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Learn more: PMC Disclaimer | PMC Copyright Notice Future Oncol . 2026 Mar 20;22(9):1047–1053. doi: 10.1080/14796694.2026.2644463 Search in PMC Search in PubMed View in NLM Catalog Add to search AGMT mCRC Registry Third-Line and Beyond: a multicentric real-world platform with integrated imaging and biosample database for later-line metastatic colorectal cancer Florian Huemer Florian Huemer a Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria b Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing – original draft Find articles by Florian Huemer a, b, ✉ , Gudrun Piringer Gudrun Piringer c Department of Oncology and Hematology, Kepler University Hospital, Linz, Austria d Medical Faculty, Johannes Kepler University Linz, Linz, Austria Writing – review & editing Find articles by Gudrun Piringer c, d , Wolfgang Eisterer Wolfgang Eisterer e Abteilung für Innere Medizin, Klinikum Klagenfurt, Klagenfurt, Austria Writing – review & editing Find articles by Wolfgang Eisterer e , Sonja Heibl Sonja Heibl f Department of Internal Medicine IV, Hospital Wels-Grieskirchen, Wels, Austria Writing – review & editing Find articles by Sonja Heibl f , Holger Rumpold Holger Rumpold g Department of Internal Medicine I for Hematology with Stem Cell Transplantation, Hemostaseology, and Medical Oncology, Ordensklinikum Linz, Linz, Austria Writing – review & editing Find articles by Holger Rumpold g , Ewald Wöll Ewald Wöll h Department of Internal Medicine, St. Vinzenz Hospital Zams, Tyrol, Austria Writing – review & editing Find articles by Ewald Wöll h , Georg Schreil Georg Schreil i Department of Internal Medicine, State Hospital Pyhrn Eisenwurzen, Steyr, Austria Writing – review & editing Find articles by Georg Schreil i , Thamer Sliwa Thamer Sliwa j Abteilung für Innere Medizin und Hämato-Onkologie, LKH Hochsteiermark, Leoben, Austria Writing – review & editing Find articles by Thamer Sliwa j , Thomas Winder Thomas Winder k Department of Internal Medicine II, Academic Teaching Hospital Feldkirch, Feldkirch, Austria l University of Zurich, Zurich, Switzerland Writing – review & editing Find articles by Thomas Winder k, l , Gerald Prager Gerald Prager m Department of Medicine I, Division of Oncology, Medical University Vienna, Vienna, Austria Writing – review & editing Find articles by Gerald Prager m , Birgit Grünberger Birgit Grünberger n Klinische Abteilung für Innere Medizin III, Hämatologie und internistische Onkologie, Universitäts-Klinikum Wiener Neustadt, Wiener Neustadt, Austria Writing – review & editing Find articles by Birgit Grünberger n , Florian Moik Florian Moik o Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria Writing – review & editing Find articles by Florian Moik o , Arno Amann Arno Amann p Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria Writing – review & editing Find articles by Arno Amann p , Hossein Taghizadeh Hossein Taghizadeh q Department of Internal Medicine, Universitätsklinikum St. Pölten, St. Pölten, Austria Writing – review & editing Find articles by Hossein Taghizadeh q , Dora Niedersüß-Beke Dora Niedersüß-Beke r Department of Internal Medicine I, Centre for Oncology and Haematology, Vienna Healthcare Group, Vienna, Austria Writing – review & editing Find articles by Dora Niedersüß-Beke r , Richard Greil Richard Greil b Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria Funding acquisition, Project administration, Writing – review & editing Find articles by Richard Greil b, * , Lukas Weiss Lukas Weiss a Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria b Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing – review & editing Find articles by Lukas Weiss a, b, * Author information Article notes Copyright and License information a Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria b Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria c Department of Oncology and Hematology, Kepler University Hospital, Linz, Austria d Medical Faculty, Johannes Kepler University Linz, Linz, Austria e Abteilung für Innere Medizin, Klinikum Klagenfurt, Klagenfurt, Austria f Department of Internal Medicine IV, Hospital Wels-Grieskirchen, Wels, Austria g Department of Internal Medicine I for Hematology with Stem Cell Transplantation, Hemostaseology, and Medical Oncology, Ordensklinikum