S.U.G.A.R: A Case to Outline Tactics for the Prevention of Alpelisib-Induced Hyperglycemia.

Postmenopausal patients with metastatic breast cancer (mBC) may live years with their disease on therapies with minimal toxicities but they will eventually progress on first-line therapy. For those eligible for second-line therapy, PIK3CA mutation testing is recommended in estrogen receptor-positive, her2-negative disease. If present, alpelisib, a PI3K inhibitor, has been shown to improve progression-free survival. Hyperglycemia is a common side effect of alpelisib. We describe a case of diabetic ketoacidosis (DKA) necessitating treatment in the intensive care unit (ICU) in a woman with type 2 diabetes mellitus (T2DM) started on alpelisib. A 76-year-old female with diet-controlled T2DM and mBC was placed on second-line treatment with alpelisib after progression on first-line therapy. After more than 2 weeks of treatment, the patient presented to the emergency department with nausea and vomiting. Lab results showed DKA and she was admitted to the ICU for further management. This case highlights the need for a multidisciplinary approach to caring for patients who are started on a PI3K inhibitor. We propose 5 guidelines to prevent hyperglycemia in those started on apelisib: (1) strict criteria for initiating alpelisib, (2) understand the steps needed to prevent hyperglycemia, (3) get help from a multidisciplinary team, (4) act immediately when hyperglycemia is noted, and (5) record blood glucose values. By implementing these steps, we hope to prevent critical hyperglycemic episodes in vulnerable patients on alpelisib.

Assessing the effect of blood type on death and a novel scoring system to assess clinical course in patients with COVID-19.

BACKGROUND: Coronavirus disease (COVID-19) continues to lead to worldwide morbidity and mortality. This study examined the association between blood type and clinical outcomes in patients with COVID-19 measured by a calculated morbidity score and mortality rates. The secondary aim was to investigate the relationship between patient characteristics and COVID-19 associated clinical outcomes and mortality. METHODS: Logistic regression was used to determine what factors were associated with death. A total morbidity score was constructed based on overall patient's COVID-19 clinical course. This score was modeled using Quasi-Poisson regression. Bayesian variable selection was used for the logistic regression to obtain a posterior probability that blood type is important in predicting worsened clinical outcomes and death. RESULTS: Neither blood type nor Rh+ status was a significant moderator of death or morbidity score in regression analyses. Increased age (adjusted Odds Ratio=3.37, 95% CI=2.44-4.67), male gender (aOR=1.35, 95% CI=1.08-1.69), and number of comorbid conditions (aOR=1.28, 95% CI=1.01-1.63) were significantly associated with death. Significant factors in predicting total morbidity score were age (adjusted Multiplicative Effect=1.45; 95% CI=1.349-1.555) and gender (aME=1.17; 95% CI=1.109-1.243). The posterior probability that blood type influenced death was only 10%. CONCLUSIONS: There is strong evidence that blood type was not a significant predictor of clinical course or death in patients hospitalized with COVID-19. Older age and male gender led to worse clinical outcomes and higher rates of death; older age, male gender, and comorbidities predicted a worse clinical course and higher morbidity score. Race was not a significant predictor of death in our population and was associated with an increased, albeit not significant, morbidity score.

An Update on Screening and Prevention for Breast and Gynecological Cancers in Average and High Risk Individuals.

Breast and gynecological cancers affect almost 900,000 women and therefore most health care providers will be involved at some point in the management of women with cancer. As the prognosis of all cancers is much more favorable when diagnosed in early stages, it is imperative that all health care providers are familiar not only with current screening guidelines for the average population, but also with the identification of high risk individuals who may benefit from more intense screening as well as available interventions to prevent disease or decrease risk. The purpose of this review article is to provide relevant information to physicians and other health care providers to aid in identifying patients that are classified as "high risk" for developing breast or a gynecologic cancer, outlining what interventions exist for adequate screening and risk reduction strategies, and to provide an update on current screening guidelines for individuals at average and high risk.

Patient-Derived Xenografts as an Innovative Surrogate Tumor Model for the Investigation of Health Disparities in Triple Negative Breast Cancer.

Despite a decline in overall incidence rates for cancer in the past decade, due in part to impressive advancements in both diagnosis and treatment, breast cancer (BC) remains the leading cause of cancer-related deaths in women. BC alone accounts for ∼30% of all new cancer diagnoses in women worldwide. Triple-negative BC (TNBC), defined as having no expression of the estrogen or progesterone receptors and no amplification of the HER2 receptor, is a subtype of BC that does not benefit from the use of estrogen receptor-targeting or HER2-targeting therapies. Differences in socioeconomic factors and cell intrinsic and extrinsic characteristics have been demonstrated in Black and White TNBC patient tumors. The emergence of patient-derived xenograft (PDX) models as a surrogate, translational, and functional representation of the patient with TNBC has led to the advances in drug discovery and testing of novel targeted approaches and combination therapies. However, current established TNBC PDX models fail to represent the diverse patient population and, most importantly, the specific ethnic patient populations that have higher rates of incidence and mortality. The primary aim of this review is to emphasize the importance of using clinically relevant translatable tumor models that reflect TNBC human tumor biology and heterogeneity in high-risk patient populations. The focus is to highlight the complexity of BC as it specifically relates to the management of TNBC in Black women. We discuss the importance of utilizing PDX models to study the extracellular matrix (ECM), and the distinct differences in ECM composition and biophysical properties in Black and White women. Finally, we demonstrate the crucial importance of PDX models toward novel drug discovery in this patient population.

