Levendag P C, Schmitz P I, Jansen P P, Eijkenboom W M, Visser A G, Kolkman-Deurloo I K, Sipkema D, Visch L L, Senan S
Department of Radiation Oncology, University Hospital Rotterdam, Daniel den Hoed Cancer Center, The Netherlands.
J Clin Oncol. 1998 Jun;16(6):2213-20. doi: 10.1200/JCO.1998.16.6.2213.
A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT.
The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied.
The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT.
High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.
越来越多的数据表明,鼻咽癌(NPC)的局部控制与所给予的放射剂量有关。我们在一家机构开展了一项高剂量放疗(RT)的研究,其中纳入了高剂量率(HDR)近距离放疗(BT)。将这些结果与未接受BT的对照组所获得的数据一起进行分析。
BT组包括42例连续患者,其中29例根据肿瘤、淋巴结、转移系统分期为T1至3期,13例为T4期,34例为N+疾病。BT通过专门设计的可弯曲鼻咽施源器在门诊进行,并且优化了剂量分布。T1至3期肿瘤的治疗包括60 Gy的外照射放疗(ERT),随后给予6次3 Gy的BT(每天2次)。有咽旁肿瘤扩展和/或T4期肿瘤的患者接受70 Gy的ERT和4次3 Gy的BT。非BT组由1965年至1991年期间治疗的所有患者组成(n = 109),其中82例为T1至3期,27例为T4期,80例为N+疾病。采用局部失败时间(TTLF)、远处失败时间(TTDF)、无病生存期(DFS)、特定病因生存期(CSS)作为终点,并使用年龄、肿瘤分期、淋巴结分期和分级等预后因素进行多变量Cox比例风险分析。由于非BT组的总治疗时间差异很大,因此研究了局部失败(LF)对物理剂量以及根据总治疗时间(OTT)校正的生物等效剂量(BED)(BEDcor10)的依赖性。
BT组的3年局部无复发生存率更高(86%对60%;单变量分析,P = .004)。多变量分析显示,BT与非BT相比,TTLF的风险比为0.24(P = .003),TTDF为0.35(P = .038),DFS为0.31(P < .001)及CSS为0.44(P = .01)。最佳预后组为由接受BT治疗的T1至3期、N0至2b期肿瘤患者组成,其5年TTLF为94%,CSS为91%。相比之下,最差预后组,即5年TTLF为47%,CSS为24%,由未接受BT的T4期和/或N2c至3期肿瘤患者组成。
通过优化的HDR - BT,可对NPC患者给予高剂量放疗(73至95 Gy),且发病率最低。BT增敏的使用被证明具有显著益处,特别是对于T1至3期、N0至2b期疾病的患者。物理剂量和BEDcor10呈现的陡峭剂量 - 效应关系表明结果与剂量相关。该分析确定了一个预后较差的组,对其应采用化疗(CHT)强化治疗。