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1.
J Surg Res ; 281: 289-298, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36228339

RESUMO

The immune system is a complex and interconnected system that has evolved to protect its host from foreign pathogens. CD8+ T cells are a type of immune cell that can be directly lethal to tumor cells. However, their tumor killing capabilities can be inhibited by checkpoint molecules. During the last decade, the development of medications that block these checkpoint molecules has revolutionized treatment for some cancer types and indications for use continue to grow. As usage of immunotherapy increases, toxicities and adverse events unique to immunotherapy are becoming more prevalent. Here, we review the commonly targeted inhibitory molecules along with their food and drug administration-approved indications in various cancer therapeutic regimens, immunotherapy-related toxicities, and how this may impact surgical planning.


Assuntos
Neoplasias , Cirurgiões , Humanos , Inibidores de Checkpoint Imunológico , Linfócitos T CD8-Positivos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico
2.
Clin Imaging ; 93: 106-112, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35307225

RESUMO

BACKGROUND: Pneumonitis has been described as a side effect of immunotherapy as well as traditional chemotherapy. Although immune-related adverse event (IRAE) pneumonitis has been extensively characterized, the relationship between IRAE pneumonitis and pneumonitis secondary to chemotherapy is less clear. Here, we present the first analysis of radiographic features of pneumonitis secondary to immunotherapy compared to chemotherapy. METHODS: Using our radiology records system, we searched chest computed tomography (CT) reports for the term "pneumonitis". We evaluated medical records to establish chronicity of pneumonitis occurring after medication administration and excluded cases where radiation therapy appeared to be the cause of pneumonitis. We also obtained information regarding demographic, clinical, and treatment characteristics for comparison. RESULTS: Patients treated with immunotherapy demonstrated more specific features of pneumonitis including consolidation, ground glass opacities, septal thickening, traction bronchiectasis, and pulmonary nodules compared to those treated with chemotherapy. Immunotherapy treatment correlated with the development of pulmonary nodules (p = 0.048), and administration of more than one immunotherapy agent correlated with a greater incidence of development of nodules (p = 0.050). Radiographic features in patients treated with immunotherapy all decreased over time. Conversely, in patients treated with chemotherapy the incidence of ground glass opacities, traction bronchiectasis, pulmonary nodules, and mediastinal/hilar adenopathy increased over time. CONCLUSIONS: IRAE-pneumonitis has distinct features and a distinct clinical course compared to pneumonitis secondary to chemotherapy. Importantly, IRAE-pneumonitis features decreased over time, suggesting that careful consideration of the benefit-risk ratio may allow for continuation of immunotherapy in some patients who develop pneumonitis.


Assuntos
Bronquiectasia , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico por imagem , Imunoterapia/efeitos adversos , Bronquiectasia/complicações
3.
Clin. transl. oncol. (Print) ; 24(11): 2241-2249, noviembre 2022.
Artigo em Inglês | IBECS | ID: ibc-210152

RESUMO

Immune checkpoint inhibitors are one of the most effective treatments available in advanced non-small cell lung cancer. However, at present, there are no clinical or analytical biomarkers that define which patients benefit with certainty from these treatments. In our study, we evaluated whether excess weight could be a good predictive biomarker of benefit from these drugs.MethodsWe studied a population of 79 patients, divided into a study group with 39 patients diagnosed with non-small cell lung cancer treated with immunotherapy and 40 patients in a control group, diagnosed with different advanced cancers, treated with non-immunotherapy treatment. We analyzed according to the presence of excess weight or not, the treatment’s outcome in the study group and in the control group (objective response, and progression-free and overall survival).ResultsIn our study, we detected a better response rate to immunotherapy in patients with excess weight (62.50 vs 26.08%, OR 4.72, p = 0.02), and a better median progression-free survival (14.19 vs 5.03 months, HR 0.50, p = 0.058) and median overall survival (33.84 months vs 20.76 months, HR 0.43, p = 0.01) in the study group. These findings were specific to the immunotherapy group since in the control group, with patients who did not receive immune checkpoint inhibitors, these findings were not found.ConclusionOur study suggests that patients with excess weight who receive anti-PD-1 immune checkpoint inhibitors diagnosed with non-small cell lung cancer have a better outcome. This effect is specific to patients receiving immunotherapy. (AU)


