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4. Benefit of adjuvant chemotherapy on recurrence free survival per consensus molecular subtype in stage III colon cancer.

Author

van de Weerd, Simone, Torang, Arezo, van den Berg, Inge, Lammers, Veerle, van den Bergh, Saskia, Brouwer, Nelleke, Nagtegaal, Iris D., Koopman, Miriam, Vink, Geraldine R., van der Baan, Frederieke H., van Krieken, Han, Koster, Jan, Ijzermans, Jan N., Roodhart, Jeanine M. L., and Medema, Jan Paul

Subjects
ADJUVANT chemotherapy, COLON cancer, COLON tumors, TUMOR classification, COLORECTAL cancer
Abstract

The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018. Patients treated with and without adjuvant chemotherapy were matched based on tumor location, T‐ and N‐stage (n = 522). Tumor material was available for 464 patients, with successful RNA extraction and CMS subtyping achieved in 390 patients (surgery alone group: 192, adjuvant chemotherapy group: 198). In the overall cohort, CMS4 was associated with poorest prognosis (HR 1.55; p =.03). Multivariate analysis revealed favorable RFS for the adjuvant chemotherapy group in CMS1, CMS2, and CMS4 tumors (HR 0.19; p =.01, HR 0.27; p <.01, HR 0.19; p <.01, respectively), while no significant difference between treatment groups was observed within CMS3 (HR 0.68; p =.51). CMS subtyping in this non‐randomized cohort identified patients with poor prognosis and patients who may not benefit significantly from adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Published
2025
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5. Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab

Author

Externen Med. Onco, Cancer, Onderzoek Medische Oncologie, JC onderzoeksprogramma Kanker, MS Medische Oncologie, Zwart, Koen, van Nassau, Sietske C M W, van der Baan, Frederieke H, Koopman, Miriam, Snaebjornsson, Petur, van Gestel, Anna J, Vink, Geraldine R, Roodhart, Jeanine M L, Externen Med. Onco, Cancer, Onderzoek Medische Oncologie, JC onderzoeksprogramma Kanker, MS Medische Oncologie, Zwart, Koen, van Nassau, Sietske C M W, van der Baan, Frederieke H, Koopman, Miriam, Snaebjornsson, Petur, van Gestel, Anna J, Vink, Geraldine R, and Roodhart, Jeanine M L

Published
2024

6. DNA damage induces p53-independent apoptosis through ribosome stalling

Author

CMM Groep Snippert, Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, Boon, Nicolaas J, Oliveira, Rafaela A, Körner, Pierré-René, Kochavi, Adva, Mertens, Sander, Malka, Yuval, Voogd, Rhianne, van der Horst, Suzanne E M, Huismans, Maarten A, Smabers, Lidwien P, Draper, Jonne M, Wessels, Lodewyk F A, Haahr, Peter, Roodhart, Jeanine M L, Schumacher, Ton N M, Snippert, Hugo J, Agami, Reuven, Brummelkamp, Thijn R, CMM Groep Snippert, Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, Boon, Nicolaas J, Oliveira, Rafaela A, Körner, Pierré-René, Kochavi, Adva, Mertens, Sander, Malka, Yuval, Voogd, Rhianne, van der Horst, Suzanne E M, Huismans, Maarten A, Smabers, Lidwien P, Draper, Jonne M, Wessels, Lodewyk F A, Haahr, Peter, Roodhart, Jeanine M L, Schumacher, Ton N M, Snippert, Hugo J, Agami, Reuven, and Brummelkamp, Thijn R

Published
2024

7. Trastuzumab plus pertuzumab for HER2-amplified advanced colorectal cancer: Results from the drug rediscovery protocol (DRUP)

Author

Pathologie Pathologen staf, Cancer, Pathologie Moleculair, MS Medische Oncologie, Spiekman, Ilse A C, Zeverijn, Laurien J, Geurts, Birgit S, Verkerk, Karlijn, Mohammad, Soemeya F Haj, Noort, Vincent van der, Roepman, Paul, de Leng, Wendy W J, Jansen, Anne M L, Gootjes, Elske C, de Groot, Derk-Jan A, Kerver, Emile D, Voorthuizen, Theo van, Roodhart, Jeanine M L, Iersel, Liselot B J Valkenburg-van, Gelderblom, Hans, Voest, Emile E, Verheul, Henk M W, Pathologie Pathologen staf, Cancer, Pathologie Moleculair, MS Medische Oncologie, Spiekman, Ilse A C, Zeverijn, Laurien J, Geurts, Birgit S, Verkerk, Karlijn, Mohammad, Soemeya F Haj, Noort, Vincent van der, Roepman, Paul, de Leng, Wendy W J, Jansen, Anne M L, Gootjes, Elske C, de Groot, Derk-Jan A, Kerver, Emile D, Voorthuizen, Theo van, Roodhart, Jeanine M L, Iersel, Liselot B J Valkenburg-van, Gelderblom, Hans, Voest, Emile E, and Verheul, Henk M W

Published
2024

8. Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer

Author

Unit Opleiding Aios, Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, Kramer, Astrid, Greuter, Marjolein J E, Schraa, Suzanna J, Vink, Geraldine R, Phallen, Jillian, Velculescu, Victor E, Meijer, Gerrit A, van den Broek, Daan, Koopman, Miriam, Roodhart, Jeanine M L, Fijneman, Remond J A, Retèl, Valesca P, Coupé, Veerle M H, Unit Opleiding Aios, Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, Kramer, Astrid, Greuter, Marjolein J E, Schraa, Suzanna J, Vink, Geraldine R, Phallen, Jillian, Velculescu, Victor E, Meijer, Gerrit A, van den Broek, Daan, Koopman, Miriam, Roodhart, Jeanine M L, Fijneman, Remond J A, Retèl, Valesca P, and Coupé, Veerle M H

Published
2024

9. Benefit of adjuvant chemotherapy on recurrence free survival per consensus molecular subtype in stage III colon cancer

Author

van de Weerd, Simone, Torang, Arezo, van den Berg, Inge, Lammers, Veerle, van den Bergh, Saskia, Brouwer, Nelleke, Nagtegaal, Iris D., Koopman, Miriam, Vink, Geraldine R., van der Baan, Frederieke H., van Krieken, Han, Koster, Jan, Ijzermans, Jan N., Roodhart, Jeanine M. L., Medema, Jan Paul, van de Weerd, Simone, Torang, Arezo, van den Berg, Inge, Lammers, Veerle, van den Bergh, Saskia, Brouwer, Nelleke, Nagtegaal, Iris D., Koopman, Miriam, Vink, Geraldine R., van der Baan, Frederieke H., van Krieken, Han, Koster, Jan, Ijzermans, Jan N., Roodhart, Jeanine M. L., and Medema, Jan Paul

Abstract

The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018. Patients treated with and without adjuvant chemotherapy were matched based on tumor location, T- and N-stage (n = 522). Tumor material was available for 464 patients, with successful RNA extraction and CMS subtyping achieved in 390 patients (surgery alone group: 192, adjuvant chemotherapy group: 198). In the overall cohort, CMS4 was associated with poorest prognosis (HR 1.55; p =.03). Multivariate analysis revealed favorable RFS for the adjuvant chemotherapy group in CMS1, CMS2, and CMS4 tumors (HR 0.19; p =.01, HR 0.27; p <.01, HR 0.19; p <.01, respectively), while no significant difference between treatment groups was observed within CMS3 (HR 0.68; p =.51). CMS subtyping in this non-randomized cohort identified patients with poor prognosis and patients who may not benefit significantly from adjuvant chemotherapy.

