Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study.

BACKGROUND: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. METHODS: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. RESULTS: From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. CONCLUSIONS: Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT01733628.

Correction: Crespo et al. Protective Effect of Protocatechuic Acid on TNBS-Induced Colitis in Mice Is Associated with Modulation of the SphK/S1P Signaling Pathway. Nutrients 2017, 9, 288.

In the original publication [...].

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.

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

Nab-Paclitaxel plus Gemcitabine and FOLFOXThis randomized, open-label, phase II trial compared nab-paclitaxel/gemcitabine followed by modified FOLFOX versus nab-paclitaxel/gemcitabine alone for the first-line treatment of metastatic pancreatic ductal adenocarcinoma. Patients receiving nab-paclitaxel plus gemcitabine followed by modified FOLFOX-6 (oxaliplatin, leucovorin, and 5-fluorouracil) had a 12-month and 24-month overall survival of 55.3% and 22.4%, respectively, compared with 35.4% and 7.6% in the control group; there was a higher incidence of grade 3 or higher neutropenia and thrombocytopenia. No significant differences in febrile neutropenia, epistaxis or hemorrhage of grade 3 or higher in either group were reported. Two toxic deaths (2.6%) occurred in the experimental group.

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.

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.

Correction: Méndez-Blanco et al. Stabilization of Hypoxia-Inducible Factors and BNIP3 Promoter Methylation Contribute to Acquired Sorafenib Resistance in Human Hepatocarcinoma Cells. Cancers 2019, 11, 1984.

In the original publication [...].

Glenohumeral internal rotation deficit in general population with shoulder pain: A descriptive observational study.

Glenohumeral internal rotation deficit (GIRD) is one of the most important factors influencing injury risk in the arm of overhead athletes. Some studies have shown that the GIRD of athletes with shoulder pain was higher than those without shoulder pain, establishing a relation between shoulder pain and GIRD. However, there are no studies that relate to GIRD and shoulder pain or the risk factors that affect GIRD in the population with this ailment. This study aimed to: determine if GIRD could be found clinically and between which values it oscillates in patients with shoulder pain, and explore if there are any potential associations between GIRD and some sociodemographic data, and orthopedic or radiological findings. A descriptive observational study design was adopted to determine if GIRD could be found clinically in patients with shoulder pain and to gain further evidence in the potential associations between GIRD and sociodemographic data, and orthopedic or radiological findings. All those patients without exclusion criteria between October 1,2020 and March 31,2021 were included. Exclusion criteria consisted of being under 18 years old but younger than 80 years old, showing shoulder pain in both shoulders and having a joint prosthesis in at least one of the 2 shoulders, tumor, or infection. A total of 67 patients aged between 25 and 75 years (52.7 ±â€…11.8 years, 36 male and 31 female). More than 82% of patients with shoulder pain showed a GIRD higher than 20º. The mean GIRD was 37.6 ±â€…17.09º. The 95th percentile was 66.22º. From sociodemographic data could be extracted that: patients who have children showed a lower GIRD, patients with right shoulder pain, or whose dominance coincided with a painful shoulder showed a higher GIRD. The orthopedic findings revealed that patients with a positive Jobe test showed a lower GIRD. The linear model considering both sociodemographic and orthopedic findings showed that GIRD was reduced by having children and by BMI. GIRD shows a high incidence in patients with shoulder pain. The descendant, BMI, and positive Jobe test were negatively associated with the GIRD.

The Social Values of Nursing Staff and the Perceived Quality of Their Professional Lives.

This study's main purpose involves exploring the relationship between the social values of nursing staff and the perception they have of their professional lives. A further aim is to examine how their terms of employment and tenure of service relate to the quality of their careers and their social values. The research consisted of a non-experimental quantitative approach of a descriptive nature involving 380 nursing staff at four public hospitals in Madrid (Spain). The values were appraised by means of the Schwarz Value Survey (SVS) and the quality of their careers was measured through the Quality of Professional Life (QPL-35) questionnaire. The results reveal significant correlations between the two, highlighting the significance of such values as universalism, benevolence, achievement and power depending on their terms of employment, on the one hand, and all the values in the Schwartz model according to the length of their tenure on the other. The findings suggest that terms of employment and tenure are significantly related to the axiological profile of nursing staff and the quality of their professional lives. This study provides major empirical evidence that contributes to our understanding of how social values and the quality of professional lives are interwoven within the field of nursing in Spain.

