery cohort. Results: In the discovery cohort, four irPR features (tumor-infiltrating lymphocytes, lymphoid aggregates, neutrophils, and foamy macrophages) were integrated to construct the immunotherapeutic response score (ITRS), classifying patients as ITRSlow (0–1) or ITRShigh (2–4). ITRS low patients showed significantly improved OS (HR = 4.17; 95% CI 1.64–10.60; P = 0.003) and RFS (HR = 2.07; 95% CI 1.32–3.23; P = 0.001), with longer median RFS (32.3 vs 8.5 months). ITRS remained independently associated with OS (HR = 2.81; 95% CI 1.06–7.43; P = 0.038) and RFS (HR = 2.10; 95% CI 1.32–3.33; P = 0.002) and was validated in an independent cohort. FFPE transcriptomic profiling (n = 41) showed that ITRS low tumors were immune-inflamed, with enrichment of immune-related GO/KEGG pathways and globally higher immune/stromal infiltration (higher ESTIMATE immune/stromal scores, lower tumor purity; all P < 0.001). Unsupervised clustering identified hot/cold states, with hot tumors enriched in ITRS low (65.4% vs 13.3%, P = 0.003); CD8 + T-cell infiltration was higher across MCPcounter/CIBERSORT/TIMER and was accompanied by stronger antigen presentation (MHC-II gene sets) and increased CD8 + T-cell activation/cytotoxicity as well as exhaustion signatures (all P < 0.05), supporting an immune-active microenvironment linked to favorable outcomes. Conclusions: An irPR feature–based ITRS robustly predicts both OS and RFS in HCC patients following ICT. The ITRS is readily applicable in routine diagnostic pathology practice and provides novel insights into the biological mechanisms underlying immunotherapy resistance.

Association of caregiver and patient burden with ALK-positive advanced non–small cell lung cancer in Germany, the United Kingdom, and the United States.

e20768 Background: Patients with advanced NSCLC (aNSCLC) can experience significant disease burden with respect to symptoms, side effects and impairments to daily living activities. Thus, many patients require caregiver support. This study investigated the caregiver and patient burden associated with ALK-positive (ALK+) aNSCLC across Germany (DE), the United Kingdom (UK), and United States (US). Methods: Data were drawn from the Adelphi NSCLC Disease Specific Programme: a cross-sectional survey of 162 oncologists/pulmonologists in DE, UK and US, between Dec 2023-May 2024. Physicians provided information for up to nine consecutively consulting patients; six who were diagnosed with aNSCLC, one with a confirmed ALK mutation, and two with a confirmed ALK mutation who received 1 st line brigatinib treatment. Across these samples, physician-reported data was provided for 587 ALK+ patients, of which 127 patients voluntarily completed a survey. All analyses were descriptive. Results: Of patients with aNSCLC who were ALK+ (n=587; DE:167; UK:225; US:195), the median age was 65 years, majority of patients were male (52%) and stage IVA at aNSCLC diagnosis (60%). The majority of patients (59%) did not require additional support, while partner/spouse (29%) was the most common source of additional care. Patient’s received a median (IQR) of 15.0 (5.0, 20.0) hours of care per week from their partner/spouse (n=88). Table 1 shows physician-reported caregiver and patient burden data. In the patient-reported data (n=127; DE: 88; UK: 21; US: 18), patients reported that their aNSCLC most severely impacted their ability to work (24% severe or very severe). Need for caregiver support was reported by 42% of patients, received for a median (IQR) of 20.0 (14.2, 40.0) hours per week. The most common activities requiring caregiver support were transportation and meal preparation (both 28%). Conclusions: Patients with ALK+ aNSCLC who required assistance relied heavily on partners or spouses, who provided substantial weekly care. Patient-reported impacts on work and everyday function highlight the meaningful burden on both patients and caregivers, reinforcing the need for treatment strategies that lessen symptom and functional challenges to reduce caregiver demands. Physician-reported caregiver and patient burden data, overall n=587. Activities of daily living (ADL) requiring help from caregiver(s), n (%) Housecleaning + home maintenance Shopping + meal preparation Transportation Other ADL Unknown n=18895 (51%)90 (48%)77 (41%)103 (55%)41 (22%) Most common (Top 3) aNSCLC symptoms at time of data collection, n (%) Cough Fatigue Dyspnoea n=534359 (67%)260 (49%)195 (37%)

