The Mediating Role of Exercise in Depression and Fatigue in Patients with Advanced Cancer.

This study explored the interconnections between sociodemographic elements, depression, fatigue, and exercise in patients suffering from incurable neoplasm, particularly emphasizing the mediating influence of exercise on the relationship between depression and fatigue This was a prospective, multicenter, observational study involving 15 hospitals across Spain. After three months of systemic cancer treatment, participants completed the Brief Symptom Inventory (BSI), the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ) and the Fatigue Assessment Scale (FAS) to measure levels of depression, fatigue, and exercise, respectively. A total of 616 subjects participated in this study. Activity levels differed markedly according to educational attainment, marital, and work status. There was a negative correlation between physical activity and depression, and a positive correlation between depression and fatigue (ß = -0.18, and ß = 0.46, respectively). Additionally, physical activity inversely influenced fatigue levels (ß = 0.21). Physical activity served as a partial intermediary in the link between depression and fatigue among patients with advanced, unresectable cancer. Healthcare providers are urged to consider both the physical and emotional dimensions of cancer treatment, implementing physical activity programs to enhance overall patient quality of life and mental health.

Physical Activity in Patients with Advanced Cancer: Sociodemographic, Clinical, and Psychological Correlates.

As cancer progresses, patients may experience physical decline, which can impair their ability to carry out essential daily tasks. The aim of this study was to analyze the levels of physical activity in patients with advanced cancer undergoing systemic treatment and its relationship with sociodemographic, clinical, and psychological factors. A prospective, cross-sectional, multicenter study was carried out in 15 oncology departments in Spain. Patients with locally advanced, unresectable, or metastatic cancer who were candidates for systemic treatment were included. Participants completed demographic information and psychological scales. In total, 508 patients were included in the study, the majority of whom were male, over the age of 65, and diagnosed with bronchopulmonary tumors (36%) and metastatic disease. Based on their physical activity levels, participants were categorized as sedentary (20%, n = 190), engaging in light physical activity (43%, n = 412), or demonstrating moderate physical activity (37%, n = 351). Patients who were over 65 years old; had a worse baseline status (ECOG ≥ 1); lacked a partner; had a lower educational level; or were retired or unemployed were found to have lower levels of physical activity. Those with sedentary physical activity reported higher levels of psychological distress, anxiety, depression, somatization, and physical symptoms, as well as worse functional status, global health status, and well-being. Understanding the complex interplay between physical activity and sociodemographic, clinical, and psychological factors can help neuroscientists develop tailored exercise interventions that address the unique needs of advanced cancer patients.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH–AEG–SEPD–SEOM–GETECCU / Manejo de las toxicidades digestivas secundarias al tratamiento con inhibidores de checkpoint: documento de posicionamiento de la AEEH-AEG-SEPD-SEOM-GETECCU

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.(AU)

El descubrimiento de los inhibidores de checkpoint inmunológicos (ICI) es uno de los logros más importantes en los últimos años en Oncología. Sin embargo, su uso en aumento ha conlllevado a un incremento de los efectos adversos inmunomediados (irAEs). Los eventos hepáticos y gastrointestinales incluyen la hepatitis, colitis y síntomas de tracto digestivo superior, que son de los irAEs más frecuentes, con incidencias entre el 2 y 40%, ésta última en paciente tratados con combo de ICI. Basados en la evidencia científica tanto de ensayo clínicos randomizados como de estudio de vida real, este documento de consenso aporta recomendaciones sobre el diagnóstico, tratamiento y pronóstico de los efectos adversos hepáticos y gastrointestinales asociados con la inmunoterapia.(AU)

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial.

