المؤلفون: Carolijn J. M. de Bresser, Bart-Jeroen Petri, Arthur J. A. T. Braat, Bart de Keizer, Mark J. C. van Treijen, Jan Willem Dankbaar, Frank A. Pameijer, Marius G. J. Kok, Mischa de Ridder, Bernadette P. M. van Nesselrooij, Remco de Bree, Gert J. de Borst, Johannes A. Rijken

المصدر: Cancers, Vol 16, Iss 5, p 986 (2024)

مصطلحات موضوعية: head and neck paraganglioma, [68Ga]Ga-DOTATOC PET/CT, MRI, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: The Dutch guideline for patients suspected of head and neck paragangliomas (HNPGLs) recommends magnetic resonance imaging (MRI) and/or computed tomography (CT) of the head and neck area. Additionally, it suggests considering additional nuclear imaging. The aim of this study was to evaluate the outcomes of [68Ga]Ga-DOTATOC PET/CT compared to MRI in patients with suspected HNPGLs and carriers of genetic variations. Methods: In this single-center pilot study, retrospective data were obtained from consecutive patients between 2016 and 2023. Both MRI and [68Ga]Ga-DOTATOC PET/CT were performed within 12 months. The primary outcome was the location of HNPGLs. Results: A total of 25 consecutive patients were included, and 7 patients (28.0%, p = 0.5) showed differences between the imaging modalities, of whom 5 patients had unexpected localizations with additional uptake by somatostatin receptors (SSTR) on the [68Ga]Ga-DOTATOC PET/CT. Conclusions: The authors recommend performing baseline imaging with [68Ga]Ga-DOTATOC PET/CT (if available) in variant carriers and using MRI/CT for follow-up according to the regional protocol, thereby shifting the gold standard for baseline imaging from MRI/CT to [68Ga]Ga-DOTATOC PET/CT.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/16/5/986Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/5472e51753c14c9babd69480cf5c32cbTest

المؤلفون: Sander C. Ebbers, Muriël Heimgartner, Maarten W. Barentsz, Rachel S. van Leeuwaarde, Mark J. C. van Treijen, Marnix M. E. G. Lam, Arthur J. A. T. Braat

المصدر: European Journal of Hybrid Imaging, Vol 5, Iss 1, Pp 1-11 (2021)

مصطلحات موضوعية: PRRT, [68Ga]Ga-DOTA-TOC PET/CT, Time-to-new treatment, Progression-free survival, PET-based response, Medical physics. Medical radiology. Nuclear medicine, R895-920

الوصف: Abstract Background Early [68Ga]Ga-DOTA-TOC PET/CT imaging after peptide receptor radionuclide therapy (PRRT) in neuroendocrine neoplasm patients is often used as a prognosticator for survival, but lacks validity. This study investigates the prognostic value of changes in PET parameters after PRRT. Methods Baseline and follow-up [68Ga]Ga-DOTA-TOC PET/CT scans of all patients treated with PRRT were delineated automatically. Total lesion somatostatin receptor expression (TL-SSTR) and somatostatin receptor expressing tumor volume (SSTR-TV) were used as covariates in Cox proportional hazard models to predict time-to-new treatment. Results In twenty patients, median time-to-new treatment was 19.3 months (range [3.8; 36.2]). Absolute and percentual changes in both PET parameters were not associated with time-to-new treatment. A significant relation between independent baseline and follow-up SSTR-TV and follow-up TL-SSTR, and time-to-new treatment was identified. Conclusions Automatically derived [68Ga]Ga-DOTA-TOC PET/CT parameters are easy to acquire and may be of prognostic value after completing PRRT. Acquiring SSTR-TV or TL-SSTR parameters at baseline and during follow-up can be of value in identifying a patient’s prognosis.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2510-3636Test

الوصول الحر: https://doaj.org/article/954a8c00fd4e4562a111bc0e730a3491Test

المؤلفون: Mark J. C. van Treijen, Catharina M. Korse, Rachel S. van Leeuwaarde, Lisette J. Saveur, Menno R. Vriens, Wieke H. M. Verbeek, Margot E. T. Tesselaar, Gerlof D. Valk

