Untangling the Multidisciplinary Care Web: Streamlining Care Through an Immune-Related Adverse Events (IRAE) Tumor Board.
Ontology highlight
ABSTRACT:
SUBMITTER: Kennedy LC
PROVIDER: S-EPMC7489785 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:There is growing recognition of immune related adverse events (irAEs) from immune checkpoint therapies being correlated with treatment outcomes in certain malignancies. There are currently limited data or consensus to guide management of irAEs with regards to treatment rechallenge. We conducted a retrospective analysis with an IRB-approved protocol of adult patients seen at the WVU Cancer Institute between 2011-2019 with a histopathologic diagnosis of active cancers and were treated with immune checkpoint inhibitors (ICI) therapy. Demographics were similar between the ICI interrupted irAE groups within cancer types. Overall, out of 548 patients who received ICI reviewed, there were 133 cases of ≥1 irAE found of any grade. Being treated with anti-CTLA-4 inhibitor ICI was associated with lower risk of death compared to anti-PD-1 ICI. The overall survival difference observed for irAE positive patients, between rechallenged (37.8 months, reinitiated with/without interruption; 38.6 months, reinitiated after interruption) and interrupted/non-reinitiated (i.e., discontinued) groups (24.9 months) was not statistically significant, with a numerical trend favoring the former. Our exploratory study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.
| S-EPMC7956829 | biostudies-literature
Project description:Immune-oncology is a major breakthrough in cancer treatment and has become the standard of care for a wide variety of solid organ malignancies. Unfortunately, manipulation of the immune system with checkpoint inhibitors may result in an immune-based attack of normal tissues which can lead to treatment discontinuation. These immune-related adverse events (irAEs) are diverse and affect several organs, constituting a new clinical challenge in the management of cancer patients. The complexity of this scenario requires a multidisciplinary approach that allows the early identification, diagnosis and treatment of specific irAE, ruling out other non-related adverse events. Hospital Clinic has a multidisciplinary team seeking to develop a coordinated strategy to facilitate the access of patients with suspected irAEs to specialised care resulting in harmonised management that guarantees the best patient care. The aim of the manuscript was to describe the current evidence on the management of irAEs reflecting a coordinated multidisciplinary approach to face this clinical challenge regardless of the immunotherapy indication.
| S-EPMC7699587 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs.MethodsSix hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment.ResultsPatients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67).ConclusionAn increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.
| S-EPMC10757154 | biostudies-literature
Project description:Checkpoint inhibitors are part of the family of immunotherapies and are increasingly being used in a wide variety of cancers. Immune-related adverse events pose a major challenge in the treatment of cancer patients. Pneumonitis is a rare immune-related adverse event that presents in distinct patterns. The goal of this chapter is to instruct readers on the incidence and clinical manifestations of pneumonitis and to offer guidance in the evaluation and treatment of patients with pneumonitis.
| S-EPMC7161534 | biostudies-literature
Project description:Neurodegenerative diseases affect a significant portion of the aging population. Several lines of evidence suggest a positive association between environmental exposures, which are common and cumulative in a lifetime, and development of neurodegenerative diseases. Environmental or occupational exposure to manganese (Mn) has been implicated in neurodegeneration due to its ability to induce mitochondrial dysfunction, oxidative stress, and α-synuclein (α-Syn) aggregation. The role of the α-Syn protein vis-a-vis Mn is controversial, as it seemingly plays a duplicitous role in neuroprotection and neurodegeneration. α-Syn has low affinity for Mn, however an indirect interaction cannot be ruled out. In this review we will examine the current knowledge surrounding the interaction of α-Syn and Mn in neurodegenerative process.
| S-EPMC4972813 | biostudies-literature
Project description:Purpose: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies. It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors. Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials.Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC). Extensive drug repurposing screens, pharmacokinetic, pharmacodynamic, and efficacy studies were used to triage active compounds for combination preclinical trials with "standard-of-care" surgery and radiotherapy.Results: Mouse models displayed distinct patterns of response to surgery, irradiation, and chemotherapy that varied with tumor subtype. Repurposing screens identified 3-hour infusions of gemcitabine as a relatively nontoxic and efficacious treatment of SEP and CPC. Combination neurosurgery, fractionated irradiation, and gemcitabine proved significantly more effective than surgery and irradiation alone, curing one half of all animals with aggressive forms of SEP.Conclusions: We report a comprehensive preclinical trial platform to assess the therapeutic activity of conventional and novel treatments among rare brain tumor subtypes. It also enables the development of complex, combination treatment regimens that should deliver optimal trial designs for clinical testing. Postirradiation gemcitabine infusion should be tested as new treatments of SEP and CPC. Clin Cancer Res; 24(7); 1654-66. ©2018 AACR.
| S-EPMC5884708 | biostudies-literature
Project description:BackgroundDespite providing clinical benefit, immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in a number of patients. This study explored the development pattern in irAEs research from a bibliometric perspective.MethodsWe obtained articles and reviews related to irAEs from the Web of Science Core Collection (WoSCC) (retrieved on September 13, 2022). Using the R package "Bibliometrix", the main bibliometric features were calculated, and a three-filed plot was generated to show the relationship between authors, institutions, and topics. VOSviewer was used for co-authorship and keyword co-occurrence analysis and visualization. CiteSpace was used to detect burst references and keywords.ResultsA total of 3995 publications on irAEs were included. The United States (US), Japan, and China had the highest publications. The Journal for ImmunoTherapy of Cancer had the highest number of publications. In addition to "immune-related adverse events", "immune checkpoint inhibitors", "immunotherapy", and "nivolumab" were the most frequently used keywords.ConclusionsA bibliometric analysis of 17 years of irAEs research was conducted to map a basic knowledge structure including countries, institutions, authors, journals, and publications. The findings provided a comprehensive perspective on the broad future of this research area.
