Clinical outcomes and ctDNA correlates for CAPOX BETR: a phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma.

Preclinical studies suggest that simultaneous HER2/VEGF blockade may have cooperative effects in gastroesophageal adenocarcinomas. In a single-arm investigator initiated clinical trial for patients with untreated advanced HER2+ gastroesophageal adenocarcinoma, bevacizumab was added to standard of care capecitabine, oxaliplatin, and trastuzumab in 36 patients (NCT01191697). Primary endpoint was objective response rate and secondary endpoints included safety, duration of response, progression free survival, and overall survival.

Recommendations for Tumor Mutational Burden Assay Validation and Reporting: A Joint Consensus Recommendation of the Association for Molecular Pathology, College of American Pathologists, and Society for Immunotherapy of Cancer.

Tumor mutational burden (TMB) has been recognized as a predictive biomarker for immunotherapy response in several tumor types. Several laboratories offer TMB testing, but there is significant variation in how TMB is calculated, reported, and interpreted among laboratories. TMB standardization efforts are underway, but no published guidance for TMB validation and reporting is currently available.

Molecular Pathology of Ovarian Epithelial Neoplasms: Predictive, Prognostic, and Emerging Biomarkers.

This review focuses on the diagnostic, prognostic, and predictive molecular biomarkers in ovarian epithelial neoplasms in the context of their morphologic classifications. Currently, most clinically actionable molecular findings are reported in high-grade serous carcinomas; however, the data on less common tumor types are rapidly accelerating. Overall, the advances in genomic knowledge over the last decade highlight the significance of integrating molecular findings with morphology in ovarian epithelial tumors for a wide-range of clinical applications, from assistance in diagnosis to predicting response to therapy.

Rapid tumor DNA analysis of cerebrospinal fluid accelerates treatment of central nervous system lymphoma.

Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown cause. Participants underwent genotyping of CSF-derived DNA using a quantitative polymerase chain reaction-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF, and H3F3A genes within 80 minutes of sample acquisition.

Programmed Death Ligand-1 and Tumor Mutation Burden Testing of Patients With Lung Cancer for Selection of Immune Checkpoint Inhibitor Therapies: Guideline From the College of American Pathologists, Association for Molecular Pathology, International Association for the Study of Lung Cancer, Pulmonary Pathology Society, and LUNGevity Foundation.

Context.—: Rapid advancements in the understanding and manipulation of tumor-immune interactions have led to the approval of immune therapies for patients with non-small cell lung cancer. Certain immune checkpoint inhibitor therapies require the use of companion diagnostics, but methodologic variability has led to uncertainty around test selection and implementation in practice.

Liquid biopsy-based circulating tumour (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results.

Aims: Liquid biopsy (LBx)-based next-generation sequencing (NGS) of circulating tumour DNA (ctDNA) can facilitate molecular profiling of haematopoietic neoplasms (HNs), particularly when tissue-based NGS is infeasible.

Methods And Results: We studied HN LBx samples tested with FoundationOne Liquid CDx, FoundationOne Liquid, or FoundationACT between July 2016 and March 2022. We identified 271 samples: 89 non-Hodgkin lymphoma (NHL), 43 plasma-cell neoplasm (PCN), 41 histiocytoses, 27 myelodysplastic syndrome (MDS), 25 diffuse large B-cell lymphoma (DLBCL), 22 myeloproliferative neoplasm (MPN), 14 Hodgkin lymphoma (HL), and 10 acute myeloid leukaemia (AML).

Compromised Outcomes in Stage IV Non-Small-Cell Lung Cancer With Actionable Mutations Initially Treated Without Tyrosine Kinase Inhibitors: A Retrospective Analysis of Real-World Data.

Purpose: Identification and targeting of actionable oncogenic drivers (AODs) in advanced non-small-cell lung cancer (NSCLC) has dramatically improved outcomes. However, genomic testing uptake is variable and hampered by factors including slow turnaround time, frequently resulting in initial non-tyrosine kinase inhibitor (TKI) treatment. We investigate how this behavior affects outcomes.

Slide-to-Slide Tissue Transfer and Array Assembly From Limited Samples for Comprehensive Molecular Profiling.

Tissue microarrays (TMA) have become an important tool in high-throughput molecular profiling of tissue samples in the translational research setting. Unfortunately, high-throughput profiling in small biopsy specimens or rare tumor samples (eg, orphan diseases or unusual tumors) is often precluded owing to limited amounts of tissue. To overcome these challenges, we devised a method that allows tissue transfer and construction of TMAs from individual 2- to 5-μm sections for subsequent molecular profiling.

Clinical Implications and Treatment Strategies for ESR1 Fusions in Hormone Receptor-Positive Metastatic Breast Cancer: A Case Series.

In hormone receptor-positive metastatic breast cancer (HR+ MBC), endocrine resistance is commonly due to genetic alterations of ESR1, the gene encoding estrogen receptor alpha (ERα). While ESR1 point mutations (ESR1-MUT) cause acquired resistance to aromatase inhibition (AI) through constitutive activation, far less is known about the molecular functions and clinical consequences of ESR1 fusions (ESR1-FUS). This case series discusses 4 patients with HR+ MBC with ESR1-FUS in the context of the existing ESR1-FUS literature.

Molecular Biomarkers of Response to Cancer Immunotherapy.

Harnessing the immune system to advance cancer therapy has offered a new weapon in the quiver of clinical oncology. The lack of uniform, robust, or durable responses in many patients has necessitated the development of approaches for the accurate prediction of subgroups that are most likely to benefit from immunotherapy. This has led to the development and regulatory approval of predictive biomarkers, as well as associated companion diagnostics.

Recurrent Loss of Heterozygosity in Pancreatic Neuroendocrine Tumors.

Chromosomal aneuploidies are prognostic markers across a wide variety of tumor types, and recent literature suggests that pancreatic neuroendocrine tumors are no different. In this study 214 patients with grade 1, 2, or 3 pancreatic neuroendocrine tumors had their tissue examined for chromosomal copy number alterations using next-generation sequencing. Univariate and multivariate statistical analyses were performed with all-cause mortality and disease-specific mortality as the end comparators.

Clinicopathologic Evaluation and Molecular Profiling of Recurrent Stage IA Endometrial Endometrioid Carcinoma: A Case-control Study.

Most low-grade, early-stage endometrial endometrioid carcinomas (EEC) have an excellent prognosis; however, recurrences occur in a small subset with several studies reporting an increase in CTNNB1 exon 3 mutations in this population. Herein we evaluated 10 recurrent low-grade (FIGO 1 or 2), early-stage (FIGO IA) EECs matched to 10 nonrecurrent EECs to further characterize their clinicopathologic features and molecular phenotype. Cases were matched to controls based on size, grade, and depth of invasion.