| Objective:Cervical cancer is the most common tumor of the female reproductive system.With the progress of social economy,education and medical technology,the survival rate of cervical cancer is increasing and patients pay more attention to the quality of life after treatment.Radiotherapy is one of the most common treatment for cervical cancer.Mostly,the early stage patients received radical surgery of cervical cancer need radiation therapy as adjuvant therapy.Ovary is the radiation sensitive organs,low dose of radiation may cause irreversible exhaustion,resulting in young patients with early menopause and irritable perimenopausal syndrome such as hot flashes,night sweats,a series of lipid metabolic abnormalities,osteoporosis and the complication of heart head blood-vessel.Life quality of the survival declines seriously.Therefore,for young patients with cervical cancer received radiotherapy,how to retain the endocrine function of ovary has become a research focus domestic and overseas in recent years.The dose of postoperative adjuvant radiotherapy for patients with early stage cervical cancer is 45-50 Gy.ovary is located in the pelvic radiotherapy field,which may lead to ovarian exhaustion after radiotherapy.Ovarian transposition removes the ovaries out of the pelvic cavity during radical surgery of cervical cancer to avoid the damage from radiotherapy.However,the probability of successfully retaining the endocrine function of ovary after radiotherapy is not high in domestic reports at present.Therefore,the main purpose of our project is to study how to preserve ovarian endocrine function more effectively in young patients with cervical cancer who received postoperative radiotherapy after ovarian transposition.And the relationship between ovarian dose and displacement position is analyzed.Our findings could provide suggestions on displacement position for surgeons.The correlation between the volume dose of irradiated ovarian tissue and the endocrine function of ovary after radiotherapy was analyzed.We try to explore the critical value of volume dose of irradiated ovarian tissue in patients preserved normal endocrine function of ovary.Furthermore,the advantages of three precise radiotherapy technologis,including intensity-modulated radiotherapy(IMRT),volumetric modulated arc therapy(VMAT)and spiral tomography radiotherapy(TOMO),in reducing the dose of unilateral and bilateral ovaries were evaluated.Methods:In the first part of this study,a retrospective analysis was performed in 150 young patients with cervical cancer between June 2011 and January 2017.All patients received radical surgery,intraoperative ovarian transposition and postoperative adjuvant radiotherapy in our hospital.The patients were divided into the satisfied group and the unsatisfied group according to whether the maximum dose(Dmax)of displaced ovary was less than or equal to 400cGy in the radiotherapy plan.The position of displaced ovary and clinical data of the two groups were compared to evaluate the effect of the position on the ovarian dose.In the second part,150 patients mentioned above were followed-up for 1 year to acquire data of their ovarian endocrine function.The probability of preserving endocrine function of ovary in our hospital was assessed.The patients were divided into two groups according to whether the endocrine function of ovary was normal.Single factor and multiple factors statistical analysis were performed to analyze the influence factors of successful preservation of ovarian endocrine function.The relationship between successful preservation of ovarian endocrine function and the radiation dose of ovarian tissue was explored and the reference value of limit dose of ovarian tissue was given.In the third part,10 young patients with cervical cancer who had received radical surgery,bilateral ovarian transposition and postoperative adjuvant radiotherapy in our hospital were chosen as research objectives.On the basis of the existing planning target volume(PTV),three radiotherapy plans of IMRT,VMAT and TOMO were designed for every patient.The purpose is to evalute the advantages of three radiotherapy technology in reducing the dose of unilateral and bilateral ovaries.Results:In the first part of this study,64(42.7%)of the 150 patients had bilateral ovarian transposition,78(52%)had right ovarian transposition and 8(5.3%)had left ovarian transposition.32(15%)ovaries were above PTV,who' Dmax were all less than or equal to 400cGy.Part or all of 182(85%)ovaries were below the upper bound of PTV,38 of them gave up the dose limitation because the ovaries were too close to the radiotherapy fields.During the remaining 144 patients,57(39.6%)ovaries' Dmax was satisfied.There were significant differences in the placement and dose of ovaries between the two groups.The receiver operator characteristic curve(ROC curve)was drawn and then found that the distance between the ovary and the iliac crest plane was