| Objective:Nasopharyngeal carcinoma(NPC)is a common malignant tumor in Asia,especially in China.Because of its special characteristics,radical surgery is impossible.NPC is usually sensitive to chemoradiotherapy.Therefore,radiotherapy(RT)is the standard of care for patients with newly diagnosed nasopharyngeal carcinoma.However,the efficacy of the conventional radiotherapy is limited,because ofits poor homogeneity and high doses of adjacent normal tissues induced high incidences of acute and chronic toxicities and patients’ poor quality of life.Three-dimensional conformal radiation therapy(3D-CRT),especially the rapid development of intensity-modulated radiation therapy(IMRT)and image-guided radiation therapy(IGRT)in recent years,is superior to two-dimensional radiotherapy in the dose distribution,the accuracy of treatment and the protection of normal tissues.These techniques have become the main treatment modalities for NPC.Because of the complicated anatomy,the improvement of treatment accuracy and normal tissue sparing are still necessary for IMRT.Because of the prolonged survival of patients with NPC,enhancing the treatment accuracy and improving quality of life are more and more important.Helical Tomotherapy(abbreviated as Tomotherapy)is a new method of intensity-modulated radiotherapy.The main part of a medical linear accelerator is installed in the spiral CT slide ring rack.Tomotherapy is the only method using the homologous CT imaging.This design concept makes Tomotherapy integrating IMRT and IGRT.The dose distribution in the range of 40 cm×160 cm adjustment is realized by the spiral CT rotating scanning mode and the guidance of the fault image,without worrying about the location or shape of tumor lesions.Tomotherapy is a typical representative of modern imaging-guided radiotherapy.The anatomy of the nasopharynx is very sophisticated and it is crucial to identify the tumor volume and infiltration before radiotherapy.The progress in imaging techniques including magnetic resonance imaging(MRI)and positron emission tomography coupled with computed tomography(PET-CT)has improved initial extension assessment in nasopharyngeal carcinoma and therefore enhanced the precision of RT planning.However,the PET-CT is not economic and with a poor availability.MRI is widely used in the diagnosis and treatment of NPC because of its high resolution,multiple sequences,and without ionizing radiation.Emerging MRI techniques(e.g.diffusion-weighted imaging(DWI)and intravoxel incoherent motion(IVIM))are revolutionized based on the conventional MRI and have a superior capacity for differentiating tumor,inflammation,and normal tissue by taking advantages of more interstitial tissues,high cell density,copious blood supply,and metabolic abnormalities in tumor tissues.These techniques can not only differentiate the tumor tissue,inflammation,and normal tissues but also can early detect the vascular and metabolic changes and observe the radiation sensitivity in order to tailor the individualized treatment.These techniques are also helpful to detect the metabolic changes and identify treatment-related normal tissue injuries to interfere with early and minimize the injuries.This study investigated Tomotherapy and IVIM-MRI and aimed to improve the accuracy of the simulation and treatment.This study investigated the role of Tomotherapy in NPC treatment and comprehensively compared with IMRT in terms of dosimetry,registration methods,and set-up errors.Through the comparisons,pros and cons of Tomotherapywere objectively evaluated for the treatment of NPC.The diffusion and perfusion of tumor tissue and parotid before and after RT were evaluated by DWI and IVIM-MRI to assess the radiation sensitivity and changes of the parotid function.Methods:1.We retrospectively analyzed patients with newly diagnosed and histopatholo-gically confirmed nasopharyngeal squamous carcinoma from 2015 March to 2016 November.The staging varied from stage II to stage IVb according to AJCC 7th.Radiotherapy was indicated for these patients.IMRT was therefore given.(1)Treatment planning wascompared between 7-field IMRT,9-field IMRT,and Tomotherapy.Then we evaluated the homogeneity index(HI),conformity index(CI),and dose distribution in organ at risk(OAR).(2)MVCT was scanned before Tomotherapy was given to each patient.The MVCT image and the CT image went through registration;there are bone registration,bone and soft tissue regis-tration,all pixel registration,and automatic registration.