Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma Treated with Radiation Therapy: A Case Report and Review of the Literature.

Introduction: Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma or MALToma) is a prevalent type of primary pulmonary lymphoma. Typically, the primary therapeutic approaches involve surgery or chemotherapy, although there have been instances of radiation therapy being employed.

Case Report: We present a case of pulmonary MALToma that exhibited progression despite rituximab therapy.

De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma.

Mutations affecting isocitrate dehydrogenase (IDH) enzymes are prevalent in glioma, leukemia, and other cancers. Although mutant IDH inhibitors are effective against leukemia, they seem to be less active in aggressive glioma, underscoring the need for alternative treatment strategies. Through a chemical synthetic lethality screen, we discovered that IDH1-mutant glioma cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including dihydroorotate dehydrogenase (DHODH).

Broad spectrum of regorafenib activity on mutant KIT and absence of clonal selection in gastrointestinal stromal tumor (GIST): correlative analysis from the GRID trial.

Background: In the phase 3 GRID trial, regorafenib improved progression-free survival (PFS) independent of KIT mutations in exons 9 and 11. In this retrospective, exploratory analysis of the GRID trial, we investigated whether a more comprehensive KIT mutation analysis could identify mutations that impact treatment outcome with regorafenib and a regorafenib-induced mutation pattern.

Methods: Archived tumor samples, collected at any time prior to enrollment in GRID, were analyzed by Sanger sequencing (n = 102) and next-generation sequencing (FoundationONE; n = 47).

Phase I Assessment of Safety and Therapeutic Activity of BAY1436032 in Patients with IDH1-Mutant Solid Tumors.

Purpose: BAY1436032, an inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), was active against multiple IDH1-R132X solid tumors in preclinical models. This first-in-human study was designed to determine the safety and pharmacokinetics of BAY1436032, and to evaluate its potential pharmacodynamics and antitumor effects.

Patients And Methods: The study comprised of dose escalation and dose expansion cohorts.

Initial presentation of Pulmonary Langerhans cell histiocytosis as recurrent spontaneous pneumothoraces.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare cystic lung disease. The natural history is often unpredictable making it difficult to diagnose. We report a 63-year-old male with dyspnoea, chronic cough and recurrent respiratory tract infections, who developed progressive multifocal cystic lesions on pulmonary nodule surveillance over 4 years.

Safety and efficacy of BAY1436032 in IDH1-mutant AML: phase I study results.

The mutant IDH1 (mIDH1) inhibitor BAY1436032 demonstrated robust activity in preclinical AML models, supporting clinical evaluation. In the current dose-escalation study, BAY1436032 was orally administered to 27 mIDH1 AML subjects across 4 doses ranging from 300 to 1500 mg twice-daily. BAY1436032 exhibited a relatively short half-life and apparent non-linear pharmacokinetics after continuous dosing.

Synergistic activity of IDH1 inhibitor BAY1436032 with azacitidine in IDH1 mutant acute myeloid leukemia.

Mutant IDH1 (mIDH1) inhibitors have shown single-agent activity in relapsed/refractory AML, though most patients eventually relapse. We evaluated the efficacy and molecular mechanism of the combination treatment with azacitidine, which is currently the standard of care in older AML patients, and mIDH1 inhibitor BAY1436032. Both compounds were evaluated in vivo as single agents and in combination with sequential (azacitidine, followed by BAY1436032) or simultaneous application in two human IDH1 mutated AML xenograft models.

Analysis of Biomarkers and Association With Clinical Outcomes in Patients With Differentiated Thyroid Cancer: Subanalysis of the Sorafenib Phase III DECISION Trial.

Purpose: The phase III DECISION trial (NCT00984282; EudraCT:2009-012007-25) established sorafenib efficacy in locally recurrent or metastatic, progressive, differentiated thyroid cancer (DTC) refractory to radioactive iodine. We conducted a retrospective, exploratory biomarker analysis of patients from DECISION.

Experimental Design: Candidate biomarkers [15 baseline plasma proteins, baseline and during-treatment serum thyroglobulin, and relevant tumor mutations (, , , and )] were analyzed for correlation with clinical outcomes.

Impact and importance of a centralised review panel for lymphoma diagnostics in the WHO era: a single-centre experience.