Assuntos
Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Intervalo Livre de Progressão , Terapêutica , Pacientes
4.
Sci Rep ; 12(1): 20038, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414662

RESUMO

Immune-related cutaneous adverse events (irCAEs) in patients treated with programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors may be associated with better clinical outcomes. However, the extent to which these results can be extrapolated to all tumour types remains unclear. Herein, we conducted a meta-analysis of patients with cancer receiving anti-PD-1/PD-L1 immunotherapy, to determine the cumulative incidence of irCAEs and their association with survival. We systematically searched six databases (PubMed, Embase, Cochrane, CNKI, CSPD, and CQVIP database) for all cohort studies reporting the relationship between irCAEs and patient survival from the time of database construction to 1 November, 2020. The primary outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), with complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) as secondary outcomes. Patients with irCAEs exhibited higher ORR, and were more likely to report CR and PR and less likely to develop PD than those who did not experience irCAEs. Moreover, the occurrence of irCAEs was significantly associated with both favourable PFS and OS. Therefore, patients with irCAEs have better survival benefit and a significantly lower risk of tumour progression or death. Hence, the occurrence of irCAEs may be a useful marker for predicting the clinical efficacy of anti-PD-1/PD-L1 immunotherapy.


Assuntos
Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Intervalo Livre de Progressão , Bases de Dados Factuais
5.
Expert Opin Biol Ther ; 22(11): 1393-1404, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36369948

RESUMO

INTRODUCTION: Newly approved immunotherapies for neuromyelitis optica spectrum disorder (NMOSD) have transformed the treatment landscape and improved disability outcomes. However, there are many remaining questions regarding transitioning immunotherapies in NMOSD that have not been addressed by randomized controlled trials. AREAS COVERED: This review focuses on the practical questions of managing and switching immunotherapies for NMOSD, including how to transition between immunotherapies, deciding when and if therapy should be discontinued, and transitioning during pregnancy or breastfeeding. EXPERT OPINION: Clinical experience and retrospective studies of real-world outcomes and complications associated with therapy, as well as therapy transitions, will help inform practice patterns moving forward. Strategies for transitioning between immunotherapies should consider the pharmacokinetics and the onset of clinical efficacy for each drug. Despite all the currently approved preventative immunotherapies, there are limited treatment options for those suffering from significant disability after their initial attack, and remyelination therapies are an important area for future research.


Assuntos
Neuromielite Óptica , Gravidez , Feminino , Humanos , Neuromielite Óptica/tratamento farmacológico , Estudos Retrospectivos , Fatores Imunológicos/uso terapêutico , Imunoterapia/efeitos adversos , Resultado do Tratamento
6.
Front Immunol ; 13: 1001506, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405741

RESUMO

Background: Hepatocellular carcinoma (HCC) is the most prevalent pathological type of liver cancer worldwide with high mortality and poor prognosis. N6-methyladenosine (m6A) can modify RNAs such as mRNA, lncRNA, miRNA, and tRNA, thereby playing a critical role in the pathogenesis of HCC. However, the role of m6A-associated small nuclear RNA (snRNA) in the prognostic value and immunotherapeutic response in HCC remains unclear. Materials and methods: In this study, snRNA expression data, gene mutation data, and clinical data of HCC patients were acquired from The Cancer Genome Atlas (TCGA) database. We used the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to identify significant prognostic m6A-associated snRNAs, and then developed a multivariate Cox model based on the selected snRNAs. HCC patients were split into low- and high-risk groups based on the median risk score. We subsequently performed Kaplan-Meier curve analysis to estimate overall survival (OS) by clinicopathological characteristics and tumor mutational burden (TMB) status in low- and high-risk HCC patients. Finally, we compared the immunotherapeutic response as represented by tumor immune dysfunction and exclusion (TIDE) scores between the two risk groups. Results: Eight m6A-associated snRNAs were selected as independent predictors to develop the risk model. Our results revealed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group on clinicopathologic characteristics, including age (≤65 years and >65 years), gender (male), grade (G I-II and G III-IV) and TNM staging (Stage I-II and Stage III-IV). In addition, the OS of low-TMB and low-risk group was longer than that of high-TMB and high-risk group. The TIDE score indicated that HCC patients in the high-risk group were more susceptible to immunotherapy. Conclusion: Our study suggests that m6A-associated snRNAs may be useful biomarkers for the prognosis of HCC and that m6A-associated snRNA models can predict the effect of immunotherapy in HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Masculino , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , RNA Nuclear Pequeno , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Imunoterapia/efeitos adversos
8.
BMC Med ; 20(1): 426, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36345004

