The complication sum score: A Delphi-based approach to summarize treatment related complications for esophageal cancer

M. L. Frederiks; M. Berbée; B. P.L. Wijnhoven; E. Schuit; P. S.N. van Rossum; G. J. Meijer; S. Mook; J. J.M.E. Nuyttens; H. Rütten; M. D. den Hartogh; B. van Etten; J. A. Langendijk; H. W.M. van Laarhoven; C. T. Muijs; C. T. Muijs; B. P.L. Wijnhoven; H. W.M. van Laarhoven; M. Berbee; J. A. Langendijk; H. P. van der Laan; A. van der Schaaf; J. J.M.E. Nuyttens; H. Rutten; Y. L.B. Klaver; M. L. Frederiks; R. H.A. Verhoeven; B. van Etten; J. J. de Haan; W. Kleder; M. I. van Berge Henegouwen; Z. van Kesteren; B. Mostert; W. Schillemans; M. Sosef; F. A.R.M. Warmerdam; R. Canters; J. P. Ruurda; N. Haj Mohammad; B. Klarenbeek; M. D. den Hartogh; H. Westdorp

doi:10.1016/j.ctro.2026.101146

The complication sum score: A Delphi-based approach to summarize treatment related complications for esophageal cancer

M. L. Frederiks^*
, M. Berbée
, B. P.L. Wijnhoven
, E. Schuit
, P. S.N. van Rossum
, G. J. Meijer
, S. Mook
, J. J.M.E. Nuyttens
, H. Rütten
, M. D. den Hartogh
, B. van Etten
, J. A. Langendijk
, H. W.M. van Laarhoven
, C. T. Muijs
, C. T. Muijs
, B. P.L. Wijnhoven
, H. W.M. van Laarhoven
, M. Berbee
, J. A. Langendijk
, H. P. van der Laan

A. van der Schaaf, J. J.M.E. Nuyttens, H. Rutten, Y. L.B. Klaver, M. L. Frederiks^*, R. H.A. Verhoeven, B. van Etten, J. J. de Haan, W. Kleder, M. I. van Berge Henegouwen, Z. van Kesteren, B. Mostert, W. Schillemans, M. Sosef, F. A.R.M. Warmerdam, R. Canters, J. P. Ruurda, N. Haj Mohammad, B. Klarenbeek, M. D. den Hartogh, H. Westdorp,

^*Corresponding author for this work

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

Abstract

AbstractBackground and purposePrevention of treatment-related complications remains a major challenge in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) ± surgery. A single measure, reflecting the total complication burden, may provide a clear overall picture of patient burden and enables a direct comparison of alternative treatment strategies. We developed a Complication Sum Score (CSS) to quantify symptomatic complications.Materials and methodsA Delphi consensus procedure was used to develop the CCS using the expertise of health professionals to assess the impact of a spectrum of complications. The impact of each complication was scored on a 0–100 scale. Consensus for these scores was defined as an interquartile range ≤ 20. The association between the CSS and hospital/ICU stay, overall survival (OS) at 1 year and quality of life (QoL) was assessed in a multicenter dataset of patients with EC, using multivariable (logistic) regression analysis, correcting for possible confounders.ResultsForty-five experts completed the two-round Delphi procedure. Consensus was reached for all (36) complications. In 1225 patients, that underwent nCRT and esophagectomy, a higher CSS was significantly associated with a longer hospital (coefficient = 0.43[0.38–0.48], p < 0.01) and ICU stay (coefficient = 0.23[0.19–0.26], p < 0.01), and a worse OS (odds ratio = 1.005[1.004–1.006], p < 0.01). Among the patients that completed a QoL questionnaire after surgery (n = 98) an increased CSS was associated with worse QoL (coefficient = -0.24[-0.01–0.49], p = 0.06).ConclusionThe CSS offers a comprehensive tool to quantify treatment-related complications in a single score in EC patients that receive nCRT followed by surgical resection.

Original language	English
Article number	101146
Journal	Clinical and translational radiation oncology
Volume	59
DOIs	https://doi.org/10.1016/j.ctro.2026.101146
Publication status	Published - Jul 2026

Keywords

Delphi consensus
Esophageal cancer
Neoadjuvant chemoradiotherapy
Normal tissue complication probability
Treatment-related toxicity

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The complication sum score: A Delphi-based approach to summarize treatment related complications for esophageal cancerFinal published version, 3.06 MBLicence: CC BY

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Frederiks, M. L., Berbée, M., Wijnhoven, B. P. L., Schuit, E., van Rossum, P. S. N., Meijer, G. J., Mook, S., Nuyttens, J. J. M. E., Rütten, H., den Hartogh, M. D., van Etten, B., Langendijk, J. A., van Laarhoven, H. W. M., Muijs, C. T., Muijs, C. T., Wijnhoven, B. P. L., van Laarhoven, H. W. M., Berbee, M., Langendijk, J. A. (2026). The complication sum score: A Delphi-based approach to summarize treatment related complications for esophageal cancer. Clinical and translational radiation oncology, 59, Article 101146. https://doi.org/10.1016/j.ctro.2026.101146

