Incidence and Outcomes of Patients With Mismatch Repair Deficient Rectal Cancer Operated in 2016: A Nationwide Cohort From The Netherlands.

Introduction: Data regarding the incidence and outcomes of mismatch repair deficient (dMMR) rectal cancer is limited. This study characterizes dMMR rectal cancer patients, comparing response after neoadjuvant radiotherapy and oncological outcomes to mismatch repair proficient (pMMR) rectal cancer patients.

Method: A retrospective cross-sectional cohort study was conducted in 67 Dutch centers.

A hepatocellular carcinoma model with and without parenchymal liver damage that integrates technical and pathophysiological advantages for therapy testing.

Hepatocellular Carcinoma (HCC) is the most common form of primary liver cancer, with cirrhosis being its strongest risk factor. Interestingly, an increasing number of HCC cases is also observed without cirrhosis. We developed an HCC model via intrasplenic injection of highly tumorigenic HCC cells, which, due to cellular tropism, invade the liver and allow for a controllable disease progression.

Two case reports of breast cancer combined with synchronous primary intrahepatic cholangiocarcinoma/mixed liver cancer.

Rationale: This case report discusses multiple primary malignant tumors, which refer to the occurrence of 2 or more different histological types of malignant tumors simultaneously or successively in the same individual.

Patient Concerns: We present 2 female patients who were admitted to the hospital due to a "left breast mass" and were found to have multiple solid masses in the liver upon imaging.

Diagnoses: Postoperative pathology revealed that one patient had breast invasive ductal carcinoma was complicated with primary intrahepatic cholangiocarcinoma and mixed hepatocellular carcinoma with intrahepatic cholangiocarcinoma.

Dual inhibition of HERs and PD-1 counteract resistance in KRAS-mutant head and neck cancer.

Background: Basket clinical trials targeting the KRAS-mutation in solid tumors have shown initial promise, including in orphan KRAS head and neck cancer (HNC). However, development of resistance to KRAS-mutant-specific inhibitors (KRASi) remains a major obstacle. Here, we investigated the intrinsic (tumor-cell autonomus) and tumor-microenvironment (TME) mechanisms of resistance to the KRASi-MRTX849 and AMG510 in a unique syngenic murine KRAS-mutated HNC cell line.

A novel mouse model recapitulating the MMR-defective SCLC subtype uncovers an actionable sensitivity to immune checkpoint blockade.

Purpose: Small cell lung cancer (SCLC) has an extremely poor prognosis. Despite high initial response rates to chemotherapy and modest survival improvements with the addition of immune checkpoint inhibitors (ICI), almost all patients experience relapse and fatal outcomes. Recent genomic insights uncovered extensive molecular heterogeneity in addition to the almost uniform loss of RB1 and TRP53.

Benchmark of screening markers for KEAP1/NFE2L2 mutations and joint analysis with the K1N2-score.

Our recently published K1N2-score robustly predicts KEAP1/NFE2L2-mutations and pathway activation status, while its accessibility might be limited. We tested if the RNA expression data of six pathway-related genes and NQO1-IHC might be a reliable alternative using 348 KEAP1/NFE2L2 mutation-enriched NSCLC. While TXNRD1 RNA testing was the best-performing single-gene test, the combination of single-gene screening and validation with the K1N2-score achieved the highest performance when predicting mutation status or pathway activation.

Protocol compliance in a multicentric phase III trial investigating scheduled adaptive radiotherapy and dose painting in head and neck cancer.

Purpose: To report on quality assurance (QA) and protocol adherence (PA) in a multicentre phase III trial for head and neck cancer, evaluate patterns of protocol deviations and investigate the effect of PA on study outcomes.

Methods: All 221 patients from the ARTFORCE trial (NCT01504815) were included in this study. Pre- and per-treatment QA measures included protocol guidelines, a dummy run, early case reviews and trial meetings.

The Immunomodulatory Effect of Different FLT3 Inhibitors on Dendritic Cells.

Background: FMS-like tyrosine kinase 3 (FLT3) mutations or internal tandem duplication occur in 30% of acute myeloid leukemia (AML) cases. In these cases, FLT3 inhibitors (FLT3i) are approved for induction treatment and relapse. Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the recommended post-induction therapy for suitable patients.

Improving cancer outcomes through enhanced leadership and strategy training for cancer healthcare professionals - A course developed by the European School of Oncology (ESO), the European Cancer Organization (ECO) and Sharing Progress in Cancer Care (SPCC).

Leadership as a key building block of a health system plays a crucial role in achieving high performance and helps deliver change and shape the policy agenda and its implementation. Echoing the emerging need for effective leaders in Oncology, the "Improving Cancer Outcomes and Leadership Course" was developed jointly by the European School of Oncology (ESO), the European Cancer Organization (ECO) and Sharing Progress in Cancer Care (SPCC). The course was offered as a hybrid event online and in Warsaw in June 2022.

Uptake of Risk-Reducing Surgeries in an International Real-World Cohort of Hispanic Women.

Purpose: Women with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake.

Analysis of the efficacy of Prostatic Artery Embolization in the treatment of Benign Prostatic Hyperplasia.

Objectives: To investigate the safety and efficacy of prostatic artery embolization (PAE) in the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH), and to investigate predictors of clinical success of PAE.

