3720 - Development of a Prediction Model for Cisplatin Tolerability during Chemoradiation in Older Adults with Head and Neck Squamous Cell Carcinoma

A. Ruhle^1,2, M. Weymann³, M. Behrens³, S. Marschner⁴, C. Kut⁵, M. Haderlein⁶, A. Fabian⁷, C. Senger⁸, J. Kraft⁹, J. von der Grün^10,11, E. Chen¹², C. Zamboglou^2,13, M. Guckenberger¹¹, C. Belka¹⁴, A. Mayer¹⁵, A. L. Grosu², P. Balermpas¹¹, C. Stromberger⁸, H. Quon⁵, and N. H. Nicolay^1,2; ¹Department of Radiation Oncology, University of Leipzig Medical Center, Leipzig, Germany, ²Department of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany, ³Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany, ⁴Department of Radiation Oncology, University Hospital, Ludwig-Maximilians-University, Munich, Germany, ⁵Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, ⁶Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany, ⁷German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (dkfz), Heidelberg, Germany, ⁸Department of Radiooncology and Radiotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany, ⁹Department of Radiation Oncology, University Hospital Würzburg, Würzburg, Germany, ¹⁰Department of Radiotherapy and Oncology, Goethe-University Frankfurt am Main, Frankfurt, Germany, ¹¹Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, ¹²University Hospitals Seidman Cancer Center, Department of Radiation Oncology, Cleveland, OH, ¹³Department of Radiation Oncology, German Oncology Center, European University of Cyprus, Limassol, Cyprus, ¹⁴Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany, ¹⁵Department of Radiation Oncology, University Medical Center Mainz, Mainz, Germany

Purpose/Objective(s): Treating head and neck squamous cell carcinoma (HNSCC) in older adults presents unique challenges due to considerations of frailty and accompanying comorbidities. While cisplatin-based chemoradiation is standard for locoregionally advanced HNSCC (LA-HNSCC), many older patients cannot tolerate concomitant cisplatin. Cumulative cisplatin doses of =200 mg/m² are associated with improved locoregional control, but factors predicting cisplatin tolerability in older adults are unclear. Therefore, we developed a prediction model for cisplatin tolerability in this population. Materials/

Methods: This study examines patients from an international registry, comprising 1,269 older (=65 years) individuals diagnosed with LA-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx, and treated with definitive (chemo)radiation between 2005 and 2019. Data were retrospectively collected from 15 academic centers across Europe and the United States. 363 patients had been treated with single-agent cisplatin with information about cumulative cisplatin dose available and were used for model development. Baseline blood parameters were obtained up to 5 days before initiation of radiotherapy. Multiple imputation of missing data was conducted using k-nearest neighbor imputation. Different models, such as generalized linear (GL), support vector machine (SVM) and random forest (RF) models, were compared in terms of their predictive performance regarding the completion of the prescribed cisplatin dose of =200 mg/m².
Results: Median age of the cohort was 71 years (IQR, 67-75), median ECOG and age-adjusted Charlson Comorbidity Index were 1 (IQR, 0-1) and 4 (IQR, 3-5), respectively. 193 (53.2%) of the 363 analyzed patients achieved a cumulative cisplatin dose of =200 mg/m². In the GL model with 5 repeats of 10-fold cross-validation, laryngeal cancer (p<0.01), positive HPV status in oropharyngeal cancer patients (p<0.01), and higher levels of hemoglobin (p<0.01), CRP (p<0.05), and eGFR (p<0.01) were associated with a higher probability of achieving a cumulative cisplatin dose of =200 mg/m². 90 (72.0%) out of 125 older adults with HPV-positive oropharyngeal cancer, but only 36 (40.4%) of 89 oropharyngeal cancer patients with negative/unknown HPV status achieved a cumulative cisplatin dose of =200 mg/m². HPV status, hemoglobin level, CRP concentration, and eGFR were identified as the most important features in the RF model. AUC values of the GL, SVM, and RF models were 0.70, 0.71, and 0.75, while Brier scores were 0.23, 0.22, and 0.21, respectively.
Conclusion: The RF model, mainly based on HPV status and baseline blood values, showed the best performance in predicting a cumulative cisplatin of =200 mg/m² during chemoradiation in older adults with LA-HNSCC. Upon successful external validation, this model may identify patients at risk for chemotherapy discontinuation and could aid treatment decisions regarding optimized chemoradiation in older adults with LA-HNSCC.