Running on empty: Diesel-Contaminated sediments impair feeding and behaviour in the marine gastropod Tritia neritea.

The embodied impact of trauma complicates the work of helping our patients access more enlivened states of being. Like all trauma, the intersecting traumas of racism, misogyny, and sexual violence can lead to chronic autonomic nervous system dysregulation that forecloses the capacities for fantasy, imagination, and insight so central to the psychoanalytic process. Somatic approaches can be enlisted to support the patient in developing an “embodied observing ego” that tracks present moment bodily experiences signaling the presence of anxiety, defense, core affect, and trauma survival responses. As self-regulatory capacity increases, the patient is helped to consciously execute trauma survival responses which had previously been inhibited or truncated. This approach, informed by the work of Pierre Janet (1919/1925) and contemporary neurobiology and traumatology (e.g., Levine, 1997; T. Ogden, 2019), and by sensorimotor psychotherapy in particular (T. Ogden, 2019), allows patients to experience a previously inaccessible stage of “triumph,” and unlocks their capacities for meaning making and integration. I outline this embodied psychodynamic approach through clinical illustrations from my work with an Indian American woman grappling with the effects of racialized and gendered trauma.

Triple therapy of transcatheter arterial chemoembolization (TACE) combined with lenvatinib and anti-PD-1 antibodies has demonstrated excellent efficacy in unresectable hepatocellular carcinoma (uHCC). However, tumor drug resistance is still a major problem and the rate of complete response in uHCC following triple therapy is relatively low. This study aimed to investigate the efficacy and safety of sequential radiotherapy after triple therapy in patients with uHCC to improve tumor response rate. This retrospective study included 29 patients with uHCC who received sequential radiotherapy after achieving partial response (PR) or stable disease (SD) in tumor response per the modified Response Evaluation Criteria in Solid Tumors (mRECIST) after triple therapy. The overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were analyzed to evaluate the efficacy of this regimen. Treatment-related adverse events were assessed to determine the safety profile. Among the 29 patients, the median OS had not yet reached, and the median PFS was 19.43 months. The 24-month OS and PFS rates were 72.8% and 46.5%, respectively. The lesions of 6 patients initially with tumor response of PR achieved complete response, and the lesions fo 12 patients with SD achieved PR after sequential radiotherapy. All adverse events were manageable, and no treatment-related death occurred. Sequential radiotherapy after triple therapy enhanced tumor response and survival benefits for uHCC patients, with manageable adverse effects.

While thyroid dysfunction during PD-L1 inhibitor therapy correlates with efficacy in recurrent/metastatic nasopharyngeal carcinoma, the prognostic value of basal thyroid function remains unclear. This study investigated the relationship between baseline serum thyroid-stimulating hormone (TSH) and clinical outcomes. We conducted a multicenter, retrospective analysis of 153 recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) patients from a prospective phase 2 trial of the PD-L1 inhibitor KL-A167. Patients were stratified by baseline TSH levels. Multivariate Cox and logistic regression models were used to analyze Progression-Free Survival (PFS), Overall Survival (OS), and Objective Response Rate (ORR). High basal TSH (n = 58) was independently associated with significantly prolonged OS (HR 0.56, 95% CI: 0.36-0.88; p = 0.011) and PFS (HR 0.60, 95% CI: 0.41-0.87; p = 0.008) compared to the Low/Normal TSH group (n = 95). Although ORR was numerically higher in the High TSH group (27.6% vs. 17.9%), the difference was not statistically significant (p = 0.23). Subgroup analyses indicated consistent benefits across most clinical strata. Thyroid immune-related adverse events occurred in 32/153 (20.9%), similarly between groups (20.7% vs 21.1%, p = 0.957), and were not significantly associated with either OS (HR 0.65, 95% CI: 0.38-1.11, p = 0.117) or PFS (HR 0.88, 95% CI: 0.54-1.44, p = 0.613) by time-varying Cox regression. Elevated basal TSH levels are independently associated with improved survival in R/M NPC patients receiving KL-A167. Baseline TSH may serve as a simple, non-invasive biomarker for risk stratification and personalizing immunotherapy in this population.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health challenge, exacerbated by prolonged treatment regimens, variable vaccine efficacy, and the emergence of drug-resistant strains. Beyond conventional pathogen-targeted antibiotics, increasing attention has focused on host-directed therapies (HDTs) that aim to enhance intrinsic immune mechanisms to improve disease control and treatment outcomes. Among these, autophagy, a conserved cellular process responsible for the degradation and recycling of damaged organelles, proteins, and intracellular pathogens, has emerged as a promising, yet complex, target in TB. Autophagy contributes to host defense by restricting intracellular M. tuberculosis survival, shaping innate and adaptive immune responses, and intersecting with antimicrobial effector pathways. However, the literature presents seemingly contradictory findings, with autophagy reported as both protective and insufficient, or even subverted, during infection. In the present Perspective, we critically examine these discrepancies and reconcile them by highlighting the influence of infection burden, disease stage, host cell type, and experimental context on autophagic outcomes. We further discuss how M. tuberculosis actively modulates autophagy to promote persistence and how the host counterbalances these strategies through interconnected immune pathways. Importantly, we position autophagy modulation within the broader framework of HDT for TB, critically evaluating pharmacological agents known to influence autophagic pathways, their potential therapeutic benefits, and their current limitations. We also address key translational challenges, including strain heterogeneity, cell-specific targeting, and drug delivery to infected macrophages. Finally, we outline future directions required to safely and effectively harness autophagy as an adjunctive strategy to shorten treatment duration and improve clinical outcomes in TB.

