Uncovering further diversity of Ochoterenatrema Caballero, 1943 (Digenea: Lecithodendriidae) in South American bats.

Ochoterenatrema Caballero, 1943 is a genus of lecithodendriid digeneans that prior to this study included 8 species parasitic in bats in the Western Hemisphere. Species of Ochoterenatrema possess a unique morphological feature in form of the pseudogonotyl on the sinistral side of the ventral sucker. In this study, we describe 2 new species of Ochoterenatrema from bats in Ecuador. The new species are readily differentiated from their congeners by a combination of morphological characters, including the distribution of vitelline follicles, length of oesophagus, sucker ratio and the body shape, among other features. We have generated partial nuclear 28S rDNA and mitochondrial cox1 gene DNA sequences from both new species. The newly obtained sequences were used to differentiate among species and study the phylogenetic interrelationships among Ochoterenatrema spp. The internal topology of the clade was weakly supported, although the cox1 tree was much better resolved than the 28S tree. Comparison of sequences revealed 0-1.2% interspecific divergence in 28S and 3.3-20.5% interspecific divergence in cox1 among Ochoterenatrema spp. The new findings demonstrate that bats in South America likely harbor multiple additional undescribed species of Ochoterenatrema. More extensive sampling from broader geographic and host ranges, especially in North America, should allow for a better understanding of the evolution of host associations and morphological traits of this lineage of lecithodendriid digeneans.

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study.

BACKGROUND: The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers. METHODS: Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review. RESULTS: A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9-54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%-13.5%), and median duration of response was 18.4 (range, 4.2-47.2+) months. ORR was 8.7% (95% CI, 2.4%-20.8%) among patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 (n = 46) and 5.7% (95% CI, 1.2%-15.7%) among patients with PD-L1 CPS <1 (n = 53). Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9-6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grade 3-5, 14.6%). CONCLUSIONS: Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These results provide evidence of modest antitumor activity in this setting regardless of tumor PD-L1 expression. Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker-driven patient selection or combination of immune checkpoint inhibitors with other agents, in order to achieve higher response rates than observed in this study.

Leveraging natural history biorepositories as a global, decentralized, pathogen surveillance network.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic reveals a major gap in global biosecurity infrastructure: a lack of publicly available biological samples representative across space, time, and taxonomic diversity. The shortfall, in this case for vertebrates, prevents accurate and rapid identification and monitoring of emerging pathogens and their reservoir host(s) and precludes extended investigation of ecological, evolutionary, and environmental associations that lead to human infection or spillover. Natural history museum biorepositories form the backbone of a critically needed, decentralized, global network for zoonotic pathogen surveillance, yet this infrastructure remains marginally developed, underutilized, underfunded, and disconnected from public health initiatives. Proactive detection and mitigation for emerging infectious diseases (EIDs) requires expanded biodiversity infrastructure and training (particularly in biodiverse and lower income countries) and new communication pipelines that connect biorepositories and biomedical communities. To this end, we highlight a novel adaptation of Project ECHO's virtual community of practice model: Museums and Emerging Pathogens in the Americas (MEPA). MEPA is a virtual network aimed at fostering communication, coordination, and collaborative problem-solving among pathogen researchers, public health officials, and biorepositories in the Americas. MEPA now acts as a model of effective international, interdisciplinary collaboration that can and should be replicated in other biodiversity hotspots. We encourage deposition of wildlife specimens and associated data with public biorepositories, regardless of original collection purpose, and urge biorepositories to embrace new specimen sources, types, and uses to maximize strategic growth and utility for EID research. Taxonomically, geographically, and temporally deep biorepository archives serve as the foundation of a proactive and increasingly predictive approach to zoonotic spillover, risk assessment, and threat mitigation.

Comparison of clinical outcomes among cancer patients treated in and out of clinical trials.

