Zelefsky M J, Leibel S A, Gaudin P B, Kutcher G J, Fleshner N E, Venkatramen E S, Reuter V E, Fair W R, Ling C C, Fuks Z
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Int J Radiat Oncol Biol Phys. 1998 Jun 1;41(3):491-500. doi: 10.1016/s0360-3016(98)00091-1.
Three-dimensional conformal radiation therapy (3D-CRT) is a technique designed to deliver prescribed radiation doses to localized tumors with high precision, while effectively excluding the surrounding normal tissues. It facilitates tumor dose escalation which should overcome the relative resistance of tumor clonogens to conventional radiation dose levels. The present study was undertaken to test this hypothesis in patients with clinically localized prostate cancer.
A total of 743 patients with clinically localized prostate cancer were treated with 3D-CRT. As part of a phase I study, the tumor target dose was increased from 64.8 to 81 Gy in increments of 5.4 Gy. Tumor response was evaluated by post-treatment decrease of serum prostate-specific antigen (PSA) to levels of < or = 1.0 ng/ml and by sextant prostate biopsies performed > or = 2.5 years after completion of 3D-CRT. PSA relapse-free survival was used to evaluate long-term outcome. The median follow-up was 3 years (range: 1-7.6 years).
Induction of an initial clinical response was dose-dependent, with 90% of patients receiving 75.6 or 81.0 Gy achieving a PSA nadir < or = 1.0 ng compared with 76% and 56% for those treated with 70.2 Gy and 64.8 Gy, respectively (p < 0.001). The 5-year actuarial PSA relapse-free survival for patients with favorable prognostic indicators (stage T1-2, pretreatment PSA < or = 10.0 ng/ml and Gleason score < or = 6) was 85%, compared to 65% for those with intermediate prognosis (one of the prognostic indicators with a higher value) and 35% for the group with unfavorable prognosis (two or more indicators with higher values) (p < 0.001). PSA relapse-free survival was significantly improved in patients with intermediate and unfavorable prognosis receiving > or = 75.6 Gy (p < 0.05). A positive biopsy at > or = 2.5 years after 3D-CRT was observed in only 1/15 (7%) of patients receiving 81.0 Gy, compared with 12/25 (48%) after 75.6 Gy, 19/42 (45%) after 70.2 Gy, and 13/23 (57%) after 64.8 Gy (p < 0.05).
The data provide evidence for a significant effect of dose escalation on the response of human prostate cancer to irradiation and defines new standards for curative radiotherapy in this disease.
三维适形放射治疗（3D-CRT）是一种旨在将规定的辐射剂量高精度地传递至局部肿瘤，同时有效避开周围正常组织的技术。它有助于提高肿瘤剂量，从而克服肿瘤克隆源性细胞对传统辐射剂量水平的相对抗性。本研究旨在对临床局限性前列腺癌患者验证这一假说。
共有743例临床局限性前列腺癌患者接受了3D-CRT治疗。作为一项I期研究的一部分，肿瘤靶区剂量以5.4 Gy的增量从64.8 Gy增至81 Gy。通过治疗后血清前列腺特异性抗原（PSA）降至≤1.0 ng/ml以及在3D-CRT完成后≥2.5年进行的前列腺六分区活检来评估肿瘤反应。采用PSA无复发生存率来评估长期疗效。中位随访时间为3年（范围：1 - 7.6年）。
初始临床反应的诱导呈剂量依赖性，接受75.6或81.0 Gy的患者中90%的PSA最低点≤1.0 ng，而接受70.2 Gy和64.8 Gy治疗的患者中这一比例分别为76%和56%（p < 0.001）。预后良好指标（T1 - 2期、治疗前PSA≤10.0 ng/ml且Gleason评分≤6）患者的5年精算PSA无复发生存率为85%，预后中等（其中一项预后指标值较高）的患者为65%，预后不良（两项或更多指标值较高）的患者为35%（p < 0.001）。接受≥75.6 Gy的预后中等和不良的患者，其PSA无复发生存率有显著改善（p < 0.05）。在接受81.0 Gy的患者中，仅1/15（7%）在3D-CRT后≥2.5年活检结果为阳性，而接受75.6 Gy后为12/25（48%），接受70.2 Gy后为19/42（45%），接受64.8 Gy后为13/23（57%）（p < 0.05）。
这些数据为剂量递增对人类前列腺癌放疗反应的显著影响提供了证据，并为该疾病的根治性放疗确定了新的标准。