Bladder cancer (BCa) arises from the interaction between environmental exposures and the host’s immunity and microbiome. Once considered sterile, the urinary tract is now known to harbor a resident urinary microbiome (UM) that dynamically interacts with the immune system and is influenced by systemic immunomodulatory effects of the gut microbiome (GM) brought on by the emerging gut–bladder axis. Accumulating evidence links alterations in UM and GM leading to BCa development, progression, and recurrence. Loss of protective taxa (e.g., Lactobacillus, Bifidobacterium and Ruminococcus) and enrichment of pro-inflammatory or genotoxic bacteria (e.g., Fusobacterium, Acinetobacter, Prevotella and Enterobacteriaceae) are associated with immune evasion and systemic inflammation. Microbial metabolites, especially short-chain fatty acids (SCFAs), play a key role in shaping tumor immunity and show diagnostic and prognostic potential, with specific microbial signatures correlating with recurrence risk, survival, and treatment response. Therapeutically, growing evidence suggests that microbiome composition influences immunotherapy response, highlighting opportunities for microbiome-based interventions. This review aims to summarize the rationale to implement microbial modulation strategies (e.g., dietary modulation, probiotics, fecal microbiota transplantation (FMT), and emerging synbiotic or postbiotic approaches) while addressing their current limitations and future requirements in order to develop microbiome-guided therapies, diagnostics and prognostic tools for BCa.

Microplastics (MPs) are ubiquitous marine pollutants whose ecological impacts can be modulated by temperature. Temperature regulates copepod physiological responses in marine environments. Copepods can show stress responses at deviations from the optimal temperature range, particularly during early life stages. Naupliar stages are more sensitive to environmental stressors. This developmental stage can present population-level vulnerability. This study aimed to investigate the effects of MPs, temperature, and their interaction on the survival and development of Acartia hudsonica nauplii. This study investigated survival and development under nine experimental conditions via combining three MP concentrations (0, 100, and 10,000 μg/L) with three temperatures (15, 20, and 25 °C). The survival rate differed significantly among temperature treatments. The differences between MP exposure treatments were significant in terms of survival rate only at 15 °C. Stage-specific and cumulative developmental times were shortest at 20 °C. The final naupliar stage (NVI) attainment rate was significantly affected by both temperature and MP concentration. These results indicate that temperature is the dominant stressor for the naupliar stages of A. hudsonica. The effect of MPs was modulated by temperature, as the effect decreased under high-temperature conditions. Therefore, the ecological effects of MPs should be evaluated in terms of considering their interactions with temperature in aquatic environments.

Joint modeling of binary and survival outcomes has emerged as a powerful statistical approach for analyzing correlated longitudinal and time-to-event data, particularly in clinical and epidemiological research. This study develops and evaluates a joint model for binary and survival responses with a shared covariance structure, addressing the limitations of traditional separate modeling approaches. The shared covariance structure enables efficient estimation of correlated outcomes, enhancing predictive accuracy and interpretability in clustered data settings. The study’s objective was to evaluate the performance of the joint model of binary and survival response with the shared covariance structure through simulation studies. Maximum likelihood estimation and Newton-Raphson iterative optimization were employed for parameter estimation, while simulation scenarios assessed bias, root mean square error, empirical standard errors, asymptotic standard error and coverage probabilities. The practical application of the model can be used to identify factors associated with Antiretroviral Therapy (ART) interruption and viral loads suppression. These health outcomes require robust statistical models capable of jointly analyzing binary treatment adherence indicators and survival outcomes which is the motivation of this work. Findings indicate that the joint model performs efficiently, providing unbiased and consistent parameter estimates. The model offers methodological and practical contributions, particularly for informing clinical interventions, improving ART adherence strategies, and shaping HIV policy and programmatic responses. Received: January 24, 2026Revised: March 11, 2026Accepted: March 23, 2026

