Publications by authors named "T A Alonzo"
Acute Myeloid Leukemia (AML) is an aggressive cancer with dismal outcomes, vast subtype heterogeneity, and suboptimal risk stratification. In this study, we harmonized DNA methylation data from 3,314 patients across 11 cohorts to develop the Acute Leukemia Methylome Atlas (ALMA) of diagnostic relevance that predicted 27 WHO 2022 acute leukemia subtypes with an overall accuracy of 96.3% in discovery and 90.
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- Several genomic subsets of mutations in acute myeloid leukemia (AML) patients were studied to understand their impact on outcomes and the underlying biology, revealing that type D mutations correlated with poorer survival rates compared to other types.
- In a cohort of over 4,000 patients, a study found that those with type A, B, and rare variants had more favorable overall survival rates, while type D patients exhibited significantly worse outcomes.
- The research highlighted that codon optimality in type D mutations affects gene expression and translation efficiency, leading to poorer prognostic implications and indicating the need for a potential reclassification of type D patients to higher-risk groups.
Background/aims: For cancers with low incidence, low event rates, and a time-to-event endpoint, a randomized non-inferiority trial designed based on the logrank test can require a large sample size with significantly prolonged enrollment duration, making such a non-inferiority trial not feasible. This article evaluates a design based on a non-inferiority test of proportions, compares its required sample size to the non-inferiority logrank test, assesses whether there are scenarios for which a non-inferiority test of proportions can be more efficient, and provides guidelines in usage of a non-inferiority test of proportions.
Methods: This article describes the sample size calculation for a randomized non-inferiority trial based on a non-inferiority logrank test or a non-inferiority test of proportions.
Purpose: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice trial assigned patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with tumors that harbored prespecified genomic alterations in the cyclinD-CDK4/6-INK4a-Rb pathway with intact Rb expression were assigned and treated with the cdk4/6 inhibitor palbociclib.
Methods: Patients received palbociclib orally once daily for 21 days of 28-day cycles until disease progression, intolerable toxicity, or up to 2 years.
Phase II Study of Samotolisib in Children and Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Pathway Alterations: Pediatric MATCH APEC1621D.
JCO Precis Oncol
September 2024
Purpose: Patients age 1-21 years with relapsed or refractory solid and CNS tumors were assigned to phase II studies of molecularly targeted therapies on the National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial. Patients whose tumors harbored predefined genetic alterations in the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and lacked mitogen-activated protein kinase pathway activating alterations were treated with the PI3K/mTOR inhibitor samotolisib.
Methods: Patients received samotolisib twice daily in 28-day cycles until disease progression or unacceptable toxicity.