Published
2024

10. Harnessing the Potential of Real-World Evidence in the Treatment of Colorectal Cancer: Where Do We Stand?

Author

Onderzoek Medische Oncologie, Cancer, JC onderzoeksprogramma Kanker, MS Medische Oncologie, Epi Kanker Team B, Epi Kanker, van Nassau, Sietske C M W, Bol, Guus M, van der Baan, Frederieke H, Roodhart, Jeanine M L, Vink, Geraldine R, Punt, Cornelis J A, May, Anne M, Koopman, Miriam, Derksen, Jeroen W G, Onderzoek Medische Oncologie, Cancer, JC onderzoeksprogramma Kanker, MS Medische Oncologie, Epi Kanker Team B, Epi Kanker, van Nassau, Sietske C M W, Bol, Guus M, van der Baan, Frederieke H, Roodhart, Jeanine M L, Vink, Geraldine R, Punt, Cornelis J A, May, Anne M, Koopman, Miriam, and Derksen, Jeroen W G

Published
2024

11. Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation:incidence and clinical implications

Author

Filipe, Wills F, Buisman, Florian E, Franssen, Stijn, Krul, Myrtle F, Grünhagen, Dirk J, Bennink, Roel J, Bolhuis, Karen, Bruijnen, Rutger C G, Buffart, Tineke E, Burgmans, Mark C, van Delden, Otto M, Doornebosch, Pascal G, Gobardhan, Paul D, Graven, Laura, de Groot, Jan Willem B, Grootscholten, Cecile, Hagendoorn, Jeroen, Harmsen, Paul, Homs, Marjolein Y V, Klompenhouwer, Elizabeth G, Kok, Niels F M, Lam, Marnix G E H, Loosveld, Olaf J L, Meier, Mark A J, Mieog, J Sven D, Oostdijk, Ad H J, Outmani, Loubna, Patijn, Gijs A, Pool, Stefan, Rietbergen, Daphne D D, Roodhart, Jeanine M L, Speetjens, Frank M, Swijnenburg, Rutger Jan, Versleijen, Michelle W J, Verhoef, Cornelis, Kuhlmann, Koert F D, Moelker, Adriaan, Groot Koerkamp, Bas, Filipe, Wills F, Buisman, Florian E, Franssen, Stijn, Krul, Myrtle F, Grünhagen, Dirk J, Bennink, Roel J, Bolhuis, Karen, Bruijnen, Rutger C G, Buffart, Tineke E, Burgmans, Mark C, van Delden, Otto M, Doornebosch, Pascal G, Gobardhan, Paul D, Graven, Laura, de Groot, Jan Willem B, Grootscholten, Cecile, Hagendoorn, Jeroen, Harmsen, Paul, Homs, Marjolein Y V, Klompenhouwer, Elizabeth G, Kok, Niels F M, Lam, Marnix G E H, Loosveld, Olaf J L, Meier, Mark A J, Mieog, J Sven D, Oostdijk, Ad H J, Outmani, Loubna, Patijn, Gijs A, Pool, Stefan, Rietbergen, Daphne D D, Roodhart, Jeanine M L, Speetjens, Frank M, Swijnenburg, Rutger Jan, Versleijen, Michelle W J, Verhoef, Cornelis, Kuhlmann, Koert F D, Moelker, Adriaan, and Groot Koerkamp, Bas

Abstract

INTRODUCTION: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy.METHODS:The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging ( 99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. RESULTS: Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%.CONCLUSION: Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.

Published
2024

12. Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer.

Author

Kramer, Astrid, Greuter, Marjolein J. E., Schraa, Suzanna J., Vink, Geraldine R., Phallen, Jillian, Velculescu, Victor E., Meijer, Gerrit A., van den Broek, Daan, Koopman, Miriam, Roodhart, Jeanine M. L., Fijneman, Remond J. A., Retèl, Valesca P., and Coupé, Veerle M. H.

Abstract

Background: Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT. Objectives: We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation. Methods: A validated Markov model, simulating 1000 stage II CC patients from diagnosis to death, was supplemented with ctDNA data. Five ACT selection strategies were evaluated: the current guideline (pT4, pMMR), ctDNA-only, and three strategies that combined ctDNA status with pT4 and pMMR status in different ways. For each strategy, the costs, life years, quality-adjusted life years (QALYs), recurrences, and CC deaths were estimated. Sensitivity analyses were performed to assess the impact of the costs of ctDNA testing, strategy adherence, ctDNA as a predictive biomarker, and ctDNA test performance. Results: Model predictions showed that compared to current guidelines, the ctDNA-only strategy was less effective (+2.2% recurrences, −0.016 QALYs), while the combination strategies were more effective (−3.6% recurrences, +0.038 QALYs). The combination strategies were not cost-effective, since the incremental cost-effectiveness ratio was €67,413 per QALY, exceeding the willingness-to-pay threshold of €50,000 per QALY. Sensitivity analyses showed that the combination strategies would be cost-effective if the ctDNA test costs were lower than €1500, or if ctDNA status was predictive of treatment response, or if the ctDNA test performance improved substantially. Conclusion: Adding ctDNA to current high-risk clinicopathological features (pT4 and pMMR) can improve patient selection for ACT and can also potentially be cost-effective. Future studies should investigate the predictive value of post-surgery ctDNA status to accurately evaluate the cost-effectiveness of ctDNA testing for ACT decisions in stage II CC. Plain language summary: Effectiveness and cost-effectiveness of circulating tumour DNA-guided selection for adjuvant chemotherapy in patients with stage II colon cancer Most patients with stage II colon cancer (CC) are cured by surgery. Therefore, guidelines recommend to only offer adjuvant chemotherapy to patients who have a tumor with high-risk features. However, current selection is suboptimal, leading to recurrence of cancer in 13% of low-risk patients and unnecessary administration of chemotherapy in some high-risk patients. Previous studies indicate that a biomarker, so-called circulating tumour DNA (ctDNA), could improve the selection of high-risk patients for adjuvant chemotherapy, as patients who have detectable ctDNA in their blood after surgery are likely to develop a recurrence. Despite its potential, implementation is still pending. Our study assessed the long-term effectiveness and costs associated with various ctDNA-guided strategies for selecting high-risk patients for adjuvant chemotherapy in stage II CC. We used an health-economic model to simulate a cohort of 1000 Dutch patients with stage II CC from diagnosis to death. Next, we compared the health outcomes and costs of the ctDNA-guided strategies to those when selection is based on the Dutch guideline. We found that a combination of the Dutch guideline and ctDNA was the most effective strategy, but not cost-effective. Additional analyses showed that ctDNA-guided selection were cost-effective if the costs of the ctDNA test were below 1500 euros, if the ctDNA test performed significantly better, or if patients with detectable ctDNA responded better to chemotherapy. Thus, while post-surgery ctDNA status is a good indicator for recurrence risk, specific criteria related to ctDNA test performance and costs, in addition to combining ctDNA with current high-risk features, should be met to achieve cost-effective implementation. Looking ahead, future studies should explore how patients with detectable ctDNA respond to chemotherapy for next assessments of the cost-effectiveness of ctDNA-guided strategies in selecting patients with stage II CC for adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Published
2024
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14. DNA damage induces p53-independent apoptosis through ribosome stalling.

