Artificial intelligence (AI) has emerged as a promising tool to enhance lesion detection (CADe) and characterization (CADx) during colonoscopy. However, its effectiveness in faecal immunochemical test (FIT)-based colorectal cancer (CRC) screening remains controversial.

Colorectal cancer (CRC) is a major health burden globally and in China, where 3%-5% of cases involve the BRAFV600E mutation, which is associated with aggressive disease and therefore a poor prognosis. Although the combination of encorafenib and cetuximab has demonstrated improved survival in BRAFV600E mutant metastatic CRC (mCRC), such treatments remain unavailable as chemotherapy-free options in China.

Treatments for leptomeningeal metastasis (LM) are limited and prognosis is poor. In this phase 2, nonrandomized, single-arm, multicenter study, we evaluated a tucatinib-trastuzumab-capecitabine regimen in patients with newly diagnosed LM and human epidermal growth factor receptor 2-positive (HER2+) breast cancer. The primary endpoint was overall survival; secondary endpoints included central nervous system progression-free survival, LM objective response, neurological symptom improvement, pharmacokinetics and safety. The trial met its prespecified interim efficacy threshold and exceeded the historical control of 4.4 months. Among 17 enrolled women, all had magnetic resonance imaging-confirmed LM, 15 (88%) were symptomatic and 8 (47%) had abnormal cerebrospinal fluid cytology. For a median follow-up of 18 months (range 9.0-26.7 months), 6 of 17 (41%) remained alive. Tucatinib reached therapeutic levels in the cerebrospinal fluid. The median overall survival was 10 months (95% confidence interval 4.1 months, not reached). The median time to central nervous system progression was 6.9 months (95% confidence interval 2.8, 13.8 months). Of 13 response-evaluable patients, 5 (38%) achieved composite LM objective response. Of 12 evaluable patients, 7 (58%) had improved neurological deficits. This prospective study suggests clinical benefit with a systemic regimen for HER2+ LM including objective responses, improved symptoms and extended survival. These data support systemic therapy as an approach in HER2+ breast cancer LM. ClinicalTrials.gov registration: NCT03501979 .

The expanding clinical use of helical tomotherapy (HT) has raised concerns regarding its potential to increase low-dose lung exposure and the risk of radiation pneumonitis (RP) in thoracic radiotherapy. While a few retrospective studies have compared dosimetric parameters and RP rates between HT and fixed-field intensity-modulated radiation therapy (IMRT), their findings remain inconsistent, necessitating a prospective randomized controlled trial for clarification.

Uveal melanoma is a rare melanoma subtype characterized by a liver-dominant pattern of metastasis which is associated with a lack of durable responses to immunotherapies. Adoptive cell transfer of autologous tumor-infiltrating lymphocytes (TILs) has been shown to induce responses in a subset of patients with metastatic uveal melanoma. The safety and feasibility of locoregional administration of TIL therapy via hepatic arterial infusion (HAI) have not previously been evaluated.

Patients with peripheral T cell lymphoma (PTCL) who achieved tumor response with first-line standard therapy were at high risk of disease relapse. We explored golidocitinib (150 mg once daily) as maintenance therapy for this group of patients (JACKPOT26, NCT06511869). This study included two cohorts: patients achieving a complete response (Cohort 1 (CR), N = 30) and a partial response (Cohort 2 (PR), N = 18) during induction stage. All enrolled patients were transplant ineligible or did not have a transplant plan. All dosed patients were included in the efficacy and safety analysis. In Cohort 1, the 24-month disease free survival (DFS) rate was 74.2% with golidocitinib treatment. In nodal subtypes (AITL, NOS, ALK- ALCL), the 24-month DFS rate was 62.7%. In Cohort 2, median progression free survival (PFS) was 17.4 months, and 24-month PFS rate was 48.6%. Nine out of 18 patients with initial PR achieved complete response, leading to a complete response rate of 50.0%, and median duration of response of 23.9 months. The most common ≥grade 3 treatment-related treatment-emergent adverse events (TRAEs) were hematological adverse events in nature, including neutrophil count decreased (47.9%), white blood cell count decreased (31.3%), lymphocyte count decreased (14.6%) and leukopenia (12.5%). The majority of these TRAEs were reversible and clinically manageable. TRAEs leading to treatment interruption and discontinuation occurred in 60.4% and 10% of patients, respectively. No TRAEs leading to fatal outcomes were reported. This study suggests the potential of golidocitinib as maintenance therapy for patients with PTCL.

Epigenetic regulators represent a novel strategy to modulate the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). In preclinical models, DNA hypomethylating agents enhance cytotoxic T-cell infiltration, synergize with PD-1 blockade, and improve survival when combined with immune checkpoint blockade. This single-institution, phase II study evaluated the safety, efficacy, and biomarkers of azacitidine plus pembrolizumab in patients with previously treated PDAC.

To report updated results of the phase 3 PHILA trial, which evaluated the efficacy and safety of pyrotinib or placebo in combination with trastuzumab and docetaxel in patients with untreated human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer.

Cyclin-dependent kinase (CDK) dysregulation is common in pediatric cancers. The dual CDK2/9 inhibitor fadraciclib has shown preclinical antitumor activity, alone and in combination, supporting clinical evaluation in children.

