Stock R G, Stone N N, Tabert A, Iannuzzi C, DeWyngaert J K
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Int J Radiat Oncol Biol Phys. 1998 Apr 1;41(1):101-8. doi: 10.1016/s0360-3016(98)00006-6.
No dose-response study has ever been performed for I-125 prostate implants using modern techniques of implant evaluation and modern treatment outcome end points. The amount of activity per volume implanted was increased over time based on review of postimplant dosimetry. This resulted in different delivered dose levels. This study explores the relationship between dose, biochemical failure, and biopsy results.
134 patients with T1-T2 prostate cancer were implanted with I-125 radioactive seeds and followed from 12 to 74 months (median: 32) postimplant. No patient received external beam irradiation or hormonal therapy. All patients implanted with I-125 had Gleason scores < or =6. One month postimplant, a CT-based three-dimensional dosimetric evaluation was performed on all patients. Using TG43 guidelines, dose-volume histograms were calculated. The dose delivered to the gland was defined as the D90 (dose delivered to 90% of prostate tissue as defined by CT). The D90s ranged from 26.8 to 256.3 Gy (median: 140.8 Gy). Biochemical failure was defined as two consecutive rises in prostate specific antigen (PSA) or a nadir level above 1.0 ng/ml. Posttreatment prostate biopsies (six to eight core samples) were routinely performed at 2 years postimplant.
Improvements in freedom from biochemical failure (FFBF) rates were seen with increasing D90 levels. The 4-year FFBF rates for patients with D90 values < 100 Gy, 100-119.9 Gy, 120-13.9 Gy, 140-159.9 Gy, and > or =160 Gy were 53, 82, 80, 95, and 89%, respectively (p = 0.02). Patients receiving a D90 < 140 Gy (65 patients) were similar with respect to presenting disease prognostic factors to those receiving a D90 > or =140 Gy (69 patients). Patients receiving a D90 < 140 Gy had a 4-year FFBF rate of 68% compared to a rate of 92% for those receiving a D90 > or =140 Gy (p = 0.02). Two-year posttreatment biopsies were negative in 70% (33 of 47) of patients with a D90 < 140 Gy compared to a rate of 83% (24 of 29) in patients with a D90 > or =140 Gy (p = 0.2). A multivariate analysis using dose, PSA, score, and stage revealed that dose was the most significant predictor of biochemical failure (p = 0.001). This dose response was more pronounced in patients presenting with PSA levels > 10 ng/ml. In these patients, the 4-year FFBF rates were 51 and 100% for the low and high dose groups, respectively (p = 0.009) and the negative biopsy rates were 64% (14 of 22) and 100% (8 of 8), respectively (p = 0.05). In patients with presenting PSA <10 ng/ml, the 4-year FFBF rates were 82 and 88% for the low and high dose groups, respectively (p = 0.29).
A dose response was observed at a level of 140 Gy. Adequate I-125 implants should deliver a dose of 140-160 Gy using TG43 guidelines.
从未使用现代植入物评估技术和现代治疗结果终点对I - 125前列腺植入物进行过剂量反应研究。根据植入后剂量测定的回顾，随时间推移，每单位植入体积的活度增加。这导致了不同的给予剂量水平。本研究探讨剂量、生化失败和活检结果之间的关系。
134例T1 - T2期前列腺癌患者接受I - 125放射性粒子植入，并在植入后12至74个月（中位数：32个月）进行随访。没有患者接受外照射或激素治疗。所有接受I - 125植入的患者Gleason评分≤6分。植入后1个月，对所有患者进行基于CT的三维剂量学评估。使用TG43指南计算剂量体积直方图。给予腺体的剂量定义为D90（根据CT定义，给予90%前列腺组织的剂量）。D90范围为26.8至256.3 Gy（中位数：140.8 Gy）。生化失败定义为前列腺特异性抗原（PSA）连续两次升高或最低点水平高于1.0 ng/ml。植入后2年常规进行治疗后前列腺活检（6至8个芯样）。
随着D90水平升高，无生化失败（FFBF）率有所改善。D90值<100 Gy、100 - 119.9 Gy、120 - 139.9 Gy、140 - 159.9 Gy和≥160 Gy的患者4年FFBF率分别为53%、82%、80%、95%和89%（p = 0.02）。接受D90<140 Gy的患者（65例）与接受D90≥140 Gy的患者（69例）在疾病预后因素方面相似。接受D90<140 Gy的患者4年FFBF率为68%，而接受D90≥140 Gy的患者为92%（p = 0.02）。D90<140 Gy的患者中，70%（47例中的33例）治疗后2年活检为阴性，而D90≥140 Gy的患者中这一比例为83%（29例中的24例）（p = 0.2）。使用剂量、PSA、评分和分期进行多变量分析显示，剂量是生化失败的最显著预测因素（p = 0.001）。这种剂量反应在PSA水平>10 ng/ml的患者中更为明显。在这些患者中，低剂量组和高剂量组的4年FFBF率分别为51%和100%（p = 0.009），活检阴性率分别为64%（22例中的14例）和100%（8例中的8例）（p = 0.05）。在PSA<10 ng/ml的患者中，低剂量组和高剂量组的4年FFBF率分别为82%和88%（p = 0.29）。
在140 Gy水平观察到剂量反应。使用TG43指南，合适的I - 125植入应给予140 - 160 Gy的剂量。