BACKGROUND: The prognostic value of the Systemic Inflammation Response Index (SIRI) in advanced pancreatic cancer is recognized, but its correlation with patients´ nutritional status and outcomes remains unexplored. AIM: To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer. METHODS: The PANTHEIA-Spanish Society of Medical Oncology (SEOM) study is a multicentric (16 Spanish hospitals), observational, longitudinal, non-interventional initiative, promoted by the SEOM Real World-Evidence work group. This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI. The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers. Patients with pathologically confirmed metastatic pancreatic adenocarcinoma, treated from January 2020 to January 2023, were included. The index was calculated using the product of neutrophil and monocyte counts, divided by lymphocyte counts, obtained within 15 days before initiation chemotherapy. This study evaluated associations between overall survival (OS), SIRI and weight loss. RESULTS: A total of 50 patients were included. 66% of these patients were male and the median age was 66 years. Metastasis sites: 36% liver, 12% peritoneal carcinomatosis, 10% lung, and 42% multiple locations. Regarding the first line palliative chemotherapy treatments: 50% received gemcitabine plus nab-paclitaxel; 28%, modified fluorouracil, leucovorin, irinotecan and oxaliplatin, and 16% were administered gemcitabine. 42% had a weight loss > 5% in the three months (mo) preceding diagnosis. 21 patients with a SIRI ≥ 2.3 × 103/L exhibited a trend towards a lower median OS compared to those with a SIRI < 2.3 × 103/L (4 vs 18 mo; P < 0.000). Among 21 patients with > 5% weight loss before diagnosis, the median OS was 6 mo, in contrast to 19 mo for those who did not experience such weight loss (P = 0.003). Patients with a weight loss > 5% showed higher SIRI levels. This difference was statistically significant (P < 0.000). For patients with a SIRI < 2.3 × 103/L, those who did not lose > 5% of their weight had an OS of 20 mo, compared to 11 mo for those who did (P < 0.001). No association was found between carbohydrate antigen 19-9 levels ≥ 1000 U/mL and weight loss. CONCLUSION: A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss. An elevated SIRI is suggested as a predictor of survival, emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Fear of Recurrence in Advanced Cancer Patients: Sociodemographic, Clinical, and Psychological Correlates.

Fear of cancer recurrence significantly impacts advanced cancer patients, prompting emotional distress and increased healthcare utilization. This present study aims to analyze the fear of recurrence among patients with advanced cancer undergoing systemic treatment and its relationship with sociodemographic, clinical, and psychological factors. A multicenter cross-sectional study was conducted in 15 oncology departments across Spain, involving patients with locally advanced, unresectable, or metastatic cancer eligible for systemic treatment. Participants provided demographic information and completed instruments such as the Cancer Worry Scale, Brief Symptom Inventory, Mishel Uncertainty in Illness Scale, and the Duke-UNC-11 Functional Social Support Questionnaire (DUFSSQ). A total of 1195 participants participated: median age 66, 56% male, mostly metastatic cancers (80%), and common tumor sites. Two fear groups emerged: 28% low and 72% high levels of fear. High fear was associated with being female, being younger, lower levels of education, and worse survival estimates. High fear correlated with more depression, anxiety, somatic symptoms, uncertainty, and stronger social support. Multivariate analyses indicated that younger patients, those with shorter survival estimates, higher depression and anxiety scores, more uncertainty, and stronger social support had a greater likelihood of experiencing fear of recurrence, while the opposite was true for older patients. This study underscores distinct fear of recurrence profiles in advanced cancer patients, emphasizing the need for targeted interventions and support. Future research should delve deeper into understanding their repercussions for improving patient care and well-being.

Is there a preferred platinum and fluoropyrimidine regimen for advanced HER2-negative esophagogastric adenocarcinoma? Insights from 1293 patients in AGAMENON-SEOM registry.

