المؤلفون: Baudin, Eric, Capdevila, Jaume, Hörsch, Dieter, Singh, Simron, Caplin, Martyn, Wolin, Edward M, Buikhuisen, Wienecke, Raderer, Markus, Dansin, Eric, Grohe, C., Ferone, D., Houchard, Aude, Truong Thanh, Xuan-Mai, Reidy-Lagunes, Diane

المصدر: Endocrine-Related Cancer ; ISSN 1351-0088 1479-6821

الوصف: Prospective data are lacking on early somatostatin analog (SSA) therapy in bronchopulmonary neuroendocrine tumors (BP-NETs; typical and atypical carcinoids [TCs and ACs]). SPINET (EudraCT: 2015-004992-62; NCT02683941) was a phase III, double-blind study of lanreotide autogel/depot (LAN; 120 mg every 28 days) plus best supportive care (BSC) versus placebo plus BSC, with an optional open label treatment phase (LAN plus BSC). Patients had metastatic/unresectable, somatostatin receptor (SSTR)-positive TCs or ACs. Recruitment was stopped early owing to slow accrual; eligible patients from the double-blind phase transitioned to open-label LAN. The adapted primary endpoint was progression free survival (PFS) during either phase for patients receiving LAN. Seventy-seven patients were randomized (LAN, n=51 [TCs, n=29; ACs, n=22]; placebo, n=26 [TCs, n=16; ACs, n=10). Median (95% confidence interval [CI]) PFS during double-blind and OL phases in patients receiving LAN was 16.6 (11.3; 21.9) months overall (primary endpoint), 21.9 (12.8, not calculable [NC]) months in TCs and 13.8 (5.4; 16.6) months in ACs. During double-blind treatment, median (95% CI) PFS was 16.6 (11.3; 21.9) months for LAN versus 13.6 (8.3; NC) months for placebo (not significant); corresponding values were 21.9 (13.8; NC) and 13.9 (13.4; NC) months, respectively, in TCs and 13.8 (5.4; 16.6) and 11.0 (2.8; 16.9) months, respectively, in ACs. Patients’ quality of life did not deteriorate and LAN was well tolerated. Although recruitment stopped early and the predefined sample size was not met, SPINET is the largest prospective study to date of SSA therapy in SSTR positive TCs and ACs and suggests clinical benefit in TCs.

الإتاحة: https://doi.org/10.1530/erc-23-0337Test
https://erc.bioscientifica.com/view/journals/erc/aop/erc-23-0337/erc-23-0337.xmlTest
https://erc.bioscientifica.com/downloadpdf/journals/erc/aop/erc-23-0337/erc-23-0337.xmlTest

المؤلفون: La-Salvia, Anna, Lens-Pardo, Alberto, López-López, Ángel, Carretero-Puche, Carlos, Capdevila, Jaume, Benavent, Marta, Jiménez-Fonseca, Paula, Castellano, Daniel, Alonso, Teresa, Teule, Alexandre, Custodio, Ana, Tafuto, Salvatore, La Casta, Adelaida, Spada, Francesca, López-Gonzalvez, Ángeles, Gil-Calderón, Beatriz, Espinosa-Olarte, Paula, Barbas, Coral, García-Carbonero, Rocío, Soldevilla, Beatriz

المساهمون: Pfizer, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, Instituto de Salud Carlos III, European Commission, Asociación Española Contra el Cáncer, Benavent, Marta, Soldevilla, Beatriz, Consejo Superior de Investigaciones Científicas https://ror.org/02gfc7t72Test

مصطلحات موضوعية: Neuroendocrine tumors, Metabolomics, Plasma metabolites, Prognostic biomarker

الوصف: © The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0Test/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com ; [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 ...

وصف الملف: application/pdf

العلاقة: #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095166-B-I00/ES/MAS ALLA DE LA HUELLA METABOLICA: HACIA LA IDENTIFICACION EXHAUSTIVA EN METABOLOMICA/; B2017/BMD-3751/NOVELREN-CM; PEJD-2019-PRE/BMD-17058; PEJD-2016-PRE/BMD-2666; PEJD-2017-PRE/BMD-4981; Publisher's version; The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1093/ejendo/lvad160Test; https://doi.org/10.1093/ejendo/lvad160Test; Sí; European Journal of Endocrinology 190(1): 62-74 (2024); http://hdl.handle.net/10261/360512Test

