Prolonged Time to Surgery in Patients with Residual Disease after Neoadjuvant Chemoradiotherapy for Esophageal Cancer

Hidde C. G. Overtoom; Ben M. Eyck; Berend J. van der Wilk; Bo J. Noordman; Pieter C. van der Sluis; Bas P. L. Wijnhoven; J. Jan B. van Lanschot; Sjoerd M. Lagarde; Michail Doukas; Ate van der Gaast; Bianca Mostert; Roelf Valkema; Manon C. W. Spaander; Joost J. M. E. Nuyttens; Peter Paul L. O. Coene; Lieke Hol; Ewout F. W. Courrech Staal; Mike Kliffen; B. C. M. Haberkorn; Jan Willem T. Dekker; Rutger Quispel; M. R. J. ten Broek; A. van Tilburg; K. J. Neelis; Joos Heisterkamp; W. L. Hazen; I. A. C. Vermeltfoort; A. A. M. van der Wurff; L. V. Beerepoot; T. Rozema; Ewout A. Kouwenhoven; A. van der Linde; A. Agool; J. van Baarlen; R. Hoekstra; E. M. Hendriksen; Grard A. P. Nieuwenhuijzen; Erik J. Schoon; Mark J. Roef; Gisena van Lijnschoten; Annemarie M. J. Thijs; Maurice J. C. van der Sangen; Jean-Pierre E. N. Pierie; Sietske Corporaal; J. J. M. Balink; Judith Nieken; W. Edward Fiets; V. Oppedijk; Camiel Rosman; Peter D. Siersema; Marcel J. R. Janssen; Rachel S. van der Post; S. A. Radema; Heidi Rütten; Johanna W. van Sandick; Jolanda M. van Dieren; E. Owers; P. Snaebjornsson; F. E. M. Voncken; Meindert N. Sosef; Liekele E. Oostenbrug; Wendy M. J. Schreurs; R. G. Riedl; Fabienne A. R. M. Warmerdam; Jeroen Buijsen; Edwin S. van der Zaag; G. Willemien Erkelens; Marc D. Zuijdwijk; H. Doornewaard; Cathrien S. van Driel; K. Muller; Henk H. Hartgrink; Jurjen J. Boonstra; Lioe-Fee de Geus-Oei; Marije Slingerland; Irene Lips; Susan Quix; Ewout W. Steyerberg

doi:10.1097/SLA.0000000000006488

Prolonged Time to Surgery in Patients with Residual Disease after Neoadjuvant Chemoradiotherapy for Esophageal Cancer

Hidde C. G. Overtoom^*
, Ben M. Eyck
, Berend J. van der Wilk
, Bo J. Noordman
, Pieter C. van der Sluis
, Bas P. L. Wijnhoven
, J. Jan B. van Lanschot
, Sjoerd M. Lagarde
, Michail Doukas
, Ate van der Gaast
, Bianca Mostert
, Roelf Valkema
, Manon C. W. Spaander
, Joost J. M. E. Nuyttens
, Peter Paul L. O. Coene
, Lieke Hol
, Ewout F. W. Courrech Staal
, Mike Kliffen
, B. C. M. Haberkorn
, Jan Willem T. Dekker

Rutger Quispel, M. R. J. ten Broek, A. van Tilburg, K. J. Neelis, Joos Heisterkamp, W. L. Hazen, I. A. C. Vermeltfoort, A. A. M. van der Wurff, L. V. Beerepoot, T. Rozema, Ewout A. Kouwenhoven, A. van der Linde, A. Agool, J. van Baarlen, R. Hoekstra, E. M. Hendriksen, Grard A. P. Nieuwenhuijzen, Erik J. Schoon, Mark J. Roef, Gisena van Lijnschoten, Annemarie M. J. Thijs, Maurice J. C. van der Sangen, Jean-Pierre E. N. Pierie, Sietske Corporaal, J. J. M. Balink, Judith Nieken, W. Edward Fiets, V. Oppedijk, Camiel Rosman, Peter D. Siersema, Marcel J. R. Janssen, Rachel S. van der Post, S. A. Radema, Heidi Rütten, Johanna W. van Sandick, Jolanda M. van Dieren, E. Owers, P. Snaebjornsson, F. E. M. Voncken, Meindert N. Sosef, Liekele E. Oostenbrug, Wendy M. J. Schreurs, R. G. Riedl, Fabienne A. R. M. Warmerdam, Jeroen Buijsen, Edwin S. van der Zaag, G. Willemien Erkelens, Marc D. Zuijdwijk, H. Doornewaard, Cathrien S. van Driel, K. Muller, Henk H. Hartgrink, Jurjen J. Boonstra, Lioe-Fee de Geus-Oei, Marije Slingerland, Irene Lips, Susan Quix, Ewout W. Steyerberg

