Evaluation and management of acute high-grade immunotherapy-related neurotoxicity.

Immune checkpoint inhibitor monoclonal antibodies allow the host's immune system to attack tumors, which has revolutionized cancer care over the last decade. As the use of immune checkpoint inhibitors has expanded, so have autoimmune-like complications known as immune-related adverse events. These include the infrequent but increasingly more common, potentially deadly neurological immune related adverse events. When feeling acutely ill, patients will often seek care not from their oncologist but from their family physician, clinics, emergency, and urgent care sites, or other available providers. Thus, while assessing acutely ill cancer patients who are experiencing neurological symptoms, non-oncologists should be prepared to recognize, diagnose, and treat neurological immune related adverse events in addition to more familiar conditions. This narrative review is designed to update acute care clinicians on current knowledge and to present a symptom-based framework for evaluating and treating neurological immune related adverse events based on the leading immunotoxicity organizations' latest recommendations.

"Triple Threat" Conditions Predict Mortality Among Patients With Advanced Cancer Who Present to the Emergency Department.

BACKGROUND: Delirium, poor performance status, and dyspnea predict short survival in the palliative care setting. OBJECTIVE: Our goal was to determine whether these three conditions, which we refer to as a "triple threat," also predict mortality among patients with advanced cancers in the emergency department (ED). METHODS: The study sample included 243 randomly selected, clinically stable patients with advanced cancer who presented to our ED. The analysis included patients who had delirium (Memorial Delirium Assessment Scale score ≥ 7), poor performance status (Eastern Cooperative Oncology Group performance status score of 3 or 4), or dyspnea as a presenting symptom. We obtained survival data from medical records. We calculated predicted probability of dying within 30 days and association with number of symptoms after the ED visit using logistic regression analysis. RESULTS: Twenty-eight patients died within 30 days after presenting to the ED. Death within 30 days occurred in 36% (16 of 44) of patients with delirium, 28% (17 of 61) of patients with poor performance status, and 14% (7 of 50) of patients with dyspnea, with a predicted probability of 30-day mortality of 0.38 (95% confidence interval [CI] 0.25-0.53), 0.28 (95% CI 0.18-0.40), and 0.15 (95% CI 0.07-0.29), respectively. The predicted probability of death within 30 days for patients with two or three of the conditions was 0.49 (95% CI 0.34-0.66) vs. 0.05 (95% CI 0.02-0.09) for patients with none or one of the conditions. CONCLUSIONS: Patients with advanced cancers who present to the ED and have at least two triple threat conditions have a high probability of death within 30 days.

Carotid Blowout Syndrome in the Emergency Department: A Case Report and Review of the Literature.

BACKGROUND: Carotid blowout syndrome (CBS) is an infrequent but dangerous oncologic emergency that must be recognized due to a mortality rate that approaches 40% and neurologic morbidity that approaches 60%. Patients present with a variety of symptoms ranging from asymptomatic to frank hemorrhage, and appropriate recognition and management may improve their outcomes. CASE REPORT: A man in his late 60s with squamous cell carcinoma of the oropharynx presented to the emergency department (ED) with hemoptysis and several episodes of post-tussive emesis with large clots. He had been cancer free for multiple years after treatment with chemotherapy and radiation to the neck. Evaluation revealed a necrotic tumor on the posterior pharynx on bedside laryngoscopy and an external carotid pseudoaneurysm that was stented by interventional radiology. The patient experienced recurrent hemorrhage several months later and opted for palliative measures and expired of massive hemorrhage in the ED on a subsequent visit. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: CBS can be fatal, and early suspicion and recognition are key to ensure that a threatened or impending carotid blowout are appropriately managed. Once carotid blowout is suspected, early resuscitation and consultation with interventional radiology and vascular surgery is warranted.

Cardiotoxicity associated with immune checkpoint inhibitors and CAR T-cell therapy.

