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1. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group

Author

Vincent, Jeroen, Wegdam, Johannes A., Haberkorn, Brigitte C.M., van der Harst, Erwin, Hendriks, Mathijs P., Schreurs, W.H. Hermien, Cense, Huib A., Rietbroek, Ron C., de Gier, Marie-José, van Breugel, Edwin A., de Vos, Aad I., Brosens, Rebecca P.M., Doornebosch, P.G., de Jongh, Felix E., Vles, Wouter J., den Boer, Marien O., Leijtens, Jeroen W.A., Gelderblom, A.J. Hans, Peeters, Koen C.M.J., Kuenen, Bart C., Pultrum, Bareld B., van Dodewaard-de Jong, Joyce M., Consten, Esther C.J., van de Wouw, A.J. Yes, Konsten, J.L.M., Hoekstra, R., Lutke Holzik, Martijn F., Vos, Allert H., van Hoogstraten, M.J., Schlesinger, Nis H., Creemers, Geert-Jan, de Hingh, Ignace H.J.T., Kjær, Monica L., Petersen, Lone N., Seiersen, Michael, Altaf, Rahim, van Cruijsen, Hester, Hess, Daniël A., van Leeuwen-Snoeks, Lobke L., Pronk, Apollo, Baeten, Coen I.M., van der Deure, Wendy M., Bosscha, Koop, Schut, Heidi, Leclercq, W.K.G., Simkens, L.H.J., Reijnders, Koen, van Arkel, Kees, van Grevenstein, W.M.U. Helma, van de Ven, Anthony W.H., Vuylsteke, Ronald J.C.L.M., Kuijer, Philomeen, Bakker, Sandra D., Goei, Hauwy, Helgason, Helgi H., van Acker, Gijs J.D., Temizkan, Mehmet, van Tilburg, Marc W.A., Gerhards, Michael F., Kerver, E.D., Gootjes, Elske, Nieboer, Peter, Bleeker, Wim A., Bleeker, G.R., van der Kruijssen, D.E.W., Elias, S.G., van de Ven, P.M., van Rooijen, K.L., Lam-Boer, J.’t, Mol, L., Punt, C.J.A., Sommeijer, D.W., Tanis, P.J., Nielsen, J.D., Yilmaz, M.K., van Riel, J.M.G.H., Wasowiz-Kemps, D.K., Loosveld, O.J.L., van der Schelling, G.P., de Groot, J.W.B., van Westreenen, H.L., Jakobsen, H.L., Fromm, A.L., Hamberg, P., Verseveld, M., Jaensch, C., Liposits, G.I., van Duijvendijk, P., Oulad Hadj, J., van der Hoeven, J.A.B., Trajkovic, M., de Wilt, J.H.W., and Koopman, M.

Published
2024
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2. First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group

Author

Van Gulik, Thomas, Huiskens, Joost, Van Tinteren, Harm, Dejong, Cornelis H.C., Grünhagen, Dirk J., Patijn, Gijs A., Ruers, Theo J.M., Chapelle, Thiery, Hermans, John J., Leclercq, Wouter K.G., Valkenburg-van Iersel, Liselot B.J., Grootscholten, Cecile, Van Dodewaard-de Jong, Joyce M., Vincent, Jeroen, Houtsma, Danny, Los, Maartje, Den Boer, Marien, Trajkovic-Vidakovic, Marija, Van Voorthuizen, Theo, Koopman, Miriam, Vestjens, Johanneke H.M.J.V., Torrenga, Hans, Mekenkamp, Leonie J., Veldhuis, Gerrit Jan, Polee, Marco B., Dohmen, Serge E., Schut, Heidi, Vulink, Annelie J.E., Van Halteren, Henk K., Oulad Hadj, Jamal, Schiphorst, Pieter-Paul J.B.M., Hoekstra, Ronald, Bond, Marinde J G, Bolhuis, Karen, Loosveld, Olaf J L, de Groot, Jan Willem B, Droogendijk, Helga, Helgason, Helgi H, Hendriks, Mathijs P, Klaase, Joost M, Kazemier, Geert, Liem, Mike S L, Rijken, Arjen M, Verhoef, Cornelis, de Wilt, Johannes H W, de Jong, Koert P, Gerhards, Michael F, van Amerongen, Martinus J, Engelbrecht, Marc R W, van Lienden, Krijn P, Molenaar, I Quintus, de Valk, Bart, Haberkorn, Brigitte C M, Kerver, Emile D, Erdkamp, Frans, van Alphen, Robbert J, Mathijssen-van Stein, Daniëlle, Komurcu, Aysun, Lopez-Yurda, Marta, Swijnenburg, Rutger-Jan, and Punt, Cornelis J A

Published
2023
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3. CABA-V7: a prospective biomarker selected trial of cabazitaxel treatment in AR-V7 positive prostate cancer patients

Author

Isebia, Khrystany T., Mostert, Bianca, Belderbos, Bodine P.S., Buck, Stefan A.J., Helmijr, Jean C.A., Kraan, Jaco, Beaufort, Corine M., Van, Mai N., Oomen - de Hoop, Esther, Sieuwerts, Anieta M., van IJcken, Wilfred F.J., van den Hout - van Vroonhoven, Mirjam C.G.N., Brouwer, Rutger W.W., Oole, Edwin, Hamberg, Paul, Haberkorn, Brigitte C.M., Helgason, Helgi H., de Wit, Ronald, Sleijfer, Stefan, Mathijssen, Ron H.J., Martens, John W.M., Jansen, Maurice P.H.M., van Riet, Job, and Lolkema, Martijn P.

Published
2022
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4. Quality of Life and Survival of Metastatic Colorectal Cancer Patients Treated With Trifluridine-Tipiracil (QUALITAS)

Author

Beerepoot, Laurens V., Creemers, Geert-Jan, van Cruijsen, Hester, de Groot, Jan Willem B., van Halteren, Henk K., Helgason, Helgi H., Hendriks, Mathijs P., Hoekstra, Ronald, van Huis-Tanja, Lieke H., Kapiteijn, Ellen, Los, Maartje, van Meerten, Esther, Peters, Natascha A.J.B., Pruijt, Johannes F.M., van Ufford-Mannesse, Patricia Quarles, Sie, Mark P.S., Sommeijer, Dirkje W., Spierings, Leontine E.A.M.M., Terheggen, Frederiek, Tjin-A-Ton, Manuel L.R., Valkenburg-van Iersel, Liselot B.J., van Voorthuizen, Theo, de Vos-Geelen, Judith, Vulink, Annelie J.E., J van de Wouw, Agnès, Hamers, Patricia A.H., Vink, Geraldine R., Elferink, Marloes A.G., Stellato, Rebecca K., Dijksterhuis, Willemieke P.M., Punt, Cornelis J.A., Koopman, Miriam, and May, Anne M.