Author

Boon, Nicolaas J., Oliveira, Rafaela A., Körner, Pierré-René, Kochavi, Adva, Mertens, Sander, Malka, Yuval, Voogd, Rhianne, van der Horst, Suzanne E. M., Huismans, Maarten A., Smabers, Lidwien P., Draper, Jonne M., Wessels, Lodewyk F. A., Haahr, Peter, Roodhart, Jeanine M. L., Schumacher, Ton N. M., Snippert, Hugo J., Agami, Reuven, and Brummelkamp, Thijn R.

Published
2024

15. Stromal localization of inactive CD8+ T cells in metastatic mismatch repair deficient colorectal cancer.

Author

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, and Vercoulen, Yvonne

Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Prognostic value of Lynch syndrome, BRAFV600E, and RAS mutational status in dMMR/MSI‐H metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts

Author

Zwart, Koen, primary, van der Baan, Frederieke H., additional, Cohen, Romain, additional, Aparicio, Thomas, additional, de la Fouchardiére, Christelle, additional, Lecomte, Thierry, additional, Punt, Cornelis J. A., additional, Sefrioui, David, additional, Verheijden, Rik J., additional, Vink, Geraldine R., additional, Wensink, G. Emerens, additional, Zaanan, Aziz, additional, Koopman, Miriam, additional, Tougeron, David, additional, and Roodhart, Jeanine M. L., additional

Published
2023
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19. Drug-repurposing screen on patient-derived organoids identifies therapy-induced vulnerability in KRAS-mutant colon cancer

Author

Mertens, Sander, Huismans, Maarten A, Verissimo, Carla S, Ponsioen, Bas, Overmeer, Rene, Proost, Natalie, van Tellingen, Olaf, van de Ven, Marieke, Begthel, Harry, Boj, Sylvia F, Clevers, Hans, Roodhart, Jeanine M L, Bos, Johannes L, Snippert, Hugo J G, Mertens, Sander, Huismans, Maarten A, Verissimo, Carla S, Ponsioen, Bas, Overmeer, Rene, Proost, Natalie, van Tellingen, Olaf, van de Ven, Marieke, Begthel, Harry, Boj, Sylvia F, Clevers, Hans, Roodhart, Jeanine M L, Bos, Johannes L, and Snippert, Hugo J G

Abstract

Patient-derived organoids (PDOs) are widely heralded as a drug-screening platform to develop new anti-cancer therapies. Here, we use a drug-repurposing library to screen PDOs of colorectal cancer (CRC) to identify hidden vulnerabilities within therapy-induced phenotypes. Using a microscopy-based screen that accurately scores drug-induced cell killing, we have tested 414 putative anti-cancer drugs for their ability to switch the EGFRi/MEKi-induced cytostatic phenotype toward cytotoxicity. A majority of validated hits (9/37) are microtubule-targeting agents that are commonly used in clinical oncology, such as taxanes and vinca-alkaloids. One of these drugs, vinorelbine, is consistently effective across a panel of >25 different CRC PDOs, independent of RAS mutational status. Unlike vinorelbine alone, its combination with EGFR/MEK inhibition induces apoptosis at all stages of the cell cycle and shows tolerability and effective anti-tumor activity in vivo, setting the basis for a clinical trial to treat patients with metastatic RAS-mutant CRC.

Published
2023

20. Lymphatic Invasion of Plakoglobin-Dependent Tumor Cell Clusters Drives Formation of Polyclonal Lung Metastases in Colon Cancer

Author

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, 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, and Kranenburg, Onno

Abstract

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

Published
2023

21. Prognostic value of Lynch syndrome, BRAF V600E, and RAS mutational status in dMMR/MSI-H metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts.

Author

Onderzoek Medische Oncologie, Cancer, JC onderzoeksprogramma Kanker, Epi Kanker Team B, MS Medische Oncologie, Unit Opleiding Aios, Zwart, Koen, van der Baan, Frederieke H, Cohen, Romain, Aparicio, Thomas, de la Fouchardiére, Christelle, Lecomte, Thierry, Punt, Cornelis J A, Sefrioui, David, Verheijden, Rik J, Vink, Geraldine R, Wensink, G Emerens, Zaanan, Aziz, Koopman, Miriam, Tougeron, David, Roodhart, Jeanine M L, Onderzoek Medische Oncologie, Cancer, JC onderzoeksprogramma Kanker, Epi Kanker Team B, MS Medische Oncologie, Unit Opleiding Aios, Zwart, Koen, van der Baan, Frederieke H, Cohen, Romain, Aparicio, Thomas, de la Fouchardiére, Christelle, Lecomte, Thierry, Punt, Cornelis J A, Sefrioui, David, Verheijden, Rik J, Vink, Geraldine R, Wensink, G Emerens, Zaanan, Aziz, Koopman, Miriam, Tougeron, David, and Roodhart, Jeanine M L

Published
2023

22. Drug-repurposing screen on patient-derived organoids identifies therapy-induced vulnerability in KRAS-mutant colon cancer

Author

CMM Groep Snippert, Cancer, CMM Groep Bos, Hubrecht Institute with UMC, CMM, MS Medische Oncologie, CMM Groep Van Mil, Mertens, Sander, Huismans, Maarten A, Verissimo, Carla S, Ponsioen, Bas, Overmeer, Rene, Proost, Natalie, van Tellingen, Olaf, van de Ven, Marieke, Begthel, Harry, Boj, Sylvia F, Clevers, Hans, Roodhart, Jeanine M L, Bos, Johannes L, Snippert, Hugo J G, CMM Groep Snippert, Cancer, CMM Groep Bos, Hubrecht Institute with UMC, CMM, MS Medische Oncologie, CMM Groep Van Mil, Mertens, Sander, Huismans, Maarten A, Verissimo, Carla S, Ponsioen, Bas, Overmeer, Rene, Proost, Natalie, van Tellingen, Olaf, van de Ven, Marieke, Begthel, Harry, Boj, Sylvia F, Clevers, Hans, Roodhart, Jeanine M L, Bos, Johannes L, and Snippert, Hugo J G

