A taxonomy of the factors contributing to the overtreatment of cancer patients at the end of life. What is the problem? Why does it happen? How can it be addressed?

Many patients with cancer approaching the end of life (EOL) continue to receive treatments that are unlikely to provide meaningful clinical benefit, potentially causing more harm than good. This is called overtreatment at the EOL. Overtreatment harms patients by causing side-effects, increasing health care costs, delaying important discussions about and preparation for EOL care, and occasionally accelerating death.

Benchmarking lung cancer screening programmes with adaptive screening frequency against the optimal screening schedules derived from the ENGAGE framework: a comparative microsimulation study.

Background: Lung cancer screening recommendations employ annual frequency for eligible individuals, despite evidence that it may not be universally optimal. The impact of imposing a structure on the screening frequency remains unknown. The ENGAGE framework, a validated framework that offers fully dynamic, analytically optimal, personalised lung cancer screening recommendations, could be used to assess the impact of screening structure on the effectiveness and efficiency of lung cancer screening.

Mutational and Co-Mutational Landscape of Early Onset Colorectal Cancer.

Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs.

Flow-Through Flaps as a Robust Method for Advanced Free Flap Reconstruction in the Head and Neck: A Multi-Institutional Experience.

Background: Flow-through flaps (FTFs) are an advanced technique in which a free flap is anastomosed to the pedicle of another free flap to reconstruct extensive head and neck defects when recipient vessels are scarce.

Methods: A multi-institutional cohort of FTFs used for head and neck reconstruction were reviewed. For comparison, FTF outcomes were compared to free flaps that required vein grafts (VG) to reach distant recipient vessels.

Configuring thermal ablation volumes for treatment of distinct tumor shapes: a repeatability study using a robotic approach.

Objectives: In the current clinical practice of thermal ablation treatment for liver tumors, achieving consistent and effective clinical outcomes across tumors of varying shapes, sizes and locations remains challenging. The aim of this study was to evaluate the repeatability of a novel robotic approach for configurable ablation of distinct tumor shapes and compare it to the standard ablation technique for creating ellipsoidal ablation volumes.

Materials And Methods: The repeatability was evaluated in terms of width variability in created ablation volumes.

Genomic and Transcriptomic Profiling of Digital Papillary Adenocarcinomas Reveals Alterations in Matrix Remodeling and Metabolic Genes.

Background: Digital papillary adenocarcinoma (DPAC) is a rare but aggressive cutaneous malignant sweat gland neoplasm that occurs on acral sites. Despite its clinical significance, the cellular and genetic characteristics of DPAC remain incompletely understood.

Methods: We conducted a comprehensive genomic and transcriptomic analysis of DPAC (n = 14) using targeted next-generation DNA and RNA sequencing, along with gene expression profiling employing the Nanostring Technologies nCounter IO 360 Panel.

Hyper-CVAD and Sequential Blinatumomab Without and With Inotuzumab in Young Adults With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia.

Adding inotuzumab ozogamicin (InO) to hyper-CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL). Patients with newly diagnosed B-ALL received up to four cycles of hyper-CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.

Early outcomes following local salvage treatment with MRI-assisted low-dose rate brachytherapy (MARS) for MRI-visible postsurgical bed recurrences and focal intraprostatic recurrences.

Background: To determine outcomes of MRI-assisted radiosurgery (MARS) for salvage brachytherapy using the radioisotope Pd after various upfront treatments including surgery, external beam radiotherapy, and brachytherapy.

Methods: We retrospectively reviewed data for patients who underwent salvage MARS for intraprostatic lesions or prostate bed recurrences from 2016 to 2022. Biochemical recurrence, prostate cancer-specific, and overall survival, and the cumulative incidences of toxicities, were determined by Kaplan-Meier estimates.

Defining the optimal radiation-induced lymphopenia metric to discern its survival impact in esophageal cancer.

Background: A detrimental association between radiation-induced lymphopenia (RIL) and oncologic outcomes in esophageal cancer patients has been established. However, an optimal metric for RIL remains undefined, but is important for application of this knowledge in clinical decision-making and trial designs. The aim of this study was to find the optimal RIL metric discerning survival.

Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR+/HER2- metastatic breast cancer in the US real-world setting.

Background: Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice.

Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells.

CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226.

Navigating the Economic Burden of Multiple Myeloma: Insights into Cost-effectiveness of CAR-T and Bispecific Antibody Therapies.

Purpose Of Review: Multiple myeloma is a chronic malignancy and with evolving treatment options, understanding the economic burden and cost-effectiveness of therapies is crucial for clinicians and researchers.

Recent Findings: In this, we review the recent approval of Bispecific antibodies and CAR-T for myeloma and their cost implications, including direct and indirect costs. We compare this to current regimens and provide cost comparisons in this review.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients With Advanced Thymoma or Thymic Carcinoma.

Background: Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare thoracic tumors of the anterior mediastinum. For those with advanced disease, platinum-based chemotherapy is used as first-line treatment. However, there is no standard regimen established for TET at progression after initial therapy, and treatment options for advanced/recurrent TETs are limited.

Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets.

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.

Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells that express IL-10.

Disseminated cancer cells in the peritoneal fluid often colonize omental fat-associated lymphoid clusters but the mechanisms are unclear. Here, we identify that innate-like B cells accumulate in the omentum of mice and women with early-stage ovarian cancer concomitantly with the extrusion of chromatin fibers by neutrophils called neutrophil extracellular traps (NETs). Studies using genetically modified NET-deficient mice, pharmacologic inhibition of NETs, and adoptive B cell transfer show that NETs induce expression of the chemoattractant CXCL13 in the pre-metastatic omentum, stimulating recruitment of peritoneal innate-like B cells that in turn promote expansion of regulatory T cells and omental metastasis through producing interleukin (IL)-10.

The Prognostic Role of HPV or p16INK4a Status in Penile Squamous Cell Carcinoma: A Meta-Analysis.

Background: HPV infection is implicated in approximately half of global penile squamous cell carcinoma (PSCC) cases. Previous studies on HPV DNA and p16INK4a status in PSCC have yielded inconclusive prognostic findings. This meta-analysis aims to elucidate the prognostic role of HPV in PSCC by pooling data on disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS).

Investigation of mesenchymal stem cell secretome on breast cancer gene expression: A bioinformatic approach to identify differentially expressed genes, functional networks, and potential therapeutic targets.

The mesenchymal stem cell (MSC) secretome plays a pivotal role in shaping the tumor microenvironment, influencing both cancer progression and potential therapeutic outcomes. In this research, by using publicly available dataset GSE196312, we investigated the role of MSC secretome on breast cancer cell gene expression. Our results raveled differentially expressed genes, including the upregulation of Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 1 (PREX1), C-C Motif Chemokine Ligand 28 (CCL28), and downregulation of Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type I Alpha 3 Chain (COL1A3), Collagen Type III Alpha 1 Chain (COL3A1), which contributing to extra cellular matrix (ECM) weakening and promoting cell migration.

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.