Current Status Of Nasopharyngeal Carcinoma Combined With Chemotherapy And Combined Chemotherapy In The Treatment Of Pituitary And Thyroid Function And Its Dose Study

Part I Retrospectively analysis about the long-term endocrine status of Nasopharyngeal carcinoma patients after treatment with Intersity-Modulated RadiotherapyObjective To investigate the frequency and associative factors of long-term endocrine dysfunction of initial NPC patients after the treatment of IMRT and concurrent chemotherapy, and further analysis the relationship between the hormone levels and absorbing dose of the glands.Methods and Materials Retrospectively reviewing the NPC patient received radical radiotherapy in FuDan University cancer center between Jan2008and Dec2011,98patients met the inclusive criteria. To collect the clinical information of these patients, re-contour the glands by the same standard and caculate the accurate absorbing dose and other dosimetry parameters. To detect the hormone status including FT3、FT4、TSH、LH、PRL、FSH、ACTH、E、T in peripheral blood by ECLIA during the follow-up. To analysis the data, independent T-tes or chi-square test was used to explore the relationship between dose and hormone levels and logistic regression analysis model was used to realize the univariate and multivariate analysis using the PASW18.0statistical package.Results The median age of98patients included was47years (17-70years), the median follow-up period was17months (6-51months). The overall endocrine alteration rate was54.1%, disorder rates of each endocrinal axis were as follow:TSH33.7%、FSH and LH20.4%, PRL11.2%, ACTH1%.29patients were found secondary hypothyroidism,4patients were found primary hypothyroidism, and11patients experienced hyperprolactinemia. The mean dose of pituitary and thyroid were respectively5120.8cGy and4972.9cGy. The overall endocrine alteration was associated with several dosemetry parameters of pituitary and thyroid. TSH and FT4were most significant correlated to the V40(P=0.000) and Dmean (P=0.002) of thyroid. PRL and FSH were both associated with V55(P=0.044, P=0.047) of pituitary. TSH、PRL and FSH were correlated to the follow-up period (P=0.001,0.09,0.003). As the follow-up time prolonged, the rates of dysfunction rise. Among them, PRL and FSH also affected by sexual and age, more disorders were found in female and young patients.Conclusion1. At the IMRT era, there still exist high rate of endocrine dysfunction, but lower than CRT.2. Dysfucntion of hypothalamic-pituitary-thyroid axis is more common in NPC patients due to the dual injury of the pituitary and thyroid.3. Long-term endocrine abnormality is associated with radiation dose, follow-up period, sexual and age. Part II Prospectively exploration about the short-term trends of endocrine change in NPC patients with standard synthetically treatmentObjective To explore the dynamic trends of endocrine changes and the relations between irradiation dose and hormone changes during the RT and short-term after the RT in NPC patients treated with IMRT and combined chemotherapy, to provide the evident to the protection of glands in the RTMethods and Materials Prospectively included66consecutive initial NPC patients since Nov.2012, assigned different synthetically treatment to them according the clinical stage. Collected clinical information, contoured the pituitary and thyroid gland and got the absorbing dose and DVH parameters. Detected the hormone levels in the peripheral blood at different times including baseline (T1), before RT after induction chemotherapy (T2), after RT (T3) and6months after RT (T4). The detecting items and methods was the same as Part Ⅰ. To analysis the trends of hormone levels in different times by paired T-test, to realized the univariate and multivariate analysis by logistic regression mole. α=0.05was set as the criteria of statistical significant.Results The median age of66patients was45years (15-66years). LH, FSH, T, E was found obvious disorder after induction chemotherapy, female patients’ hormone present to be menopausal status. The difference was statistical significant (P<0.05). Other hormone remained normal after induction chemotherapy. At T3, some patients appeared temporary thyrotoxicosis, FT4rose and TSH feedback dropped. FSH, LH, T, E remained abnormal. PRL slightly rose but still in the normal range. Those changes were all statistically significant (P<0.05). At T4, the FSH, LH, T, E of parts patients recovered to normal. However,3patients presented primary hypothyroidism and5patients secondary hypothyroidism. PRL also started to perform abnormal. Dmean of thyroid and pituitary were respectively4840.55cGy and4810.95cGy. At T3, there were no siginificant asscociative dose parameters except PRL and part changes of FT3, LH which correlated to the pituitary dose. At T4, the changes of FT4and TSH were most significant associated with V40(P=0.030and P=0.021) of thyroid. LH, FSH, T, E were also related to the thyroid dose. Univariate and multivariate analysis showed that only gonad axis was correlated to the sexual. Conclusion1. Endocrine disturbance already appeared at the IMRT and short-term follow-up.2. The main effect of chemotherapy was on hypothalamic-pituitary-gonads axis; however some patients can recover without treatment.3. Pituitary and thyroid need dose-limited protection during IMRT, the limited dose of pituitary and thyroid were suggested lower than50-55Gy and40Gy.4. Endocrine function should be monitoring at6months after RT at the latest.