Development and internal validation of a multinomial NTCP model for the severity of acute dyspnea after radiotherapy for lung cancer.

Abstract

Dyspnea evolution after radiotherapy for lung cancer is complex with potential symptom deterioration and improvement from baseline. We developed and internally validated a multinomial normal tissue complication probability (NTCP) model predicting dyspnea grade. Patient-reported dyspnea was collected pre-treatment and during 6 months follow-up for 182 stage I-IV lung cancer patients treated with radical (chemo)radiotherapy. Dyspnea changes (ΔDys) from the baseline grade (Dys₀) to the follow-up grade (Dys) were evaluated. A multinomial logistic regression model simultaneously predicting 3 grades of Dys (Dys ≥ 3, Dys = 2 and Dys ≤ 1 (reference level)) was optimized. Reference NTCP models predicting Dys ≥ 2 and Dys ≥ 3 risks irrespective of Dys₀ were generated for comparison. Models were shrunken and performance was assessed using optimism-corrected AUC (bootstrapping). Rates of ΔDys ≥ 1 (deterioration) and ΔDys ≤ -1 (improvement) at 6 months were 31.9% and 12.6%. Dys ≥ 3, Dys = 2 and Dys ≤ 1 rates were 13.7%, 20.9% and 65.4%, respectively. The multinomial model (combining the risk factors Dys₀ and MLD and the protective factor chemotherapy treatment) predicted Dys ≥ 3, Dys = 2 and Dys ≤ 1 with AUC (95% CI) of 0.72 (0.65-0.75) 0.76 (0.72-0.79) and 0.78 (0.74-0.80), respectively. Reference Dys ≥ 2 and Dys ≥ 3 models showed worse AUC: 0.64 (0.59-0.67) and 0.66 (0.50-0.70), respectively. Dyspnea grade could be predicted with high accuracy using a multinomial NTCP model, yielding personalized dyspnea symptom improvement and deterioration risks.