BACKGROUND: The optimal chemotherapy backbone for HER2-negative advanced esophagogastric cancer, either in combination with targeted therapies or as a comparator in clinical trials, is uncertain. The subtle yet crucial differences in platinum-based regimens' safety and synergy with combination treatments need consideration. METHODS: We analyzed cases from the AGAMENON-SEOM Spanish registry of HER2-negative advanced esophagogastric adenocarcinoma treated with platinum and fluoropyrimidine from 2008 to 2021. This study focused exclusively on patients receiving one of the four regimens: FOLFOX (5-FU and oxaliplatin), CAPOX (capecitabine and oxaliplatin), CP (capecitabine and cisplatin) and FP (5-FU and cisplatin). The aim was to determine the most effective and tolerable platinum and fluoropyrimidine-based chemotherapy regimen and to identify any prognostic factors. RESULTS: Among 1293 patients, 36% received either FOLFOX (n = 468) or CAPOX (n = 466), 20% CP (n = 252), and 8% FP (n = 107). FOLFOX significantly increased PFS (progression free survival) compared to CP, with a hazard ratio of 0.73 (95% CI 0.58-0.92, p = 0.009). The duration of treatment was similar across all groups. Survival outcomes among regimens were similar, but analysis revealed worse ECOG-PS (Eastern Cooperative Oncology Group-Performance Status), > 2 metastatic sites, bone metastases, hypoalbuminemia, higher NLR (neutrophil-to-lymphocyte ratio), and CP regimen as predictors of poor PFS. Fatigue was common in all treatments, with the highest incidence in FOLFOX (77%), followed by FP (72%), CAPOX (68%), and CP (60%). Other notable toxicities included neuropathy (FOLFOX 69%, CAPOX 62%), neutropenia (FOLFOX 52%, FP 55%), hand-foot syndrome in CP (46%), and thromboembolic events (FP 12%, CP 11%). CONCLUSIONS: FOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.

Nab-Paclitaxel plus Gemcitabine and FOLFOX in Metastatic Pancreatic Cancer.

BACKGROUND: Sequential nab-paclitaxel plus gemcitabine followed by modified FOLFOX-6 (oxaliplatin, leucovorin, and 5-fluorouracil) (nab-P/Gem-mFOLFOX) showed a good safety and clinical profile in metastatic pancreatic ductal adenocarcinoma (mPDAC) in the phase I SEQUENCE trial. METHODS: The safety and efficacy of sequential nab-P/Gem-mFOLFOX was compared with standard nab-paclitaxel plus gemcitabine (nab-P/Gem) as first-line treatment in a multi-institutional, randomized, open-label, phase II trial in patients with untreated mPDAC. We randomly assigned patients in a 1:1 ratio to receive nab-P/Gem on days 1, 8, and 15 followed by mFOLFOX on day 29 of a 6-week cycle (experimental group) or nab-P/Gem on days 1, 8, and 15 of a 4-week cycle (control group). The primary end point was the 12-month overall survival rate. RESULTS: A total of 157 patients were randomly assigned: 78 to nab-P/Gem-mFOLFOX and 79 to nab-P/Gem. Patients receiving nab-P/Gem-mFOLFOX had a 12-month overall survival of 55.3% (95% confidence interval [CI], 44.2 to 66.5) versus 35.4% (95% CI, 24.9 to 46) in the control group (P=0.02). Similarly, the 24-month survival was 22.4% (95% CI, 13 to 31.8) with nab-P/Gem-mFOLFOX versus 7.6% (95% CI, 1.8 to 13.4) with control treatment. The median overall survival was 13.2 months (95% CI, 10.1 to 16.2) with nab-P/Gem-mFOLFOX and 9.7 months (95% CI, 7.5 to 12) with nab-P/Gem (hazard ratio for death, 0.68; 95% CI, 0.48 to 0.95). The safety profile showed a higher incidence of grade 3 or higher neutropenia (35 of 76 vs. 19 of 79 patients, P=0.004), grade 3 or higher thrombocytopenia (18 of 78 vs. 6 of 79 patients, P=0.007), and two treatment-related deaths (2.6%) with nab-P/Gem-mFOLFOX compared with none with control treatment. CONCLUSIONS: Sequential nab-P/Gem-mFOLFOX showed a significantly higher 12-month survival when compared with the standard nab-P/Gem treatment; this came with greater treatment toxicity. (Funded by Celgene; EuCT number, 2014-005350-19; ClinicalTrials.gov number, NCT02504333.)

Prospective study of predictors for anxiety, depression, and somatization in a sample of 1807 cancer patients.

