Boonstra Philip S, Taylor Jeremy M G, Smolska-Ciszewska Beata, Behrendt Katarzyna, Dworzecki Tomasz, Gawkowska-Suwinska Marzena, Bialas Brygida, Suwinski Rafal
1 Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
2 Radiotherapy Clinic and Teaching Hospital, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Br J Radiol. 2016;89(1061):20150957. doi: 10.1259/bjr.20150957. Epub 2016 Feb 23.
There is disagreement regarding the value of the α/β ratio for prostate cancer. Androgen deprivation therapy (ADT) may dominate the effects of dose fractionation on prostate-specific antigen (PSA) response and confound estimates of the α/β ratio. We estimate this ratio from combined data on external beam radiation therapy (EBRT) and brachytherapy (BT)-treated patients, providing a range of doses per fraction, while accounting for the effects of ADT.
We analyse data on 289 patients with local prostate cancer treated with EBRT (2 Gy per fraction) or EBRT plus one or two BT boosts of 10 Gy each. The timing of ADT was heterogeneous. We develop statistical models to estimate the α/β ratio based upon PSA measurements at 1 year as a surrogate for the surviving fraction of cancer cells as well as combined biochemical + clinical recurrence-free survival (bcRFS), controlling for ADT.
For the PSA-based end point, the α/β ratio estimate is 7.7 Gy [95% confidence interval (CI): 4.1 to 12.5]. Based on the bcRFS end point, the estimate is 18.0 Gy (95% CI: 8.2 to ∞).
Our model-based estimates of the α/β ratio, which account for the effects of ADT and other important confounders, are higher than some previous estimates.
Although dose inhomogeneities and other limitations may limit the scope of our findings, the data suggest caution regarding the assumptions of the α/β ratio for prostate cancer in some clinical environments.
关于前列腺癌的α/β比值的价值存在分歧。雄激素剥夺疗法(ADT)可能主导剂量分割对前列腺特异性抗原(PSA)反应的影响,并混淆α/β比值的估计。我们根据外照射放疗(EBRT)和近距离放疗(BT)治疗患者的综合数据来估计该比值,提供一系列分次剂量,同时考虑ADT的影响。
我们分析了289例局部前列腺癌患者的数据,这些患者接受了EBRT(每次分割2 Gy)或EBRT加一次或两次每次10 Gy的BT增敏治疗。ADT的时机是异质性的。我们开发统计模型,基于1年时的PSA测量值作为癌细胞存活分数的替代指标以及综合生化+临床无复发生存期(bcRFS)来估计α/β比值,同时控制ADT的影响。
对于基于PSA的终点,α/β比值估计为7.7 Gy [95%置信区间(CI):4.1至12.5]。基于bcRFS终点,估计值为18.0 Gy(95% CI:8.2至∞)。
我们基于模型对α/β比值的估计考虑了ADT和其他重要混杂因素的影响,高于一些先前的估计值。
尽管剂量不均匀性和其他局限性可能限制我们研究结果的范围,但数据表明在某些临床环境中,对于前列腺癌α/β比值的假设需谨慎。