Genomic amplifications identified by circulating tumor DNA analysis guide prognosis in metastatic castration-resistant prostate cancer.

Purpose: Analysis of circulating tumor DNA (ctDNA) in patients with metastatic prostate cancer (mPC) provides an opportunity to identify and monitor genomic alterations during a patient's treatment course. We evaluated whether the presence of specific gene amplifications (GAs) and plasma copy number (PCN) alterations are associated with disease features.

Methods: This is a single-institution retrospective study of patients with mPC who underwent ctDNA profiling using Guardant360 (Guardant Health Inc.

First-in-human phase Ib trial of M9241 (NHS-IL12) plus avelumab in patients with advanced solid tumors, including dose expansion in patients with advanced urothelial carcinoma.

Background: In preclinical studies, combining M9241 (a novel immunocytokine containing interleukin (IL)-12 heterodimers) with avelumab (anti-programmed death ligand 1 antibody) resulted in additive or synergistic antitumor effects. We report dose-escalation and dose-expansion results from the phase Ib JAVELIN IL-12 trial investigating M9241 plus avelumab.

Methods: In the dose-escalation part of JAVELIN IL-12 (NCT02994953), eligible patients had locally advanced or metastatic solid tumors; in the dose-expansion part, eligible patients had locally advanced or metastatic urothelial carcinoma (UC) that had progressed with first-line therapy.

Elevated serum CEA is associated with liver metastasis and distinctive circulating tumor DNA alterations in patients with castration-resistant prostate cancer.

Background: Elevated serum carcinoembryonic antigen (CEA) is used to identify "treatment emergent" forms of castration-resistant prostate cancer (CRPC) such as aggressive variant prostate cancer (AVPC). However, its individual utility as a prognostic marker and the genetic alterations associated with its expression have not been extensively studied in CRPC.

Methods: This study retrospectively analyzed clinical outcomes and circulating tumor DNA profiles in 163 patients with CRPC and elevated or normal serum CEA.

Spectrum of Alterations in Cell-Free DNA of Patients with Advanced Urothelial Carcinoma.

Detecting genomic alterations (GAs) in advanced urothelial carcinoma (aUC) can expand treatment options by identifying candidates for targeted therapies. Erdafitinib is FDA-approved for patients with platinum-refractory aUC with activating mutation or fusion in . We explored the prevalence and spectrum of GAs identified with plasma cfDNA NGS testing (Guardant360) in 997 patients with aUC.

Cabozantinib use in metastatic renal cell carcinoma patients in clinical practice: Evaluation of dosing patterns, tolerability, and outcomes compared to clinical trials.

Introduction: Despite first-line approval in metastatic renal cell carcinoma (mRCC), the tyrosine kinase inhibitor cabozantinib is associated with frequent treatment-limiting side effects. Dose reductions in published trials of the drug and in clinical practice are commonplace. We analyzed our institution's real-world experience with cabozantinib dosing in patients with mRCC to assess strategies to improve tolerability and patient outcomes.

Circulating tumor DNA alterations in patients with metastatic castration-resistant prostate cancer.

Background: Because cell-free DNA (cfDNA) analysis facilitates the noninvasive genomic profiling of metastatic castration-resistant prostate cancer (mCRPC), the authors evaluated the association between cfDNA alterations and outcomes and evolution with therapy.

Methods: Patients with mCRPC underwent cfDNA genomic profiling using Guardant360, which examines major cancer-associated genes. Clinical factors, therapy information, failure-free survival, and overall survival (OS) were obtained for select patients.

High frequency of rare structural chromosome abnormalities at relapse of cytogenetically normal acute myeloid leukemia with FLT3 internal tandem duplication.

FLT3 internal tandem duplication (ITD) mutations are present in acute myeloid leukemia (AML) in 30% of patients with acute myeloid leukemia (AML), most commonly in those with a normal karyotype, and are associated with short relapse-free survival. Both in vitro and in vivo studies of FLT3-ITD cell lines have demonstrated reactive oxygen species-mediated DNA double-strand breaks and associated error-prone DNA repair as a mechanism of genomic instability, and we hypothesized that genomic instability might be manifested by cytogenetic changes at relapse of FLT3-ITD AML. We retrospectively reviewed charts of patients with cytogenetically normal (CN) FLT3-ITD AML treated at the University of Maryland Greenebaum Cancer Center, with attention to metaphase analysis results at relapse.

Ten-day decitabine as initial therapy for newly diagnosed patients with acute myeloid leukemia unfit for intensive chemotherapy.

We retrospectively reviewed outcomes in 45 previously untreated patients with acute myeloid leukemia (AML) considered unfit for chemotherapy who were treated with 10-day courses of decitabine 20 mg/m(2) daily outside of a clinical trial, with no cut-offs for organ function or performance status (PS). Nineteen had Eastern Cooperative Group performance status (ECOG PS) ≥ 2, and 39 had ≥ 2 comorbidities. Fourteen patients (31%) achieved complete remission (CR) and five (11%) CR with incomplete count recovery, for an overall response rate of 42%, after a median of 2 (range, 1-4) courses.