Neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN) can substantially affect quality of life. The capsule and granule formulations of selumetinib (ARRY-142886, AZD6244) are approved for pediatric patients with symptomatic, inoperable NF1-PN (age ≥1 to 3 years, region dependent). SPRINKLE (ClinicalTrials.gov identifier: NCT05309668) assessed pharmacokinetics (PK), safety, and palatability of the selumetinib granule formulation in children (age ≥1 to <7 years) with symptomatic, inoperable NF1-PN.

Arm D of the AcSé-ESMART proof-of-concept phase I/II platform trial aimed to define the recommended phase II dose (RP2D), pharmacokinetics, activity, and biomarkers of the PARP inhibitor olaparib with irinotecan in pediatric patients with recurrent/refractory malignancies.

To evaluate the efficacy and safety of the anti-lymphocyte activation gene-3 (LAG-3) antibody IBI110 in combination with sintilimab and chemotherapy in patients with advanced squamous non-small cell lung cancer (sqNSCLC).

Salmonella-IL2 is an attenuated Salmonella Typhimurium strain carrying the human gene for IL-2. When orally administered in preclinical trials, the bacterium colonizes tumors and locally releases IL-2, triggering immunologically-mediated tumor cell killing without untoward side effects. A non-randomized, phase 2 study evaluated the combination of Salmonella-IL2 with standard of care (SOC) chemotherapy where patients received Salmonella-IL2 plus FOLFIRINOX (FFX). Overall survival (OS), progression-free survival (PFS), safety, and biomarker data in each arm were studied. In total, 34 patients (30 in the trial, 4 via EAP) were enrolled: 26 received Salmonella-IL2 with FOLFIRINOX. Those patients who received more than five doses of Salmonella-IL2 with FOLFIRINOX (n = 20) had a mPFS of 15 months while the mOS was 20.3 months. Even though there were no complete responses, the partial response rate and the overall response rate was 70.0%. In addition, 41 serious adverse events were noted and attributed to SOC chemotherapy agents but none to Salmonella-IL2. Addition of Salmonella-IL2 to FOLFIRINOX is associated with increased mPFS and mOS when compared to previously reported outcomes with FOLFIRINOX alone in the literature. A multicenter, randomized, phase 3 trial is warranted. ClinicalTrials.gov identifier: NCT04589234.

We previously reported a phase II Kyoto trial for platinum-resistant ovarian cancer (n = 20) using nivolumab (anti-programmed cell death-1 [PD-1] antibody). We evaluated the associations between clinical outcomes and transcriptomics and T and B cell clonality from tumor and blood cells.

Background: The five-year survival rate of patients with ovarian cancer remains less than 50%, secondary to chemotherapy resistance. Purpose: This study aims to evaluate the effects of itraconazole as a supplementary treatment with paclitaxel and carboplatin on malignancy response and in preventing the initial development of chemoresistance in chemotherapy-naïve patients with advanced ovarian epithelial cancer. Method: This randomized placebo-controlled double-blind study involved 60 chemotherapy-naïve patients with advanced epithelial ovarian malignancy who were randomized into two arms; the placebo and itraconazole groups. The placebo group received six chemotherapy cycles and four inactive capsules, while the itraconazole group received six chemotherapy cycles and 400 mg oral itraconazole for five days per cycle. Results: Following completion of six chemotherapy cycles and when contrasted with the control arm, the itraconazole arm demonstrated statistically significant improvements in tumor response. The objective response rate was 80% in the itraconazole group compared with 47% in the placebo group (p = 0.015), while the disease control rate was 100% versus 80%, respectively (p = 0.023). The median progression-free survival (PFS), defined as the time point at which 50% of patients experienced disease progression or death, was 13.5 months for the overall study population. PFS was evaluated as a fixed-time endpoint at 18 months following completion of chemotherapy for the overall study population. Progression-free survival was significantly improved in the itraconazole group, with 70% of patients remaining progression-free compared with 26.7% in the placebo group (p = 0.001). Also, the itraconazole group produced significant declines in the serum levels of CA-125 (p = 0.005) and p-glycoprotein (p = 0.042) with significant elevation in VEGFR-2 (p = 0.006) as compared to the control group. Itraconazole was safe and its use was associated with a significant improvement in the quality of life (QOL). Conclusions: Itraconazole could represent a promising add-on therapy to enhance tumor response to chemotherapy in patients with ovarian cancer.

Postoperative early recurrence (ER) of biliary tract cancers (BTCs) leads to significant medical, psychological, social, and economic disadvantages for patients. Approximately 30% of patients with curatively resected BTCs experience recurrence within the first 12 months after the surgery. JCOG1202 randomized phase III trial demonstrated the survival benefit of adjuvant S-1 in patients with resected BTCs. The objective of this exploratory study was to investigate the risk factors for ER in patients with resected BTCs in the JCOG1202 cohort.

The incidence of colorectal cancer (CRC) is increasing in individuals aged < 50 years of age. This study aimed to examine whether high-frequency follow-up after CRC surgery reduces 5-year overall mortality, cancer-specific mortality and recurrence in patients with CRC aged ≤ 50 years.

SMET12 is a bispecific T-cell engager targeting epidermal growth factor receptor (EGFR) and CD3. This phase 2 clinical trial aimed to investigate the efficacy and safety of SMET12 plus toripalimab and chemotherapy among advanced non-small-cell lung cancer (NSCLC) patients tested positive for EGFR protein, including treatment-naïve patients, patients with resistance to first-line immune checkpoint inhibitors-containing therapy and EGFR-mutated patients with resistance to first-line EGFR tyrosine kinase inhibitors (TKIs), and to examine the associations of lymphocyte numbers and differentiation patterns with therapeutic efficacy among advanced NSCLC patients.