BACKGROUND: It is unknown if participation in a cancer clinical trial confers clinical benefits to patients. There is not enough scientific evidence in this regard and the available publications are scarce and provide ambiguous and limited information. OBJECTIVE: Compare overall and progression-free survival and response to treatment among those who met the eligibility criteria and accepted to participate and those who refused to participate in cancer clinical trials. METHODS: An observational cross-sectional study with an analytical component was carried out, which included patients diagnosed with cancer who participated in phase III clinical trials and patients who, being eligible, refused to participate. The patients were cared for at the National Institute of Cancerology in Colombia between 2019 and 2022. Analysis of differences in proportions and means of sociodemographic and clinical variables was included; overall survival and progression-free survival time were described and the survival curves between groups were compared. Variables related to survival were determined using a Cox regression model and Hazard Ratios were calculated. RESULTS: 62 women and 50 men were included. In the women group, we found a statistical association between clinical trial participation and non-serious events adverse and progression. The stable disease and complete response were higher in participants than in refusers. The median progression-free survival for refusers was 7,4 m meantime for participants the median was not reached and 74,1% remained without progression at 28 months. In the men group, we also found a statistical association between clinical trial participation and the occurrence of non-serious events adverse meanwhile there were no significant differences in overall response, progression, and death, even though the proportion of progression was minor in participants 20% vs. refusers 26% respectively. The median survival was not reached for any group, even though in the participants group 55,2% were still alive at month 20 and in the refusers group still alive at 56,8% at month 45. Covariables included for the multivariate Cox regression only age had a statistical association with overall survival in the women's group and the men group any covariables reached statistical association. CONCLUSION: It can be considered that participation in clinical trials could give participants a better response to treatment, without increasing the probability of death and with the probability of decreasing the progression of the disease. Participation in trials could improve the outcomes of clinical response rates, no change in overall survival, and progression-free.

Molecular phylogenetic analysis of Neodiplostomum and Fibricola (Digenea, Diplostomidae) does not support host-based systematics.

Fibricola and Neodiplostomum are diplostomid genera with very similar morphology that are currently separated based on their definitive hosts. Fibricola spp. are normally found in mammals, while Neodiplostomum spp. typically parasitize birds. Previously, no DNA sequence data was available for any member of Fibricola. We generated nuclear ribosomal and mtDNA sequences of Fibricola cratera (type-species), Fibricola lucidum and 6 species of Neodiplostomum. DNA sequences were used to examine phylogenetic interrelationships among Fibricola and Neodiplostomum and re-evaluate their systematics. Molecular phylogenies and morphological study suggest that Fibricola should be considered a junior synonym of Neodiplostomum. Therefore, we synonymize the two genera and transfer all members of Fibricola into Neodiplostomum. Specimens morphologically identified as Neodiplostomum cratera belonged to 3 distinct phylogenetic clades based on mitochondrial data. One of those clades also included sequences of specimens identified morphologically as Neodiplostomum lucidum. Further study is necessary to resolve the situation regarding the morphology of N. cratera. Our results demonstrated that some DNA sequences of N. americanum available in GenBank originate from misidentified Neodiplostomum banghami. Molecular phylogentic data revealed at least 2 independent host-switching events between avian and mammalian hosts in the evolutionary history of Neodiplostomum; however, the directionality of these host-switching events remains unclear.

Bladder Cancer Extracellular Vesicles Elicit a CD8 T Cell-Mediated Antitumor Immunity.

Tumor-derived extracellular vesicles (TEVs) play crucial roles in mediating immune responses, as they carry and present functional MHC-peptide complexes that enable them to modulate antigen-specific CD8+ T-cell responses. However, the therapeutic potential and immunogenicity of TEV-based therapies against bladder cancer (BC) have not yet been tested. Here, we demonstrated that priming with immunogenic Extracellular Vesicles (EVs) derived from murine MB49 BC cells was sufficient to prevent MB49 tumor growth in mice. Importantly, antibody-mediated CD8+ T-cell depletion diminished the protective effect of MB49 EVs, suggesting that MB49 EVs elicit cytotoxic CD8+ T-cell-mediated protection against MB49 tumor growth. Such antitumor activity may be augmented by TEV-enhanced immune cell infiltration into the tumors. Interestingly, MB49 EV priming was unable to completely prevent, but significantly delayed, unrelated syngeneic murine colon MC-38 tumor growth. Cytokine array analyses revealed that MB49 EVs were enriched with pro-inflammatory factors that might contribute to increasing tumor-infiltrating immune cells in EV-primed MC-38 tumors. These results support the potential application of TEVs in personalized medicine, and open new avenues for the development of adjuvant therapies based on patient-derived EVs aimed at preventing disease progression.

