Early Prediction of Parotid Glands Secretory Function Based on MRI-ADC Acquired during Radiotherapy for Nasopharyngeal Carcinoma: A Phase II Prospective Study

Abstract

Radiation-induced xerostomia remains one of common side effects for radiotherapy (RT) of nasopharyngeal carcinoma (NPC) and severely affects the quality of life for the NPC patients. We aim to investigate the feasibility of predicting parotid glands secretory function based on the changes of apparent diffusion coefficient (ADC) map from diffusion weighted MRI (DWI) of bilateral parotid glands during RT for NPC patients and to analyze the correlations between the delivered radiation dose, volume reduction of parotid glands and the salivary secretary function. Seventy-five NPC patients treated with IMRT were enrolled in the study. DWI data were acquired on a 3.0T MRI system at pre-RT, the 5th and 15th fractions and immediately post-RT. The ADC maps were created in the ipsilateral (IP) and contralateral parotid gland (CP). Chewing stimulating tests were used to evaluate the saliva secretion. Pearson analysis was used to assess the correlation between ADC, delivered dose, volume reduction, and saliva secretion. Mean ADC increases and volume reductions in both parotid glands were observed during RT. These changes generally occurred in two stages. At the 5th fraction, with the average (± standard deviation) delivered doses of 5.11 ± 6.73Gy (IP) and 4.84±4.01Gy (CP), the average saliva secretions reduced from 2.35 ± 0.18g (pre-RT) to 2.25 ± 0.18g (5th fraction). During this first stage, the mean ADC increased significantly by 16.51 ± 14.82% (IP), 13.44 ± 10.87% (CP), while the volumes of parotid glands had minimal changes (IP: 23.42 ± 8.33cm3 vs 23.12 ± 8.11cm3, CP: 24.37 ± 9.13 cm3 vs 23.81 ± 9.07 cm3). The increased mean ADC had a positive correlation with the delivered dose (r1 = 0.57, r2 = 0.58) and negative correlation with the decreased saliva secretion (r1 = -0.57, r2 = -0.65). In the second stage (from the 5th fraction to post-RT), with the total mean delivered doses to the parotid glands of 27.64 ± 3.63 Gy (IP) and 26.13 ± 2.16 Gy (CP), the average saliva secretion decreased to 1.70 ± 0.14 g (15th fraction) and 1.34 ± 0.15 g (post-RT). The mean ADC increased by 40.38 ± 21.91% (IP), 40.06 ± 23.91% (CP) in this stage, while the volumes of parotid glands decreased by 41.20 ± 10.77% (IP), 39.18 ± 11.88% (CP). The radiation dose positively correlated to increased ADC, and negatively correlated to the volume reduction and decreased salivary secretion. During radiotherapy for NPC, the ADC values of parotid glands increase dramatically. The increase positively correlates to radiation dose, and negatively correlates to the volume reduction and salivary secretion decrease. The mean ADC increases at the 5th fraction even no volume change is observed, indicating that the ADC is more sensitive biomarker that may be used to predict xerostomia in an early stage during RT for NPC, leaving enough time to adapt the remaining treatment if necessary.