A phase II study of ubenimex combined with pembrolizumab, nab-paclitaxel, and carboplatin for previously untreated advanced squamous non–small cell lung cancer: TORG2241(UBE-Q).

8559 Background: Pembrolizumab plus platinum-based chemotherapy is a standard first-line treatment for previously untreated advanced squamous non-small cell lung cancer (NSCLC) based on the KEYNOTE-407 trial. Ubenimex, an oral CD13/aminopeptidase inhibitor, has immunostimulatory and antitumor activity. We conducted a phase II trial to assess the safety and efficacy of ubenimex in combination with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. Methods: This study was a prospective, multicenter, single-arm phase II trial. Eligible patients with previously untreated advanced squamous NSCLC received ubenimex orally plus 4 cycles of pembrolizumab, nab-paclitaxel, and carboplatin, followed by continuous administration of ubenimex and pembrolizumab for a maximum of 2 years. To confirm tolerability, the daily dose of ubenimex started at level 1 (30mg/day), which was increased to levels 2 (60 mg/day) and 3 (120 mg/day) according to the escalation criteria, with a standard 3 + 3 design for achieving the target dose-limiting toxicity (DLT) rate of 33%. The efficacy, safety, and tolerability of ubenimex at the determined dose level were analyzed. The primary efficacy endpoint was objective response rate (ORR) by independent central review, estimated descriptively with a 90% confidence interval; the ORR in the KEYNOTE-407 (62.6%) served as a reference value for study design. Results: No DLTs were observed across dose levels 1–3. Therefore, level 3 was selected as the recommended dose. From January 2024 to January 2025, 28 patients were enrolled from 18 institutions, and all patients were evaluable for efficacy and safety. Baseline characteristics were male/female 25/3; median age 72 (range, 40-86); ECOG PS 0/1 12/16. The ORR was 71.4% (90% CI, 54.3-84.9). With a median follow-up of 12.8 months, median progression-free survival (PFS) was 16.8 months (95% CI, 5.6-not reached); median overall survival (OS) was not reached. Grade 3/4 adverse events included pneumonitis (3.6%), anemia (46.4%), febrile neutropenia (10.7%). There was no treatment-related death. Conclusions: Ubenimex with 120 mg/day (60 mg twice daily) combined with pembrolizumab, nab-paclitaxel, and carboplatin was feasible and showed encouraging antitumor activity with manageable safety in previously untreated advanced squamous NSCLC, supporting further randomized evaluation. Clinical trial information: jRCT2031210707.

Palliative care utilization in patients with <i>EGFR</i> -mutant metastatic non-small cell lung cancer receiving first-line <i>EGFR</i> TKIs.

