e16457 Background: Significant anatomical variations of organs-at-risk (OARs), particularly the stomach and duodenum, pose major challenges in abdominal radiotherapy. This study aimed to quantitatively characterize the interfractional geometric stability of these organs during a standard treatment course to provide a scientific basis for adaptive planning and margin optimization. Methods: We retrospectively analyzed 10 patients with abdominal cancer who received radiotherapy. For each patient, diagnostic-quality kV-level fan-beam CT (kV-FBCT) scans were performed daily before each treatment fraction using an integrated linac system (uRT-linac 506). A total of 110 serial scans—including the initial planning CT (pCT) and 10 repeat scans per patient sampled during the treatment course—were retrieved. The stomach and duodenum were manually re-contoured on all scans by senior radiation oncologists. Geometric variations were evaluated using: 1) Volumetric change (ΔV%); 2) Surface-based agreement (MDA and HD); 3) Spatial overlap assessment (DSC). Results: A total of 110 daily kV-FBCT scans were evaluated. The stomach exhibited profound geometric instability, with a mean DSC of 0.62 ± 0.11 and extreme volumetric expansion up to 299.81% (mean ΔV%: 45.08% ± 60.66%). The mean MDA and HD for the stomach were 6.18 ± 3.17 mm and 26.55 ± 12.41 mm, respectively. The duodenum showed even poorer spatial overlap (mean DSC: 0.52 ± 0.12). These geometric variations remained unpredictable and significant throughout the treatment course, with no trend of anatomical stabilization observed. Conclusions: During abdominal radiotherapy, the stomach and duodenum undergo substantial and unpredictable interfractional shifts. The low DSC values and large Hausdorff distances observed via daily kV-FBCT suggest that static planning margins are insufficient. Our quantitative data underscore the necessity of online anatomical assessment and adaptive strategies to ensure safe treatment delivery near gastrointestinal structures.

e16270 Background: Lattice spatially fractionated radiotherapy (Lattice SFRT) creates highly heterogeneous “peak-and-valley” dose distributions within tumors, offering a novel approach for bulky hepatocellular carcinoma (HCC) where conventional radiotherapy is often limited. This study retrospectively evaluated the safety and preliminary efficacy of Lattice SFRT combined with concurrent systemic therapy in patients with bulky, unresectable HCC. Methods: Patients with bulky, unresectable HCC who received Lattice SFRT between March 1, 2023, and July 31, 2025, were retrospectively enrolled. All treatments were delivered at a frequency of five fractions per week consecutively. Using volumetric modulated arc therapy (VMAT), the prescribed doses were set as follows: the lattice vertices within the gross tumor volume (GTV) received 35 Gy in 5 fractions, while the entire GTV simultaneously received a lower dose of 10 Gy in 5 fractions, thus constructing a specific intratumoral dose distribution. The treatment regimen was individualized, with 10 patients receiving 2 courses and 3 patients receiving 3 courses of Lattice SFRT. The primary endpoints were objective response rate (ORR) and the incidence of treatment-related adverse events (TRAEs). Secondary endpoints included local control (LC), progression-free survival (PFS), and overall survival (OS). Results: A total of 32 patients were analyzed, of whom 71.9% (n = 23) had tumors with a maximum diameter ≥10 cm. All patients received Lattice SFRT combined with concurrent systemic therapy. After a median follow-up of 9.1 months, the ORR was 53.1%, and local control was maintained in all irradiated lesions. No significant differences were observed in LC (median 11.1 vs. 7.7 months, P = 0.537) or PFS (median 11.1 vs. 7.7 months, P = 0.268) between responders and non-responders. However, responders achieved a significantly longer OS (median not reached vs. 12.3 months, P = 0.005). No grade ≥3 treatment-related hepatic toxicity or unmanageable TRAEs occurred. Hepatic functional reserve remained stable overall after treatment, with improvement in Child-Pugh class observed in four patients (12.5%). Conclusions: For patients with bulky, unresectable HCC, an individualized, multi-course Lattice SFRT regimen employing a “whole-tumor low-dose (10 Gy/5 fx) combined with intratumoral vertex high-dose (35 Gy/5 fx)” strategy demonstrated favorable local control and survival benefit with an acceptable safety profile. These findings support its potential as a promising locoregional treatment option for this challenging patient population, warranting further validation in prospective studies.

