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1دورية أكاديمية
المؤلفون: Zwart, Maurice J.W., Van Den Broek, Bram, De Graaf, Nine, Suurmeijer, José A., Augustinus, Simone, Te Riele, Wouter W., Van Santvoort, Hjalmar C., Hagendoorn, Jeroen, Borel Rinkes, Inne H.M., Van Dam, Jacob L., Takagi, Kosei, Tran, Khé T.C., Schreinemakers, Jennifer, Van Der Schelling, George, Wijsman, Jan H., De Wilde, Roeland F., Festen, Sebastiaan, Daams, Freek, Luyer, Misha D., De Hingh, Ignace H.J.T., Mieog, Jan S.D., Bonsing, Bert A., Lips, Daan J., Abu Hilal, Mohamed, Busch, Olivier R., Saint-Marc, Olivier, Zeh, Herbert J., Zureikat, Amer H., Hogg, Melissa E., Koerkamp, Bas G., Molenaar, Isaac Q., Besselink, Marc G.
المساهمون: CTC, MS CGO, MS HOD, Cancer, Regenerative Medicine and Stem Cells
مصطلحات موضوعية: clinical outcomes, learning curve, robotic pancreatoduodenectomy, robotic surgery, Surgery
الوصف: Objective: To assess the feasibility, proficiency, and mastery learning curves for robotic pancreatoduodenectomy (RPD) in "second-generation" RPD centers following a multicenter training program adhering to the IDEAL framework. Background: The long learning curves for RPD reported from "pioneering" expert centers may discourage centers interested in starting an RPD program. However, the feasibility, proficiency, and mastery learning curves may be shorter in "second-generation" centers that participated in dedicated RPD training programs, although data are lacking. We report on the learning curves for RPD in "second-generation" centers trained in a dedicated nationwide program. Methods: Post hoc analysis of all consecutive patients undergoing RPD in 7 centers that participated in the LAELAPS-3 training program, each with a minimum annual volume of 50 pancreatoduodenectomies, using the mandatory Dutch Pancreatic Cancer Audit (March 2016-December 2021). Cumulative sum analysis determined cutoffs for the 3 learning curves: operative time for the feasibility (1) risk-adjusted major complication (Clavien-Dindo grade ≥III) for the proficiency, (2) and textbook outcome for the mastery, (3) learning curve. Outcomes before and after the cutoffs were compared for the proficiency and mastery learning curves. A survey was used to assess changes in practice and the most valued "lessons learned." Results: Overall, 635 RPD were performed by 17 trained surgeons, with a conversion rate of 6.6% (n=42). The median annual volume of RPD per center was 22.5±6.8. From 2016 to 2021, the nationwide annual use of RPD increased from 0% to 23% whereas the use of laparoscopic pancreatoduodenectomy decreased from 15% to 0%. The rate of major complications was 36.9% (n=234), surgical site infection 6.3% (n=40), postoperative pancreatic fistula (grade B/C) 26.9% (n=171), and 30-day/in-hospital mortality 3.5% (n=22). Cutoffs for the feasibility, proficiency, and mastery learning curves were reached at 15, 62, and 84 RPD. Major morbidity and ...
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2دورية أكاديمية
المؤلفون: Andel, Daan, Lam, Marnix G.E.H., de Bruijne, Joep, Smits, Maarten L.J., Braat, Arthur J.A.T., Moelker, Adriaan, Vegt, Erik, Ruiter, Simeon J.S., Noordzij, Walter, Grazi, Gianluca, Vallati, Giulio E., Bennink, Roel J., van Delden, Otto M., Kranenburg, Onno W., Ijzermans, Jan N.M., Nijkamp, Maarten W., Erdmann, Joris I., Sciuto, Rosa, Hagendoorn, Jeroen, Borel Rinkes, Inne H.M.
المساهمون: MS HOD, Lab Translational Oncology, Researchgr. Nucleaire Geneeskunde, Cancer, MS MDL 1, MS Radiologie, Regenerative Medicine and Stem Cells, MS CGO
مصطلحات موضوعية: Ho, Hepatocellular carcinoma, Holmium-166, Radiation lobectomy, Radioembolization, Unilobar radioembolization, Oncology, Genetics, Cancer Research
الوصف: Background: High dose unilobar radioembolization (also termed ‘radiation lobectomy’)—the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy—has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. Methods: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose–response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. Discussion: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. Trial registration: Netherlands Trial Register NL8902 , registered on 2020–09-15.