INTRODUCTION: The expanding use of immunotherapy and the growing population of patients with cancer has led to an increase in the reporting of immune related adverse events (irAEs). The emergency clinician should be aware of these emerging toxicities, some of which can be fatal. In this review we discuss the cardiotoxic side effects of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR T-cell) therapy. DISCUSSION: Recognizing the possible presentations of cardiotoxic irAEs is of utmost important as the diagnosis of cardiotoxicity associated with ICI and CAR T-cell can be difficult to make in the emergency department. The emergency clinician will have to presume the diagnosis and treat it without final confirmation in most cases. For this reason, if the diagnosis is suspected, early involvement of the cardiologist and oncologist is important to help guide management. Most irAEs will be treated with glucocorticoids, but in the case of CAR T-cell cardiotoxicity, Tocilizumab should be used as first line. CONCLUSION: Although cardiotoxicity is rare, it is often life-threatening. Treatment should be initiated as soon as the diagnosis is suspected, and early involvement of the cardiologist and oncologist is imperative for optimal treatment.

Clinical and Cancer-Related Predictors for Venous Thromboembolism in Cancer Patients Presenting to the Emergency Department.

BACKGROUND: The accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests. OBJECTIVE: We sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE. METHODS: We retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016. RESULTS: Cancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37-5.60], p < 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62-2.28], p < 0.001), active cancer (OR 1.35 [95% CI 1.10-1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01-1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32-2.27], p < 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort. CONCLUSIONS: Cancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.

Evaluation of Cancer Patients With Suspected Pulmonary Embolism: Performance of the American College of Physicians Guideline.

BACKGROUND: Accurate risk stratification of pulmonary embolism (PE) can reduce unnecessary imaging. We investigated the extent to which the American College of Physicians (ACP) guideline for evaluation of patients with suspected PE could be applied to cancer patients in the emergency department of a comprehensive cancer center. MATERIALS AND METHODS: Data from cancer patients who underwent CT pulmonary angiography (CTPA) between August 1, 2015, and October 31, 2015, were collected. We assessed each patient's diagnostic workup for its adherence to the ACP guideline in terms of clinical risk stratification and age-adjusted d-dimer level and the degree to which these factors were associated with PE. RESULTS: Of the 380 patients identified, 213 (56%) underwent CTPA indicated per the ACP guideline, and 78 (21%) underwent CTPA not indicated per the guideline. Only one of the patients who underwent nonindicated CTPA had a PE. Fifty-seven patients underwent unnecessary d-dimer evaluation, and 71 patients with negative d-dimer test results underwent nonindicated CTPA. PEs were found in 6 of 108 (6%) low-risk patients, 22 of 219 (10%) intermediate-risk patients, and 13 of 53 (25%) high-risk patients. The ACP guideline had negative predictive value of 99% (95% confidence interval: 93%-100%) and sensitivity of 97% (95% confidence interval: 86%-100%) in predicting PE. CONCLUSION: The ACP guideline has good sensitivity for detecting PE in cancer patients and thus can be applied in this population. Compliance with the ACP guideline when evaluating cancer patients with suspected PE could reduce the use of unnecessary imaging and laboratory studies.

Challenge of immune-mediated adverse reactions in the emergency department.

Multiple drugs of a new class of cancer treatments called immune checkpoint inhibitors, which work by enabling the immune system to attack tumour cells, have been approved for a variety of indications in recent years. Immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 and programmed death-1, are part of the normal immune system and regulate immune activation. Treatment with inhibitors of these checkpoints can significantly improve response rates, progression-free survival and overall survival of patients with cancer; it can also result in adverse reactions that present similarly to other conditions. These immune-mediated adverse reactions (IMARs) are most commonly gastrointestinal, respiratory, endocrine or dermatologic. Although patients' presentations may appear similar to other types of cancer therapy, the underlying causes, and consequently their management, may differ. Prompt recognition is critical because, with appropriate management, most IMARs resolve and patients can continue receiving immune checkpoint inhibitor treatment. Rarely, these IMARs may be life-threatening and escape detection from the usual evaluations in the emergency environment. Given the unusual spectrum and mechanism of IMARs arising from immune checkpoint inhibitors, emergency departmentED staff require a clear understanding of the evaluation of IMARs to enable them to appropriately assess and treat these patients. Treatment of IMARs, most often with high-dose steroids, differs from chemotherapy-related adverse events and when possible should be coordinated with the treating oncologist. This review summarises the ED presentation and management of IMARs arising from immune checkpoint inhibitors and includes recommendations for tools and resources for ED healthcare professionals.