@article{2e6f6508f5ff4b38af11d41709d955c3,

title = "The complication sum score: A Delphi-based approach to summarize treatment related complications for esophageal cancer",

abstract = "AbstractBackground and purposePrevention of treatment-related complications remains a major challenge in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) ± surgery. A single measure, reflecting the total complication burden, may provide a clear overall picture of patient burden and enables a direct comparison of alternative treatment strategies. We developed a Complication Sum Score (CSS) to quantify symptomatic complications.Materials and methodsA Delphi consensus procedure was used to develop the CCS using the expertise of health professionals to assess the impact of a spectrum of complications. The impact of each complication was scored on a 0–100 scale. Consensus for these scores was defined as an interquartile range ≤ 20. The association between the CSS and hospital/ICU stay, overall survival (OS) at 1 year and quality of life (QoL) was assessed in a multicenter dataset of patients with EC, using multivariable (logistic) regression analysis, correcting for possible confounders.ResultsForty-five experts completed the two-round Delphi procedure. Consensus was reached for all (36) complications. In 1225 patients, that underwent nCRT and esophagectomy, a higher CSS was significantly associated with a longer hospital (coefficient = 0.43[0.38–0.48], p < 0.01) and ICU stay (coefficient = 0.23[0.19–0.26], p < 0.01), and a worse OS (odds ratio = 1.005[1.004–1.006], p < 0.01). Among the patients that completed a QoL questionnaire after surgery (n = 98) an increased CSS was associated with worse QoL (coefficient = -0.24[-0.01–0.49], p = 0.06).ConclusionThe CSS offers a comprehensive tool to quantify treatment-related complications in a single score in EC patients that receive nCRT followed by surgical resection.",

keywords = "Delphi consensus, Esophageal cancer, Neoadjuvant chemoradiotherapy, Normal tissue complication probability, Treatment-related toxicity",

author = "Frederiks, \{M. L.\} and M. Berb{\'e}e and Wijnhoven, \{B. P.L.\} and E. Schuit and \{van Rossum\}, \{P. S.N.\} and Meijer, \{G. J.\} and S. Mook and Nuyttens, \{J. J.M.E.\} and H. R{\"u}tten and \{den Hartogh\}, \{M. D.\} and \{van Etten\}, B. and Langendijk, \{J. A.\} and \{van Laarhoven\}, \{H. W.M.\} and Muijs, \{C. T.\} and Muijs, \{C. T.\} and Wijnhoven, \{B. P.L.\} and \{van Laarhoven\}, \{H. W.M.\} and M. Berbee and Langendijk, \{J. A.\} and \{van der Laan\}, \{H. P.\} and \{van der Schaaf\}, A. and Nuyttens, \{J. J.M.E.\} and H. Rutten and Klaver, \{Y. L.B.\} and Frederiks, \{M. L.\} and Verhoeven, \{R. H.A.\} and \{van Etten\}, B. and \{de Haan\}, \{J. J.\} and W. Kleder and \{van Berge Henegouwen\}, \{M. I.\} and \{van Kesteren\}, Z. and B. Mostert and W. Schillemans and M. Sosef and Warmerdam, \{F. A.R.M.\} and R. Canters and Ruurda, \{J. P.\} and \{Haj Mohammad\}, N. and B. Klarenbeek and \{den Hartogh\}, \{M. D.\} and H. Westdorp",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/",

year = "2026",

month = jul,

doi = "10.1016/j.ctro.2026.101146",

language = "English",

volume = "59",

journal = "Clinical and translational radiation oncology",

issn = "2405-6308",

publisher = "Elsevier Ireland Ltd",

}

Frederiks, ML, Berbée, M, Wijnhoven, BPL, Schuit, E, van Rossum, PSN, Meijer, GJ, Mook, S, Nuyttens, JJME, Rütten, H, den Hartogh, MD, van Etten, B, Langendijk, JA, van Laarhoven, HWM, Muijs, CT, Muijs, CT, Wijnhoven, BPL, van Laarhoven, HWM, Berbee, M, Langendijk, JA, van der Laan, HP, van der Schaaf, A, Nuyttens, JJME, Rutten, H, Klaver, YLB, Frederiks, ML, Verhoeven, RHA, van Etten, B, de Haan, JJ, Kleder, W, van Berge Henegouwen, MI, van Kesteren, Z, Mostert, B, Schillemans, W, Sosef, M, Warmerdam, FARM, Canters, R, Ruurda, JP , Haj Mohammad, N, Klarenbeek, B, den Hartogh, MD, Westdorp, H 2026, 'The complication sum score: A Delphi-based approach to summarize treatment related complications for esophageal cancer', Clinical and translational radiation oncology, vol. 59, 101146. https://doi.org/10.1016/j.ctro.2026.101146

TY - JOUR

T1 - The complication sum score

T2 - A Delphi-based approach to summarize treatment related complications for esophageal cancer

AU - Frederiks, M. L.

AU - Berbée, M.

AU - Wijnhoven, B. P.L.

AU - Schuit, E.

AU - van Rossum, P. S.N.