المصدر: Frontiers in Endocrinology, Vol 9 (2018)

مصطلحات موضوعية: biomarker, multigene transcripts, neuroendocrine tumors, gastroenteropancreatic, NET, chromogranin A, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Background: Available neuroendocrine biomarkers are considered to have insufficient accuracy to discriminate patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) from healthy controls. Recent studies have demonstrated a potential role for circulating neuroendocrine specific transcripts analysis—the NETest—as a more accurate biomarker for NETs compared to available biomarkers. This study was initiated to independently validate the discriminative value of the NETest as well as the association between tumor characteristics and NETest score.Methods: Whole blood samples from 140 consecutive GEP-NET patients and 113 healthy volunteers were collected. Laboratory investigators were blinded to the origin of the samples. NETest results and chromogranin A (CgA) levels were compared with clinical information including radiological imaging to evaluate the association with tumor characteristics.Results: The median NETest score in NET patients was 33 vs. 13% in controls (p < 0.0001). The NETest did not correlate with age, gender, tumor location, grade, load, or stage. Using the cut-off of 14% NETest sensitivity and specificity were 93 and 56%, respectively, with an AUC of 0.87. The optimal cut-off for the NETest in our population was 20%, with sensitivity 89% and specificity 72%. The upper limit of normal for CgA was established as 100 μg/l. Sensitivity and specificity of CgA were 56 and 83% with an AUC of 0.76. CgA correlated with age (rs = 0.388, p < 0.001) and tumor load (rs = 0.458, p < 0.001).Conclusions: The low specificity of the NETest precludes its use as a screening test for GEP-NETs. The superior sensitivity of the NETest over CgA (93 vs. 56%; p < 0.001), irrespective of the stage of the disease, emphasize its potential as a marker of disease presence in follow up as well as an indicator for residual disease after surgery.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fendo.2018.00740/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/4dfd490fb0cd4cbeaeb0d07ae1133492Test

المؤلفون: Mark J C van Treijen, Catharina M Korse, Wieke H Verbeek, Margot E T Tesselaar, Gerlof D Valk

المصدر: Endocrine Connections, Vol 11, Iss 10, Pp 1-12 (2022)

مصطلحات موضوعية: gastroenteropancreatic neuroendocrine tumors, liquid biopsy, treatment response, surveillance, gene expression signature, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Objective: Up to now, serial NETest measurements in individuals assessing the disease course of gastroenteropancreatic neuroendocrine tumors (GEPNETs) at long-term follow-up and treatment response were not studied. Design: The study was a longitudinal validation study of serial NETest measurements – a blood-based gene expression signature – in 132 patients with GEPNETs on therapy or watch-and-wait strategy. Methods: Serial samples were collected during 46 (range: 6–71) months of follow-up. NETest scores were compared with Response Evaluation Criteria in Solid Tumors version 1.1-defined treatment response (e.g. no evidence of disease (NED ), stable disease (SD) or progressive disease (PD)). Results: Consecutive NETest scores fluctuated substantially (range: 0–10 0) over time in individuals with SD (n = 28) and NED (n = 30). Follow-up samples were significantly higher in SD (samples 3–5) and NED subgroups (samples 2–5) compared with baseline results, without changes in imaging. In 82% of untreated patien ts with PD, consecutive NETest scores consistently remained high. In patients undergoing systemic treatment, the median pre-treatment NETest score in treatment-responders was 76.5 (n = 22) vs 33 (n = 12) in non-responders (P = 0.001). Patients with low pre-treatment scores had 21 months reduced progression-free survival (10 vs 31 months; P = 0.01). The accuracy of the NETest for treatment response prediction was 0.73 (P = 0.009). Conclusion: In patients not undergoing treatment, consecutive low NETest scores are associated with indolent behavior. Patients who develop PD exhibit elevated scores. Elevated results have important predictive value for treatment responsiveness and could be used for individualizing decisions on systemic therapy. The clinical value of follow-up NETest scores for patients who choose to watch and wait requires further study.