In cancer patients, psychological distress, which encompasses anxiety, depression, and somatization, arises from the complex interplay of emotional and behavioral reactions to the diagnosis and treatment, significantly influencing their functionality and quality of life. The aim was to investigate factors associated with psychological distress in cancer patients. This prospective and multicenter study, conducted by the Spanish Society of Medical Oncology (SEOM), included two cohorts of patients with cancer (localized resected or advanced unresectable). They completed surveys assessing psychological distress (BSI-18) before and after cancer treatment and coping (MINI-MAC) and spirituality (FACIT-sp) prior to therapy. A multivariable logistic regression analysis and a Structural Equation Modeling (SEM) were conducted. Between 2019 and 2022, 1807 patients were evaluated, mostly women (54%), average age 64 years. The most frequent cancers were colorectal (30%), breast (25%) and lung (18%). Men had lower levels of anxiety and depression (OR 0.66, 95% CI 0.52-0.84; OR 0.72, 95% CI 0.56-0.93). Colorectal cancer patients experienced less anxiety (OR 0.63, 95% CI 0.43-0.92), depression (OR 0.55, 95% CI 0.37-0.81), and somatization (OR 0.59, 95% CI 0.42-0.83). Patients with localized cancer and spiritual beliefs had reduced psychological distress, whereas those with anxious preoccupation had higher level. SEM revealed a relationship between psychological distress and coping strategies, emphasizing how baseline anxious preoccupation exacerbates post-treatment distress. This study suggests that age, sex, extension and location of cancer, coping and spirituality influence psychological distress in cancer patients.

Análisis del éxito de las números uno en la prueba MIR de 2022 y 2023. El impacto de la preparación y el efecto del azar / Analysis of the success of the highest scoring candidates in Spain’s Resident Medical Intern (MIR) examinations of 2022 and 2023. The impact of preparation and the effect of serendipity

Introducción: El examen de médico interno residente (examen MIR) es la prueba que permite el acceso a la formación médica especializada en España. Su objetivo es distribuir las plazas disponibles para las diferentes especialidades médicas entre los graduados en Medicina, teniendo en cuenta para ello tanto su expediente como los resultados de la prueba. La realización de un examen de test tiene un cierto componente de aleatoriedad.Objetivos: Analizar el rendimiento de las números uno de las convocatorias de 2021-2022 y 2022-2023 a lo largo de su preparación, así como conocer qué resultados podrían obtener en caso de que repitieran el mismo examen un millón de veces. Material y métodos: Se hizo uso de la información relativa al rendimiento de los estudiantes que prepararon las pruebas con cursos intensivos MIR Asturias, así como de los principios de la teoría de respuesta al ítem.Resultados. En 11 (33,3%) y 14 (42,4%) de las 33 pruebas realizadas a lo largo de la preparación, las números uno se clasificaron entre los 10 primeros. A partir de las simulaciones de las pruebas MIR de 2022 y 2023, se obtuvo que la primera clasificada de 2022 quedaría entre los 185 primeros de la prueba, y la de 2023, entre los 92 primeros.Conclusiones: Para obtener un número de orden entre los primeros clasificados es necesario disponer de un ability elevado, el cual se consigue a través de una preparación sólida. Además, el azar tiene un cierto nivel de influencia sobre los resultados de los opositores presentados a la prueba.(AU)

Introduction: The MIR exam is the test that allows access to specialized medical training in Spain. Its objective is to distribute the available places for the different medical specialties among Medicine graduates, taking into account both their record and the results of the test. Taking a test exam has a certain element of randomness.Objectives: Analyze the performance of the number ones of the 2021-2022 and 2022-2023 calls throughout their preparation, as well as know what results they could obtain if they repeated the same exam one million times. Material and methods: Information related to the performance of the students who prepared the tests with MIR Asturias Intensive Courses was used, as well as the principles of item response theory.Results. In 11 (33.3%) and 14 (42.4%) of the 33 tests carried out throughout the preparation, number one was classified among the top 10. From the simulations of the 2022 and 2023 MIR tests, it was obtained that the first classified in 2022 would be among the top 185 in the test and in 2023 among the top 92. Conclusions: To obtain an order number among the first classified it is necessary to have a high ability, which is achieved through solid preparation. In addition, randomness has a certain level of influence on the results of the opponents presented to the test.(AU)

Psychometric Properties and Measurement Invariance of the Herth Hope Index in Spanish Cancer Patients.

