Defining Practice Capacity for Cancer Care Delivery to Adolescents and Young Adults in the Community Setting: 2022 Landscape Assessment Results.

Adolescents and young adults (AYAs) commonly receive cancer care in the community setting, but the availability of treatment options, resources, and support services for this population is not well known. The National Cancer Institute Community Oncology Research Program (NCORP) funds a network of practices whose mission is to increase access to cancer care and clinical trials in the community setting. We describe our interdisciplinary methodological approach to identify and characterize NCORP practices where AYAs receive cancer care.

Brain and Brain Stem Necrosis After Reirradiation for Recurrent Childhood Primary Central Nervous System Tumors: A PENTEC Comprehensive Review.

Purpose: Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation.

Methods And Materials: A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA.

Rates of Downstream Procedures and Complications Associated With Lung Cancer Screening in Routine Clinical Practice : A Retrospective Cohort Study.

Background: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) reduces lung cancer mortality but can lead to downstream procedures, complications, and other potential harms. Estimates of these events outside NLST (National Lung Screening Trial) have been variable and lacked evaluation by screening result, which allows more direct comparison with trials.

Objective: To identify rates of downstream procedures and complications associated with LCS.

Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer: The TBCRC 043 Phase 2 Randomized Clinical Trial.

Importance: Agents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the standard of care in patients with PD-L1-positive metastatic disease. In contrast to microtubule-targeting agents, the effect of combining platinum compounds with programmed cell death 1 (PD-1)/PD-L1 immunotherapy has not been extensively determined.

Objective: To evaluate the efficacy of atezolizumab with carboplatin in patients with metastatic TNBC.

Genetic Ancestry-specific Molecular and Survival Differences in Admixed Patients With Breast Cancer.

Objective: We aim to determine whether incremental changes in genetic ancestry percentages influence molecular and clinical outcome characteristics of breast cancer in an admixed population.

Background: Patients with breast cancer are predominantly characterized as "Black" or "White" based on self-identified race/ethnicity or arbitrary genetic ancestry cutoffs. This limits scientific discovery in populations that are admixed or of mixed race/ethnicity as they cannot be classified based on historical race/ethnicity boxes or genetic ancestry cutoffs.

Disparities in outcomes between Black and White patients in North America with thoracic malignancies and COVID-19 infection (TERAVOLT).

Background: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied.

Methods: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities.

The Development and Testing of a Point-of-Sale E-Cigarette Health Communication Campaign.

Adolescents and young adults continue to use e-cigarettes, and communication campaigns are needed to decrease use among these populations. We developed and tested a point-of-sale communication campaign focused on e-cigarette chemical exposure. We developed messages based on formative research and tested them (versus text-only messages) in a nationally-representative online survey among adolescents and young adults (16-25) (Phase 1).

Development of F-Labeled hydrophilic -cyclooctene as a bioorthogonal tool for PET probe construction.

We report the development of a hydrophilic F-labeled a-TCO derivative [F]3 (log  = 0.28) through a readily available precursor and a single-step radiofluorination reaction (RCY up to 52%). We demonstrated that [F]3 can be used to construct not only multiple small molecule/peptide-based PET agents, but protein/diabody-based imaging probes in parallel.

Kaposi's sarcoma-associated herpesvirus viral protein kinase augments cell survival.

Oncogenic viruses have developed various strategies to antagonize cell death and maintain lifelong persistence in their host, a relationship that may contribute to cancer development. Understanding how viruses inhibit cell death is essential for understanding viral oncogenesis. Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with three different cancers in the human population, including Kaposi's sarcoma (KS), the most common cancer in HIV patients.

Uptake of Lung Cancer Screening CT After a Provider Order for Screening in the PROSPR-Lung Consortium.

Background: Uptake of lung cancer screening (LCS) has been slow with less than 20% of eligible people who currently or formerly smoked reported to have undergone a screening CT.

Objective: To determine individual-, health system-, and neighborhood-level factors associated with LCS uptake after a provider order for screening.

Design And Subjects: We conducted an observational cohort study of screening-eligible patients within the Population-based Research to Optimize the Screening Process (PROSPR)-Lung Consortium who received a radiology referral/order for a baseline low-dose screening CT (LDCT) from a healthcare provider between January 1, 2015, and June 30, 2019.

Utilizing a Proximity Dependent Labeling Strategy to Study Cancer-Immune Intercellular Interactions In Vitro and In Vivo.

Immune cells play a critical role in surveilling and defending against cancer, emphasizing the importance of understanding how they interact and communicate with cancer cells to determine cancer status, treatment response, and the formation of the tumor microenvironment (TME). To this end, we conducted a study demonstrating the effectiveness of an enzyme-mediated intercellular proximity labeling (EXCELL) method, which utilizes a modified version of the sortase A enzyme known as mgSrtA, in detecting and characterizing immune-tumor cell interactions. The mgSrtA enzyme is expressed on the membrane of tumor cells, which is able to label immune cells that interact with tumor cells in a proximity-dependent manner.

Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C).

Substrate polyubiquitination drives a myriad of cellular processes, including the cell cycle, apoptosis and immune responses. Polyubiquitination is highly dynamic, and obtaining mechanistic insight has thus far required artificially trapped structures to stabilize specific steps along the enzymatic process. So far, how any ubiquitin ligase builds a proteasomal degradation signal, which is canonically regarded as four or more ubiquitins, remains unclear.

Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota.

Restriction of methionine (MR), a sulfur-containing essential amino acid, has been reported to repress cancer growth and improve therapeutic responses in several preclinical settings. However, how MR impacts cancer progression in the context of the intact immune system is unknown. Here we report that while inhibiting cancer growth in immunocompromised mice, MR reduces T cell abundance, exacerbates tumour growth and impairs tumour response to immunotherapy in immunocompetent male and female mice.

Children's Oncology Group 2023 blueprint for research: Cancer care delivery research.

The National Cancer Institute (NCI) has a 40-year history of initiatives to encourage the participation of community oncology sites into clinical trials research and clinical care. In 2014, the NCI re-organized to form the NCI Community Oncology Research Program (NCORP) network across seven research bases, including the Children's Oncology Group (COG), and numerous community sites. The COG portfolio for Cancer Care Delivery Research (CCDR), mirroring the larger NCORP network, has included two studies addressing guideline congruence, as an important marker of quality cancer care, and another focusing on financial toxicity, addressing the pervasive problems of healthcare cost.

Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5.

UBR5 is a nuclear E3 ligase that ubiquitinates a vast range of substrates for proteasomal degradation. This HECT domain-containing ubiquitin ligase has recently been identified as an important regulator of oncogenes, e.g.

Losing a part of life: experiences of cancer survivors accessing treatment and sheltering in place during the COVID-19 pandemic.

Purpose: To explore experiences of sheltering in place and accessing treatment during the initial stages of the COVID-19 pandemic among survivors with cancer receiving tyrosine kinase inhibitor (TKI) therapy.

Methods: Participants from two pilot studies evaluating TKI therapy use in the Southeastern United States during the start of the COVID-19 pandemic (March 2020) were interviewed. Identical interview guides were used across both studies to assess participants' experiences accessing cancer treatment, sheltering in place, and coping during the COVID-19 pandemic.

Preoperative Treatment of Locally Advanced Rectal Cancer.

Background: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain.

Methods: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy.

Effect of HPV self-collection kits on cervical cancer screening uptake among under-screened women from low-income US backgrounds (MBMT-3): a phase 3, open-label, randomised controlled trial.

Background: Most cervical cancer in the USA occurs in under-screened women. The My Body, My Test-3 (MBMT-3) trial sought to assess the efficacy of mailed human papillomavirus (HPV) self-collection kits with appointment-scheduling assistance to increase uptake of cervical cancer screening among under-screened women from low-income backgrounds compared with scheduling assistance alone.

Methods: MBMT-3 is a phase 3, open-label, two-arm, randomised controlled trial.

Dosage sensitivity to Pumilio1 variants in the mouse brain reflects distinct molecular mechanisms.

Different mutations in the RNA-binding protein Pumilio1 (PUM1) cause divergent phenotypes whose severity tracks with dosage: a mutation that reduces PUM1 levels by 25% causes late-onset ataxia, whereas haploinsufficiency causes developmental delay and seizures. Yet PUM1 targets are derepressed to equal degrees in both cases, and the more severe mutation does not hinder PUM1's RNA-binding ability. We therefore considered the possibility that the severe mutation might disrupt PUM1 interactions, and identified PUM1 interactors in the murine brain.

Multi-omics analyses reveal ClpP activators disrupt essential mitochondrial pathways in triple-negative breast cancer.

ClpP activators ONC201 and related small molecules (TR compounds, Madera Therapeutics), have demonstrated significant anti-cancer potential in and studies, including clinical trials for refractory solid tumors. Though progress has been made in identifying specific phenotypic outcomes following ClpP activation, the exact mechanism by which ClpP activation leads to broad anti-cancer activity has yet to be fully elucidated. In this study, we utilized a multi-omics approach to identify the ClpP-dependent proteomic, transcriptomic, and metabolomic changes resulting from ONC201 or the TR compound TR-57 in triple-negative breast cancer cells.

Differential transcript usage analysis incorporating quantification uncertainty via compositional measurement error regression modeling.

Differential transcript usage (DTU) occurs when the relative expression of multiple transcripts arising from the same gene changes between different conditions. Existing approaches to detect DTU often rely on computational procedures that can have speed and scalability issues as the number of samples increases. Here we propose a new method, CompDTU, that uses compositional regression to model the relative abundance proportions of each transcript that are of interest in DTU analyses.