Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Falência Hepática Aguda/induzido quimicamente , Sunitinibe/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Evolução Fatal , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/secundário , Humanos , Mesilato de Imatinib/uso terapêutico , Neoplasias Hepáticas/secundário , MasculinoAssuntos
Carcinoma/diagnóstico , Doenças do Ceco/diagnóstico , Neoplasias do Ceco/diagnóstico , Infecções por Citomegalovirus/diagnóstico , Granuloma de Células Plasmáticas/diagnóstico , Doenças do Ceco/virologia , Infecções por Citomegalovirus/complicações , Diagnóstico Diferencial , Granuloma de Células Plasmáticas/virologia , Humanos , Imunocompetência , Masculino , Pessoa de Meia-IdadeAssuntos
Doença de Crohn/complicações , Doenças do Íleo/complicações , Perfuração Intestinal/complicações , Enfisema Subcutâneo/etiologia , Tomografia Computadorizada por Raios X , Idoso , Humanos , Doenças do Íleo/diagnóstico por imagem , Doenças do Íleo/cirurgia , Perfuração Intestinal/diagnóstico por imagem , Perfuração Intestinal/cirurgia , Masculino , Enfisema Subcutâneo/diagnóstico por imagem , Técnicas de SuturaAssuntos
Doença de Crohn/diagnóstico , Enteropatias Parasitárias/diagnóstico , Abscesso Hepático Amebiano/diagnóstico , Adulto , Antiprotozoários/uso terapêutico , Colonoscopia , Doença de Crohn/tratamento farmacológico , Diagnóstico Diferencial , Erros de Diagnóstico , Drenagem/métodos , Entamoeba/isolamento & purificação , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Enteropatias Parasitárias/terapia , Abscesso Hepático Amebiano/terapia , Masculino , Metronidazol/uso terapêutico , Tomografia Computadorizada por Raios X , Ultrassonografia de IntervençãoAssuntos
Falso Aneurisma/complicações , Colestase/etiologia , Artéria Hepática/patologia , Idoso , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/terapia , Colangiografia , Colangiopancreatografia Retrógrada Endoscópica , Coledocolitíase/diagnóstico , Colestase/diagnóstico , Colestase/diagnóstico por imagem , Terapia Combinada , Neoplasias do Ducto Colédoco/diagnóstico , Diagnóstico Diferencial , Drenagem , Embolização Terapêutica , Feminino , Artéria Hepática/diagnóstico por imagem , Humanos , Radiografia Intervencionista , Úlcera Gástrica/complicações , Tomografia Computadorizada por Raios XRESUMO
Background: Immune checkpoint inhibitors (ICIs) have been proposed as the standard first-line and subsequent treatment for metastatic non-small cell lung cancer (NSCLC). This study analyzed whether patients with good lung immune prognostic index (LIPI) have a better response to ICIs and the relationship between immune-related adverse events (irAEs) and response in clinical practice. Methods: This was an observational, retrospective, single-center study. Patients with stage IV NSCLC between 2016 and 2021 were included in the study. Toxicity was assessed according to The Common Terminology Criteria for Adverse Events. Response assessment was performed according to RECIST 2.0 and immuno-related criteria. Descriptive and survival analyses were conducted. Degree of toxicity and response to treatment (based on treatment and histology) were assessed. LIPI and response were assessed. LIPI included dNLR (absolute neutrophil count/(white blood cell count - absolute neutrophil count)) ≥ 3 and lactate dehydrogenase (LDH) greater than the upper limit of normal. Patients were stratified into good (G), intermediate (I), and poor (P) prognostic groups. Results: A total of 168 patients were included (130 men and 38 women, mean age 64.3 years). ICI use in the first- or second-line treatment was 65% and 35%, respectively. Fifteen (9%) patients showed complete response (CR), 50 (30%) showed partial response (PR), 39 (22%) had stable disease (SD), 45 (28%) had progressive disease (PD), and 19 (11%) were not evaluated (NE). Patients with good prognostic LIPI (dNLR < 3 and normal LDH levels) showed a better response. Progression-free survival (PFS) was 19 months in G, 6 months in I, and 2 months in P. Overall survival (OS) was 27 months in G, 8 months in I, and 3 months in P. One hundred fourteen patients died (56% G, 76% I, 93% P). Patients with adenocarcinoma were 116 (77 with irAEs G1-4 (13 CR, 31 PR, 21 SD, eight PD, and four NE)), and without were 39 (three PR, six SD, 21 PD, and nine NE). Fifty-two patients had squamous carcinoma (27 with irAEs G1-4 (two CR, 12 PR, nine SD, and four PD)), and 25 did not (four PR, three SD, 12 PD, and six NE)). IrAEs appearance was observed in longer PFS (19 vs. 2 months) and OS (27 vs. 4 months; P < 0.0001). Conclusions: LIPI was a positive predictor of response to ICI. The presence of irAEs is associated with a better immune response. In contrast, the absence of toxicity predicted a worse prognosis.