e24076 Background: Patients with metastatic EGFR -mutant NSCLC experience prolonged survival with EGFR tyrosine kinase inhibitors (TKIs), particularly in the osimertinib era. Despite extended disease trajectories, the timing and frequency of palliative care (PC) involvement in this population remain poorly characterized. In contrast to chemotherapy-treated NSCLC cohorts, where early PC integration is common, patients receiving oral targeted therapy may experience delayed or absent PC referral due to perceived clinical stability. We evaluated patterns of palliative care utilization and associated clinical characteristics in a real-world EGFR TKI cohort at a single academic institution. Methods: We conducted a retrospective cohort study of 112 patients with EGFR -mutant metastatic NSCLC who initiated first-line EGFR tyrosine kinase inhibitor (TKI) therapy at Northwell Health between 2012 and 2025. Primary outcome was receipt of a formal palliative care consultation. Secondary outcomes included timing of referral relative to treatment initiation and death. Logistic regression was used to identify factors associated with palliative care referral, adjusting for age (≥75 vs &lt; 75 years), ECOG performance status (0-1 vs ≥2), baseline brain metastases, and first-line EGFR TKI. Results: Among 112 patients (median age 72), only 28 patients (25%) received palliative care referrals. Referral was more common among patients aged ≥75 years (54% vs 31%, p = 0.035). In multivariable analysis, age ≥75 remained independently associated with referral (OR 2.68, 95% CI 1.04-7.10, p = 0.04), while ECOG ≥2 (p = 0.52), brain metastases (p = 0.54), and TKI choice (p = 0.46) were not significant predictors. Median time to referral was 70.9 weeks (IQR 13.2-99.6) after first-line TKI initiation. Nine of 28 referrals (32%) occurred after second-line therapy initiation. Among 28 deceased patients, 15 (53.5%) received referral within 90 days of death. Even among 30 patients achieving ≥3 years survival, 24 (80%) never received palliative care referral and referral rates remained low across age groups ( &lt; 75 years: 13.6%; ≥75 years: 37.5%) and brain metastasis status (absent: 17%; present: 28.6%). Conclusions: Palliative care referral in EGFR -mutant metastatic NSCLC was infrequent and often occurred late in the disease course, with referral patterns more strongly associated with age than functional status. Most referrals occurred near the end of life rather than earlier in the treatment trajectory. These findings suggest a potential care-delivery gap among patients treated with oral targeted therapies and indicate that existing models of early palliative care integration, largely developed in chemotherapy-treated populations, may not be consistently applied in this long-surviving group.

Establishment and application of a quadruple target real-time PCR assay for detecting Yersinia pestis

In order to establish an efficient method for high-throughput detection of Yersinia pestis (Y. pestis) , a quadruple target real-time polymerase chain reaction assay was developed based on the specific target genes of Y. pestis ( caf1 , pla , ymt , and ypo-1094 ). Its sensitivity, specificity, and repeatability were evaluated, and clinical serum samples were tested by the established method. The results showed that no cross-reactivity was observed with other bacterial nucleic acids. The optimal linear detection range for caf1 , pla , ymt , and ypo-1094 was 12.09 × 10 - ⁶-12.09 × 10 1 ng/μL, and the lower limit of detection was 12.09 × 10 −4 ng/μL. Four different DNA concentrations of caf1 , pla , ymt , and ypo-1094 (10 −4 , 10 −3 , 10 −2 , 10 −1 and 10 1 ng/μL) were tested five times, achieving good repeatability. In the clinical sample detection, all the Y. pestis – positive samples were identified. The established method has potential for clinical use for rapid detection of Y. pestis with high specificity and high sensitivity.

Orthogonally polarized switchable ultrafast fiber laser using long-period grating

We demonstrate an orthogonally polarized switchable nonlinear polarization rotation (NPR) mode-locked fiber laser using a long-period grating (LPG). The LPG is inscribed in a single-mode fiber using a femtosecond laser, which can couple the fundamental core mode to an orthogonally polarized cladding mode, producing wavelength-dependent orthogonal polarization selectivity within a broadband spectral range. By integrating the LPG into an NPR mode-locked fiber laser, two laser outputs at 1556.1 and 1564.0 nm corresponding to the orthogonally polarized states can be switched by tuning the cavity polarization controllers. Furthermore, by varying the pump power while maintaining the cavity polarization state, the repetition frequencies of the orthogonally polarized lasers at the two wavelengths can be tuned from 211.67 to 680.36 MHz and from 105.84 to 555.64 MHz, respectively. The measured degrees of polarization of the two orthogonally polarized mode-locked outputs reach 98% and 87%, respectively. This work provides a novel approach for generating ultrashort pulses with switchable orthogonal polarization states, which is promising for linear and nonlinear applications.

