Supervised Exercise for Patients With Metastatic Breast Cancer: A Cost-Utility Analysis Alongside the PREFERABLE-EFFECT Randomized Controlled Trial.

Purpose: To evaluate the cost utility of a 9-month supervised exercise program for patients with metastatic breast cancer (mBC), compared with control (usual care, supplemented with general activity advice and an activity tracker). Evidence on the cost-effectiveness of exercise for patients with mBC is essential for implementation in clinical practice and is currently lacking.

Methods: A cost-utility analysis was performed alongside the multinational PREFERABLE-EFFECT randomized controlled trial, conducted in 8 centers across Europe and Australia.

Effect of physical exercise on white matter microstructure in chemotherapy-treated breast cancer patients: a randomized controlled trial (PAM study).

Physical exercise is a promising intervention to improve brain white matter integrity. In the PAM study, exercise intervention effects on white matter integrity were investigated in breast cancer patients. Chemotherapy-treated breast cancer patients with cognitive problems were randomized 2-4 years post-diagnosis to an exercise (n = 91) or control group (n = 90).

Coronary Artery Calcium Scores After Prophylactic Premenopausal Bilateral Salpingo-Oophorectomy.

Background: Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at high familial risk of ovarian cancer leads to immediate menopause. Although early natural menopause is associated with increased cardiovascular disease risk, evidence on long-term cardiovascular disease risk after early surgical menopause is scarce.

Objectives: We sought to determine the long-term influence of the timing of RRSO on the development of coronary artery calcium (CAC), an established marker for cardiovascular disease risk.

Conquering Overtreatment of DCIS: Lessons from PRECISION.

As we cannot reliably distinguish indolent, low-risk ductal carcinoma in situ (DCIS) from potentially progressive, high-risk DCIS, all women with DCIS diagnosis undergo intensive treatment without any benefit. The PREvent ductal Carcinoma In Situ Invasive Overtreatment Now team was established to unravel DCIS biology and develop new multidisciplinary approaches for accurate risk stratification to tackle the global problem of DCIS overdiagnosis and overtreatment. See related article by Bressan et al.

Enhanced Recovery After Surgery for patients undergoing radical cystectomy: Surgeons' perspectives and recommendations ten years after its implementation.

Background And Objectives: Enhanced Recovery After Surgery (ERAS) guidelines for Radical Cystectomy (RC) were published over ten years ago. Aim of this systematic review is to update ERAS recommendations for patients undergoing RC and to give an expert opinion on the relevance of each single ERAS item.

Methods: A systematic review was performed to identify the impact of each single ERAS item on RC outcomes.

A conserved switch to less catalytically active Polycomb repressive complexes in non-dividing cells.

Polycomb repressive complex 2 (PRC2), composed of the core subunits EED, SUZ12, and either EZH1 or EZH2, is critical for maintaining cellular identity in multicellular organisms. PRC2 deposits H3K27me3, which is thought to recruit the canonical form of PRC1 (cPRC1) to promote gene repression. Here, we show that EZH1-PRC2 and cPRC1 are the primary Polycomb complexes on target genes in non-dividing, quiescent cells.

DYRK1A-TGF-β signaling axis determines sensitivity to OXPHOS inhibition in hepatocellular carcinoma.

Intervening in mitochondrial oxidative phosphorylation (OXPHOS) has emerged as a potential therapeutic strategy for certain types of cancers. Employing kinome-based CRISPR screen, we find that knockout of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) synergizes with OXPHOS inhibitor IACS-010759 in liver cancer cells. Targeting DYRK1A combined with OXPHOS inhibitors activates TGF-β signaling, which is crucial for OXPHOS-inhibition-triggered cell death.

Multicenter In-House Evaluation of an Amplicon-Based Next-Generation Sequencing Panel for Comprehensive Molecular Profiling.

Background: Predicting response to targeted cancer therapies increasingly relies on both simple and complex genetic biomarkers. Comprehensive genomic profiling using high-throughput assays must be evaluated for reproducibility and accuracy compared with existing methods.