The role of combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) in advanced hepatocellular carcinoma (HCC) remains unclear. We aimed to evaluate the efficacy and safety of RT plus ICI compared to ICI alone. We systematically searched PubMed, Web of Science, and Cochrane CENTRAL from inception to April 2025. Eligible studies were clinical trials or retrospective cohorts comparing RT+ICI with ICI alone in patients with advanced HCC. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). Risk of bias was assessed using ROBINS-I. Data were synthesized using a random-effects meta-analysis. Eight studies comprising 392 patients were included. RT+ICI was associated with improved outcomes: OS (62.8% vs. 45%), PFS (25.4% vs. 3.6%), ORR (51.1% vs. 27.6%), and DCR (83.1% vs. 60.6%) compared with ICI alone. AEs were more frequent with combination therapy (76.2% vs. 61%). Heterogeneity was moderate to high across several outcomes, and all included studies were retrospective. RT combined with ICIs shows promising improvements in survival and tumor response compared to ICI alone in advanced HCC, albeit with increased toxicity. Large randomized trials are needed to confirm efficacy, optimize RT regimens, and identify patients most likely to benefit.

Total-body irradiation (TBI) and partial-body irradiation (PBI) mouse models have been used for many years to develop safe and effective medical countermeasures (MCMs) against the acute radiation syndrome (ARS). ARS MCM development will benefit from a demonstration of the impact on survival from (a) the handling stress associated with repeat dose administrations, and (b) radiation beam quality with additional filtering of the orthovoltage X-ray beam, which we provide here. An open source "R" statistical tool is also provided to aid in generating dose response relationships (DRR) for establishing institutional lethality profiles. Compiled results from 27 TBI and 28 PBI studies in C57BL/6J male and female mice show the impact of the number of vehicle dose administrations and beam hardening on survival. For dose administration frequency, irradiated, non-dosed groups were compared with groups receiving increasing numbers of vehicle doses. Linear probit plots and lethality estimates were generated for the Thoraeus filter (tin, copper and aluminum) with and without 5 days of twice daily (5 × BID) dosing and for the aluminum filter without vehicle administration. A Wald test compared the slopes and intercepts of the probit estimates to assess differences in estimated lethality. Log-rank tests were used to determine the impact of vehicle administrations on observed lethality. A statistically significant reduction in survival was observed with increasing numbers of vehicle doses in the TBI model and for females in the PBI model using aluminum filtration. Repeated vehicle administrations (5× BID) also resulted in lower survival than in non-dosed males and females with the Thoraeus filter. Probit estimates of lethality when comparing non-dosed and 5× BID dosed groups indicate lower radiation doses were needed to achieve lethality in the 5× BID dosed groups, which were statistically significant in most log rank tests. When comparing the impact of filtration on survival, there was a statistically significant difference in intercepts for the estimated lethality values for each filter type, and the hardened Thoraeus-filtered beam required nearly 2 Gy of additional radiation dose to achieve the same survival as the aluminum filter. Lastly, our freely available "R" tool accurately generated probit estimates and confidence intervals (CI) when compared with estimates and CIs generated by a certified statistician using the STATA STS statistical package. Our results show that handling stress should be taken into consideration in designing ARS MCM development studies. Beam hardening with the removal of the low-energy photons and characteristic X rays resulted in a consistent shift in the DRRs for both males and females, with the "softer" aluminum beam resulting in greater mortality as compared to the Thoraeus-filtered beam. These findings will inform effective dose administration strategies in the design of ARS MCM development studies and aid in radiation dose harmonization efforts across the radiation community.

