Abstract
Purpose: Radiation-induced lung disease (RILD), defined as dyspnea in this study, is a risk for patients receiving high-dose thoracic irradiation. This study is a TRIPOD (Transparent Reporting of A Multivariable Prediction Model for Individual Prognosis or Diagnosis) Type 4 validation of previously-published dyspnea models via secondary analysis of esophageal cancer SCOPE1 trial data. We quantify the predictive performance of these two models for predicting the maximal dyspnea grade ≥ 2 within 6 months after the end of high-dose chemo-radiotherapy for primary esophageal cancer.Materials and methods: We tested the performance of two previously published dyspnea risk models using baseline, treatment and follow-up data on 258 esophageal cancer patients in the UK enrolled into the SCOPE1 multi-center trial. The tested models were developed from lung cancer patients treated at MAASTRO Clinic (The Netherlands) from the period 2002 to 2011. The adverse event of interest was dyspnea ≥ Grade 2 (CTCAE v3) within 6 months after the end of radiotherapy. As some variables were missing randomly and cannot be imputed, 212 patients in the SCOPE1 were used for validation of model 1 and 255 patients were used for validation of model 2. The model parameter Forced Expiratory Volume in 1 s (FEV1), as a predictor to both validated models, was imputed using the WHO performance status. External validation was performed using an automated, decentralized approach, without exchange of individual patient data.Results: Out of 258 patients with esophageal cancer in SCOPE1 trial data, 38 patients (14.7%) developed radiation-induced dyspnea (≥ Grade 2) within 6 months after chemo-radiotherapy. The discrimination performance of the models in esophageal cancer patients treated with high-dose external beam radiotherapy was moderate, area under curve (AUC) of 0.68 (95% CI 0.55–0.76) and 0.70 (95% CI 0.58–0.77), respectively. The curves and AUCs derived by distributed learning were identical to the results from validation on a local host.Conclusion: We have externally validated previously published dyspnea models using an esophageal cancer dataset. FEV1 that is not routinely measured for esophageal cancer was imputed using WHO performance status. Prediction performance was not statistically different from previous training and validation sets. Risk estimates were dominated by WHO score in Model 1 and baseline dyspnea in Model 2. The distributed learning approach gave the same answer as local processing, and could be performed without accessing a validation site's individual patients-level data.
Highlights
In radiation therapy, radical radiation doses are expected to provide better local control than lower palliative doses, the risk of radiation-induced adverse events is increased
The goal of this study is to verify two hypotheses: (I) that a common thoracic radiation-induced lung disease (RILD) model may be feasible for a different index tumor and (II) that it is feasible to perform an external validation of a toxicity model between two sites via a distributed learning approach without any exchange of patient-specific records
The discrimination performance of the models in esophageal cancer patients treated with high-dose external beam radiotherapy are moderate, area under the receiveroperator curve (AUC) of 0.68 and 0.70, respectively
Summary
Radical radiation doses are expected to provide better local control than lower palliative doses, the risk of radiation-induced adverse events is increased. Clinical symptoms of radiation-induced lung disease (RILD) include dyspnea, cough, and fever, which can have a serious effect on the patient’s quality of life. 10–20% of patients with lung cancer who receive (chemo)-radiotherapy developing moderate to severe symptomatic RILD [1]. Radiation-induced dyspnea (RILD in this study) is a side-effect for patients treated with high-dose thoracic irradiation. Studies have reported the predictors for radiationinduced dyspnea for lung cancer patients treated with (chemo)radiotherapy [2, 3]. There is no published study reporting the risk factors of radiation-induced dyspnea for patients with primary esophageal cancer, which might be explained by the fact that dyspnea is not routinely assessed during follow-up of esophageal cancer treatment
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