Treatment of glenohumeral internal rotation deficit in the general population with shoulder pain: An open single-arm clinical trial.

BACKGROUND: Maladaptation can provoke important alterations in the arthrokinematics such as an internal rotation reduction in the dominant shoulder compared with the nondominant shoulder known as glenohumeral internal rotation deficit (GIRD). Though the number of studies investigating GIRD in athletic population, there are not studies reporting the efficacy of the GIRD treatment in the nonathlete population, a kind of study required to improve our understanding of patient care with this pathology. This study aimed to describe the efficacy of the GIRD treatment in nonathlete population with shoulder pain. METHODS: An open single-arm trial with 35 patients was adopted for evaluating the efficacy of GIRD treatment in patients with shoulder pain. All patients with shoulder pain who attended the consultation, accepted, and agreed to participate in the study between October 2020 and March 2021 were included. A treatment sequence including joint manual therapy techniques and soft tissue release techniques was applied in the consultation. Then, patients were instructed to adapt the daily active biological stimulus at home. The IR before (IR0) and after (IR1) the treatment was considered the outcome measure. The GIRD was calculated as the difference between the IR of the non-painful shoulder and the IR of the painful shoulder before (GIRD0) and after treatment (GIRD1). A paired Student t test was used to compare the GIRD of each patient before and after the treatment. RESULTS: Treatment of the patients significantly increased the IR of the painful shoulder in all the patients (P-value < .0001) So, the mean IR0 was 26.09 ± 14.46º (23.64-28.53), and after the treatment the mean IR1 was 67.98 ± 15.03º (65.48-70.52). The mean difference after the treatment (IR1-IR0) was 41.89 ± 14.74º (39.4-44.39). The treatment also significantly reduced GIRD (P-value < .0001). So, the mean GIRD0 was 42.95 ± 16.26º (40.2-45.7), and after the treatment the mean GIRD1 was -1.05 ± 17.18º (-3.96 to 1.85). CONCLUSIONS: The treatment administrated in this study significantly increased the internal rotation of the treated and painful shoulder and reduced the GIRD from the first consultation. LEVEL OF EVIDENCE: Level 3.

Total neoadjuvant therapy with or without aflibercept in rectal cancer: 3-year results of GEMCAD-1402.

BACKGROUND: The results of the Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD)-1402 phase II randomized trial suggested that adding aflibercept to modified fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) induction, followed by chemoradiation and surgery, could increase the pathological complete response (pCR) rate in patients with high-risk, locally advanced rectal cancer. Here we update results up to 3 years of follow-up and evaluate the predictive value of consensus molecular subtypes identified with immunohistochemistry (IHC). METHODS: Patients with magnetic resonance imaging-defined T3c-d and/or T4 and/or N2 rectal adenocarcinoma in the middle or distal third were randomly assigned to mFOLFOX6 induction, with aflibercept (mF+A; n = 115) or without aflibercept (mF; n = 65), followed by capecitabine plus radiotherapy and surgery. The risk local relapse, distant metastases, disease-free survival (DFS), and overall survival (OS) were estimated at 3 years. Selected samples were classified via IHC into immune-infiltrate, epithelial, or mesenchymal subtypes. RESULTS: mF+A and mF had 3-year DFS of 75.2% (95% confidence interval [CI] = 66.1% to 82.2%) and 81.5% (95% CI = 69.8% to 89.1%), respectively; 3-year OS of 89.3% (95% CI = 82.0% to 93.8%) and 90.7% (95% CI = 80.6% to 95.7%), respectively; 3-year cumulative local relapse incidences of 5.2% (95% CI = 1.9% to 11.0%) and 6.1% (95% CI = 1.7% to 15.0%), respectively; and 3-year cumulative distant metastases rates of 17.3% (95% CI = 10.9% to 25.5%) and 16.9% (95% CI = 8.7% to 28.2%), respectively. pCRs were achieved in 27.5% (n = 22 of 80) and 0% (n = 0 of 10) of patients with epithelial and mesenchymal subtypes, respectively. CONCLUSION: Adding aflibercept to mFOLFOX6 induction was not associated with improved DFS or OS. Our findings suggested that consensus molecular subtypes identified with IHC subtypes could be predictive of pCR with this treatment.