Advance care planning: challenges at the emergency department of a cancer care center.

INTRODUCTION: Code status discussions form an important part of advance care planning (ACP) as it enables physicians to respect the patient's wishes for end-of-life care. However, in some cases, code status discussions can be challenging causing the physician to go against the patient's wishes and the code of medical ethics. This is especially true in an emergency setting. In this paper, we will discuss three cases of advanced cancer patients, where code status discussions posed challenges to healthcare providers. CASE REPORTS: In the first case, the patient was a 26-year-old male diagnosed with advanced osteosarcoma. Code status was discussed with him, while he was still functional, wherein he agreed to a do-not-resuscitate (DNR) order. However, at the time of end-of-life care, despite of previous code status agreement, the patient's mother insisted on full code. As a result, the DNR order was reverted and the patient was intubated. The second case discusses an 83-year-old female patient with metastatic gastric cancer. Code status was extensively discussed with the patient and her son who agreed to sign a DNR order. This case posed a challenge because when the patient's condition deteriorated, her son demanded cardioversion and other aggressive treatment measures without any chest compressions or intubation. In the third case, the patient was a 40-year-old woman with advanced metastatic adenocarcinoma with neuroendocrine features of the parotid. On admission to the ED, as per the patient's wishes expressed by her husband, a DNR/DNI order was placed. However, this order had to be reverted when the patient's aunt and sister opposed vehemently to the DNR/DNI order. CONCLUSION: The three cases demonstrate the challenges that can arise in the implementation of code status order in the ED as it pertains for end-of-life care. In any scenario, respecting the patient's wishes and adherence to the code of medical ethics take precedence over any familial objections arising difficulties with coping.

Association of body composition with outcome of docetaxel chemotherapy in metastatic prostate cancer: a retrospective review.

BACKGROUND: Docetaxel, a lipophilic drug, is indicated for castration-resistant metastatic prostate cancer. Most men with such disease would have had androgen-deprivation therapy, which decreases muscle and increases body fat. Obesity and body composition changes may influence the outcomes of docetaxel therapy. METHODS: We conducted a retrospective review of 333 patients with metastatic prostate cancer treated with docetaxel at a comprehensive cancer center between October 7, 2004 and December 31, 2012. Body composition parameters were measured based on the areas of muscle and adipose tissues in the visceral and subcutaneous compartments on CT images at L3-4 levels. Dose calculations, toxicity and adverse reaction profiles, and overall survival were analyzed. RESULTS: Obese patients were younger at the diagnosis of prostate cancer and had a shorter duration from diagnosis to docetaxel therapy. Analysis of body composition found that a high visceral fat-to-subcutaneous fat area ratio (VSR) was associated with poor prognosis but a high visceral fat-to-muscle area ratio (VMR) and high body mass index were associated with increased duration from starting docetaxel to death, allowing such men to catch up with patients with normal body mass index in overall survival from cancer diagnosis to death. Cox proportional hazard regression showed that age ≥65 years, high VSR, abnormal serum alkaline phosphatase, and >10% reduction of initial dosage were significant predictors of shorter time between starting docetaxel and death, and that high VMR, obesity, and weekly regimens were significant predictors of longer survival after docetaxel. CONCLUSION: Obese and overweight patients may benefit more from weekly docetaxel regimens using the reference dosage of 35 mg/m2 without empirical dosage reduction.