Development and Validation of a Predictive Model for Toxicity of Neoadjuvant Chemoradiotherapy in Rectal Cancer in the CAO/ARO/AIO-04 Phase III Trial

Markus Diefenhardt, Daniel Martin, Ethan B. Ludmir, Maximilian Fleischmann, Ralf Dieter Hofheinz, Michael Ghadimi, Rebekka Kosmala, Bülent Polat, Tim Friede, Bruce D. Minsky, Claus Rödel, Emmanouil Fokas

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: There is a lack of predictive models to identify patients at risk of high neoadjuvant chemoradiotherapy (CRT)-related acute toxicity in rectal cancer. Patient and Methods: The CAO/ARO/AIO-04 trial was divided into a development (n = 831) and a validation (n = 405) cohort. Using a best subset selection approach, predictive models for grade 3–4 acute toxicity were calculated including clinicopathologic characteristics, pretreatment blood parameters, and baseline results of quality-of-life questionnaires and evaluated using the area under the ROC curve. The final model was internally and externally validated. Results: In the development cohort, 155 patients developed grade 3–4 toxicities due to CRT. In the final evaluation, 15 parameters were included in the logistic regression models using best-subset selection. BMI, gender, and emotional functioning remained significant for predicting toxicity, with a discrimination ability adjusted for overfitting of AUC 0.687. The odds of experiencing high-grade toxicity were 3.8 times higher in the intermediate and 6.4 times higher in the high-risk group (p < 0.001). Rates of toxicity (p = 0.001) and low treatment adherence (p = 0.007) remained significantly different in the validation cohort, whereas discrimination ability was not significantly worse (DeLong test 0.09). Conclusion: We developed and validated a predictive model for toxicity using gender, BMI, and emotional functioning. Such a model could help identify patients at risk for treatment-related high-grade toxicity to assist in treatment guidance and patient participation in shared decision making.

Original languageEnglish (US)
Article number4425
JournalCancers
Volume14
Issue number18
DOIs
StatePublished - Sep 2022

Keywords

  • chemoradiotherapy
  • neoadjuvant
  • rectal cancer
  • risk score
  • toxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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