Application Of CEUS In Individual Treatment Of Nasopharyngeal Carcinoma

Part ⅠContrast-enhanced Ultrasound as an early predictor of radiation based therapeutic response for lymph node metastases of nasopharyngeal carcinomaBackground and purpose:Published literature indicated that functional MR imaging including DWI, MRS and DCE-MRI, and FDG-PET can predict short-term therapeutic effect of chemoradiation in head and neck cancer primary tumor and neck nodal metastases. But the functional parameters were diverse in all kinds of clinical trials or animal experiments, and predictive sensitivity, specificity and accuracy existed differences. It’s contentious how to estimate or utilize these parameters for clinical physicians, and if some patients were contraindicated to abovementioned examination, what methods can subrogate them? That contrast enhanced ultrasound （CEUS） is characteristic of non-invasive, easy reproducibility, non-allergy and non-nephrotoxicity, attracted many attention in clinic day by day, for example, liver caner monitoring and guidance, staging of gastric cancer and estimation of therapeutic effect of chemotherapy. The purpose of the study is to assess the early predictive value of parametric CEUS in metastatic neck nodes of nasopharyngeal carcinoma （NPC） patients with chemoradiation therapy, then direct therapy of individual treatment for NPC patients.Materials and methods:Sixty-seven patients diagnosed as NPC with neck lymph node metastases underwent twice CEUS examination for metastatic lymph nodes, including pretreatment and in-treatment （at the5th fraction radiotherapy） respectively. Twice contrast parameters were acquired through Esaote’s Qontrast₄.0software, mainly including Peak Intensity （PIpre and PIin）, Time To Peak （TTPpre and TTPin）. Neck magnetic resonance imaging （MRI） examination was used as the standard imaging modality for therapeutic effect evaluation of metastatic lymph nodes, based on response evaluation criteria in solid tumors （RECIST criteria1.1）.Results:Of67cases,48cases received complete response,19cases revieved partial response. The changes of PI and TTP were observed significantly between twice CEUS examination （P<0.05）.PIpre, PIin and PIratio correlated positively with therapeutic effect （p=0.368,0.81and0.734respectively）, PIΔ correlated negatively with therapeutic effect （p=-0.777）. Logistic regression indicated that PIin and PIratio were both significant predictors of short-term response （P<0.01）. Receptor operation characterisitics （ROC） curve indicated that PIin and PIratio were a good predictor in treatment response （AUC=0.936and0.931respectively）. And the best cut-off value of PIin and PIratio were bigger or equal to29.4and0.69. The predictive sensitivity and specificity of PIin and PIratio were94.3%,88.2%and92.5%,83.8%respectively.Conclusion:Parametric CEUS may be used to predict chemoradiation response and treatment effect for the NPC patients with neck node metastases. Part ⅡApplication of CEUS in Chemo-radiation response of head and neck squamous cell carcinoma with neck nodal metastasesPurpose:Based on the relationship between MVD and CEUS parameters, to observe the relationship between CEUS parameters and treatment response of Head and neck squamous cell carcinoma （HNSCC）.Materials and methods:Altogether26patients diagnosed as head and neck squamous cell carcinoma with neck nodal metastases by pathology were enrolled into the study, except nasopharyngeal carcinoma. All subjects underwent twice CEUS examination at pretreatment and the5th fraction radiotherapy ending respectively. Twice contrast parameters were acquired through Esaote’s Qontrast₄.0software, mainly including Peak Intensity （definition of PIpre and PIin as pretreatment and the5th fraction RT respectively）, Time To Peak （definition of TTPpre and TTPin as pretreatment and the5th fraction RT respectively）. Neck magnetic resonance imaging （MRI） examination was used as the standard imaging modality for therapeutic effect evaluation of metastatic lymph nodes, based on response evaluation criteria in solid tumors （RECIST criteria1.1）.Results:of26patients,19cases were partial response,7cases were complete response（table1）, the change of PI and TTP between twice CEUS were observed significantly differently （P<0.05）（fig1,2）, and PIpre,PIin were different in