Methods: This study is a multicenter evaluation of the Oncomine™ Comprehensive Assay Plus (OCA Plus) Pan-Cancer Research Panel for comprehensive genomic profiling of solid tumors.

Computer-aided design and fabrication of statistically shaped nasal prostheses: A feasibility study.

Statement Of Problem: A nasal prosthesis may compensate for a partial or complete defect of the nose associated with trauma or amputation. However, the design and production is time-consuming, expensive, and expertize-dependent. Computer-generated prosthesis models and 3D printing can optimize the process.

Radiation doses to the breast and predicted breast cancer risk among patients treated for Hodgkin lymphoma with modern radiotherapy.

Purpose: To contrast breast radiation exposure from chest radiotherapy in 2006-2021 with 1965-1997, and to compare breast cancer (BC) risk 25 years after treatment predicted by two models.

Methods: Radiation dose distributions to the breast from 101 chest radiotherapies given 2006-2021 for Hodgkin lymphoma (HL) or other lymphoma in one German and two Dutch hospitals were compared with doses received by 505 Dutch HL patients treated 1965-1997 and sampled into a nested case-control study, weighted to represent a HL patient cohort. Dose-volume histograms, mean dose and doses to 10 breast segments were evaluated.

Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of Diffuse Large B-cell Lymphoma.

Differentiation of antigen-activated B cells into pro-proliferative germinal center (GC) B cells depends on the activity of the transcription factors MYC and BCL6, and the epigenetic writers DOT1L and EZH2. GCB-like Diffuse Large B Cell Lymphomas (GCB-DLBCLs) arise from GCB cells and closely resemble their cell of origin. Given the dependency of GCB cells on DOT1L and EZH2, we investigated the role of these epigenetic regulators in GCB-DLBCLs and observed that GCB-DLBCLs synergistically depend on the combined activity of DOT1L and EZH2.

Development and Validation of a Deep Learning Model Based on MRI and Clinical Characteristics to Predict Risk of Prostate Cancer Progression.

Purpose To validate a deep learning (DL) model for predicting the risk of prostate cancer (PCa) progression based on MRI and clinical parameters and compare it with established models. Materials and Methods This retrospective study included 1607 MRI scans of 1143 male patients (median age, 64 years; IQR, 59-68 years) undergoing MRI for suspicion of clinically significant PCa (csPCa) (International Society of Urological Pathology grade > 1) between January 2012 and May 2022 who were negative for csPCa at baseline MRI. A DL model was developed using baseline MRI and clinical parameters (age, prostate-specific antigen [PSA] level, PSA density, and prostate volume) to predict the time to PCa progression (defined as csPCa diagnosis at follow-up).

Risk of cancer and reoperation after ileorectal anastomosis and ileal pouch-anal anastomosis in familial adenomatous polyposis.

Objectives: To prevent colorectal cancer (CRC), most patients with familial adenomatous polyposis (FAP) undergo (procto)colectomy with ileorectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA). After surgery, these patients remain at risk of developing cancer in the remnant rectum or rectal cuff/pouch. We aimed to compare the long-term risk of cancer following IRA or IPAA in FAP.

Benefit and Harms of Radical Nephroureterectomy as Part of a Multimodal Treatment Strategy for Upper Tract Urothelial Carcinoma Patients Presenting with Clinical Evidence of Regional Lymph Node Metastasis: A Systematic Review and Meta-analysis by the European Association of Urology Guidelines.

Background And Objective: Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate.

The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).

Background: Many patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit of TT which only intervenes in one pathway. This hypothesis was tested in the Drug Rediscovery Protocol (DRUP).

Deintensification of Radiotherapy Use in Treatment of Ductal Carcinoma In Situ in the Netherlands-A Nationwide Overview From 2008 Until 2022.

