The treatment for endometrial cancer is rapidly evolving with the development of molecular analysis and novel strategies. Surgical resection, cytotoxic chemotherapy, endocrine or hormonal treatment, and radiation have been the staples of treatment for decades. However, precision based approaches for tumours are rapidly becoming a part of these strategies. Biomarker driven treatments are now a part of primary and recurrent treatment algorithms. This review aims to describe the current state of molecular analysis and treatment for endometrial cancer as well as to elucidate potential approaches for the near future.
Background: The aim of this study was to evaluate whether molecular classification prognosticates treatment response in women with endometrial cancers and endometrial intraepithelial neoplasia (EIN) treated with levonorgestrel intrauterine system (LNG-IUS). Methods: Patients treated with LNG-IUS for endometrial cancer or EIN from 2013 to 2018 were evaluated. Using immunohistochemistry and single gene sequencing of POLE, patients were classified into four groups as per the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE): POLE-mutated, mismatch repair-deficient (MMRd), p53 wild type (p53wt), and p53-abnormal (p53abn). Groups were assessed relative to the primary outcome of progression or receipt of definitive treatment. Results: Fifty-eight subjects with endometrioid endometrial cancer or EIN treated with LNG-IUS were included. Of these, 22 subjects (37.9%) had endometrial cancer and 36 subjects (62.1%) had EIN. Per the ProMisE algorithm, 44 patients (75.9%) were classified as p53wt, 6 (10.3%) as MMRd, 4 (6.9%) as p53abn, and 4 (6.9%) as POLE-mutated. Of the 58 patients, 11 (19.0%) progressed or opted for definitive therapy. Median time to progression or definitive therapy was 7.5 months, with p53abn tumors having the shortest time to progression or definitive therapy. Conclusions: Molecular classification of endometrial cancer and EIN prior to management with LNG-IUS is feasible and may predict patients at risk of progression.
Importance Hyperemesis gravidarum (HEG) affects 0.3% to 3% of pregnancies and requires additional therapies beyond those commonly used for less severe instances of nausea and vomiting of pregnancy (NVP). Differentiating between NVP and HEG is a vital yet challenging function for any obstetrician. The literature for management of HEG is lacking compared with that of NVP. Objective Review etiology of NVP/HEG highlights key considerations in the workup of HEG as they compare to NVP and explore management options for recalcitrant HEG focusing principally on how they affect maternal and fetal outcomes and secondarily on where data are nonprescriptive. Evidence Acquisition This was a literature review primarily using PubMed and Google Scholar. Results Short-course corticosteroids and treatment for Helicobacter pylori have the most favorable risk-reward profiles of the 4 pharmacologic therapies evaluated. Mirtazapine and diazepam may have a place in highly selected patients. If nutritional supplementation is required, enteral nutrition is strictly preferred to parenteral nutrition. Postpyloric feeding approaches are less likely to induce vomiting. Surgically placed feeding tubes are less likely to be dislodged and may be worth the invasive insertion procedure if nasogastric or nasojejunal tubes are not tolerated. Conclusions and Relevance Hyperemesis gravidarum is a diagnosis reserved for refractory cases of NVP and therefore by definition poses treatment challenges. Any clinical presentation that lent itself to prescriptive, algorithmic management would likely fall short of the diagnostic criteria for HEG. However, data can inform management on a patient-by-patient basis or at least help patient and provider understand risks and benefits of therapies reserved for refractory cases. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to evaluate the epidemiology and pathophysiology of HEG, especially as compared with NVP; assess second-line pharmacologic therapies for HEG, with particular focus on the data available for those interventions; and compare different options for nutritional support.
Venous thromboembolism (VTE) is a major cause of both morbidity and mortality in patients with cancer. Venous thromboembolism, which includes both deep vein thrombosis and pulmonary embolism, affects a sizable portion of patients with malignancy and can have potentially life threatening complications. Accurate assessment of risk as well as diagnosis and treatment of this process is paramount to preventing death in this high risk population. Various risk models predictive of venous thromboembolism in patients with cancer have been developed, and knowledge of these rubrics is essential for the treating oncologist. Subgroups of particular interest are inpatients receiving chemotherapy, postoperative patients after surgical debulking, and patients undergoing radiotherapy. Numerous newer drugs have become available for the prevention of venous thromboembolism in patients with cancer who are at high risk of developing the disease. These include the class of drugs called direct oral anticoagulants, (DOACs) which do not require the same monitoring that other modalities have previously required and are taken by mouth, preventing the discomfort associated with subcutaneous strategies. The appropriate risk stratification and intervention to prevent venous thromboembolism are vital to the treatment of patients with cancer.
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