Values Of Magnetic Resonance Diffusion-weighted Imaging On Prediction Of Radiosensitivity In Nasopharyngeal Carcinoma And Its Mechanisms

Background and Purpose The effect of radiotherapy for nasopharyngealcarcinoma (NPC) is closely related to radiosensitivity in the carcinoma,but currently, there is still no effective way to predict thisradiosensitivity. Magnetic Resonance Diffusion-weighted imaging (MR-DWI),a molecular and functional imaging technique providing apparent diffusioncoefficient (ADC) as a quantitative parameter, is somewhat correlatedwith responses to radiotherapy and chemotherapy for cervical cancer,liver cancer and head and neck cancer. This study intends to explore thepredictive value of MR-DWI for detecting radiosensitivity innasopharyngeal carcinoma and relevant mechanism with animal models andpatients, and to provide an experimental basis for its clinicalapplication. Materials and Methods1.Nude mice bearing humannasopharyngeal carcinoma were randomly divided into control group andirradiation group (a single dose of irradiation with15Gy). ADC valueswere measured before irradiation(ADC0) and the next day after irradiation(ADC1).The ADC value change(ΔADC) after irradiation was indicated by(ADC1-ADC0)/ADC0*100%, and the change in xenograft volume (ΔVx) atX days after irradiation by (Vx-V0)/V0*100%. The difference in the volumechange between control group and irradiation group was defined asradiation-related volume change,δVX=ΔVxc-ΔVxt.2. Hypoxia imagingof nasopharyngeal carcinoma xenografts with99mTc-HL91SPECT wasconducted in nude mice to analyze the correlation of the ADC value withthe radioactivity ratios of target-to-nontarget.3. In addition, nude mice with nasopharyngeal carcinoma xenografts were randomly divided intonon-irradiated group and five other groups (1d,2d,3d,5d and7d,respectively, after irradiation). The correlation between dynamicchanges in ADC value and those in HIF-1α expression level was analyzed.4. Patients with nasopharyngeal carcinoma were enrolled from April2010to November2011, who received intensity-modulated radiotherapy with orwithout chemotherapy. ADC values of nasopharyngeal primary tumor weremeasured before treatment (ADC0) and two weeks after radiotherapy (ADC1).The ADC difference(△ADC) was represented by (ADC1-ADC0)/ADC0*100%.Three months after the end of radiotherapy, short-term effect was assessedwith WHO criteria, Response Evaluation Criteria in Solid Tumors.Results1.No significant difference was detected between CNE1xenografts and CNE2xenografts in ADC0value, while significantdifference was found between ADC1value and△ADC of the two groups. Anegative correlation between△ADC and δVX came to appear from the secondday after irradiation. Multiple linear regression analysis showed thatΔADC was a factor with independent influence on δVx14days afterirradiation.2. The ADC value of nasopharyngeal carcinoma xenografts wasnegatively correlated with the radioactivity ratios, acquired4hoursafter the use of hypoxia imaging with HL-91, of xenografts andcontralateral normal tissue.3. The ADC value change was significantlynegatively correlated with HIF-1α protein and mRNA levels innasopharyngeal carcinoma xenografts after irradiation.4. Among the134NPC patients who were eligible,121received combination chemotherapy.Three months after radiotherapy nasopharyngeal local residues werechecked in23cases (17.2%), and no residues in111cases (82.8%).△ADC values of the group with residues and that with no residues were49.77%±31.02%and68.35%±34.22%, respectively, which weresignificantly different (t=-2.406,P=0.017). The findings from the logistic regression analysis indicated that△ADC was an independentprognostic factor for the short-term effect of intensity-modulatedradiation therapy on nasopharyngeal carcinoma. Conclusion MR-DWImay be adopted to predict the radiosensitivity in nasopharyngealcarcinoma, and its mechanism may have some relevance to hypoxia.