Lymphoma diagnosis is complex, requiring a wide array of adjunctive tests to reach accurate diagnoses. We retrospectively examined the rates of concordance between referral and review lymphoma diagnoses on cases referred to St James's Hospital, Dublin for multidisciplinary team review between 2013 and 2016. Frequency and cost of adjunctive diagnostic tests performed were also analysed.

Risk Stratification in Multinodular Goiter: A Retrospective Review of Sonographic Features, Histopathological Results, and Cancer Risk.

Purpose: In the management of thyroid nodules, although the potential for malignancy exists, there is also the potential for overtreatment of subclinical disease. Although the TI-RADS (Thyroid Imaging-Reporting and Data System) system outlines a risk stratification score based on suspicious ultrasound findings, it has not been universally accepted. Many TI-RADS 2 or 3 patients proceed to fine needle aspiration biopsy (FNAB), potentially unnecessarily.

AKT1 (E17K) mutation profiling in breast cancer: prevalence, concurrent oncogenic alterations, and blood-based detection.

Background: The single hotspot mutation AKT1 [G49A:E17K] has been described in several cancers, with the highest incidence observed in breast cancer. However, its precise role in disease etiology remains unknown.

Methods: We analyzed more than 600 breast cancer tumor samples and circulating tumor DNA for AKT1 (E17K) and alterations in other cancer-associated genes using Beads, Emulsions, Amplification, and Magnetics digital polymerase chain reaction technology and targeted exome sequencing.

Biomarker Analyses of Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib with or without Erlotinib in the SEARCH Trial.

Purpose: Sorafenib is the current standard therapy for advanced hepatocellular carcinoma, but validated biomarkers predicting clinical outcomes are lacking. This study aimed to identify biomarkers predicting prognosis and/or response to sorafenib, with or without erlotinib, in hepatocellular carcinoma patients from the phase III SEARCH trial.

Experimental Design: A total of 720 patients were randomized to receive oral sorafenib 400 mg twice daily plus erlotinib 150 mg once daily or placebo.

Pulmonary Nodular Lymphoid Hyperplasia presenting cavitating pulmonary nodules.

Pulmonary Nodular Lymphoid Hyperplasia (PNLH) is a rare benign pulmonary disorder characterized by a localized, reactive polyclonal lymphoproliferation. Although the radiological features of this disease have not been clearly defined, they usually consist of a solitary non-cavitatory pulmonary nodule. In this report, we describe two cases of histologically confirmed PNLH presenting as multiple bilateral cavitatory lesions on CT Thorax.

Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial.

Background: Tumour mutational status is an important determinant of the response of metastatic colorectal cancer to targeted treatments. However, the genotype of the tissue obtained at the time of diagnosis might not accurately represent tumour genotype after multiple lines of treatment. This retrospective exploratory analysis investigated the clinical activity of regorafenib in biomarker subgroups of the CORRECT study population defined by tumour mutational status or plasma protein levels.

Case Study: Diffuse Large B-Cell Lymphoma Arising in Ovarian Mature Cystic Teratoma.

We describe an unexpected finding of diffuse large B-cell lymphoma associated with mature cystic teratoma of the ovary. A 68-yr-old woman with a complex left ovarian cystic mass on imaging underwent bilateral salpingo-oophorectomy, lymphadenectomy, appendicectomy, and omentectomy. Histopathologic examination revealed nodules of malignant non-Hodgkin lymphoma within the teratoma.

Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib.

Background: Regorafenib, a multi-kinase inhibitor, is used in the treatment of patients with metastatic colorectal cancer refractory to standard therapy. However, this benefit was limited to 1.4 months improvement in overall survival, with more than half of patients experiencing grade 3 to 4 adverse events.

A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma.

Purpose: There is an unmet need for treatment options in hepatocellular carcinoma (HCC). Sorafenib is currently the only approved systemic treatment for HCC. Refametinib, an oral, allosteric MEK inhibitor, has demonstrated antitumor activity in combination with sorafenib in vitro and in vivo.

A pathologist's survey on the reporting of sessile serrated adenomas/polyps.

Aim: The purpose of this survey was to ascertain reporting habits of pathologists towards sessile serrated adenomas/polyps (SSA/P).

Methods: A questionnaire designed to highlight diagnostic criteria, approach and clinical implications of SSA/P was circulated electronically to 45 pathologists in the UK and North America.

Results: Forty-three of 45 pathologists agreed to participate.