ACTION: a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma.

Background: H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma.

AIRR-C IG Reference Sets: curated sets of immunoglobulin heavy and light chain germline genes.

Introduction: Analysis of an individual's immunoglobulin (IG) gene repertoire requires the use of high-quality germline gene reference sets. When sets only contain alleles supported by strong evidence, AIRR sequencing (AIRR-seq) data analysis is more accurate and studies of the evolution of IG genes, their allelic variants and the expressed immune repertoire is therefore facilitated.

Methods: The Adaptive Immune Receptor Repertoire Community (AIRR-C) IG Reference Sets have been developed by including only human IG heavy and light chain alleles that have been confirmed by evidence from multiple high-quality sources.

Disrupting CD38-driven T cell dysfunction restores sensitivity to cancer immunotherapy.

A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma. T cell exhaustion, resulting from chronic antigen exposure in the tumour microenvironment, is a major driver of ICB resistance. Here, we show that CD38, an ecto-enzyme involved in nicotinamide adenine dinucleotide (NAD) catabolism, is highly expressed in exhausted CD8 T cells in melanoma and is associated with ICB resistance.

Chronic Use of Prescription Pain Medication and Outcomes in Patients With Burn Injury: A Burn Model System National Database Study.

Objective: This study attempts to examine long-term pain medication usage after burn injury and its association with functional and psychosocial outcomes.

Design: This is a multicenter retrospective cohort study utilizing the Burn Model System National Longitudinal Database. Participants injured from 2015 to 2021 were divided into two groups, those taking and not taking prescription pain medication at 12 mos after injury.

Gratitude, optimism, and satisfaction with life and patient-reported outcomes in patients undergoing hematopoietic stem cell transplantation.

Objective: Associations between positive psychological well-being (PPWB) and patient-reported outcomes (PROs, e.g., quality of life [QOL]) have yet to be studied extensively in patients with hematologic malignancies who are allogeneic hematopoietic stem cell transplant (HSCT) survivors, despite substantial evidence that PPWB impacts PROs of other medical populations.

A phase I study of ATR inhibitor gartisertib (M4344) as a single agent and in combination with carboplatin in patients with advanced solid tumours.

Background: Gartisertib is an oral inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), a key kinase of the DNA damage response. We aimed to determine the safety and tolerability of gartisertib ± carboplatin in patients with advanced solid tumours.

Methods: This phase I open-label, multicenter, first-in-human study comprised four gartisertib cohorts: A (dose escalation [DE]; Q2W); A2 (DE; QD/BID); B1 (DE+carboplatin); and C (biomarker-selected patients).

A Positive Psychology Intervention for Caregivers of Hematopoietic Stem Cell Transplantation Survivors (PATH-C): Initial Testing and Single-Arm Pilot Trial.

Caregivers of patients with hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation (HSCT) play a crucial role in supporting their loved ones through physical, emotional, and practical challenges. This role has been associated with high levels of psychological distress and low levels of positive psychological well-being (PPWB). Positive psychology interventions for caregivers in other disease groups (eg, breast cancer) have been associated with improved outcomes.

Unanswered questions following reports of secondary malignancies after CAR-T cell therapy.

Reports of T cell malignancies after CAR-T cell therapy should be investigated, but existing data from follow-up studies suggest a low risk compared with other cancer treatments.

Tofacitinib is Effective in Treating Refractory Immune Checkpoint Inhibitor Hepatitis.

Immune checkpoint inhibitors (ICI) have improved metastatic melanoma outcomes; however, toxicities, such as hepatitis, can be dose-limiting or even fatal. Systemic glucocorticoids and antimetabolite immunosuppressive medications remain the mainstay of treatment for ICI-hepatitis, but options for patients refractory to these therapies are limited. Herein we present 3 cases of glucocorticoid-refractory ICI-hepatitis treated with tofacitinib, an inhibitor of Janus kinase (JAK) 1 and 3.

DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair.

DNA is an organic molecule that is highly vulnerable to chemical alterations and breaks caused by both internal and external factors. Cells possess complex and advanced mechanisms, including DNA repair, damage tolerance, cell cycle checkpoints, and cell death pathways, which together minimize the potentially harmful effects of DNA damage. However, in cancer cells, the normal DNA damage tolerance and response processes are disrupted or deregulated.