2590 Background: The immunosuppressive (“cold”) tumor microenvironment (TME) limits patient response to checkpoint inhibitors. Oncolytic viruses (OVs) can selectively replicate in tumor cells, leading to robust TME-remodeling. Reported here is the first clinical evaluation of a dual TME-modulating strategy based on an oncolytic HSV2 platform, whereby OH2, a clinically validated oncolytic HSV2 expressing GM-CSF, which enhances tumor lysis, antigen release, and dendritic cell recruitment in the TME, is co-injected with BS006, a second HSV2-based OV, which expresses a PD-L1/CD3 bispecific antibody that can redirect bystander T cells to tumor cells in the TME. Methods: BS008-001 is a multicenter, open-label phase Ib /II trial in heavily pre-treated patients with advanced solid tumors. Patients received biweekly sequential intratumoral injections of OH2 (fixed dose: 10⁷ CCID₅₀/mL) followed by BS006 (dose escalation: 10⁶–10⁷ CCID₅₀/mL), with identical volumes being injected at the same lesion. The primary endpoint is safety and tolerability; secondary endpoints included efficacy outcomes assessed by RECIST 1.1/iRECIST. Results: As of January 5, 2026, a total of 15 patients with a mean age of 59.3 were enrolled (4 soft tissue sarcoma, 3 colorectal cancer, 2 melanoma, 2 biliary tract tumors, 2 breast cancer, 1 pancreatic cancer, and 1 liver cancer). 93.3% of the patients had a baseline ECOG score of 1. The mean maximum diameter of the target lesion at baseline was 91.3 mm. 100% of the patients had distant metastases to internal organs such as the liver and lungs. Safety: Incidence of TRAEs in the Safety Set was 53.3% (8/15) with mild grade 1-2 reactions, including fever (40.0%) and decreased lymphocyte count (20.0%). 1 patient developed Grade ≥3 TRAE (6.7%), but no DLT-causing AEs or premature withdrawal from the trial occurred. Efficacy: In the 13 patients with evaluable advanced multi-line solid tumors, ORR was 7.7% and DCR 38.5%. 1 melanoma patient achieved 1 PR after 11 treatments, with the total diameter of the target lesions significantly decreasing by 70.8% to 30.4 mm; another melanoma patient received 39 doses over a treatment duration of 18.9 months (SD), whereas 1 subject with leiomyosarcoma achieved SD and survived for 27.1 months. While the mOS of the 15 patients has not yet been reached, landmark 1-year OS is 78% (95% CI: 47%-92%), with 3 patients still on treatment. Conclusions: Sequential intratumoral administration of OH2 and BS006 in heavily pre-treated patients is feasible and safe and results in reasonable DCR, with some patients achieving long-term clinical benefits. This study supports the clinical relevance of an HSV2-based platform combination of 2 oncolytic viruses encoding GM-CSF and T-cell redirected bispecific antibodies to warm up the cold TME. Further clinical research of the platform is warranted.

e15663 Background: Colorectal cancer is the third most common tumors and the second leading cause of cancer-related deaths worldwide. Most patients are diagnosed with locally advanced rectal cancer (LARC), which is associated with high recurrence risks and low survival rates. The standard treatment for LARC is preoperative neoadjuvant chemoradiotherapy combined with total mesorectal excision (TME). However, only a small proportion of patients achieve pathological complete response (pCR) after treatment, and approximately 30% develop distant metastases following neoadjuvant therapy. How to strengthen or optimize the preoperative neoadjuvant therapy of LARC to benefit more patients is a critical focus of current clinical research. High-dose-rate brachytherapy (HDR-BT) offers the potential to deliver higher radiation doses to tumors while sparing surrounding tissues and organs from radiation damage. Limited studies have investigated the combination of total neoadjuvant therapy (TNT) with HDR-BT. This retrospective study aims to compare the efficacy and safety of TNT combined with HDR-BT versus TNT alone, with the goal of providing new insights into comprehensive treatment strategies for LARC patients. Methods: Patients with LARC who received neoadjuvant therapy in our hospital from May 2016 to July 2024 were retrospectively screened according to inclusion and exclusion criteria. Clinical information, neoadjuvant treatment regimens, and serological indexes were collected. Pathological staging, tumor regression grade, R0 resection status, overall survival (OS), disease-free survival (DFS), Recurrence-free survival (RFS), and incidence of adverse reactions were recorded. The efficacy and safety of the two groups were compared. Results: This study included a total of 86 patients, with 50 in the TNT group and 36 in the TNT+HDR-BT group. There was no statistical significance in the distribution of clinical characteristics, concurrent and consolidation chemotherapy regimens between the two groups. In the TNT+HDR-BT group, 11 patients (31.4%) achieved pathological complete response (pCR), which was numerically higher than 10.0% in the TNT group (P = 0.013). The median follow-up time in the TNT+HDR-BT group and the TNT group was 68.7 months and 56.7 months, respectively. 5 year DFS was 72.2% in the TNT+HDR-BT group and 59.8% in the TNT group (HR = 0.66, 95% CI 0.31-1.43, P = 0.292). 5 year RFS was 82.5% in the TNT+HDR-BT group and 67.2% in the TNT group (HR = 0.45, 95% CI 0.17-1.16, P = 0.091). 5 year OS was 87.9% in the TNT+HDR-BT group and 70.3% in the TNT group (HR = 0.34, 95% CI 0.11-1.04, P = 0.046). Conclusions: Compared with TNT, TNT combined with HDR-BT in the treatment of LARC patients significantly increased the proportion of pCR and showed a trend of better survival outcomes.