The resistance to treatment and the high chance of death associated with cancer still remain key problems that need breakthrough in biology and medicine. Ferroptosis is a newly discovered form of regulated cell death that is driven by iron and lipid peroxidation. Research reveals that ferroptosis plays an important role in tumour initiation, progression, and treatment. Furthermore, this process is mediated by distinct and dynamic molecular mechanisms. All of this information about the importance of ferroptosis will provide new targets and opportunities for cancer therapies. Cross-talk with other cell death pathways (e.g. apoptosis, necroptosis, autophagy) can modulate ferroptosis, and in some contexts these interactions may inhibit ferroptosis execution or activate adaptive survival responses in tumour cells. Ferroptosis has an initiation stage, a subsequent execution stage, and lastly a termination stage. Moreover, the sensitivity and response mechanisms of tumour cells to ferroptosis have significant differences in the early stage, progressive stage, metastatic stage, recurrent stage, etc. Due to the heterogeneous microenvironmental characteristics of hypoxic regions, immune-infiltrated regions and fibrotic regions in the spatial area of the tumour microenvironment (TME), these regions dynamically interact with ferroptosis. At present, strategies based on ferroptosis for tumour therapy have shown great promise. The use of advanced stimulus-responsive nanotechnology with classical ferroptosis inducers will enable the precise delivery and slow release of these inducers to enhance therapeutic efficacy and minimise damage to normal tissues. Nonetheless, several hurdles remain for clinical translation. A detailed examination of the complex regulatory networks in the TME, the development of scalable manufacturing processes for nanosystems, and the identification of non-invasive biomarkers to monitor the efficacy of ferroptosis are critical breakthrough points in the translation of ferroptosis-based therapy from bench to bedside.

Nicotine facilitates the progression of Lung Adenocarcinoma (LUAD) by activating signaling pathways and remodeling the Tumor Microenvironment (TME). However, the molecular classification based on nicotine response spectrum and its clinical relevance remained unclear. We retrieved 52 nicotine response-related genes from the MSigDB database and analyzed RNA-seq data obtained from TCGA-LUAD and GSE31210 cohorts. Distinct molecular subtypes were identified by consensus clustering analysis. Next, differential gene expression analysis and functional enrichment analysis were conducted. A prognostic RiskScore model was constructed using LASSO and Cox regression, and validated via Kaplan-Meier and ROC analyses. Immune microenvironment features were assessed using CIBERSORT, ESTIMATE, and TIDE algorithms, while pathway associations were explored via GSEA. Two distinct molecular subtypes (C1 and C2) were identified, with C1 showing a more favorable prognosis. A RiskScore model developed based on five genes (KCNK1, CPS1, ABCC2, TCN1, PGC) can effectively stratify patients into high- and low-risk groups, with the high-risk group exhibiting a worse overall survival (OS) (p < 0.001). The two risk groups demonstrated distinct enrichment of pathways. Notably, the low-risk group exhibited increased infiltration of regulatory T cells and M2 macrophages and lower TIDE scores, suggesting better immunotherapy response. A nomogram combining RiskScore and AJCC stage demonstrated strong predictive accuracy. This study was the first to classify nicotine response-related molecular subtypes for LUAD, offering novel insights into nicotine-driven progression of LUAD. The RiskScore and nomogram may aid in risk stratification and personalized management, though further experimental validation is still needed. This study established a nicotine response-related prognostic model for LUAD, revealing its utility in predicting survival and immune therapy responses. Our findings provided novel biomarkers for personalized precision medicine in LUAD.

Cancer-associated fibroblasts (CAFs) are central to the pancreatic ductal adenocarcinoma (PDAC) microenvironment, promoting tumor progression and therapeutic resistance. However, the expression landscape of CAF membrane proteins in PDAC remains poorly defined. We integrated scRNA-seq (n = 33; 87,949 cells), spatial transcriptomics (n = 2; 7,011 spots), and bulk RNA-seq (n = 7; 642 samples) to systematically identify PDAC-specific CAF membrane genes. A LASSO-based Cox model was developed to construct a prognostic signature, PaFMS, and evaluated through multi-cohort validation. Functional enrichment, immune infiltration, drug sensitivity, and immunotherapy response analyses were further conducted. Validation was performed using multiple database-driven analyses. We identified a PDAC-enriched myoCAF-c1 cluster closely associated with epithelial-mesenchymal transition (EMT) and angiogenesis. From this cluster, 33 candidate CAF membrane genes were defined, whose protein-protein interactions were predominantly linked to extracellular matrix organization and collagen remodeling, and spatially colocalized with myoCAF-c1 and EMT regions. An 11-gene prognostic signature, PaFMS that robustly stratified patients across six independent cohorts, achieving high predictive accuracy for overall survival. High-risk patients exhibited proliferative signaling activation, immune suppression, and reduced T/B-cell infiltration. PaFMS was associated with responses to 33 anticancer agents and predicted enhanced benefit from anti-PD-L1 immunotherapy in the low-risk group. Multi-cohort validation confirmed the expression specificity of PaFMS genes, including PLAU, TMEM158, and TRIM59. Together, these findings reveal that myoCAF-c1 promotes angiogenesis and tumor progression, and establish PaFMS as a robust CAF membrane-based prognostic model in PDAC with potential utility for precision prognosis and therapeutic decision-making. KEY MESSAGES: Integrated single-cell, spatial, and bulk RNA-seq analyses identified PDAC-specific CAF membrane genes. Discovered a PDAC-enriched myoCAF-c1 subtype linked to EMT and angiogenesis. Developed an 11-gene CAF membrane-based prognostic model (PaFMS) validated across six cohorts. PaFMS predicts patient survival, drug sensitivity, and immunotherapy response in PDAC.