significant for the prediction of ovary above PTV.Its optimal cutoff value was 1.12 cm(AUC:0.899,95%CI:0.853-0.946,sensitivity:0.969,specificity:0.676).144 ovaries that were part or all of them below the uper bound of PTV and received limitation of ovary dose were divided into two groups according to whether the Dmax was satisfied.The distance of ovary to the center line,to the iliac crest plane,to the lateral and uper bound of PTV in the two groups showed significant difference(P<0.05).Logistic multifactor regression analysis showed that the lateral distance of ovary to PTV is the independent prognostic factors for satisfactory ovary dose.ROC curve showed that the lateral distance of ovary to PTV was significant in predicting the satisfactory Dmax of ovary.Its optimal cutoff value was 3.265 cm(AUC:0.779,95%CI:0.703-0.856,sensitivity:0.807,specificity:0.676).In the second part,150 patients were followed-up for one year.77 patients had complete follow-up data.All 77 patients had normal ovarian function before radiotherapy,and only 34 patients(44.2%)had normal ovarian function 3 months after radiotherapy.But,56 patients(72.7%)had normal ovarian function 1 year after radiotherapy,which was significantly higher than that 3 months after radiotherapy(P=0.000).77 patients were divided into two groups according to whether ovarian function was normal at 3 months after radiotherapy.There was significant difference about ovarian Dmean,D90,D80,D70,D60,D50,D40,D30,D20,D10,V2,V3 in the two groups.Multiple factors analysis showed that D30 was an independent prognostic factor for normal ovarian function.ROC curve showed that ovarian D30 was significant in predicting normal endocrine function of ovary.The optimal cutoff value was 303 cGy(AUC:0.674,95%CI:Sensitivity:0.442,specificity:0.147).However,when the patients were grouped according to whether the ovarian function was normal one year after radiotherapy,only patients with bilateral ovarian preservation showed more normal function of ovary than those with unilateral ovarian preservation(P<0.05),and there was no statistical difference on other factors.In the third part,10 young patients with cervical cancer who underwent radical surgery,bilateral ovarian transposition and postoperative adjuvant radiotherapy were selected to compare three radiation methods of IMRT VMRT and TOMO in reducing the irradiation dose of bilateral ovaries and unilateral ovaries.We found that when the bilateral ovaries doses were restricted,TOMO could reduce the PTV Dmax?Dmin and the Dmax of the right ovaries compared with IMRT and VMAT,and there were significant differences(P<0.05).The CI of PTV for IMRT is the highest of the three groups.TOMO can also reduse the dose of bladder,intestine,bone marrow and spinal cord better compared with the IMRT and VMAT.However,there was no significant difference of dose between IMRT and VMAT.10 patients with unilateral ovary dose limited did not achieve the purpose of better reducing the dose of the retained ovary and OARs,better optimizing the dose of PTV compared with the patients with bilateral ovary dose limited.Conclusion:The first part of the study confirmed that ovarian transposition in patients with cervical cancer can significantly affect the ovarian dose during postoperative adjuvant radiotherapy.It was the first time we found that the ovarian transposition reach at least 1.12 cm above the lower boundary from the iliac crest plane can make the ovary above PTV and obtain a satisfactory dose.When all or part of the ovary is below the upper bound of PTV,a satisfactory dose can be obtained when the ovary is at least 3.265cm from the horizontal distance of PTV.The second part of the study found for the first time that the ovarian endocrine function that lost 3 months after radiotherapy is likely to return to normal one year after radiotherapy.It was found that D30 is an independent prognostic factor of normal endocrine function of ovary at 3 months after radiotherapy.The ovary had the greatest hope to retain endocrine function when the ovarian D30 is limited below 303cGy.The rate of normal ovarian endocrine function of patients with bilateral ovarian dose limitation during radiotherapy is significantly higher compared with patients with unilateral ovary dose limitation,so it is suggested that surgeons should try to perform bilateral ovarian transposition during surgery.In the third part of the study,we found TOMO is more advantageous in reducing the irradiation dose of the right ovaries and other OARs.10 patients with unilateral ovary dose limited did not achieve the purpose of better reducing the dose of the retained ovary and OARs,better optimizing the dose of PTV compared with the patients with bilateral ovary dose limited.So for patients with bilateral ovarian transposition,we should try to preserve the endocrine function of bilateral ovaries through technical methods. |
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