| I Clinical Analysis of Radiation-induced Inner Ear Damages on Patients by Radio-chemotherapy under Nasopharyngeal Carcinoma IMRT TechnologyBackground and PurposeOur country is the highly NPC prone country. At present, radiotherapy is the most effective therapy for nasopharyngeal carcinoma as well as one of the main therapies for other malignant tumors of head and neck. In recent years,5-year-survival rate upon treatment of tumors of head and neck has been improved obviously, however, the subsequent long-term side effects are also been acquired more and more, in which radiation-induced ear disease incidence ranks second among the advanced complications. Sensorineural Hearing Loss (SNHL) upon radiotherapy is a common sequela for patients by NPC radiotherapy, especially for the patients combined with chemotherapy. Characteristics of this damage are delayed occurrence, progressive severity and irreversible hearing reduction, while there is no effective prevention and treatment currently. Therefore, the protection for inner ear damages on patients by chemotherapy is becoming especially important. With the development of radiotherapeutical physics and radiation biology, IMRT has become the standard radiotherapy technology and dose limit for inner ear is possible for plan formulation and implementation of radiotherapy. We plan, through the value of bone conduction4K Hz electro audiometry, to conduct related retrospective analysis, acquire the effects of the factors such as age, dose of patients by chemotherapy under NPC IMRT technology on the incidence of SNHL, try to find out the limit value of radiotherapeutic dose for cochlea and provide reference limit value of inner ear dose for the formulation of radiotherapy plan. Materials and MethodsTotally29cases of radiochemotherapeutic plans fully in accordance between2009and2011are included in this study. All cases are proved to be NPC pathologically and treated by IMRT radiotherapy and PF chemotherapy. Ages of all cases are≤55(to decrease the effect of aged SNHL on results of hearing test). Before radiotherapy, all their hearing levels are normal, all the tumors have no local or areal recurrence and systemic transfer upon follow-up survey, and they have complete physical examination records and audiological testing data, including tympanic membrane description, electro audiometry and acoustic impedance test. When grouping, we excluded the patients with secretory otitis media (middle ear effusion may affect the value of bone conduction audiometry) whose tympanic camity chart of acoustic impedance before and after radiotherapy is Type B. Electro audiometry and acoustic impedance before radiotherapy, upon completion of radiotherapy,3months after radiotherapy,6months after radiotherapy,1year after radiotherapy and2years after radiotherapy are both followed up for survey, and the deadline of the grouped patients is at least12months after radiotherapy. The related linear regression analysis, logistic analysis and odds ratio analysis are conducted based on the value of bone conduction4K Hz electro audiometry (the increase of≥10dB of threshold value is deemed meaningful) to analyze the factors related to radiation-induced inner ear damages and determine dose limit for inner ear.ResultsEar58conforms to the conditions of electro audiometry analysis, and25.8%ears deteriorates after radiotherapy.1. Multiple linear regression analysis finds that: both radiotherapeutic dose (p=0.01and assessment value is0.46) and age (p=0.002and assessment value is0.47) are related to the incidence of SNHL statistically.2. Logistic regression analysis finds that:both radiotherapeutic dose (p=0.02and assessment value is0,76) and age (p=0.005and assessment value is0.14) are related to the incidence of SNHL statistically.3. Odds Ratio analysis finds that:assessment value of dose is1.001and assessment value of age is1.151, both are the risk factors of the incidence of SNHL,4. The study on the relativity to incidence of SNHL after dosage and radiotherapy finds that:the comparative differences of doses between the benign group and the deteriorative group have statistical significance (Dose of the benign group is36.87Gy and that of the deteriorative group is39.43Gy, P=0.0492), therefore, we recommend that the limit value of cochlear dose shall be less than37Gy during the formulation of radiotherapy plan.ConclusionsFor patients by radio-chemotherapy under NPC IMRT technology, whether by linear regression model, logistic regression model or Odds Ratio analysis, the conclusions acquired are consistent. Both cochlea radiation dose and age are related to the incidence of SNHL after radiotherapy statistically. In order to prevent the SNHL occurrence of patients by radio-chemotherapy under NPC IMRT technology, the dose value is recommenced to be less than37Gy. Background and PurposeAs shown from the previous studies, cochlear radiation