Development and validation of a nomogram for prediction of recovery from moderate-severe xerostomia post-radiotherapy in nasopharyngeal carcinoma patients

Abstract

Purpose: Aim to create and validate a comprehensive nomogram capable of accurately predicting the transition from moderate-severe to normal-mild xerostomia post-radiotherapy (postRT) in patients with nasopharyngeal carcinoma (NPC).

Materials and methods: We constructed and internally verified a prediction model using a primary cohort comprising 223 patients who were pathologically diagnosed with NPC from February 2016 to December 2019. LASSO regression model was used to identify the clinical factors and relevant variables (the pre-radiotherapy (XQ-preRT) and immediate post-radiotherapy (XQ-postRT) xerostomia questionnaire scores, as well as the mean dose (D_mean) delivered to the parotid gland (PG), submandibular gland (SMG), sublingual gland (SLG), tubarial gland (TG), and oral cavity). Cox proportional hazards regression analysis was performed to develop the prediction model, which was presented as a nomogram. The models' performance with regard to calibration, discrimination, and clinical usefulness was evaluated. The external validation cohort comprised 78 patients.

Results: Due to better discrimination and calibration in the training cohort, age, gender, XQ-postRT, and D_mean of PG, SMG, and TG were included in the individualized prediction model (C-index of 0.741 (95% CI:0.717 to 0.765). Verification of the nomogram's performance in internal and external validation cohorts revealed good discrimination (C-index of 0.729 (0.692 to 0.766) and 0.736 (0.702 to 0.770), respectively) and calibration. Decision curve analysis revealed that the nomogram was clinically useful. The 12-month and 24-month moderate-severe xerostomia rate was statistically lower in the SMG-spared arm (28.4% (0.230 to 35.2) and 5.2% (0.029 to 0.093), respectively) than that in SMG-unspared arm (56.8% (0.474 to 0.672) and 12.5% (0.070 to 0.223), respectively), with an HR of 1.84 (95%CI: 1.412 to 2.397, p = 0.000). The difference in restricted mean survival time for remaining moderate-severe xerostomia between the two arms at 24 months was 5.757 months (95% CI, 3.863 to 7.651; p = 0.000).

Conclusion: The developed nomogram, incorporating age, gender, XQ-postRT, and D_mean to PG, SMG, and TG, can be used for predicting recovery from moderate-severe xerostomia post-radiotherapy in NPC patients. Sparing SMG is highly important for the patient's recovery.

Keywords: Nasopharyngeal carcinoma; Radiotherapy; Salivary glands; Xerostomia.