BackgroundSustained TGF-β1 secretion is a key driver of radiation-induced inflammation and fibrosis (RIF), but the underlying mechanisms remain incompletely defined. This study investigated whether radiation-induced mitochondrial dysfunction activates cytosolic mitochondrial DNA (mtDNA) sensing via the cGAS-STING-NF-κB axis to perpetuate TGF-β1 release, and evaluated the therapeutic potential of Captopril.MethodsHuman endothelial cells (EA.hy926) received fractionated X-ray irradiation (total 40 Gy/20 fractions) to establish a long-term radiation model (EA-R). Mitochondrial integrity, cytosolic mtDNA release, and pathway activation were assessed using siRNA and inhibitors. Clinical relevance was evaluated in normal tissue specimens from 119 rectal cancer patients (68 with radiotherapy vs. 51 without) and a prospective randomized trial of 204 abdominal cancer patients (Captopril, n=100; Control, n=104).ResultsFractionated irradiation induced persistent mitochondrial dysfunction in EA-R cells, characterized by reduced complex I activity, decreased membrane potential, and disrupted cristae architecture. This damage triggered TDP-43 translocation to mitochondria, leading to sustained, membrane potential-dependent mtDNA release into the cytoplasm. Cytosolic mtDNA activated the cGAS-STING-NF-κB pathway, resulting in continuously elevated TGF-β1 secretion for over one year post-irradiation. Knockdown of cGAS or STING, or NF-κB inhibition, significantly attenuated TGF-β1 production. Overexpression of NDUFS1 restored mitochondrial function and suppressed the cascade. In clinical specimens, irradiated rectal tissues showed significantly higher expression of TDP-43, STING, and TGF-β1 (P < 0.0001). In the prospective trial, Captopril significantly lowered serum TGF-β1 levels at one month post-radiotherapy (P < 0.01) and reduced acute toxicities, including hematological toxicity (P = 0.001), elevated transaminase (P = 0.018), and elevated bilirubin (P = 0.034).ConclusionsRadiation triggers TDP-43-dependent mtDNA release via mitochondrial dysfunction, activating the cGAS-STING-NF-κB axis to sustain TGF-β1 production. Captopril suppresses this pathway, reduces TGF-β1, and mitigates acute radiation toxicities, identifying mitochondrial retrograde signaling as a potential therapeutic target for preventing RIF.

Influenza A (H1N1), which is a highly contagious respiratory pathogen, poses a serious public health threat. Its effective control necessitates rapid and accurate detection methods. Here, we developed a novel quantum dot (QDs) nanobeacon-based biosensor that synergistically integrates the precise target recognition and trans-cleavage activity of CRISPR/Cas13a with the isothermal, enzyme-free signal amplification power of catalytic hairpin assembly (CHA) for sensitive detection of H1N1 RNA. This system achieves dual signal amplification, enabling detection with a remarkably low limit of detection (LOD) of 95.2 aM within 40 min. Excellent specificity distinguishes H1N1 from other common influenza viruses. Crucially, the programmability of crRNA endows the method with broad versatility. Beyond influenza virus detection, it was successfully applied to SARS-CoV-2 RNA detection, achieving an LOD of 87.0 aM, demonstrating its potential for diverse pathogen diagnostics. These results collectively demonstrate the high performance and adaptability of this diagnostic platform, highlighting its significant promise for future applications in the rapid and sensitive detection of diverse viral pathogens.

