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.

Molecular Testing for the World Health Organization Classification of Central Nervous System Tumors: A Review.

Importance: Molecular techniques, including next-generation sequencing, genomic copy number profiling, fusion transcript detection, and genomic DNA methylation arrays, are now indispensable tools for the workup of central nervous system (CNS) tumors. Yet there remains a great deal of heterogeneity in using such biomarker testing across institutions and hospital systems. This is in large part because there is a persistent reluctance among third-party payers to cover molecular testing.

LUCAT1-Mediated Competing Endogenous RNA (ceRNA) Network in Triple-Negative Breast Cancer.

Breast cancer is a heterogeneous disease comprising multiple molecularly distinct subtypes with varied prevalence, prognostics, and treatment strategies. Among them, triple-negative breast cancer, though the least prevalent, is the most aggressive subtype, with limited therapeutic options. Recent emergence of competing endogenous RNA (ceRNA) networks has highlighted how long noncoding RNAs (lncRNAs), microRNAs (miRs), and mRNA orchestrate a complex interplay meticulously modulating mRNA functionality.

Multiplex digital profiling of DNA methylation heterogeneity for sensitive and cost-effective cancer detection in low-volume liquid biopsies.

Molecular alterations in cancerous tissues exhibit intercellular genetic and epigenetic heterogeneity, complicating the performance of diagnostic assays, particularly for early cancer detection. Conventional liquid biopsy methods have limited sensitivity and/or ability to assess epigenetic heterogeneity of rare epiallelic variants cost-effectively. We report an approach, named REM-DREAMing (Ratiometric-Encoded Multiplex Discrimination of Rare EpiAlleles by Melt), which leverages a digital microfluidic platform that incorporates a ratiometric fluorescence multiplex detection scheme and precise digital high-resolution melt analysis to enable low-cost, parallelized analysis of heterogeneous methylation patterns on a molecule-by-molecule basis for the detection of cancer in liquid biopsies.

Phase 2 Trial of Veliparib, Local Irradiation and Temozolomide in Patients with Newly Diagnosed High-Grade Glioma: A Children's Oncology Group Study.

Background: The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy.

Methods: We conducted a single-arm, non-randomized phase 2 clinical trial to determine whether treatment with veliparib and radiotherapy, followed by veliparib and temozolomide, improves progression-free survival in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations compared to patient level data from historical cohorts with closely matching clinical and molecular features.

Phase 1 Study of Adjuvant Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor-Transduced Pancreatic Tumor Cell Vaccine, Low-Dose Cyclophosphamide, and Stereotactic Body Radiation Therapy Followed by FOLFIRINOX in High-Risk Resected Pancreatic Ductal Adenocarcinoma.

Purpose: Local and distant progression remains common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase 1 trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy), and stereotactic body radiation therapy (SBRT) followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC.

Patients And Methods: The study design was a modified 3+3.

Imetelstat: A new addition to the Therapeutic Landscape of Lower-Risk MDS.

Anemia is the most prevalent cytopenia in lower-risk myelodysplastic neoplasms (LR-MDS). There is a paucity of drugs for red blood cell transfusion dependence (RBC-TD) and erythropoiesis-stimulating agents (ESAs) are the mainstay of therapy in many centers. Imetelstat, an oligonucleotide telomerase inhibitor, was recently approved for RBC-TD LR-MDS adults who are ineligible or failed prior ESA therapy.

Using a Pre-Radiation Window to Identify Potentially Active Cytotoxic Agents in Adults with Newly Diagnosed Glioblastoma.

Background: Therapies shown to improve outcomes in patients with recurrent cancers are commonly used in the neoadjuvant setting to optimize surgery, reduce radiation fields, and treat micro-metastatic disease. While pre-radiation chemotherapy (PRC) use has flourished in systemic cancers, it has not in glioblastomas. This review documents these trajectories and highlights the potential of PRC to rapidly and safely screen cytotoxic drugs for efficacy in patients with newly diagnosed glioblastoma.

pSTAT3 Expression is Increased in Advanced Prostate Cancer in Post-Initiation of Androgen Deprivation Therapy.

Background: The transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) plays a role in carcinogenesis and is involved in processes, such as proliferation, differentiation, drug resistance and immunosuppression. STAT3 can be activated by phosphorylation of tyrosine at position 705 (pSTAT3) or serine at 727 (pSTAT3). High expression levels of pSTAT3 are implicated in advanced stages of prostate cancer (PCa) and are known to interact with the androgen receptor signaling pathway.

ZNFX1 is a Novel Master Regulator in Epigenetically-induced Pathogen Mimicry and Inflammasome Signaling in Cancer.

DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining DNMTis and PARPis upregulates expression of a little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). We demonstrate that ZNFX1 is a novel master regulator for PMR induction in mitochondria, serving as a gateway for STING-dependent PMR.

DNA Methylation-Derived Immune Cell Proportions and Cancer Risk in Black Participants.

This study describes associations between immune cell types and cancer risk in a Black population; elevated regulatory T-cell proportions that were associated with increased overall cancer and lung cancer risk, and elevated memory B-cell proportions that were associated with increased prostate and all cancer risk.

Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma.

Background: Muscle-invasive urothelial carcinoma is an aggressive disease with high rates of relapse. Whether pembrolizumab as adjuvant therapy would be effective in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery is unknown.

Methods: In this phase 3 trial, we randomly assigned patients, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks for 1 year or to undergo observation.

Value of Engagement in Digital Health Technology Research: Evidence Across 6 Unique Cohort Studies.

Background: Wearable digital health technologies and mobile apps (personal digital health technologies [DHTs]) hold great promise for transforming health research and care. However, engagement in personal DHT research is poor.

Objective: The objective of this paper is to describe how participant engagement techniques and different study designs affect participant adherence, retention, and overall engagement in research involving personal DHTs.

Entinostat as a combinatorial therapeutic for rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma. For the alveolar subtype (ARMS), the presence of the PAX3::FOXO1 fusion gene and/or metastases are strong predictors of poor outcome. Metastatic PAX3::FOXO1 ARMS often responds to chemotherapies initially, only to subsequently relapse and become resistant with most patients failing to survive beyond 8 years post-diagnosis.

Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer progressing on enzalutamide: cohorts 4 and 5 of the phase 2 KEYNOTE-199 study.

Background: KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.

Methods: Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines.

Blood Leukocyte DNA Methylation Markers of Periodontal Disease and Risk of Lung Cancer in a Case-Control Study Nested in the CLUE II Cohort.

Background: Periodontal disease and DNA methylation markers have separately been associated with lung cancer risk. Examining methylation levels at genomic regions previously linked to periodontal disease may provide insights on the link between periodontal disease and lung cancer.

Methods: In a nested case-control study drawn from the CLUE II cohort, we measured DNA methylation levels in 208 lung cancer cases and 208 controls.

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors.

PURPOSEAccess to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis.METHODSThree-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.