Caspase-2 is essential for proliferation and self-renewal of nucleophosmin-mutated acute myeloid leukemia.

Mutation in nucleophosmin (NPM1) causes relocalization of this normally nucleolar protein to the cytoplasm (NPM1c+). Despite NPM1 mutation being the most common driver mutation in cytogenetically normal adult acute myeloid leukemia (AML), the mechanisms of NPM1c+-induced leukemogenesis remain unclear. Caspase-2 is a proapoptotic protein activated by NPM1 in the nucleolus.

Clinicogenomic predictors of outcomes in patients with hepatocellular carcinoma treated with immunotherapy.

Introduction: Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes.

Methods: The primary objective of this retrospective study was to define the clinical, pathologic, and genomic factors associated with outcomes to ICI therapy in patients with HCC.

Morbidity and mortality in patients with stage IV pancreatic adenocarcinoma and acute cholangitis: Outcomes and risk prognostication.

Background: Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC.

Methods: We conducted a single-center, retrospective observational study using institutional databases.

Immune checkpoint inhibitor therapy in locally advanced MSI GI malignancies.

Locally advanced gastrointestinal (GI) malignancies have conventionally been treated in a multimodal fashion that combines (neo)adjuvant chemotherapy with or without radiation and definitive surgical resection. Clinical data have demonstrated the reduced responsiveness of GI malignancies with microsatellite instability (MSI) to both adjuvant and neoadjuvant systemic chemotherapy when compared with microsatellite stable (MSS) disease. The elevated tumor mutational burden associated with MSI tumors of all types sensitizes these tumors to the effects of immune checkpoint blockade in the metastatic setting, which led to tumor-agnostic approval of immune checkpoint inhibitors in this context.

Precision medicine for pancreatic cancer: characterizing the clinicogenomic landscape and outcomes of KRAS G12C-mutated disease.

Background: Mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogene alteration in pancreatic ductal adenocarcinoma, and KRAS glycine to cystine substitution at codon 12 (G12C) mutations (KRAS G12Cmut) are observed in 1%-2%. Several inhibitors of KRAS G12C have recently demonstrated promise in solid tumors, including pancreatic cancer. Little is known regarding clinical, genomics, and outcome data of this population.

Real-World Analysis of the Clinical and Economic Impact of the 21-Gene Recurrence Score (RS) in Invasive Lobular Early-Stage Breast Carcinoma in Ireland.

This study, using real-world data, assesses the impact of RS testing on treatment pathways and the associated economic consequences of such testing. This paper pertains to lobular breast cancer. A retrospective, observational study was undertaken between 2011 and 2019 on a cross-section of hormone receptor-positive (HR+), HER2-negative, lymph node-negative, early-stage breast cancer patients.

Molecular and Clinical Determinants of Acquired Resistance and Treatment Duration for Targeted Therapies in Colorectal Cancer.

Purpose: Targeted therapies have improved outcomes for patients with metastatic colorectal cancer, but their impact is limited by rapid emergence of resistance. We hypothesized that an understanding of the underlying genetic mechanisms and intrinsic tumor features that mediate resistance to therapy will guide new therapeutic strategies and ultimately allow the prevention of resistance.

Experimental Design: We assembled a series of 52 patients with paired pretreatment and progression samples who received therapy targeting EGFR (n = 17), BRAF V600E (n = 17), KRAS G12C (n = 15), or amplified HER2 (n = 3) to identify molecular and clinical factors associated with time on treatment (TOT).

Immune checkpoint blockade induced sarcoid-like reaction mimicking progression of disease in a patient with microsatellite instable colorectal cancer: case report and review of the literature.

Background: Oncologists are prescribing checkpoint inhibitors with greater frequency, and an awareness of and ability to recognize immune-related adverse events (irAEs) is a key part of the safe administration of these drugs.

Case Description: Herein, we report the case of a 26-year-old male diagnosed with metastatic right-sided colon cancer to the liver, with tumor immunohistochemistry demonstrating loss of and , and a pathogenic mutation in identified on germline testing, consistent with Lynch Syndrome. The patient received first-line treatment with pembrolizumab.

Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.

Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received ≥1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21 months (interquartile range, 6-38).

Pneumonitis in Patients Receiving Thoracic Radiotherapy and Osimertinib: A Multi-Institutional Study.