e15133 Background: High-dose vitamin C (HDVC) has demonstrated synergistic or sensitizing effects with chemotherapy and radiotherapy in preclinical studies. However, its clinical translation has been largely limited due to suboptimal pharmacokinetics, characterized by a short half-life and insufficient duration of effective plasma concentration. To investigate whether optimizing the dosing regimen can prolong the maintenance of effective plasma vitamin C concentrations in patients with advanced hepatobiliary and pancreatic malignancies, thereby providing a new strategy to enhance its clinical antitumor effects. Methods: 18 patients with advanced hepatobiliary and pancreatic malignancies were enrolled and assigned to three dosing cohorts: Cohort A (0.5 g/kg once daily, qd), Cohort B (0.5 g/kg every 12 hours, q12h), and Cohort C (0.75 g/kg every 12 hours, q12h), with 6 patients in each group. All patients received standard antitumor therapy concurrently with HDVC, administered via a central venous catheter for 7 consecutive days. Plasma vitamin C concentrations were measured by high-performance liquid chromatography (HPLC) at fixed time points daily. Results: No significant differences in baseline plasma vitamin C concentrations were observed among the three cohorts. Compared with the once-daily regimen (0.5 g/kg qd), the every-12-hour regimen (0.5 g/kg q12h) significantly enhanced the maintenance level of plasma vitamin C concentration. However, increasing the dose to 0.75 g/kg q12h did not further elevate the plasma concentration. Regarding safety, only one patient experienced nausea and discomfort, with no other significant adverse events observed. Conclusions: In patients with advanced hepatobiliary and pancreatic malignancies, increasing the dosing frequency (e.g., to every 12 hours) under the same total daily dose can more effectively maintain the plasma concentration of HDVC with a favorable safety profile. This provides a feasible dosing optimization approach to potentially improve its antitumor efficacy. A further dose increase to 0.75 g/kg q12h did not demonstrate additional pharmacokinetic benefits in this study. Clinical trial information: NCT07121036 .

In the past few years, the global uncontrollable spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has underscored the need for rapid, sensitive, and accurate detection methods. Given the continuous mutation characteristics of viruses, single-target detection carries the risk of false-positive or false-negative results, whereas dual-target detection can effectively mitigate such risks. Therefore, thermosensitive polymer poly(N-isopropylacrylamide) (PNIPAM) was integrated with an isothermal amplification method—circle-to-circle amplification (C2CA) in this study, enabling individual and simultaneous detection of the SARS-CoV-2 S1 protein and N gene, respectively. PNIPAM-capture probe conjugates enabled specific target recognition and thermal separation from complex matrices, while C2CA achieved exponential signal amplification by leveraging two cascaded rolling circle amplification (RCA) reactions. During single-target detection, the method exhibited linear ranges of 0.1–1000 pg/mL for S1 protein detection and 0.1–1000 pM for Ng detection, with the limit of detection (LOD) of 55 fg/mL and 11.2 fM, respectively. The spiked recovery experiment demonstrated that this method possesses high specificity and robust anti-interference capability. Furthermore, in order to improve the accuracy and efficiency, simultaneous detection was achieved by integrating S1 protein and Ng detection into a single reaction system and labeling differential fluorophores. The LOD was 68.3 fg/mL for S1 protein and 33.1 fM for Ng, respectively. This method combines the advantages of homogeneous reaction and isothermal amplification, eliminating the need for complex instruments and cumbersome procedures, thereby making it suitable for resource-limited settings.

This study aimed to evaluate the efficacy and safety of apatinib, an oral VEGFR2 tyrosine kinase inhibitor, combined with docetaxel and S-1 (DS) as first-line therapy for metastatic gastric cancer (mGC) patients whose median overall survival (mOS) with chemotherapy typically remains below 12 months. In this prospective, multi-center, single-arm phase II trial (NCT03154983), patients received docetaxel (75 mg/m2, day 1) and S-1 (body surface area-based dosing, days 1-14) every 3 weeks, plus daily apatinib (500 mg), for up to 6 planned cycles. 45 patients were enrolled, with a median follow-up time of 12.4 months. Median progression-free survival (PFS) and overall survival (OS) were 7.6 months (95% CI: 5.8%-9.4%) and 12.4 months (95% CI: 9.3%-15.5%), respectively in the full analysis set. Patients completing ≥4 cycles achieved a better mOS of 14.5 months (95% CI: 12.0%-17.1%). The objective response rate (ORR) and disease control rate (DCR) were 62.2% (95% CI, 46.5%-76.2%) and 82.2% (95% CI, 67.9%-92.0%), respectively, including one complete response (CR). Grade 3-4 treatment-related adverse events occurred in 48.9% of patients, most commonly oral mucositis and neutropenia. These findings support apatinib plus DS as a promising biomarker-independent first-line treatment strategy for mGC.