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Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host-microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients' microbial gut ecosystems were rich and diverse, and the intestinal barrier's integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.
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Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes.
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(1) Despite the effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer, there is a lack of knowledge about predictive biomarkers. The objective of our study is to analyze different subsets of T-lymphocytes and natural killer (NK) cells as predictive biomarkers in a cohort of patients with nonsmall cell lung cancer (NSCLC) treated with ICI. (2) This is an observational, prospective study with 55 NSCLC patients treated with ICI. A total of 43 T and NK cell subsets are analyzed in peripheral blood, including the main markers of exhaustion, differentiation, memory, activation, and inhibition. (3) Regarding the descriptive data, Granzyme B+CD4+ Treg lymphocytes stand out (median 17.4%), and within the NK populations, most patients presented cytotoxic NK cells (CD56+CD3-CD16+GranzymeB+; median 94.8%), and about half of them have highly differentiated adaptive-like NK cells (CD56+CD3-CD16+CD57+ (mean 59.8%). A statistically significant difference was observed between the expression of PD1 within the CD56bright NK cell subpopulation (CD56+CD3-CD16-PD-1+) (p = 0.047) and a better OS. (4) Circulating immune cell subpopulations are promising prognostic biomarkers for ICI. Pending on validation with a larger sample, here we provide an analysis of the major circulating T and NK cell subsets involved in cancer immunity, with promising results despite a small sample size.
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Background and Aims: Malnutrition is a condition that has a great impact on oncology patients. Poor nutritional status is often associated with increased morbidity and mortality, increased toxicity, and reduced tolerance to chemotherapy, among other complications. The recently developed GLIM criteria for malnutrition aim to homogenize its diagnosis, considering the baseline disease status. We aimed to evaluate the performance of these new criteria for the prediction of complications and mortality in patients with cancer. Methods: This work is a prospective, single-center study. All outpatients under active treatment for head and neck, upper gastrointestinal, and colorectal tumors between February and October 2020 were recruited. These patients were followed up for 6 months, assessing the occurrence of complications and survival based on GLIM diagnoses of malnutrition. Results: We enrolled 165 outpatients, 46.66% of whom were malnourished. During the 6-month follow-ups, patients with malnutrition (46.7%, according to GLIM criteria) had a ~3-fold increased risk of hospital admission (p < 0.001) and occurrence of severe infection (considered as those requiring hospitalization, intravenous antibiotics, and/or drainage by interventional procedures) (p = 0.002). Similarly, malnourished patients had a 3.5-fold increased risk of poor pain control and a 4.4-fold increased need for higher doses of opioids (both p < 0.001). They also had a 2.6-fold increased risk of toxicity (p = 0.044) and a 2.5-fold increased likelihood of needing a dose decrease or discontinuation of cancer treatment (p = 0.011). The 6-month survival of malnourished patients was significantly lower (p = 0.023) than in non-malnourished patients. Conclusions: Diagnoses of malnutrition according to the GLIM criteria in oncology patients undergoing active treatment predict increased complications and worse survival at 6-month follow-ups, making them a useful tool for assessing the nutritional status of oncology patients.