RESUMO

BACKGROUND: Currently, immunotherapy is widely used in the treatment of various stages of non-small cell lung cancer. According to clinical experience and results of previous studies, immunotherapy as neoadjuvant therapy seems to exhibit better efficacy against early resectable non-small cell lung cancer as compared to advanced lung cancer, which is often defined as unresectable non-small cell lung cancer. However, this observation has not been established in clinical studies. This systematic review aimed to evaluate the efficacy of immunotherapy in early and late lung cancer, wherein objective response rate (ORR) and disease control rate (DCR) were used as evaluation indexes. The present study also evaluated the safety of immunotherapy in early and late lung cancer, wherein the rate of treatment-related adverse reactions (TRAEs) was used as an indicator. METHODS: Electronica databases, including PubMed, Cochrane Library, Embase, and other databases, were searched to identify relevant studies. Besides this, all the available reviews, abstracts, and meeting reports from the main international lung cancer meetings were searched manually. ORR, DCR, and TRAEs were extracted as the primary outcomes. RESULTS: A total of 52 randomized controlled trials involving 13,660 patients were shortlisted. It was observed that immunotherapy alone significantly improved DCR in early lung cancer in comparison to advanced lung cancer. Importantly, the improvement in ORR was not to the same extent as reported in the case of advanced lung cancer. The combination of immunotherapy with other therapies, especially immunochemotherapy, significantly improved ORR and DCR in early lung cancer. In terms of safety, immunotherapy either alone or in combination with other therapies exhibited a better safety profile in early lung cancer than in advanced lung cancer. CONCLUSIONS: Altogether, the benefits of immunotherapy in early lung cancer appeared to be better than those observed in advanced lung cancer, especially with the regard to the regimen of immunotherapy in combination with chemotherapy. In terms of safety, both immunotherapy alone and its combination with chemotherapy were found to be safer in early lung cancer as compared to advanced lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
PLoS One ; 17(11): e0277248, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36355837

RESUMO

Immune checkpoint inhibitors, introduced in recent years, have revolutionized the treatment of many cancers. However, the toxicity associated with this therapy may cause severe adverse events. In the case of advanced lung cancer or metastatic melanoma, a significant number (10%) of patients treated with CTLA-4 inhibitor incur damage to the pituitary gland. In order to reduce the risk of hypophysitis and other severe adverse events, steroids may be combined with CTLA-4 inhibitor; they reduce toxicity, but they also diminish the anti-cancer effect of the immunotherapy. This trade-off between tumor reduction and the risk of severe adverse events poses the following question: What is the optimal time to initiate treatment with steroid. We address this question with a mathematical model from which we can also evaluate the comparative benefits of each schedule of steroid administration. In particular, we conclude that treatment with steroid should not begin too early, but also not very late, after immunotherapy began; more precisely, it should start as soon as tumor volume, under the effect of CTLA-4 inhibitor alone, begins to decrease. We can also compare the benefits of short term treatment of steroid at high doses to a longer term treatment with lower doses.