وصف الملف: application/pdf
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3دورية أكاديمية
المؤلفون: Wensink, G. E., Bolhuis, Karen, Elferink, Marloes A.G., Fijneman, Remond J.A., Kranenburg, Onno, Borel Rinkes, Inne H.M., Koopman, Miriam, Swijnenburg, Rutger Jan, Vink, Geraldine R., Hagendoorn, Jeroen, Punt, Cornelis J.A., Roodhart, Jeanine M.L., Elias, Sjoerd G.
المساهمون: Zorg MOD, Unit Opleiding Aios, Cancer, Lab Translational Oncology, Regenerative Medicine and Stem Cells, MS CGO, MS Medische Oncologie, Onderzoek Medische Oncologie, Epi Kanker Team B, Epi Kanker Team C, JC onderzoeksprogramma Kanker
مصطلحات موضوعية: Surgery
الوصف: Background: Patients who develop early extrahepatic recurrence (EHR) may not benefit from local treatment of colorectal liver metastases (CRLMs). This study aimed to develop a prediction model for early EHR after local treatment of CRLMs using a national data set. Methods: A Cox regression prediction model for EHR was developed and validated internally using data on patients who had local treatment for CRLMs with curative intent. Performance assessment included calibration, discrimination, net benefit, and generalizability by internal–external cross-validation. The prognostic relevance of early EHR (within 6 months) was evaluated by landmark analysis. Results: During a median follow-up of 35 months, 557 of the 1077 patients had EHR and 249 died. Median overall survival was 19.5 (95 per cent c.i. 15.6 to 23.0) months in patients with early EHR after CRLM treatment, compared with not reached (45.3 months to not reached) in patients without an early EHR. The EHR prediction model included side and stage of the primary tumour, RAS/BRAFV600E mutational status, and number and size of CRLMs. The range of 6-month EHR predictions was 5.9–56.0 (i.q.r. 12.9–22.0) per cent. The model demonstrated good calibration and discrimination. The C-index through 6 and 12 months was 0.663 (95 per cent c.i. 0.624 to 0.702) and 0.661 (0.632 to 0.689) respectively. The observed 6-month EHR risk was 6.5 per cent for patients in the lowest quartile of predicted risk compared with 32.0 per cent in the highest quartile. Conclusion: Early EHR after local treatment of CRLMs can be predicted.
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4دورية أكاديمية
المؤلفون: Küçükköse, Emre, Laoukili, Jamila, Gorelick, Alexander N., Degner, Sebastian, Laclé, Miangela M., van den Bent, Lotte, Peters, Niek A., Verheem, André, Hung, Wei Ting, Frenkel, Nicola C., Wassenaar, Emma C.E., Lansu, Nico, Lenos, Kristiaan J., Vermeulen, Louis, Koopman, Miriam, Roodhart, Jeanine M.L., Kops, Geert J.P.L., Borel Rinkes, Inne H.M., Hagendoorn, Jeroen, Naxerova, Kamila, Kranenburg, Onno
المساهمون: Lab Translational Oncology, Cancer, Pathologie Pathologen staf, MS CGO, MS Medische Oncologie, Hubrecht Institute with UMC, Regenerative Medicine and Stem Cells
مصطلحات موضوعية: Lymphatics, Metastasis Mechanism, Organ Tropism, Patient-Derived Organoids, Gastroenterology, Hepatology, Journal Article
الوصف: Background & Aims: Patients with colon cancer with liver metastases may be cured with surgery, but the presence of additional lung metastases often precludes curative treatment. Little is known about the processes driving lung metastasis. This study aimed to elucidate the mechanisms governing lung vs liver metastasis formation. Methods: Patient-derived organoid (PDO) cultures were established from colon tumors with distinct patterns of metastasis. Mouse models recapitulating metastatic organotropism were created by implanting PDOs into the cecum wall. Optical barcoding was applied to trace the origin and clonal composition of liver and lung metastases. RNA sequencing and immunohistochemistry were used to identify candidate determinants of metastatic organotropism. Genetic, pharmacologic, in vitro, and in vivo modeling strategies identified essential steps in lung metastasis formation. Validation was performed by analyzing patient-derived tissues. Results: Cecum transplantation of 3 distinct PDOs yielded models with distinct metastatic organotropism: liver only, lung only, and liver and lung. Liver metastases were seeded by single cells derived from select clones. Lung metastases were seeded by polyclonal clusters of tumor cells entering the lymphatic vasculature with very limited clonal selection. Lung-specific metastasis was associated with high expression of desmosome markers, including plakoglobin. Plakoglobin deletion abrogated tumor cell cluster formation, lymphatic invasion, and lung metastasis formation. Pharmacologic inhibition of lymphangiogenesis attenuated lung metastasis formation. Primary human colon, rectum, esophagus, and stomach tumors with lung metastases had a higher N-stage and more plakoglobin-expressing intra-lymphatic tumor cell clusters than those without lung metastases. Conclusions: Lung and liver metastasis formation are fundamentally distinct processes with different evolutionary bottlenecks, seeding entities, and anatomic routing. Polyclonal lung metastases originate from ...