(3)The setup-errors in all directions were analyzed after the manual registration and referredto for the outer boundary of the CTV.2.Next,we included patients with newly diagnosed and histopathologically confirmed nasopharyngeal squamous carcinoma from 2015 March to 2016 November.The staging varied from stage I to stage IVbaccording to AJCC 7th.Radiotherapy was indicated for these patients.IMRT or Tomotherapy was given and the total dose was 70Gy-74Gy/35f-37f.Treatment response was assessed at one month after the treatment end using MRI,sequences of which included coronal and transverse fat-suppressed T2;transverse T1 and T2 weighted images;coronal,transverse,and sagittal fat-suppressed contrast-enhanced T1;and transverse DWI and IVIM-MRI.IVIM-MRI was scanned before the injection of gadolinium diamine.After IVIM images were then imported to DWI-Tool,the IVIM parameters D,D*and f were calculated respectively and the consistency with ADC was evaluated.The tumor area(gross tumor and cervical lymphade-nopathy)and normal tissue(parotid)were definedas the region of interest(ROI).Changes in the blood perfusion in the tumor area and normal tissue were followed-up and compared for each patient and for patients receiving different treatment techniques.Results:1.Tomotherapy plan,7-field plan,and 9-field plan were developed respectively for 31 patients.(1)CI:the mean value of Tomotherapy plan was 0,85±0.02 and superior to 9-field IMRT(0.81±0.05,P<0.001)and 7-field IMRT(0.78±0.03,P<0.001)(2)HI:the mean value of Tomotherapy plan was 0.06±0.01 and superior to 9-field IMRT(0.15±0.028,P<0.001)and 7-field IMRT(0.15±0.03,P<0.001).(3)Organ at risk(OAR):Tomotherapy decreased the doses of the submandibular gland,brain stem,cord,and right inner ear et al.significantly.The doses of parotid,lens,and optic nerve were slightly more than IMRT but all of them are within the threshold dose2.In total,fify patients were enrolled.Except D*value,ADC,D,and f values of the tumor area increased significantly after radiotherapy.Except D*value of right parotid,ADC and IVIM of parotid also rose obviously.The change of ADC values of right parotid in patients receiving Tomotherapy escalated after treatment more significantly compared to the IMRT group.There were no differences between changes of D,D*and f values in parotid and ACD and IVIM values in the tumor area before and after Tomotherapyand changes before and after IMRT.The treat-ment response at one month after treatment was 100%(CR plus PR).The median follow-up was 19 months.Two patients failed after the treatment.One patient developed bone metastasis and local recurrence,and the progression-free survival(PFS)was 8 months.One patient developed local recurrence and PFS was 21 months.For this patient,the values of ADC,D,D*,and f changed slightly after treatment.3.For 110 groups of MVCT scan image data of the 15 patients randomly selected,the selected data are in line with the normal distribution.The setup-errors of three kinds of automatic registration and manual registration indicated that bone registration or bone and soft tissue registration was preferable to all pixel registration.4.Data of 856 MVCT validation data from 28 patients suggested that under the head neck and shoulders immobilization systems,the setup-errors in all directions were shown as below:1.668±0.464mm for X(left and right),1.777±0.454mm for Y(head and foot),and 1.272±0.474mm for Z(dorsoventral)respectively.The angle of rotation along the long axis of the body was 0.984±0.313°,95%confidence interval were 1.577-1.759mm,1.688-1.866mm,1.179-1.365mm and 0.923°-1.046°,respectively.Conclusion:1.Tomotherapyplan can significantly improve the uniformity and conformability of the dose distribution within the tumor area,which may reduce the risk of relapse;Tomotherapy can significantly reduce the dose of submandibular gland,brainstem,spinal cord and part of the inner ear,which can effectively reduce the adverse reactions;image registration of NPC Tomotherapy with bone registration or bone and soft tissue registration is preferred;under the use of the head neck and shoulders immobilization systems during simulation and treatment of NPC patients,the setup-error is less than 2mm;during the delineation,the CTV-PTV 2mm can be covered more than 95%of the tumor region.2.IVIM-MRI can well reflect the microstructure changes of parotid and nasopharyngeal primary lesions before and after radiotherapy in nasopharyngeal carcinoma patients,and provide the feasibility for subsequent judgment of prognosis and early detection of tumor recurrence.Because of the short follow-up period,the relationship between the changes of IVIM parameters and prognosis should be further validation. |