Assuntos
Melanoma , Segunda Neoplasia Primária , Humanos , Antígeno CTLA-4 , Ipilimumab/uso terapêutico , Inibidores de Checkpoint Imunológico , Imunoterapia/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Segunda Neoplasia Primária/tratamento farmacológico , Esteroides/uso terapêutico , Modelos Teóricos
10.
Dermatologie (Heidelb) ; 73(12): 937-942, 2022 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-36350371

RESUMO

Neurocognitive impairments of memory, speech, and attention can occur in cancer patients as a direct result of the cancer but also in the context of therapy. With the development of modern immunotherapies and their use in combination with surgery and radiation therapy, the number of long-term survivors has significantly increased. As a result, detrimental effects on brain function and structure in cancer patients not only during treatment but also after completion of therapy have become a key issue in clinical oncology. Early diagnosis and treatment of neurocognitive disorders is of great importance for quality of life, therapy adherence, and overall survival of the affected patients. In this review, we discuss the underlying mechanisms with a special focus on metastatic melanoma. Furthermore, practice-relevant diagnostics, prophylaxis, and intervention options are discussed.


Assuntos
Disfunção Cognitiva , Melanoma , Segunda Neoplasia Primária , Humanos , Qualidade de Vida , Melanoma/complicações , Imunoterapia/efeitos adversos , Sobreviventes/psicologia , Disfunção Cognitiva/etiologia
11.
Expert Rev Respir Med ; 16(10): 1043-1055, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36369920

RESUMO

INTRODUCTION: Many data already suggested that cancer and IPF are underlined by a number of common pathogenic biologic pathways. However, fewer data regards the interconnections, in terms of synergy or increased toxicities, of drugs used in cancer and IPF. Particularly, how the specific therapy influences the concurrent condition and prognostic factors of response in patients with both lung cancer and IPF are far to be clarified. Similarly, identification of features of IPF patients with higher risk of developing pulmonary adverse events when treated with chemotherapy, immune checkpoint inhibitors, TKIs, or radiotherapy is of primary importance in clinical practice. AREAS COVERED: We will discuss the scientific rationale, based on the extensive analysis of literature data, by consulting several databases for combining anticancer and antifibrotic treatments and for the design of novel therapeutic strategies. The role of immunotherapy in cancer aroused in IPF context will be discussed with specific interested, based on the continuously increasing role of immune checkpoint inhibition against lung tumors. EXPERT OPINION: This work will help to improve knowledge, based on a multidisciplinary perspective, on IPF and cancer patients, which identify an unmet clinical need. A better management during each phase of disease progression will require the design innovative trials and the development of new drugs and molecules both in the oncologic and respiratory medicine pipeline.


Assuntos
Fibrose Pulmonar Idiopática , Neoplasias Pulmonares , Pneumologia , Humanos , Fibrose Pulmonar Idiopática/terapia , Neoplasias Pulmonares/tratamento farmacológico , Imunoterapia/efeitos adversos , Progressão da Doença
12.
Nature ; 611(7937): 818-826, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36385524

RESUMO

Immune-related adverse events, particularly severe toxicities such as myocarditis, are major challenges to the utility of immune checkpoint inhibitors (ICIs) in anticancer therapy1. The pathogenesis of ICI-associated myocarditis (ICI-MC) is poorly understood. Pdcd1-/-Ctla4+/- mice recapitulate clinicopathological features of ICI-MC, including myocardial T cell infiltration2. Here, using single-cell RNA and T cell receptor (TCR) sequencing of cardiac immune infiltrates from Pdcd1-/-Ctla4+/- mice, we identify clonal effector CD8+ T cells as the dominant cell population. Treatment with anti-CD8-depleting, but not anti-CD4-depleting, antibodies improved the survival of Pdcd1-/-Ctla4+/- mice. Adoptive transfer of immune cells from mice with myocarditis induced fatal myocarditis in recipients, which required CD8+ T cells. The cardiac-specific protein α-myosin, which is absent from the thymus3,4, was identified as the cognate antigen source for three major histocompatibility complex class I-restricted TCRs derived from mice with fulminant myocarditis. Peripheral blood T cells from three patients with ICI-MC were expanded by α-myosin peptides. Moreover, these α-myosin-expanded T cells shared TCR clonotypes with diseased heart and skeletal muscle, which indicates that α-myosin may be a clinically important autoantigen in ICI-MC. These studies underscore the crucial role for cytotoxic CD8+ T cells, identify a candidate autoantigen in ICI-MC and yield new insights into the pathogenesis of ICI toxicity.