Published
2022
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5. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase 3 CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group

Author

van der Kruijssen, D.E.W., primary, Elias, S.G., additional, van de Ven, P.M., additional, van Rooijen, K.L., additional, Lam-Boer, J. ’t, additional, Mol, L., additional, Punt, C.J.A., additional, Sommeijer, D.W., additional, Tanis, P.J., additional, Nielsen, J.D., additional, Yilmaz, M.K., additional, Van Riel, J.M.G.H., additional, Wasowiz-Kemps, D.K., additional, Loosveld, O.J.L., additional, van der Schelling, G.P., additional, de Groot, J.W.B., additional, van Westreenen, H.L., additional, Jakobsen, H.L., additional, Fromm, A.L., additional, Hamberg, P., additional, Verseveld, M., additional, Jaensch, C., additional, Liposits, G.I., additional, van Duijvendijk, P., additional, Hadj, J. Oulad, additional, van der Hoeven, J.A.B., additional, Trajkovic, M., additional, de Wilt, J.H.W., additional, Koopman, M., additional, Vincent, Jeroen, additional, Wegdam, Johannes A., additional, Haberkorn, Brigitte C.M., additional, van der Harst, Erwin, additional, Hendriks, Mathijs P., additional, Schreurs, W.H. (Hermien), additional, Cense, Huib A., additional, Rietbroek, Ron C., additional, Gier, Marie-José de, additional, de Widt-Levert, Louise M., additional, van Breugel, Edwin A., additional, de Vos, Aad I., additional, Brosens, Rebecca P.M., additional, Doornebosch, P.G., additional, de Jongh, Felix E., additional, Vles, Wouter J., additional, den Boer, Marien O., additional, Leijtens, Jeroen W.A., additional, Gelderblom, A.J. (Hans), additional, Peeters, Koen C.M.J., additional, Kuenen, Bart C., additional, Pultrum, Bareld B., additional, van Dodewaard-de Jong, Joyce M., additional, Consten, Esther C.J., additional, van de Wouw, A.J. (Yes), additional, Konsten, J.L.M., additional, Hoekstra, R., additional, Lutke Holzik, Martijn F., additional, Vos, Allert H., additional, van Hoogstraten, M.J., additional, Schlesinger, Nis H., additional, Creemers, Geert-Jan, additional, de Hingh, Ignace H.J.T., additional, Kjær, Monica L., additional, Petersen, Lone N., additional, Seiersen, Michael, additional, Altaf, Rahim, additional, van Cruijsen, Hester, additional, HessL, Daniël A., additional, van Leeuwen-Snoeks, obke L., additional, Pronk, Apollo, additional, Baeten, Coen I.M., additional, van der Deure, Wendy M., additional, Bosscha, Koop, additional, Schut, Heidi, additional, Leclercq, W.K.G., additional, Simkens, L.H.J., additional, Reijnders, Koen, additional, van Arkel, Kees, additional, van Grevenstein, W.M.U. (Helma), additional, van de Ven, Anthony W.H., additional, Vuylsteke, Ronald J.C.L.M., additional, Kuijer, Philomeen, additional, Bakker, Sandra D., additional, Goei, Hauwy, additional, Helgason, Helgi H., additional, van Acker, Gijs J.D., additional, Temizkan, Mehmet, additional, van Tilburg, Marc W.A., additional, Gerhards, Michael F., additional, Kerver, E.D., additional, Gootjes, Elske, additional, Nieboer, Peter, additional, Bleeker, Wim A., additional, and Vink, G.R., additional

Published
2024
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6. Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to 5 Years after Diagnosis

Author

Epi Kanker Team B, Cancer, Biostatistiek Onderwijs, Apotheek Bereidingen, Anatomie, MS CGO, MS Hematologie, MS Medische Oncologie, Epi Kanker, JC onderzoeksprogramma Cancer, Smit, Karel C, Derksen, Jeroen W G, Stellato, Rebecca K, van Lanen, Anne-Sophie, Wesselink, Evertine, Belt, Eric J Th, Cloos-van Balen, Marissa, Coene, Peter Paul L O, Dekker, Jan Willem T, de Groot, Jan Willem, Haringhuizen, Annebeth W, van Halteren, Henk K, van Heek, Tjarda T, Helgason, Helgi H, Hendriks, Mathijs P, de Hingh, Ignace H J T, Hoekstra, Ronald, Houtsma, Danny, Janssen, Johan J B, Kok, Niels, Konsten, Joop L M, Los, Maartje, Meijerink, Martijn R, Mekenkamp, Leonie J M, Peeters, Koen C M J, Polée, Marco B, Rietbroek, Ron C, Schiphorst, Anandi H W, Schrauwen, Ruud W M, Schreinemakers, Jennifer, Sie, Mark P S, Simkens, Lieke, Sonneveld, Eric J A, Terheggen, Frederiek, Valkenburg-van Iersel, Liselot, Vles, Wouter J, Wasowicz-Kemps, Daria K, de Wilt, Johannes H W, Kok, Dieuwertje E, Winkels, Renate M, Kampman, Ellen, van Duijnhoven, Fränzel J B, Koopman, Miriam, May, Anne M, Epi Kanker Team B, Cancer, Biostatistiek Onderwijs, Apotheek Bereidingen, Anatomie, MS CGO, MS Hematologie, MS Medische Oncologie, Epi Kanker, JC onderzoeksprogramma Cancer, Smit, Karel C, Derksen, Jeroen W G, Stellato, Rebecca K, van Lanen, Anne-Sophie, Wesselink, Evertine, Belt, Eric J Th, Cloos-van Balen, Marissa, Coene, Peter Paul L O, Dekker, Jan Willem T, de Groot, Jan Willem, Haringhuizen, Annebeth W, van Halteren, Henk K, van Heek, Tjarda T, Helgason, Helgi H, Hendriks, Mathijs P, de Hingh, Ignace H J T, Hoekstra, Ronald, Houtsma, Danny, Janssen, Johan J B, Kok, Niels, Konsten, Joop L M, Los, Maartje, Meijerink, Martijn R, Mekenkamp, Leonie J M, Peeters, Koen C M J, Polée, Marco B, Rietbroek, Ron C, Schiphorst, Anandi H W, Schrauwen, Ruud W M, Schreinemakers, Jennifer, Sie, Mark P S, Simkens, Lieke, Sonneveld, Eric J A, Terheggen, Frederiek, Valkenburg-van Iersel, Liselot, Vles, Wouter J, Wasowicz-Kemps, Daria K, de Wilt, Johannes H W, Kok, Dieuwertje E, Winkels, Renate M, Kampman, Ellen, van Duijnhoven, Fränzel J B, Koopman, Miriam, and May, Anne M

Published
2024

7. Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to Five Years after Diagnosis

