Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

Urine proteomics defines an immune checkpoint-associated nephritis signature.

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients.

Contemporary Approach to the Diagnosis and Classification of Intestinal T-cell Lymphomas.

We provide an overview of recent advances in the diagnosis and classification of intestinal T- and NK-cell lymphomas and lymphoproliferative disorders that primarily involve the gastrointestinal (GI) tract. It should be mentioned that systemic T- and NK-cell lymphomas can present initially in the GI tract but are not the focus of this review. Here, we focus on the clinical and pathologic findings of enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, intestinal T-cell lymphoma not otherwise specified, indolent T-cell lymphoproliferative disorder of the GI tract and indolent NK-cell lymphoproliferative disorder of the GI tract (previously known as NK-cell enteropathy).

Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Purpose: Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs.

Adjuvant radiation therapy improves outcome of patients with surgical resected adrenocortical carcinoma.

Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of recurrence and poor prognosis. Previous studies revealed controversial roles of adjuvant radiation therapy (RT) in patient management. This study aimed to investigate the role of adjuvant RT in postoperative ACC patients.

Contribution of Nuclear Fragmentation to Dose and RBE in Carbon-Ion Radiotherapy.

Variable relative biological effectiveness (RBE) of carbon radiotherapy may be calculated using several models, including the microdosimetric kinetic model (MKM), stochastic MKM (SMKM), repair-misrepair-fixation (RMF) model, and local effect model I (LEM), which have not been thoroughly compared. In this work, we compared how these four models handle carbon beam fragmentation, providing insight into where model differences arise. Monoenergetic and spread-out Bragg peak carbon beams incident on a water phantom were simulated using Monte Carlo.

Herpesvirus Infections After Chimeric Antigen Receptor T-Cell Therapy and Bispecific Antibodies: A Review.

In this narrative review, we explore the burden and risk factors of various herpesvirus infections in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAb) for the treatment of hematologic malignancies. Antiviral prophylaxis for herpes simplex/varicella zoster viruses became part of the standard of care in this patient population. Breakthrough infections may rarely occur, and the optimal duration of prophylaxis as well as the timing of recombinant zoster immunization remain to be explored.

The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with Advanced Anal Cancer.

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).

Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types.

Spatial Distribution of Tumor Cells in Clear Cell Renal Cell Carcinoma Is Associated with Metastasis and a Matrisome Gene Expression Signature.

Predicting the behavior of clear cell renal cell carcinoma (ccRCC) is challenging using standard-of-care histopathologic examination. Indeed, pathologic RCC tumor grading, based on nuclear morphology, performs poorly in predicting outcomes of patients with International Society of Urological Pathology/World Health Organization grade 2 and 3 tumors, which account for most ccRCCs. We applied spatial point process modeling of H&E-stained images of patients with grade 2 and grade 3 ccRCCs ( = 72) to find optimum separation into two groups.

A Multidisciplinary Approach to Diagnosing Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Practical Recommendations and Insights from Countries of the Gulf Cooperation Council.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive orphan hematopoietic malignancy characterized by cutaneous and systemic hematologic involvement. BPDCN is frequently misidentified, but early, accurate diagnosis is critical to extending patient survival using tagraxofusp, a first-in-class CD123-targeted therapy, and increasing their chances of receiving a potentially curative stem cell transplantation. Cases of BPDCN in countries of the Gulf Cooperation Council are lower than the extrapolated incidence from other geographic locations due to lack of awareness of key diagnostic features, lack of consensus on the minimal phenotype for diagnosis, and lack of local immunohistochemistry testing facilities, contributing to underdiagnosis in this region.

Genetic Variations in Gene Contribute to Renal Cell Carcinoma Susceptibility: A Genotype-Phenotype Correlation Study.

Background: This study aimed to investigate the polymorphic genotypes of rs937282, rs937283, rs2279744, and rs769412, as well as the combined effects of genotypes and environmental factors on RCC susceptibility.

Methods: A total of 135 RCC patients and 590 controls were recruited for genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Quantitative PCR was performed to assess MDM2 mRNA levels among 30 healthy individuals and 22 RCC patients.

SSTR2-Targeted Theranostics in Hepatocellular Carcinoma.

Background: While the clinical use of radiolabeled somatostatin analogs is well established in neuroendocrine tumors, there is growing interest in expanding their application to other somatostatin receptor 2 (SSTR2)-expressing cancers. This study investigates the potential utility of SSTR2-targeted theranostics in hepatocellular carcinoma (HCC).

Methods: SSTR2 expression in HCC cell lines and clinical samples was evaluated using qRT-PCR, Western blot analysis, and a public dataset.

Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.

Acute myeloid leukemias (AMLs) comprise a group of genetically heterogeneous hematological malignancies that result in the abnormal growth of leukemic cells and halt the maturation process of normal hematopoietic stem cells. Despite using molecular and cytogenetic risk classification to guide treatment decisions, most AML patients survive for less than five years. A deeper comprehension of the disease's biology and the use of new, targeted therapy approaches could potentially increase cure rates.

Direct-Acting Oral Anticoagulants in the Management of Cerebral Venous Sinus Thrombosis-Where Do We Stand?

Background: Cerebral venous sinus thrombosis (CVT) is a rare cause of stroke, constituting 0.5-3% of all strokes with an extremely varied spectrum of presentation, predisposing factors, neuroimaging findings, and eventual outcomes. A high index of suspicion is needed because timely diagnosis can significantly alter the natural course of the disease, reduce acute complications, and improve long-term outcomes.

Exploring Trusted Sources of HPV Vaccine Information Among Mexican American Parents in El Paso, Texas.

Hispanic populations are disproportionately impacted by HPV-associated cancers. An HPV vaccine is available that protects against 90% of HPV-associated cancers. Understanding the factors associated with HPV vaccine uptake, including identifying whom individuals trust to recommend the HPV vaccine, is an important step toward developing public health interventions for promoting the HPV vaccine among Hispanic people.

Spatial transcriptome reveals histology-correlated immune signature learnt by deep learning attention mechanism on H&E-stained images for ovarian cancer prognosis.

Background: The ability to predict the prognosis of patients with ovarian cancer can greatly improve disease management. However, the knowledge on the mechanism of the prediction is limited. We sought to deconvolute the attention feature learnt by a deep learning convolutional neural networks trained with whole-slide images (WSIs) of hematoxylin-and-eosin (H&E)-stained tumor samples using spatial transcriptomic data.

A paper-based HPV E7 oncoprotein assay for cervical precancer detection at the point of care.

Cervical cancer, while preventable through screening and treatment of cervical precancer, remains a global challenge with a disproportionately high burden of disease in resource-limited settings, especially in low- and middle-income countries (LMICs). Lack of affordable, easy-to-use screening and diagnostic tests contributes to this disparity. Most commercially available tests are not appropriate for use in LMICs due to resource constraints.

A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

The Determinants of Toxicity in the Treatment of Prostate Cancer with a Focal, Intraprostatic "Microboost".

Purpose: A single phase III trial has demonstrated that prostate radiotherapy with a focal, intra-prostatic "microboost" can improve disease control without an overall increase in toxicity. It is unclear how these results generalize to other treatment schedules and protocols.

Methods: A systematic search of PubMed and the Cochrane Review was performed for studies published on or before September 1, 2023.

Single-cell analysis of neoplastic plasma cells identifies myeloma pathobiology mediators and potential targets.

Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138 cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models.

Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258.

Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).

Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status.