Background: Clear cell sarcoma (CCS) is an ultrarare sarcoma driven by a specific chromosomal translocation, most commonly the EWS RNA binding protein 1-activating transcription factor 1 fusion (EWSR1::ATF1), for which chemotherapy shows limited activity, with a median progression-free survival (PFS) of approximately 3 months in retrospective series. In the present trial, a CCS cohort was selected based on signals of activity observed in the IMMUNOSARC I phase I/II trial evaluating nivolumab in combination with sunitinib in sarcomas. Methods: Patients aged 12 to 80 years with advanced, progressive, and measurable CCSs were enrolled after central pathology review, and molecular confirmation of an EWSR1 rearrangement was required. Sunitinib was administered at 37.5 mg/d during the first 2 weeks and then at 25 mg/d along with nivolumab at 240 mg every 2 weeks. The primary end point was the 6-month PFS rate, defined under the null (H0) and alternative (H1) hypotheses as 25% and 55%, respectively. Under Simon's 2-stage minimax design (α = 0.05, power = 0.90), a minimum of 10 of 23 patients needed to be progression-free at 6 months. Results: At the time of cutoff, 23 patients were evaluable for the primary end point. With a median follow-up of 23.0 months (95% confidence interval [CI], 10.0 to 35.0 months), the 6-month PFS rate was 50.1% (95% CI, 29.1% to 71.1%), while the median PFS was 6.2 months (95% CI, 3.0 to 9.3 months). Of 21 patients who underwent at least 1 radiological assessment, 3 (14.3%) achieved partial response, 14 (66.7%) had stable disease, and 4 (19.0%) had progressive disease. The median overall survival was 17.0 months (95% CI, 95% CI, 5.6 to 28.5 months). The main all-grade drug-related toxicities were lymphocytopenia (46.2%), leukopenia (38.5%), anemia (38.5%), and neutropenia (38.5%). Two grade 4 toxicities were reported: Alanine aminotransferase increased and ischemia (each 3.8%), while 31 grade 3 toxicities occurred, with anemia and lymphocytopenia being the most common (each 23.1%). A higher programmed death-ligand 1 composite score was associated with better PFS: 21.2 months (95% CI, 6.0 to 36.4 months) versus 4.2 months (95% CI, 2.7 to 5.6 months), P = 0.045. Conclusions: While further studies are needed, initial findings suggest that nivolumab plus sunitinib could be a valuable addition to the current armamentarium for CCS management. Trial registration: ClinicalTrials.gov ID NCT03277924 (date of registration: 2017 September 6).

The United Kingdom relapsed Wilms tumour (UKW-R) trial aimed to improve the historically low survival rates after relapse of Wilms tumour (WT) through a prospective national risk-stratified protocol. The trial also evaluated efficacy and toxicity of high-dose melphalan.

Stereotactic body radiotherapy (SBRT) has been proven effective for treating small hepatocellular carcinoma (sHCC); however, the comparative efficacy of SBRT and surgical resection remains unknown. This analysis aims to compare the outcomes of SBRT and resection in treating recurrent sHCC.

The current standard treatment for limited-stage small cell lung cancer (LS-SCLC) is concurrent chemoradiotherapy (cCRT) plus consolidation immunotherapy, with or without prophylactic cranial irradiation (PCI). However, it remains unknown whether administering immunotherapy concurrently with chemoradiotherapy confers additional benefit. This clinical trial is designed to investigate the efficacy and safety using durvalumab with chemoradiotherapy for LS-SCLC.

TIGIT and PD-1 trigger distinct but interconnected immunosuppressive pathways. We investigated first-line domvanalimab (Fc-silent anti-TIGIT) plus zimberelimab (anti-PD-1) in PD-L1-high (≥50%), stage IIIB-IV NSCLC.

The proteasome inhibitor bortezomib and purine nucleoside analog clofarabine combination had greater than additive activity in the NCI-ALMANAC preclinical screen. We conducted a phase 1 trial (NCT02211755) to evaluate the combination's safety and efficacy in patients.

T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) is an inhibitory receptor linked to decreased antitumor activity of immune cells. S095018 is a human anti-TIM-3 IgG2 antibody that blocks the binding of phosphatidyl serine to TIM-3. Sym021 is a humanized IgG1 antibody that inhibits the binding of programmed cell death protein-1 (PD-1) to its ligands programmed death-ligand 1 (PD-L1) and PD-L2.

PD-1 and PD-L1 inhibitors have been shown to synergise with anti-angiogenic agents in non-small-cell lung cancer (NSCLC). We aimed to compare benmelstobart plus anlotinib with pembrolizumab in patients with previously untreated, driver gene-negative, PD-L1-positive, advanced NSCLC.

To evaluate the efficacy, safety and underlying mechanisms of toripalimab combined with anlotinib as maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC) who achieved disease control after first-line platinum-etoposide chemotherapy.

KPT-9274, a potentially first-in-class, dual NAMPT/PAK4 inhibitor, has shown single-agent anticancer activity in hematologic and solid tumor cell lines and xenografts. KPT-9274 has shown anti-tumor activity in combination with nivolumab in nonclinical models.

This study aimed to report the incidence, common reasons, and associated risk factors for unplanned hospital presentations during chemotherapy treatment.