Linz, Linz, Austria h Department of Internal Medicine, St. Vinzenz Hospital Zams, Tyrol, Austria i Department of Internal Medicine, State Hospital Pyhrn Eisenwurzen, Steyr, Austria j Abteilung für Innere Medizin und Hämato-Onkologie, LKH Hochsteiermark, Leoben, Austria k Department of Internal Medicine II, Academic Teaching Hospital Feldkirch, Feldkirch, Austria l University of Zurich, Zurich, Switzerland m Department of Medicine I, Division of Oncology, Medical University Vienna, Vienna, Austria n Klinische Abteilung für Innere Medizin III, Hämatologie und internistische Onkologie, Universitäts-Klinikum Wiener Neustadt, Wiener Neustadt, Austria o Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria p Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria q Department of Internal Medicine, Universitätsklinikum St. Pölten, St. Pölten, Austria r Department of Internal Medicine I, Centre for Oncology and Haematology, Vienna Healthcare Group, Vienna, Austria ✉ CONTACT Florian Huemer [email protected] Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, Salzburg 5020, Austria * Senior authors contributed equally. Roles Florian Huemer : Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing – original draft Gudrun Piringer : Writing – review & editing Wolfgang Eisterer : Writing – review & editing Sonja Heibl : Writing – review & editing Holger Rumpold : Writing – review & editing Ewald Wöll : Writing – review & editing Georg Schreil : Writing – review & editing Thamer Sliwa : Writing – review & editing Thomas Winder : Writing – review & editing Gerald Prager : Writing – review & editing Birgit Grünberger : Writing – review & editing Florian Moik : Writing – review & editing Arno Amann : Writing – review & editing Hossein Taghizadeh : Writing – review & editing Dora Niedersüß-Beke : Writing – review & editing Richard Greil : Funding acquisition, Project administration, Writing – review & editing Lukas Weiss : Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing – review & editing Received 2025 Dec 14; Accepted 2026 Mar 9; Collection date 2026. © 2026 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. PMC Copyright notice PMCID: PMC13064558 PMID: 41860053 ABSTRACT Background The treatment landscape of systemic third- and later-line therapy in metastatic colorectal cancer (mCRC) continues to evolve. We, therefore, established the Austrian Group of Medical Tumor Therapy (AGMT) mCRC Registry Third-Line and Beyond to characterize clinical outcome with later-line therapies in routine practice and to support embedded translational and radiomic analyses. Methods The AGMT mCRC Registry Third-Line and Beyond is a prospective and retrospective, multicenter, national, non-interventional registry of mCRC patients that have received ≥3 palliative systemic therapies. The registry aims to enroll ≥500 mCRC patients at 15 hospitals in Austria. The electronic case report form (eCRF) captures patient, tumor, and treatment characteristics as well as clinical outcome based on medical records. Imaging studies performed during routine care are recorded in an imaging database to enable blinded independent central review and radiomic analyses. This registry includes a biosample database, allowing tumor samples obtained during routine clinical practice to be used for translational research projects. Conclusions The AGMT mCRC Registry Third-Line and Beyond will generate real-world evidence on treatment patterns and effectiveness of later-line therapies in mCRC patients. In addition, the platform is designed to serve as a validation resource for clinical, radiomic, and translational research projects. Clinical registry registration www.clinicaltrials.gov identifier is NCT06678919 . KEYWORDS: mCRC, metastatic colorectal cancer, later-line, Third-Line, imaging database, biosample database, clinical outcome, validation cohort 1. Introduction Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States and Europe [ 1 , 2 ]. Although selected patients with oligometastatic CRC undergo systemic therapy and surgery/local ablative therapy in curative intent, the treatment approach for the majority of metastatic CRC (mCRC) patients remains palliative with a median overall survival (OS) ranging between 9–38 months depending on various prognostic and predictive factors [ 3–6 ]. The therapeutic armamentarium ≥third-line (3 L) has continuously evolved in recent years and has improved clinical outcome among mCRC “all-comers” as well as biomarker-driven mCRC sub-cohorts [ 7–13 ]. However, due to sociodemographic and medical characteristics, the percentage of mCRC patients reaching palliative 3 L therapy differs considerably between randomized, controlled trial cohorts (53%) and patients treated in clinical practice (27%) [ 14 , 15 ]. The application of regorafenib as well as trifluridine/tipiracil (FTD-TPI) statistically significantly improved survival in the respective randomized, placebo-controlled phase III trials up to a median OS (mOS) of 6.4–7.1 months [ 7 , 8 ]. The effectiveness of these agents has been corroborated in retrospective analyses in the real-world setting [ 16 ]. In the meanwhile, the combination of FTD-TPI + bevacizumab yielded longer survival compared to FTD-TPI monotherapy (mOS: 10.8 versus 7.5 months, HR: 0.61, p < 0.001) in the phase III SUNLIGHT Trial, establishing a new therapeutic standard ≥3 L for mCRC all-comers [ 9 ]. The tyrosine kinase inhibitor (TKI) fruquintinib improved OS compared with placebo among FTD-TPI and/or regorafenib pre-treated mCRC patients in the phase III FRESCO-2 study (HR: 0.66), supporting its use as a ≥4 L therapy option in routine clinical practice [ 17 ]. However, fruquintinib has not been prospectively tested against regorafenib in a head-to-head comparison so far and therapy sequencing (fruquintinib followed by regorafenib or vice versa ) is still a matter of debate in clinical practice, particularly in Caucasian mCRC patients [ 18 ]. Because the relevant targetable molecular subgroups occur at low frequencies (microsatellite instability – high [MSI-H] ~4%, BRAF V600E mutation ~8%, HER2-positive ~2%, KRAS G12C mutation ~3%) and as targeted therapies are increasingly used in earlier treatment lines in these small sub-cohorts, assessing the effectiveness of biomarker-driven therapies in the ≥3 L setting remains challenging in routine practice [ 6 , 19 , 20 ]. In this context, multicentric registry results and international collaborations are of utmost importance to depict the performance of targeted therapies in these small biomarker-driven mCRC sub-cohorts, respectively. Immune-checkpoint-inhibitor (ICI) therapy has shown impressive long-lasting responses and OS in the small subset (5%) of so-called “hot” MSI-H or POLE and POLD1 mutant mCRC, which is characterized by a high tumor mutational burden and tumor neoantigen burden [ 19–21 ]. However, the application of ICI blockade ± TKI failed in several clinical trials in “cold” microsatellite-stable (MSS) mCRC [ 22 , 23 ]. In contrast to the aforementioned negative trials, the phase III STELLAR-303 Trial could show a superior OS with zanzalintinib plus atezolizumab compared with regorafenib among mCRC patients [ 24 ]. Owing to the comparatively low barriers to accessing anticancer agents in Austria, off-label use based on positive phase I & II trial results (e.g., regorafenib + ipilimumab + nivolumab in MSS mCRC) is feasible [ 25 ]. Translational analyses of the latter treatment approaches within clinical registries may lead to a deeper understanding of response prediction in MSS mCRC patients undergoing palliative TKI + ICI therapy. The AGMT mCRC Registry Third-Line and Beyond will provide real-world insights into treatment patterns and the effectiveness of later-line therapies in mCRC. Furthermore, the platform is structured to support clinical, radiomic, and translational research by providing well-characterized validation cohorts and subgroups of utmost interest (e.g., MSS mCRC patients undergoing TKI + ICI therapy). 2. Materials and methods 2.1. Objectives The AGMT mCRC Registry Third-Line and Beyond ( NCT06678919 ) is an ongoing retrospective and prospective tumor registry aiming at depicting the treatment landscape, shift of treatment patterns and the clinical outcome of mCRC patients ≥3 L therapy. Besides the collection of patient, tumor, and treatment characteristics from medical records, the platform was used for establishing an imaging and biosample database based on imaging studies and biosamples collected during routine clinical care. The latter measures provide the opportunity for blinded independent central review (BICR), radiomic as well as translational research projects in the respective sub-cohorts of interest. 