Influence of 12-Week Concurrent Training on Exosome Cargo and Its Relationship with Cardiometabolic Health Parameters in Men with Obesity.

Exosome release varies depending on the physiological state of the cell, so they could play a fundamental role in obesity, the biggest pandemic in today's societies. The beneficial effects that physical activity has both on weight and cardiovascular parameters may be mediated by exosomes released in response to exercise. Thus, we aimed (I) to study the influence of a 12-week CT intervention on exosome cargo modifications in men with obesity and (II) to determine whether changes in exosomes after the intervention were related to changes in cardiometabolic health parameters in our cohorts. An experimental, controlled design was performed in twelve (nine with valid data) adult male obese patients (mean values: 41.6 years old, 97.6 kg and 32.4 kg/m2) who were randomly divided into a control group (n = 4) and a training group (n = 5), which completed 36 sessions of CT (concurrent training) for 12 weeks. Before and after the training period, cardiometabolic health parameters were evaluated and blood samples to measure exosomes and proteins were drawn. No changes were observed in the levels of any exosomal markers and proteins; however, associations of changes between CD81 and both fat mass and weight, Flot-1 and VO2max, HSP70 and both CRP and left ventricle diastolic diameter or CD14 and leptin were found (all p ≤ 0.05). Although the current CT was not able to clearly modify the exosome cargo, a certain medium to large clinical effect was manifested considering the nature of this study. Moreover, the associations found between the promoted changes in cardiometabolic parameters and exosome-carried proteins could indicate a relationship to be considered for future treatments in patients with obesity.

Effects of submaximal and supramaximal accentuated eccentric loading on mass and function.

Introduction: Eccentric-overload (EO) resistance training emerges as an alternative to more optimally prescribe intensity relative to the force generation capabilities of the eccentric muscle contraction. Given the difficulties to individually prescribe absolute eccentric loads relative to each person's eccentric ability, setting the load relative to the concentric one-repetition maximum (1-RM) is the most used EO training approach. Therefore, we investigated the effects of submaximal and supramaximal (i.e., eccentric loads above 100% of 1-RM) accentuated eccentric training on changes in lean mass, anabolic hormonal responses and muscle function. Methods: Physically active university students (n = 27) were randomly assigned to two training groups. Participants in the training groups performed dominant leg isotonic training twice a week for 10 weeks (four sets of eight repetitions). Isotonic resistance was generated by an electric-motor device at two different percentages of 1-RM for the eccentric phase; 90% submaximal load, SUB group) and 120% (supramaximal load, SUPRA group). Concentric load was the same for both groups (30% of 1-RM). Changes in total thigh lean mass (TTLM), anabolic hormonal responses (growth hormone, IGF-1, IL-6, and total testosterone), unilateral leg-press 1-RM, maximal voluntary isometric contractions (MVIC), local muscle endurance (XRM), muscle power at 40 (PP40), 60 (PP60) and 80% (PP80) of the 1-RM, and unilateral vertical jump height before and after training were compared between groups. Results: After training, both SUB and SUPRA groups showed similar increases (p < 0.05) in MVIC (19.2% and 19.6%), XRM (53.8% and 23.8%), PP40 (16.2% and 15.7%), TTLM (2.5% and 4.2%), IGF-1 (10.0% and 14.1%) and IL-6 (58.6% and 28.6%). However, increases in 1-RM strength (16.3%) and unilateral vertical jump height (10.0%-13.4%) were observed for SUPRA only. Indeed, SUPRA was shown to be more favorable than SUB training for increasing 1-RM [ES = 0.77 (1.49-0.05)]. Unilateral muscle power at medium and high intensity (10.2% and 10.5%) also increased in SUB but without significant differences between groups. Discussion: Similar functional and structural effects were demonstrated after 10 weeks EO training with submaximal and supramaximal eccentric loads. Although supramaximal loading might be superior for increasing 1-RM, the use of this approach does not appear to be necessary in healthy, active individuals.

Legal Positivism's Internal Morality.