Background:Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. Objective:This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. Methods:In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. Results:Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. Conclusions:In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

High-dose vitamin C (HDVC) has a short half‑life of approximately 2 h, and once‑daily dosing results in sub‑therapeutic plasma concentrations for most of the dosing interval, potentially limiting its pro‑oxidant antitumor activity. In this phase I study, 18 patients with advanced solid tumors were assigned to three cohorts (n = 6 each): Group A (0.5 g/kg once daily, total daily dose 0.5 g/kg), Group B (0.5 g/kg every 12 h, total daily dose 1.0 g/kg), and Group C (0.75 g/kg every 12 h, total daily dose 1.5 g/kg). Plasma trough concentrations were measured daily for 7 days. Compared to Group A, Group B exhibited significantly higher trough concentrations throughout the study (P < 0.05), demonstrating superior maintenance of therapeutic levels. Further dose escalation to 0.75 g/kg twice daily (Group C) provided no additional trough concentration benefit versus Group B (P > 0.05), consistent with the plateau in peak concentrations at single doses above approximately 70 g/m² (∼1.0 g/kg). All regimens were well tolerated, with only one mild nausea (5.6%) and no serious adverse events. Fractionated dosing (0.5 g/kg every 12 h) significantly improves trough concentration maintenance with good tolerability. This optimized regimen (total daily dose 1.0 g/kg) provides a rational pharmacokinetic basis for future phase II trials designed to evaluate whether sustained pro‑oxidant levels translate into enhanced clinical efficacy.

Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces chemoradiotherapy‑induced muscle loss, weight loss, and malnutrition. This randomized phase II trial evaluated whether a multidisciplinary, mHealth‑based multimodal rehabilitation program could preserve handgrip strength and muscle mass in abdominal cancer patients undergoing CCRT. In this prospective, multicenter, randomized, open‑label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC, n=57) or standard care (SC, n=54). The MRC program was delivered by a dedicated multidisciplinary team comprising oncologists, rehabilitation physicians, nurses, clinical nutritionists, and psychologists. Using the AINST mHealth platform and wearable heart rate monitors, the team provided coordinated, individualized exercise, nutritional, and psychological interventions based on weekly assessments and real‑time data. The SC group received routine oncology care. The primary endpoint was change in handgrip strength from baseline to CCRT completion. Secondary endpoints included body weight, skeletal muscle mass, nutritional biomarkers, quality of life, psychological status, and adverse events. Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high, with 83.9% (47/56) of MRC patients achieving preset exercise targets. Compared with SC, the MRC group demonstrated significantly less decline in handgrip strength at all time points (all p < 0.001). The MRC group also showed better preservation of body weight (mean difference 1.3 kg, p=0.005) and a significantly lower proportion of patients with >5% weight loss (10.7% vs. 32.7%, p=0.005). Skeletal muscle mass was also better preserved (mean difference 1.3 kg, p<0.001). The MRC group had less decline in serum albumin (p=0.009) and prealbumin (p=0.019), and lower incidences of ≥G3 leukopenia (5.4% vs. 19.2%, p=0.037) and ≥G1 thrombocytopenia (16.1% vs. 34.6%, p=0.026). Nutritional and psychological benefits persisted at 4‑week post‑CCRT follow‑up. A multidisciplinary, mHealth‑based multimodal rehabilitation program effectively preserves handgrip strength, muscle mass, and nutritional status while reducing treatment toxicity in abdominal cancer patients undergoing CCRT. The multicenter implementation using standardized digital tools supports its scalability and translation into real‑world clinical pathways. Clinical Trial Registration: ClinicalTrials.gov NCT05325554.Registration Date 03/08/2022.

A novel colorimetric aptasensor based on silver nanoparticles (AgNPs) and Ag+-dependent urease inhibition has been designed. Sensitive detection of adenosine triphosphate (ATP) and platelet-derived growth factor BB (PDGF-BB) were achieved by employing the competitive assay and sandwich assay, respectively. The method conjugated the aptamer with magnetic beads to construct a magnetic recognition module, and employed poly-C DNA modified AgNPs as the signal amplification module. Target binding to the magnetic recognition module triggers magnetic capture of AgNPs, which were subsequently oxidized to release abundant Ag+. These ions efficiently inhibited urease activity, thus blocking urea hydrolysis and preventing pH increase, thereby achieving cascaded signal amplification. The colorimetric mechanism of this method relies on converting the resultant pH change into a color transition of the acid-base indicator phenol red, with the absorbance ratio of A559/A432 decreasing as target compound’s concentration increases. To validate the generality of this strategy, we designed competitive and sandwich assays for different targets, both achieving satisfactory detection performance. The competitive assay for ATP exhibited a linear range from 1 nM to 10 µM and a detection limit (LOD) of 0.70 nM, while the sandwich assay for PDGF-BB showed a linear range of 1 pM to 10 nM with a LOD of 0.82 pM. The average recoveries in human serum samples were 90.5

