Zelefsky M J, Cowen D, Fuks Z, Shike M, Burman C, Jackson A, Venkatramen E S, Leibel S A
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer. 1999 Jun 1;85(11):2460-8. doi: 10.1002/(sici)1097-0142(19990601)85:11<2460::aid-cncr23>3.0.co;2-n.
The current study was undertaken to evaluate the incidence and predictors of late toxicity in patients with localized prostate carcinoma treated with high dose three-dimensional conformal radiotherapy (3D-CRT).
A total of 743 patients with prostate carcinoma classified as T1c-T3 were treated with 3D-CRT that targeted the prostate and seminal vesicles. A minimum tumor dose of 64.8 gray (Gy) was given to 96 patients (13%), 70.2 Gy to 266 patients (365), 75.6 Gy to 320 patients (43%), and 81.0 Gy to 61 patients (8%). The median follow-up time was 42 months (range, 18-109 months). Late toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale.
Late gastrointestinal (GI) and urinary (GU) toxicities were absent or minimal (Grade 0 or 1) in 90% of patients. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GI toxicities was 11% and 0.75%, respectively. A multivariate analysis identified doses > or =75.6 Gy (P<0.001), history of diabetes mellitus (P = 0.01), and the presence of acute GI symptoms during treatment (P = 0.02) as independent predictors of Grade > or =2 late GI toxicity. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GU toxicities was 10% and 3%, respectively. Doses > or =75.6 Gy (P = 0.008) and acute GU symptoms (P<0.001) were independent predictors of Grade > or =2 late GU toxicity. Among 544 patients who were potent before treatment (73% of all patients), 211 (39%) became impotent after 3D-CRT. The 5-year actuarial risk of potency loss was 60%. Doses > or =75.6 Gy (P<0.001) and the use of neoadjuvant androgen deprivation (P = 0.01) were independent predictors of posttreatment erectile dysfunction.
The incidence of severe late complications after high dose 3D-CRT was minimal. Radiation doses > or =75.6 Gy and the presence of acute treatment-related symptoms during 3D-CRT correlated with a higher incidence of Grade > or =2 late GI and GU toxicities. In addition to higher doses, the use of androgen deprivation therapy increased the likelihood of permanent impotence in these patients. Intensity-modulated radiotherapy, which makes it possible to enhance the conformality of the dose distribution, has recently been implemented in an attempt to reduce the incidence of moderate grade toxicities in patients receiving high dose 3D-CRT.
本研究旨在评估接受高剂量三维适形放疗（3D-CRT）的局限性前列腺癌患者迟发性毒性的发生率及预测因素。
共有743例T1c-T3期前列腺癌患者接受了针对前列腺和精囊的3D-CRT治疗。96例患者（13%）接受的最小肿瘤剂量为64.8格雷（Gy），266例患者（36%）为70.2 Gy，320例患者（43%）为75.6 Gy，61例患者（8%）为81.0 Gy。中位随访时间为42个月（范围18-109个月）。迟发性毒性根据放射治疗肿瘤学组的发病评分标准进行分级。
90%的患者无迟发性胃肠道（GI）和泌尿系统（GU）毒性或毒性轻微（0级或1级）。2级和3级迟发性GI毒性的5年精算发生率分别为11%和0.75%。多因素分析确定剂量≥75.6 Gy（P<0.001）、糖尿病史（P = 0.01）以及治疗期间出现急性GI症状（P = 0.02）是≥2级迟发性GI毒性的独立预测因素。2级和3级迟发性GU毒性的5年精算发生率分别为10%和3%。剂量≥75.6 Gy（P = 0.008）和急性GU症状（P<0.001）是≥2级迟发性GU毒性的独立预测因素。在治疗前性功能正常的544例患者（占所有患者的73%）中，211例（39%）在3D-CRT后出现阳痿。性功能丧失的5年精算风险为60%。剂量≥75.6 Gy（P<0.001）和使用新辅助雄激素剥夺治疗（P = 0.01）是治疗后勃起功能障碍的独立预测因素。
高剂量3D-CRT后严重迟发性并发症的发生率极低。剂量≥75.6 Gy以及3D-CRT期间出现与治疗相关的急性症状与≥2级迟发性GI和GU毒性的较高发生率相关。除了更高的剂量外，雄激素剥夺治疗的使用增加了这些患者永久性阳痿的可能性。调强放疗能够提高剂量分布的适形性，最近已被应用于试图降低接受高剂量3D-CRT患者中度毒性的发生率。