Author

Smit, Karel C., Derksen, Jeroen W.G., Stellato, Rebecca K., van Lanen, Anne-Sophie, Wesselink, Evertine, Belt, Eric J.T., Cloos-van Balen, Marissa, Coene, Peter Paul L.O., Dekker, Jan Willem T., de Groot, Jan Willem, Haringhuizen, Annebeth W., van Halteren, Henk K., van Heek, Tjarda T., Helgason, Helgi H., Hendriks, Mathijs P., de Hingh, Ignace H.J.T., Hoekstra, Ronald, Houtsma, Danny, Janssen, Johan J.B., Kok, Niels, Konsten, Joop L.M., Los, Maartje, Meijerink, Martijn R., Mekenkamp, Leonie J.M., Peeters, Koen C.M.J., Polée, Marco B., Rietbroek, Ron C., Schiphorst, Anandi H.W., Schrauwen, Ruud W.M., Schreinemakers, Jennifer, Sie, Mark P.S., Simkens, Lieke, Sonneveld, Eric J.A., Terheggen, Frederiek, Valkenburg-van Iersel, Liselot, Vles, Wouter J., Wasowicz-Kemps, Daria K., de Wilt, Johannes H.W., Kok, Dieuwertje E., Winkels, Renate M., Kampman, Ellen, van Duijnhoven, Fränzel J.B., Koopman, Miriam, May, Anne M., Smit, Karel C., Derksen, Jeroen W.G., Stellato, Rebecca K., van Lanen, Anne-Sophie, Wesselink, Evertine, Belt, Eric J.T., Cloos-van Balen, Marissa, Coene, Peter Paul L.O., Dekker, Jan Willem T., de Groot, Jan Willem, Haringhuizen, Annebeth W., van Halteren, Henk K., van Heek, Tjarda T., Helgason, Helgi H., Hendriks, Mathijs P., de Hingh, Ignace H.J.T., Hoekstra, Ronald, Houtsma, Danny, Janssen, Johan J.B., Kok, Niels, Konsten, Joop L.M., Los, Maartje, Meijerink, Martijn R., Mekenkamp, Leonie J.M., Peeters, Koen C.M.J., Polée, Marco B., Rietbroek, Ron C., Schiphorst, Anandi H.W., Schrauwen, Ruud W.M., Schreinemakers, Jennifer, Sie, Mark P.S., Simkens, Lieke, Sonneveld, Eric J.A., Terheggen, Frederiek, Valkenburg-van Iersel, Liselot, Vles, Wouter J., Wasowicz-Kemps, Daria K., de Wilt, Johannes H.W., Kok, Dieuwertje E., Winkels, Renate M., Kampman, Ellen, van Duijnhoven, Fränzel J.B., Koopman, Miriam, and May, Anne M.

Abstract

Introduction: Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until five years post-diagnosis.Methods: Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and six, twelve, twenty-four, and sixty (T6 to T60) months post-diagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population.Results: In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared to men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared to the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6.Conclusions: Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at six months post-diagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support.

Published
2024

8. Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to Five Years after Diagnosis

Author

Smit, Karel C., primary, Derksen, Jeroen W.G., additional, Stellato, Rebecca K., additional, van Lanen, Anne-Sophie, additional, Wesselink, Evertine, additional, Belt, Eric J. Th., additional, Cloos-van Balen, Marissa, additional, Coene, Peter Paul L.O., additional, Dekker, Jan Willem T., additional, de Groot, Jan Willem, additional, Haringhuizen, Annebeth W., additional, van Halteren, Henk K., additional, van Heek, Tjarda T., additional, Helgason, Helgi H., additional, Hendriks, Mathijs P., additional, de Hingh, Ignace H.J.T., additional, Hoekstra, Ronald, additional, Houtsma, Danny, additional, Janssen, Johan J.B., additional, Kok, Niels, additional, Konsten, Joop L.M., additional, Los, Maartje, additional, Meijerink, Martijn R., additional, Mekenkamp, Leonie J.M., additional, Peeters, Koen C.M.J., additional, Polée, Marco B., additional, Rietbroek, Ron C., additional, Schiphorst, Anandi H.W., additional, Schrauwen, Ruud W.M., additional, Schreinemakers, Jennifer, additional, Sie, Mark P.S., additional, Simkens, Lieke, additional, Sonneveld, Eric J.A., additional, Terheggen, Frederiek, additional, Valkenburg-van Iersel, Liselot, additional, Vles, Wouter J., additional, Wasowicz-Kemps, Daria K., additional, de Wilt, Johannes H.W., additional, Kok, Dieuwertje E., additional, Winkels, Renate M., additional, Kampman, Ellen, additional, van Duijnhoven, Fränzel J.B., additional, Koopman, Miriam, additional, and May, Anne M., additional

Published
2023
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9. Metronomic cyclophosphamide attenuates mTOR-mediated expansion of regulatory T cells, but does not impact clinical outcome in patients with metastatic renal cell cancer treated with everolimus

Author

Werter, Inge M., Huijts, Charlotte M., Lougheed, Sinéad. M., Hamberg, Paul, Polee, Marco B., Tascilar, Metin, Los, Maartje, Haanen, John B. A. G., Helgason, Helgi H., Verheul, Henk M., de Gruijl, Tanja D., van der Vliet, Hans J., and for the Dutch WIN-O Consortium

Published
2019
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10. mFast‐SeqS‐based aneuploidy score in circulating cell‐free DNA is a prognostic biomarker in prostate cancer

Author

Isebia, Khrystany T., primary, Mostert, Bianca, additional, Deger, Teoman, additional, Kraan, Jaco, additional, de Weerd, Vanja, additional, Oomen‐de Hoop, Esther, additional, Hamberg, Paul, additional, Haberkorn, Brigitte C. M., additional, Helgason, Helgi H., additional, de Wit, Ronald, additional, Mathijssen, Ron H. J., additional, Lolkema, Martijn P., additional, Wilting, Saskia M., additional, van Riet, Job, additional, and Martens, John W. M., additional

Published
2023
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11. First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group

Author

Bond, Marinde J G, primary, Bolhuis, Karen, additional, Loosveld, Olaf J L, additional, de Groot, Jan Willem B, additional, Droogendijk, Helga, additional, Helgason, Helgi H, additional, Hendriks, Mathijs P, additional, Klaase, Joost M, additional, Kazemier, Geert, additional, Liem, Mike S L, additional, Rijken, Arjen M, additional, Verhoef, Cornelis, additional, de Wilt, Johannes H W, additional, de Jong, Koert P, additional, Gerhards, Michael F, additional, van Amerongen, Martinus J, additional, Engelbrecht, Marc R W, additional, van Lienden, Krijn P, additional, Molenaar, I Quintus, additional, de Valk, Bart, additional, Haberkorn, Brigitte C M, additional, Kerver, Emile D, additional, Erdkamp, Frans, additional, van Alphen, Robbert J, additional, Mathijssen-van Stein, Daniëlle, additional, Komurcu, Aysun, additional, Lopez-Yurda, Marta, additional, Swijnenburg, Rutger-Jan, additional, Punt, Cornelis J A, additional, Van Gulik, Thomas, additional, Huiskens, Joost, additional, Van Tinteren, Harm, additional, Dejong, Cornelis H.C., additional, Grünhagen, Dirk J., additional, Patijn, Gijs A., additional, Ruers, Theo J.M., additional, Chapelle, Thiery, additional, Hermans, John J., additional, Leclercq, Wouter K.G., additional, Valkenburg-van Iersel, Liselot B.J., additional, Grootscholten, Cecile, additional, Van Dodewaard-de Jong, Joyce M., additional, Vincent, Jeroen, additional, Houtsma, Danny, additional, Los, Maartje, additional, Den Boer, Marien, additional, Trajkovic-Vidakovic, Marija, additional, Van Voorthuizen, Theo, additional, Koopman, Miriam, additional, Vestjens, Johanneke H.M.J.V., additional, Torrenga, Hans, additional, Mekenkamp, Leonie J., additional, Veldhuis, Gerrit Jan, additional, Polee, Marco B., additional, Dohmen, Serge E., additional, Schut, Heidi, additional, Vulink, Annelie J.E., additional, Van Halteren, Henk K., additional, Oulad Hadj, Jamal, additional, Schiphorst, Pieter-Paul J.B.M., additional, and Hoekstra, Ronald, additional

Published
2023
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12. mFast-SeqS-based aneuploidy score in circulating cell-free DNA is a prognostic biomarker in prostate cancer