PURPOSE:To explore the population of patients who could benefit from adjuvant radiation therapy (RT) and investigated the value of postoperative chemoradiation therapy (CRT) in patients with gastric cancer after D2 resection. METHODS AND MATERIALS:This randomized clinical trial enrolled patients between October 1, 2011, and December 31, 2019. Patients with gastric cancer who underwent D2 gastrectomy were randomized (1:1) to receive postoperative CRT or adjuvant chemotherapy after surgery. The adjuvant chemotherapy group received 8 cycles of SOX (S-1 + oxaliplatin) chemotherapy. RT was given after 4 to 6 cycles of SOX chemotherapy. RT comprised 45 Gy in 25 fractions of 1.8 Gy over 5 weeks by intensity modulated RT concurrently with S-1 chemotherapy. The primary endpoint was 3-year disease-free survival (DFS). RESULTS:A total of 312 patients (median [IQR] age, 58 [50-64] years) were enrolled, including 157 patients randomized to the adjuvant chemotherapy group and 155 patients randomized to the adjuvant CRT group. The 3-year DFS was 66.7% for the control arm and 70.7% for the experimental arm (hazard ratio [HR], 0.82; 95% CI, 0.54-1.25; P = .35). We defined patients with pN stage ≥ N2 and extraperigastric lymph node metastasis as the high-risk group and the remaining patients as the low-risk group. The 3-year DFS rates for the high-risk group and the low-risk group were 59.3% and 76.8%, respectively (HR, 2.11; 95% CI, 1.39-3.22; P < .01). For high-risk patients, the 3-year DFS rates in the adjuvant chemotherapy and adjuvant CRT groups were 53.0% and 71.0%, respectively (HR, 0.53; 95% CI, 0.29-0.97; P < .05). More grade 3 and 4 acute toxic effects were observed in the adjuvant chemotherapy group than in the CRT group (41 patients [26.1%] vs 28 patients [18.5%]; P = .11), but the difference was not significant. CONCLUSIONS:Subgroup analysis of this randomized clinical trial revealed that high-risk patients can benefit from adjuvant CRT.

Objective:While albumin and the weight-standardized hand grip strength(HGS/W)serve as valuable prognostic indicators for cancer patients,their correlation with the prognosis in frail cancer patients remains inadequately explored.This study aimed to investigate the prognostic importance of the albumin level and HGS/W in cancer patients with frailty and to further investigate their combined prognostic value.Moreover,this comprehensive evaluation aimed to facilitate timely intervention and treatment for frail patients. Methods:The research enrolled 5,794 cancer patients identified with frailty from a multicenter research database.The diagnosis of frailty was based on the FRAIL scale.An Albumin-HGS/W score was constructed by combining the albumin and HGS/W values.Cox proportional hazard regression was utilized to examine the association between the albumin level and HGS/W and patient outcomes. Results:Among these patients,2,543 were females and 3,251 were males,with a median age of 60.0 years.Optimal stratification based on patient survival revealed the ideal threshold for HGS/W to be 0.48 for males and 0.39 for females,and for albumin to be 38 for both sexes.The fully adjusted model revealed that higher Albumin-HGS/W scores were correlated with a poorer patient prognosis.Notably,an Albumin-HGS/W score of 2 was associated with a higher risk of mortality compared with a score of 0 in the total population(HR:1.813,95%CI:1.580-2.080,P<0.001). Conclusions:Low albumin or HGS/W values are associated with low survival in cancer patients with frailty.Elevated Albumin-HGS/W scores were linked to decreased survival rates in cancer patients with frailty.