Interrelationships of Anenterotrema (Digenea: Dicrocoeliidae) from Neotropical bats (Mammalia: Chiroptera) with description of a new species from Molossus molossus in Brazil.

Anenterotrema is a small genus of dicrocoeliids (Digenea: Dicrocoeliidae) containing 6 species found in Neotropical bats. Members of this genus are characterized by the lack of digestive system organs and, unlike the majority of dicrocoeliids, parasitize the intestine of their definitive hosts. In this study, we have morphologically examined newly collected specimens belonging to four species of Anenterotrema from Brazil, Ecuador, and Panama. Based on the data in original descriptions and our analysis of quality new specimens, we resurrected Anenterotrema freitasi, previously synonymized with A. eduardocaballeroi. We also described a new species of Anenterotrema from Molossus molossus in the Brazilian Amazon. The new species differs from congeners in several morphological features, most prominently in the size and structure of its highly muscular, protuberant ventral sucker. It is also characterized by the lack of the semi-circular thickening of the tegument around the oral sucker typical for some members of the genus. We used partial DNA sequences of the large ribosomal subunit gene (28S) and mitochondrial cytochrome c oxidase subunit 1 gene (cox1) to test the monophyly of Anenterotrema, and study the interrelationships and determine the inter- and intraspecific variation of three Anenterotrema spp. collected from different bat species in Brazil, Ecuador and Panama.

Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells.

BACKGROUND: Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application. METHODS: Here we compared two microfluidic devices for the recovery of circulating melanoma cells. The presence of CTCs in 43 blood samples from patients with metastatic melanoma was evaluated using a combination of immunocytochemistry and transcript analyses of five genes by RT-PCR and 19 genes by droplet digital PCR (ddPCR), whereby a CTC score was calculated. Circulating tumour DNA (ctDNA) from the same patient blood sample, was assessed by ddPCR targeting tumour-specific mutations. RESULTS: Our analysis revealed an extraordinary heterogeneity amongst melanoma CTCs, with multiple non-overlapping subpopulations. CTC detection using our multimarker approach was associated with shorter overall and progression-free survival. Finally, we found that CTC scores correlated with plasma ctDNA concentrations and had similar pharmacodynamic changes upon treatment initiation. CONCLUSIONS: Despite the high phenotypic and molecular heterogeneity of melanoma CTCs, multimarker derived CTC scores could serve as viable tools for prognostication and treatment response monitoring in patients with metastatic melanoma.

Development of chronic pain in males with traumatic spinal cord injury: role of circulating levels of the chemokines CCL2 and CXCL10 in subacute stage.

STUDY DESIGN: Longitudinal study. OBJECTIVES: To assess the impact of spinal cord injury (SCI) on circulating levels of chemokines (CCL2 and CXCL10) and its relation with pain development. SETTING: National Hospital for SCI patients. METHODS: We longitudinally studied changes in the circulating levels of CCL2 and CXCL10 in 27 male patients with complete SCI who were evaluated in the early subacute phase and indeed 3 and 6 months after injury measuring at each time-point serum levels of CCL2 and CXCL10. Patients were telephonically interviewed about pain 1 year after SCI. RESULTS: In the early subacute phase, patients with pain showed higher CXCL10 and similar CCL2 levels as opposed to those without pain. Moreover, CCL2 concentrations were positively associated with pain intensity. The results obtained by analysing the temporal profile of the chemokines suggested that CXCL10 was inclined to decrease over time, while CCL2 increased over time. CONCLUSION: The results of this preliminary study, the first performed in humans with traumatic SCI, suggest a link between changes in the circulating chemokine profile and pain development in subacute SCI stage as well as with severity in a more chronic stage. Large series studies will evaluate whether the circulating chemokine status can be useful as a biomarker for assessing the patients' risk for pain development.

A simple model for estimating changes in rainfall erosivity caused by variations in rainfall patterns.

