{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:24:59Z","timestamp":1787855099260,"version":"build-2784847793"},"reference-count":10,"publisher":"Walter de Gruyter GmbH","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2026-0757_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Advanced medullary thyroid carcinoma (MTC) is commonly monitored using calcitonin (CT) and carcinoembryonic antigen (CEA) kinetics. Pro-gastrin-releasing peptide (ProGRP) and carbohydrate antigen 19-9 (CA 19.9) have emerged as potential complementary markers, but their longitudinal prognostic value remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0757_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a retrospective longitudinal cohort study including 23 patients with metastatic MTC followed for a median of 37\u00a0months. CT and CEA were measured routinely every three to six months, while ProGRP and CA 19-9 were retrospectively assessed in stored serum samples. Patient-specific log-linear regression was used to calculate biomarker slopes. Discriminative performance for structural progression and disease-related death was evaluated and associations assessed using Kaplan-Meier analysis and log-rank testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0757_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ProGRP slope showed the strongest discrimination for disease-related death, followed by CA 19-9 and CEA, whereas CT slope alone demonstrated limited prognostic value. For structural progression, ProGRP and CEA had the highest performance. A discordant pattern (i.e.\u00a0increasing ProGRP and\/or CA 19-9 vs. decreasing CT) was more frequent in fatal cases. In multivariable penalized models, ProGRP slope remained the most consistently associated marker after internal validation. Kaplan\u2013Meier analysis confirmed earlier progression and reduced survival in patients with higher ProGRP slopes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0757_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dynamic changes in ProGRP were more strongly associated with adverse outcomes than traditional markers in advanced medullary thyroid carcinoma and may reflect aggressive tumor behavior not captured by CT. Due to the limited number of disease-related deaths, hazard ratio estimates for overall survival were imprecise and prospective validation in larger cohorts is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2026-0757","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:13:34Z","timestamp":1782310414000},"page":"2307-2314","source":"Crossref","is-referenced-by-count":0,"title":["ProGRP dynamics as a prognostic predictor in advanced medullary thyroid carcinoma"],"prefix":"10.1515","volume":"64","author":[{"given":"Alfredo","family":"Campenni","sequence":"first","affiliation":[{"name":"Nuclear Medicine Unit, Biomedical, Dental Sciences and Morpho-Functional Imaging , University of Messina , Messina , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra Petranovi\u0107","family":"Ov\u010dari\u010dek","sequence":"additional","affiliation":[{"name":"Department of Oncology and Nuclear Medicine , University Hospital Center Sestre Milosrdnice , Zagreb , Croatia"},{"name":"School of Medicine, University of Zagreb , Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"D\u2019Aurizio","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Pathology , University Hospital of Udine , Udine , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria M.","family":"Ruggeri","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Clinical and Experimental Medicine , University of Messina , Messina , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4296-429X","authenticated-orcid":false,"given":"Daniela","family":"Terracciano","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences , University of Naples \u201cFederico II\u201d , Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0230-0974","authenticated-orcid":false,"given":"Luca","family":"Giovanella","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Thyroid Center, Gruppo Ospedaliero Moncucco , Lugano , Switzerland"},{"name":"Nuclear Medicine and Thyroid Center, University Hospital of Zurich , Zurich , Switzerland"},{"name":"Clinical Chemistry and Endocrinology, Sonic-Medysin , Luzern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"2026082718023511196_j_cclm-2026-0757_ref_001","doi-asserted-by":"crossref","unstructured":"Wells, SA, Asa, SL, Dralle, H, Elisei, R, Evans, DB, Gagel, RF, et al.. Revised American thyroid association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015;25:567\u2013610. https:\/\/doi.org\/10.1089\/thy.2014.0335.","DOI":"10.1089\/thy.2014.0335"},{"key":"2026082718023511196_j_cclm-2026-0757_ref_002","doi-asserted-by":"crossref","unstructured":"Giovanella, L, Fontana, M, Keller, F, Campenni\u2019, A, Ceriani, L, Paone, G. Circulating pro-gastrin releasing peptide (ProGRP) in patients with medullary thyroid carcinoma. Clin Chem Lab Med 2021;59:1569\u201373. https:\/\/doi.org\/10.1515\/CCLM-2021-0361.","DOI":"10.1515\/cclm-2021-0361"},{"key":"2026082718023511196_j_cclm-2026-0757_ref_003","doi-asserted-by":"crossref","unstructured":"Elisei, R, Lorusso, L, Romei, C, Bottici, V, Mazzeo, S, Giani, C, et al.. Medullary thyroid cancer secreting carbohydrate antigen 19-9 (Ca 19-9): a fatal case report. J\u00a0Clin Endocrinol Metab 2013;98:3550\u20134. https:\/\/doi.org\/10.1210\/JC.2013-1940.","DOI":"10.1210\/jc.2013-1940"},{"key":"2026082718023511196_j_cclm-2026-0757_ref_004","doi-asserted-by":"crossref","unstructured":"Giovanella, L, D\u2019aurizio, F, Petranovi\u00b4c, P, Ov\u010dari\u010dek, P. Circulating biomarkers in medullary thyroid carcinoma: bridging laboratory complexities and clinical application through algorithm design. J\u00a0Clin Med 2025;14:5645. https:\/\/doi.org\/10.3390\/JCM14165645.","DOI":"10.3390\/jcm14165645"},{"key":"2026082718023511196_j_cclm-2026-0757_ref_005","doi-asserted-by":"crossref","unstructured":"Giovanella, L, D\u2019Aurizio, F, Ov\u010dari\u010dek, PP, Hillebrand, JJ, Giovanella, L, D\u2019Aurizio, F, et al.. Laboratory diagnostics and follow-up of medullary thyroid cancer. J\u00a0Mol Endocrinol 2026;1. https:\/\/doi.org\/10.1530\/JME-25-0185.","DOI":"10.1530\/JME-25-0185"},{"key":"2026082718023511196_j_cclm-2026-0757_ref_006","doi-asserted-by":"crossref","unstructured":"Molina, R, Filella, X, Aug\u00e9, JM. ProGRP: a new biomarker for small cell lung cancer. Clin Biochem 2004;37:505\u201311. https:\/\/doi.org\/10.1016\/j.clinbiochem.2004.05.007.","DOI":"10.1016\/j.clinbiochem.2004.05.007"},{"key":"2026082718023511196_j_cclm-2026-0757_ref_007","unstructured":"Lv, SP, Wang, Y, Huang, L, Wang, F, Zhou, JG, Ma, H. Meta-analysis of serum gastrin-releasing peptide precursor as a biomarker for diagnosis of small cell lung cancer. Asian Pac J Cancer Prev APJCP 2017;18:391\u20137. https:\/\/doi.org\/10.22034\/APJCP.2017.18.2.391."},{"key":"2026082718023511196_j_cclm-2026-0757_ref_008","doi-asserted-by":"crossref","unstructured":"Rosiek, V, Kogut, A, Kos-Kud\u0142a, B. Pro-gastrin-releasing peptide as a biomarker in lung neuroendocrine neoplasm. 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