^*Corresponding author for this work

Affiliatie VU

Erasmus University Rotterdam
Maasstad Hospital
Reinier de Graaf Groep
ETZ Elisabeth
Dr. Bernard Verbeeten Instituut
Zorggroep Twente
Catharina Hospital
Stichting Laboratoria voor Pathologie en Medische Microbiologie
Medical Centre Leeuwarden
Pathology Friesland
Radiotherapeutic Institute Friesland
Radboud University Nijmegen
Antoni van Leeuwenhoek Hospital
Zuyderland
Maastricht University
Gelre Ziekenhuizen
Leiden University

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Objective: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer. Summary Background Data: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity. Methods: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT. Results: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95%CI 1.52-9.59). Other outcomes were comparable between both groups. Conclusion: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.

Original language	English
Article number	10.1097/SLA.0000000000006488
Journal	Annals of surgery
DOIs	https://doi.org/10.1097/SLA.0000000000006488
Publication status	E-pub ahead of print - 2024

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Overtoom, H. C. G., Eyck, B. M., van der Wilk, B. J., Noordman, B. J., van der Sluis, P. C., Wijnhoven, B. P. L., van Lanschot, J. J. B., Lagarde, S. M., Doukas, M., van der Gaast, A., Mostert, B., Valkema, R., Spaander, M. C. W., Nuyttens, J. J. M. E., Coene, P. P. L. O., Hol, L., Courrech Staal, E. F. W., Kliffen, M., Haberkorn, B. C. M., ... Steyerberg, E. W. (2024). Prolonged Time to Surgery in Patients with Residual Disease after Neoadjuvant Chemoradiotherapy for Esophageal Cancer. Annals of surgery, Article 10.1097/SLA.0000000000006488. Advance online publication. https://doi.org/10.1097/SLA.0000000000006488

@article{fa0c4944f1834439a3b4da0f5f6023d5,

title = "Prolonged Time to Surgery in Patients with Residual Disease after Neoadjuvant Chemoradiotherapy for Esophageal Cancer",

abstract = "Objective: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer. Summary Background Data: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity. Methods: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT. Results: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95\%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95\%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95\%CI 1.52-9.59). Other outcomes were comparable between both groups. Conclusion: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.",