Published
2023

23. A Case of Yellow Airway Secretions and Oral Fluid

Author

CDL Klinisch Chemici in opleiding, MS Medische Oncologie, Cancer, CDL Cluster Front office & ext. business, Infection & Immunity, CDL Cluster 24/7 centraal laboratorium, Other research (not in main researchprogram), Zuidhof, Hidde R, van Schelt, Martijn, Roodhart, Jeanine M L, Ten Berg, Maarten J, Kemperman, Hans, CDL Klinisch Chemici in opleiding, MS Medische Oncologie, Cancer, CDL Cluster Front office & ext. business, Infection & Immunity, CDL Cluster 24/7 centraal laboratorium, Other research (not in main researchprogram), Zuidhof, Hidde R, van Schelt, Martijn, Roodhart, Jeanine M L, Ten Berg, Maarten J, and Kemperman, Hans

Published
2023

24. Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases

Author

Wensink, G E, primary, Bolhuis, Karen, additional, Elferink, Marloes A G, additional, Fijneman, Remond J A, additional, Kranenburg, Onno, additional, Borel Rinkes, Inne H M, additional, Koopman, Miriam, additional, Swijnenburg, Rutger-Jan, additional, Vink, Geraldine R, additional, Hagendoorn, Jeroen, additional, Punt, Cornelis J A, additional, Roodhart, Jeanine M L, additional, and Elias, Sjoerd G, additional

Published
2023
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25. Modeling resistance of colorectal peritoneal metastases to immune checkpoint blockade in humanized mice

Author

Küçükköse, Emre, primary, Heesters, Balthasar A, additional, Villaudy, Julien, additional, Verheem, André, additional, Cercel, Madalina, additional, van Hal, Susan, additional, Boj, Sylvia F, additional, Borel Rinkes, Inne H M, additional, Punt, Cornelis J A, additional, Roodhart, Jeanine M L, additional, Laoukili, Jamila, additional, Koopman, Miriam, additional, Spits, Hergen, additional, and Kranenburg, Onno, additional

Published
2022
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26. Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients

Author

van de Weerd, Simone, primary, Smit, Marloes A., additional, Roelands, Jessica, additional, Mesker, Wilma E., additional, Bedognetti, Davide, additional, Kuppen, Peter J. K., additional, Putter, Hein, additional, Tollenaar, Rob A. E. M., additional, Roodhart, Jeanine M. L., additional, Hendrickx, Wouter, additional, Medema, Jan Paul, additional, and van Krieken, J. Han J. M., additional

Published
2022
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27. External Validation of the Colon Life Nomogram for Predicting 12-Week Mortality in Dutch Metastatic Colorectal Cancer Patients Treated with Trifluridine/Tipiracil in Daily Practice

Author

Hamers, Patricia A. H., primary, Wensink, G. Emerens, additional, van Smeden, Maarten, additional, Vink, Geraldine R., additional, Smabers, Lidwien P., additional, Lunenberg, Renee A., additional, Laclé, Miangela M., additional, Koopman, Miriam, additional, May, Anne M., additional, and Roodhart, Jeanine M. L., additional

Published
2022
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28. Prognostic value of Lynch syndrome, BRAFV600E, and RAS mutational status in dMMR/MSI‐H metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts.

Author

Zwart, Koen, van der Baan, Frederieke H., Cohen, Romain, Aparicio, Thomas, de la Fouchardiére, Christelle, Lecomte, Thierry, Punt, Cornelis J. A., Sefrioui, David, Verheijden, Rik J., Vink, Geraldine R., Wensink, G. Emerens, Zaanan, Aziz, Koopman, Miriam, Tougeron, David, and Roodhart, Jeanine M. L.

Subjects
COLORECTAL cancer, HEREDITARY nonpolyposis colorectal cancer, PROGNOSIS, METASTASIS, CANCER chemotherapy, REGRESSION analysis
Abstract

Background: Current knowledge on prognostic biomarkers (especially BRAFV600E/RAS mutations) in metastatic colorectal cancer (mCRC) is mainly based on mCRC patients with proficient mismatch repair (pMMR) tumors. It is uncertain whether these biomarkers have the same prognostic value in mCRC patients with deficient mismatch repair (dMMR) tumors. Methods: This observational cohort study combined a population‐based Dutch cohort (2014–2019) and a large French multicenter cohort (2007–2017). All mCRC patients with a histologically proven dMMR tumor were included. Results: In our real‐world data cohort of 707 dMMR mCRC patients, 438 patients were treated with first‐line palliative systemic chemotherapy. Mean age of first‐line treated patients was 61.9 years, 49% were male, and 40% had Lynch syndrome. BRAFV600E mutation was present in 47% of tumors and 30% harbored a RAS mutation. Multivariable regression analysis on OS showed significant hazard rates (HR) for known prognostic factors as age and performance status, however showed no significance for Lynch syndrome (HR: 1.07, 95% CI: 0.66–1.72), BRAFV600E mutational status (HR: 1.02, 95% CI: 0.67–1.54), and RAS mutational status (HR: 1.01, 95% CI: 0.64–1.59), with similar results for PFS. Conclusion: BRAFV600E and RAS mutational status are not associated with prognosis in dMMR mCRC patients, in contrast to pMMR mCRC patients. Lynch syndrome is also not an independent prognostic factor for survival. These findings underline that prognostic factors of patients with dMMR mCRC are different of those with pMMR, which could be taken into consideration when prognosis is used for clinical decision‐making in dMMR mCRC patients and underline the complex heterogeneity of mCRC. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Consensus molecular subtype 4 (CMS4)-targeted therapy in primary colon cancer: A proof-of-concept study

Author

Peters, Niek A., primary, Constantinides, Alexander, additional, Ubink, Inge, additional, van Kuik, Joyce, additional, Bloemendal, Haiko J., additional, van Dodewaard, Joyce M., additional, Brink, Menno A., additional, Schwartz, Thijs P., additional, Lolkema, Martijn P.J.K., additional, Lacle, Miangela M., additional, Moons, Leon M., additional, Geesing, Joost, additional, van Grevenstein, Wilhelmina M.U., additional, Roodhart, Jeanine M. L., additional, Koopman, Miriam, additional, Elias, Sjoerd G., additional, Borel Rinkes, Inne H.M., additional, and Kranenburg, Onno, additional

Published
2022
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31. Modeling resistance of colorectal peritoneal metastases to immune checkpoint blockade in humanized mice

Author

Lab Translational Oncology, Cancer, Hubrecht Institute with UMC, MS CGO, Regenerative Medicine and Stem Cells, Epi Kanker Team B, MS Medische Oncologie, Küçükköse, Emre, Heesters, Balthasar A, Villaudy, Julien, Verheem, André, Cercel, Madalina, van Hal, Susan, Boj, Sylvia F, Borel Rinkes, Inne H M, Punt, Cornelis J A, Roodhart, Jeanine M L, Laoukili, Jamila, Koopman, Miriam, Spits, Hergen, Kranenburg, Onno, Lab Translational Oncology, Cancer, Hubrecht Institute with UMC, MS CGO, Regenerative Medicine and Stem Cells, Epi Kanker Team B, MS Medische Oncologie, Küçükköse, Emre, Heesters, Balthasar A, Villaudy, Julien, Verheem, André, Cercel, Madalina, van Hal, Susan, Boj, Sylvia F, Borel Rinkes, Inne H M, Punt, Cornelis J A, Roodhart, Jeanine M L, Laoukili, Jamila, Koopman, Miriam, Spits, Hergen, and Kranenburg, Onno

