Predictors of Immunotherapy Efficacy in Metastatic Non-Small Cell Lung Cancer: Lung Immune Prognostic Index and Immune-Related Toxicity.

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.

Biomarkers of Immunotherapy Response in Patients with Non-Small-Cell Lung Cancer: Microbiota Composition, Short-Chain Fatty Acids, and Intestinal Permeability.

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.

A Subset of PD-1-Expressing CD56bright NK Cells Identifies Patients with Good Response to Immune Checkpoint Inhibitors in Lung Cancer.

(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.

Diagnosis of Malnutrition According to GLIM Criteria Predicts Complications and 6-Month Survival in Cancer Outpatients.

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.

Comparation of different malnutrition screening tools according to GLIM criteria in cancer outpatients.

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.

Mastectomía contralateral profiláctica con reconstrucción inmediata en pacientes con cáncer de mama unilateral sin mutación germinal en BRCA1/2 / Prophylactic contralateral mastectomy with immediate reconstruction in patients with unilateral breast cancer without germline BRCA1/2 mutations

Introducción No existe un consenso sobre las indicaciones de mastectomía contralateral en pacientes diagnosticadas de cáncer de mama unilateral sin mutación germinal en BRCA1/2. Estudios previos han identificado algunos factores que pueden influir en la toma de la decisión dependientes del tumor, como el tamaño o histología, de la paciente, como la edad, y de la cirugía como la posibilidad de realizar una reconstrucción inmediata o la experiencia del cirujano.MétodosEstudio retrospectivo de una cohorte de 176 pacientes diagnosticadas de CM entre 2010 y 2016 a las que se les realizó cirugía mamaria. Se ha analizado la asociación de características del tumor y de la paciente con la toma de decisión de realizar mastectomía contralateral (MC) o no-MC. Asimismo, se han analizado los datos relacionados con la cirugía y la recurrencia por grupos mediante la curva de incidencia acumulada y el test de Gray.ResultadosEl número de MC se ha incrementado en nuestro centro. No hemos encontrado diferencias significativas en el desarrollo de complicaciones posquirúrgicas entre los 2 grupos de pacientes, pero sí en la estancia hospitalaria, siendo superior para MC. También hemos observado diferencias entre ambas cohortes en edad y tipo de tumor, siendo la MC más frecuente en aquellas pacientes más jóvenes y subtipo luminal A. Hemos hallado diferencias en la incidencia acumulada de recidiva entre ambos subgrupos (p=0,034).ConclusionesEn nuestra cohorte la MC se realiza más frecuentemente en pacientes más jóvenes y con cáncer de mama luminal A.(AU)

Introduction There is no consensus on the indications for contralateral mastectomy (CM) in patients diagnosed with unilateral breast cancer without germline BRCA1/2 mutations. Prior studies have identified some factors that could influence decision-making. These factors include tumoural size and histological type; patient-related factors, such as age; and surgical factors such as the possibility of immediate reconstruction and the surgeon's experience.MethodsRetrospective study of a cohort of 176 patients diagnosed with breast cancer between 2010 and 2016 who underwent breast surgery. We analysed the association between tumoural and patient-related characteristics with the decision to perform CM or not. We also analysed data related to surgery and recurrence by groups by using the cumulative incidence curve and the Gray test.ResultsThe number of CM has increased in our centre. We found no significant differences in the occurrence of post-surgical complications between the two patient groups but length of hospital stay was higher in CM. We also found differences between the two cohorts in age and tumoural type, with CM being more frequent in younger patients and those with luminal A subtype. Differences were found in the cumulative incidence of recurrence between subgroups (p=0.034).ConclusionsIn our cohort, CM was more frequent in younger patients and in those with luminal A breast cancer.(AU)

GLIM vs ESPEN criteria for the diagnosis of early malnutrition in oncological outpatients.

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.