الإتاحة: https://doi.org/10.1093/ejendo/lvad160Test
http://hdl.handle.net/10261/360512Test

المؤلفون: Brose, Marcia S, Capdevila, Jaume, Elisei, Rossella, Bastholt, Lars, Führer-Sakel, Dagmar, Leboulleux, Sophie, Sugitani, Iwao, Taylor, Matthew H, Wang, Zhuoying, Wirth, Lori J, Worden, Francis P, Bernard, John, Caferra, Paolo, Colzani, Raffaella M, Liu, Shiguang, Schlumberger, Martin

المصدر: Endocrine-Related Cancer ; volume 31, issue 8 ; ISSN 1351-0088 1479-6821

الوصف: The VERIFY study aimed to determine the efficacy of vandetanib in patients with differentiated thyroid cancer (DTC) that is either locally advanced or metastatic and refractory to radioiodine (RAI) therapy. Specifically, VERIFY is a randomized, double-blind, multicenter phase III trial aimed to determine the efficacy and safety of vandetanib in tyrosine kinase inhibitor-naive patients with locally advanced or metastatic RAI-refractory DTC with documented progression (NCT01876784). Patients were randomized 1:1 to vandetanib or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included best objective response rate, overall survival (OS), safety, and tolerability. Patients continued to receive randomized treatment until disease progression or for as long as they were receiving clinical benefit unless criteria for treatment discontinuation were met. Following randomization, 117 patients received vandetanib, and 118 patients received a placebo. Median PFS was 10.0 months in the vandetanib group and 5.7 months in the placebo group (hazard ratio: 0.75; 95% CI: 0.55–1.03; P = 0.080). OS was not significantly different between treatment arms. Common Terminology Criteria for Adverse Events (CTCAE) of grade ≥3 were reported in 55.6% of patients in the vandetanib arm and 25.4% in the placebo arm. Thirty-three deaths (28.2%; one related to study treatment) occurred in the vandetanib arm compared with 16 deaths (13.6%; two related to treatment) in the placebo arm. No statistically significant improvement was observed in PFS in treatment versus placebo in patients with locally advanced or metastatic, RAI-refractory DTC. Moreover, active treatment was associated with more adverse events and more deaths than placebo, though the difference in OS was not statistically significant.

الإتاحة: https://doi.org/10.1530/erc-23-0354Test
https://erc.bioscientifica.com/view/journals/erc/31/8/ERC-23-0354.xmlTest
https://erc.bioscientifica.com/downloadpdf/journals/erc/31/8/ERC-23-0354.xmlTest

المؤلفون: Singh, Simron, Ferone, Diego, Capdevila, Jaume, Chan, Jennifer Ang, de Herder, Wouter W., Halperin, Daniel, Mailman, Josh, Hellström, Lisa, Liedman, Hanna, Svedberg, Agneta, Tiberg, Fredrik

المصدر: Singh , S , Ferone , D , Capdevila , J , Chan , J A , de Herder , W W , Halperin , D , Mailman , J , Hellström , L , Liedman , H , Svedberg , A & Tiberg , F 2024 , ' Methodology of the SORENTO clinical trial : a prospective, randomised, active-controlled phase 3 trial assessing the efficacy and safety of high exposure octreotide subcutaneous depot (CAM2029) in patients with GEP-NET ' , Trials , vol. 25 , no. 1 , 58 . https://doi.org/10.1186/s13063-023-07834-8Test

الوصف: Background: The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile. Retrospective data have highlighted a potential benefit of high-exposure SRL for improved disease control in patients who did not adequately respond to the current SoC SRL treatment. This trial will investigate the efficacy and tolerability of CAM2029 compared to the current SoC, including octreotide LAR and lanreotide autogel (ATG). Methods: SORENTO is a prospective, multicentre, randomised, active-controlled, open-label phase 3 trial aiming to demonstrate superiority of treatment with 20 mg octreotide subcutaneous depot (CAM2029) every 2 weeks (Q2W) compared to treatment with the Investigator’s choice of SRL therapy at standard doses for tumour control (octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks [Q4W]) as assessed by progression-free survival (PFS) in approximately 300 patients with unresectable/metastatic and well-differentiated GEP-NET. Upon confirmation of disease progression (determined by a Blinded Independent Review Committee [BIRC] and defined as per RECIST 1.1), patients may enter an open-label extension treatment period with once weekly dosing, to investigate the effects of higher frequency dosing. Overall survival follow-up will end a maximum of 2 years after primary analysis. The primary endpoint will be analysed after 194 confirmed PFS events. Discussion: This is the first ...