author = "Overtoom, \{Hidde C. G.\} and Eyck, \{Ben M.\} and \{van der Wilk\}, \{Berend J.\} and Noordman, \{Bo J.\} and \{van der Sluis\}, \{Pieter C.\} and Wijnhoven, \{Bas P. L.\} and \{van Lanschot\}, \{J. Jan B.\} and Lagarde, \{Sjoerd M.\} and Michail Doukas and \{van der Gaast\}, Ate and Bianca Mostert and Roelf Valkema and Spaander, \{Manon C. W.\} and Nuyttens, \{Joost J. M. E.\} and Coene, \{Peter Paul L. O.\} and Lieke Hol and \{Courrech Staal\}, \{Ewout F. W.\} and Mike Kliffen and Haberkorn, \{B. C. M.\} and Dekker, \{Jan Willem T.\} and Rutger Quispel and \{ten Broek\}, \{M. R. J.\} and \{van Tilburg\}, A. and Neelis, \{K. J.\} and Joos Heisterkamp and Hazen, \{W. L.\} and Vermeltfoort, \{I. A. C.\} and \{van der Wurff\}, \{A. A. M.\} and Beerepoot, \{L. V.\} and T. Rozema and Kouwenhoven, \{Ewout A.\} and \{van der Linde\}, A. and A. Agool and \{van Baarlen\}, J. and R. Hoekstra and Hendriksen, \{E. M.\} and Nieuwenhuijzen, \{Grard A. P.\} and Schoon, \{Erik J.\} and Roef, \{Mark J.\} and \{van Lijnschoten\}, Gisena and Thijs, \{Annemarie M. J.\} and \{van der Sangen\}, \{Maurice J. C.\} and Pierie, \{Jean-Pierre E. N.\} and Sietske Corporaal and Balink, \{J. J. M.\} and Judith Nieken and \{Edward Fiets\}, W. and V. Oppedijk and Camiel Rosman and Siersema, \{Peter D.\} and Janssen, \{Marcel J. R.\} and \{van der Post\}, \{Rachel S.\} and Radema, \{S. A.\} and Heidi R{\"u}tten and \{van Sandick\}, \{Johanna W.\} and \{van Dieren\}, \{Jolanda M.\} and E. Owers and P. Snaebjornsson and Voncken, \{F. E. M.\} and Sosef, \{Meindert N.\} and Oostenbrug, \{Liekele E.\} and Schreurs, \{Wendy M. J.\} and Riedl, \{R. G.\} and Warmerdam, \{Fabienne A. R. M.\} and Jeroen Buijsen and \{van der Zaag\}, \{Edwin S.\} and Erkelens, \{G. Willemien\} and Zuijdwijk, \{Marc D.\} and H. Doornewaard and \{van Driel\}, \{Cathrien S.\} and K. Muller and Hartgrink, \{Henk H.\} and Boonstra, \{Jurjen J.\} and \{de Geus-Oei\}, Lioe-Fee and Marije Slingerland and Irene Lips and Susan Quix and Steyerberg, \{Ewout W.\}",

year = "2024",

doi = "10.1097/SLA.0000000000006488",

language = "English",

journal = "Annals of surgery",

issn = "0003-4932",

publisher = "Lippincott Williams and Wilkins",

}

Overtoom, HCG, Eyck, BM, van der Wilk, BJ, Noordman, BJ, van der Sluis, PC, Wijnhoven, BPL, van Lanschot, JJB, Lagarde, SM, Doukas, M, van der Gaast, A, Mostert, B, Valkema, R, Spaander, MCW, Nuyttens, JJME, Coene, PPLO, Hol, L, Courrech Staal, EFW, Kliffen, M, Haberkorn, BCM, Dekker, JWT, Quispel, R, ten Broek, MRJ, van Tilburg, A, Neelis, KJ, Heisterkamp, J, Hazen, WL, Vermeltfoort, IAC, van der Wurff, AAM, Beerepoot, LV, Rozema, T, Kouwenhoven, EA, van der Linde, A, Agool, A, van Baarlen, J, Hoekstra, R, Hendriksen, EM, Nieuwenhuijzen, GAP, Schoon, EJ, Roef, MJ, van Lijnschoten, G, Thijs, AMJ, van der Sangen, MJC, Pierie, J-PEN, Corporaal, S, Balink, JJM, Nieken, J, Edward Fiets, W, Oppedijk, V, Rosman, C, Siersema, PD, Janssen, MJR, van der Post, RS, Radema, SA, Rütten, H, van Sandick, JW, van Dieren, JM, Owers, E, Snaebjornsson, P, Voncken, FEM, Sosef, MN, Oostenbrug, LE, Schreurs, WMJ, Riedl, RG, Warmerdam, FARM, Buijsen, J, van der Zaag, ES, Erkelens, GW, Zuijdwijk, MD, Doornewaard, H, van Driel, CS, Muller, K, Hartgrink, HH, Boonstra, JJ, de Geus-Oei, L-F, Slingerland, M, Lips, I, Quix, S & Steyerberg, EW 2024, 'Prolonged Time to Surgery in Patients with Residual Disease after Neoadjuvant Chemoradiotherapy for Esophageal Cancer', Annals of surgery. https://doi.org/10.1097/SLA.0000000000006488

TY - JOUR

T1 - Prolonged Time to Surgery in Patients with Residual Disease after Neoadjuvant Chemoradiotherapy for Esophageal Cancer

AU - Overtoom, Hidde C. G.

