上颈部纤维化对鼻咽癌患者放射性后组颅神经损伤的影响

The effect of fibrosis in the upper neck on radiation-related cranial nerve palsy in patients with nnsopharyngeal carcinoma

目的探讨鼻咽癌患者中放射性后组颅神经（第Ⅸ-Ⅻ颅神经）损伤的影响因素,重点探讨其与上颈部纤维化的关系。方法分析317例生存5年以上的鼻咽癌患者。入组患者均为单程放疗,以^60Co或6MVX线照射,分别采用面颈联合野（62例）和耳前野放疗（255例）。鼻咽原发灶照射的中位剂量为71Gy（55-86Gy）,上颈部照射的中位剂量为61Gy（34-72Gy）。24例加用192Ir鼻咽腔内近距离放疗联合化疗45例。结果中位随访时间为11.4年（5.1-38.0年）。81例（25.5%）患者发生放射性后组颅神经损伤,年平均发病率为1.8%,5、10和20年的累积发病率分别为5.7%、17.4%和37.3%。根据SOMA标准,54例（17%）患者上颈部发生严重（3-4级）放射性纤维化。在上颈部出现严重放射性纤维化的患者中,放射性后组颅神经损伤的5年和10年累积发生率分别为22.2%和42.0%,而在无或轻度放射性纤维化患者中的发生率则分别为4.6%和12.1%,经Log-rank检验,两组病例之间差异有统计学意义（P〈0.001）。单因素分析结果还显示,鼻咽部总剂量大于70Gy（与≤70Gy相比）和采用耳前野放疗（与面颈联合野相比）的放射性后组颅神经损伤的发生率增加（P〈0.05）。在多因素分析中,上述3个影响因素差异仍具有统计学意义。结论放射性后组颅神经损伤除了与鼻咽部的放疗总剂量和放射野有关外,上颈部纤维化亦是重要的独立的影响因素,颅神经周围的纤维化可能是放射性颅神经损伤的发生机制之一。

Objective To analyse the effect of fibrosis in the upper neck on the development of radiation-induced cranial nerve palsy （CNP） in nasopharyngeal carcinoma （NPC） patients after radiation treatment. Methods Between Feb. 2000 and Feb. 2002, 317 consecutive patients with NPC who survival at least 5 years came to our radiotherapy center for follow-up, who were analyzed in this study. Patients who received re-irradiation were excluded. All patients received definitive external beam radiotherapy （EBRT） with either Cobalt-60 or megavoltage linear accelerators. The median radiotherapy dose was 71 Gy （range 55-86 Gy） to the primary disease, 61 Gy （range 34-72 Gy） to the upper neck. High-dose-rate brachytherapy with Ir-192 source was used in 24 patients either as part of definitive treatment or as a boost for residual disease in the nasopharynx. Forty-five patients also received chemotherapy whh various regimens. Results The median follow-up was 11.4 years （range 5.1-38.0 years）. A total of 81 patients （25.5%） developed radiation-induced posterior CN group （CN Ⅸ-Ⅻ ） palsy with an average annual rate of 1.8 %. The cumulative incidence of CNP was 5.7% , 17.4% and 37.3% at 5-, 10- and 20-year respectively. Fifty-four （17%） patients showed severe fibrosis （G3-4） in the upper neck. Univariate and multivariate analysis showed that the total dose of radiation to the nasopharynx and upper neck fibrosis were independent risk factors for developing CNP after RT for NPC. Neck severe fibrosis was associated with approximately two-fold risk of developing CNP （RR = 1.936, 95% CI： 1.521-2.466, P 〈 0.001 ）. Radiation technique with pre-anric field and a total dose of 〉 70 Gy to the nasopharynx were associated with increased risk of developing CNP. Other factors, including gender, age, N classifications, chemotherapy, unconventional fractionation radiation, total radiation dose to the upper neck, and brachytherapy did not influence the risk of CNP. Conclusions Patients who had severe fibrosis in the upper neck may be at increased risk of radiation-induced posterior group CNP. Perhaps the fibrosis of the surrounding tissues led to damaging to the CN nerve. It should be prudent when pre-anric radiation field were used.