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BACKGROUND: Many studies have assessed different malnutrition screening tools in oncologic patients. However, very few have been carried out using the new GLIM criteria for malnutrition. The objective of our study is to compare the most recommended screening tools with respect to the new GLIM criteria for malnutrition in cancer patients. METHODS: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department at the Lozano Blesa Hospital in Zaragoza. We recruited 165 patients with tumors of the upper-gastrointestinal-tract, colorectal, and head-and-neck region undergoing outpatient treatment. All of them received MST, MUST, Nutriscore, MNA and CONUT screening tools, as well as the GLIM diagnostic criteria, which was used as the gold standard. RESULTS: MNA-SF showed the best sensitivity (0.99) and lowest specificity while CONUT had the best specificity (0.89) and lowest sensitivity to detect cancer-related malnutrition. We observed high variability in the diagnostic capabilities of Nutriscore when tumor location was considered, reducing sensitivity in patients with colorectal cancer compared to those with tumors of the upper-gastrointestinal-tract or head-and-neck location (0.25, 0.83, and 0.91 respectively). The highest index of agreement between the screening tools was found between MST, MUST and Nutriscore tests. Regarding the GLIM criteria, the highest agreement index was presented by MUST tool (0.66), while CONUT presented the lowest (0.12). CONCLUSIONS: Selecting the screening tool according to the type of cancer and its location may allow us to optimize its use and increase its performance, exploiting the advantages of each of them in the different populations.
Assuntos
Desnutrição , Neoplasias , Estudos Transversais , Detecção Precoce de Câncer , Humanos , Desnutrição/diagnóstico , Neoplasias/complicações , Avaliação Nutricional , Estado Nutricional , Pacientes AmbulatoriaisRESUMO
BACKGROUND & AIMS: Malnutrition is one of the most prevalent problems among oncological patients. It reduces the response to treatments and negatively impacts survival. In 2019, a consensus criteria for diagnosing malnutrition (GLIM criteria) were proposed by most scientific nutrition societies. The objective of our work is 1) to assess the diagnostic capacity of the GLIM criteria in ambulatory patients with cancer and 2) to compare the GLIM with the ESPEN criteria to evaluate the contributions of these new criteria with respect to the existing ones. METHODS: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department in the Lozano Blesa Clinical Hospital in Zaragoza (Spain). One hundred and sixty-five outpatients with tumors in the upper gastrointestinal tract, head and neck, and colorectal locations were recruited. All of them received the MST, MUST, and Nutriscore screening tools along with the ESPEN and GLIM diagnostic criteria. RESULTS: The prevalence of malnutrition was 46.7% according to the GLIM criteria and 21.2% using the ESPEN tool. Patients diagnosed by GLIM had a higher body mass index (BMI, 24.3 kg/m2) and muscle mass (MM, 16.1 kg/m2) than those diagnosed by ESPEN (21.2 kg/m2 and 14.3 kg/m2 respectively, both p = 0.001). The MST, MUST, and Nutriscore tools had a higher degree of concordance with GLIM compared to ESPEN (MST 0.53 vs 0.26; MUST 0.36 vs 0.66; Nutriscore 0.28 vs 0.54). CONCLUSIONS: The found prevalence of malnutrition in cancer patients is higher using the GLIM instead of ESPEN criteria. This disparity can be explained at least in part by the difficulty of the ESPEN criteria for malnutrition to diagnose patients with high baseline BMI or MM. The use of criteria with greater sensitivity, such as the new GLIM criteria, could help early diagnosis and thus early intervention in cancer patients.