وصف الملف: electronic resource

العلاقة: https://ec.bioscientifica.com/view/journals/ec/11/10/EC-22-0146.xmlTest; https://doaj.org/toc/2049-3614Test

الوصول الحر: https://doaj.org/article/0a52c0ea1c9a45a8b31c3f40d1ebdd11Test

المؤلفون: Olaf M. Dekkers, Gerlof D. Valk, Wouter T Zandee, M. R. Vriens, Wouter W. de Herder, Bas Havekes, Mirthe J Klein Haneveld, Annenienke C van de Ven, Peter H. Bisschop, Carolina R.C. Pieterman, Madeleine L. Drent, Annemarie A Verrijn Stuart, Mark J C van Treijen, Rachel S van Leeuwaarde

المساهمون: Internal Medicine, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Gastroenterology Endocrinology Metabolism, Interne Geneeskunde, MUMC+: MA Endocrinologie (9), RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Endocrinology, AMS - Ageing & Vitality, AMS - Musculoskeletal Health

المصدر: Journal of Clinical Endocrinology and Metabolism, 106, 3515-3525
Journal of Clinical Endocrinology and Metabolism, 106(12), 3515-3525. Endocrine Society
Journal of Clinical Endocrinology and Metabolism, 106(12), 3515-3525. ENDOCRINE SOC
Journal of Clinical Endocrinology and Metabolism, 106(12), 3515-3525. The Endocrine Society
Journal of Clinical Endocrinology & Metabolism, 106(12), 3515-3525. Oxford University Press
Journal of Clinical Endocrinology and Metabolism, 106, 12, pp. 3515-3525
Journal of clinical endocrinology and metabolism, 106(12), 3515-3525. The Endocrine Society
Klein Haneveld, M J, van Treijen, M J C, Pieterman, C R C, Dekkers, O M, van de Ven, A, de Herder, W W, Zandee, W T, Drent, M L, Bisschop, P H, Havekes, B, Vriens, M R, Verrijn Stuart, A A, Valk, G D & van Leeuwaarde, R S 2021, ' Initiating Pancreatic Neuroendocrine Tumor (pNET) Screening in Young MEN1 Patients : Results from the DutchMEN Study Group ', Journal of Clinical Endocrinology and Metabolism, vol. 106, no. 12, pp. 3515-3525 . https://doi.org/10.1210/clinem/dgab569Test

مصطلحات موضوعية: Oncology, Male, Databases, Factual, Endocrinology, Diabetes and Metabolism, Neuroendocrine Tumors/diagnosis, Clinical Biochemistry, Disease, Biochemistry, multiple endocrine neoplasia type 1, Endocrinology, Medicine, Age of Onset, Multiple endocrine neoplasia, Child, Early Detection of Cancer, Netherlands, ENDOCRINE NEOPLASIA TYPE-1, education.field_of_study, INTERVAL-CENSORED-DATA, Middle Aged, Prognosis, Penetrance, age-related penetrance, Tumor Burden, Survival Rate, Neuroendocrine Tumors, Child, Preschool, Cohort, surveillance, Female, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, Diagnostic Imaging, medicine.medical_specialty, pancreatic NET, Adolescent, Population, Context (language use), Netherlands/epidemiology, Databases, Young Adult, SDG 3 - Good Health and Well-being, Internal medicine, Humans, MEN1, Pancreatic Neoplasms/diagnosis, education, Preschool, Survival analysis, Factual, Aged, Retrospective Studies, business.industry, Biochemistry (medical), medicine.disease, Pancreatic Neoplasms, Multiple Endocrine Neoplasia Type 1/physiopathology, Early Detection of Cancer/methods, business, Follow-Up Studies

الوصف: ContextNonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate.ObjectiveThe aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients.MethodsPancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥ 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease.ResultsFive of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET–free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively.ConclusionAnalyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2ce36b25c25d31e1a499d42dbc31157Test
https://doi.org/10.1210/clinem/dgab569Test