2.2. Study design The AGMT mCRC Registry Third-Line and Beyond is a non-interventional, national, multicentric, ambispective tumor registry conducted in Austria across 15 study sites. The study sites include university hospitals and community hospitals. Study sites are instructed to consecutively include patients meeting the inclusion criteria. This long-term registry is planned to enroll ≥500 mCRC patients to provide a substantial number of all-comers as well as a limited number of patients within small biomarker-defined subgroups (e.g., MSI-H, BRAF V600E mutation, HER2-positive, KRAS G12C mutation), enabling international collaborations to support adequately powered subgroup analysis in, e.g., rare molecular subgroups. Due to the non-interventional character patients will be treated at the physicians’ discretion. The registry extracts data from medical records without altering standard care; longitudinal follow-up continues until death or loss to follow-up. Recruitment started in Q4 of 2024 and 334 patients have already been enrolled by January 2026. Due to the ambispective nature of the registry, eligible patients may be retrospectively included for treatments after 1 September 2017 ( Figure 1 , Table 1 ). The cutoff date has been defined based on the availability of activity and safety results of FTD-TPI + bevacizumab among pre-treated mCRC patients in the phase I/II, single-arm C-TASK FORCE Study [ 26 ]. Figure 1. Open in a new tab Study design of the ambispective AGMT mCRC Registry Third-Line and Beyond. BICR: blinded independent central review. Table 1. Prospective and retrospective data collection of mCRC patients ≥3 L therapy within the AGMT mCRC Registry Third-Line and Beyond. AGMT mCRC Registry Third-Line and Beyond Data/material collected ≥500 patients, 15 study sites Characteristics of the registry Patient characteristics Tumor characteristics Prior systemic therapies((neo-)adjuvant, palliative) Surgeries and local ablative therapies(e.g., SBRT, RFA, MWA, HIPEC) Documentation of CT scans during routine clinical care(≥3 L therapy) Documentation of biosamples obtained during routine clinical care Clinical end points(ORR, PFS, TTNT, OS) Prospective and retrospective Representative for the Austrian health care system with a rapid and broad access to evidence-based cancer treatments Translational research ORR and PFS assessment by BICR & radiomic analyses Multi-sponsored Long-term registry Validation cohorts(clinical data, CT images, biosamples) Open in a new tab mCRC: metastatic colorectal cancer, SBRT: stereotactic body radiation therapy, radiofrequency ablation, MWA: microwave ablation, HIPEC: hyperthermic intraperitoneal chemotherapy, CT: computed tomography, ORR: overall response rate, PFS: progressions-free survival, TTNT: time to next treatment, OS: overall survival, BICR: blinded independent central review. The study protocol was reviewed and approved by the ethics committees of the Provincial Government of Salzburg (1083/2024) and the local ethics committee for each study site, respectively. Patients will provide a written informed consent (IC) before study inclusion. In accordance with Austrian legislation and the ethics committee approval, no IC is required from deceased patients. For documentation in the registry, no further diagnostic or therapeutic measures are required than those already necessary in general. Only routine data, that have already been recorded in the patients’ medical charts are transferred to the electronic case report form (eCRF, Supplementary Table S1). 2.3. Inclusion criteria Age ≥18 years. Histologically confirmed mCRC. Planned systemic therapy after ≥2 prior palliative systemic therapy lines including 5-FU, oxaliplatin, irinotecan, anti-VEGF; anti-EGFR in case of RAS/BRAF wild-type status. Planned systemic therapy after ≥1 line in case of 1 L therapy with mFOLFOXIRI ± anti-VEGF or ±anti-EGFR or ineligibility to receive 5-FU, oxaliplatin, and/or irinotecan. Patients undergoing immune-checkpoint-inhibitor therapy in palliative intent can be enrolled irrespective of therapy line. 2.4. Exclusion criteria Due to the non-interventional design of the registry, there are no specific exclusion criteria 2.5. Measures and study procedures Overall survival (OS) with the respective treatment protocols ≥3 L. Progression-free survival (PFS) with the respective treatment protocols ≥3 L. Time to next treatment (TTNT) with the respective treatment protocols ≥3 L. Overall response rate (ORR) with the respective treatment protocols ≥3 L. Blinded independent central review (BICR) based on the imaging database with the respective treatment protocols ≥3 L. Identification of predictive biomarkers for mCRC patient sub-cohorts of interest based on the biosample database. Disease assessment will be performed by CT imaging studies obtained during clinical routine (approximately every three months) and outpatient follow-up visits. The survival status will be regularly ascertained through the national cancer registry to mitigate loss-to-follow-up bias. The basic approach of this registry involves descriptive statistics, time-to-event analyses, and exploratory analyses for biannual interim reports as well as specific projects. 2.6. Data source and quality control Data are collected from eCRF entries made by the respective study sites in REDCap (Research Electronic Data Capture) based on medical records of routine clinical care. To maintain patient confidentiality, each patient is assigned a unique patient identifying number upon enrollment. This number accompanies the patients’ medical and other registry information throughout the lifetime of the registry. The code that allows for the assignment of pseudonymized data to patient is stored at the study site and only the local PI and the delegated staff of the study center involved in the registry have access to the data. At the start of the study, study center staff were trained in the use of the eCRF and standardized data entry procedures. The registry uses an eCRF that integrates multiple automated plausibility and data validation checks to ensure high data quality. These include predefined data fields and selectable response options, as well as cross-field logic rules designed to prevent inconsistent or implausible entries. These features minimize the risk of data entry errors or inconsistencies across participating centers. Although no on-site monitoring is conducted, routine remote data quality reviews are performed. At least biannually, all records are systematically reviewed for plausibility, logical consistency, and completeness. When discrepancies or implausible data are identified, data queries are sent to the participating centers to ensure the ongoing accuracy, completeness, and integrity of the registry database. 2.7. Biosample database The registry will be accompanied by a biosample database. Biosamples will be documented in the eCRF for future analyses from all patients that have signed an additional genetic informed consent. No informed consent is required for samples, which have been stored in the past for routine diagnostic purposes from deceased patients. Prospective sample collection includes blood (20 mL), tissue, buccal swab/saliva, urine, and stool samples. Only tumor tissue samples obtained during routine clinical care will be used. The biosamples will remain at the respective center until scientific, translational research questions arise. Scientific projects must be submitted to an ethic-committee before implementation. 2.8. Imaging database The registry will also include an imaging database, recording the respective dates of computed tomography (CT) scans during ≥3 L therapy as well as the radiology institutes, which had carried out the imaging studies during routine clinical practice. Centralized analysis (e.g., BICR or body composition analyses) of the pseudonymized CT scans necessitates submission to the ethic-committee before transfer. BICR will be carried out by experienced, board-certified radiologists according to the RECIST criteria. 