Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: A retrospective study.

PURPOSE: This study investigated thyroid dysfunction with immune checkpoint inhibitors (ICIs) in terms of proportions affected, risk factors, thyroid sequelae, and overall survival (OS). METHODS: Among patients with normal baseline free T4 (fT4) and thyroid stimulating hormone (TSH) receiving ICIs at a large cancer centre, proportions of hyperthyroidism/hypothyroidism were determined (any, subclinical [normal fT4, abnormal TSH], overt [abnormal fT4, abnormal TSH], isolated hyperthyroxinaemia/hypothyroxinaemia and secondary) with onset times and subsequent thyroid statuses. Associations of overt dysfunction with OS were estimated using Cox regression and methods robust to immortal time bias (time-dependent Cox regression and 3- and 6-month landmark analyses). Associations of baseline variables with overt hyperthyroidism and hypothyroidism were estimated using Fine and Gray regression. RESULTS: Of 1349 patients, 34.2% developed hyperthyroidism (10.3% overt), including 54.9% receiving combination ICIs, while 28.2% developed hypothyroidism (overt 9.3%, secondary 0.5%). A third of overt hypothyroidism cases occurred without preceding hyperthyroidism. Subclinical thyroid dysfunction returned directly to normal in up to half. Overt hyperthyroidism progressed to overt hypothyroidism in 55.4% (median 1.6 months). Melanoma treatment in the adjuvant vs. advanced setting caused more overt hyperthyroidism (12.1% vs. 7.5%) and overt hypothyroidism (14.5% vs. 9.7%). Baseline eGFR < 60 mL/min/1.73 m2 (HR=1.68, 1.07-2.63) was associated with overt hyperthyroidism and sex (HR=0.60, 0.42-0.87) and TSH (4th vs. 1st quartile HR=1.87, 1.10-3.19) with overt hypothyroidism. Overt dysfunction was associated with OS in the Cox analysis (HR=0.65, 0.50-0.85, median follow-up 22.2 months) but not in the time-dependent Cox (HR=0.79, 0.60-1.03) or landmark analyses (3-month HR=0.74, 0.51-1.07; 6-month HR=0.91, 0.66-1.24). CONCLUSION: Thyroid dysfunction affects up to half of patients receiving ICIs. The association with OS is unclear after considering immortal time bias. The clinical courses include recovery, thyrotoxicosis and de novo overt hypothyroidism. Adjuvant treatment for melanoma, where longer-term harms are of concern, causes more frequent/aggressive dysfunction.

Provision of acute oncology services in the UK: data from the Society for Acute Medicine Benchmarking Audit 2022 (SAMBA22).

Acute oncology services (AOS) manage acute cancer-related presentations alongside acute medical teams. This study assessed AOS provision against national peer review measures and the burden of acute cancer-related admissions. The 2022 Society for Acute Medicine Benchmarking Audit surveyed UK hospitals, collecting hospital-level and patient-level data for all medical admissions over a 24-h period. Logistic regression models were constructed to identify differences in patient outcomes for cancer-related admissions. Most hospitals (n=120 or 91.6%) reported having an AOS. There was heterogeneity in AOS provision, with many failing to meet peer-review measures. Of the 7,116 patients, 542 (7.6%) were cancer-related admissions. Cancer-related admissions had greater clinical acuity (p<0.05), length of stay (p<0.001) and 14-day mortality (adjusted odds ratio (OR)=3.54, 95% confidence interval (CI): 2.41-5.22, p<0.001) compared with other medical admissions. Increasing availability of AOS with integration of ambulatory pathways are vital next steps to improving care for acute cancer-related admissions.

A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC Neutropenia, Infection, and Myelosuppression Study Group initiative.

PURPOSE: Limited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10-20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice. METHODS: This prospective, real-world, observational, multinational, multicenter study (December 2016-October 2019) recruited patients with solid tumors or Hodgkin's/non-Hodgkin's lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration). RESULTS: In total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2-3, and 1% in cycles 4-6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia. CONCLUSIONS: Overall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician's judgement.

The need for ambulatory emergency oncology: exemplified by the management of immune checkpoint inhibitor toxicity.