Assuntos
Miocardite , Camundongos , Animais , Miocardite/induzido quimicamente , Miocardite/terapia , Antígeno CTLA-4 , Miosinas Ventriculares , Linfócitos T CD8-Positivos/metabolismo , Imunoterapia/efeitos adversos , Fatores Imunológicos , Autoantígenos
13.
Medicine (Baltimore) ; 101(46): e31761, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401365

RESUMO

Immune checkpoint inhibitors (ICIs) have changed the status of tumor immunotherapy. ICIs-related adverse events (irAEs) have the high incidence and are difficult to predict and prevent. Researches have suggested that changes of cytokines were associated with irAEs. This study focused on the changes of interleukin-6 (IL-6) and interferon-γ in patients before and after irAEs and trying to find the biomarkers of irAEs. Collect basic data of patients who were treated with ICIs in China-Japan Friendship Hospital from January 2017 to August 2021 and had irAEs. Make statistics on IL-6 and INF-γ in the blood before and after irAEs. A total of 10 patients were enrolled, including 7 males and 3 females. According to statistical analysis, the IL-6 concentration level after irAEs was significantly higher than before, and the difference was statistically significant (P = .023); the interferon-γ concentration level was not changed significantly from before, the difference was not statistically significant (P = .853). The elevation of IL-6 was associated with the occurrence of adverse reactions in ICIs.


Assuntos
Inibidores de Checkpoint Imunológico , Interleucina-6 , Humanos , Masculino , Feminino , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Interferon gama , Imunoterapia/efeitos adversos
14.
Klin Onkol ; 35(5): 346-357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36443091

RESUMO

BACKGROUND: Systemic anti-cancer immunotherapy provides a substantial progress in options of current oncology treatment. Yet, this therapeutic approach is potentially associated with a significant gastrointestinal toxicity. AIM: The purpose of this paper is to provide a comprehensive review on pathogenesis, clinical features, dia gnostics and therapy of these toxicities. Review of current knowledge: Check-point inhibitors brought a major progress in anti-cancer immunotherapy and improved significantly prognosis of several malignancies (e. g. metastatic malignant melanoma, non-small-cell lung cancer, gastric and colorectal cancers in high-risk population associated with presence of pathogenic mutations, renal cell carcinoma, squamous cell carcinoma of the head and neck and urothelial carcinoma). They include monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4; e. g. ipilimumab, tremelimumab), programmed death-1 receptor (PD-1; e. g. pembrolizumab, nivolumab) and its ligand PD-L1 (e. gatezolizumab, avelumab). Chimeric antigen receptor (CAR) T-cell therapy is another new option for haematological malignancies and metastatic colorectal cancer. Major symptoms of gastrointestinal toxicity caused by systemic immunotherapy include diarrhoea (20-50%), entero-colitis (1-10%) and laboratory or clinical signs of hepatopathy (~10%). Anti-cancer immunotherapy can be also complicated by infections (Clostridium difficile, Mycoplasma and/ or cytomegalovirus). There is no data on other possible complications so far. However, it can be assumed that these will also include bile acid malabsorption as well as small intestinal bacterial overgrowth syndrome. Treatment of gastrointestinal complications of immunotherapy should be graded according to their severity. It includes symptomatic medications (e. g. loperamide), systemic glucocorticoids and anti-TNF monoclonal antibodies (alone or together with mycofenolate mofetil or tacrolimus in the most severe cases). CONCLUSIONS: Awareness of possible complications of systemic anti-cancer immunotherapy is crucial for patients safety. It is mandatory to consider immune-related adverse events, complicating infections, bile acids malabsorption and small intestinal bacterial overgrowth syndrome. Prompt proper dia gnostics and immediate vigorous therapy infl uence the outcome of patients signifi cantly. A strictly individualized approach is indispensable.