The CJLSG1901 phase 2 study evaluated efficacy and safety of pembrolizumab plus pemetrexed in older populations. A novel first-line approach for older patients with metastatic non-squamous non-small cell lung cancer (NSCLC) was assessed.

The ALICE trial demonstrated that adding atezolizumab to anthracycline-based immunomodulatory chemotherapy improved progression-free survival (PFS) in patients with metastatic triple-negative breast cancer (mTNBC), including those with PD-L1-negative tumors. Here, we report the patient-reported outcome measures (PROMs).

This first-in-human phase I/IIa study evaluated auceliciclib, a second-generation, highly selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor with potent antitumour activity, high brain penetration, and a wide preclinical therapeutic index. The trial assessed safety, tolerability, pharmacokinetics, and preliminary efficacy of auceliciclib as monotherapy in advanced solid tumours (phase I) and in combination with temozolomide for recurrent/relapsed high-grade glioma (phase IIa).

Supervised exercise may provide greater functional and quality of life benefits than unsupervised programs after cancer and is recommended for those with or at risk of breast cancer-related lymphedema. These exploratory analyses compared the effect of low- vs high-supervision exercise on the secondary survivorship outcomes of the SAFE breast cancer trial.

The recently-updated TROG 99.03/ALLGLow5 multicentre randomised controlled trial showed that long-term progression-free survival (PFS) in early-stage (I-II) follicular lymphoma (ESFL) after involved-field radiotherapy (IFRT) was dramatically improved by adjuvant rituximab-cyclophosphamide/vincristine/prednisolone (R-CVP) but not CVP. Secondary analyses are presented here.

Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive malignancy. Dabrafenib plus trametinib has shown efficacy in BRAFV600E-mutant ATC, but effective therapies remain limited for patients without this mutation. This study aimed to evaluate the efficacy and safety of anlotinib plus sintilimab in BRAFV600E-negative ATC.

Linked color imaging (LCI) has been shown to improve the visibility of gastric lesions and may enhance the detection of gastric superficial neoplasia (GSN). The aim was to compare the detection performance of LCI versus white light imaging (WLI) in patients referred for endoscopic resection of GSNs.

A multicenter, randomized phase II trial to compare two first-line triplet treatments for advanced pancreatic ductal adenocarcinoma (PDAC).

Ovarian cancer remains a formidable therapeutic challenge due to late diagnosis, high recurrence rates, and limited treatment options. Mesothelin (MSLN) is highly expressed in ovarian cancer, making it a promising target for immunotherapy. Given this target profile, the authors developed a novel T-cell receptor (TCR)-like chimeric antigen receptor (CAR) T-cell therapy targeting MSLN, designated KT127.

To evaluate the diagnostic value of a magnetic resonance imaging (MRI)-based imaging heterogeneity scoring system for differentiating high-grade glioma (HGG) from primary central nervous system lymphoma (PCNSL). This multicenter retrospective study analyzed clinical and preoperative MRI data from 314 pathologically confirmed cases (HGG = 167, PCNSL = 147), comprising 211 patients with single lesions (HGG = 130, PCNSL = 81) and 103 with multifocal lesions (HGG = 37, PCNSL = 66). Patients were randomly assigned to training (single-lesion: n = 147; multifocal: n = 72) and validation (single-lesion: n = 64; multifocal: n = 31) sets in a 7:3 ratio. Distinctive imaging features were used to construct separate logistic regression (LR) models for single-lesion and multifocal-lesion cases, with corresponding scoring systems developed. A baseline model incorporating conventional predictors was developed for comparison. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves (area under the curve [AUC], 95% confidence interval [CI]), Hosmer-Lemeshow tests (goodness-of-fit), calibration curves, and decision curve analysis (DCA). A sensitivity analysis was performed on excluded steroid-treated patients. For single-lesion cases, the training and validation AUCs were 0.940 (95%CI: 0.897-0.983) and 0.908 (0.836-0.981), respectively. Multifocal models achieved training and validation AUCs of 0.960 (0.921-0.999) and 0.927 (0.805-1.000). The heterogeneity scoring system demonstrated significant incremental value over the baseline model (ΔAUC: +0.160-0.290). Hosmer-Lemeshow tests indicated excellent model fit (single-lesion training: χ²= 2.489, P = 0.778; validation: χ² = 6.193, P= 0.185; multifocal training: χ² = 1.760, P = 0.881; validation: χ² = 9.241, P = 0.055). DCA demonstrated substantial net clinical benefit across threshold probabilities. The scoring systems established diagnostic thresholds as follows: ≥ 19 points for HGG (single-lesion) and > 19 points (multifocal), with lower scores indicating PCNSL. Center-stratified validation and repeated cross-validation confirmed strong generalizability across institutions (AUC: 0.934-0.941). The system maintained robust performance in the sensitivity analysis of steroid-treated patients. This MRI heterogeneity-based scoring system provides robust diagnostic accuracy for distinguishing HGG from PCNSL, serving as an objective clinical decision-support tool.

Neuroendocrine neoplasms (NEN) are a heterogeneous disease and chemotherapy (CT) represents the standard first-line treatment for those with a Ki-67 index >20%.