Published
2022

32. Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients

Author

MS Medische Oncologie, Cancer, van de Weerd, Simone, Smit, Marloes A, Roelands, Jessica, Mesker, Wilma E, Bedognetti, Davide, Kuppen, Peter J K, Putter, Hein, Tollenaar, Rob A E M, Roodhart, Jeanine M L, Hendrickx, Wouter, Medema, Jan Paul, van Krieken, J Han J M, MS Medische Oncologie, Cancer, van de Weerd, Simone, Smit, Marloes A, Roelands, Jessica, Mesker, Wilma E, Bedognetti, Davide, Kuppen, Peter J K, Putter, Hein, Tollenaar, Rob A E M, Roodhart, Jeanine M L, Hendrickx, Wouter, Medema, Jan Paul, and van Krieken, J Han J M

Published
2022

33. External Validation of Two Established Clinical Risk Scores Predicting Outcome after Local Treatment of Colorectal Liver Metastases in a Nationwide Cohort

Author

Bolhuis, Karen, primary, Wensink, G. Emerens, additional, Elferink, Marloes A. G., additional, Bond, Marinde J. G., additional, Dijksterhuis, Willemieke P. M., additional, Fijneman, Remond J. A., additional, Kranenburg, Onno W., additional, Rinkes, Inne H. M. Borel, additional, Koopman, Miriam, additional, Swijnenburg, Rutger-Jan, additional, Vink, Geraldine R., additional, Hagendoorn, Jeroen, additional, Punt, Cornelis J. A., additional, Elias, Sjoerd G., additional, and Roodhart, Jeanine M. L., additional

Published
2022
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34. External validation of the MSKCC nomogram to estimate five-year overall survival after surgery for stage I–III colon cancer in a Dutch population

Author

Bond, Marinde J. G., primary, Hamers, Patricia A. H., additional, Vink, Geraldine R., additional, van Grevenstein, Wilhelmina M. U., additional, Laclé, Miangela M., additional, van Smeden, Maarten, additional, Koopman, Miriam, additional, Roodhart, Jeanine M. L., additional, Punt, Cornelis J. A., additional, and May, Anne M., additional

Published
2022
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35. Mismatch Repair Status in Patient-Derived Colorectal Cancer Organoids Does Not Affect Intrinsic Tumor Cell Sensitivity to Systemic Therapy

Author

Küçükköse, Emre, primary, Wensink, G. Emerens, additional, Roelse, Celine M., additional, van Schelven, Susanne J., additional, Raats, Daniëlle A. E., additional, Boj, Sylvia F., additional, Koopman, Miriam, additional, Laoukili, Jamila, additional, Roodhart, Jeanine M. L., additional, and Kranenburg, Onno, additional

Published
2021
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37. The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care

Author

Derksen, Jeroen W. G., Vink, Geraldine R., Elferink, Marloes A. G., Roodhart, Jeanine M. L., Verkooijen, Helena M., van Grevenstein, Wilhelmina M. U., Siersema, Peter D., May, Anne M., Koopman, Miriam, Beets, Geerard L., Belt, Eric J. Th., Berbée, Maaike, Beverdam, Frederique H., Blankenburgh, Ruud, Coene, Peter Paul L. O., van Cruijsen, Hester, Dekker, Jan Willem T., van Dodewaard-de Jong, Joyce M., Erdkamp, Frans L. G., de Groot, Jan Willem B., Haringhuizen, Annebeth W., Helgason, Helgi H., Hendriks, Mathijs P., de Hingh, Ignace H. J. T., Hoekstra, Ronald, Ijzermans, Jan N. M., Jansen, Jan, Kloppenberg, Frank W. H., van Lent, Anja U. G., Los, Maartje, Meijerink, Martijn R., Mekenkamp, Leonie J. M., Nieboer, Peter, Peeters, Koen C. M. J., Peters, Natascha A. J. B., Polée, Marco B., Pruijt, Johannes F. M., Punt, Cornelis J. A., van Ufford-Mannesse, Patricia Quarles, Rietbroek, Ron C., Schiphorst, Anandi H. W., van der Velden, Arjan Schouten, Schrauwen, Ruud W. M., Sie, Mark P. S., Simkens, Lieke, Sommeijer, Dirkje W., Sonneveld, Dirk J. A., Spierings, Leontine E. A., Stockmann, Hein B. A. C., Talsma, Koen, Terheggen, Frederiek, ten Tije, Albert J., Tjin-A-Ton, Manuel L. R., Valkenburg-van Iersel, Liselot B. J., Veenstra, Renzo P., van der Velden, Ankie M. T., Vermaas, Maarten, Vles, Wouter J., Vogelaar, Jeroen F. J., van Voorthuizen, Theo, de Vos, Aad I., Wegdam, Johannes A., de Wilt, Johannes H. W., Zimmerman, David D. E., Surgery, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Epidemiologie, CCA - Cancer Treatment and quality of life, Radiology and nuclear medicine, Internal medicine, and VU University medical center

Subjects
Male, medicine.medical_specialty, Colorectal cancer, Epidemiology, Science, Population, MODELS, MEDLINE, Logistic regression, Representativeness heuristic, Article, 03 medical and health sciences, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, Cancer epidemiology, Medical research, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Multidisciplinary approach, COLON, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Registries, education, Aged, Netherlands, Aged, 80 and over, education.field_of_study, Multidisciplinary, business.industry, Middle Aged, medicine.disease, Cancer registry, TRIALS, Outcomes research, 030220 oncology & carcinogenesis, Family medicine, Cohort, Medicine, Female, business, Colorectal Neoplasms
Abstract

Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system.

Published
2021
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38. Patient-derived organoids as a predictive biomarker for treatment response in cancer patients

Author

Onderzoek Medische Oncologie, Cancer, Epi Kanker Team A, JC onderzoeksprogramma Kanker, MS Medische Oncologie, Hubrecht Institute with UMC, Lab Translational Oncology, Regenerative Medicine and Stem Cells, Wensink, G Emerens, Elias, Sjoerd G, Mullenders, Jasper, Koopman, Miriam, Boj, Sylvia F, Kranenburg, Onno W, Roodhart, Jeanine M L, Onderzoek Medische Oncologie, Cancer, Epi Kanker Team A, JC onderzoeksprogramma Kanker, MS Medische Oncologie, Hubrecht Institute with UMC, Lab Translational Oncology, Regenerative Medicine and Stem Cells, Wensink, G Emerens, Elias, Sjoerd G, Mullenders, Jasper, Koopman, Miriam, Boj, Sylvia F, Kranenburg, Onno W, and Roodhart, Jeanine M L

