Kam Michael K M, Teo Peter M L, Chau Ricky M C, Cheung K Y, Choi Peter H K, Kwan W H, Leung S F, Zee Benny, Chan Anthony T C
Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1440-50. doi: 10.1016/j.ijrobp.2004.05.022.
To evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of nasopharyngeal carcinoma (NPC), including the role of dose escalation above 66 Gy level.
Between July 2000 and September 2002, 63 newly diagnosed NPC patients were treated with IMRT. The disease was Stage I in 9 (14%), Stage II in 18 (29%), Stage III in 22 (35%), and Stage IV in 14 (22%). The prescribed dose was 66 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the planning target volume (PTV), and 54-60 Gy to the clinically negative neck. All 20 (100%) patients with T1-2a tumors received intracavitary brachytherapy (ICB) boost, and 15/42 (36%) patients with T2b-T4 tumors received conformal boost (8 Gy/4 fractions). Nineteen patients with advanced stage disease also received either neoadjuvant or concurrent chemotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method.
With a median follow-up of 29 months (range 8-45 months), 4 patients developed local in-field failure, 1 patient developed regional relapse, and 13 patients developed distant metastases. All 4 patients with local failure had either T3 or T4 disease before primary treatment and did not have ICB or conformal boost. The 3-year actuarial LRFS, NRFS, DMFS, and OS were 92%, 98%, 79%, and 90%, respectively. Multivariate analysis showed that dose escalation above 66 Gy was significantly associated with better PFS and DMFS, whereas GTV size was a significant adverse factor for OS. The worst acute mucositis was Grade 1 or 2 in 36 (59%), and Grade 3 in 25 (41%) patients. Acute dysphagia requiring tube feeding occurred in 5 (8%) patients. The proportion of patients with Grade 2-3 xerostomia was 57% at 3 months, and 23% at 2 years after IMRT. Within the subset of patients with a mean parotid dose of <31 Gy, the proportions with Grade 2-3 xerostomia were 30% and 17% at 3 months and 2 years, respectively.
Our experience of using IMRT in the primary treatment of NPC showed a very high rate of locoregional control and favorable toxicity profile. Furthermore, we found that dose escalation above 66 Gy of IMRT-based therapy was a significant determinant of progression-free survival and distant metastasis-free survival for advanced T-stage tumors. Distant metastases represent the predominant mode of treatment failure.
评估调强放射治疗（IMRT）在鼻咽癌（NPC）初始治疗中的疗效，包括剂量提升至66 Gy以上的作用。
2000年7月至2002年9月期间，63例新诊断的NPC患者接受IMRT治疗。疾病分期为I期9例（14%），II期18例（29%），III期22例（35%），IV期14例（22%）。肿瘤大体体积（GTV）和阳性颈部淋巴结的处方剂量为66 Gy，计划靶体积（PTV）为60 Gy，临床阴性颈部为54 - 60 Gy。所有20例（100%）T1 - 2a期肿瘤患者接受腔内近距离放疗（ICB）增敏，42例T2b - T4期肿瘤患者中的15例（36%）接受适形增敏（8 Gy/4次分割）。19例晚期疾病患者还接受了新辅助或同步化疗。根据放射治疗肿瘤学组（RTOG）放射损伤评分标准对急性和晚期正常组织效应进行分级。采用Kaplan - Meier法估计局部无复发生存率（LRFS）、区域无复发生存率（NRFS）、远处转移无复发生存率（DMFS）和总生存率（OS）。
中位随访29个月（范围8 - 45个月），4例患者出现局部野内失败，1例患者出现区域复发，13例患者出现远处转移。所有4例局部失败患者在初始治疗前均为T3或T4期疾病，且未接受ICB或适形增敏。3年精算LRFS、NRFS、DMFS和OS分别为92%、98%、79%和90%。多因素分析显示，IMRT剂量提升至66 Gy以上与更好的无进展生存期（PFS）和DMFS显著相关，而GTV大小是OS的显著不利因素。最严重的急性黏膜炎在36例（59%）患者中为1或2级，25例（41%）患者中为3级。5例（8%）患者出现需要鼻饲的急性吞咽困难。IMRT后3个月时2 - 3级口干患者比例为57%，2年时为23%。在平均腮腺剂量<31 Gy的患者亚组中，3个月和2年时2 - 3级口干患者比例分别为30%和17%。
我们在NPC初始治疗中使用IMRT的经验显示局部区域控制率非常高且毒性特征良好。此外，我们发现基于IMRT的治疗剂量提升至66 Gy以上是晚期T分期肿瘤无进展生存期和远处转移无复发生存期的重要决定因素。远处转移是主要治疗失败模式。
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