المؤلفون: Chantal A Lebbink, Lisa H de Vries, Inne H M Borel Rinkes, Arthur J A T Braat, Rachel S van Leeuwaarde, Lutske Lodewijk, Mark J C van Treijen, Menno R Vriens, Gerlof D Valk, Hanneke M van Santen, Bart de Keizer

المصدر: European journal of endocrinology. 187(1)

مصطلحات موضوعية: Iodine Radioisotopes, Endocrinology, Fluorodeoxyglucose F18, Endocrinology, Diabetes and Metabolism, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Humans, General Medicine, Thyroid Neoplasms, Adenocarcinoma, Neoplasm Recurrence, Local, Thyroglobulin, Retrospective Studies

الوصف: Objective To evaluate the usefulness of [18F]fluorodeoxyglucose (FDG) positron emissive tomography (PET)/CT in patients with low detectable thyroglobulin levels suspicious for persistent or recurrent differentiated thyroid cancer (DTC). Methods A retrospective case series study evaluating FDG PET/CT in patients with detectable thyroglobulin (Tg) levels (≥0.20 and Results Twenty-seven patients underwent FDG PET/CT. Median Tg level at FDG PET/CT was 2.00 ng/mL (range 0.30–9.00). FDG PET/CT was positive in 14 patients (51.9%): lesions suspicious for lymph node metastases were depicted in 12 patients, and lung metastases in 2. DTC was confirmed in 13/14 FDG PET/CT-positive patients. In 9/13 patients with a negative FDG PET/CT, DTC was confirmed ≤3 months after FDG PET/CT. The sensitivity, PPV, specificity and NPV were 59.1, 92.9, 80.0 and 30.8%, respectively. Conclusions This case series shows that FDG PET/CT might be useful to detect persistent or recurrent DTC in patients with low detectable Tg. However, when FDG PET/CT is negative, this does not rule out DTC and further investigations are necessary.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::699c040b118ddccb4e810ee22b667703Test
https://pubmed.ncbi.nlm.nih.gov/35521710Test

المؤلفون: Lisette J. Saveur, Wieke H. M. Verbeek, Catharina M. Korse, Mark J C van Treijen, Dennis van der Zee, Gerlof D. Valk, Margot E. T. Tesselaar, Birthe C. Heeres, Menno R. Vriens, Femke C.R. Staal, Monique Maas

المصدر: Neuroendocrinology. 111:586-598

مصطلحات موضوعية: Adult, Male, Oncology, endocrine system, medicine.medical_specialty, Validation study, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Neuroendocrine tumors, 030218 nuclear medicine & medical imaging, Disease course, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Text mining, Predictive Value of Tests, Stomach Neoplasms, Internal medicine, Intestinal Neoplasms, Biomarkers, Tumor, Humans, Medicine, Liquid biopsy, Aged, Gastroenteropancreatic neuroendocrine tumor, Aged, 80 and over, biology, Endocrine and Autonomic Systems, business.industry, Chromogranin A, Middle Aged, Prognosis, medicine.disease, Progression-Free Survival, Pancreatic Neoplasms, Neuroendocrine Tumors, biology.protein, Biological Assay, Female, business, Watchful waiting, Follow-Up Studies

الوصف: Reliable prediction of disease status is a major challenge in managing gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The aim of the study was to validate the NETest®, a blood molecular genomic analysis, for predicting the course of disease in individual patients compared to chromogranin A (CgA). NETest® score (normal ≤20%) and CgA level (normal p = ns). The optimal cutoffs for predicting SD/PD were 33% for the NETest® and 140 µg/L for CgA. Multivariate analyses identified NETest® as the strongest predictor for PD (odds ratio: 5.7 [score: 34–79%]; 12.6 [score: ≥80%]) compared to CgA (odds ratio: 3.0), tumor grade (odds ratio: 3.1), or liver metastasis (odds ratio: 7.7). The NETest® NPV for SD was 87% at 12 months. The PPV for PD was 47 and 64% (scores 34–79% and ≥80%, respectively). NETest® metrics were comparable in the watchful waiting, treatment, and no evidence of disease (NED) subgroups. For CgA (>140 ng/mL), NPV and PPV were 83 and 52%. CgA could not predict PD in the watchful waiting or NED subgroups. The NETest® reliably predicted SD and was the strongest predictor of PD. CgA had lower utility. The ­NETest® anticipates RECIST-defined disease status up to 1 year before imaging alterations are apparent.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0bb761cab1991aa4dd808e62d36d9b0Test
https://doi.org/10.1159/000509091Test