Published
2021

39. Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era

Author

Verpleegafdeling Medische Oncologie, Onderzoek Medische Oncologie, Cancer, Epidemiology & Health Economics, JC onderzoeksprogramma Kanker, MS Medische Oncologie, Wensink, G Emerens, Elferink, Marloes A G, May, Anne M, Mol, Linda, Hamers, Patricia A H, Bakker, Sandra D, Creemers, Geert-Jan, de Groot, Jan Willem B, de Klerk, Gerty J, Haberkorn, Brigitte C M, Haringhuizen, Annebeth W, Hoekstra, Ronald, Hunting, J Cornelis B, Kerver, Emile D, Mathijssen-van Stein, Danielle, Polée, Marco B, Pruijt, Johannes F M, Quarles van Ufford-Mannesse, Patricia, Radema, Sandra, Rietbroek, Ronald C, Simkens, Lieke H J, Tanis, Bea C, Ten Bokkel Huinink, Daan, Tjin-A-Ton, Manuel L R, Tromp-van Driel, Cathrien S, Troost, Monique M, van de Wouw, Agnes J, van den Berkmortel, Franchette W P J, van der Pas, Anke J M, van der Velden, Ankie M T, van Dijk, Marjan A, van Dodewaard-de Jong, Joyce M, van Druten, Edith B, van Voorthuizen, Theo, Jan Veldhuis, Gerrit, Verheul, Henk M W, Vestjens, Hanneke J H M J, Vincent, Jeroen, Kranenburg, Onno W, Punt, Cornelis J A, Vink, Geraldine R, Roodhart, Jeanine M L, Koopman, Miriam, Verpleegafdeling Medische Oncologie, Onderzoek Medische Oncologie, Cancer, Epidemiology & Health Economics, JC onderzoeksprogramma Kanker, MS Medische Oncologie, Wensink, G Emerens, Elferink, Marloes A G, May, Anne M, Mol, Linda, Hamers, Patricia A H, Bakker, Sandra D, Creemers, Geert-Jan, de Groot, Jan Willem B, de Klerk, Gerty J, Haberkorn, Brigitte C M, Haringhuizen, Annebeth W, Hoekstra, Ronald, Hunting, J Cornelis B, Kerver, Emile D, Mathijssen-van Stein, Danielle, Polée, Marco B, Pruijt, Johannes F M, Quarles van Ufford-Mannesse, Patricia, Radema, Sandra, Rietbroek, Ronald C, Simkens, Lieke H J, Tanis, Bea C, Ten Bokkel Huinink, Daan, Tjin-A-Ton, Manuel L R, Tromp-van Driel, Cathrien S, Troost, Monique M, van de Wouw, Agnes J, van den Berkmortel, Franchette W P J, van der Pas, Anke J M, van der Velden, Ankie M T, van Dijk, Marjan A, van Dodewaard-de Jong, Joyce M, van Druten, Edith B, van Voorthuizen, Theo, Jan Veldhuis, Gerrit, Verheul, Henk M W, Vestjens, Hanneke J H M J, Vincent, Jeroen, Kranenburg, Onno W, Punt, Cornelis J A, Vink, Geraldine R, Roodhart, Jeanine M L, and Koopman, Miriam

Published
2021

40. European practice patterns and barriers to smoking cessation after a cancer diagnosis in the setting of curative versus palliative cancer treatment

Author

Derksen, Jeroen W. G., Warren, Graham W., Jordan, Karin, Rauh, Stefan, Vera Garcia, Ruth, O'Mahony, Deirdre, Ahmed, Samreen, Vuylsteke, Peter, Radulovic, Sinisa, Tsoukalas, Nikolaos, Wysocki, Piotr J., Borner, Markus, Cesas, Alvydas, Elme, Anneli, Minn, Heikki, Ullenhag, Gustav J., Roodhart, Jeanine M. L., Koopman, Miriam, May, Anne M., Derksen, Jeroen W. G., Warren, Graham W., Jordan, Karin, Rauh, Stefan, Vera Garcia, Ruth, O'Mahony, Deirdre, Ahmed, Samreen, Vuylsteke, Peter, Radulovic, Sinisa, Tsoukalas, Nikolaos, Wysocki, Piotr J., Borner, Markus, Cesas, Alvydas, Elme, Anneli, Minn, Heikki, Ullenhag, Gustav J., Roodhart, Jeanine M. L., Koopman, Miriam, and May, Anne M.

Abstract

Background: Smoking cessation after a cancer diagnosis is associated with improved overall survival. Few studies have reported oncologists' cessation practice patterns, but differences between the curative and palliative settings have not been described. We aimed to study the oncologist's perceptions on patients' tobacco use, current practices and barriers to providing smoking cessation support, while distinguishing between treatment with curative (C) and palliative (P) intent. Methods: In 2019, an online 34-item survey was sent to approximately 6235 oncologists from 16 European countries. Responses were descriptively reported and compared by treatment setting. Results: Responses from 544 oncologists were included. Oncologists appeared to favour addressing tobacco in the curative setting more than in the palliative setting. Oncologists believe that continued smoking impacts treatment outcomes (C: 94%, P: 74%) and that cessation support should be standard cancer care (C: 95%, P: 63%). Most routinely assess tobacco use (C: 93%, P: 78%) and advise patients to stop using tobacco (C: 88%, P: 54%), but only 24% (P)–39% (C) routinely discuss medication options, and only 18% (P)–31% (C) provide cessation support. Hesitation to remove a pleasurable habit (C: 13%, P: 43%) and disbelieve on smoking affecting outcomes (C: 3%, P: 14%) were disparate barriers between the curative and palliative settings (p < 0.001), but dominant barriers of time, resources, education and patient resistance were similar between settings. Conclusion: Oncologists appear to favour addressing tobacco use more in the curative setting; however, they discuss medication options and/or provide cessation support in a minority of cases. All patients who report current smoking should have access to evidence-based smoking cessation support, also patients treated with palliative intent given their increasing survival.

Published
2020
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41. European practice patterns and barriers to smoking cessation after a cancer diagnosis in the setting of curative versus palliative cancer treatment.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'oncologie médicale, Derksen, Jeroen W G, Warren, Graham W, Jordan, Karin, Rauh, Stefan, Vera García, Ruth, O'Mahony, Deirdre, Ahmed, Samreen, Vuylsteke, Peter, Radulovic, Sinisa, Tsoukalas, Nikolaos, Wysocki, Piotr J, Borner, Markus, Cesas, Alvydas, Elme, Anneli, Minn, Heikki, Ullenhag, Gustav J, Roodhart, Jeanine M L, Koopman, Miriam, May, Anne M, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'oncologie médicale, Derksen, Jeroen W G, Warren, Graham W, Jordan, Karin, Rauh, Stefan, Vera García, Ruth, O'Mahony, Deirdre, Ahmed, Samreen, Vuylsteke, Peter, Radulovic, Sinisa, Tsoukalas, Nikolaos, Wysocki, Piotr J, Borner, Markus, Cesas, Alvydas, Elme, Anneli, Minn, Heikki, Ullenhag, Gustav J, Roodhart, Jeanine M L, Koopman, Miriam, and May, Anne M

