Herold D, Hanks G, Movsas B, Hanlon A
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Radiat Oncol Investig. 1997;5(1):15-9. doi: 10.1002/(SICI)1520-6823(1997)5:1<15::AID-ROI3>3.0.CO;2-N.
With three-dimensional conformal therapy, doses > 75 Gy have been delivered to the prostate with acceptable levels of morbidity; however, higher doses do appear to increase late gastrointestinal (GI) and genitourinary (GU) morbidity. Because patients with pretreatment prostate-specific antigen (PSA) values < 10 ng/ml can achieve 3-year actuarial bNED control rates of 90% after treatment with external beam radiotherapy to doses < 71 Gy, one might question the need for further dose escalation in this population. In this report, we examined the relationship between dose and PSA nadir for 90 patients with pretreatment PSA values < 10 ng/ml entered into a dose escalation study from March 1987 to October 1992. We wanted to see if nadir response data would predict a different outcome from our 3-year bNED control reports. All patients were treated with external beam radiotherapy to ICRU reporting point doses of 6,598 cGy to 7,895 cGy (median of 7,068 cGy). Minimum follow-up was 36 months (median, 47 months). Seven hundred thirty-nine posttreatment PSA nadir values were analyzed, yielding an average of 8.2 values per patient. Estimates of rates of bNED control and time to reach a posttreatment PSA of 1.0 ng/ml were calculated using the Kaplan-Meier product limit method. The log-rank test was used to evaluate differences in rates according to dose levels. Linear regression and Cox proportional hazard modeling were used to relate dose to bNED control on a continuum. Escalating doses from 66 to 79 Gy failed to increase the percentage of patients achieving nadir values < 1 ng/ml and similarly failed to increase the 3-year actuarial bNED control. Linear regression (P = .81) and the chi-square test of association (P = .23) supported the lack of a dose effect on nadir continuously and categorically, respectively, and the Cox regression model supported the conclusion that dose on a continuum has no effect on bNED control (P = .34). Furthermore, time to reach a posttreatment PSA level of 1.0 ng/ml was not statistically dependent on dose level (P = .13). Based on this study and prior reports demonstrating a dose response for late GI/GU morbidity, we question whether further dose escalation in this subgroup of patients is justified.
采用三维适形治疗时，已将大于75 Gy的剂量给予前列腺，其发病率处于可接受水平；然而，更高的剂量似乎确实会增加晚期胃肠道（GI）和泌尿生殖系统（GU）的发病率。由于治疗前前列腺特异性抗原（PSA）值<10 ng/ml的患者在接受剂量<71 Gy的外照射放疗后，3年精算无生化复发生存（bNED）控制率可达90%，因此有人可能会质疑在该人群中进一步增加剂量的必要性。在本报告中，我们研究了1987年3月至1992年10月进入剂量递增研究的90例治疗前PSA值<10 ng/ml患者的剂量与PSA最低点之间的关系。我们想看看最低点反应数据是否能预测出与我们的3年bNED控制报告不同的结果。所有患者均接受外照射放疗，国际辐射单位与测量委员会（ICRU）报告点剂量为6598 cGy至7895 cGy（中位数为7068 cGy）。最短随访时间为36个月（中位数为47个月）。分析了739个治疗后PSA最低点值，每位患者平均有8.2个值。使用Kaplan-Meier乘积限界法计算bNED控制率和达到治疗后PSA为1.0 ng/ml的时间估计值。对数秩检验用于评估不同剂量水平下的发生率差异。线性回归和Cox比例风险模型用于在连续体上关联剂量与bNED控制。将剂量从66 Gy增加到79 Gy未能提高PSA最低点值<1 ng/ml的患者百分比，同样也未能提高3年精算bNED控制率。线性回归（P = 0.81）和关联卡方检验（P = 0.23）分别从连续和分类方面支持了剂量对最低点缺乏影响，Cox回归模型支持了连续剂量对bNED控制无影响的结论（P = 0.34）。此外，达到治疗后PSA水平1.0 ng/ml的时间在统计学上不依赖于剂量水平（P = 0.13）。基于本研究以及先前显示晚期GI/GU发病率存在剂量反应的报告，我们质疑在该亚组患者中进一步增加剂量是否合理。