Author

Isebia, Khrystany T, Mostert, Bianca, Deger, Teoman, Kraan, Jaco, de Weerd, Vanja, Oomen-de Hoop, Esther, Hamberg, Paul, Haberkorn, Brigitte C M, Helgason, Helgi H, de Wit, Ronald, Mathijssen, Ron H J, Lolkema, Martijn P, Wilting, Saskia M, van Riet, Job, Martens, John W M, Isebia, Khrystany T, Mostert, Bianca, Deger, Teoman, Kraan, Jaco, de Weerd, Vanja, Oomen-de Hoop, Esther, Hamberg, Paul, Haberkorn, Brigitte C M, Helgason, Helgi H, de Wit, Ronald, Mathijssen, Ron H J, Lolkema, Martijn P, Wilting, Saskia M, van Riet, Job, and Martens, John W M

Abstract

Multiple prognostic biomarkers, including circulating tumour cell (CTC) counts, exist in metastatic castration-resistant prostate cancer (mCRPC) patients, but none of them have been implemented into daily clinical care. The modified fast aneuploidy screening test-sequencing system (mFast-SeqS), which yields a genome-wide aneuploidy score, is able to reflect the fraction of cell-free tumour DNA (ctDNA) within cell-free DNA (cfDNA) and may be a promising biomarker in mCRPC. In this study, we investigated the prognostic value of dichotomized aneuploidy scores (< 5 vs. ≥ 5) as well as CTC counts (< 5 vs. ≥ 5) in 131 mCRPC patients prior to treatment with cabazitaxel. We validated our findings in an independent cohort of 50 similarly treated mCRPC patients. We observed that, similar to the dichotomized CTC count [HR: 2.92; 95% confidence interval (CI);1.84–4.62], dichotomized aneuploidy scores (HR: 3.24; CI: 2.12–4.94) significantly correlated with overall survival in mCRPC patients. We conclude that a dichotomized aneuploidy score from cfDNA is a prognostic marker for survival in mCRPC patients within our discovery cohort and in an independent mCRPC validation cohort. Therefore, this easy and robust minimally-invasive assay can be readily implemented as a prognostic marker in mCRPC. A dichotomized aneuploidy score might also be used as a stratification factor in clinical studies to account for tumour load.

Published
2023

13. Physical Activity Is Associated with Improved Overall Survival among Patients with Metastatic Colorectal Cancer

Author

Smit, Karel C., Derksen, Jeroen W.G., Beets, Geerard L.O., Belt, Eric J.Th, Berbée, Maaike, Coene, Peter Paul L.O., Van Cruijsen, Hester, Davidis, Marjan A., Dekker, Jan Willem T., Van Dodewaard-De Jong, Joyce M., Haringhuizen, Annebeth W., Helgason, Helgi H., Hendriks, Mathijs P., Hoekstra, Ronald, De Hingh, Ignace H.J.T., Ijzermans, Jan N.M., Janssen, Johan J.B., Konsten, Joop L.M., Los, Maartje, Mekenkamp, Leonie J.M., Nieboer, Peter, Peeters, Koen C.M.J., Peters, Natascha A.J.B., Pruijt, Hans J.F.M., 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., Sommeijer, Dirkje W., Sonneveld, Dirk J.A., Stockmann, Hein B.A.C., Tent, Marleen, Terheggen, Frederiek, Tjin-A-Ton, Manuel L.R., Valkenburg-Van Iersel, Liselot, Van Der Velden, Ankie M.T., Vles, Wouter J., Van Voorthuizen, Theo, Wegdam, Johannes A., De Wilt, Johannes H.W., Koopman, Miriam, May, Anne M., Smit, Karel C., Derksen, Jeroen W.G., Beets, Geerard L.O., Belt, Eric J.Th, Berbée, Maaike, Coene, Peter Paul L.O., Van Cruijsen, Hester, Davidis, Marjan A., Dekker, Jan Willem T., Van Dodewaard-De Jong, Joyce M., Haringhuizen, Annebeth W., Helgason, Helgi H., Hendriks, Mathijs P., Hoekstra, Ronald, De Hingh, Ignace H.J.T., Ijzermans, Jan N.M., Janssen, Johan J.B., Konsten, Joop L.M., Los, Maartje, Mekenkamp, Leonie J.M., Nieboer, Peter, Peeters, Koen C.M.J., Peters, Natascha A.J.B., Pruijt, Hans J.F.M., 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., Sommeijer, Dirkje W., Sonneveld, Dirk J.A., Stockmann, Hein B.A.C., Tent, Marleen, Terheggen, Frederiek, Tjin-A-Ton, Manuel L.R., Valkenburg-Van Iersel, Liselot, Van Der Velden, Ankie M.T., Vles, Wouter J., Van Voorthuizen, Theo, Wegdam, Johannes A., De Wilt, Johannes H.W., Koopman, Miriam, and May, Anne M.

Abstract

Regular physical activity (PA) is associated with improved overall survival (OS) in stage I-III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9±10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299-0.807, p value=0.005) and 0.485 (95% CI 0.303-0.778, p value=0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278-0.816, p value=0.007)) and MVPA-SL (0.389 (95% CI 0.224-0.677, p value<0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412-0.961, p value=0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS.

Published
2022

14. CABA-V7:a prospective biomarker selected trial of cabazitaxel treatment in AR-V7 positive prostate cancer patients

Author

Isebia, Khrystany T., Mostert, Bianca, Belderbos, Bodine P.S., Buck, Stefan A.J., Helmijr, Jean C.A., Kraan, Jaco, Beaufort, Corine M., Van, Mai N., Oomen - de Hoop, Esther, Sieuwerts, Anieta M., van IJcken, Wilfred F.J., van den Hout - van Vroonhoven, Mirjam C.G.N., Brouwer, Rutger W.W., Oole, Edwin, Hamberg, Paul, Haberkorn, Brigitte C.M., Helgason, Helgi H., de Wit, Ronald, Sleijfer, Stefan, Mathijssen, Ron H.J., Martens, John W.M., Jansen, Maurice P.H.M., van Riet, Job, Lolkema, Martijn P., Isebia, Khrystany T., Mostert, Bianca, Belderbos, Bodine P.S., Buck, Stefan A.J., Helmijr, Jean C.A., Kraan, Jaco, Beaufort, Corine M., Van, Mai N., Oomen - de Hoop, Esther, Sieuwerts, Anieta M., van IJcken, Wilfred F.J., van den Hout - van Vroonhoven, Mirjam C.G.N., Brouwer, Rutger W.W., Oole, Edwin, Hamberg, Paul, Haberkorn, Brigitte C.M., Helgason, Helgi H., de Wit, Ronald, Sleijfer, Stefan, Mathijssen, Ron H.J., Martens, John W.M., Jansen, Maurice P.H.M., van Riet, Job, and Lolkema, Martijn P.