Introduction: Thoracic radiotherapy (TRT) is increasingly used in patients receiving osimertinib for advanced NSCLC, and the risk of pneumonitis is not established. We investigated the risk of pneumonitis and potential risk factors in this population.

Methods: We performed a multi-institutional retrospective analysis of patients under active treatment with osimertinib who received TRT between April 2016 and July 2022 at two institutions.

Portal Vein or Superior Mesenteric Vein Thrombosis with Dose-Escalated Radiation for Borderline or Locally Advanced Pancreatic Cancer.

Purpose: Portal vein and superior mesenteric vein thrombosis (PVT/SMVT) are potentially morbid complications of radiation dose-escalated local therapy for pancreatic cancer. We retrospectively reviewed records for patients treated with and without intraoperative radiation (IORT) to identify risk factors for PVT/SMVT.

Methods: Ninety-six patients with locally advanced or borderline resectable pancreatic adenocarcinoma received neoadjuvant therapy followed by surgical exploration from 2009 to 2014.

Caspase-2 is essential for proliferation and self-renewal of nucleophosmin-mutated acute myeloid leukemia.

Mutation in nucleophosmin (NPM1) causes relocalization of this normally nucleolar protein to the cytoplasm ( ). Despite NPM1 mutation being the most common driver mutation in cytogenetically normal adult acute myeloid leukemia (AML), the mechanisms of NPM1c+-induced leukemogenesis remain unclear. Caspase-2 is a pro-apoptotic protein activated by NPM1 in the nucleolus.

Pancreatic Cancer: Targeted Therapy and Beyond.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death in the US by 2030, despite accounting for only 5% of all cancer diagnoses. Germline g-mutated PDAC represents a key subgroup with a favorable prognosis, due at least in part to additional approved and guideline-endorsed therapeutic options compared with an unselected PDAC cohort. The relatively recent incorporation of PARP inhibition into the treatment paradigm for such patients has resulted in renewed optimism for a biomarker-based approach to the management of this disease.

Clinical Utility of F-2-Fluoro-deoxy-d-glucose PET Imaging in Locally Advanced Esophageal/Gastroesophageal Junction Adenocarcinoma.

Esophageal adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, is uncommon in the United States, but is associated with a rising incidence in young adults, and has a traditionally poor prognosis. Despite the incremental benefits that have been made with multimodality approaches to locally advanced disease, most patients will go on to develop metastatic disease, and long-term outcomes remain suboptimal. Over the last decade, PET-CT has emerged as a key tool in the management of this disease, with several prospective and retrospective studies evaluating its role in this disease.

Outcomes following cryoablation of stage IA non-small cell lung cancer in patients with and without interstitial lung disease: A retrospective single-center cohort study.

Objective: To compare the safety and efficacy of cryoablation of treatment-naïve stage IA non-small cell lung cancer (NSCLC) in patients with and without interstitial lung disease (ILD).

Materials And Methods: This retrospective single-center cohort study evaluated 33 consecutive patients (24 females, median age 75 years, Eastern Cooperative Oncology Group performance score 0-3) with ILD (9 patients) and without ILD (24 patients) who underwent 39 percutaneous cryoablations to treat 42 stage IA (8th IASLC edition) NSCLC measuring 1.2 cm (range 0.

Dramatic, durable response to therapy in gBRCA2-mutated pancreas neuroendocrine carcinoma: opportunity and challenge.

Poorly differentiated pancreatic neuroendocrine tumors (PDNEC), are a subtype of pancreatic cancer encompassing both small cell and large cell neuroendocrine carcinoma subtypes, and are characterized as distinct in terms of biology and prognosis compared to the more common pancreatic adenocarcinoma. Until recently, there has been a paucity of data on the genomic features of this cancer type. We describe a male patient diagnosed with PDNEC and extensive metastatic disease in the liver at diagnosis.

Durable Response after Olaparib Treatment for Perihilar Cholangiocarcinoma with Germline BRCA2 Mutation.

Introduction: Despite major advances in surveillance and management, advanced cholangiocarcinoma (CCA) still carries a dismal prognosis. In recent years, several actionable genomic alterations in pancreatobiliary malignancies have been identified. For instance, homologous recombination deficiency (HRD) has been considered a predictive biomarker of clinical response to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors.