Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Cancer Biol Ther. 2012 Dec;13(14):1449-53. doi: 10.4161/cbt.22006. Epub 2012 Sep 6.
Recent modeling efforts, based on reported outcomes following salvage radiotherapy (SRT) for prostate cancer, predict the likelihood of biochemical control (tumor control probability, TCP) as a function of pre-treatment prostate specific antigen (PSA) and SRT dose. Similar instruments predict the risk of grade ≥ 3 late toxicity (normal tissue complication probability, NTCP) as a function of SRT dose. Here we explore how changes in the parameters of those models might affect the optimal SRT dose and clinical outcomes.
Baseline TCP and NTCP model parameters were established in a previous report. Pre-treatment PSA was set at 0.4 ng/mL. Model parameters were modified to explore four scenarios: (1) improving the safety of SRT, (2) increasing tumor cell radiosensitivity, (3) increasing the cure rate achievable with SRT and (4) adoption of hypofractionated SRT schedules. The "optimal" SRT dose, defined as the dose that maximized the likelihood of achieving biochemical control without causing late toxicity, was identified for each scenario.
Improving the safety of SRT increased the optimal SRT dose, while radiosensitization decreased the optimal dose. Both changes were predicted to increase the probability of biochemical control and decrease late toxicity rates. Increasing the cure rate achievable with SRT (eg: improving patient selection or combining SRT with effective systemic therapy) provided the greatest gains in TCP. Adoption of a hypofractionated SRT schedule was predicted to improve both biochemical control and late toxicity.
Modeling exercises demonstrate the significant gains that may be achieved with improved implementation of SRT for prostate cancer. Strategies to realize the effects modeled in this report should be explored in clinical trials.
最近的建模工作基于前列腺癌挽救性放疗（SRT）后报告的结果，预测了生化控制（肿瘤控制概率，TCP）的可能性，其作为治疗前前列腺特异性抗原（PSA）和 SRT 剂量的函数。类似的工具预测了≥3 级晚期毒性（正常组织并发症概率，NTCP）的风险，作为 SRT 剂量的函数。在这里，我们探讨了这些模型参数的变化如何影响最佳 SRT 剂量和临床结果。
在之前的报告中建立了基线 TCP 和 NTCP 模型参数。治疗前 PSA 设定为 0.4ng/ml。修改模型参数以探讨四种情况：（1）提高 SRT 的安全性，（2）提高肿瘤细胞的放射敏感性，（3）提高 SRT 可实现的治愈率，（4）采用 SRT 分割方案。为每种情况确定了“最佳”SRT 剂量，定义为在不引起晚期毒性的情况下最大程度地提高生化控制可能性的剂量。
提高 SRT 的安全性增加了最佳 SRT 剂量，而放射增敏降低了最佳剂量。这两种变化都预计会增加生化控制的可能性，并降低晚期毒性的发生率。提高 SRT 可实现的治愈率（例如：改善患者选择或将 SRT 与有效的系统治疗相结合）可最大程度地提高 TCP。采用 SRT 分割方案预计会改善生化控制和晚期毒性。
建模研究表明，通过改进前列腺癌的 SRT 实施可以获得显著的收益。应该在临床试验中探索实现本报告中模型效果的策略。