BACKGROUND:The prognosis of triple-negative breast cancer (TNBC) is notably unfavorable, necessitating the development of novel treatments to enhance therapeutic outcomes. The underlying mechanisms contributing to the pathogenesis of TNBC remain incompletely understood. RNA 5'-phosphate and 3'-OH ligase 1 (RLIG1) was found to be the first RNA ligase in humans and may be related to cancer development, but no reports have been reported. We observe RLIG1 elevated expression levels in TNBC tissues compared to adjacent non-cancerous tissues, with high RLIG1 expression correlating with reduced overall survival in TNBC patients. METHODS:We investigated RLIG1 in TNBC using bioinformatics tools, cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), colony formation, flow cytometry, and western blotting. Mechanistic insights were gained via mass spectrometry, co-immunoprecipitation, and immunofluorescence. RESULTS:Here, we found that interfering with RLIG1 can effectively hinder tumor cell cycle progression and proliferation in vitro, as well as inhibit tumor growth in vivo. Mechanistically, RLIG1 was identified as an oncogene that stimulates the mTORC1 signaling pathway in TNBC cells. Furthermore, the interaction between RLIG1 and ERK was confirmed, with RLIG1 promoting cell cycle transition and proliferation through mediating ERK phosphorylation. CONCLUSIONS:Our research offers novel insights into the biological role of RLIG1, indicating its potential as a therapeutic target for TNBC.

BACKGROUND:Although several PD-1 or PD-L1 inhibitors combined with antiangiogenic agents have been approved as first-line treatment of advanced hepatocellular carcinoma, treatment needs remain unmet given the high incidence and mortality of hepatocellular carcinoma and due to factors such as regional approval status, medical insurance restrictions, and cost considerations. In this phase 3 HEPATORCH study, we aimed to compare the efficacy and safety of toripalimab plus bevacizumab versus sorafenib in patients with previously untreated advanced hepatocellular carcinoma. METHODS:We did a randomised, open-label, phase 3 study in 57 hospitals across mainland China, Taiwan, and Singapore. Using a central interactive web response system, eligible patients aged 18-75 years with unresectable or metastatic hepatocellular carcinoma were randomly assigned (1:1) through a stratified block randomisation method to receive 240 mg toripalimab (intravenously, once every 3 weeks) plus 15 mg/kg bevacizumab (intravenously, once every 3 weeks) or 400 mg sorafenib (oral, twice daily). Randomisation was stratified by macrovascular invasion or extrahepatic spread (presence vs absence), ECOG performance status score (0 vs 1), and history of locoregional therapy (yes vs no). The co-primary endpoints were progression-free survival (assessed by the Independent Review Committee per Response Evaluation Criteria in Solid Tumors, version 1.1) and overall survival. Efficacy analysis was performed in the intention-to-treat population (ie, all patients randomly assigned to a treatment group). Safety was assessed in all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT04723004, and is completed. FINDINGS:Between Nov 23, 2020, and Jan 21, 2022, 545 patients were screened for study inclusion, of whom 219 did not meet the screening criteria. 326 patients were randomly assigned to receive an intervention: 162 patients were assigned to the toripalimab plus bevacizumab group and 164 were assigned to the sorafenib group, with median age 58·0 years (IQR 50·0-66·0) and 56·0 years (49·0-61·0) years, respectively. All 326 patients were included in the intention-to-treat population and the safety population. 282 (87%) patients were male and 44 (14%) were female. At the primary analysis of progression-free survival (data cutoff Aug 10, 2022), median follow-up was 9·4 months (IQR 7·0-12·0). Toripalimab plus bevacizumab significantly prolonged progression-free survival compared with sorafenib (median 5·8 months [95% CI 4·6-7·2] vs 4·0 months [2·8-4·2]; hazard ratio [HR] 0·69 [95% CI 0·53-0·91; p=0·0086). At the final analysis of overall survival (May 31, 2024), median follow-up was 16·4 months (IQR 7·1-29·5). Toripalimab plus bevacizumab significantly improved overall survival compared with sorafenib (median 20·0 months [95% CI 15·3-23·4] vs 14·5 months [11·4-18·8]; HR 0·76 [95% CI 0·58-0·99; p=0·039). Grade 3 or higher adverse events occurred in 102 (63%) patients in the toripalimab plus bevacizumab group compared with 100 (61%) in the sorafenib group, and led to discontinuation of treatment in 21 (13·0%) participants in the toripalimab plus bevacizumab group and 20 (12%) participants in the sorafenib group. The incidence of treatment-related fatal adverse events (two [1%] vs one [1%]) was similar between the toripalimab plus bevacizumab and sorafenib groups. The most common (incidence ≥5% in the toripalimab plus bevacizumab group) grade 3-4 adverse events were hypertension (26 [16%] in the toripalimab plus bevacizumab group vs 19 [12%] in the sorafenib group), thrombocytopenia (16 [10%] vs four [2%]), upper gastrointestinal haemorrhage (ten [6%] vs one [1%]), anaemia (nine [6%] vs seven [4%]), and abnormal hepatic function (nine [6%] vs five [3%]). The most common (incidence ≥2% in the toripalimab plus bevacizumab group) serious adverse events were upper gastrointestinal haemorrhage (12 [7%] vs one [1%]), abnormal hepatic function (eight [5%] vs five [3%]), ascites (six [4%] vs three [2%]), and gastrointestinal haemorrhage (four [2%] vs three [2%]). INTERPRETATION:Among patients with previously untreated advanced hepatocellular carcinoma, toripalimab plus bevacizumab resulted in significantly longer progression-free survival and overall survival than did sorafenib, with an acceptable safety profile. Based on these results, the regimen has been approved for use in China by the National Medical Products Administration. FUNDING:Shanghai Junshi Biosciences. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