Overview of breast cancer collaborative stage data items--their definitions, quality, usage, and clinical implications: a review of SEER data for 2004-2010.

BACKGROUND: Surveillance, Epidemiology, and End Results (SEER) Program registries began collecting new data items, known as site-specific factors (SSFs), related to breast cancer treatment, prediction, and prognosis under the Collaborative Stage version 2 (CSv2) Data Collection System for cases diagnosed in 2010. The objectives of this report are to: 1) assess the completeness of the new SSFs and discuss their limitations and 2) discuss key changes in American Joint Committee on Cancer (AJCC) staging between the 6th and 7th editions. METHODS: We used data from the 18 SEER population-based registries (SEER-18), which included 71,983 women diagnosed with breast cancer in 2010. RESULTS: Of the 18 SSFs examined in this study, 6 SSFs were more than 75% complete. Information on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), was available for more than 90% of the invasive breast cancer cases. These data are required to categorize the distinct subtypes of breast cancer. The majority of cases also had information on other prognostic factors such as Bloom-Richardson score/grade (83%) and the size of invasive component in the tumor (76%). As a result of changes in staging criteria, nearly 10% of cases categorized as stage IIA according to the 6th edition of the AJCC staging manual were downstaged to stage IB under the 7th edition. CONCLUSIONS: The Collaborative Stage data collection system enables registries to collect current, relevant, and standardized data items that are consistent with the evolving view of breast cancer as a heterogeneous disease.

Comparison between endoscopic ultrasound and magnetic resonance imaging for the staging of pancreatic cancer.

OBJECTIVE: Preoperative staging of pancreatic cancer is crucial for proper therapy. Through this study, we aimed to compare the ability of endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) to effectively detect and stage pancreatic cancer. METHODS: One hundred twenty-seven patients undergoing EUS-fine-needle aspiration and MRI for the workup of pancreatic cancer were captured in a prospective database for comparison. The final surgical stage was recorded in patients who went to surgery. RESULTS: Of 127 patients, 48 were surgically explored, and of these, 22 (46%) underwent pancreaticoduodenectomy. Agreement in the patients' staging between EUS and MRI was 94 (74%) of 127. Magnetic resonance imaging was more likely to report metastatic disease or arterial involvement. The overall correlation between EUS and MRI was marginal (κ = 0.42; 95% CI, 0.26-0.58). Of the 48 surgically explored patients, 12 (25%) were understaged by MRI, 13 (27%) were understaged by EUS, and 1 (2%) were overstaged. Endoscopic US and MRI had a sensitivity of 34 (97.2%) of 35 for stage II tumors and 35 (100%) of 35 for lower-stage tumors, respectively. CONCLUSION: Endoscopic US and MRI had marginal correlation for staging, especially the more advanced tumors. Although EUS has the added advantage of tissue acquisition for confirmation, the tumors understaged by both the modalities were different. Therefore, both tests should be performed for accurate staging.

Endoscopic ultrasound staging is adversely affected by placement of a self-expandable metal stent: fact or fiction?

OBJECTIVES: Accurate preoperative staging of pancreatic cancer (Pca) is crucial to direct management. There is a perception that endoscopic ultrasound (EUS) staging should be performed before biliary decompression because of artifact caused by self-expandable metal stents (SEMS). Our aim is to determine whether placement of SEMS affects the staging of Pca. METHODS: Fifty-five patients (35 men; mean age, 67 years) with newly diagnosed Pca staged in the last 5 years and captured prospectively were divided into 2 groups matched by age, sex, and final staging. The staging accuracy of EUS in patients who had a SEMS (n = 28) was compared with patients without a SEMS (n = 27). The gold standard was surgical pathology, or cytologic confirmation of metastatic disease. Multivariate analysis was effected on age, sex, presence of SEMS, and presence of metastasis to assess prediction of staging inaccuracy. RESULTS: Endoscopic ultrasound correctly staged 14 (52%) of 27 patients in the no-SEMS group and 13 (46%) of 28 in the SEMS group. Logistic regression analysis identified only metastasis as a predictor of inaccuracy in EUS staging. CONCLUSIONS: Endoscopic ultrasound staging of Pca does not seem to be affected by the presence of a SEMS. The major reason for misstaging in both groups was failure to detect metastatic disease.