The role of nanotechnology in male fertility assessment

Synergistically Competitive Coordination for Modulating Electrolyte Solvation Structures Toward High‐Performance Low‐Temperature Sodium Metal Batteries

ABSTRACT With low melting points and viscosities, linear ether‐based solvents effectively lower the Na + desolvation energy barrier in low‐temperature sodium metal batteries. Among them, 1,2‐diethoxyethane (DEE) is considered a promising solvent due to its relatively weak solvating ability at low temperatures; however, its two oxygen atoms remain electronically isolated, forming quasi‐chelating bidentate coordination structures with Na + and still triggering a high desolvation energy barrier under extremely cold conditions. Herein, a novel electrolyte based on the concept of synergistic‐competitive coordination is designed by introducing dimethoxymethane (DMM) as a cosolvent into the DEE‐based electrolyte, where the lone‐pair electrons on oxygen atoms in DMM are partially delocalized, thus reducing its electron‐donating capability toward Na + and reconstructing the Na + solvation structure. Molecular dynamics simulations reveal that DMM competes with DEE for Na + coordination sites, thereby weakening the Na + ‐DEE interaction, lowering the desolvation energy barrier, and promoting anion‐involved coordination under severe cold conditions. Consequently, Na||Na symmetric cells run stably for over 3500 h at −40°C, while Na||Cu cells show 99.7% coulombic efficiency over 200 cycles at −20°C. Moreover, NaFe 1/3 Ni 1/3 Mn 1/3 O 2 ||Na full cell retains 78.7% capacity after 200 cycles at −20°C, while Na 3 V 2 (PO 4 ) 3 ||Na full cell maintains an impressive 99.2% reversible capacity over 300 cycles at −40°C.

An intelligent assessment method for English translation teaching model based on improved BERT and attention mechanism

Caveolin-1 deficiency improved glucose metabolism via modulation of β-cell autophagy in high-fat diet-fed mice

Effect of "watch and wait" on fear of recurrence in rectal cancer: A multicenter cross-sectional study.

12116 Background: Total neoadjuvant therapy (TNT) is now the standard of care for locally advanced rectal cancer. Watch-and-wait (WW) is the most commonly used approach for patients with a complete clinical response. This study aimed to investigate fear of recurrence, presence of depression, clinical symptoms, and functional capacities in WW patients and to identify differences between them and patients who underwent surgery after TNT. Methods: In this multicenter, cross-sectional study, patients were interviewed individually and completed the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF), Patient Health Questionnaire-9 (PHQ-9), and EORTC QLQ-ANL27. The EORTC QLQ-ANL27 results in two parameters: the symptom scale (SS) and the functional scale (FS). Results: The study included 121 patients who received TNT. The median age was 60 (54-65), and male patients were in the majority at 71 (58.7%). The most common disease location was the distal rectum at 56 (46.3%). In clinical staging, the most common findings were T3 disease at 86 (71.1%) and N1 lymph node status at 63 (52.1%). The number of patients followed up with WW after TNT was 17 (14%). 27 (22.3%) patients achieved a pathological complete response (pCR) after surgery. The median disease-free survival was 21 (11-37.5) months. In surgical patients (n = 104), FCR was 16 (7.25-21), while in WW patients (n = 17), FCR was 18 (9-25), p = 0.464. The PHQ-9 score was 3 (1–10) in surgical patients and 5 (1–9) in WW patients, p = 0.669. SS was 31.7 (21.5-38.8) in surgical patients and 15.9 (12.1-38.6) in WW patients, p = 0.045. FS was 84 (61.3-87.8) in WW patients and 68.2 (61.1-78.4) in surgical patients, p = 0.045. When WW patients and pCR patients were also evaluated, no statistically significant difference was observed in terms of FCR and PHQ-9. SS was 15.9 (12.1-38.6) in WW patients and 31.8 (21.7-49.2) in pCR patients, p = 0.027. FS was 84 (61.3-87.8) in WW patients and 68.1 (50.7-78.2) in pCR patients, p = 0.027. pCR patients were evaluated according to the presence of a permanent stoma. In patients with a stoma (n:9), FCR was 19 (17.5-24.5), while in patients without a permanent stoma (n:18), FCR was 11.5 (3.75-20), p = 0.022. PHQ-9 was 12 (1.5-17) in those with a permanent stoma and 1.5 (1-8) in those without a permanent stoma, p = 0.020.There was no difference between these two groups in terms of SS and FS, p = 0.253. Conclusions: In WW patients, the fear of recurrence does not increase compared to those who underwent surgery after TNT; the level of depression is similar, but their symptoms are fewer, and their functional capacities are better. Considering both the fear of recurrence and the severe depression levels in patients who are particularly pCR and followed up with a permanent stoma, the decision to undergo WW should always be taken into account.

