Zietman A L
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Mol Urol. 2000 Fall;4(3):203-8;discussion 215.
Neoadjuvant androgen suppression (NAS) can reduce the number of tumor clonogens prior to radiation, thus increasing the tumor control probability. Also, NAS may sensitize tumor cells to radiation if cell kill by both modalities follows a common pathway. The timing and sequence of NAS and radiation are important, with radiation being most effective if given at the point of maximal tumor regression. The biologic rationale for NAS + radiation has been reinforced by results from randomized trials, in particular RTOG 8610. However, many murine adenocarcinomas respond to androgen deprivation by a reduction in the proliferation rate and arrest in G(0), and in vitro data suggest that this arrest may interfere with radiation-induced cell killing. The mechanism of cell killing after low-dose-rate radiation (brachytherapy) may be different from that after high-dose-rate treatment. There are no reported experimental data assessing the interaction of NAS and brachytherapy to determine whether the combination offers a theoretical advantage or is potentially deleterious. Whether we understand the mechanism or not, clinical trials seem to support a positive interaction of NAS with external-beam radiation, but we have only begun to explore the timing and sequence that will provide the maximal effect. It cannot be assumed that the same advantage will hold with brachytherapy.
新辅助雄激素抑制（NAS）可在放疗前减少肿瘤克隆原的数量，从而提高肿瘤控制概率。此外，如果两种治疗方式的细胞杀伤遵循共同途径，NAS可能会使肿瘤细胞对放疗敏感。NAS与放疗的时间安排和顺序很重要，如果在肿瘤最大程度消退时进行放疗，则最为有效。随机试验，特别是RTOG 8610的结果强化了NAS + 放疗的生物学原理。然而，许多小鼠腺癌通过降低增殖率和停滞在G(0)期来响应雄激素剥夺，体外数据表明这种停滞可能会干扰辐射诱导的细胞杀伤。低剂量率放疗（近距离放疗）后的细胞杀伤机制可能与高剂量率治疗后的不同。目前尚无评估NAS与近距离放疗相互作用以确定联合治疗是否具有理论优势或潜在危害的实验数据报道。无论我们是否了解其机制，临床试验似乎都支持NAS与外照射放疗的积极相互作用，但我们才刚刚开始探索能产生最大效果的时间安排和顺序。不能假定近距离放疗也会有同样的优势。