Abstract

Background: Metastatic castration-resistant prostate cancer (mCRPC) patients with positive AR-V7 expression in their circulating tumour cells (CTCs) rarely derive benefit from abiraterone and enzalutamide. Design: We performed a prospective, multicenter, single arm phase II clinical trial (CABA-V7) in mCRPC patients previously treated with docetaxel and androgen deprivation therapy. Objective: In this trial, we investigated whether cabazitaxel treatment resulted in clinically meaningful PSA response rates in patients with positive CTC-based AR-V7 expression and collected liquid biopsies for genomic profiling. Results: Cabazitaxel was found to be modestly effective, with only 12% of these patients obtaining a PSA response. Genomic profiling revealed that CTC-based AR-V7 expression was not associated with other known mCRPC-associated alterations. CTC-based AR-V7 status and dichotomised CTC counts were observed as independent prognostic markers at baseline. Conclusions: AR-V7 positivity predicted poor overall survival (OS). However, cabazitaxel-treated AR-V7 positive patients and those lacking AR-V7 positivity, who received cabazitaxel as standard of care, appeared to have similar OS. Therefore, despite the low response rate, cabazitaxel may still be an effective treatment in this poor prognosis, AR-V7 positive patient population.

Published
2022

15. Physical Activity Is Associated with Improved Overall Survival among Patients with Metastatic Colorectal Cancer

Author

Epi Kanker Team B, Cancer, MS Medische Oncologie, Epidemiology & Health Economics, JC onderzoeksprogramma Kanker, Smit, Karel C, Derksen, Jeroen W G, Beets, Geerard L O, Belt, Eric J Th, Berbée, Maaike, Coene, Peter Paul L O, van Cruijsen, Hester, Davidis, Marjan A, Dekker, Jan Willem T, van Dodewaard-de Jong, Joyce M, Haringhuizen, Annebeth W, Helgason, Helgi H, Hendriks, Mathijs P, Hoekstra, Ronald, de Hingh, Ignace H J T, IJzermans, Jan N M, Janssen, Johan J B, Konsten, Joop L M, Los, Maartje, Mekenkamp, Leonie J M, Nieboer, Peter, Peeters, Koen C M J, Peters, Natascha A J B, Pruijt, Hans J F M, Quarles van Ufford-Mannesse, Patricia, Rietbroek, Ron C, Schiphorst, Anandi H W, Schouten van der Velden, Arjan, Schrauwen, Ruud W M, Sie, Mark P S, Sommeijer, Dirkje W, Sonneveld, Dirk J A, Stockmann, Hein B A C, Tent, Marleen, Terheggen, Frederiek, Tjin-A-Ton, Manuel L R, Valkenburg-van Iersel, Liselot, van der Velden, Ankie M T, Vles, Wouter J, van Voorthuizen, Theo, Wegdam, Johannes A, de Wilt, Johannes H W, Koopman, Miriam, May, Anne M, On Behalf Of The Plcrc Study Group, Epi Kanker Team B, Cancer, MS Medische Oncologie, Epidemiology & Health Economics, JC onderzoeksprogramma Kanker, Smit, Karel C, Derksen, Jeroen W G, Beets, Geerard L O, Belt, Eric J Th, Berbée, Maaike, Coene, Peter Paul L O, van Cruijsen, Hester, Davidis, Marjan A, Dekker, Jan Willem T, van Dodewaard-de Jong, Joyce M, Haringhuizen, Annebeth W, Helgason, Helgi H, Hendriks, Mathijs P, Hoekstra, Ronald, de Hingh, Ignace H J T, IJzermans, Jan N M, Janssen, Johan J B, Konsten, Joop L M, Los, Maartje, Mekenkamp, Leonie J M, Nieboer, Peter, Peeters, Koen C M J, Peters, Natascha A J B, Pruijt, Hans J F M, Quarles van Ufford-Mannesse, Patricia, Rietbroek, Ron C, Schiphorst, Anandi H W, Schouten van der Velden, Arjan, Schrauwen, Ruud W M, Sie, Mark P S, Sommeijer, Dirkje W, Sonneveld, Dirk J A, Stockmann, Hein B A C, Tent, Marleen, Terheggen, Frederiek, Tjin-A-Ton, Manuel L R, Valkenburg-van Iersel, Liselot, van der Velden, Ankie M T, Vles, Wouter J, van Voorthuizen, Theo, Wegdam, Johannes A, de Wilt, Johannes H W, Koopman, Miriam, May, Anne M, and On Behalf Of The Plcrc Study Group

Published
2022

16. FOLFOXIRI + bevacizumab versus FOLFOX/FOLFIRI + bevacizumab in patients with initially unresectable colorectal liver metastases (CRLM) and right-sided and/or RAS/BRAFV600E-mutated primary tumor: Phase III CAIRO5 study of the Dutch Colorectal Cancer Group.

Author

Punt, Cornelis J. A., primary, Bond, Marinde J.G., additional, Bolhuis, Karen, additional, Loosveld, Olaf, additional, Helgason, Helgi H., additional, de Groot, Jan Willem, additional, Hendriks, Mathijs P., additional, Kerver, Emile D., additional, Liem, Mike S.L., additional, Rijken, Arjen M., additional, Verhoef, Cornelis, additional, de Wilt, Johannes H.W., additional, De Jong, Koert P., additional, Kazemier, Geert, additional, van Amerongen, Martinus J., additional, Engelbrecht, Marc R.W., additional, Klaase, Joost M., additional, Komurcu, Aysun, additional, Lopez-Yurda, Marta I., additional, and Swijnenburg, Rutger-Jan, additional

Published
2022
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17. Quality of Life and Survival of Metastatic Colorectal Cancer Patients Treated With Trifluridine-Tipiracil (QUALITAS)

Author

Hamers, Patricia A.H., primary, Vink, Geraldine R., additional, Elferink, Marloes A.G., additional, Stellato, Rebecca K., additional, Dijksterhuis, Willemieke P.M., additional, Punt, Cornelis J.A., additional, Koopman, Miriam, additional, May, Anne M., additional, Beerepoot, Laurens V., additional, Creemers, Geert-Jan, additional, van Cruijsen, Hester, additional, de Groot, Jan Willem B., additional, van Halteren, Henk K., additional, Helgason, Helgi H., additional, Hendriks, Mathijs P., additional, Hoekstra, Ronald, additional, van Huis-Tanja, Lieke H., additional, Kapiteijn, Ellen, additional, Los, Maartje, additional, van Meerten, Esther, additional, Peters, Natascha A.J.B., additional, Pruijt, Johannes F.M., additional, van Ufford-Mannesse, Patricia Quarles, additional, Sie, Mark P.S., additional, Sommeijer, Dirkje W., additional, Spierings, Leontine E.A.M.M., additional, Terheggen, Frederiek, additional, Tjin-A-Ton, Manuel L.R., additional, Valkenburg-van Iersel, Liselot B.J., additional, van Voorthuizen, Theo, additional, de Vos-Geelen, Judith, additional, Vulink, Annelie J.E., additional, and J van de Wouw, Agnès, additional

Published
2022
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19. Trajectories of health-related quality of life and psychological distress in patients with colorectal cancer: A population-based study