BACKGROUND: The aim of this study was to evaluate the psychometric properties, differential item functioning, factorial invariance, and convergent validity of the Spanish version of the Herth Hope Index (HHI) in patients with cancer. METHOD: Exploratory and confirmatory factor analyses were conducted to explore the scale, dimensionality, functioning of items, test for strong measurement invariance across sex, age, tumor site, and expected survival, and an extended structural equation model to assess external validity in a cross-sectional, multicenter, prospective study of 863 cancer patients from 15 Spanish hospitals. RESULTS: The results do not support the original 3-factor scale but instead suggest a one-factor structure, which explained 62% of the common variance. Scores from the unidimensional structure exhibited satisfactory reliability (ω = .88). A strong invariance solution demonstrated excellent fit across sex, age, tumor site, and survival. HHI exhibited substantial associations with resilience coping strategies and spiritual well-being. CONCLUSIONS: The findings of our study contribute to the diversity of earlier empirical findings regarding the construct of hope. Despite this, our results indicate that the Spanish version of the HHI is a short, easy-to-administer, valid, reliable tool for evaluating cancer patients' levels of hope.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Dynamic nature of BRAF or KRAS p.G12C mutations in second-line therapy for advanced colorectal cancer patients: do early and late effects exist?

INTRODUCTION: The mitogen-activated protein kinase (MAPK) signalling network aberrations in metastatic colorectal cancer (mCRC) generate intrinsic dynamic effects and temporal variations that are crucial but often overlooked in clinical trial populations. Here, we investigate the time-varying impact of MAPK pathway mutation genotype on each treatment line's contribution to the overall clinical course. METHODS: The PROMETEO study focused on mCRC patients undergoing second-line treatment at 20 hospitals. We evaluated genotypes and employed flexible models to analyse the dynamic effect of each mutation. RESULTS: We examined data derived from 1160 patients. The effects of KRAS G12C or G12V, and BRAF V600E are clearly time-varying, with unexpected consequences such as the deleterious effect of BRAF V600E vs other genotypes dissipating over time when subjects receive antiangiogenics, or KRAS G12V and G12C showing increasing aggressiveness over time. Thus, contrary to expectations, the 12-month survival rate from the second line for those who survived >6 months was 49.9% (95% CI, 32.7-67.3) for KRAS G12C and 59% (95% CI, 38.5-80.6) for BRAF V600E. CONCLUSIONS: The dynamic perspective is essential for understanding the behaviour of tumours with specific genotypes, especially from the second line onward. This may be relevant in patient monitoring and treatment decision-making, particularly in cases with distinct mutations.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2 % to 40 %, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Psychological factors and prognostic communication preferences in advanced cancer: multicentre study.

OBJECTIVES: Communication regarding prognosis to patients with advanced cancer is fundamental for informed medical decision making. Our objective was to analyse (1) the proportion of subjects with advanced cancer who prefer to know their prognosis, (2) the characteristics associated with patients' preference for prognostic information, (3) the psychological factors that impact the preference to know prognosis and 4) the concordance between preference for prognostic information perceived among physicians and patients. METHODS: A prospective, cross-sectional design was adopted. Data were collected from 748 participants with advanced cancer at 15 tertiary hospitals in Spain. Participants completed the following questionnaires: Mental Adjustment to Cancer; Trust in the Physician; Uncertainty in Illness Scale Patient's Prognostic Preferences. RESULTS: Fifty-two per cent of advanced cancer sufferers preferred to know the prognosis of their disease. Compared with participants who preferred not to know, those who did reported more uncertainty, greater satisfaction with their physician and higher scores on positive attitude (all p=0.001). Thirty-seven per cent of the physicians believed that patients want to know their prognosis, indicating that they underestimate the number of such patients. No significant differences were found regarding preference to know prognosis as a function of sociodemographic and clinical variables. CONCLUSIONS: A substantial proportion of individuals with advanced cancer prefer to know the prognosis of their disease. It appears that knowing their prognosis was mainly motivated by a need to maintain a positive attitude, lessen uncertainty and by satisfaction with the physician. It is important to explore patients' preferences for information to offer more personalised communication.

Efficacy and safety of chemotherapy in young patients with advanced gastroesophageal adenocarcinoma: data from the Spanish AGAMENON-SEOM registry.

BACKGROUND: Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10-15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma. METHODS: Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years. RESULTS: Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively, p = 0.579), progression-free survival (6.1 vs. 6.83 months, p = 0.158) and overall survival (11.07 vs. 10.81 months, p = 0.82), even after adjusting for potential confounding factors. Grade 3-4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients. CONCLUSIONS: In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts. In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.

Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival.

OBJECTIVE: Metabolic profiling is a valuable tool to characterize tumor biology but remains largely unexplored in neuroendocrine tumors (NETs). Our aim was to comprehensively assess the metabolomic profile of NETs and identify novel prognostic biomarkers and dysregulated molecular pathways. DESIGN AND METHODS: Multiplatform untargeted metabolomic profiling (GC-MS, CE-MS, and LC-MS) was performed in plasma from 77 patients with G1-2 extra-pancreatic NETs enrolled in the AXINET trial (NCT01744249) (study cohort) and from 68 non-cancer individuals (control). The prognostic value of each differential metabolite (n = 155) in NET patients (P < .05) was analyzed by univariate and multivariate analyses adjusted for multiple testing and other confounding factors. Related pathways were explored by Metabolite Set Enrichment Analysis (MSEA) and Metabolite Pathway Analysis (MPA). RESULTS: Thirty-four metabolites were significantly associated with progression-free survival (PFS) (n = 16) and/or overall survival (OS) (n = 27). Thirteen metabolites remained significant independent prognostic factors in multivariate analysis, 3 of them with a significant impact on both PFS and OS. Unsupervised clustering of these 3 metabolites stratified patients in 3 distinct prognostic groups (1-year PFS of 71.1%, 47.7%, and 15.4% (P = .012); 5-year OS of 69.7%, 32.5%, and 27.7% (P = .003), respectively). The MSEA and MPA of the 13-metablolite signature identified methionine, porphyrin, and tryptophan metabolisms as the 3 most relevant dysregulated pathways associated with the prognosis of NETs. CONCLUSIONS: We identified a metabolomic signature that improves prognostic stratification of NET patients beyond classical prognostic factors for clinical decisions. The enriched metabolic pathways identified reveal novel tumor vulnerabilities that may foster the development of new therapeutic strategies for these patients.

State of the scientific evidence and recommendations for the management of older patients with gastric cancer.

Gastric cancer is one of the most frequent and deadly tumours worldwide. However, the evidence that currently exists for the treatment of older adults is limited and is derived mainly from clinical trials in which older patients are poorly represented. In this article, a group of experts selected from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Group for the Treatment of Digestive Tumours (TTD), and the Spanish Multidisciplinary Group on Digestive Cancer (GEMCAD) reviews the existing scientific evidence for older patients (≥65 years old) with gastric cancer and establishes a series of recommendations that allow optimization of management during all phases of the disease. Geriatric assessment (GA) and a multidisciplinary approach should be fundamental parts of the process. In early stages, endoscopic submucosal resection or laparoscopic gastrectomy is recommended depending on the stage. In locally advanced stage, the tolerability of triplet regimens has been established; however, as in the metastatic stage, platinum- and fluoropyrimidine-based regimens with the possibility of lower dose intensity are recommended resulting in similar efficacy. Likewise, the administration of trastuzumab, ramucirumab and immunotherapy for unresectable metastatic or locally advanced disease is safe. Supportive treatment acquires special importance in a population with different life expectancies than at a younger age. It is essential to consider the general state of the patient and the psychosocial dimension.

Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH-AEG-SEPD-SEOM-GETECCU

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2 % to 40 %, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events (AU)

El descubrimiento de los inhibidores de checkpoint inmu nológicos (ICI) es uno de los logros más importantes en los últimos años en Oncología. Sin embargo, su uso en aumen to ha conlllevado a un incremento de los efectos adversos inmunomediados (irAEs). Los eventos hepáticos y gastroin testinales incluyen la hepatitis, colitis y síntomas de tracto digestivo superior, que son de los irAEs más frecuentes, con incidencias entre el 2 % y 40 %, esta última en paciente tratados con combo de ICI. Basados en la evidencia científica tanto de ensayo clínicos randomizados como de estudio de vida real, este documento de consenso aporta recomenda ciones sobre el diagnóstico, tratamiento y pronóstico de los efectos adversos hepáticos y gastrointestinales asociados con la inmunoterapia. (AU)