AU - Meijer, G. J.

AU - Mook, S.

AU - Nuyttens, J. J.M.E.

AU - Rütten, H.

AU - den Hartogh, M. D.

AU - van Etten, B.

AU - Langendijk, J. A.

AU - van Laarhoven, H. W.M.

AU - Muijs, C. T.

AU - Wijnhoven, B. P.L.

AU - van Laarhoven, H. W.M.

AU - Berbee, M.

AU - Langendijk, J. A.

AU - van der Laan, H. P.

AU - van der Schaaf, A.

AU - Nuyttens, J. J.M.E.

AU - Rutten, H.

AU - Klaver, Y. L.B.

AU - Frederiks, M. L.

AU - Verhoeven, R. H.A.

AU - van Etten, B.

AU - de Haan, J. J.

AU - Kleder, W.

AU - van Berge Henegouwen, M. I.

AU - van Kesteren, Z.

AU - Mostert, B.

AU - Schillemans, W.

AU - Sosef, M.

AU - Warmerdam, F. A.R.M.

AU - Canters, R.

AU - Ruurda, J. P.

AU - Haj Mohammad, N.

AU - Klarenbeek, B.

AU - den Hartogh, M. D.

AU - Westdorp, H.

N1 - Publisher Copyright: © 2026 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

PY - 2026/7

Y1 - 2026/7

N2 - AbstractBackground and purposePrevention of treatment-related complications remains a major challenge in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) ± surgery. A single measure, reflecting the total complication burden, may provide a clear overall picture of patient burden and enables a direct comparison of alternative treatment strategies. We developed a Complication Sum Score (CSS) to quantify symptomatic complications.Materials and methodsA Delphi consensus procedure was used to develop the CCS using the expertise of health professionals to assess the impact of a spectrum of complications. The impact of each complication was scored on a 0–100 scale. Consensus for these scores was defined as an interquartile range ≤ 20. The association between the CSS and hospital/ICU stay, overall survival (OS) at 1 year and quality of life (QoL) was assessed in a multicenter dataset of patients with EC, using multivariable (logistic) regression analysis, correcting for possible confounders.ResultsForty-five experts completed the two-round Delphi procedure. Consensus was reached for all (36) complications. In 1225 patients, that underwent nCRT and esophagectomy, a higher CSS was significantly associated with a longer hospital (coefficient = 0.43[0.38–0.48], p < 0.01) and ICU stay (coefficient = 0.23[0.19–0.26], p < 0.01), and a worse OS (odds ratio = 1.005[1.004–1.006], p < 0.01). Among the patients that completed a QoL questionnaire after surgery (n = 98) an increased CSS was associated with worse QoL (coefficient = -0.24[-0.01–0.49], p = 0.06).ConclusionThe CSS offers a comprehensive tool to quantify treatment-related complications in a single score in EC patients that receive nCRT followed by surgical resection.

AB - AbstractBackground and purposePrevention of treatment-related complications remains a major challenge in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) ± surgery. A single measure, reflecting the total complication burden, may provide a clear overall picture of patient burden and enables a direct comparison of alternative treatment strategies. We developed a Complication Sum Score (CSS) to quantify symptomatic complications.Materials and methodsA Delphi consensus procedure was used to develop the CCS using the expertise of health professionals to assess the impact of a spectrum of complications. The impact of each complication was scored on a 0–100 scale. Consensus for these scores was defined as an interquartile range ≤ 20. The association between the CSS and hospital/ICU stay, overall survival (OS) at 1 year and quality of life (QoL) was assessed in a multicenter dataset of patients with EC, using multivariable (logistic) regression analysis, correcting for possible confounders.ResultsForty-five experts completed the two-round Delphi procedure. Consensus was reached for all (36) complications. In 1225 patients, that underwent nCRT and esophagectomy, a higher CSS was significantly associated with a longer hospital (coefficient = 0.43[0.38–0.48], p < 0.01) and ICU stay (coefficient = 0.23[0.19–0.26], p < 0.01), and a worse OS (odds ratio = 1.005[1.004–1.006], p < 0.01). Among the patients that completed a QoL questionnaire after surgery (n = 98) an increased CSS was associated with worse QoL (coefficient = -0.24[-0.01–0.49], p = 0.06).ConclusionThe CSS offers a comprehensive tool to quantify treatment-related complications in a single score in EC patients that receive nCRT followed by surgical resection.

KW - Delphi consensus

KW - Esophageal cancer

KW - Neoadjuvant chemoradiotherapy

KW - Normal tissue complication probability

KW - Treatment-related toxicity

UR - https://www.scopus.com/pages/publications/105034765475

U2 - 10.1016/j.ctro.2026.101146

DO - 10.1016/j.ctro.2026.101146

M3 - Article

C2 - 42005718

AN - SCOPUS:105034765475

SN - 2405-6308

VL - 59

JO - Clinical and translational radiation oncology

JF - Clinical and translational radiation oncology

M1 - 101146

ER -

The complication sum score: A Delphi-based approach to summarize treatment related complications for esophageal cancer

Abstract

Keywords

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