Author

Qaderi, Seyed M., primary, van der Heijden, Joost A.G., additional, Verhoeven, Rob H.A., additional, de Wilt, Johannes H.W., additional, Custers, Jose A.E., additional, Beets, Geerard L., additional, Belt, Eric J.Th., additional, Berbée, Maaike, additional, Beverdam, Frederique H., additional, Blankenburgh, Ruud, additional, Coene, Peter Paul L.O., additional, de Groot, Jan Willem B., additional, de Hingh, Ignace H.J.T., additional, de Vos, Aad I., additional, Dekker, Jan Willem T., additional, Erdkamp, Frans L.G., additional, Haringhuizen, Annebeth W., additional, Helgason, Helgi H., additional, Hendriks, Mathijs P., additional, Hoekstra, Ronald, additional, Ijzermans, Jan N.M., additional, Jansen, Jan, additional, Kloppenberg, Frank W.H., additional, Los, Maartje, additional, Meijerink, Martijn R., additional, Mekenkamp, Leonie J.M., additional, Nieboer, Peter, additional, Peeters, Koen C.M.J., additional, Peters, Natascha A.J.B., additional, Polée, Marco B., additional, Pruijt, Johannes F.M., additional, van Ufford-Mannesse, Patricia Quarles, additional, Rietbroek, Ron C., additional, Schiphorst, Anandi H.W., additional, van der Velden, Arjan Schouten, additional, Schrauwen, Ruud W.M., additional, Sie, Mark P.S., additional, Simkens, Lieke, additional, Sommeijer, Dirkje W., additional, Sonneveld, Dirk J.A., additional, Spierings, Leontine E.A., additional, Stockmann, Hein B.A.C., additional, Talsma, Koen, additional, ten Tije, Albert J., additional, Terheggen, Frederiek, additional, Tjin-A-Ton, Manuel L.R., additional, Valkenburg-van Iersel, Liselot B.J., additional, van Cruijsen, Hester, additional, Velden, Ankie M.T. van der, additional, van Dodewaard-de Jong, Joyce M., additional, van Lent, Anja U.G., additional, van Voorthuizen, Theo, additional, Vermaas, Maarten, additional, Vles, Wouter J., additional, Vogelaar, Jeroen F.J., additional, and Zimmerman, David D.E., additional

Published
2021
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20. 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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22. Work Ability in Patients With Stage I to IV Colon Cancer: Results of the Dutch Prospective Colorectal Cancer Cohort

Author

Franken, Mira D., Vink, Geraldine, van Grevenstein, Wilhelmina M.U., Verkooijen, Helena M., Punt, Cornelis J.A., Koopman, Miriam, May, Anne M., Beets, Geerard L., Belt, Eric J.Th., Berbée, Maaike, Beverdam, Frederique H., Blankenburgh, Ruud, Coene, Peter Paul L.O., de Groot, Jan Willem B., de Hingh, Ignace H.J.T., de Vos, Aad I., de Wilt, Johannes H.W., Dekker, Jan Willem T., Erdkamp, Frans L.G., Haringhuizen, Annebeth W., Helgason, Helgi H., Hendriks, Mathijs P., Hoekstra, Ronald, Ijzermans, Jan N.M., Jansen, Jan, Kloppenberg, Frank W.H., Los, Maartje, Meijerink, Martijn R., Mekenkamp, Leonie J.M., Nieboer, Peter, Peeters, Koen C.M.J., Peters, Natascha A.J.B., Pruijt, Johannes F.M., van Ufford-Mannesse, Patricia Quarles, Rietbroek, Ron C., Schiphorst, Anandi H.W., Sie, Mark P.S., Simkens, Lieke H.J., Sommeijer, Dirkje W., Spierings, Leontine E.A., Stockmann, Hein B.A.C., ten Tije, Albert J., Terheggen, Frederiek, Tjin-A-Ton, Manuel L.R., Valkenburg-van Iersel, Liselot B.J., van Cruijsen, Hester, van der Velden, Ankie M.T., van Dodewaard-de Jong, Joyce M., van Lent, Anja U.G., Voorthuizen, Theo van, Vermaas, Maarten, Vles, Wouter J., Vogelaar, Jeroen F.J., and Zimmerman, David D.E.

Published
2023
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23. Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): Study protocol for a trial within a cohort study

Author

Schraa, S. J., Van Rooijen, K. L., Van Der Kruijssen, D. E.W., Rubio Alarcón, C., Phallen, J., Sausen, M., Simmons, J., Coupé, V. M.H., Van Grevenstein, W. M.U., Elias, S., Verkooijen, H. M., Laclé, M. M., Bosch, L. J.W., Van Den Broek, D., Meijer, G. A., Velculescu, V. E., Fijneman, R. J.A., Vink, G. R., Koopman, M., Dunker, Mich S., Lutke Holzik, Martijn F., Hoekstra, Ronald, Sommeijer, Dirkje W., Van Der Bilt, Jarmila D.W., Consten, Esther C.J., Cirkel, Geert A., Burghgraef, Thijs A., Van Der Schans, Emma M., Nieboer, Peter, Rietbroek, Ron C., Dekker, Jan Willem T., Verschoor, Arjan J., Talsma, Koen A.K., Brosens, Rebecca P.M., Helgason, Helgi H., Marinelli, Andreas W.K.S., De Hingh, Ignace H.J.T., Oldenhuis, Corina N., Jansen, Jan, Van Halteren, Henk K., Stockmann, Hein B.A.C., Beeker, Aart, Bosscha, Koop, Pruijt, Hans F.M., Spierings, Leontine E.A.M.M., Valkenburg-Van Iersel, Liselot B.J., Vles, Wouter J., De Jongh, Felix E., Van Cruijsen, Hester, Heikens, Joost T., Zimmerman, David D.E., Van Alphen, Robert J., Schiphorst, Anandi H.W., Van Leeuwen-Snoeks, Lobke L., Vogelaar, Jeroen F.J., Peters, Natascha A.J.B., Epidemiology and Data Science, APH - Methodology, CCA - Cancer Treatment and quality of life, Pathology, Internal medicine, Orthopedic Surgery and Sports Medicine, VU University medical center, Surgery, ​Robotics and image-guided minimally-invasive surgery (ROBOTICS), RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Medische Oncologie (9), Medical Biology, Nephrology, and Oncology

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Neoplasm, Residual, Colorectal cancer, Cost-Benefit Analysis, COLORECTAL-CANCER, Circulating Tumor DNA, Study Protocol, 0302 clinical medicine, RESIDUAL DISEASE, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Prospective Studies, Colectomy, Netherlands, Randomized Controlled Trials as Topic, RISK, education.field_of_study, RANDOMIZED CONTROLLED-TRIAL, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Colon cancer, Oxaliplatin, Chemotherapy, Adjuvant, CELL-FREE DNA, 030220 oncology & carcinogenesis, Colonic Neoplasms, Practice Guidelines as Topic, SURVIVAL, Female, medicine.drug, Cohort study, Adult, medicine.medical_specialty, Population, TwiCs, lcsh:RC254-282, Disease-Free Survival, LEUCOVORIN, Capecitabine, 03 medical and health sciences, Internal medicine, Genetics, medicine, Biomarkers, Tumor, Humans, RECURRENCE, education, Neoplasm Staging, Intention-to-treat analysis, business.industry, Liquid Biopsy, ctDNA, Patient Acceptance of Health Care, medicine.disease, Minimal residual disease, FLUOROURACIL, Adjuvant chemotherapy, 030104 developmental biology, Quality of Life, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Background Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. Methods/design MEDOCC-CrEATE follows the ‘trial within cohorts’ (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. Discussion The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. Trial registration Netherlands Trial Register: NL6281/NTR6455. Registered 18 May 2017, https://www.trialregister.nl/trial/6281

Published
2020
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25. Gene Expression Profiling to Identify the Histogenetic Origin of Metastatic Adenocarcinomas of Unknown Primary

Author

Horlings, Hugo M., primary, van Laar, Ryan K., additional, Kerst, Jan-Martijn, additional, Helgason, Helgi H., additional, Wesseling, Jelle, additional, van der Hoeven, Jacobus J.M., additional, Warmoes, Marc O., additional, Floore, Arno, additional, Witteveen, Anke, additional, Lahti-Domenici, Jaana, additional, Glas, Annuska M., additional, Van't Veer, Laura J., additional, and de Jong, Daphne, additional

Published
2008
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28. First-Line Systemic Treatment for Initially Unresectable Colorectal Liver Metastases: Post Hoc Analysis of the CAIRO5 Randomized Clinical Trial.

