3681 - Long Term Outcomes And Late Toxicity of Diffusion-Weighted Magnetic Resonance Imaging-Guided Dose Painting Radiotherapy in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized,

F. Liu¹, H. Wang^2,3, C. Jiang¹, C. Fan¹, W. Liu¹, X. Ye¹, Y. Li¹, X. Wu¹, K. Chen¹, Y. Qiu¹, L. He¹, S. Xiao¹, Q. Zhao¹, W. Wu¹, C. Tan^1,4, Y. Li⁴, and R. He^1,5; ¹Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China, ²Department of Radiation Oncology, Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China, ³Key Laboratory of Translational Radiation Oncology, Hunan Province, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China, ⁴Hengyang Medical School, University of South China, Hengyang, China, ⁵Hunan Normal University School of Medicine, Changsha, China

Purpose/Objective(s): We hypothesized that diffusion-weighted magnetic resonance imaging (DWI)-guided dose-painting radiotherapy (DP-RT) is associated with improved long term local tumor control and survival, and does not increase late toxicity in locoregionally advanced nasopharyngeal carcinoma (NPC). The purpose of this randomized phase 2 study was to compare the long term efficacy and late toxicity of DWI guided DP-RT to conventional magnetic resonance imaging (MRI)-based RT in locoregional advanced NPC. Materials/

Methods: A total of 260 patients with stage III-IVa (8th AJCC) NPC disease were randomly assigned in a 1:1 ratio to receive induction chemotherapy followed by chemoradiotherapy by DWI-guided DP-RT (group A, n = 130) or conventional MRI-based RT (group B, n = 130) in this phase 2 clinical trial. All patients were treated with intensity modulated radiation therapy (IMRT). In group A, 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) according to MRI before induction chemotherapy. The dose to GTVnx-DWI was escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group B, planning gross tumor volume of nasopharynx (PGTVnx) was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. Long term efficacy and late toxicity were evaluated. This trial is registered with chictr.org.cn (ChiCTR1800015779).
Results: A total of 260 patients were included in the trial (130 patients in group A and 130 in group B). At a median follow-up of 62 months, DWI-guided DP-IMRT was associated with improved 5-year disease-free survival (DFS; 90.8% vs 80.8%, P = 0.021), overall survival (91.5% vs 82.3%, P = 0.028), local recurrence-free survival (LRFS; 91.5% vs 80.8%, P = 0.012), and distant metastasis-free survival (DMFS; 91.5% vs 81.5%, P = 0.018). No statistically significant differences in late toxic effects were observed. The occurrence rates of all grades (93.1% vs 92.3% for DWI-guided DP-RT vs conventional MRI-based RT) and = grade 3 (10.8% vs 11.5%) late toxicities were comparable (P > 0.05). The most common = grade 3 late toxicities included ototoxicity (6.9% vs 6.1%), dry mouth (1.5% vs 2.3%), and trismus (0.7% vs 1.5%). All types were similar between treatment groups. Multivariate analyses showed that DP (DWI-guided DP-RT vs conventional MRI-based RT) was associated with DFS, OS, LRFS, and DMFS. Epstein-Barr virus DNA level was associated with DFS, OS and LRFS.
Conclusion: DWI-guided DP-RT combined with chemotherapy provides a long-term survival benefit compared to conventional MRI-based RT for patients with locoregionally advanced NPC, without increasing the risk of late toxic effects.