وصف الملف: application/pdf

العلاقة: https://pure.eur.nl/en/publications/6edd6054-e1bf-47db-adc7-75174a14a4e1Test

الإتاحة: https://doi.org/10.1186/s13063-023-07834-8Test
https://pure.eur.nl/en/publications/6edd6054-e1bf-47db-adc7-75174a14a4e1Test
https://pure.eur.nl/ws/files/126658358/s13063-023-07834-8.pdfTest
http://www.scopus.com/inward/record.url?scp=85182475496&partnerID=8YFLogxKTest

المؤلفون: Singh, Simron, Ferone, Diego, Capdevila, Jaume, Chan, Jennifer Ang, de Herder, Wouter W., Halperin, Daniel, Mailman, Josh, Hellström, Lisa, Liedman, Hanna, Svedberg, Agneta, Tiberg, Fredrik

المصدر: Singh , S , Ferone , D , Capdevila , J , Chan , J A , de Herder , W W , Halperin , D , Mailman , J , Hellström , L , Liedman , H , Svedberg , A & Tiberg , F 2024 , ' Methodology of the SORENTO clinical trial : a prospective, randomised, active-controlled phase 3 trial assessing the efficacy and safety of high exposure octreotide subcutaneous depot (CAM2029) in patients with GEP-NET ' , Trials , vol. 25 , no. 1 , 58 . https://doi.org/10.1186/s13063-023-07834-8Test

الوصف: Background: The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile. Retrospective data have highlighted a potential benefit of high-exposure SRL for improved disease control in patients who did not adequately respond to the current SoC SRL treatment. This trial will investigate the efficacy and tolerability of CAM2029 compared to the current SoC, including octreotide LAR and lanreotide autogel (ATG). Methods: SORENTO is a prospective, multicentre, randomised, active-controlled, open-label phase 3 trial aiming to demonstrate superiority of treatment with 20 mg octreotide subcutaneous depot (CAM2029) every 2 weeks (Q2W) compared to treatment with the Investigator’s choice of SRL therapy at standard doses for tumour control (octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks [Q4W]) as assessed by progression-free survival (PFS) in approximately 300 patients with unresectable/metastatic and well-differentiated GEP-NET. Upon confirmation of disease progression (determined by a Blinded Independent Review Committee [BIRC] and defined as per RECIST 1.1), patients may enter an open-label extension treatment period with once weekly dosing, to investigate the effects of higher frequency dosing. Overall survival follow-up will end a maximum of 2 years after primary analysis. The primary endpoint will be analysed after 194 confirmed PFS events. Discussion: This is the first ...

وصف الملف: application/pdf

العلاقة: https://pure.eur.nl/en/publications/6edd6054-e1bf-47db-adc7-75174a14a4e1Test

الإتاحة: https://doi.org/10.1186/s13063-023-07834-8Test
https://pure.eur.nl/en/publications/6edd6054-e1bf-47db-adc7-75174a14a4e1Test
https://pure.eur.nl/ws/files/126658358/s13063-023-07834-8.pdfTest
http://www.scopus.com/inward/record.url?scp=85182475496&partnerID=8YFLogxKTest

المؤلفون: Singh, Simron, Ferone, Diego, Capdevila, Jaume, Chan, Jennifer Ang, de Herder, Wouter W., Halperin, Daniel, Mailman, Josh, Hellström, Lisa, Liedman, Hanna, Svedberg, Agneta, Tiberg, Fredrik

المصدر: Trials ; volume 25, issue 1 ; ISSN 1745-6215

مصطلحات موضوعية: Pharmacology (medical), Medicine (miscellaneous)