| S-EPMC9797501 | biostudies-literature
Project description:BackgroundUp to 40% of cancer patients on immune checkpoint inhibitors develop clinically significant immune-related adverse events (irAEs). The role of host immune status and function in predisposing patients to the development of irAEs remains unknown.MethodsSera from 65 patients receiving immune checkpoint inhibitors and 13 healthy controls were evaluated for 40 cytokines at pre-treatment, after 2-3 weeks and after 6 weeks and analysed for correlation with the development of irAEs.ResultsOf the 65 cancer patients enrolled, 55% were women; the mean age was 65 years and 98% received anti-PD1/PDL1 therapy. irAEs occurred in 35% of cases. Among healthy controls, cytokine levels were stable over time and lower than those in cancer patients at baseline. Significant increases in CXCL9, CXCL10, CXCL11 and CXCL13 occurred 2 weeks post treatment, and in CXCL9, CXCL10, CXCL11, CXCL13, IL-10 and CCL26 at 6 weeks post treatment. Patients who developed irAEs had lower levels of CXCL9, CXCL10, CXCL11 and CXCL19 at baseline and exhibited greater increases in CXCL9 and CXCL10 levels at post treatment compared to patients without irAEs.ConclusionsPatients who developed irAEs have lower baseline levels and greater post-treatment increases in multiple cytokine levels, suggesting that underlying immune dysregulation may be associated with heightened risk for irAEs.
| S-EPMC6325132 | biostudies-literature
Project description:BACKGROUND:Prehospital emergency care has developed rapidly during the past decades. The care is given in a complex context which makes prehospital care a potential high-risk activity when it comes to patient safety. Patient safety in the prehospital setting has been only sparsely investigated. The aims of the present study were 1) To investigate the incidence of adverse events (AEs) in prehospital care and 2) To investigate the factors contributing to AEs in prehospital care. METHODS:We used a retrospective study design where 30 randomly selected prehospital medical records were screened for AEs each month in three prehospital organizations in Sweden during a period of one year. A total of 1080 prehospital medical records were included. The record review was based on the use of 11 screening criteria. RESULTS:The reviewers identified 46 AEs in 46 of 1080 (4.3%) prehospital medical records. Of the 46 AEs, 43 were classified as potential for harm (AE1) (4.0, 95% CI?=?2.9-5.4) and three as harm identified (AE2) (0.3, 95% CI?=?0.1-0.9). However, among patients with a life-threatening condition (priority 1), the risk of AE was higher (16.5%). The most common factors contributing to AEs were deviations from standard of care and missing, incomplete, or unclear documentation. The most common cause of AEs was the result of action(s) or inaction(s) by the emergency medical service (EMS) crew. CONCLUSIONS:There were 4.3 AEs per 100 ambulance missions in Swedish prehospital care. The majority of AEs originated from deviations from standard of care and incomplete documentation. There was an increase in the risk of AE among patients who the EMS team assessed as having a life-threatening condition. Most AEs were possible to avoid.
| S-EPMC6345067 | biostudies-other
Project description:BackgroundImmune checkpoint inhibitors have reshaped the standard of care in oncology. However, they have been associated with potentially life-threatening immune-related adverse events. With the growing indications of immune checkpoint inhibitors and their position as a pillar of cancer treatment, intensive care physicians will be increasingly confronted with their side effects. The outcome of patients with severe immune-related adverse events in the intensive care unit remains unknown. This retrospective multicentric study aims to describe the characteristics of patients admitted to the intensive care units of 4 academic hospitals in Paris area while receiving immune checkpoint inhibitor treatment between January 2013 and October 2019.ResultsOver the study period, 112 cancer patients who received immune checkpoint inhibitors were admitted to the intensive care unit within 60 days after the last dose. ICU admission was related to immune-related adverse events (n = 29, 26%), other intercurrent events (n = 39, 35%), or complications related to tumor progression (n = 44, 39%). Immune-related adverse events were pneumonitis (n = 8), colitis (n = 4), myocarditis (n = 3), metabolic disorders related to diabetes (n = 3), hypophysitis (n = 2), nephritis (n = 2), meningitis or encephalitis (n = 2), hepatitis (n = 2), anaphylaxis (n = 2) and pericarditis (n = 1). Primary tumors were mostly melanomas (n = 14, 48%), non-small-cell lung cancers (n = 7, 24%), and urothelial carcinomas (n = 5, 17%). Diagnosis of melanoma and a neutrophil/lymphocyte ratio < 10 were associated with immune-related diagnosis versus other reasons for ICU admission. During their ICU stay, immune-related adverse events patients needed vasopressors (n = 7), mechanical ventilation (n = 6), and extra-corporeal membrane oxygenation (n = 2). One-year survival was significantly higher for patients admitted for irAE compared to patients admitted for other reasons (p = 0.004).ConclusionsAdmission to the intensive care unit related to immune-related adverse event was associated with better outcome in cancer patients treated with immune checkpoint inhibitors. Our results support the admission for an intensive care unit trial for patients with suspected immune-related adverse events.
| S-EPMC7567777 | biostudies-literature