H&amp;E 2.0: Artificial intelligence–driven prediction of N256-glycosylated CEACAM5/6 expression in esophageal and gastric adenocarcinomas.

4018 Background: The antibody-drug conjugate (ADC) EBC-129 has shown promising clinical responses in a Phase 1A/B trial, where higher H-scores correlate with responses, slated to start Phase 2. It specifically targets N256-glycosylated CEACAM5/6, highly expressed on solid tumours, including gastro-oesophageal adenocarcinomas. Recent advances in deep learning enabled the extraction of morphological features from stained pathological images to predict protein expression from haematoxylin and eosin (H&amp;E) images. We investigated the feasibility of training deep learning models on H&amp;E images of gastro-oesophageal carcinomas and assessed the models’ ability to predict EBC-129 antigen (Ag) expression directly from H&amp;E images. Methods: H&amp;E and immunohistochemistry (IHC) images from same sections of oesophageal and gastric adenocarcinoma TMA tissues (n = 103 cores) were acquired at the same magnification. Tumour and EBC-positive areas were annotated in FIJI, with images pre-processed in Python to obtain 112x112-pixel H&amp;E image patches. Cell patches with tumour + EBC + labels were classified positive while patches with all other labels were classified negative. Six cores were held-out for testing while class balancing was conducted for the remaining 97 cores, where image patches were split 80:20 for training and validation respectively. Deep learning prediction of Ag was tested using two model architectures (DenseNet121 and ResNet50 - with no pre-trained weights) employing k-fold cross validation (k = 5). Performance metrics were recorded for the best model of each split, with mean and standard deviation values tabulated across 5 splits to determine the best performing model architecture family, followed by core-level metrics to determine the best performing individual model. Results: Feasibility and predictive potential of deep learning models was demonstrated, with superior performance metrics exhibited by the DenseNet121 model. It outperformed ResNet50 across all metrics for the combined held-out test set: AUC (0.796 ± 0.092 vs 0.748 ± 0.105), balanced accuracy (0.727 ± 0.075 vs 0.664 ± 0.100), F1 score (0.756 ± 0.059 vs 0.742 ± 0.070) and AUPRC (0.426 ± 0.132 vs 0.404 ± 0.157). Friedman test and post-hoc Conover’s test revealed significant (p &lt; 0.05) differences in metrics amongst the 10 models, where subsequent rank sum of mean metric values showed that DenseNet121 fold2_epoch09 performed best across the held-out test cores, displaying robustness and generalisability. Conclusions: There is potential of deep learning models to predict EBC-129 Ag expression from H&amp;E images and suggest possible triaging of patients suitable for treatment. Immediate next steps include examining virtual stain plots for comparison to ground truth IHC images. Future work will extend to pancreatic ductal adenocarcinoma, building on encouraging findings from the Phase 1 trial.