AU - Eyck, Ben M.

AU - van der Wilk, Berend J.

AU - Noordman, Bo J.

AU - van der Sluis, Pieter C.

AU - Wijnhoven, Bas P. L.

AU - van Lanschot, J. Jan B.

AU - Lagarde, Sjoerd M.

AU - Doukas, Michail

AU - van der Gaast, Ate

AU - Mostert, Bianca

AU - Valkema, Roelf

AU - Spaander, Manon C. W.

AU - Nuyttens, Joost J. M. E.

AU - Coene, Peter Paul L. O.

AU - Hol, Lieke

AU - Courrech Staal, Ewout F. W.

AU - Kliffen, Mike

AU - Haberkorn, B. C. M.

AU - Dekker, Jan Willem T.

AU - Quispel, Rutger

AU - ten Broek, M. R. J.

AU - van Tilburg, A.

AU - Neelis, K. J.

AU - Heisterkamp, Joos

AU - Hazen, W. L.

AU - Vermeltfoort, I. A. C.

AU - van der Wurff, A. A. M.

AU - Beerepoot, L. V.

AU - Rozema, T.

AU - Kouwenhoven, Ewout A.

AU - van der Linde, A.

AU - Agool, A.

AU - van Baarlen, J.

AU - Hoekstra, R.

AU - Hendriksen, E. M.

AU - Nieuwenhuijzen, Grard A. P.

AU - Schoon, Erik J.

AU - Roef, Mark J.

AU - van Lijnschoten, Gisena

AU - Thijs, Annemarie M. J.

AU - van der Sangen, Maurice J. C.

AU - Pierie, Jean-Pierre E. N.

AU - Corporaal, Sietske

AU - Balink, J. J. M.

AU - Nieken, Judith

AU - Edward Fiets, W.

AU - Oppedijk, V.

AU - Rosman, Camiel

AU - Siersema, Peter D.

AU - Janssen, Marcel J. R.

AU - van der Post, Rachel S.

AU - Radema, S. A.

AU - Rütten, Heidi

AU - van Sandick, Johanna W.

AU - van Dieren, Jolanda M.

AU - Owers, E.

AU - Snaebjornsson, P.

AU - Voncken, F. E. M.

AU - Sosef, Meindert N.

AU - Oostenbrug, Liekele E.

AU - Schreurs, Wendy M. J.

AU - Riedl, R. G.

AU - Warmerdam, Fabienne A. R. M.

AU - Buijsen, Jeroen

AU - van der Zaag, Edwin S.

AU - Erkelens, G. Willemien

AU - Zuijdwijk, Marc D.

AU - Doornewaard, H.

AU - van Driel, Cathrien S.

AU - Muller, K.

AU - Hartgrink, Henk H.

AU - Boonstra, Jurjen J.

AU - de Geus-Oei, Lioe-Fee

AU - Slingerland, Marije

AU - Lips, Irene

AU - Quix, Susan

AU - Steyerberg, Ewout W.

PY - 2024

Y1 - 2024

N2 - Objective: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer. Summary Background Data: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity. Methods: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT. Results: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95%CI 1.52-9.59). Other outcomes were comparable between both groups. Conclusion: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.

AB - Objective: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer. Summary Background Data: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity. Methods: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT. Results: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95%CI 1.52-9.59). Other outcomes were comparable between both groups. Conclusion: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.

UR - https://www.scopus.com/pages/publications/85201661008

UR - https://www.ncbi.nlm.nih.gov/pubmed/39140597

U2 - 10.1097/SLA.0000000000006488

DO - 10.1097/SLA.0000000000006488

M3 - Article

C2 - 39140597

SN - 0003-4932

JO - Annals of surgery

JF - Annals of surgery

M1 - 10.1097/SLA.0000000000006488

ER -

Prolonged Time to Surgery in Patients with Residual Disease after Neoadjuvant Chemoradiotherapy for Esophageal Cancer

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