Assuntos
Antineoplásicos Imunológicos , Síndrome da Alça Cega , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células de Transição , Neoplasias Pulmonares , Neoplasias da Bexiga Urinária , Humanos , Inibidores do Fator de Necrose Tumoral , Imunoterapia/efeitos adversos , Anticorpos Monoclonais
15.
Front Immunol ; 13: 1058819, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439167

RESUMO

Background: With approval of anti-PD-1/PD-L1, metastatic non-small cell lung cancer (NSCLC) has entered the era of immunotherapy. Since immune-related adverse events (irAEs) occur commonly in patients receiving anti-PD-1/PD-L1, the landscape of death causes may have changed in metastatic NSCLC. We aim to compare patterns of death causes in metastatic NSCLC between the pre-immunotherapy and immunotherapy era to identify the consequent landscape transition of death causes. Methods: In this cohort study, 298,48patients with metastatic NSCLC diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results Program. Unsupervised clustering with Bayesian inference method was performed for all patients' death causes, which separated them into two death patterns: the pre-immunotherapy era group and the immunotherapy era group. Relative risk (RR) of each death cause between two groups was estimated using Poisson regression. Reduced death risk as survival time was calculated with locally weighted scatterplot smooth (Lowess) regression. Results: Two patterns of death causes were identified by unsupervised clustering for all patients. Thus, we separated them into two groups, the immunotherapy era (2015-2017, N=40,172) and the pre-immunotherapy era (2000-2011, N=166,321), in consideration of obscure availability to immunotherapy for patients diagnosed in 2012-2014, when the follow-up cutoff was set as three years. Although all-cause death risk had reduced (29.2%, 13.7% and 27.8% for death risks of lung cancer, non-cancer and other cancers), non-cancer deaths in the immunotherapy era (N=2,100, 5.2%; RR=1.155, 95%CI: 1.101-1.211, P<0.001) significantly increased than that in the pre-immunotherapy era (N=7,249, 5.0%), which included causes of chronic obstructive pulmonary disease, cerebrovascular disease, pneumonia and influenza, septicemia, infectious diseases, accidents and adverse effects, hypertension, and chronic liver disease and cirrhosis. However, cancer-caused deaths (excluding lung cancer) had no significant changes. Conclusions: The real-world landscape of death causes has changed in metastatic NSCLC when entering the immunotherapy era, and the increased non-cancer diseases may contribute to the changes that may be associated with commonly occurring irAEs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/etiologia , Antígeno B7-H1 , Neoplasias Pulmonares/patologia , Causas de Morte , Estudos de Coortes , Teorema de Bayes , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Fatores Imunológicos
16.
BMJ Case Rep ; 15(10)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36223974

RESUMO

Thyroid storm is a rare and life-threatening condition associated with excess thyroid hormones. Early detection of thyroid storm is the key to decreasing the morbidity and mortality associated with this condition. We present a rare case of thyroid storm induced by combination therapy with nivolumab and ipilimumab in a patient with advanced non-small cell lung cancer (NSCLC). Because of prominent hyperthyroidism with gastrointestinal symptoms and signs of heart failure, the patient was diagnosed with thyroid storm 3 weeks after initiating this combination immunotherapy. The patient had no history of thyroid disease but was positive for antithyroid antibodies. This case report suggests that thyroid function and symptoms of suspected thyroid storm should be evaluated routinely within 3 weeks from the initiation of therapy when combination therapy is administered in patients with NSCLC positive for antithyroid antibodies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Crise Tireóidea , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/efeitos adversos , Ipilimumab/efeitos adversos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/efeitos adversos , Crise Tireóidea/etiologia , Hormônios Tireóideos
17.
Front Immunol ; 13: 994053, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211357