المؤلفون: Wenzel M. Hackeng, Madelon van Emst, Inne H.M. Borel Rinkes, Lodewijk A.A. Brosens, Koen M.A. Dreijerink, Gerlof D. Valk, G. Johan A. Offerhaus, Mark J C van Treijen, Dirk-Jan van Beek, Folkert H.M. Morsink, Menno R. Vriens, Aranxa S M Kok

المساهمون: Internal medicine, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Amsterdam Gastroenterology Endocrinology Metabolism

المصدر: American Journal of Surgical Pathology. Lippincott Williams and Wilkins
Hackeng, W M, van Beek, D-J, Kok, A S M, van Emst, M, Morsink, F H M, van Treijen, M J C, Borel Rinkes, I H M, Dreijerink, K M A, Offerhaus, G J A, Valk, G D, Vriens, M R & Brosens, L A A 2021, ' Metastatic patterns of duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 ', American Journal of Surgical Pathology . https://doi.org/10.1097/PAS.0000000000001811Test

مصطلحات موضوعية: Adult, Male, endocrine system, Pathology, medicine.medical_specialty, Databases, Factual, Neuroendocrine tumors, Pathology and Forensic Medicine, Metastasis, Duodenal Neoplasms, Gastrins, medicine, Biomarkers, Tumor, Multiple Endocrine Neoplasia Type 1, Humans, MEN1, Multiple endocrine neoplasia, Lymph node, Aged, Homeodomain Proteins, Gastrinoma, business.industry, Middle Aged, medicine.disease, Carcinoma, Neuroendocrine, Pancreatic Neoplasms, medicine.anatomical_structure, Ki-67 Antigen, Lymphatic Metastasis, Trans-Activators, PDX1, Surgery, Female, Anatomy, Neoplasm Grading, Pancreas, business, Transcription Factors

الوصف: Patients with multiple endocrine neoplasia 1 syndrome (MEN1) often develop multifocal duodenopancreatic neuroendocrine tumors (dpNETs). Nonfunctional pancreatic neuroendocrine tumors (PanNETs) and duodenal gastrinomas are the most frequent origins of metastasis. Current guidelines recommend surgery based on tumor functionality, size ≥ 2 cm, grade or presence of lymph node metastases. However, in case of multiple primary tumors it is often unknown which specific tumor metastasized. This study aims to unravel the relationship between primary dpNETs and metastases in patients with MEN1 by studying endocrine differentiation. First, it was shown that expression of the endocrine differentiation markers ARX and PDX1 was concordant in 18 unifocal sporadic neuroendocrine tumors (NETs) and matched metastases. Thereafter, ARX, PDX1, Ki67 and gastrin expression, and the presence of alternative lengthening of telomeres were determined in 137 microscopic and macroscopic dpNETs and 36 matched metastases in 10 patients with MEN1. ARX and PDX1 H-score clustering was performed to infer relatedness. For patients with multiple metastases, similar intrametastases transcription factor expression suggests that most metastases (29/32) originated from a single NET of origin, while few patients may have multiple metastatic primary NETs. In 6 patients with MEN1 and hypergastrinemia, periduodenopancreatic lymph node metastases expressed gastrin, and clustered with minute duodenal gastrinomas, not with larger PanNETs. PanNET metastases often clustered with high grade or alternative lengthening of telomeres-positive primary tumors. In conclusion, for patients with MEN1-related hypergastrinemia and PanNETs, a duodenal origin of periduodenopancreatic lymph node metastases should be considered, even when current conventional and functional imaging studies do not reveal duodenal tumors preoperatively.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a3721c777fde1cdf44390134d4a77dc4Test
https://pubmed.ncbi.nlm.nih.gov/34560682Test

