Early Efficacy Prediction And Dynamic Monitoring Of Nasopharyngeal Carcinoma Based On DWI-ADC Acquired During Radiotherapy: A Prospective Study

Research background and purpose:Radiotherapy（RT）is one of the main treatment models for nasopharyngeal carcinoma（NPC）.In clinical diagnosis and treatment,we have found that the prognosis of NPC with the same TNM stage was different with the same treatment strategy.In recent years,attention has been paid to the study of multimodal images in NPC,pretreatment CT perfusion imaging has been found to be a useful non-invasive tool for predicting therapeutic response to NPC.Studies have shown that the pretreatment apparent diffusion coefficient（ADC）value of primary NPC lesions may be a prognostic factor of NPC.However,most studies of multimodal image only concentrate on pre-treatment,there is still a lack of more and accurate dynamic data.Our previous study found that the mean three-dimensional ADC（3D-ADC）value of parotid gland in patients with NPC began to increase at the 5th fraction of RT,but there was no significant change in volume.This study aims to observe the changes of mean 3D-ADC values for gross tumor volume（GTV-T）and positive lymph nodes（GTV-LN）during RT for patients with NPC,explore the potential relationship among mean 3D-ADC values,volumes of GTV-T and GTV-LN during and after RT,and investigate the feasibility of predicting efficacy based on dynamic ADC values from Diffusion-weighted imaging（DWI）of GTV-T and GTV-LN during RT.Materials and Methods:From January 01,2021 to November 30,2021,patients with squamous NPC（II-IVA,the 8th edition TNM staging）were prospectively included in Sichuan cancer hospital.All patients received concurrent chemoradiotherapy（CCRT）.The planned total dose of 66 to 70Gy in 33 fractions at 5 fractions per week using Image-guided intensity modulated radiotherapy（IGRT）.Concurrent chemotherapy regimen chose cisplatin-based chemotherapy for 3 cycles.The patients received MRI and DWI scan at pre-RT,the 5th fraction of RT（RT-5th）,at the 15th fraction of RT（RT-15th）,at the completion of RT（post-RT）and 3 months after the completion of radiotherapy（RT-3m）,respectively.The ADC values of GTV-T and GTV-LN were acquired using MIM（MIM Software Inc,US）.Pearson and Spearman correlation analysis was used to explore the correlation between 3D ADC values and changes of GTV-T and GTV-LN volumes.RECIST 1.1criteria was used to evaluate the efficacy.Univariate analyses were conducted using independent samples t-test and chi-square test.Multivariate analyses were calculated using the logistic regression model.Receiver-operating characteristic（ROC）curve was used to determine the cut-off value.Result:1 A total of 52 patients with nasopharyngeal squamous cell carcinoma（stage III-IVA,AICC 8th edition）were included in this study.The median age was 48.5 years（range 23-79 years）.There were 32 males and 20 females.After the completion of CCRT,the objective response rate（ORR）of all the patients was 100%,of which the complete response（CR）was 34.6%and the partial response（PR）was 65.4%.3 months after the completion of CCRT,the ORR was 100%,the CR was 61.5%and PR was38.5%.2 The mean 3D ADC values for GTV-T and GTV-LN increased gradually from with increasing number of RT fractions.These changes can be divided into two stages.For the first stage（from pre-RT to the RT-5th）,the mean 3D-ADC value of GTV-T and GTV-LN increased significantly by 18.98%and 22.74%respectively,while the volumes of GTV-T and GTV-LN had minimal changes（GTV-T:17.073 cm³ vs 16.689 cm³,GTV-LN:4.701 cm3 vs 4.558 cm3）.As for the second stage（from the RT-5th to post-RT）,the mean 3D-ADC value of GTV-T and GTV-LN continued to increase by 53.68%and 51.45%respectively,while the volumes decreased by 79.3%（GTV-T）and 61.66%（GTV-LN）.3.Correlation analysis showed that the increased mean 3D-ADC values of GTV-T from pre-RT to the RT-5th were positively correlated with the volume reduction from pre and post-RT（r=0.38）,and negatively correlated with the efficacy of GTV-T at post-RT（r=-0.427）and RT-3m（r=-0.393）.The increased mean 3D-ADC values of GTV-LN from pre-RT to the RT-5th were negatively correlated with the efficacy of GTV-LN at post-RT（r=-0.485）.4 Univariate analysis showed the age,T stage,V _{pre-RT T} andΔADC_{RT-5th T}were the prediction factors for treatment efficacy of GTV-T at RT-3m.The N category,ADC _{pre-RT LN} and V _{pre-RT LN} were the prediction factors for treatment efficacy of GTV-LN at RT-3m.Multivariate analysis showed that theΔADC_{RT-5th T}was the only independent prediction factor for treatment efficacy of GTV-T at RT-3m.In patients with N2-3disease,the V _{pre-RT LN} was an independent prediction factor for treatment efficacy of GTV-LN at the RT-3m.5 ROC analysis showed thatΔADC_{RT-5th T} predicted GTV-T efficacy at RT-3m with an AUC value of 0.752(cut-off value:149.29×10^-6mm²/s,sensitivity 83.3%,specificity75%).ΔADC_{RT-5th LN}(cut-off:147.1×10^-6mm²/s)combined with V _{pre-RT LN} had an AUC value of 0.861（sensitivity 85.71%,specificity 83.72%）for predicting GTV-LN efficacy at RT-3m.Conclusion:1 Mean 3D-ADC values of GTV-T and GTV-LN increased dramatically during RT for NPC patients.2 The mean 3D-ADC values of GTV-T and GTV-LN increased significantly at the RT-5th,while the change of volume was not significant.3 The mean 3D-ADC changes at the RT-5th might be a potential and new imaging biomarker to predict the treatment efficacy of NPC patients early.