dose of NPC patients treated by radiochemotherapy shall be limited to37Gy to prevent SNHL. According to reports of previous studies, when cochlear dose is higher than41-50Gy, the incidence rate of SNHL reaches31%, which will up to62%when cochlear dose is60-90Gy, therefore, in order to ensure dose in gross tumor volume of the nasopharynx, the cochlear dose is appropriately limited to47Gy, and the lower dose limit may affect dose of gross tumor volume. Therefore, it is necessary to find more protection methods of inner ear damages to prevent SNHL after radiotherapy.Melanin is widely distributed in mammal, including inner ear of human, such as melanocyte in dark cell of human vestibular organs, stria vascularis and endolymphytic sac. Lots of literature confirmed that melanin has a protective effect on noise damages, ototoxic drugs and presbycusis. Due to capacity of melanin to chelate metallic cation, eliminate oxyradical, as well as store and transform energy, so that it has a protective effect on cochlear radiation-induced damages, but it has no related reports so far. As shown from the existing studies:there is tyrosine, enzymatic activity in vestibule, cochlea and endolymphatic sac of mottled animal so that melanocyte in their inner ear can actively synthesize melanin. Due to genetic defects of tyrosinase, albino animals can not synthesize melanin in body, therefore, it has no melanin in melanocyte of their inner ears. Due to such differences in inner ears of albino guinea pigs and mottled ones, the function of melanin in inner ears can be researched through comparison between them. It is proposed to create radiation model of guinea pigs with1OGy,15Gy,20Gy, then through comparative differences of inner ear damages between the two kinds of guinea pigs under three dose grads in two time points of24hours and2weeks to explore whether the melanin has a protective effect in radiation-induced inner ear damages.Materials and MethodsThe guinea pigs are divided into mottled group and albino group, which are given different irradiation with1000cGy,1500cGy,2000cGy, then cut off their heads after irradiation of24hours and2weeks, and do stretched preparation of cochlear and production of frozen sections to observe damages of hair cell, stria vascularis and spiral ligament.1. Select the third cochlear basilar membrane to do stretched preparation and staining of blue tetrazolium, and observe arrangement of the hair cells through microscope and calculate cells to figure out the miss rate.2. Conventional frozen sections, HE staining, measuring thickness of the third stria vascularis, cell density, number of blood capillary, as well as thickness of spiral ligament and the cell density.3. Conduct related statistical analysis to the results.ResultsIn models of radiation-induced inner ear damages, the results are as follows:1. Melanin:whether the albino group is irradiated or not, it has no melanin; the melanin of mottled group is in an increasing trend with increasing of irradiation dose and prolonging of irradiation time, increasing of the melanin is more obvious after2weeks upon irradiation.2. Status of hair cell:with the extension of irradiation time and increment of irradiation dose, hair cell disorder and miss rate of the two groups of guinea pigs are both increased, but under the condition of same dose and time, disorder of arrangement and miss rate of the albino group is higher than that of the mottled group.3. Status of stria vascularis:with increment of irradiation dose and extension of time after irradiation, thickness of stria vascularis of albino group is reduced, while that of the mottled group is essentially the same, even in a thickening trend; number of cells in stria vascularis has no obvious difference after irradiation of24hours.2weeks after irradiation, karyote of the albino group and the mottled group are both reduced, while karyote of albino group is reduced more obviously than that of the mottled group.4. Status of blood capillary:after irradiation, the numbers of blood capillary of the two groups of guinea pigs are both increased, but no significant differences between the two groups.5. Status of spiral ligament:with increment of irradiation dose and extension of time after irradiation, fibrocyte of spiral ligament of the two groups of guinea pigs are on a decreasing trend, while the albino group is more obvious than the mottled group.ConclusionsNumber of melanin in inner ear is in negative correlation with damage changes of stria vascularis cells of inner ear, spiral ligament cells and basilar membrane hair cells. Such correlation is move obvious in two weeks than in24hours after irradiation, but microcirculation relationship of melanin and stria vascularis is not obvious.In radiation-induced inner ear damages, inner ear melanin may have a correlation with incidence of SNHL after irradiation, which deserves further study... |