3. Discussion High-quality real-world evidence is essential to determine whether improvements in clinical endpoints observed in randomized, controlled trials translate into clinical practice among all-comers as well as biomarker-driven mCRC populations. Elderly, frail, and comorbid patients are often underrepresented in clinical trials and small, predominantly single-center retrospective analyses may contribute to discrepancies between trial outcomes and real-world results [ 9 , 27 , 28 ]. The focus of the AGMT mCRC Registry Third-Line and Beyond lies on later-line therapies (≥3 L) and due to the planned long-term and multicentric approach, this registry aims at enrolling adequate patient numbers (≥500) and providing robust data quality to investigate realistic effectiveness of (new) therapeutic standards and therapy sequencing strategies outside of clinical trials. Due to the establishment of ICI therapy as the standard therapeutic approach in palliative first-line MSI-H/dMMR mCRC, and owing to the low prevalence of this molecular subtype, these patients were recruited into the registry irrespective of treatment line. A strength of this registry is the establishment of an imaging database offering the opportunity for ORR assessment by BICR according to RECIST criteria, which are rarely applied in retrospective analyses of real-world cohorts [ 29 ]. Furthermore, imaging studies can be used for body composition analyses during the respective later-line therapy protocols as well as for a multidisciplinary assessment of local ablative therapy options in later-line mCRC [ 30 ]. The biosample database of the registry harbors the potential for the identification of tumor-tissue-based predictive biomarkers and responders among all-comer later-line therapies (on the horizon), such as, e.g., FTD-TPI + bevacizumab or TKI + ICI combinations in “cold” MSS mCRC [ 9 , 24 , 25 ]. 3.1. Limitations Real-world data collection is subject to heterogeneity in clinical documentation, imaging intervals, and treatment decisions across participating centers, which may impact data completeness and comparability with clinical trial populations. In addition, the optional nature of the biobanking component and variability in sample availability and pre-analytics may limit the feasibility of certain translational analyses. To partly mitigate heterogeneity in imaging-based response assessment, the registry incorporates an imaging database with the option for BICR. Differences in technical equipment across participating centers and community-based radiology centers may impact on the consistency of feature extraction in radiomic analyses. Variability in technical platforms between centers may influence the interpretation of biomarker results. We emphasize, that the AGMT mCRC Registry Third-Line and Beyond is a national, Austrian registry; therefore, differences in healthcare systems and the timing of drug approvals may limit the generalizability of the findings to global populations. 4. Conclusion The AGMT mCRC Registry Third-Line and Beyond (ClinicalTrials.gov: NCT06678919 ) will generate clinically meaningful interdisciplinary evidence on treatment patterns and outcomes of later-line therapies in mCRC patients in the real-world setting in Austria. The platform is expected to serve as a valuable resource for collaborative clinical, radiomic, and translational research projects. Supplementary Material Supplementary Table 1.docx IFON_A_2644463_SM1423.docx (35.5KB, docx) Acknowledgments The authors thank study sites as well as the AGMT Team for their great efforts in this project. Funding Statement The registry is sponsored by Austrian Group of Medical Tumor Therapy (AGMT) and has received financial support from Takeda Pharma, Servier, Merck Austria, and Amgen. The supporters do not have any involvement in study design, selection or enrollment of patients, data collection, storage, analysis, interpretation of the data, preparation of manuscripts or the decision to submit manuscripts for publication. Article highlights High-quality real-world evidence is essential to determine whether improvements in clinical endpoints observed in randomized, controlled trials translate into clinical practice in metastatic colorectal cancer (mCRC). The Austrian Group of Medical Tumor Therapy (AGMT) mCRC Registry Third-Line and Beyond is a non-interventional, national, multicentric, ambispective tumor registry conducted in Austria. The registry will provide real-world insights into treatment patterns and clinical outcome (overall survival, progression-free survival, time to next treatment, overall response rate) among mCRC patients ≥3 L therapy. Recruitment started in Q4 of 2024 and 334 patients have already been enrolled in this long-term registry by January 2026. The registry will be accompanied by a biosample database, harboring the potential for translational projects. The registry will