| BackgroundCervical cancer is one of the most common type of gynecological cancer,resulting in cancer-related death of women worldwide.Based on GLOBOCAN estimates,about 527,600 new cervical cancer cases and above 265,000 deaths occurred in 2012,in which over 85%of cervical cancer deaths occurred in developing parts of the world.In the past,women often developed cervical cancer at 40-60 years old;however,these patients have been younger under the influence of various factors recently.Therapeutic management of cervical cancer principally consisted of surgery,radiotherapy,or chemotherapy,whereas concurrent chemoradiation therapy(CCRT)has been considered as the standard treatment in locally advanced cervical cancer.Response to CCRT could mainly be determined by clinical assessment initially,nevertheless it was too subjective to distinguish whether the tumor necrosis,inflammation,fibrosis or residual,especially the deep tumor.So it is difficult to evaluate the curative effect in the early stage of treatment,which will guide the clinician to adjust the treatment plan.Therefore,it is urgent to search an objective and accurate method for early detection of tumor response.At present,imaging technologies have played important roles in the efficacy assessments of cervical cancer.Conventional imaging techniques usually evaluated tumor response by identifying the morphologic criteria with a change in tumor dimension.However,these morphologic changes in gross tumor size significantly lag behind the biological and molecular changes that occur early in responders.In the past decade,several functional imaging techniques,such as diffusion-weighted(DW)magnetic resonance imaging(MRI),dynamic contrast-enhanced(DCE)MRI and intravoxel incoherent motion(IVIM)MRI have been introduced to evaluate the early response of chemo-radiotherapy in cervical cancer.These allow for early evaluation of changes in microenvironment,cell structure and blood perfusion in the lesions.However,most of these technologies are not used in routine surveillance due to high cost,long scan time,potential contrast agent’s adverse reaction and etc.,especially for patients who require long-term follow-ups.With the superiority of low cost,security,convenience and accuracy,ultrasound is considered as the first-line imaging technique to be used in cervical cancer.At present,the color Doppler,power Doppler,contrast-enhanced ultrasound,elastography imaging and three-dimensional power Doppler ultrasound(3D-PDU)were used to evaluate the efficacy of radiotherapy and chemotherapy for cervical cancer.Color and power Doppler ultrasound showed the hemodynamic changes of cervical cancer;whereas contrast enhanced ultrasound reflected the blood perfusion of tumor from the microcirculation level.Based on the tumor blood supply,these three techniques examined the change of tumor vessels blood and volume after therapy to evaluate the tumor survival and proliferation ability,thus playing important roles in the therapeutic efficacy and recurrence monitoring.Elastography Imaging is a new developed non-invasive technique,which reflects the change of the hardness of the structure by analyzing the displacement of the region of interest.In general,the strain is lower in malignant tissue compared to benign tissue.Elastography has been successfully applied in cancer detection and differential diagnosis in several organs,such as cervix,breast,liver and thyroid,which opens up a new horizon and provides a new method for tumor diagnosis.Several studies have shown the potential of elastography in monitoring and predicting the therapeutic response in patients with rectal cancer,pancreatic ductal carcinoma following CCRT.Nevertheless,there are some limitations:first,the above four techniques are based on the two-dimensional section of the maximum diameter of the tumor,and the overall information of the tumor is limited;second,since Color Doppler,power Doppler ultrasound and contrast-enhanced ultrasound could not measure the tumor hemodynamic parameters at the same point or region of interest at pre-therapy and post-therapy,they are poor reproducibility.In the last decade,three-dimensional power Doppler ultrasound(3D-PDU)was introduced,with better delineation of the whole morphological and vascular characteristics in tumor.It has been reported that 3D vascular indices exhibited higher values in cervical cancer groups than those of normal cervix groups.Furthermore,effective anti-cancer treatment can be reflected by the decrease in 3D vascular indices due to the alteration of microvasculature induced by local fibrosis and angiolysis.However,to the best of our knowledge,elastography and 3D-PDU as biomarkers for early prediction of therapeutic response in cervical cancers has yet to be reported.Accordingly,the purpose of our study was to investigate whether the strain ratio and 3D vascular indices can be used as imaging biomarkers in evaluating early response in 1 or 2 weeks after the initiation of treatment in patients with locally advanced cervical cancer.Chapter 1 Elastography imaging for early detection and prediction of tumor response to concurrent chemo-radiotherapy in cervical cancer ObjectiveTo investigate the feasibility of elastography imaging in early detecting and predicting treatment response in patients receiving concurrent chemo-radiotherapy(CCRT)for cervical cancer.Material and MethodsBetween October 2014 and June 2016,36 patients with locally advanced cervical cancer were enrolled in a feasibility study approved by the institutional review board.All patients underwent CCRT and received strain elastography examinations at 4 time points:pre-therapy(baseline),1 week and 2 weeks during,as well as immediately post CCRT.Treatment response was evaluated by MRI at the time of diagnosis and immediately after CCRT.Based on the MRI findings,the treatment outcome was characterized as complete response(CR),partial response(PR),stable disease(SD)and progressive disease(PD).Strain ratio of the normal parametrial tissue vs.cervical tumor in the same depth was calculated and compared with the clinical outcome.ResultsA total of 36 patients were included in the analyses:25 were classified as CR,11 as PR,and 0 in the SD/PD groups.Strain ratios were significantly different among the time points in both the CR group(F=87.004,p<0.001)and PR group(F=38.317,p<0.001).Strain ratios between the CR group and PR group were significantly different at corresponding time points(p<0.05),except for pre-treatment(t=0.664,p=0.551).Compared to the baseline,a significant decrease of strain ratios in the CR group was observed at week 15 week 2 and therapy completion(all p<0.001),while PR group fell down obviously in week 2 and therapy completion(both p<0.05),but not at week 1 during CCRT(p=0.084).ConclusionsWe have conducted a prospective longitudinal study to evaluate tumor response in women receiving CCRT for locally advanced cervical cancers.During the treatment,strain ratios showed different trends in CR and PR groups.The obvious decrease of strain ratio at week 1 after therapy initiation was found in CR group,which suggests the potential of strain elastography as a surrogate biomarker to evaluate an early therapeutic response.Chapter 2 Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for cervical cancerObjectiveTo investigate the feasibility of three-dimensional power Doppler ultrasound(3D-PDU)imaging in early predicting treatment response in patients receiving concurrent chemo-radiotherapy(CCRT)for cervical cancer.Material and MethodsBetween October 2014 and October 2016,35 patients with locally advanced cervical cancer were enrolled in a feasibility study approved by the institutional review board.Each patient who received CCRT underwent 3D-PDU examinations at 4 time points:pre-therapy(baseline),1 week and 2 weeks during,as well as immediately post CCRT.Final tumor response was determined by change in tumor size using MRI.Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome.ResultsFrom the MRI evaluations:22 patients were classified as complete response(CR)and 13 as partial response(PR).Cervical tumor volume was positively correlated with VI,FI and VFI(Pearson correlation,r=0.484,r=0.566,r=0.505).No significant differences were found in tumor volume and 3D vascular indices between CR and PR groups.During the treatment,this study showed that 3D vascular indices(VI and VFI)significantly increased at 1 week(p=0.015 p=0.03,respectively)then decreased at 2 weeks and obviously decreased at therapy completion(both p<0.05),whereas tumors significantly decreased in volume at 2 weeks after therapy initiation(p<0.001).ConclusionThis study has demonstrated the potential of 3D-PDU imaging in monitoring and early predicting tumor response in patients with cervical cancer induced by CCRT. |
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