A randomized phase II trial of diffusion-weighted MR imaging-guided radiotherapy plus chemotherapy versus standard chemoradiotherapy in locoregional advanced nasopharyngeal carcinoma.

6018 Background: We hypothesized that diffusion-weighted MR imaging (DWI) guided dose-painting radiotherapy (DP-RT) was associated with improved tumor control and survival compared with standard CT-based radiotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). The purpose of this randomized phase II trial was to compare the efficacy and toxicity of DWI guided DP-RT plus chemotherapy versus standard CT-based radiotherapy plus chemotherapy in locoregionally advanced NPC. Methods: Two hundred and fifty-six patients with stage III-IVa (8th AJCC) NPC were randomly assigned to receive DWI-guided dose-painting radiotherapy plus chemotherapy (DP-RT group, n = 128) or standard CT-based radiotherapy plus chemotherapy (CT-based RT group, n = 128). Patients in both groups received 3 cycles of induction chemotherapy followed by cisplatin-based concurrent chemoradiotherapy. In DP-RT group, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean). The dose to GTVnx-DWI was escalated to DT 75.2 Gy/32 Fx in patients with T1-2 disease, and DT 77.55 Gy/33 Fx in those with T3-4 disease, in 2.35 Gy per fraction. In CT-based RT group (n = 128), PGTVnx was irradiated at DT 70.4-72.6 Gy/32-33 Fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn, number ChiCTR1800015779. Results: Compared with standard CT-based radiotherapy, DWI-guided DP-RT significantly improved 2-year local recurrence-free survival (LRFS, 100% vs. 95.4%; P = 0.024), distant metastasis-free survival (DMFS, 97.9% vs. 90.6%; P = 0.006), disease free survival (DFS, 93.2% vs. 86.8%; P = 0.021), and overall survival (OS, 100% vs. 95.2%; P = 0.038). No statistically significant differences in acute and late toxic effects were observed. Multivariate analysis showed that dose painting (DWI-guided DP-RT vs CT-based RT without DP) was a significant independent prognostic factor for DMFS and DFS (P = 0.021 and P = 0.020, respectively). Conclusions: Diffusion-weighted MR imaging guided dose-painting radiotherapy plus chemotherapy is associated with a considerable survival benefit, without increasing toxicity, as compared with standard CT-based radiotherapy plus chemotherapy, among patients with locoregionally advanced nasopharyngeal carcinoma. Clinical trial information: ChiCTR1800015779.