Psychometric Properties and Measurement Invariance of the Herth Hope Index in Spanish Cancer Patients / Propiedades Psicométricas y Medida de Invarianza del Índice de Esperanza de Herth en Pacientes Oncológicos Españoles

Background: The aim of this study was to evaluate the psychometric properties, differential item functioning, factorial invariance, and convergent validity of the Spanish version of the Herth Hope Index (HHI) in patients with cancer. Method: Exploratory and confirmatory factor analyses were conducted to explore the scale, dimensionality, functioning of items, test for strong measurement invariance across sex, age, tumor site, and expected survival, and an extended structural equation model to assess external validity in a cross-sectional, multicenter, prospective study of 863 cancer patients from 15 Spanish hospitals. Results: The results do not support the original 3-factor scale but instead suggest a one-factor structure, which explained 62% of the common variance. Scores from the unidimensional structure exhibited satisfactory reliability (ω= .88). A strong invariance solution demonstrated excellent fit across sex, age, tumor site, and survival. HHI exhibited substantial associations with resilience coping strategies and spiritual well-being. Conclusions: The findings of our study contribute to the diversity of earlier empirical findings regarding the construct of hope. Despite this, our results indicate that the Spanish version of the HHI is a short, easy-to-administer, valid, reliable tool for evaluating cancer patients’ levels of hope.(AU)

Antecedentes: El objetivo de este estudio fue evaluar las propiedades psicométricas, el funcionamiento de los ítems, la invariancia factorial y la validez convergente de la versión española del Herth Hope Index (HHI) en pacientes con cáncer. Método: Estudio transversal, multicéntrico, prospectivo de 863 pacientes con cáncer de 15 hospitales españoles. Se realizaron análisis factoriales exploratorios y confirmatorios para explorar la dimensionalidad, el funcionamiento de los ítems, la invariancia de medición según el sexo, la edad, el sitio del tumor y la supervivencia esperada, y la validez externa. Resultados: Los resultados obtenidos no respaldan la escala original de 3 factores y en cambio sugieren una estructura de un factor, que explicó el 62% de la varianza común, con una confiabilidad satisfactoria (ω = .88). Una solución de invariancia fuerte demostró un excelente ajuste en función del sexo, la edad, el sitio del tumor y la supervivencia. HHI reveló asociaciones sustanciales con la resiliencia y el bienestar espiritual. Conclusiones: Nuestros resultados indican que la versión en español del HHI es una herramienta corta, fácil de administrar, válida y confiable para evaluar el nivel de esperanza de los pacientes con cáncer.(AU)

High-protein home parenteral nutrition in malnourished oncology patients: a systematic literature review.

INTRODUCTION: Up to 83% of oncology patients are affected by cancer-related malnutrition, depending on tumour location and patient age. Parenteral nutrition can be used to manage malnutrition, but there is no clear consensus as to the optimal protein dosage. The objective of this systematic literature review (SLR) was to identify studies on malnourished oncology patients receiving home parenteral nutrition (HPN) where protein or amino acid delivery was reported in g/kg bodyweight/day, and to compare outcomes between patients receiving low (< 1 g/kg bodyweight/day), standard (1-1.5 g/kg/day), and high-protein doses (> 1.5 g/kg/day). METHODS: Literature searches were performed on 5th October 2021 in Embase, MEDLINE, and five Cochrane Library and Centre for Reviews and Dissemination databases. Searches were complemented by hand-searching of conference proceedings, a clinical trial registry, and bibliographic reference lists of included studies and relevant SLRs/meta-analyses. RESULTS: Nineteen publications were included; sixteen investigated standard protein, two reported low protein, and one included both, but none assessed high-protein doses. Only one randomised controlled trial (RCT) was identified; all other studies were observational studies. The only study to compare two protein doses reported significantly greater weight gain in patients receiving 1.15 g/kg/day than those receiving 0.77 g/kg/day. CONCLUSION: At present, there is insufficient evidence to determine the optimal protein dosage for malnourished oncology patients receiving HPN. Data from non-HPN studies and critically ill patients indicate that high-protein interventions are associated with increased overall survival and quality of life; further studies are needed to establish whether the same applies in malnourished oncology patients.