Programmed cell death protein-1 (PD-1) blockade has shown promising clinical efficacy in hepatocellular carcinoma (HCC), yet the underlying immunological mechanisms governing response and resistance remain unclear. This study aimed to delineate the temporal and spatial dynamics of T-cell clonotypes and their relationship with pathological response in neoadjuvant PD-1 blockade therapy in HCC. By integrating T-cell receptor (TCR) repertoire analysis with transcriptomic profiling, we sought to elucidate the immune landscape alterations associated with treatment outcomes.

Several animal studies have demonstrated the safety and efficacy of a flexible auxiliary single-arm transluminal endoscopic robot in assisting gastric endoscopic submucosal dissection (ESD). This study aimed to assess its performance for the first time in a real clinical setting.We conducted this prospective, single-blind, pilot randomized controlled trial at a tertiary teaching hospital. Patients with gastric high grade intraepithelial neoplasia or intramucosal carcinoma were randomized to either robot-assisted or conventional ESD. The primary outcome was procedure time. Secondary outcomes included R0 and en bloc resection rates, dissection time, and procedure-related complications.48 patients underwent successful procedures without perforation. Despite no significant difference in procedure time between robot-assisted and conventional ESD (58.21 vs. 39.21 minutes; P = 0.08), a learning curve effect was observed, with shorter procedure times in the last 12 cases with robot assistance compared with the last 12 conventional ESDs (56.82 vs. 63.10 minutes; P = 0.71). Muscular injuries were significantly reduced with robot assistance (1.50 vs. 9.00; P < 0.001). No significant difference was found in R0 (95.8% vs. 91.7%; P > 0.99) and en bloc (100% vs. 95.8%; P > 0.99) resection rates between robot-assisted and conventional ESD, respectively.This preliminary evidence supports the feasibility of robot-assisted gastric ESD.

Garsorasib, a KRAS G12C inhibitor, has previously demonstrated its efficacy and safety in patients with KRAS G12C-mutated non-small-cell lung cancer (NSCLC). Here, we present long-term follow-up data from a pooled analysis of the phase 1/2 study.

We investigated whether serum levels of biomarkers of inflammation, immune activation, and angiogenesis, which have been implicated in the pathogenesis of Kaposi sarcoma (KS), were associated with tumor burden and treatment response of advanced AIDS-KS.

Metastatic pheochromocytoma and paraganglioma (MPP) currently lack definitive curative therapies. The treatment of MPP presents a formidable challenge. Anlotinib hydrochloride, characterized as a multi-targeted tyrosine kinase receptor inhibitor, has demonstrated potential in this domain. This study, a phase 2 trial (NCT04860700), aimed to evaluate the efficacy and safety profiles of anlotinib hydrochloride in patients suffering from MPP. The primary objective was to determine the disease control rate (DCR) and objective response rate (ORR) as determined by the RECIST 1.1 criteria. Secondary objectives were to evaluate the biochemical response, progression-free survival (PFS), and safety. Twenty-nine patients with MPP were enrolled. We found that 24.1% (7/29) of patients discontinued the treatment after 1-2 cycles because of a significant increase in hormone levels or adverse events. Among 22 patients who could be evaluated by the RECIST 1.1 criteria, the overall DCR was 95.5% (21/22), and the ORR was 31.8% (7/22). The PFS was calculated to be 22.6 ± 3.2 months. There is no significant difference in ORR or PFS between patients with and without germline mutations. The most common adverse events included arterial hypertension (24/29, 82.8%), subclinical primary hypothyroidism (11/29, 37.9%), hyperlipidemia (10/29, 34.5%), rash (8/29, 27.6%), and fatigue (8/29, 27.6%). We conclude that among the evaluable patients, anlotinib showed promising efficacy with high DCR. Close monitoring remains essential because of treatment-related adverse events.

Given the poor prognosis of IDH wild-type (IDH-wt) and telomerase reverse transcriptase promoter mutation (TERTp-mut) histological grade 2 to 3 gliomas, the World Health Organization has reclassified it as molecular glioblastoma. However, the effectiveness of chemoradiotherapy (CRT) in these patients remains unclear, especially in comparison to radiotherapy alone (RT). This study aims to assess CRT's efficacy in this population.

The potential for immunotherapy in patients with locally advanced gastric cancer (LAGC) is recently confirmed. To report the 3-year follow-up data are aimed from a novel clinical trial. This is a prospective single-arm phase II trial. Patients with LAGC received neoadjuvant tislelizumab plus SOX before surgery. Biopsies are obtained before treatment, and tumor samples post-treatment underwent single-cell RNA sequencing (scRNA-seq). Spatial transcriptomics is conducted for validation. Cox regression models and Kaplan-Meier analysis are applied. A total of 49 patients are enrolled, and the median progression-free (PFS) and overall survival (OS) are not achieved. The 3-year PFS and OS rates are 64.1% and 73.2%, respectively. scRNA-seq of 22, 248 cells from tumors from seven patients with LAGC enabled annotation of three cancer-associated fibroblast (CAF) phenotypes. Spatial transcriptomics of gastric cancer samples validate the classification, showing inflammatory CAFs (iCAFs) negatively correlated with immunotherapy efficacy. Patients with LAGC show a favorable prognosis after neoadjuvant tislelizumab plus SOX treatment. CAF heterogeneity is crucial for patients with gastric cancer undergoing immunotherapy, and iCAFs is associated with an immunosuppressive microenvironment during PD-1 blockade with SOX therapy and validated by in vitro experiments. Patients with LAGC with higher iCAF scores are resistant to SOX PD-1 blockade.