Methods: A retrospective analysis was used to collect 107 patients [median age 81.0 (73.

Long-Term Human Immune Reconstitution, T-Cell Development, and Immune Reactivity in Mice Lacking the Murine Major Histocompatibility Complex: Validation with Cellular and Gene Expression Profiles.

Background: Humanized mice transplanted with CD34 hematopoietic cells (HPCs) are broadly used to study human immune responses and infections in vivo and for testing therapies pre-clinically. However, until now, it was not clear whether interactions between the mouse major histocompatibility complexes (MHCs) and/or the human leukocyte antigens (HLAs) were necessary for human T-cell development and immune reactivity.

Methods: We evaluated the long-term (20-week) human hematopoiesis and human T-cell development in NOD Scid Gamma (NSG) mice lacking the expression of MHC class I and II (NSG-DKO).

NAT10 resolves harmful nucleolar R-loops depending on its helicase domain and acetylation of DDX21.

Background: Aberrant accumulation of R-loops leads to DNA damage, genome instability and even cell death. Therefore, the timely removal of harmful R-loops is essential for the maintenance of genome integrity. Nucleolar R-loops occupy up to 50% of cellular R-loops due to the frequent activation of Pol I transcription.

Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET-Mutated Non-Small Cell Lung Cancer-Results from the Drug Rediscovery Protocol.

Purpose: To provide patients with MET-mutated advanced non-small cell lung cancer (METmut aNSCLC) access to crizotinib, further substantiate evidence of its efficacy and safety in this setting, and find potential biomarkers for nonresponse.

Patients And Methods: In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring MET exon 14 skipping or other MET mutations received crizotinib 250 mg BID until disease progression or intolerable toxicity.

Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).

Background: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

Objectives: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

Repurposing chemotherapy-induced peripheral neuropathy grading.

Background And Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is perceived differently by patients and physicians, complicating its assessment. Current recommendations advocate combining clinical and patient-reported outcomes measures, but this approach can be challenging in patient care. This multicenter European study aims to bridge the gap between patients' perceptions and neurological impairments by aligning both perspectives to improve treatment decision-making.

Neoadjuvant Immunotherapy Alone for Patients With Locally Advanced and Resectable Metastatic Colorectal Cancer of dMMR/MSI-H Status.

Background: The use of programmed death-1 blockade has a significant therapeutic effect in patients with mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. However, data on preoperative single-agent programmed death-1 blockade are rare.

Objective: This study aims to evaluate the effectiveness and safety of preoperative programmed death-1 blockade as a conversion strategy in patients with locally advanced and resectable metastatic mismatch repair-deficient/microsatellite instability-high colorectal cancer.

A translational framework to DELIVER nanomedicines to the clinic.

Nanomedicines have created a paradigm shift in healthcare. Yet fundamental barriers still exist that prevent or delay the clinical translation of nanomedicines. Critical hurdles inhibiting clinical success include poor understanding of nanomedicines' physicochemical properties, limited exposure in the cell or tissue of interest, poor reproducibility of preclinical outcomes in clinical trials, and biocompatibility concerns.

Analysis of re-recurrent rectal cancer after curative treatment of locally recurrent rectal cancer.

Purpose: Substantiating data guiding clinical decision making in locally recurrent rectal cancer (LRRC) is lacking, specifically in target volume (TV) definition for chemoradiotherapy (CRT). A case-by-case review of local re-recurrences (re-LRRC) after multimodal treatment for LRRC was performed, to determine location of re-LRRC and assess whether treatment could have been improved.

Methods: All patients treated with curative intent for LRRC at the Catharina Hospital Eindhoven from October 2016 onwards, in whom complete imaging of (re-)LRRC and radiotherapy was available, were retrieved.

Circular RNAs in human diseases.

Circular RNAs (circRNAs) are a unique class of RNA molecules formed through back-splicing rather than linear splicing. As an emerging field in molecular biology, circRNAs have garnered significant attention due to their distinct structure and potential functional implications. A comprehensive understanding of circRNAs' functions and potential clinical applications remains elusive despite accumulating evidence of their involvement in disease pathogenesis.

Non-invasive multimodal CT deep learning biomarker to predict pathological complete response of non-small cell lung cancer following neoadjuvant immunochemotherapy: a multicenter study.

Objectives: Although neoadjuvant immunochemotherapy has been widely applied in non-small cell lung cancer (NSCLC), predicting treatment response remains a challenge. We used pretreatment multimodal CT to explore deep learning-based immunochemotherapy response image biomarkers.

Methods: This study retrospectively obtained non-contrast enhanced and contrast enhancedbubu CT scans of patients with NSCLC who underwent surgery after receiving neoadjuvant immunochemotherapy at multiple centers between August 2019 and February 2023.

Effects of Different Combinations of Phytochemical-Rich Fruits and Vegetables on Chronic Disease Risk Markers and Gene Expression Changes: Insights from the MiBLEND Study, a Randomized Trial.

Adequate fruit and vegetable (F and V) intake, as recommended by the World Health Organization (over 400 g/day), is linked to reduced chronic disease risk. However, human intervention trials, especially with whole F and V and in complex combinations, are lacking. The MiBlend Study explored the effects of various phytochemical-rich F and V combinations on chronic disease risk markers, phytochemical absorption, and gene expression in blood.