Abstract

BACKGROUND: Smoking cessation after a cancer diagnosis is associated with improved overall survival. Few studies have reported oncologists' cessation practice patterns, but differences between the curative and palliative settings have not been described. We aimed to study the oncologist's perceptions on patients' tobacco use, current practices and barriers to providing smoking cessation support, while distinguishing between treatment with curative (C) and palliative (P) intent. METHODS: In 2019, an online 34-item survey was sent to approximately 6235 oncologists from 16 European countries. Responses were descriptively reported and compared by treatment setting. RESULTS: Responses from 544 oncologists were included. Oncologists appeared to favour addressing tobacco in the curative setting more than in the palliative setting. Oncologists believe that continued smoking impacts treatment outcomes (C: 94%, P: 74%) and that cessation support should be standard cancer care (C: 95%, P: 63%). Most routinely assess tobacco use (C: 93%, P: 78%) and advise patients to stop using tobacco (C: 88%, P: 54%), but only 24% (P)-39% (C) routinely discuss medication options, and only 18% (P)-31% (C) provide cessation support. Hesitation to remove a pleasurable habit (C: 13%, P: 43%) and disbelieve on smoking affecting outcomes (C: 3%, P: 14%) were disparate barriers between the curative and palliative settings (p < 0.001), but dominant barriers of time, resources, education and patient resistance were similar between settings. CONCLUSION: Oncologists appear to favour addressing tobacco use more in the curative setting; however, they discuss medication options and/or provide cessation support in a minority of cases. All patients who report current smoking should have access to evidence-based smoking cessation support, also patients treated with palliative intent given their increasing survival.

Published
2020

42. Colorectal Cancer Modeling with Organoids: Discriminating between Oncogenic RAS and BRAF Variants

Author

CMM Sectie Molecular Cancer Research, CMM, CMM Groep Bos, Zorg Medisch Oncologische Disciplines, MS Medische Oncologie, Cancer, CMM Groep Snippert, Post, Jasmin B, Roodhart, Jeanine M L, Snippert, Hugo J G, CMM Sectie Molecular Cancer Research, CMM, CMM Groep Bos, Zorg Medisch Oncologische Disciplines, MS Medische Oncologie, Cancer, CMM Groep Snippert, Post, Jasmin B, Roodhart, Jeanine M L, and Snippert, Hugo J G

Published
2020

43. European practice patterns and barriers to smoking cessation after a cancer diagnosis in the setting of curative versus palliative cancer treatment

Author

MS Hematologie, Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, Epidemiology & Health Economics, JC onderzoeksprogramma Kanker, Derksen, Jeroen W G, Warren, Graham W, Jordan, Karin, Rauh, Stefan, Vera García, Ruth, O'Mahony, Deirdre, Ahmed, Samreen, Vuylsteke, Peter, Radulovic, Sinisa, Tsoukalas, Nikolaos, Wysocki, Piotr J, Borner, Markus, Cesas, Alvydas, Elme, Anneli, Minn, Heikki, Ullenhag, Gustav J, Roodhart, Jeanine M L, Koopman, Miriam, May, Anne M, MS Hematologie, Cancer, Onderzoek Medische Oncologie, MS Medische Oncologie, Epidemiology & Health Economics, JC onderzoeksprogramma Kanker, Derksen, Jeroen W G, Warren, Graham W, Jordan, Karin, Rauh, Stefan, Vera García, Ruth, O'Mahony, Deirdre, Ahmed, Samreen, Vuylsteke, Peter, Radulovic, Sinisa, Tsoukalas, Nikolaos, Wysocki, Piotr J, Borner, Markus, Cesas, Alvydas, Elme, Anneli, Minn, Heikki, Ullenhag, Gustav J, Roodhart, Jeanine M L, Koopman, Miriam, and May, Anne M

Published
2020

44. Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era

Author

Wensink, G. Emerens, primary, Elferink, Marloes A. G., additional, May, Anne M., additional, Mol, Linda, additional, Hamers, Patricia A. H., additional, Bakker, Sandra D., additional, Creemers, Geert-Jan, additional, de Groot, Jan Willem B., additional, de Klerk, Gerty J., additional, Haberkorn, Brigitte C. M., additional, Haringhuizen, Annebeth W., additional, Hoekstra, Ronald, additional, Hunting, J. Cornelis B., additional, Kerver, Emile D., additional, Mathijssen-van Stein, Danielle, additional, Polée, Marco B., additional, Pruijt, Johannes F. M., additional, Quarles van Ufford-Mannesse, Patricia, additional, Radema, Sandra, additional, Rietbroek, Ronald C., additional, Simkens, Lieke H. J., additional, Tanis, Bea C., additional, ten Bokkel Huinink, Daan, additional, Tjin-A-Ton, Manuel L. R., additional, Tromp-van Driel, Cathrien S., additional, Troost, Monique M., additional, van de Wouw, Agnes J., additional, van den Berkmortel, Franchette W. P. J., additional, van der Pas, Anke J. M., additional, van der Velden, Ankie M. T., additional, van Dijk, Marjan A., additional, van Dodewaard-de Jong, Joyce M., additional, van Druten, Edith B., additional, van Voorthuizen, Theo, additional, Jan Veldhuis, Gerrit, additional, Verheul, Henk M. W., additional, Vestjens, Hanneke J. H. M. J., additional, Vincent, Jeroen, additional, Kranenburg, Onno W., additional, Punt, Cornelis J. A., additional, Vink, Geraldine R., additional, Roodhart, Jeanine M. L., additional, and Koopman, Miriam, additional

Published
2020
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45. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance

Author

Houthuijzen, Julia M, Oosterom, Ilse, Hudson, Brian D, Hirasawa, Akira, Daenen, Laura G M, McLean, Chelsea M, Hansen, Steffen V F, van Jaarsveld, Marijn T M, Peeper, Daniel S, Jafari Sadatmand, Sahar, Roodhart, Jeanine M L, van de Lest, Chris H A, Ulven, Trond, Ishihara, Kenji, Milligan, Graeme, Voest, Emile E, LS Veterinaire biochemie, dB&C FR-RMSC FR, and dES RMSC

Subjects
GPR40, FFAR4, PIFA, FFAR1
Abstract

Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) induces systemic resistance to a broad range of DNA-damaging chemotherapeutics. We show that 16:4(n-3) exerts its effect by activating splenic F4/80(+)/CD11b(low) macrophages, which results in production of chemoprotective lysophosphatidylcholines (LPCs). Pharmacologic studies, together with analysis of expression patterns, identified GPR120 on F4/80(+)/CD11b(low) macrophages as the relevant receptor for 16:4(n-3). Studies that used splenocytes from GPR120-deficient mice have confirmed this conclusion. Activation of the 16:4(n-3)-GPR120 axis led to enhanced cPLA2 activity in these splenic macrophages and secretion of the resistance-inducing lipid mediator, lysophosphatidylcholine(24:1). These studies identify a novel and unexpected function for GPR120 and suggest that antagonists of this receptor might be effective agents to limit development of chemotherapy resistance.-Houthuijzen, J. M., Oosterom, I., Hudson, B. D., Hirasawa, A., Daenen, L. G. M., McLean, C. M., Hansen, S. V. F., van Jaarsveld, M. T. M., Peeper, D. S., Jafari Sadatmand, S., Roodhart, J. M. L., van de Lest, C. H. A., Ulven, T., Ishihara, K., Milligan, G., Voest, E. E. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance.

