Wolden Suzanne L, Chen William C, Pfister David G, Kraus Dennis H, Berry Sean L, Zelefsky Michael J
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):57-62. doi: 10.1016/j.ijrobp.2005.03.057. Epub 2005 Jun 2.
We previously demonstrated that intensity-modulated radiation therapy (IMRT) significantly improves radiation dose distribution over three-dimensional planning for nasopharynx cancer and reported positive early clinical results. We now evaluate whether IMRT has resulted in improved outcomes for a larger cohort of patients with longer follow-up.
Since 1998, all 74 patients with newly diagnosed, nonmetastatic nasopharynx cancer were treated with IMRT using accelerated fractionation to 70 Gy; 59 received a hyperfractionated concomitant boost, and more recently 15 received once-daily treatment with dose painting. With the exception of Stage I disease (n = 5) and patient preference (n = 1), 69 patients received concurrent and adjuvant platinum-based chemotherapy similar to that in the Intergroup 0099 trial.
median age 45; 32% Asian; 72% male; 65% World Health Organization III; 6% Stage I, 16% Stage II, 30% Stage III, 47% Stage IV. Median follow-up is 35 months. The 3-year actuarial rate of local control is 91%, and regional control is 93%; freedom from distant metastases, progression-free survival, and overall survival at 3 years are 78%, 67%, and 83%, respectively. There was 100% local control for Stage T1/T2 disease, compared to 83% for T3/T4 disease (p = 0.01). Six patients failed at the primary site, with median time to local tumor progression 16 months; 5 were exclusively within the 70 Gy volume, and 1 was both within and outside the target volume. There is a trend for improved local control with IMRT when compared to local control of 79% for 35 patients treated before 1998 with three-dimensional planning and chemotherapy (p = 0.11). Six months posttherapy, 21%, 13%, 15%, and 0% of patients with follow-up audiograms (n = 24 patients) had Grade 1, 2, 3, and 4 sensorineural hearing loss, respectively. For patients with >1 year follow-up (n = 59), rates of long-term xerostomia were as follows: 26% none, 42% Grade 1, 32% Grade 2, and zero Grade 3.
The pattern of primary site failure within the target volume suggests locally advanced T stage disease may require a higher biologic dose to gross tumor. Rates of severe (Grade 3-4) ototoxicity and xerostomia are low with IMRT as a result of normal-tissue protection. Distant metastases are now the dominant form of failure, emphasizing the need for improved systemic therapy.
我们之前证明,调强放射治疗(IMRT)相较于鼻咽癌三维计划显著改善了放射剂量分布,并报告了早期积极的临床结果。我们现在评估IMRT对更大队列患者进行更长时间随访是否带来了更好的结果。
自1998年以来,74例新诊断的非转移性鼻咽癌患者均接受IMRT治疗,采用加速分割照射至70 Gy;59例接受超分割同步加量照射,最近15例接受剂量调强的每日一次治疗。除I期疾病患者(n = 5)和患者偏好(n = 1)外,69例患者接受了与Intergroup 0099试验类似的同步和辅助铂类化疗。
中位年龄45岁;32%为亚洲人;72%为男性;65%为世界卫生组织III期;6%为I期,16%为II期,30%为III期,47%为IV期。中位随访时间为35个月。3年局部控制精算率为91%,区域控制为93%;3年无远处转移生存率、无进展生存率和总生存率分别为78%、67%和83%。T1/T2期疾病的局部控制率为100%,而T3/T4期疾病为83%(p = 0.01)。6例患者原发部位失败,局部肿瘤进展的中位时间为16个月;5例仅在70 Gy靶区内,1例在靶区内及靶区外。与1998年前接受三维计划和化疗的35例患者79%的局部控制率相比,IMRT有改善局部控制的趋势(p = 0.11)。治疗后6个月,有随访听力图的患者(n = 24例)中,分别有21%、13%、15%和0%发生1级、2级、3级和4级感音神经性听力损失。对于随访时间>1年的患者(n = 59),长期口干发生率如下:无口干26%,1级42%,2级32%,3级为零。
靶区内原发部位失败模式表明局部晚期T分期疾病可能需要对大体肿瘤给予更高的生物剂量。由于对正常组织的保护,IMRT导致的严重(3 - 4级)耳毒性和口干发生率较低。远处转移现在是主要的失败形式,强调了改善全身治疗的必要性。