Aims: Ductal Carcinoma In Situ (DCIS) treated by breast-conserving surgery followed by radiotherapy aims to decrease the probability of locally recurrent disease. The role of whole breast irradiation, specifically in DCIS having low recurrence risk and low risk of becoming invasive, is increasingly debated. Also, the added value of applying boost irradiation in DCIS has been questioned.

Generation of effective and specific human TCRs against tumor/testis antigen NY-ESO-1 in mice with humanized T cell recognition system.

Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.

Endocrine dysfunction in long-term survivors of pediatric head and neck rhabdomyosarcoma.

Objective: Survivors of pediatric head and neck rhabdomyosarcoma (HNRMS) are at risk of developing endocrinopathies following local treatment, resulting from radiation damage to the pituitary gland, hypothalamus, or thyroid gland, often at a young age. Our aim was to determine the prevalence of endocrine dysfunction in long-term HNRMS survivors and compare the prevalence of anterior pituitary insufficiency (API) among different local treatment strategies: external beam radiation with photons, external beam radiation with protons, microscopically radical surgery combined with external irradiation, and macroscopic radical surgery combined with brachytherapy.

Design And Methods: Head and neck rhabdomyosarcoma survivors treated between 1993 and 2017, with ≥2 years of follow-up, without recurrent disease or secondary malignancy were eligible for this study.

Local and systemic biodistribution of a small-molecule radiopharmaceutical probe after transcatheter embolization and intra-arterial delivery in a porcine orthotopic renal tumor model.

Background: Small-molecule biomacromolecules target tumor-specific antigens. They are employed as theranostic agents for imaging and treatment. Intravenous small-molecule radioligands exhibit rapid tumor uptake and excretion.

MRI of the Rectum: A Decade into DISTANCE, Moving to DISTANCED.

Over the past decade, advancements in rectal cancer research have reshaped treatment paradigms. Historically, treatment for locally advanced rectal cancer has focused on neoadjuvant long-course chemoradiotherapy, followed by total mesorectal excision. Interest in organ preservation strategies has been strengthened by the introduction of total neoadjuvant therapy with improved rates of complete clinical response.

NAC regulates metabolism and cell fate in intestinal stem cells.

Intestinal stem cells (ISCs) face the challenge of integrating metabolic demands with unique regenerative functions. Studies have shown an intricate interplay between metabolism and stem cell capacity; however, it is still not understood how this process is regulated. Combining ribosome profiling and CRISPR screening in intestinal organoids, we identify the nascent polypeptide-associated complex (NAC) as a key mediator of this process.

A Repurposed Drug Selection Pipeline to Identify CNS-Penetrant Drug Candidates for Glioblastoma.

Background: Glioblastoma is an aggressive and incurable type of brain cancer. Little progress has been made in the development of effective new therapies in the past decades. The blood-brain barrier (BBB) and drug efflux pumps, which together hamper drug delivery to these tumors, play a pivotal role in the gap between promising preclinical findings and failure in clinical trials.

Enhancing Data Completeness in Early Detection Pathway of Prostate Cancer: Integration of a Dashboard-Driven Feedback Tool to Improve Quality of Care.

: Quality assurance in data collection is essential as data quality directly impacts the accuracy and reliability of outcomes. In the context of early detection of prostate cancer, improving data completeness is a key focus for enhancing patient care. This study aimed to evaluate the effectiveness of a data-driven feedback tool, visualized through a dashboard, in improving the completeness of data collection by healthcare professionals.

Clinical Introduction of Stem Cell Sparing Radiotherapy to Reduce the Risk of Xerostomia in Patients with Head and Neck Cancer.

Background/objectives: Studies have shown that dose to the parotid gland stem cell rich (SCR) regions should be reduced to lower the risk of xerostomia after radiotherapy (RT). This study aimed to assess whether stem cell sparing (SCS)-RT can be adopted in routine clinical practice.

Methods: Multiple planning studies were performed to compare SCS-RT with standard (ST)-RT using 30 head and neck cancer patients.