الوصف: Background The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile. Retrospective data have highlighted a potential benefit of high-exposure SRL for improved disease control in patients who did not adequately respond to the current SoC SRL treatment. This trial will investigate the efficacy and tolerability of CAM2029 compared to the current SoC, including octreotide LAR and lanreotide autogel (ATG). Methods SORENTO is a prospective, multicentre, randomised, active-controlled, open-label phase 3 trial aiming to demonstrate superiority of treatment with 20 mg octreotide subcutaneous depot (CAM2029) every 2 weeks (Q2W) compared to treatment with the Investigator’s choice of SRL therapy at standard doses for tumour control (octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks [Q4W]) as assessed by progression-free survival (PFS) in approximately 300 patients with unresectable/metastatic and well-differentiated GEP-NET. Upon confirmation of disease progression (determined by a Blinded Independent Review Committee [BIRC] and defined as per RECIST 1.1), patients may enter an open-label extension treatment period with once weekly dosing, to investigate the effects of higher frequency dosing. Overall survival follow-up will end a maximum of 2 years after primary analysis. The primary endpoint will be analysed after 194 confirmed PFS events. Discussion This is the ...

الإتاحة: https://doi.org/10.1186/s13063-023-07834-8Test

المؤلفون: Elisei, Rossella, Grande, Enrique, Kreissl, Michael C, Leboulleux, Sophie, Puri, Tarun, Fasnacht, Nicolas, Capdevila, Jaume

المساهمون: Elisei, Rossella, Grande, Enrique, Kreissl, Michael C, Leboulleux, Sophie, Puri, Tarun, Fasnacht, Nicola, Capdevila, Jaume

مصطلحات موضوعية: RET, medullary thyroid cancer, papillary thyroid cancer, receptor-tyrosine kinase, thyroid cancer, tyrosine kinase inhibitor

الوصف: The incidence of thyroid cancer is increasing worldwide with the disease burden in Europe second only to that in Asia. In the last several decades, molecular pathways central to the pathogenesis of thyroid cancer have revealed a spectrum of targetable kinases/kinase receptors and oncogenic drivers characteristic of each histologic subtype, such as differentiated thyroid cancer, including papillary, follicular, and medullary thyroid cancer. Oncogenic alterations identified include B-Raf proto-oncogene (BRAF) fusions and mutations, neurotrophic tyrosine receptor kinase (NTRK) gene fusions, and rearranged during transfection (RET) receptor tyrosine kinase fusion and mutations. Multikinase inhibitors (MKIs) targeting RET in addition to multiple other kinases, such as sorafenib, lenvatinib and cabozantinib, have shown favourable activity in advanced radioiodine-refractory differentiated thyroid cancer or RET-altered medullary thyroid cancer; however, the clinical utility of MKI RET inhibition is limited by off-target toxicity resulting in high rates of dose reduction and drug discontinuation. Newer and selective RET inhibitors, selpercatinib and pralsetinib, have demonstrated potent efficacy and favourable toxicity profiles in clinical trials in the treatment of RET-driven advanced thyroid cancer and are now a therapeutic option in some clinical settings. Importantly, the optimal benefits of available specific targeted treatments for advanced RET-driven thyroid cancer require genetic testing. Prior to the initiation of systemic therapy, and in treatment-naive patients, RET inhibitors may be offered as first-line therapy if a RET alteration is found, supported by a multidisciplinary team approach.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37207147; info:eu-repo/semantics/altIdentifier/wos/WOS:000987574600001; volume:13; numberofpages:15; journal:FRONTIERS IN ONCOLOGY; https://hdl.handle.net/11568/1207867Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85159874687; https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1141314/fullTest

الإتاحة: https://doi.org/10.3389/fonc.2023.1141314Test
https://hdl.handle.net/11568/1207867Test

المؤلفون: Aubergeon, Lucie, Baudin, Eric, Berruti, Alfredo, Grisanti, Salvatore, Oordt, CWillemien Menke-vander Houven van, Haak, Harm, Fassnacht, Martin, Capdevila, Jaume, Subbiah, Vivek, Jimenez, Camilo, Fouchardière, Christelle de la, Granberg, Dan, Kroiss, Matthias, Daugaard, Gedske, Toussaint, Hélène, Magalhaes, Joao Gamelas, Martinez, Jennifer, Belyn, Camille, Kervevan, Jerome, Ventujol, Chloé, Bonny, Christophe, Paillarse, Jean-Michel, Chene, Laurent

المصدر: Regular and Young Investigator Award Abstracts

الإتاحة: https://doi.org/10.1136/jitc-2023-sitc2023.0630Test

المؤلفون: Dijkstra, Esmée A., Nilsson, Per J., Hospers, Geke A.P., Bahadoer, Renu R., Meershoek-Klein Kranenbarg, Elma, Roodvoets, Annet G.H., Putter, Hein, Berglund, Åke, Cervantes, Andrés, Crolla, Rogier M.P.H., Hendriks, Mathijs P., Capdevila, Jaume, Edhemovic, Ibrahim, Marijnen, Corrie A.M., van de Velde, Cornelis J.H., Glimelius, Bengt, van Etten, Boudewijn