different treatment response （P<0.05）,however, TTPpre and TTPin were not different in statistics（fig.4,5）.Conclusion:In different treatment response of HNSCC, parameter PI of CEUS was different, which may be a predictor for treatment response. Part ⅢDiagnostic value of CEUS combined with EUS for suspicious nodal metastases in neck of NPCAim:To explore the diagnostic value of CEUS combined with EUS for suspicious nodal metastases in neck of NPC.Materials and methods:Altogether29cases, who were diagnosed as NPC by pathology and diagnosed as suspicious nodal metastases in neck by traditional imaging, were enrolled into the study. They were all performed CEUS and EUS examination. Then comparing with pathology of neck nodes, the accuracy,sensitivity, specificity, positive predictive value（PPV）,negative predictive value（NPV）, youden index（YI） was calculated in order to indentify the diagnostic value of CEUS combined with EUS in NPC patients with suspicious nodal metastases.Results:Altogether29patients involved with57lymph nodes were enrolled into the study. Of57lymph nodes,32nodes were diagnostic as malignant lesions and25cases were benign by pathology. The accuracy,sensitivity, specificity, positive predictive value（PPV）,negative predictive value（NPV）, Youden index（YI） of conventional US is75.4%（43/57）、78.1%（25/32）、72.0%（18/25）、78.1%（25/32）、72.0%（18/25）,0.51; respectively;and89.5%（51/57）.87.5%（28/32）,92.0%（23/25）、93.3%（28/30）、85.2%（23/27）、0.795in EUS; and91.2%（52/57）、93.8%（30/32）,88.0%（22/25）、90.9%（30/33）、91.7%（22/24）、0.818in CEUS, and93.0%（53/57）、100%（32/32）、84.0%（21/25）、88.9%（32/36）、100%（21/21）、0.840in CEUS combined with EUS.Conclusion:CEUS combined with EUS can improve the diagnostic value for NPC patients with suspicious nodal metastases, which may be referred as treatment regimen. Part ⅣCorrelation between Parameters of CEUS and MVD of transplanted NPC in nude mice treated by cisplatinBackground and aims:In the previous reports, functional imaging including DWI, DCE-MRI and FDG-PET can be used to predict therapeutic effect of tumor, the reason is that parameters of above modalities can reflect metabolism of cancer cells or blood supply in tumor tissue. In the current study, the aim is to explore the association between the change of MVD in transplanted NPC in nude mice treated by cisplatin and parameters of CEUS.Methods and materials:A total of16BALB/c nude mice with subcutaneous xenograft NPC were enrolled into the study and divided into two groups randomly. Group A（n=10） was treated by cisplatin, Group B（n=6） was treated by saline as control. They were all performed CEUS examination before and the first, the seventh day after the treatment. The size of tumors were recorded every day. The digital archive of CEUS were analyzed by Esaote’s Qontrast₄.0software, and the parameters of CEUS were acquired mainly including PI and TTP, Three PI and TTP were defined as PIpre, PI1and PI7, TTPpre, TTP1and TTP7respectively. Correlation coefficient was calculated between change of tumor size and parameters of CEUS. The tumor tissues were removed for pathological examination, and the microvascular density （MVD） was evaluated by immunohistochemistry （IHC）, then the relationship between MVD and parameters of CEUS was analyzed.Results:The change of PI and TTP before and after treatment were observed in group A, PI1was decreased comparing PIpre and the decrement in PI7was pronounced （P<0.05）（table2）. The difference between TTPpre and TTP1was not significant in statistics, while the difference between TTPpre and TTP7was observed in statistics （P<0.05）, and TTP had a tendency to increase after the treatment with Cisplatine.The size of tumor treated by cisplatine had a tendency to decrease. In group B, the change of PI and TTP was not observed before and after the treatment, and the size of tumor had a tendency to increase. Comparison between group A and group B in tumor size after treatment, the difference was significant in statistics （P<0.05）. PIpre, PI1and PI7correlated positively with MVD to different extent （correlation coefficient r=0.801,0.925,0.989respectively, P<0.05）. The PI7had a linear correlation with MVD （MVD=1.866xPI7-45.957）.Conclusion:Of parameters in CEUS, PI can reflect the change of MVD in xenograpft tumor, which may be used to predict the chemoradiation effect of NPC.