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5دورية أكاديمية
المؤلفون: Andel, Daan, Lam, Marnix G.E.H., de Bruijne, Joep, Smits, Maarten L.J., Braat, Arthur J.A.T., Moelker, Adriaan, Vegt, Erik, Ruiter, Simeon J.S., Noordzij, Walter, Grazi, Gianluca, Vallati, Giulio E., Bennink, Roel J., van Delden, Otto M., Kranenburg, Onno W., Ijzermans, Jan N.M., Nijkamp, Maarten W., Erdmann, Joris I., Sciuto, Rosa, Hagendoorn, Jeroen, Borel Rinkes, Inne H.M.
المصدر: Andel , D , Lam , M G E H , de Bruijne , J , Smits , M L J , Braat , A J A T , Moelker , A , Vegt , E , Ruiter , S J S , Noordzij , W , Grazi , G , Vallati , G E , Bennink , R J , van Delden , O M , Kranenburg , O W , Ijzermans , J N M , Nijkamp , M W , Erdmann , J I , Sciuto , R , Hagendoorn , J & Borel Rinkes , ....
مصطلحات موضوعية: /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being
الوصف: Background: High dose unilobar radioembolization (also termed ‘radiation lobectomy’)—the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy—has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. Methods: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m 2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose–response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. Discussion: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. Trial registration: Netherlands Trial Register NL8902 , registered on 2020–09-15.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1186/s12885-023-11280-9Test
https://pure.eur.nl/en/publications/c850c2a2-b339-49cc-b82c-9fb1a27edbfaTest
https://pure.eur.nl/ws/files/98934968/s12885-023-11280-9.pdfTest
http://www.scopus.com/inward/record.url?scp=85168361524&partnerID=8YFLogxKTest -
6دورية أكاديمية
المؤلفون: Dayton, Talya L., Alcala, Nicolas, Moonen, Laura, den Hartigh, Lisanne, Geurts, Veerle, Mangiante, Lise, Lap, Lisa, Dost, Antonella F.M., Beumer, Joep, Levy, Sonja, van Leeuwaarde, Rachel S., Hackeng, Wenzel M., Samsom, Kris, Voegele, Catherine, Sexton-Oates, Alexandra, Begthel, Harry, Korving, Jeroen, Hillen, Lisa, Brosens, Lodewijk A.A., Lantuejoul, Sylvie, Jaksani, Sridevi, Kok, Niels F.M., Hartemink, Koen J., Klomp, Houke M., Borel Rinkes, Inne H.M., Dingemans, Anne Marie, Valk, Gerlof D., Vriens, Menno R., Buikhuisen, Wieneke, van den Berg, José, Tesselaar, Margot, Derks, Jules, Speel, Ernst Jan, Foll, Matthieu, Fernández-Cuesta, Lynnette, Clevers, Hans
المصدر: Dayton , T L , Alcala , N , Moonen , L , den Hartigh , L , Geurts , V , Mangiante , L , Lap , L , Dost , A F M , Beumer , J , Levy , S , van Leeuwaarde , R S , Hackeng , W M , Samsom , K , Voegele , C , Sexton-Oates , A , Begthel , H , Korving , J , Hillen , L , Brosens , L A A , Lantuejoul , S , Jaksani , S , Kok , N F M , ....
