Hirata Yoshito, Aihara Kazuyuki
Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
J Theor Biol. 2015 Nov 7;384:147-52. doi: 10.1016/j.jtbi.2015.08.010. Epub 2015 Aug 28.
Intermittent androgen suppression is becoming a standard clinical option for patients who suffer from recurrence after an initial treatment of prostate cancer such as radiation therapy and radical prostatectomy. In the first mathematical model of intermittent androgen suppression (Ideta et al., 2008), the authors tried to control the trajectory of the model to a periodic orbit to enable patients to coexist with prostate cancer, even if it cannot be eradicated. Recently, we proposed a mathematical model capable of improving the quantitative reproduction of the behavior of prostate cancer under intermittent androgen suppression (Hirata et al., 2010a). Here we examine whether such a stable periodic orbit can be created for patients who eventually will have to experience the relapse of cancer at a later stage. By using a mathematical analysis, we found that the above model of Hirata et al. does not contain a non-zero periodic orbit that can be targeted for such patients, namely patients of type (ii) or type (iii) for whom intermittent androgen suppression cannot stabilize the origin where no cancer cells exist. This result might suggest that the patients must seek to delay the relapse as much as possible if the cancer cannot be eradicated. We further classify type (i) into subclasses where such a non-zero periodic orbit can either be stabilized or asymptotically stabilized.
对于那些在接受前列腺癌初始治疗(如放射治疗和根治性前列腺切除术)后复发的患者,间歇性雄激素抑制正成为一种标准的临床选择。在间歇性雄激素抑制的首个数学模型中(伊德田等人,2008年),作者试图将模型的轨迹控制到一个周期轨道,以使患者能够与前列腺癌共存,即便癌症无法被根除。最近,我们提出了一个能够改善间歇性雄激素抑制下前列腺癌行为定量再现的数学模型(平田等人,2010年a)。在此,我们研究对于那些最终在后期不得不经历癌症复发的患者,是否能够创建这样一个稳定的周期轨道。通过数学分析,我们发现平田等人的上述模型不包含可针对此类患者(即(ii)型或(iii)型患者,对于他们间歇性雄激素抑制无法使不存在癌细胞的原点稳定)的非零周期轨道。这一结果可能表明,如果癌症无法被根除,患者必须尽可能地寻求延迟复发。我们进一步将(i)型细分为这样的子类,即非零周期轨道在其中要么能够被稳定,要么能够被渐近稳定。