Author

Bond MJG, Bolhuis K, Loosveld OJL, de Groot JWB, Droogendijk H, Helgason HH, Hendriks MP, Klaase JM, Kazemier G, Liem MSL, Rijken AM, Verhoef C, de Wilt JHW, de Jong KP, Gerhards MF, van Amerongen MJ, Engelbrecht MRW, van Lienden KP, Hermans JJ, Molenaar IQ, Grünhagen DJ, de Valk B, Haberkorn BCM, Kerver ED, Erdkamp F, van Alphen RJ, Mathijssen-van Stein D, Komurcu A, May AM, Swijnenburg RJ, and Punt CJA

Abstract

Importance: In patients with colorectal cancer and unresectable liver-only metastases (CRLM), treatment with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) plus irinotecan (FOLFOXIRI) and bevacizumab vs FOLFOX/folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab increased progression-free survival, response, and R0/R1 resection/ablation rates, as well as toxic effects in RAS/BRAFV600E-variant and/or right-sided tumors. FOLFOX/FOLFIRI-panitumumab vs FOLFOX/FOLFIRI-bevacizumab increased response at the cost of more toxic effects in RAS/BRAFV600E wild-type, left-sided tumors., Objective: To present long-term outcomes of treatment with FOLFOXIRI plus bevacizumab vs FOLFOX/FOLFIRI plus bevacizumab and FOLFOX/FOLFIRI plus panitumumab vs FOLFOX/FOLFIRI + bevacizumab., Design, Setting, and Participants: The randomized phase 3 CAIRO5 trial included patients with initially unresectable CRLM in 46 Dutch centers and 1 Belgian center between November 2014 and January 2022. A liver expert panel repeatedly evaluated resectability., Intervention: Patients with RAS/BRAFV600E-variant and/or right-sided tumors randomly received FOLFOX/FOLFIRI-bevacizumab (group 1) or FOLFOXIRI-bevacizumab (group 2), and those with RAS/BRAFV600E wild-type, left-sided tumors received FOLFOX/FOLFIRI-bevacizumab (group 3) or FOLFOX/FOLFIRI-panitumumab (group 4). Adjuvant chemotherapy (ACT) after complete local treatment was recommended but not standard., Main Outcomes and Measures: Overall survival (OS) was analyzed as a secondary outcome. Other outcomes were post hoc analyses., Results: A total of 530 patients (327 male [62%] and 203 female individuals [38%]; median age, 62 [IQR, 54-69] years) were randomized: 148 in group 1, 146 in group 2, 118 in group 3, and 118 in group 4. The median OS in group 1 was 23.6 (95% CI, 20.1-27.5) vs 24.1 (95% CI, 21.0-30.9) months in group 2 (hazard ratio [HR], 0.90; 95% CI, 0.70-1.17; P = .44), and 39.9 (95% CI, 30.7-44.6) in group 3 vs 38.3 (95% CI, 35.3-51.3) months in group 4 (HR, 0.95; 95% CI, 0.68-1.32; P = .75). OS was longest after complete local treatment without early (≤6 months) recurrence (64.3 months; 95% CI, 57.6 to not reached) and salvage local treatment options after early recurrence (58.9; 95% CI, 47.3 to not reached), followed by patients without salvage local treatment after early recurrence (30.5; 95% CI, 24.4-33.4) and with incomplete local treatment (28.7; 95% CI, 25.9-38.3), and worst in patients with continued unresectability (18.3; 95% CI, 15.7-20.0). After confounder adjustment, ACT was associated with longer OS (HR, 0.66; 95% CI, 0.44-0.98) and relapse-free survival (HR, 0.65; 95% CI, 0.48-0.88) and less early recurrence without salvage local treatment (odds ratio, 0.46; 95% CI, 0.25-0.85)., Conclusions and Relevance: These results support using FOLFOX/FOLFIRI-bevacizumab for patients with initially unresectable CRLM irrespective of RAS/BRAFV600E status and tumor sidedness. Patients with complete local liver treatment with salvage local treatment in case of early recurrence had the longest OS. ACT might be considered for these patients., Trial Registration: ClinicalTrials.gov NCT02162563.

Published
2024
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29. Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to 5 Years after Diagnosis.

Author

Smit KC, Derksen JWG, Stellato RK, VAN Lanen AS, Wesselink E, Belt EJT, Balen MC, Coene PPLO, Dekker JWT, DE Groot JW, Haringhuizen AW, VAN Halteren HK, VAN Heek TT, Helgason HH, Hendriks MP, DE Hingh IHJT, Hoekstra R, Houtsma D, Janssen JJB, Kok N, Konsten JLM, Los M, Meijerink MR, Mekenkamp LJM, Peeters KCMJ, Polée MB, Rietbroek RC, Schiphorst AHW, Schrauwen RWM, Schreinemakers J, Sie MPS, Simkens L, Sonneveld EJA, Terheggen F, Iersel LV, Vles WJ, Wasowicz-Kemps DK, DE Wilt JHW, Kok DE, Winkels RM, Kampman E, VAN Duijnhoven FJB, Koopman M, and May AM

Subjects
Male, Humans, Female, Exercise, Cohort Studies, Fatigue, Quality of Life, Colorectal Neoplasms diagnosis
Abstract

Introduction: Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until 5 yr postdiagnosis., Methods: Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and 6, 12, 24, and 60 months (T6 to T60) postdiagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population., Results: In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared with men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared with the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6., Conclusions: Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at 6 months postdiagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Published
2024
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30. Physical Activity Is Associated with Improved Overall Survival among Patients with Metastatic Colorectal Cancer.

Author

Smit KC, Derksen JWG, Beets GLO, Belt EJT, Berbée M, Coene PPLO, van Cruijsen H, Davidis MA, Dekker JWT, van Dodewaard-de Jong JM, Haringhuizen AW, Helgason HH, Hendriks MP, Hoekstra R, de Hingh IHJT, IJzermans JNM, Janssen JJB, Konsten JLM, Los M, Mekenkamp LJM, Nieboer P, Peeters KCMJ, Peters NAJB, Pruijt HJFM, Quarles van Ufford-Mannesse P, Rietbroek RC, Schiphorst AHW, Schouten van der Velden A, Schrauwen RWM, Sie MPS, Sommeijer DW, Sonneveld DJA, Stockmann HBAC, Tent M, Terheggen F, Tjin-A-Ton MLR, Valkenburg-van Iersel L, van der Velden AMT, Vles WJ, van Voorthuizen T, Wegdam JA, de Wilt JHW, Koopman M, May AM, and On Behalf Of The Plcrc Study Group

Abstract

Regular physical activity (PA) is associated with improved overall survival (OS) in stage I-III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9 ± 10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299-0.807, p value = 0.005) and 0.485 (95% CI 0.303-0.778, p value = 0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278-0.816, p value = 0.007)) and MVPA-SL (0.389 (95% CI 0.224-0.677, p value < 0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412-0.961, p value = 0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS.