RESUMO

Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid clonal diseases with diverse clinical courses, and immune dysregulation plays an important role in the pathogenesis of MDS. However, immune dysregulation is complex and heterogeneous in the development of MDS. Lower-risk MDS (LR-MDS) is mainly characterized by immune hyperfunction and increased apoptosis, and the immunosuppressive therapy shows a good response. Instead, higher-risk MDS (HR-MDS) is characterized by immune suppression and immune escape, and the immune activation therapy may improve the survival of HR-MDS. Furthermore, the immune dysregulation of some MDS changes dynamically which is characterized by the coexistence and mutual transformation of immune hyperfunction and immune suppression. Taken together, the authors think that the immune dysregulation in MDS with different risk stratification can be summarized by an advanced philosophical thought "Yin-Yang theory" in ancient China, meaning that the opposing forces may actually be interdependent and interconvertible. Clarifying the mechanism of immune dysregulation in MDS with different risk stratification can provide the new basis for diagnosis and clinical treatment. This review focuses on the manifestations and roles of immune dysregulation in the different risk MDS, and summarizes the latest progress of immunotherapy in MDS.


Assuntos
Síndromes Mielodisplásicas , Yin-Yang , Humanos , Terapia de Imunossupressão , Imunoterapia/efeitos adversos , Síndromes Mielodisplásicas/terapia , Medição de Risco
18.
Front Immunol ; 13: 988849, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189293

RESUMO

With the arrival of the era of tumor immunotherapy, Immune Checkpoint Inhibitors have benefited countless tumor patients. However, the emergence of Immune-Related Adverse Events, especially Immune Checkpoint Inhibitor-Mediated Colitis (IMC), has become an important obstacle to immunotherapy. Therefore, it is very important to clarify the mechanism and influencing factors of IMC. The effect of gut microbiota on IMC is gradually becoming a research hotspot. Gut microbiota from different phyla can affect IMC by regulating innate and acquired immunity of tumor patients in various ways. In this review, we make a systematic and comprehensive introduction of the effect of gut microbiota on IMC. Through understanding the specific effects of gut microbiota on IMC, and then exploring the possibility of reducing IMC by regulating gut microbiota.


Assuntos
Colite , Microbioma Gastrointestinal , Neoplasias , Colite/induzido quimicamente , Colite/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos
19.
Front Immunol ; 13: 983581, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225926

RESUMO

Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has made a revolutionary difference in the treatment of malignant tumors, and considerably extended patients' overall survival (OS). In the world medical profession, however, there still reaches no clear consensus on the optimal duration of ICIs therapy. As reported, immunotherapy response patterns, immune-related adverse events (irAEs) and tumor stages are all related to the diversity of ICIs duration in previous researches. Besides, there lacks clear clinical guidance on the intermittent or continuous use of ICIs. This review aims to discuss the optimal duration of ICIs, hoping to help guide clinical work based on the literature.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Fatores Imunológicos/uso terapêutico , Imunoterapia/efeitos adversos , Neoplasias/induzido quimicamente , Neoplasias/tratamento farmacológico
20.
Curr Oncol ; 29(10): 6776-6786, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36290810

RESUMO

The advent of immune checkpoint inhibitors in combination with multitarget tyrosine kinase inhibitors has become a standard first-line treatment for metastatic renal cell cancer. Along with survival improvement, new toxicities have emerged. Such adverse events are still complex to be managed and some of them are rare and could be insidious or even fatal. Medical oncologists dispose of guidelines about the management of toxicities from immune checkpoint inhibitors but not for combinations. Therefore, it is still difficult to properly attribute and manage additive or overlapping adverse events. We report two clinical cases regarding rare treatment-related endocrine toxicities-hypophysitis and thyroiditis-with particular focus on their management. To this purpose, immune checkpoint-related toxicities guidelines represent the starting point. However, their implementation with additional measures is needed, considering the increasing complexity of current clinical scenarios. The goal is to correctly recognize adverse events and address side effects, so as not to discontinue effective treatments. We, therefore, aim at discussing the points of proper management of toxicities and individuating potential areas of improvement.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Imunoterapia/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Inibidores de Checkpoint Imunológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases
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