المؤلفون: Rachel S van Leeuwaarde, Hua Zhao, Ehsan Irajizad, Carolina R.C. Pieterman, Johannes F. Fahrmann, Hansini Krishna, Eunice Murage, Jody Vykoukal, Gerlof D. Valk, Jennifer B. Dennison, Lee S. Weinstein, Jaydira Del Rivero, Amanda R. Wasylishen, James Welch, Guillermina Lozano, Samir M. Hanash, Menno R. Vriens, Mary Walter, Daniel M. Halperin, R. R. Wu, Nancy D. Perrier, Sunita K. Agarwal, Jenny E Blau, Kim Anh Do, Mark J C van Treijen, Naris Nilubol, Christine B. Peterson

المصدر: The Journal of Clinical Endocrinology and Metabolism

مصطلحات موضوعية: Adult, Male, Oncology, medicine.medical_specialty, polyamines, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Neuroendocrine tumors, Biochemistry, Young Adult, chemistry.chemical_compound, Endocrinology, Duodenal Neoplasms, Men1 fl/fl Pdx1-Cre Tg mice, Commentaries, Internal medicine, Biomarkers, Tumor, Multiple Endocrine Neoplasia Type 1, Humans, Medicine, MEN1, Online Only Articles, Multiple endocrine neoplasia, Aged, Retrospective Studies, dpNETs, business.industry, Biochemistry (medical), Disease progression, Cancer, Middle Aged, Prognosis, medicine.disease, United States, Pancreatic Neoplasms, Neuroendocrine Tumors, chemistry, Tumor progression, Case-Control Studies, Disease Progression, Biomarker (medicine), Female, Polyamine, business, AcademicSubjects/MED00250, Follow-Up Studies

الوصف: Context Duodenopancreatic neuroendocrine tumors (dpNETs) frequently occur in patients with multiple endocrine neoplasia type 1 (MEN1), and metastatic dpNET is the primary cause of disease-related mortality. There is a need for biomarkers that can identify patients with MEN1-related dpNETs that are at high risk of developing distant metastasis. Polyamines have tumor-promoting roles in several cancer types. Objective We hypothesized that MEN1-dpNET–related disease progression is associated with elevated levels of circulating polyamines. Methods Through an international collaboration between The University of Texas MD Anderson Cancer Center, the National Institutes of Health, and the University Medical Center Utrecht, plasma polyamine levels were assessed using mass spectrometry in 84 patients with MEN1 (20 with distant metastatic dpNETs [patients] and 64 with either indolent dpNETs or no dpNETs [controls]). A mouse model of MEN1-pNET, Men1fl/flPdx1-CreTg, was used to test time-dependent changes in plasma polyamines associated with disease progression. Results A 3-marker plasma polyamine signature (3MP: N-acetylputrescine, acetylspermidine, and diacetylspermidine) distinguished patients with metastatic dpNETs from controls in an initial set of plasmas from the 3 participating centers. The fixed 3MP yielded an area under the curve of 0.84 (95% CI, 0.62-1.00) with 66.7% sensitivity at 95% specificity for distinguishing patients from controls in an independent test set from MDACC. In Men1fl/flPdx1-CreTg mice, the 3MP was elevated early and remained high during disease progression. Conclusion Our findings provide a basis for prospective testing of blood-based polyamines as a potential means for monitoring patients with MEN1 for harboring or developing aggressive disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d91329ee667c63d567b02ef6cda93f45Test
https://doi.org/10.1210/clinem/dgab554Test