A major challenge when coupling soil loss models with precipitation forecasts from Global Circulation Models (GCMs) is that their time resolutions do not generally agree. Precipitation forecasts from GCM must be scaled down; however, the distribution of the rainfall intensity, which can affect soil loss as much as precipitation amounts, is usually not considered in this process. Therefore, the objective of this study was to develop a statistical equation for computing event-based rainfall erosivity under changing precipitation patterns using the least amount of information possible. For this purpose, an empirical equation for predicting event-based rainfall erosivity was developed using the product of the total precipitation P and the maximum 0.5-h rainfall intensity, I0.5. This equation was calibrated using measured precipitation data from 28 sites in Central Chile and then tested with simulated data with different rainfall patterns from the CLIGEN (CLImate GENerator) weather generator. More than 53,000 rainfall events were analyzed, where the equation consistently provided R2 values of 0.99 for every dataset used, revealing its robustness when used in potential climate change scenarios in the study site. However, because computing I0.5 requires estimating precipitation at a high time resolution, the relationship was recalibrated and tested using 1 through 24-h maximum rainfall intensities. Using these intensities, the equation provided erosivity estimates with R2 ranging from 0.78 to 0.99, where better results were obtained as the resolution of the data increased. This study provides the methodology for building and testing the proposed equation and discusses its advantages and limitations.

Extracellular Vesicles in Bladder Cancer: Biomarkers and Beyond.

Tumor-derived extracellular vesicles (TEVs) are membrane-bound, nanosized vesicles released by cancer cells and taken up by cells in the tumor microenvironment to modulate the molecular makeup and behavior of recipient cells. In this report, we summarize the pivotal roles of TEVs involved in bladder cancer (BC) development, progression and treatment resistance through transferring their bioactive cargos, including proteins and nucleic acids. We also report on the molecular profiling of TEV cargos derived from urine and blood of BC patients as non-invasive disease biomarkers. The current hurdles in EV research and plausible solutions are discussed.

The GOA database: gene Ontology annotation updates for 2015.

The Gene Ontology Annotation (GOA) resource (http://www.ebi.ac.uk/GOA) provides evidence-based Gene Ontology (GO) annotations to proteins in the UniProt Knowledgebase (UniProtKB). Manual annotations provided by UniProt curators are supplemented by manual and automatic annotations from model organism databases and specialist annotation groups. GOA currently supplies 368 million GO annotations to almost 54 million proteins in more than 480,000 taxonomic groups. The resource now provides annotations to five times the number of proteins it did 4 years ago. As a member of the GO Consortium, we adhere to the most up-to-date Consortium-agreed annotation guidelines via the use of quality control checks that ensures that the GOA resource supplies high-quality functional information to proteins from a wide range of species. Annotations from GOA are freely available and are accessible through a powerful web browser as well as a variety of annotation file formats.

A New Method for Sensing Soil Water Content in Green Roofs Using Plant Microbial Fuel Cells.

Green roofs have many benefits, but in countries with semiarid climates the amount of water needed for irrigation is a limiting factor for their maintenance. The use of drought-tolerant plants such as Sedum species, reduces the water requirements in the dry season, but, even so, in semiarid environments these can reach up to 60 L m-2 per day. Continuous substrate/soil water content monitoring would facilitate the efficient use of this critical resource. In this context, the use of plant microbial fuel cells (PMFCs) emerges as a suitable and more sustainable alternative for monitoring water content in green roofs in semiarid climates. In this study, bench and pilot-scale experiments using seven Sedum species showed a positive relationship between current generation and water content in the substrate. PMFC reactors with higher water content (around 27% vs. 17.5% v/v) showed larger power density (114.6 and 82.3 µW m-2 vs. 32.5 µW m-2). Moreover, a correlation coefficient of 0.95 (±0.01) between current density and water content was observed. The results of this research represent the first effort of using PMFCs as low-cost water content biosensors for green roofs.

Active and legacy mining in an arid urban environment: challenges and perspectives for Copiapó, Northern Chile.