Cancer patients seeking emergency care can be vulnerable in increasingly overcrowded Emergency Departments and timely delivery of care is often aspirational rather than reality in many acute care systems. Ambulatory emergency care and its various international models are recognized as contributing to the safety and sustainability of emergency care services. This schema can logically be extended to the emergency oncology setting. The recent proliferation of immune checkpoint inhibitors (ICIs) has led to another opportunity for the management of oncologic complications in the ambulatory emergency care setting. More nuanced risk stratification of currently perceived high-risk toxicities may also afford the opportunity to personalize acute management. Virtual wards, which predominantly provide virtual monitoring only, and hospital at home services, which provide more comprehensive in-person assessment and interventions, may be well suited to supporting care for ICI toxicity alongside hospital-based assessment. Emergency management guidelines for immune-mediated toxicities will increasingly need to be both pragmatic and deliverable, especially as larger numbers of patients will present outside cancer centers. Identifying and modelling those suitable for emergency ambulatory care is integral to achieving this.

Improved outcomes with early immunosuppression in patients with immune-checkpoint inhibitor induced myasthenia gravis, myocarditis and myositis: a case series.

PURPOSE: Myasthenia gravis (MG) is a rare but life-threatening complication of immune-checkpoint inhibitor (ICI) therapy and often co-presents with myositis and myocarditis. Previous case series of ICI-related MG have reported high mortality rates. We present a series of ten patients from a tertiary oncology centre outlining outcomes of an early multi-modal immunosuppression strategy. METHODS: We reviewed The Christie Hospital database of immunotherapy-related toxicity from 2017 to 2020. Symptom severity was assessed using the Myasthenia Gravis Foundation of America (MGFA) classification. RESULTS: Ten patients with ICI-related MG were identified. All patients presented following 1 (n = 4) or 2 (n = 6) cycles of ICI. Symptom progression was rapid with a median of 3 days from onset of symptoms to admission. Concomitant myositis and myocarditis were observed in nine patients. AChR or MuSK autoantibodies were positive in six patients. All patients received urgent treatment with intravenous methylprednisolone (IVMP) and eight received intravenous immunoglobulin (IVIG). A single patient died from myasthenia-related symptoms; the remaining 9 patients were successfully discharged. CONCLUSION: In our cohort, we demonstrate good outcomes associated with early intensive immunosuppressive treatment with IVIG and IVMP. An agreed national treatment protocol or clinical discussion forum would be beneficial.

Intensive care unit requirements in patients treated with immune checkpoint inhibitors.

OBJECTIVE: To determine the proportion of emergency patients treated with immune checkpoint inhibitors (ICIs) that require critical care admission and their requirements. DESIGN: Prospective case series. METHODS: Analysis of acutely unwell patients treated with ICIs attending a tertiary UK cancer hospital between May 2018 and May 2022. The primary outcome measure was the percentage of patients treated with ICI therapy requiring ICU admission. The secondary outcome measure was whether this need was driven by an immune-mediated toxicity. RESULTS: Eighteen (1.2%) patients of the 1561 acutely admitted patients treated with ICI therapy required an admission to ICU. Ten (55.5%) patients were admitted due to an immune-mediated toxicity; four due to pneumonitis and four due to myasthenia gravis. Seven of 10 survived their ICU admission with 6 surviving at least 6-month post-ICU discharge. CONCLUSIONS: Only a small minority of emergency admissions in patients treated with ICIs require admission to ICU. This series adds further evidence that patients with organ failure due to immune-mediated toxicity may achieve good outcomes from ICU admission.

Catheter-related thrombosis (CRT) in patients with solid tumors: a narrative review and clinical guidance for daily care.

Central venous access devices (CVADs) including central venous catheters and peripherally inserted central catheters (PICCs) are essential in the treatment of cancer. Catheter-related thrombosis (CRT) is the most frequent non-infectious complication associated with the use of central lines. The development of CRT may cause to delays in oncologic treatment and increase morbidity leading to potentially life-threatening complications. Several local and systemic risk factors are associated with the development of CRT and should be taken into account to prevent CRT by standardizing appropriate catheter placement and maintenance. The use of primary pharmacological thromboprophylaxis in order to avoid CRT is not routinely recommended, although it can be considered in selected cases. Recommendations for the management of established CRT are based on the extrapolation of anticoagulation for lower limb venous thrombosis. The present review summarizes the current evidence and recommendations for the prevention and management of CRT and identifies areas that require further research.

Emergency management of incidental pulmonary embolism (IPE).