This article examines the jurisprudential arguments elaborated in David Dyzenhaus's The Long Arc of Legality. In particular, it looks into the main claim of the book: that the fact of 'very unjust laws' is central to illuminating the idea of law's authority, the elaboration of which Dyzenhaus takes to be the purpose of legal theory. The article analyses Dyzenhaus's own normative proposal in this matter, which consists of a version of legal positivism committed to Lon Fuller's principles of the internal morality of law, with the corollary of a conception of the judicial role as bound to a duty to apply these internal principles of legality when exercising their main function. While I cast some doubts on the feasibility of constructing the judge's function that way, in the end I celebrate Dyzenhaus's attempt at refining legal positivism's identity, especially in light of the ongoing debate with contemporary anti-positivism.

Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD.

BACKGROUND AND AIMS: Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition from simple steatosis to steatohepatitis. METHODS: EpCAM and CD133 liver proteins and EpCAM+ CD133+ EVs levels were analysed in 31 C57BL/6J mice fed with a chow or high fat, high cholesterol and carbohydrates diet (HFHCC) for 52 weeks. The hepatic origin of MVs was addressed using AlbCrexmT/mG mice fed a Western (WD) or Dual diet for 23 weeks. Besides, we assessed plasma MVs in 130 biopsy-proven NAFLD patients. RESULTS: Hepatic expression of EpCAM and CD133 and EpCAM+ CD133+ EVs increased during disease progression in HFHCC mice. GFP+ MVs were higher in AlbCrexmT/mG mice fed a WD (5.2% vs 12.1%) or a Dual diet (0.5% vs 7.3%). Most GFP+ MVs were also positive for EpCAM and CD133 (98.3% and 92.9% respectively), suggesting their hepatic origin. In 71 biopsy-proven NAFLD patients, EpCAM+ CD133+ EVs were significantly higher in those with steatohepatitis compare to those with simple steatosis (286.4 ± 61.9 vs 758.4 ± 82.3; p < 0.001). Patients with ballooning 367 ± 40.6 vs 532.0 ± 45.1; p = 0.01 and lobular inflammation (321.1 ± 74.1 vs 721.4 ± 80.1; p = 0.001), showed higher levels of these EVs. These findings were replicated in an independent cohort. CONCLUSIONS: Circulating levels of EpCAM+ CD133+ MVs in clinical and experimental NAFLD were increased in the presence of steatohepatitis, showing high potential as a non-invasive biomarker for the evaluation and management of these patients.

Executive summary consensus statement of imported diseases group (GEPI) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SETMSI), on the diagnostic and treatment of imported schistosomiasis.

Schistosomiasis is a highly prevalent disease, especially in immigrant populations, and is associated with significant morbidity and diagnostic delays outside endemic areas. For these reasons, the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SEMTSI) have developed a joint consensus document to serve as a guide for the screening, diagnosis and treatment of this disease outside endemic areas. A panel of experts from both societies identified the main questions to be answered and developed recommendations based on the scientific evidence available at the time. The document was reviewed by the members from both societies for final approval.

The AGAMENON-SEOM model for prediction of survival in patients with advanced HER2-positive oesophagogastric adenocarcinoma receiving first-line trastuzumab-based therapy.

Background: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab. Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included. The model was externally validated in an independent series (The Christie NHS Foundation Trust, Manchester, UK). Results: In all, 737 patients were recruited (AGAMENON-SEOM, n = 654; Manchester, n = 83). Median PFS and OS in the training cohort were 7.76 [95% confidence interval (CI), 7.13-8.25] and 14.0 months (95% CI, 13.0-14.9), respectively. Six covariates were significantly associated with OS: neutrophil-to-lymphocyte ratio, Eastern Cooperative Oncology Group performance status, Lauren subtype, HER2 expression, histological grade and tumour burden. The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for corrected PFS/OS of 0.606 (95% CI, 0.578-0.636) and 0.623 (95% CI, 0.594-0.655), respectively. In the validation cohort, the model is well calibrated, with a c-index of 0.650 and 0.683 for PFS and OS, respectively. Conclusion: The AGAMENON-HER2 prognostic tool stratifies HER2-positive AGA patients receiving trastuzumab and chemotherapy according to their estimated survival endpoints.