المؤلفون: Wouter W. de Herder, Hugo W. A. M. de Jong, Rachel S van Leeuwaarde, Arthur J. A. T. Braat, Margot E T Tesselaar, Johannes Hofland, Rob van Rooij, Rutger C G Bruijnen, Mark J C van Treijen, Manon N.G.J.A. Braat, Marnix G.E.H. Lam, Frank J. Wessels

المساهمون: Internal Medicine

المصدر: Lancet Oncology, 21(4), 561-570. Lancet Publishing Group
LANCET ONCOLOGY, 21(4), 561. Lancet Publishing Group

مصطلحات موضوعية: Male, medicine.medical_specialty, medicine.medical_treatment, Phases of clinical research, Octreotide, Gastroenterology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Liver disease, Holmium, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Organometallic Compounds, Journal Article, Humans, Prospective Studies, Adverse effect, Aged, Radioisotopes, business.industry, Liver Neoplasms, Common Terminology Criteria for Adverse Events, Middle Aged, medicine.disease, Embolization, Therapeutic, Radiation therapy, Neuroendocrine Tumors, Treatment Outcome, Oncology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Radionuclide therapy, Female, business

الوصف: Summary Background In patients with metastatic neuroendocrine neoplasms, the liver is the most commonly affected organ and a crucial factor for prognosis and survival. Peptide receptor radionuclide therapy can prolong progression-free survival in these patients. Additional treatment of liver disease might further improve outcomes. We aimed to investigate the safety and efficacy of additional holmium-166 (166Ho) radioembolisation after peptide receptor radionuclide therapy in patients with metastatic liver neuroendocrine neoplasms. Methods The Holmium Embolization Particles for Arterial Radiotherapy Plus 177Lu-Dotatate in Salvage Neuroendocrine Tumour Patients (HEPAR PLuS) study was a single-centre, phase 2 study done at the University Medical Center Utrecht (Utrecht, Netherlands). Patients, aged at least 18 years, with histologically proven grade 1 or 2 neuroendocrine neoplasms of all origins, an Eastern Cooperative Oncology Group performance status of 0–2, and three or more measurable liver metastases according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria received 166Ho-radioembolisation within 20 weeks after four cycles of peptide receptor radionuclide therapy (lutetium-177-dotatate [177Lu-dotatate]). The primary endpoint was objective liver tumour response in the treated liver volume, defined as complete response (disappearance of all lesions) or partial response (≥30% decrease in the sum of the longest diameters of the target lesions, compared with baseline measurements), according to RECIST 1.1, analysed per protocol at 3 months. Safety was assessed in all patients who received treatment. This study is registered with ClinicalTrials.gov , NCT02067988 . Recruitment is completed and long-term follow-up is ongoing. Findings From Oct 15, 2014, to Sept 12, 2018, 34 patients were assessed for eligibility. 31 patients received treatment and 30 (97%) patients were available for primary endpoint assessment and completed 6 months of follow-up. Three (9%) patients were excluded at screening and one (3%) patient was treated and died before the primary endpoint and was replaced. According to the per-protocol analysis 13 (43%; 95% CI 26–63) of 30 patients achieved an objective response in the treated volume. The most frequently reported Common Terminology Criteria for Adverse Events (CTCAE) grade 3–4 clinical and laboratory toxicities within 6 months included abdominal pain (three [10%] of 31 patients), increased γ-glutamyl transpeptidase (16 [54%]), and lymphocytopenia (seven [23%]). One (3%) fatal treatment-related serious adverse event occurred (radioembolisation-induced liver disease). Two (6%) patients had serious adverse events deemed to be unrelated to treatment (gastric ulcer and perforated cholecystitis). Interpretation 166Ho-radioembolisation, as an adjunct to peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm liver metastases, is safe and efficacious. Radioembolisation can be considered in patients with bulky liver disease, including after peptide receptor radionuclide therapy. A future randomised, controlled study should investigate the added benefit of this treatment on progression-free survival. Funding None.

وصف الملف: image/pdf; text/plain

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::30a714fa860e94416b79e9d4afa70242Test
https://dspace.library.uu.nl/handle/1874/395559Test