In this paper, we investigated the behavior of a natural, low-cost, and biocompatible clay, focusing on its potential use in biomedical applications, with an eye on its ability as a material that inhibits or promotes bacterial growth. The interaction of raw and acid-treated halloysite (HT) with Gram-positive and Gram-negative bacteria representative of different environments, such as the human body, food, air, soil, water, and marine environments, was explored. Environmental strains of Escherichia coli, Acinetobacter baumannii, Lactococcus lactis, and Staphylococcus aureus were isolated and examined for their responses to HT and its derivatives after acid treatment, including acidic HT (HT (H+)), precipitate (P), and supernatant (S). HT before and after acid treatment did not have any effect on the growth of this subset of opportunistic bacteria that mainly inhabit air and water. Bacteria of marine origin (Vibrio spp and Halomonas spp) were isolated from the body lesions of a spotted diseased sea urchin, Paracentrotus lividus. These species were highly sensitive to the material tested, showing an opposite survival response under treatment with the raw or the acidic HT forms. Materials were fully characterized by scanning and transmission electron microscopy (SEM and TEM) and X-ray photoelectron spectroscopy (XPS). The responses of marine bacteria exposed to HT and its derivatives were dependent on their structural and physicochemical properties, as elucidated here.

Abstract Fructooligosaccharides (FOS) are prebiotic substances that have been used in formulated feed, but little is known about their use in enrichment of live feeds. This experiment aimed to determine the best dosage of FOS enrichment on Artemia sp. for the climbing perch ( Anabas testudineus ) larvae nursery. Three treatments were analyzed based on different FOS enrichment dosages, namely A (0 mL), B (1.3 mL), and C (1.5 mL), with three replications each. The climbing perch larvae were stocked into nine rearing containers at a density of 15 larvae container −1 . After fifteen days, length growth and survival rate responses differed significantly amongst dietary groups. Treatment A and B had the same length growth (0.56 cm), which was significantly different (p&lt;0.05) from C (0.86 cm) as the largest length growth. While treatment A had the highest survival rate (82%), which was similar to B (81%). However, weight growth did not show any significant differences between treatments. Based on this, 1.3 mL FOS enrichment resulted in the most favorable responses in larval growth and survival.

Opaganib is a first-in-class oral sphingolipid metabolism inhibitor that inhibits sphingosinekinase 2 (SphK2) and dihydroceramide desaturase (DES) and that has a demonstrated safety and preliminary anti-cancer activity signal in a Phase I study. In this phase II trial, patients with metastatic castration-resistant prostate cancer who had disease progression on novel hormonal agents (NHAs) abiraterone or enzalutamide were enrolled and treated with opaganib while continuing their NHA. After safety lead-in cohorts, the trial enrolled cohort 2 (abiraterone + opaganib 500 mg Q 12 h) and cohort 3 (enzalutamide + opaganib 500 mg Q 12 h). The primary efficacy endpoint was the proportion of patients with disease control at Day 113. The postulated disease control rate was 10%. Secondary efficacy endpoints include prostate-specific antigen (PSA) progression-free survival (PSA-PFS) and PSA response rates. The primary safety endpoint was the incidence of adverse events (AEs). The disease control rates were 15% (95% CI = 4%-35%, 4 of 26 patients) in cohort 2 and 9% (95% CI = 2%-24%, 3 of 34 patients) in cohort 3. The median PSA-PFS was 56 days (95% CI = 35-112 days) in cohort 2 and 55 days (95% CI = 35-56 days) in cohort 3. The most common AEs of grade 3 or higher were hypertension (8%) and musculoskeletal AEs (8%) in cohort 2 and grade 3 anemia (18%) in cohort 3. The trial did not meet its primary objective of demonstrating 30% disease control at 113 days. However, subjects who experienced a PSA response or stabilization warrant further exploration for biomarkers of response. ClinicalTrials.gov number: NCT04207255.