Venous thrombo-embolic (VTE) disease is a common cause of complications in patients with cancer and is the second most common cause of death in oncology patients other than the malignant disease. Whilst symptomatic VTE comprises the majority of such presentations to an emergency department (ED), incidental pulmonary embolism (IPE) is an increasingly frequent reason for attendance. Many studies report that the consequences of IPE do not differ significantly from those with symptomatic presentations and thus most guidelines recommend using the same approach. The complexity of treatment in cancer patients due to increased prevalence of co-morbidities, higher risk of bleeding, abnormal platelet and renal function, greater risk of VTE recurrence, and medications with the risk of anticoagulant interaction are consistent across patients with symptomatic and IPE. One of the initial challenges of the management of IPE is the design of a pathway that provides both patients and clinicians with a seamless journey from the radiological diagnosis of IPE to their initial clinical workup and management. Increased access to ambulatory care has successfully reduced ED utilisation and improved clinical outcomes in high-risk non-oncological populations, such as those with IPE. In this clinical review, we consider IPE management, its workup, the conundrums it may present for emergency physicians and the need to consider emergency ambulatory care for this growing cohort of patients.

Risk stratification for clinical severity of pulmonary embolism in patients with cancer: a narrative review and MASCC clinical guidance for daily care.

Pulmonary embolism (PE) is a leading cause of morbidity and mortality in patients with cancer. The clinical presentation and outcomes of PE range from an acute life-threatening condition requiring intensive care to a mild symptomatic condition associated with favorable outcomes and potentially candidate for early hospital discharge. The wide clinical spectrum of PE has led to the development of risk stratification models aimed at the triage of patients in emergency care departments and optimizing the utilization of health care resources. Incidental or unsuspected PE (UPE), detected during routine staging computed tomography scans, make up a significant proportion of this cohort among the oncology population. The present narrative review is aimed at examining the currently available PE risk assessment models developed for the general population and for patients with cancer including UPE. We include general recommendations for the daily care of patients with cancer-related PE and hypothesize on the factors that would potentially favor hospitalization with early discharge or ambulatory management in this setting.

Patient and treatment characteristics of emergency presentations due to immune-mediated toxicities.

BACKGROUND: The prevalence of immune-mediated toxicities from immune checkpoint inhibitors (ICIs) is well described. However, the characteristics and treatment patterns for patients with emergency presentations owing to immune-mediated toxicity are less well known. MATERIALS AND METHODS: This study reviews all emergency presentations in patients treated with ICI at a single centre between May 2018 and March 2020. The aims were to describe and quantify patient and treatment characteristics, toxicity type and outcomes. RESULTS: 1165 patients were treated with ICI, and there were 597 emergency presentations in 370 patients. Of these, 191/597 (32%) were owing to an immune-mediated toxicity, median age was 64 years, and 127/191 (67%) were men. The most common tumour types were melanoma (53%) and lung cancer (22%), and the most common ICI received was ipilimumab + nivolumab combination immunotherapy (42%), followed by pembrolizumab monotherapy (21%) and nivolumab monotherapy (20%). The median number of cycles received was three (range 1-54), and 75/191 (39%) had previous ≥ grade 2 immune-mediated toxicity. 29% patients required second-line immunosuppression. The median time in the hospital was four days. There was a rising number of emergency presentations reflecting overall increasing use of ICI. CONCLUSIONS: Over a quarter of patients treated with ICI had an emergency presentation, and immune-mediated toxicity accounted for 32% of these. A diagnosis of melanoma, treatment with combination immunotherapy and previous ≥ grade 2 immune-mediated toxicity were common in patients with immune-mediated toxicity. These data allow better identification of patients likely to require admission and forward planning for acute oncology services.

Pulmonary Toxicities Associated With the Use of Immune Checkpoint Inhibitors: An Update From the Immuno-Oncology Subgroup of the Neutropenia, Infection & Myelosuppression Study Group of the Multinational Association for Supportive Care in Cancer.

