Prediction of Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer: Development and Validation of a Pretreatment Nomogram

Peter S.N. van Rossum, Wei Deng, David M. Routman, Amy Y. Liu, Cai Xu, Yutaka Shiraishi, Max Peters, Kenneth W. Merrell, Christopher L. Hallemeier, Radhe Mohan, Steven H. Lin

Research output: Contribution to journalArticle

Abstract

Introduction: In patients with esophageal cancer, occurrence of severe radiation-induced lymphopenia during chemoradiation therapy has been associated with worse progression-free and overall survival. The aim of this study was to develop and validate a pretreatment clinical nomogram for the prediction of grade 4 lymphopenia. Methods and Materials: A development set of consecutive patients who underwent chemoradiation therapy for esophageal cancer and an independent validation set of patients from another institution were identified. Grade 4 lymphopenia was defined as an absolute lymphocyte count nadir during chemoradiation therapy of <0.2 × 103/μL. Multivariable logistic regression analysis was used to create a prediction model for grade 4 lymphopenia in the development set, which was internally validated using bootstrapping and externally validated by applying the model to the validation set. The model was presented as a nomogram yielding 4 risk groups. Results: Among 860 included patients, 322 (37%) experienced grade 4 lymphopenia. Higher age, larger planning target volume in interaction with lower body mass index, photon- rather than proton-based therapy, and lower baseline absolute lymphocyte count were predictive in the final model (corrected c-statistic, 0.76). External validation in 144 patients, among whom 58 (40%) had grade 4 lymphopenia, yielded a c-statistic of 0.71. Four nomogram-based risk groups yielded predicted risk rates of 10%, 24%, 43%, and 70%, respectively. Conclusions: A pretreatment clinical nomogram was developed and validated for the prediction of grade 4 radiation-induced lymphopenia during chemoradiation therapy for esophageal cancer. The nomogram can risk stratify individual patients suitable for lymphopenia-mitigating strategies or potential future therapeutic approaches to ultimately improve survival.

Original languageEnglish
JournalPractical Radiation Oncology
DOIs
Publication statusAccepted/In press - 2019 Jan 1
Externally publishedYes

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Nomograms
Lymphopenia
Esophageal Neoplasms
Lymphocyte Count
Therapeutics
Proton Therapy
Radiation
Photons
Disease-Free Survival
Body Mass Index
Logistic Models
Regression Analysis
Survival

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Prediction of Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer : Development and Validation of a Pretreatment Nomogram. / van Rossum, Peter S.N.; Deng, Wei; Routman, David M.; Liu, Amy Y.; Xu, Cai; Shiraishi, Yutaka; Peters, Max; Merrell, Kenneth W.; Hallemeier, Christopher L.; Mohan, Radhe; Lin, Steven H.

In: Practical Radiation Oncology, 01.01.2019.

Research output: Contribution to journalArticle

van Rossum, Peter S.N. ; Deng, Wei ; Routman, David M. ; Liu, Amy Y. ; Xu, Cai ; Shiraishi, Yutaka ; Peters, Max ; Merrell, Kenneth W. ; Hallemeier, Christopher L. ; Mohan, Radhe ; Lin, Steven H. / Prediction of Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer : Development and Validation of a Pretreatment Nomogram. In: Practical Radiation Oncology. 2019.
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abstract = "Introduction: In patients with esophageal cancer, occurrence of severe radiation-induced lymphopenia during chemoradiation therapy has been associated with worse progression-free and overall survival. The aim of this study was to develop and validate a pretreatment clinical nomogram for the prediction of grade 4 lymphopenia. Methods and Materials: A development set of consecutive patients who underwent chemoradiation therapy for esophageal cancer and an independent validation set of patients from another institution were identified. Grade 4 lymphopenia was defined as an absolute lymphocyte count nadir during chemoradiation therapy of <0.2 × 103/μL. Multivariable logistic regression analysis was used to create a prediction model for grade 4 lymphopenia in the development set, which was internally validated using bootstrapping and externally validated by applying the model to the validation set. The model was presented as a nomogram yielding 4 risk groups. Results: Among 860 included patients, 322 (37{\%}) experienced grade 4 lymphopenia. Higher age, larger planning target volume in interaction with lower body mass index, photon- rather than proton-based therapy, and lower baseline absolute lymphocyte count were predictive in the final model (corrected c-statistic, 0.76). External validation in 144 patients, among whom 58 (40{\%}) had grade 4 lymphopenia, yielded a c-statistic of 0.71. Four nomogram-based risk groups yielded predicted risk rates of 10{\%}, 24{\%}, 43{\%}, and 70{\%}, respectively. Conclusions: A pretreatment clinical nomogram was developed and validated for the prediction of grade 4 radiation-induced lymphopenia during chemoradiation therapy for esophageal cancer. The nomogram can risk stratify individual patients suitable for lymphopenia-mitigating strategies or potential future therapeutic approaches to ultimately improve survival.",
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AU - Liu, Amy Y.

AU - Xu, Cai

AU - Shiraishi, Yutaka

AU - Peters, Max

AU - Merrell, Kenneth W.

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AU - Mohan, Radhe

AU - Lin, Steven H.

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N2 - Introduction: In patients with esophageal cancer, occurrence of severe radiation-induced lymphopenia during chemoradiation therapy has been associated with worse progression-free and overall survival. The aim of this study was to develop and validate a pretreatment clinical nomogram for the prediction of grade 4 lymphopenia. Methods and Materials: A development set of consecutive patients who underwent chemoradiation therapy for esophageal cancer and an independent validation set of patients from another institution were identified. Grade 4 lymphopenia was defined as an absolute lymphocyte count nadir during chemoradiation therapy of <0.2 × 103/μL. Multivariable logistic regression analysis was used to create a prediction model for grade 4 lymphopenia in the development set, which was internally validated using bootstrapping and externally validated by applying the model to the validation set. The model was presented as a nomogram yielding 4 risk groups. Results: Among 860 included patients, 322 (37%) experienced grade 4 lymphopenia. Higher age, larger planning target volume in interaction with lower body mass index, photon- rather than proton-based therapy, and lower baseline absolute lymphocyte count were predictive in the final model (corrected c-statistic, 0.76). External validation in 144 patients, among whom 58 (40%) had grade 4 lymphopenia, yielded a c-statistic of 0.71. Four nomogram-based risk groups yielded predicted risk rates of 10%, 24%, 43%, and 70%, respectively. Conclusions: A pretreatment clinical nomogram was developed and validated for the prediction of grade 4 radiation-induced lymphopenia during chemoradiation therapy for esophageal cancer. The nomogram can risk stratify individual patients suitable for lymphopenia-mitigating strategies or potential future therapeutic approaches to ultimately improve survival.

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