Fat-free mass index (FFMI) is a prognostic influence in cancer patients. However, for the prognosis of Chinese lung cancer (LC) patients, the threshold and impact of FFMI are not known. The aim of the present study was to examine the association between FFMI and the prognosis of Chinese patients with LC. Totally 1,881 adult patients with LC were enrolled. During a median follow-up of 41.0 months (range 23.8–64.3), we reported 938 deaths. The optimal stratification method was used to determine the gender-specific optimal threshold for FFMI. Cox regression model and Kaplan–Meier curve were used to evaluate the relationship between FFMI and prognosis. Mediation analysis was used to determine the mediating effect of inflammation. The optimal cutoff points for low FFMI in males and females were 17.27 kg/m2 and 14.84 kg/m2, respectively. Low FFMI was an independent prognostic indicator for LC patients. Patients who experienced a low FFMI were 29

e15562 Background: Human epidermal receptor growth factor 2 (HER2) -expressing or amplified has been identified in 2-6% of patients with stage III/IV colorectal cancer (CRC).however,there are currently no approved HER2-targeted therapies for CRC in China. Herein, we aimed to investigate the antitumor activity and safety of Disitamab vedotin , a novel humanized anti-HER2 antibody conjugate linked to monomethyl auristatin E via a cleavable linker, in combined with fruquintinib in patients with HER2-expressing or -amplified metastatic colorectal cancer. Methods: In this prospective, exploratory, single-arm study, patients diagnosed pathologically with mCRC, 18-75 years old harboring HER2 expression or HER2 mutation/amplification, and received at least two prior lines of treatment. HER2 expression was defined as animmunohistochemical [IHC]score of 1+, 2+ or 3+, or mutation/amplification identified by NGS. Patients received RC48 2.5mg/kg intravenously every 2 weeks. Meanwhile, fruquintinib was administered orally at 3 mg once daily until disease progression, death, intolerable toxicity, withdrawal of consent. The primary endpoint was ORR ; the secondary endpoints included DCR, PFS, OS and safety. Results: A total of 24 patients were enrolled from Nov 25, 2022 to Dec 16, 2024.HER2 statuses are as follows: 11 patients had IHC 1+ (one of whom had HER2 amplification), 6 had IHC 2+, 4 had IHC 3+, and 3 had HER2 amplification. In the metastatic setting, patients had received a median of 3 prior lines of therapy (range, 2-6). The ORR was 13.6% (3/22) and DCR was 77.3% (17/22). The median PFS was 4.11 months (95% CI: 2.56-5.65) and the median OS was 10.45 months (95% CI: 5.93-13.97). The 9-month OS rate was 55.0%, and the 12-month OS rate was 40.7%. Among the 14 patients with HER2 IHC 2+, IHC 3+ and HER2- amplification, the ORR was 23.1% (3/13), and the DCR was 84.6% (11/13)，the median PFS was 5.78 months (95% CI: 3.33-8.24) and the 9-month OS rate was 66.1%, the 12-month OS rate was 45.3%. 22 (91.7%) patients experienced adverse events , of whom 6 (27.3%) experienced grade 3 TRAEs . The most common grade 3 TRAEs were leukopenia (12.5%), neutropenia (8.3%), hyponatremia (4.2%) and hypokalemia (4.2%). No grade 4 or 5 TRAEs were observed. Additionally, 8 (33.3%) patients required dose reduction. And No patients experienced dose interruption or discontinuation due to TRAEs. Conclusions: The combination of RC48 and fruquintinib has demonstrated promising efficacy and a manageable safety in patients with HER2 -expressing or -amplified mCRC who have failed at least two lines of standard treatments.Patients with HER2 IHC 2+, 3+ and amplification appear to derive greater benefit from this therapeutic regimen. Clinical trial information: NCT05661357 .