Urban expansion in areas of active and legacy mining imposes a sustainability challenge, especially in arid environments where cities compete for resources with agriculture and industry. The city of Copiapó, with 150,000 inhabitants in the Atacama Desert, reflects this challenge. More than 30 abandoned tailings from legacy mining are scattered throughout its urban and peri-urban area, which include an active copper smelter. Despite the public concern generated by the mining-related pollution, no geochemical information is currently available for Copiapó, particularly for metal concentration in environmental solid phases. A geochemical screening of soils (n = 42), street dusts (n = 71) and tailings (n = 68) was conducted in November 2014 and April 2015. Organic matter, pH and elemental composition measurements were taken. Notably, copper in soils (60-2120 mg/kg) and street dusts (110-10,200 mg/kg) consistently exceeded international guidelines for residential and industrial use, while a lower proportion of samples exceeded international guidelines for arsenic, zinc and lead. Metal enrichment occurred in residential, industrial and agricultural areas near tailings and the copper smelter. This first screening of metal contamination sets the basis for future risk assessments toward defining knowledge-based policies and urban planning. Challenges include developing: (1) adequate intervention guideline values; (2) appropriate geochemical background levels for key metals; (3) urban planning that considers contaminated areas; (4) cost-effective control strategies for abandoned tailings in water-scarce areas; and (5) scenarios and technologies for tailings reprocessing. Assessing urban geochemical risks is a critical endeavor for areas where extreme events triggered by climate change are likely, as the mud flooding that impacted Copiapó in late March 2015.

In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin's lymphoma (NHL).

BACKGROUND: The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin's lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis. RESULTS: Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL. CONCLUSIONS: The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.

High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to Non-Hodgkin's lymphoma.

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin's lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

Immune-Related Peripheral Neuropathy Associated with Immune Checkpoint Inhibitors: Case Report and Review of Literature.

Immune checkpoint inhibitors (ICIs) are a group of drugs that have improved outcomes for patients with various cancers. Generally considered safe and well tolerated, these drugs are occasionally linked to immune-mediated or immune-related adverse events. Among these, autoimmune neurological events are rare, displaying varying incidence rates across different studies. Peripheral neuropathy, although one of the more common neurological immune-related events, is at times underestimated. This case report highlights an adult patient diagnosed with metastatic intrahepatic cholangiocarcinoma. Initially, the patient underwent chemoimmunotherapy with gemcitabine, cisplatin, and durvalumab for eight cycles, achieving partial response without significant toxicity. Following this, the patient continued with maintenance monotherapy with durvalumab every 28 days. After completing six cycles of maintenance therapy, the patient suddenly experienced paresthesia and hypoesthesia in four limbs, accompanied by apraxia in the hands that was more pronounced on the right side. Additionally, the patient reported neuropathic pain in the right arm and encountered limitations in certain instrumental activities of daily living. Diagnostic studies, including laboratory and electrophysiological studies, combined with the clinical presentation, identified immune-related peripheral polyneuropathy. Durvalumab was suspended and prednisolone therapy was initiated, resulting in a rapid resolution of all neuropathic symptoms. In addition to the clinical case, this article reviews the literature on immunotherapy-associated peripheral neuropathy.

Cost-Effectiveness of Comprehensive Genomic Profiling in Patients With Non-Small Cell Lung Cancer for the Colombian Health System.

INTRODUCTION: The use of comprehensive genomic profiling (CGP) and target therapies is associated with substantial improvements in clinical outcomes among patients with non-small cell lung cancer (NSCLC). However, the costs of CGP may increase the financial pressures of NSCLC on health systems worldwide, especially in low- and middle-income countries. This study aimed to estimate the cost-effectiveness of CGP compared with current genomic tests in patients with NSCLC from the perspective of the Colombian Health System. METHODS: To estimate the costs and benefits of CGP and its comparators, we developed a 2-stage cohort model with a lifetime horizon. In the first stage, we made up a decision tree that calculated the probability of receiving each therapy as result of identifying a specific, actionable target. In the second stage, we developed a partitioned survival model that estimated the time spent at each health state. Incremental cost-effectiveness ratios were calculated for life-years (LYs) and quality-adjusted LYs gained. All costs were expressed in 2019 international dollars (INT$). RESULTS: CGP is associated with gains of 0.06 LYs and 0.04 quality-adjusted LYs compared with current genomic tests. Incremental cost-effectiveness ratios for CGP ranged from INT$861 to INT$7848, depending on the outcome and the comparator. Sensitivity analyses show that the cost-effectiveness decision was sensitive to prices of CGP above INT$7170 per test. These results are robust to most deterministic and probabilistic sensitivity analyses. CONCLUSIONS: CGP may be cost-effective in patients with NSCLC from the perspective of the Colombian Health System (societal willingness-to-pay threshold of INT$15 630 to INT$46 890).