مصطلحات موضوعية: /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being
الوصف: Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate models. We establish patient-derived tumor organoids (PDTOs) from pulmonary NETs and derive PDTOs from an understudied subtype of NEC, large cell neuroendocrine carcinoma (LCNEC), arising from multiple body sites. PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors. Through hypothesis-driven drug sensitivity analyses, we identify ASCL1 as a potential biomarker for response of LCNEC to treatment with BCL-2 inhibitors. Additionally, we discover a dependency on EGF in pulmonary NET PDTOs. Consistent with these findings, we find that, in an independent cohort, approximately 50% of pulmonary NETs express EGFR. This study identifies an actionable vulnerability for a subset of pulmonary NETs, emphasizing the utility of these PDTO models.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1016/j.ccell.2023.11.007Test
https://pure.eur.nl/en/publications/3346d84a-3186-452f-bac4-077965c7da0eTest
https://pure.eur.nl/ws/files/121754176/Druggable_growth_dependencies_and_tumor_evolution_analysis_in_patient-derived_organoids_of_neuroendocrine_neoplasms_from_multiple_body_sites.pdfTest
http://www.scopus.com/inward/record.url?scp=85179067544&partnerID=8YFLogxKTest -
7دورية أكاديمية
المصدر: Annals of Surgery Open ; volume 4, issue 1, page e239 ; ISSN 2691-3593
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8دورية أكاديمية
المؤلفون: Küçükköse, Emre, Baars, Matthijs J.D., Amini, Mojtaba, Schraa, Suzanna J., Floor, Evelien, Bol, Guus M., Borel Rinkes, Inne H.M., Roodhart, Jeanine M.L., Koopman, Miriam, Laoukili, Jamila, Kranenburg, Onno, Vercoulen, Yvonne
المساهمون: Lab Translational Oncology, Cancer, CMM, CMM Groep Vercoulen, Infection & Immunity, Unit Opleiding Aios, Onderzoek Medische Oncologie, MS MDL 1, MS Radiotherapie, MS CGO, Regenerative Medicine and Stem Cells, MS Medische Oncologie
مصطلحات موضوعية: Oncology, Cancer Research, Journal Article
الوصف: Background: The determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in primary tumors may discriminate between non-metastatic MSI-H CRC and metastatic MSI-H CRC. Methods: We profiled 46,727 single cells using high-plex imaging mass cytometry and analyzed both differential cell type abundance, and spatial distribution of fibroblasts and immune cells in primary CRC tumors with or without metastatic capacity. We validated our findings in a second independent cohort using immunohistochemistry. Results: High-plex imaging mass cytometry and hierarchical clustering based on microenvironmental markers separated primary MSI-H CRC tumors with and without metastatic capacity. Primary tumors with metastatic capacity displayed a high stromal content and low influx of CD8+ T cells, which expressed significantly lower levels of markers reflecting proliferation (Ki67) and antigen-experience (CD45RO) compared to CD8+ T cells in non-metastatic tumors. CD8+ T cells showed intra-epithelial localization in non-metastatic tumors, but stromal localization in metastatic tumors, which was validated in a second cohort. Conclusion: We conclude that localization of phenotypically distinct CD8+ T cells within stroma may predict metastasis formation in MSI-H CRC.