We conducted a Phase II study to assess the efficacy and toxicity of nab-paclitaxel (nab-PTX) and cisplatin in combination with concurrent radiotherapy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC).

Osimertinib, the first approved third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), exhibits notable efficacy in EGFR-mutant non-small cell lung cancer (NSCLC). This is a prospective, multicenter, comprehensive genomic profile signature (GPS) study in paired tissue and plasma samples from 149 patients with advanced NSCLC harboring EGFR exon 19 deletion (Ex19del) or L858R mutation at the first-line treatment failure of osimertinib (NCT05219162). Next-generation sequencing (NGS) was used for comprehensive GPS analysis of paired tissue and plasma samples. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were used for tissue samples, while droplet digital polymerase chain reaction (ddPCR) and NGS were used for plasma samples to perform a concordance analysis of MET amplification. At the first-line treatment failure of osimertinib (study entry), EGFR alterations in tissue samples included EGFR Ex19del (49.0%, 73/149), EGFR L858R mutation (43.0%, 64/149), EGFR amplification (32.9%, 49/149), EGFR L718Q/V mutation (4.7%, 7/149), and EGFR C797S mutation (3.4%, 5/149); bypass signaling activation and downstream pathway activation alterations included TP53 mutation (69.8%, 104/149) and MET amplification (30.9%, 46/149). Among the 136 patients with EGFR Ex19del/L858R mutation in tissue samples, 72.1% (98/136), 35.3% (48/136), and 32.4% (44/136) had TP53 mutations, EGFR amplification, and MET amplification, respectively. Taking tissue samples as references, the GPS in plasma samples showed high specificity (90.7-100%) for almost all genomic alterations. Compared with FISH (gene copy number [GCN] ≥10), the overall percent agreement of tissue NGS, optimized tissue NGS (GCN ≥ 8.63), plasma NGS, and plasma ddPCR for MET amplification were 75.0% (27/36), 100% (36/36), 88.9% (32/36), and 94.4% (34/36), respectively. This study represents the largest-scale, prospective study with paired tissue and plasma samples to enable comprehensive analysis of GPS, providing a novel perspective into coalterations at the first-line treatment failure of osimertinib. A plasma sample serves as a supplement for identifying GPS when a tissue sample is unavailable. Moreover, the integration of FISH, NGS, and ddPCR provided a comprehensive assessment of MET amplification.

STELLAR (ClinicalTrials.gov identifier: NCT02796261) was a phase III, randomized, open-label trial of eflornithine + lomustine versus lomustine monotherapy in patients with recurrent grade 3 astrocytoma.

The CDK4/6 inhibitor palbociclib delays progression in patients with advanced dedifferentiated liposarcoma (DDLPS). In carcinoma models, CDK4/6 and PD-1 inhibition induce intratumoral inflammation and synergistic activity. Comprehensive assessment of tumor and host dynamics is needed to understand response and resistance to this combination.

This phase Ib/II trial (NCT04276493) assessed the antitumor activity, safety, and pharmacokinetics (PK) of zanidatamab in combination with tislelizumab and chemotherapy in patients with advanced HER2-positive (HER2+) gastric cancer/gastroesophageal junction cancer (GEJC).

The aim of this study was to evaluate the safety and feasibility of ipatasertib combined with trastuzumab and pertuzumab (HP) as maintenance therapy after first-line treatment in patients with HER2-positive metastatic breast cancer harboring PIK3CA mutations (PIK3CAmut).

The optimal conversion treatment for patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer (BRPC/LAPC) remains unclear. In this study, we present the efficacy and safety results of a phase II trial evaluating tislelizumab combined with hypofractionated radiotherapy plus nab-paclitaxel/gemcitabine (THAG) in patients with BRPC/LAPC (ChiCTR2000032955, NCT05634564).

Contemporary prostate cancer prognostic models do not include imaging and generally are based on pretreatment parameters. We sought to develop an externally validated model that used novel quantification of soft-tissue and bone disease, integrated with standard clinical and serum biomarkers, at baseline and up to 6 months of treatment.

Magnetic seeds have comparable performance to guidewires in breast lesion localization with the advantages of shorter operating time, facilitated logistics, and higher staff satisfaction. However, the high cost of the device remains a concern and warrants health economic evaluation.

Treatment approaches differ for isolated in-breast tumor recurrence (representing treatment failure) and new primary breast tumors (representing high etiologic risk). However, methods for distinguishing recurrences from second primaries (based on radiographic and histologic criteria) are subject to error. Gold-standard genomic datasets for assessing classification accuracy have been lacking.

SG001 is a humanized, IgG4 monoclonal antibody against human PD-1. This phase 1b study aimed to evaluate efficacy and safety of SG001 in advanced solid tumors.

At the primary efficacy analysis of the NATALEE phase III trial, ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) demonstrated a statistically significant improvement in invasive disease-free survival (iDFS) versus NSAI alone in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC). Continued follow-up of efficacy outcomes is important in assessing the durability of treatment benefit. We report 5-year estimates of efficacy outcomes, including an udpated analysis of overall survival (OS).

Immunotherapy-based regimens are the standard first-line treatment for KRAS G12C-mutant NSCLC, but outcomes remain suboptimal. Prior attempts to combine KRAS G12C inhibitors with immunotherapy have been challenged by toxicity. We report results from LOXO-RAS-20001, a phase 1/2 trial evaluating the combination of olomorasib with pembrolizumab in KRAS G12C-mutant NSCLC, including in first-line setting.