Published
2022
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31. [Testicular cancer in Iceland 2000-2009: Incidence and survival].

Author

Orrason AW, Agnarsson BA, Geirsson G, Helgason HH, and Gudbjartsson T

Subjects
Adult, Aged, Humans, Iceland epidemiology, Incidence, Male, Middle Aged, Neoplasm Staging, Neoplasms, Germ Cell and Embryonal epidemiology, Neoplasms, Germ Cell and Embryonal mortality, Neoplasms, Germ Cell and Embryonal pathology, Neoplasms, Germ Cell and Embryonal therapy, Retrospective Studies, Seminoma mortality, Seminoma pathology, Seminoma therapy, Survival Analysis, Survival Rate, Testicular Neoplasms mortality, Testicular Neoplasms pathology, Testicular Neoplasms therapy, Time Factors, Treatment Outcome, Young Adult, Seminoma epidemiology, Testicular Neoplasms epidemiology
Abstract

Introduction: Survival of patients with testicular germ cell tumours has improved in recent years, mainly due to new modes of chemotherapy. We analyzed incidence, staging and survival of patients diagnosed during the last ten years in Iceland and compared the results to previous studies., Materials and Methods: A retrospective study including all Icelandic males diagnosed during 2000-2009. Pathology reports were reviewed and the tumours staged (Boden-Gibb). Overall survival was estimated and seminomas (ST) and non-seminomas (N-ST) compared., Results: 97 males were diagnosed, age-adjusted incidence being 5.9/100.000 males per year. The number of ST and N-ST was almost equal, and the mean age was 35.6 (range; 15-36), but patients with ST were 11.5 years older compared to N-ST. Symptoms were similar in both groups, also tumor size (4.0 cm), which did not change during the study period. Most of the tumours were in stage I, or 78.4%, 13.4% were in stage II og 8.2% in stage III-IV. ST were diagnosed at a significantly lower stage compared to N-ST (91.7 versus 65.3% in stage I; p=0.003). No distant metastases were diagnosed in patients with ST but in 8 patients with N-ST. Four patients died during the study period, two due to N-ST but no patient died because of ST. Five-year survival for the whole patient group was 95.1%., Conclusion: The incidence of testicular carcinoma in Iceland is similar to neighbouring countries and has remained fairly constant for the last two decades. At the same time the number of patients with localized disease (stage I) as well as the size of the tumours has not changed significantly. Survival in Iceland is comparable to the best results reported elsewhere.

Published
2011
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32. Identification of serum proteins as prognostic and predictive markers of colorectal cancer using surface enhanced laser desorption ionization-time of flight mass spectrometry.

Author

Helgason HH, Engwegen JY, Zapatka M, Vincent A, Cats A, Boot H, Beijnen JH, and Schellens JH

Subjects
Adult, Aged, Biomarkers, Tumor blood, Carcinoma blood, Carcinoma pathology, Carcinoma therapy, Case-Control Studies, Colorectal Neoplasms blood, Colorectal Neoplasms pathology, Colorectal Neoplasms therapy, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Prognosis, Biomarkers, Tumor isolation & purification, Blood Proteins isolation & purification, Carcinoma diagnosis, Colorectal Neoplasms diagnosis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Abstract

Colorectal cancer (CRC) is the second most common cause of cancer related death. Prognosis is highly dependent on stage at diagnosis making early detection mandatory. This study aimed to identify novel disease specific biomarkers of CRC, validate our previously identified biomarkers of CRC and identify serum biomarkers predicting treatment response and for monitoring. Serum of patients with metastatic CRC was collected, according to a predefined schedule, prior to start of standard first-line chemotherapy with oxaliplatin and capecitabine and serially before each 3 weekly treatment cycle and analyzed for proteomic profile by standardized SELDI-TOF MS. Serum proteomic mass spectrometry data of all subjects were processed using the tbimass R-package and proteomic profiles of CRC patients were compared with those of matched normal control subjects. Furthermore, changes in proteomic profiles during the course of chemotherapy were recorded according to treatment response. In total, 42 patients with advanced CRC were treated and mean follow-up was 13.5 months. The response rate was 50% and the median overall survival 19.5 months (95% CI: 16-23). By comparing CRC patients and healthy controls we identified 13 potential biomarkers of CRC (m/z 2.0-31.9 kDa) whereas two proteins, m/z 14060 and 28100 Da (apolipoprotein A-I), were highly significant (p<0.0001). Comparison of responding and non-responding patients identified 6 proteins potentially predicting response, where of m/z 3330 Da was significant (p=0.007). Serial analysis identified 2 proteins, m/z 2022 and 28100 Da, that changed during chemotherapy in accordance with response. We identified 13 m/z values discriminating between CRC patients and healthy controls, including the previously identified apolipoprotein A-I as a candidate biomarker for CRC and treatment monitoring.

Published
2010
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33. Identification of serum proteins discriminating colorectal cancer patients and healthy controls using surface-enhanced laser desorption ionisation-time of flight mass spectrometry.

Author

Engwegen JY, Helgason HH, Cats A, Harris N, Bonfrer JM, Schellens JH, and Beijnen JH

Subjects
Algorithms, C-Reactive Protein analysis, Carcinoembryonic Antigen blood, Colorectal Neoplasms diagnosis, Female, Humans, Male, Sensitivity and Specificity, Transferrin analysis, Biomarkers, Tumor blood, Blood Proteins analysis, Colorectal Neoplasms blood, Protein Array Analysis methods, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Abstract

Aim: To detect the new serum biomarkers for colorectal cancer (CRC) by serum protein profiling with surface-enhanced laser desorption ionisation--time of flight mass spectrometry (SELDI-TOF MS)., Methods: Two independent serum sample sets were analysed separately with the ProteinChip technology (set A: 40 CRC+49 healthy controls; set B: 37 CRC+31 healthy controls), using chips with a weak cation exchange moiety and buffer pH 5. Discriminative power of differentially expressed proteins was assessed with a classification tree algorithm. Sensitivities and specificities of the generated classification trees were obtained by blindly applying data from set A to the generated trees from set B and vice versa. CRC serum protein profiles were also compared with those from breast, ovarian, prostate, and non-small cell lung cancer., Results: Mass-to-charge ratios (m/z) 3.1x10(3), 3.3x10(3), 4.5x10(3), 6.6x10(3) and 28x10(3) were used as classifiers in the best-performing classification trees. Tree sensitivities and specificities were between 65% and 90%. Most of these discriminative m/z values were also different in the other tumour types investigated. M/z 3.3x10(3), main classifier in most trees, was a doubly charged form of the 6.6x10(3)-Da protein. The latter was identified as apolipoprotein C-I. M/z 3.1x10(3) was identified as an N-terminal fragment of albumin, and m/z 28x10(3) as apolipoprotein A-I., Conclusion: SELDI-TOF MS followed by classification tree pattern analysis is a suitable technique for finding new serum markers for CRC. Biomarkers can be identified and reproducibly detected in independent sample sets with high sensitivities and specificities. Although not specific for CRC, these biomarkers have a potential role in disease and treatment monitoring.

Published
2006
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