His Pacing vs Biventricular Pacing for Cardiac Resynchronization Therapy: Long-Term Follow-Up From the His-Alternative I Trial.

A Metabolism-Driven Prognostic Model and PSMD14-SP1-GYS1 Axis Reveal Therapeutic Vulnerabilities in Melanoma.

Patients with pre-existing autoimmune disease (PAD) are often excluded from immune checkpoint inhibitor (ICI) clinical trials in thoracic oncology, creating uncertainty regarding their real-world safety and effectiveness in this population. We conducted a retrospective matched cohort study to evaluate clinical outcomes and treatment-related toxicities of ICIs in lung cancer patients with PAD compared to matched controls without PAD. Using the provincial IMPACT-MB database, lung cancer patients with PAD were matched to controls by age and sex. Demographic, disease, and treatment data were extracted from medical records. Primary outcomes included toxicity, time to treatment failure (TTF), overall survival (OS), and objective response rate (ORR). Associations were determined using Cox and logistic regression modeling. Of 1871 ICI-treated patients, 69 with PAD were identified and matched to 139 controls. Rates of immune-related adverse events were similar between PAD and control groups (45% vs. 38%, P=0.4, OR 1.29, 95% CI 0.72-2.32). In the PAD group, 20% experienced a disease flare. PAD was associated with more frequent ICI treatment holds and initiation of biologic therapy. No significant association was observed between PAD status and OS (HR 0.92, 95% CI 0.65-1.30, p=0.63) or TTF (HR 0.75, 95% CI 0.54-1.05, p=0.09). In this real-world retrospective matched cohort study, PAD was not associated with increased toxicity or inferior oncologic outcomes. One in five patients with PAD experienced autoimmune flare, underscoring the need for close monitoring. These findings support ICI use in carefully selected lung cancer patients with PAD.

Findings have linked GNAS-activating mutations, frequent in appendiceal adenocarcinoma (AA), with improved overall survival but poor response to chemotherapy. The authors hypothesized that GNAS-activating mutations are associated with differential outcomes in AA treated with chemotherapy. Patients seen at the authors' center between 2013 and 2023 who received systemic chemotherapy for metastatic/recurrent AA were identified. The primary outcome was disease event-free survival (EFS), defined as time from start of chemotherapy (5-fluorouracil/capecitabine based) to earliest disease event, including death, clinical/radiographic recurrence, or progression. Study outcomes were assessed using Kaplan-Meier estimations and Cox proportional hazards regression. The study included 48 patients. In 18 (37.5 %) of the 48 patients, GNAS-activating mutations were seen. Patients with GNAS mutations were more likely to have lower grades of disease (p = 0.003), with lower proportions of lymphovascular invasion (p = 0.005) and perineural invasion (p = 0.03), but a higher median peritoneal carcinomatosis index (p = 0.03). In the multivariable analysis, GNAS mutations (10.7 months [95 % confidence interval {CI}, 7.1-19.2] vs 20.3 months [95 % CI, 18.6-29.4; adjusted HR {aHR}, 3.75; 95 % CI, 1.84-7.63] p < 0.001) and metachronous metastases (aHR, 5.14; 95 % CI, 2.08-12.69; p < 0.001) were associated with worse EFS. Both CC0-1 resection (aHR, 0.12; 95 % CI, 0.05-0.28; p < 0.001) and CC2-3 resection (aHR, 0.28; 95 % CI, 0.10-0.81; p = 0.02) were associated with prolonged EFS. There was no significant difference in the OS from the date of metastases diagnosis between the GNASmt and GNASwt patients (HR, 0.68; 95 % CI, 0.31-1.47; p = 0.33). With systemic chemotherapy, GNAS-mutated metastatic/recurrent AAs have worse EFS despite less frequent high-risk features. Routine somatic mutation-testing of patients with AA should be considered for prognostication and possibly therapeutic decision-making.