المصدر: Collaborative investigators , Dijkstra , E A , Nilsson , P J , Hospers , G A P , Bahadoer , R R , Meershoek-Klein Kranenbarg , E , Roodvoets , A G H , Putter , H , Berglund , Å , Cervantes , A , Crolla , R M P H , Hendriks , M P , Capdevila , J , Edhemovic , I , Marijnen , C A M , van de Velde , C J H , Glimelius , B & van Etten , B 2023 , ' Locoregional Failure During and After Short-course Radiotherapy ....

الوصف: OBJECTIVE: To analyze risk and patterns of locoregional failure (LRF) in patients of the RAPIDO trial at 5 years. BACKGROUND: Multimodality treatment improves local control in rectal cancer. Total neoadjuvant treatment (TNT) aims to improve systemic control while local control is maintained. At 3 years, LRF rate was comparable between TNT and chemoradiotherapy in the RAPIDO trial. METHODS: A total of 920 patients were randomized between an experimental (EXP, short-course radiotherapy, chemotherapy, and surgery) and a standard-care group (STD, chemoradiotherapy, surgery, and optional postoperative chemotherapy). LRFs, including early LRF (no resection except for organ preservation/R2 resection) and locoregional recurrence (LRR) after an R0/R1 resection, were analyzed. RESULTS: Totally, 460 EXP and 446 STD patients were eligible. At 5.6 years (median follow-up), LRF was detected in 54/460 (12%) and 36/446 (8%) patients in the EXP and STD groups, respectively ( P =0.07), in which EXP patients were more often treated with 3-dimensional-conformed radiotherapy ( P =0.029). In the EXP group, LRR was detected more often [44/431 (10%) vs. 26/428 (6%); P =0.027], with more often a breached mesorectum (9/44 (21%) vs. 1/26 (4); P =0.048). The EXP treatment, enlarged lateral lymph nodes, positive circumferential resection margin, tumor deposits, and node positivity at pathology were the significant predictors for developing LRR. Location of the LRRs was similar between groups. Overall survival after LRF was comparable [hazard ratio: 0.76 (95% CI, 0.46-1.26); P =0.29]. CONCLUSIONS: The EXP treatment was associated with an increased risk of LRR, whereas the reduction in disease-related treatment failure and distant metastases remained after 5 years. Further refinement of the TNT in rectal cancer is mandated.

وصف الملف: application/pdf

العلاقة: https://research.rug.nl/en/publications/fdfe8091-f33e-45f0-9126-d399418b3be3Test

الإتاحة: https://doi.org/10.1097/SLA.0000000000005799Test
https://hdl.handle.net/11370/fdfe8091-f33e-45f0-9126-d399418b3be3Test
https://research.rug.nl/en/publications/fdfe8091-f33e-45f0-9126-d399418b3be3Test
https://pure.rug.nl/ws/files/784764134/locoregional_failure_during_and_after_short_course.35.pdfTest

المؤلفون: Salvia, Anna La, Lens Pardo, Alberto, López López, Angel, Carretero Puche, Carlos, Capdevila, Jaume, Benavent, Marta, Jiménez Fonseca, Paula, Castellano, Daniel, Alonso, Teresa, Teule, Alexandre, Custodio, Ana, Tafuto, Salvatore, Casta, Adelaida La, Spada, Francesca, Lopez Gonzalvez, Angeles, Gil Calderon, Beatriz, Espinosa Olarte, Paula, Barbas, Coral, Garcia Carbonero, Rocio, Soldevilla, Beatriz

المصدر: Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

مصطلحات موضوعية: Triptòfan, Porfirines, Tryptophan, Porphyrins

الوصف: 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.

وصف الملف: 13 p.; application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.1093/ejendo/lvad160Test; European Journal of Endocrinology, 2023, vol. 190, num. 1, p. 62-74; https://doi.org/10.1093/ejendo/lvad160Test; http://hdl.handle.net/2445/207657Test

الإتاحة: https://doi.org/10.1093/ejendo/lvad160Test
http://hdl.handle.net/2445/207657Test