also include an imaging database, recording the respective imaging studies that had been carried out during routine clinical practice. The imaging database offers the opportunity for radiomic analyses as well as overall response assessment by blinded independent central review, which is rarely applied in retrospective analyses of real-world cohorts. The AGMT mCRC Registry Third-Line and Beyond is expected to serve as a valuable resource for international collaborative clinical, radiomic, and translational research projects. Disclosure statement FH: Honoraria – Lilly, Pierre Fabre, Amgen, Servier, Daiichi Sankyo, BMS, Merck, Sanofi, Roche, Janssen, Astellas, Pharmamar; Johnson & Johnson; Travel support – Servier, BMS, Roche, Merck, Pharmamar, Pfizer, Pierre Fabre, Sanofi, Daiichi Sankyo, Gilead, Jazz Pharmaceuticals; Stock and other ownership: Guardant Health, Natera, Revolution Medicines. SH: SH: Honararia – Abbvie, Astra Zeneca, Gilead, Daiichi-Sankyo, Johnson&Johnson, Sanofi, Takeda, Novartis, Lilly, MSD, GSK, AOP, Roche, advisory Board – BMS, Novartis, GSK, Johnson & Johnson, Astra Zeneca, BeOne, Servier, Stemline, Alexion. EW: Advisory role: Astra Zeneca, Astella Pharma, Beigene, BMS, Daiichi Sankyo Austria, Eli Lilly, GSK, Gilead, Janssen Cilag, Jazz Pharma, Johnson&Johnson, MSD, Merck, Novartis, Eisai, Roche, Servier, Stemline, Takeda; Honoraria: Amgen, Astellas, Astra Zeneca, BMS, Celgen, Daiichi Sankyo Austria, Ebewe, Eli Lilly, Eisai, Janssen Cilag, Merck, MSD, Pierre Fabre, Pfizer, Ratiopharm, Roche, Sanofi Aventis, Takeda. GS: Honoraria: Takeda, Servier, Amgen. GP: Advisory Board/Speaker: Roche, Bayer, Merck, Amgen, Servier, Lilly, Pierre-Fabre, Incyte, Takeda, Astra Zeneca, Taiho, CECOG, Arcus, Beigene, MSD, BMS, Astellas. BG: Consulting or Advisory role: BMS, MSD, Eli Lilly, Roche, Bayer, Servier, AstraZeneca, Amgen, Daiichi-Sankyo, Pierre-Fabre, Incyte, Merck, Novartis, BeiGene, Takeda, Jazz Pharma, Travel support: Servier, Ely Lilly, Pierre fabre, Roche, Novartis. FM: travel/congress support: Novartis, Bayer; honoraria for lectures: Servier, Bristol Myers Squibb, honoraria for consulting: Johnson and Johnson, advisory role: MSD, Merck, Servier. DN-B: Honoraria: MSD, BMS, Merck Serono, Astellas, Janssen, Speakers Bureau: BMS, MSD, Merck Serono, Amgen, Astellas, Ipsen, Grant: Astellas. RG: Honoraria – Abbvie, Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Gilead, Merck, MSD, Novartis, Roche, Sandoz, Takeda; Consulting or Advisory Role – Abbvie, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Gilead, Janssen, Merck, MSD, Novartis, Roche, Takeda; Travel support – Abbvie, Amgen, Astra Zeneca, BMS, Celgene, Daiichi Sankyo, Gilead, Janssen, MSD, Novartis, Roche: Financing of Scientific Research – Amgen, Astra Zeneca, BMS, Celgene, Gilead, Merck, MSD, Novartis, Roche, Sandoz, Takeda. LW: Honoraria – Amgen, Astellas, BMS, Daiichi Sankyo, Lilly, Merck, MSD, Novocure, Pierre Fabre, Roche, Servier, Takeda; Travel support – Astra Zeneca, Merck, Pfizer, Pierre Fabre, Roche, Servier; Advisory board – Amgen, Astellas, BMS, GSK, Incyte, Lilly, Merck, MSD, Novocure, PharmaMar, Pierre Fabre, Roche, Takeda; Leadership – Austrian Breast and Colorectal Study Group (ABCSG); Stock and other ownership – Guardant Health; Research support – Novocure, Roche. All remaining authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. Reviewer disclosure Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Ethical declaration The study protocol was reviewed and approved by the ethics committees of the Provincial Government of Salzburg (1083/2024) and the local ethics committee for each study site, respectively. Patients will provide a written informed consent (IC) before study inclusion. In accordance with Austrian legislation and the ethics committee approval, no IC is required from deceased patients. Data availability statement This registry aims at providing validation cohorts for clinical-, radiomic-, and translational collaboration projects. Access to pseudonymized registry data is available upon reasonable request to the Austrian Group of Medical Tumor Therapy (AGMT, [email protected]). All requests are reviewed on a case-by-case basis to ensure scientific merit, feasibility, and compliance with ethical and legal requirements. 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