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9دورية أكاديمية
المؤلفون: Peters, Niek A., Constantinides, Alexander, Ubink, Inge, van Kuik, Joyce, Bloemendal, Haiko J., van Dodewaard, Joyce M., Brink, Menno A., Schwartz, Thijs P., Lolkema, Martijn P.J.K., Lacle, Miangela M., Moons, Leon M., Geesing, Joost, van Grevenstein, Wilhelmina M.U., Roodhart, Jeanine M.L., Koopman, Miriam, Elias, Sjoerd G., Borel Rinkes, Inne H.M., Kranenburg, Onno
المساهمون: Lab Translational Oncology, Cancer, MS CGO, Pathologie Moleculair Path., MS Medische Oncologie, RF&S Team 2 Medisch, Medisch Oncologische Disciplines, Pathologie Pathologen staf, MS MDL 1, Epi Kanker Team C, JC onderzoeksprogramma Kanker, Regenerative Medicine and Stem Cells
مصطلحات موضوعية: colorectal cancer, consensus molecular subtype 4, imatinib, ImPACCT, platelet-derived growth factor receptor (PDGFR), Oncology, Cancer Research, Journal Article
الوصف: Background: Mesenchymal Consensus Molecular Subtype 4 (CMS4) colon cancer is associated with poor prognosis and therapy resistance. In this proof-of-concept study, we assessed whether a rationally chosen drug could mitigate the distinguishing molecular features of primary CMS4 colon cancer. Methods: In the ImPACCT trial, informed consent was obtained for molecular subtyping at initial diagnosis of colon cancer using a validated RT-qPCR CMS4-test on three biopsies per tumor (Phase-1, n=69 patients), and for neoadjuvant CMS4-targeting therapy with imatinib (Phase-2, n=5). Pre- and post-treatment tumor biopsies were analyzed by RNA-sequencing and immunohistochemistry. Imatinib-induced gene expression changes were associated with molecular subtypes and survival in an independent cohort of 3232 primary colon cancer. Results: The CMS4-test classified 52/172 biopsies as CMS4 (30%). Five patients consented to imatinib treatment prior to surgery, yielding 15 pre- and 15 post-treatment samples for molecular analysis. Imatinib treatment caused significant suppression of mesenchymal genes and upregulation of genes encoding epithelial junctions. The gene expression changes induced by imatinib were associated with improved survival and a shift from CMS4 to CMS2. Conclusion: Imatinib may have value as a CMS-switching drug in primary colon cancer and induces a gene expression program that is associated with improved survival.
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10دورية أكاديمية
المؤلفون: Bolhuis, Karen, Wensink, G. Emerens, Elferink, Marloes A.G., Bond, Marinde J.G., Dijksterhuis, Willemieke P.M., Fijneman, Remond J.A., Kranenburg, Onno W., Borel Rinkes, Inne H.M., Koopman, Miriam, Swijnenburg, Rutger Jan, Vink, Geraldine R., Hagendoorn, Jeroen, Punt, Cornelis J.A., Elias, Sjoerd G., Roodhart, Jeanine M.L.
المساهمون: Cancer, Unit Opleiding Aios, Epi Kanker Team B, Lab Translational Oncology, Regenerative Medicine and Stem Cells, CTC, MS CGO, MS Medische Oncologie, Onderzoek Medische Oncologie, Epi Kanker Team C, JC onderzoeksprogramma Kanker
مصطلحات موضوعية: colorectal cancer, liver metastases, prediction model, resection, survival, Oncology, Cancer Research, Journal Article
الوصف: Optimized surgical techniques and systemic therapy have increased the number of patients with colorectal liver metastases (CRLM) eligible for local treatment. To increase postoperative survival, we need to stratify patients to customize therapy. Most clinical risk scores (CRSs) which predict prognosis after CRLM resection were based on the outcome of studies in specialized centers, and this may hamper the generalizability of these CRSs in unselected populations and underrepresented subgroups. We aimed to externally validate two CRSs in a population-based cohort of patients with CRLM. A total of 1105 patients with local treatment of CRLM, diagnosed in 2015/2016, were included from a nationwide population-based database. Survival outcomes were analyzed. The Fong and more recently developed GAME CRS were externally validated, including in pre-specified subgroups (≤70/>70 years and with/without perioperative systemic therapy). The three-year DFS was 22.8%, and the median OS in the GAME risk groups (high/moderate/low) was 32.4, 46.7, and 68.1 months, respectively (p < 0.005). The median OS for patients with versus without perioperative therapy was 47.6 (95%CI [39.8, 56.2]) and 54.9 months (95%CI [48.8, 63.7]), respectively (p = 0.152), and for below/above 70 years, it was 54.9 (95%CI [49.3–64.1]) and 44.2 months (95%CI [37.1–54.3]), respectively (p < 0.005). The discriminative ability for OS of Fong CRS was 0.577 (95%CI [0.554, 0.601]), and for GAME, it was 0.596 (95%CI [0.572, 0.621]), and was comparable in the subgroups. In conclusion, both CRSs showed predictive ability in a population-based cohort and in predefined subgroups. However, the limited discriminative ability of these CRSs results in insufficient preoperative risk stratification for clinical decision-making.
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