Published
2017

46. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance

Author

LS Veterinaire biochemie, dB&C FR-RMSC FR, dES RMSC, Houthuijzen, Julia M, Oosterom, Ilse, Hudson, Brian D, Hirasawa, Akira, Daenen, Laura G M, McLean, Chelsea M, Hansen, Steffen V F, van Jaarsveld, Marijn T M, Peeper, Daniel S, Jafari Sadatmand, Sahar, Roodhart, Jeanine M L, van de Lest, Chris H A, Ulven, Trond, Ishihara, Kenji, Milligan, Graeme, Voest, Emile E, LS Veterinaire biochemie, dB&C FR-RMSC FR, dES RMSC, Houthuijzen, Julia M, Oosterom, Ilse, Hudson, Brian D, Hirasawa, Akira, Daenen, Laura G M, McLean, Chelsea M, Hansen, Steffen V F, van Jaarsveld, Marijn T M, Peeper, Daniel S, Jafari Sadatmand, Sahar, Roodhart, Jeanine M L, van de Lest, Chris H A, Ulven, Trond, Ishihara, Kenji, Milligan, Graeme, and Voest, Emile E

Published
2017

47. Lysophospholipids secreted by splenic macrophages induce chemotherapy resistance via interference with the DNA damage response

Author

Houthuijzen, Julia M, Daenen, Laura G M, Roodhart, Jeanine M L, Oosterom, Ilse, van Jaarsveld, Marijn T M, Govaert, Klaas M, Smith, Michelle E, Sadatmand, Sahar J, Rosing, Hilde, Kruse, Fabian, Helms, Bernd J, van Rooijen, Nico, Beijnen, Jos H, Haribabu, Bodduluri, van de Lest, Chris H A, Voest, Emile E, LS Equine Muscoskeletal Biology, LS Veterinaire biochemie, Dep Biochemie en Celbiologie, LS Algemeen B&C, Sub Clinical Pharmacology, B&C BRC-SIB-TR, Tissue Repair, UIPS - Utrecht Institute for Pharmaceutical Sciences, Molecular cell biology and Immunology, CCA - Immuno-pathogenesis, LS Equine Muscoskeletal Biology, LS Veterinaire biochemie, Dep Biochemie en Celbiologie, LS Algemeen B&C, Sub Clinical Pharmacology, B&C BRC-SIB-TR, Tissue Repair, and UIPS - Utrecht Institute for Pharmaceutical Sciences

Subjects
Male, DNA damage, Receptors, Leukotriene B4, General Physics and Astronomy, Antineoplastic Agents, Drug resistance, Biology, Mass Spectrometry, General Biochemistry, Genetics and Molecular Biology, Mice, In vivo, medicine, Splenocyte, Animals, Receptor, Cisplatin, Mice, Inbred BALB C, Multidisciplinary, Leukotriene B4 receptor 2, Macrophages, Neoplasms, Experimental, General Chemistry, Mice, Inbred C57BL, Integrin alpha M, Drug Resistance, Neoplasm, Immunology, Fatty Acids, Unsaturated, Splenectomy, biology.protein, Cancer research, Lysophospholipids, Spleen, DNA Damage, medicine.drug
Abstract

Host responses to systemic anti-cancer treatment play important roles in the development of anti-cancer drug resistance. Here we show that F4/80(+)/CD11b(low) splenocytes mediate the resistance to DNA-damaging chemotherapeutics induced by two platinum-induced fatty acids (PIFAs), 12-S-keto-5,8,10-heptadecatrienoic acid and 4,7,10,13-hexadecatetraenoic acid (16:4(n-3)) in xenograft mouse models. Splenectomy or depletion of splenic macrophages by liposomal clodronate protects against PIFA-induced chemoresistance. In addition, we find that 12-S-HHT, but not 16:4(n-3), functions via leukotriene B4 receptor 2 (BLT2). Genetic loss or chemical inhibition of BLT2 prevents 12-S-HHT-mediated resistance. Mass spectrometry analysis of conditioned medium derived from PIFA-stimulated splenic macrophages identifies several lysophosphatidylcholines as the resistance-inducing molecules. When comparing cisplatin and PIFA-treated tumours with cisplatin alone treated tumours we found overall less γH2AX, a measure for DNA damage. Taken together, we have identified an intricate network of lysophospholipid signalling by splenic macrophages that induces systemic chemoresistance in vivo via an altered DNA damage response.

Published
2014
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48. Increased Plasma Levels of Chemoresistance-Inducing Fatty Acid 16:4(n-3) After Consumption of Fish and Fish Oil

Author

Daenen, Laura G. M., primary, Cirkel, Geert A., additional, Houthuijzen, Julia M., additional, Gerrits, Johan, additional, Oosterom, Ilse, additional, Roodhart, Jeanine M. L., additional, van Tinteren, Harm, additional, Ishihara, Kenji, additional, Huitema, Alwin D. R., additional, Verhoeven-Duif, Nanda M., additional, and Voest, Emile E., additional

Published
2015
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49. Lysophospholipids secreted by splenic macrophages induce chemotherapy resistance via interference with the DNA damage response

Author

LS Equine Muscoskeletal Biology, LS Veterinaire biochemie, Dep Biochemie en Celbiologie, LS Algemeen B&C, Sub Clinical Pharmacology, B&C BRC-SIB-TR, Tissue Repair, UIPS - Utrecht Institute for Pharmaceutical Sciences, Houthuijzen, Julia M, Daenen, Laura G M, Roodhart, Jeanine M L, Oosterom, Ilse, van Jaarsveld, Marijn T M, Govaert, Klaas M, Smith, Michelle E, Sadatmand, Sahar J, Rosing, Hilde, Kruse, Fabian, Helms, Bernd J, van Rooijen, Nico, Beijnen, Jos H, Haribabu, Bodduluri, van de Lest, Chris H A, Voest, Emile E, LS Equine Muscoskeletal Biology, LS Veterinaire biochemie, Dep Biochemie en Celbiologie, LS Algemeen B&C, Sub Clinical Pharmacology, B&C BRC-SIB-TR, Tissue Repair, UIPS - Utrecht Institute for Pharmaceutical Sciences, Houthuijzen, Julia M, Daenen, Laura G M, Roodhart, Jeanine M L, Oosterom, Ilse, van Jaarsveld, Marijn T M, Govaert, Klaas M, Smith, Michelle E, Sadatmand, Sahar J, Rosing, Hilde, Kruse, Fabian, Helms, Bernd J, van Rooijen, Nico, Beijnen, Jos H, Haribabu, Bodduluri, van de Lest, Chris H A, and Voest, Emile E

Published
2014

50. Notch1 regulates angio-supportive bone marrow–derived cells in mice: relevance to chemoresistance

Author

Roodhart, Jeanine M. L., primary, He, Huanhuan, additional, Daenen, Laura G. M., additional, Monvoisin, Arnaud, additional, Barber, Chad L., additional, van Amersfoort, Miranda, additional, Hofmann, Jennifer J., additional, Radtke, Freddy, additional, Lane, Timothy F., additional, Voest, Emile E., additional, and Iruela-Arispe, M. Luisa, additional

Published
2013
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