The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, with agents such as nivolumab, pembrolizumab, and cemiplimab targeting programmed cell death protein-1 (PD-1) and durvalumab, avelumab, and atezolizumab targeting PD-ligand 1 (PD-L1). Ipilimumab targets cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). These inhibitors have shown remarkable efficacy in melanoma, lung cancer, urothelial cancer, and a variety of solid tumors, either as single agents or in combination with other anticancer modalities. Additional indications are continuing to evolve. Checkpoint inhibitors are associated with less toxicity when compared to chemotherapy. These agents enhance the antitumor immune response and produce side- effects known as immune-related adverse events (irAEs). Although the incidence of immune checkpoint inhibitor pneumonitis (ICI-Pneumonitis) is relatively low, this complication is likely to cause the delay or cessation of immunotherapy and, in severe cases, may be associated with treatment-related mortality. The primary mechanism of ICI-Pneumonitis remains unclear, but it is believed to be associated with the immune dysregulation caused by ICIs. The development of irAEs may be related to increased T cell activity against cross-antigens expressed in tumor and normal tissues. Treatment with ICIs is associated with an increased number of activated alveolar T cells and reduced activity of the anti-inflammatory Treg phenotype, leading to dysregulation of T cell activity. This review discusses the pathogenesis of alveolar pneumonitis and the incidence, diagnosis, and clinical management of pulmonary toxicity, as well as the pulmonary complications of ICIs, either as monotherapy or in combination with other anticancer modalities, such as thoracic radiotherapy.

Emergency Presentations of Immune Checkpoint Inhibitor-Related Endocrinopathies.

BACKGROUND: Immune checkpoint inhibitors (ICI) are an important component of anticancer treatment, with indications across an increasing range of oncological diagnoses. ICIs are associated with a range of immune-mediated toxicities. Immune-related endocrinopathies pose a distinct challenge, given the nonspecific symptom profile and potentially life-threatening sequelae if not recognized. OBJECTIVES: To determine the frequency and clinical presentations of immune-mediated endocrinopathies in patients treated with ICIs presenting as emergencies. METHODS: A prospective observational cohort study was undertaken at a specialist oncology hospital in North West England from May 20, 2018 to May 19, 2020. Within the hospital, the Oncology Assessment Unit (OAU) acts as the receiving unit in which assessments are undertaken of all emergency presentations. All patients treated with ICIs presenting to the OAU were included. The primary outcome was diagnosis of an immune-mediated endocrinopathy. Length of inpatient stay, and 7- and 30-day mortality rates were examined. RESULTS: During the study period, 684 patients treated with ICIs presented to the OAU. Twenty-four (3.5%) patients had an acute immune-mediated endocrinopathy, of which 17 had hypophysitis, 4 diabetes mellitus, 2 thyrotoxicosis, and 1 adrenalitis. Median length of stay for patients with hypophysitis was 1 day. No patient with an immune-mediated endocrinopathy died within 30 days of presentation. CONCLUSIONS: Presentations to emergency settings with acute immune-mediated endocrinopathies are rare. Early recognition of immune-mediated toxicities is important, and particularly pertinent in ICI-related endocrinopathies, where even in life-threatening cases, the presentation can be vague and nonspecific.

Supportive care for new cancer therapies.

PURPOSE OF REVIEW: The past decade has witnessed unprecedented delivery to the clinical arena of a range of novel, innovative, and effective targeted anticancer therapies. These include immunotherapies, most prominently immune checkpoint inhibitors, as well as agents that target growth factors and cancer-related mutations. Many of these new cancer therapies are, however, associated with an array of toxicities, necessitating insight and vigilance on the part of attending physicians to achieve high-quality supportive care alongside toxicity management. In this review, we consider some of the key supportive care issues in toxicity management. RECENT FINDINGS: Although both supportive care and targeted therapies have brought significant benefits to cancer care, the management of novel cancer therapy toxicities is nevertheless often complex. This is due in large part to the fact that target organs differ widely, particularly in the case of checkpoint inhibitors, with minor dermatological disorders being most common, while others, such as pneumonitis, are more severe and potentially life threatening. Accordingly, efficient management of these immune-related adverse events requires collaboration between multiple medical specialists. SUMMARY: Supportive care is a key component in the management of new cancer therapy toxicities and needs to be incorporated into treatment pathways.

Treatment of infections in cancer patients: an update from the neutropenia, infection and myelosuppression study group of the Multinational Association for Supportive Care in Cancer (MASCC).