Elderly breast cancer patients treated with Nab-paclitaxel: Results in real clinical practice / Cáncer de mama en pacientes ancianas: experiencia con Nab-paclitaxel en la práctica clínica real

Objective Clinical trials have shown that Nab-paclitaxel is more effective than paclitaxel in the treatment of metastatic breast cancer (MBC). Although the incidence of cancer increases with age, elderly patients are under-represented in clinical trials and tend to receive suboptimal treatment to avoid toxicity. The main aim of our study was to compare progression-free survival (PFS) among patients older and younger than 65 years treated with Nab-paclitaxel in real-world clinical practice. A secondary aim was to assess overall survival (OS) as well as the response rate and toxicity. Methods and patients This single-centre study retrospectively analyzed a cohort of 60 patients with MBC treated with Nab-paclitaxel monotherapy in Hospital Clínico Lozano Blesa de Zaragoza. Results The median PFS was 5.92 months (3.62–11.2) in patients<65 years and was 5.06 months (4.31–12.4) in those ≥65 years (p=0.868). The median OS was 26.9 months (18.6–30.7) in patients < 65 years and was 20.3 months (11.4–33.6) in those ≥65 years (p=0.138). Conclusions Although patients in the cohort studied had a median age of 60.45 years, which is higher than the median age in most clinical trials, PFS and OS in conditions of real-world clinical practice were similar to previously published data. The results of the use of Nab-paclitaxel in patients older than 65 years are similar to those in younger patients, with no additional toxicity problems. The results of our study agree with those of other notable studies. (AU)

Objetivo En los ensayos clínicos se ha demostrado que el Nab-paclitaxel es más eficaz que el paclitaxel en el tratamiento del cáncer de mama metastásico (CMM). Aunque la incidencia del cáncer aumenta con la edad, los pacientes ancianos están infrarrepresentados en los ensayos clínicos, y tienden a recibir un tratamiento subóptimo para evitar toxicidades. El objetivo principal de nuestro estudio es comparar la supervivencia libre de progresión (SLP) entre las mayores y menores de 65 años tratadas con Nab-paclitaxel en la práctica clínica real. El objetivo secundario es evaluar la supervivencia global (SG), así como la tasa de respuestas y la toxicidad. Métodos y pacientes Se ha analizado de forma unicéntrica y retrospectiva, una cohorte de 60 pacientes con CMM tratadas con Nab-paclitaxel en monoterapia en el Hospital Clínico Lozano Blesa de Zaragoza. Resultados Mediana SLP<65 años: 5,92 meses (3,62-11,2) y ≥65 años, mediana: 5,06 meses (4,31-12,4) (p=0,868). Mediana de SG en <65 años: 26,9 meses (18,6-30,7) y ≥65 años: 20,3 meses (11,4-33,6) (p=0,138). Conclusiones Aunque las pacientes de la cohorte estudiada tienen una mediana de edad de 60,45 años, que es superior a la mediana de edad de la mayoría de los ensayos clínicos, la SLP y la SG en condiciones de práctica clínica real son similares a los datos publicados anteriormente. En cuanto al uso de Nab-paclitaxel en pacientes de edad avanzada, se obtienen resultados similares a las de aquellas pacientes más jóvenes, sin observarse problemas de seguridad adicionales. Además, con los datos disponibles, los resultados son congruentes con los presentados en otros estudios de impacto. (AU)

Pseudotumor asociado a citomegalovirus simulando un carcinoma de ciego en un paciente inmunocompetente / Cytomegalovirus-associated pseudotumor mimicking ceccum carcinoma in a non inmunocompromised patient

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Enfisema subcutáneo secundario a perforación intestinal en paciente con enfermedad de Crohn / Subcutaneous emphysema secondary to intestinal perforation in a patient with Crohn's disease

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No siempre es una enfermedad de Crohn: amebiasis como diagnóstico diferencial de la enfermedad inflamatoria intestinal / It is not always Crohn's disease: Amebiasis as a differential diagnosis of inflammatory bowel disease

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Obstrucción biliar secundaria a seudoaneurisma de la arteria gastroduodenal. Una inusual forma de presentación / Bile duct obstruction secondary to a pseudoaneurysm of the gastroduodenal artery. An unusual presentation

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