Dysregulated Repeat Element Viral-like Immune Response in Hepatocellular Carcinoma.

Purpose: Dysregulation of viral-like repeat RNAs are a common feature across many malignancies that are linked with immunological response, but the characterization of these in hepatocellular carcinoma (HCC) is understudied. In this study, we performed RNA hybridization (RNA-ISH) of different repeat RNAs, immunohistochemistry (IHC) for immune cell subpopulations, and spatial transcriptomics to understand the relationship of HCC repeat expression, immune response, and clinical outcomes.

Experimental Design: RNA-ISH for LINE1, HERV-K, HERV-H, and HSATII repeats and IHC for T-cell, Treg, B-cell, macrophage, and immune checkpoint markers were performed on 43 resected HCC specimens.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise.

Virtual Molecular and Precision Medicine Clinic to Improve Access to Clinical Trials for Patients With Metastatic Breast Cancer: An Academic/Community Collaboration.

Purpose: There is a demand for improved care delivery surrounding genomic testing and clinical trial enrollment among patients with metastatic breast cancer (MBC). We sought to improve the current process via real-time informal consultation and prescreening assessment for patients with MBC treated by community and academic medical oncologists by implementing a virtual molecular and precision medicine (vMAP) clinic.

Methods: The vMAP program used a virtual referral system directed to a multidisciplinary team with precision medicine expertise.

Allosteric PI3Kα Inhibition Overcomes On-target Resistance to Orthosteric Inhibitors Mediated by Secondary PIK3CA Mutations.

Unlabelled: PIK3CA mutations occur in ∼8% of cancers, including ∼40% of HR-positive breast cancers, where the PI3K-alpha (PI3Kα)-selective inhibitor alpelisib is FDA approved in combination with fulvestrant. Although prior studies have identified resistance mechanisms, such as PTEN loss, clinically acquired resistance to PI3Kα inhibitors remains poorly understood. Through serial liquid biopsies and rapid autopsies in 39 patients with advanced breast cancer developing acquired resistance to PI3Kα inhibitors, we observe that 50% of patients acquire genomic alterations within the PI3K pathway, including PTEN loss and activating AKT1 mutations.

Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions regarding the workup of patients with prostate cancer, risk stratification and management of localized disease, post-treatment monitoring, and treatment of recurrence and advanced disease. The Guidelines sections included in this article focus on the management of metastatic castration-sensitive disease, nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). Androgen deprivation therapy (ADT) with treatment intensification is strongly recommended for patients with metastatic castration-sensitive prostate cancer.

Qualitative study of Oncology Clinicians' Perceptions of Barriers to Offering Clinical Trials to Underserved Populations.

Introduction: Cancer clinical trials represent the "gold standard" for advancing novel cancer therapies. Optimizing trial participation is critical to ensuring the generalizability of findings across patients, yet trial enrollment rates, particularly among minority and socioeconomically disadvantaged populations, remain suboptimal.

Methods: We conducted in-depth interviews with oncologists at a large academic medical center to explore their (1) attitudes and perceived barriers to offering clinical trials to minority and socioeconomically disadvantaged patients, and (2) recommendations for improving the enrollment of minority and socioeconomically disadvantaged patients in cancer clinical trials.

Spatial transcriptomics reveals distinct tissue niches linked with steroid responsiveness in acute gastrointestinal GVHD.

Severe acute graft-versus-host disease (aGVHD) is associated with significant mortality and morbidity, especially in steroid-resistant (SR) cases. Spatial transcriptomic technology can elucidate tissue-based interactions in vivo and possibly identify predictors of treatment response. Tissue sections from 32 treatment-naïve patients with biopsy-confirmed lower gastrointestinal (GI) aGVHD were obtained.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM.

Positive Psychological Well-Being in Hematopoietic Stem Cell Transplantation Survivors.

Positive thoughts and emotions contribute to overall psychological health in diverse medical populations, including patients undergoing HSCT. However, few studies have described positive psychological well-being (eg, optimism, gratitude, flourishing) in patients undergoing HSCT using well-established, validated patient-reported outcome measures. We conducted cross-sectional secondary analyses of baseline data in 156 patients at 100 days post-HSCT enrolled in a randomized controlled trial of a psychological intervention (ClinicalTrials.