INTRODUCTION: Patients with hematological and advanced solid malignancies have acquired immune dysfunction, often exacerbated by treatment, posing a significant risk for the development of infections. This review evaluates the utility of current clinical and treatment guidelines, in the setting of management of infections in cancer patients. AREAS COVERED: These include causes of infection in cancer patients, management of patients with high-risk and low-risk febrile neutropenia, management of low-risk patients in an outpatient setting, the role of granulocyte colony-stimulating factor (G-CSF) in the prevention and treatment of neutropenia-related infections, management of lung infections in various clinical settings, and emerging challenges surrounding the risk of infection in cancer patients treated with novel treatments. The literature search was performed by accessing PubMed and other databases, focusing on published clinical trials of relevant anti-cancer agents and diseases, primarily covering the recent past, but also including several key studies published during the last decade and, somewhat earlier in a few cases. EXPERT REVIEW: Notwithstanding the promise of gene therapy/gene editing in hematological malignancies and some types of solid cancers, innovations introduced in clinical practice include more discerning clinical management such as the generalized use of biosimilar formulations of G-CSF and the implementation of novel, innovative immunotherapies.

Clinical impact of COVID-19 on patients with cancer treated with immune checkpoint inhibition.

BACKGROUND: Patients with cancer who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to develop severe illness and die compared with those without cancer. The impact of immune checkpoint inhibition (ICI) on the severity of COVID-19 illness is unknown. The aim of this study was to investigate whether ICI confers an additional risk for severe COVID-19 in patients with cancer. METHODS: We analyzed data from 110 patients with laboratory-confirmed SARS-CoV-2 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe and Australia. The primary objective was to describe the clinical course and to identify factors associated with hospital and intensive care (ICU) admission and mortality. FINDINGS: Thirty-five (32%) patients were admitted to hospital and 18 (16%) died. All patients who died had advanced cancer, and only four were admitted to ICU. COVID-19 was the primary cause of death in 8 (7%) patients. Factors independently associated with an increased risk for hospital admission were ECOG ≥2 (OR 39.25, 95% CI 4.17 to 369.2, p=0.0013), treatment with combination ICI (OR 5.68, 95% CI 1.58 to 20.36, p=0.0273) and presence of COVID-19 symptoms (OR 5.30, 95% CI 1.57 to 17.89, p=0.0073). Seventy-six (73%) patients interrupted ICI due to SARS-CoV-2 infection, 43 (57%) of whom had resumed at data cut-off. INTERPRETATION: COVID-19-related mortality in the ICI-treated population does not appear to be higher than previously published mortality rates for patients with cancer. Inpatient mortality of patients with cancer treated with ICI was high in comparison with previously reported rates for hospitalized patients with cancer and was due to COVID-19 in almost half of the cases. We identified factors associated with adverse outcomes in ICI-treated patients with COVID-19.

Emerging challenges in the evaluation of fever in cancer patients at risk of febrile neutropenia in the era of COVID-19: a MASCC position paper.

Patients with cancer are at higher risk of more severe COVID-19 infection and have more associated complications. The position paper describes the management of cancer patients, especially those receiving anticancer treatment, during the COVID-19 pandemic. Dyspnea is a common emergency presentation in patients with cancer with a wide range of differential diagnoses, including pulmonary embolism, pleural disease, lymphangitis, and infection, of which SARS-CoV-2 is now a pathogen to be considered. Screening interviews to determine whether patients may be infected with COVID-19 are imperative to prevent the spread of infection, especially within healthcare facilities. Cancer patients testing positive with no or minimal symptoms may be monitored from home. Telemedicine is an option to aid in following patients without potential exposure. Management of complications of systemic anticancer treatment, such as febrile neutropenia (FN), is of particular importance during the COVID-19 pandemic where clinicians aim to minimize patients' risk of infection and need for hospital visits. Outpatient management of patients with low-risk FN is a safe and effective strategy. Although the MASCC score has not been validated in patients with suspected or confirmed SARS-CoV-2, it has nevertheless performed well in patients with a range of infective illnesses and, accordingly, it is reasonable to expect efficacy in the clinical setting of COVID-19. Risk stratification of patients presenting with FN is a vital tenet of the evolving sepsis and pandemic strategy, necessitating access to locally formulated services based on MASCC and other national and international guidelines. Innovative oncology services will need to utilize telemedicine, hospital at home, and ambulatory care services approaches not only to limit the number of hospital visits but also to anticipate the complications of the anticancer treatments.

Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Therapy.

