Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort.

Navitoclax (ABT-263) is an oral BCL2 homology-3 mimetic that binds with high affinity to pro-survival BCL2 proteins, resulting in apoptosis. Sorafenib, an oral multi kinase inhibitor also promotes apoptosis and inhibits tumor angiogenesis. The efficacy of either agent alone is limited; however, preclinical studies demonstrate synergy with the combination of navitoclax and sorafenib.

Tumor-Informed Circulating Tumor DNA for Minimal Residual Disease Detection in the Management of Colorectal Cancer.

Purpose: Recurrence after curative-intent treatment occurs in 20%-50% of patients with stage II-IV colorectal cancer (CRC), underscoring the need for early detection of minimal residual disease (MRD) using circulating tumor DNA (ctDNA). Here, we examined the pattern of use of a tumor-informed ctDNA assay in CRC MRD monitoring in routine clinical practice at Mayo Clinic, Rochester.

Methods: We conducted a retrospective analysis of health records of patients with CRC who had at least one tumor-informed ctDNA assay from May 2019 through July 1, 2022.

Selecting Optimal First-Line Treatment for Microsatellite Stable and Non-Mutated RAS/BRAF Metastatic Colorectal Cancer.

Standard frontline treatment of metastatic colorectal cancer (CRC) is cytotoxic chemotherapy plus a biologic agent such as an anti-EGFR monoclonal antibody (cetuximab or panitumumab) or anti-VEGF antibody (bevacizumab). Predictive biomarkers include mismatch repair (MMR) status, and RAS and BRAF mutation status; and important factors in treatment selection include primary tumor location, intent of therapy, and potential toxicity, as well as patient age, comorbidities, and patient preference. To date, single-, double-, or triple-agent cytotoxic chemotherapy all have important roles in appropriately selected patients, with the addition of anti-VEGF or anti-EGFR antibody therapy based on the relevant predictive biomarker.

Neoadjuvant Immune Checkpoint Inhibitor Therapy for Localized Deficient Mismatch Repair Colorectal Cancer: A Review.

Importance: Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) account for 15% of all CRCs. Deficient MMR is a predictive biomarker associated with responsiveness to immune checkpoint inhibitors (ICIs) in solid tumors, including CRC. The remarkable effectiveness of ICIs in metastatic CRC has led to their evaluation in the neoadjuvant and adjuvant treatment of localized disease.

Synchronous Neoplasia Rates at Colonoscopic Diagnosis of Early-Onset vs Average-Onset Colorectal Cancer.

Importance: The incidence of early-onset colorectal cancer (CRC) (age, <50 years) continues to increase globally within high-income countries.

Objective: To examine and compare rates of synchronous neoplasia found in patients at colonoscopic diagnosis of early-onset CRC with rates found at diagnosis of average-onset CRC.

Design, Setting, And Participants: In this multisite retrospective and cross-sectional study conducted at Mayo Clinic sites and in the Mayo Clinic Health System from January 1, 2012, to December 31, 2022, 150 randomly selected patients with early-onset CRC were identified from the electronic health record and matched with 150 patients with average-onset CRC based on sex and colonoscopic indication.

Metastatic clear cell endometrial carcinoma: an unusual cause of a common clinical presentation.

A 60-year-old woman presented with melena for 2 weeks. She had undergone hysterectomy and bilateral salpingo-oophorectomy to treat clear cell endometrial carcinoma 10 months before the presentation. She was anaemic and tachycardic; abdominal CT scan revealed a large duodenal mass.

Clinical Advancement and Challenges of Expansion of Human Cord Blood Cells.

Apart from peripheral blood stem cell (PBSC), umbilical cord blood (UCB) is now a recognized source of stem cells for transplantation. UCB is an especially important source of stem cells for minority populations, which would otherwise be unable to find appropriately matched adult donors. UCB has fewer mature T lymphocytes compared with peripheral blood, thus making a UCB transplantation (UCBT) with a greater degree of HLA mismatch possible.

B-cell Prolymphocytic Leukemia: Case Report and Challenges on a Diagnostic and Therapeutic Forefront.

B-cell prolymphocytic leukemia (B-PLL) is a rare malignancy of mature B-cells with characteristic morphologic, immunophenotypic, cytogenetic, and molecular features characterized by late onset (median age 69 years), an aggressive clinical course, refractoriness to chemotherapy, and median survival of around three years. Treatment is influenced by the presence or absence of specific high-risk genetic mutations like 17P/TP53 deletion, the presence of which translates into poor prognosis. Patients without 17P deletion, who are <70 years, without significant co-morbidities, are initially treated with a combination chemotherapy regimen used for chronic lymphocytic leukemia (CLL) such as fludarabine, cyclophosphamide, and rituximab.

Hemophagocytic Lymphohistiocytosis in an AIDS Patient with Kaposi Sarcoma: A Treatment Dilemma.

Hemophagocytic lymphohistiocytosis (HLH) is a result of an abnormal activation of immune cells (T lymphocytes, natural killer cells, and macrophages) resulting in cytokine overproduction and immune destruction of cells, eventually resulting in multiorgan failure. Genetic causes are responsible for primary hemophagocytosis, but malignancies, infections, and autoimmunity underlie most of the secondary cases. We present an unusual case of a patient with AIDS and disseminated Kaposi sarcoma who was commenced on highly active antiretroviral therapy (HAART) but developed HLH secondary to immune reconstitution inflammatory syndrome (IRIS).

Association Between the Timing of Goals-of-Care Discussion and Hospitalization Outcomes in Patients With Metastatic Cancer.

Background: Patients with cancer often require acute hospitalizations, many of which are unplanned. These hospitalizations have been shown to increase in frequency near the end of life. The American College of Physicians recommends that goals-of-care (GOC) discussions be initiated early for metastatic cancers.