As part of immune surveillance, killer T lymphocytes search for cancer cells and destroy them. Some cancer cells, however, develop escape mechanisms to evade detection and destruction. One of these mechanisms is the expression of cell surface proteins which allow the cancer cell to bind to proteins on T cells called checkpoints to switch off and effectively evade T-cell-mediated destruction. Immune checkpoint inhibitors (ICIs) are antibodies that block the binding of cancer cell proteins to T-cell checkpoints, preventing the T-cell response from being turned off by cancer cells and enabling killer T cells to attack. In other words, ICIs restore innate antitumor immunity, as opposed to traditional chemotherapies that directly kill cancer cells. Given their relatively excellent risk-benefit ratio when compared to other forms of cancer treatment modalities, ICIs are now becoming ubiquitous and have revolutionized the treatment of many types of cancer. Indeed, the prognosis of some patients is so much improved that the threshold for admission for intensive care should be adjusted accordingly. Nevertheless, by modulating immune checkpoint activity, ICIs can disrupt the intricate homeostasis between inhibition and stimulation of immune response, leading to decreased immune self-tolerance and, ultimately, autoimmune complications. These immune-related adverse events (IRAEs) may virtually affect all body systems. Multiple IRAEs are common and may range from mild to life-threatening. Management requires a multidisciplinary approach and consists mainly of immunosuppression, cessation or postponement of ICI treatment, and supportive therapy, which may require surgical intervention and/or intensive care. We herein review the current literature surrounding IRAEs of interest to anesthesiologists and intensivists. With proper care, fatality (0.3%-1.3%) is rare.

The Diagnoses and Outcomes of Emergency Patients With an Elevated D-Dimer Over the Next 90 Days.

BACKGROUND: It is not known what diagnoses are associated with an elevated D-dimer in unselected patients attending emergency departments (ED), nor have their associated outcomes been determined. METHODS: This was a prospective observational study of 1612 unselected patients attending a Danish ED, with 100% follow-up for 90 days after presentation. RESULTS: The 765 (47%) ED patients with an elevated D-dimer level (ie, ≥ 0.5 mg/L) were more likely to be admitted to hospital (P <.0001), re-present to health services (P = .02), and die within 90 days (8.1% of patients, P <.0001). Only 10 patients with a normal D-dimer level (1.2%) died within 90 days. Five had chronic obstructive pulmonary disease and infection, and 5 had cancer (4 of whom also had infection). Venous thromboembolism, infection, neoplasia, anemia, heart failure, and unspecified soft tissue disorders were significantly associated with an elevated D-dimer level. Of the 72 patients with venous thromboembolism, 20 also had infection, 8 had cancer, and 4 had anemia. None of the patients with heart failure, stroke, or acute myocardial infarction with a normal D-dimer level died within 90 days. CONCLUSIONS: In this study, nearly half of all patients attending the ED had an elevated D-dimer level, and these patients were more likely to be admitted to hospital and to re-present to health services or die within 90 days. In this unselected ED patient population, elevated D-dimer levels were found to not only be significantly associated with venous thromboembolism, but to also be associated with infection, cancer, heart failure, and anemia.

Correction: Checklists for Complications During Systemic Cancer Treatment Shared by Patients, Friends, and Health Care Professionals: Prospective Interventional Cohort Study.

[This corrects the article DOI: 10.2196/19225.].

Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-related adverse events: pulmonary toxicity.

The immune checkpoints associated with the CTLA-4 and PD-1 pathways are critical modulators of immune activation. These pathways dampen the immune response by providing brakes on activated T cells, thereby ensuring more uniform and controlled immune reactions and avoiding immune hyper-responsiveness and autoimmunity. Cancer cells often exploit these regulatory controls through a variety of immune subversion mechanisms, which facilitate immune escape and tumor survival. Immune checkpoint inhibitors (ICI) effectively block negative regulatory signals, thereby augmenting immune attack and tumor killing. This process is a double-edged sword in which release of regulatory controls is felt to be responsible for both the therapeutic efficacy of ICI therapy and the driver of immune-related adverse events (IrAEs). These adverse immune reactions are common, typically low-grade and may affect virtually every organ system. In the early clinical trials, lung IrAEs were rarely described. However, with ever-expanding clinical applications and more complex ICI-containing regimens, lung events, in particular, pneumonitis, have become increasingly recognized. ICI-related lung injury is clinically distinct from other types of lung toxicity and may lead to death in advanced stage disease. Thus, knowledge regarding the key characteristics and optimal treatment of lung-IrAEs is critical to good outcomes. This review provides an overview of lung-IrAEs, including risk factors and epidemiology, as well as clinical, radiologic, and histopathologic features of ICI-related lung injury. Management principles for ICI-related lung injury, including current consensus on steroid refractory pneumonitis and the use of other immune modulating agents in this setting are also highlighted.