Fowler J F, Ritter M A
Department of Human Oncology, University of Wisconsin, Madison 53792, USA.
Int J Radiat Oncol Biol Phys. 1995 May 15;32(2):521-9. doi: 10.1016/0360-3016(95)00545-A.
The incidence of carcinoma of the prostate has recently begun to exceed that of carcinoma of the lung in males in the United States. Although survival and local tumor control after treatment are good for early stages, improvements are being sought for more locally advanced stages. Dose escalation might be of benefit and might be accomplished using "three-dimensional" conformal radiotherapy or hyperfractionation. Because carcinoma of the prostate is known to be a generally slowly growing tumor, there may be more scope for extreme hyperfractionation, even with prolongation to allow for the extra number of very small fractions. This article explores only the hyperfractionation approach, and only theoretically, to investigate when treatments might become too hyperfractionated.
The major problem was what to assume for proliferation rates in human adenocarcinomas. A literature search yielded labeling indices (S-phase proportions) often averaging about 1%, but spreading up to 6% or more in individual cases. These data are reviewed, and three bands of rate of loss of local control were chosen for the subsequent calculations: 0.5%, 1%, and 2% loss of local control per week of prolongation. Calculations were done using the linear-quadratic model for a series of doses per fraction of 1.2, 1.0, 0.8, and 0.6 Gy, given twice a day (b.i.d.) in 7, 9, 12, and 17 weeks, respectively. They were compared with a "standard" 36 fractions of 2 Gy = 72 Gy in 7 weeks. Total doses for equal late effects were calculated assuming a late alpha/beta of 3 Gy; the tumor Biologically Effective Doses were calculated assuming tumor alpha/beta values of 30, 10, and 5 Gy. The possible increases of local tumor control were estimated assuming a gamma-37 slope of 2% (per percent increase in total tumor dose).
Graphs are presented of the estimated local control as a function of dose per fraction (and overall time), for advanced tumors (starting at 30% LC) and for less advanced tumors (starting at 70%). The largest increase is always for the change from 2 Gy once a day (q.d.) to 1.2 Gy b.i.d. Further changes of local control with hyperfractionation depend upon tumor proliferation rate and on the shape of the tumor cell survival curve. The largest gains are for the more advanced tumors.
There is no great encouragement to proceed to more hyperfractionated and prolonged schedules than 1.2-1.0 Gy b.i.d. in 7-9 weeks. We await developments that might more reliably enable potential doubling time and cell survival curve shapes to be routinely determined for individual tumors, before further hyperfractionation might be considered. In the absence of tumor kinetic measurements, we might consider low grade tumors to be the ones to select for prolonged fractionation, whereas high grade tumors would be more suitable for 1.2 Gy b.i.d. with no prolongation, or for dose escalation using conventional fraction sizes and conformal radiotherapy.
在美国男性中，前列腺癌的发病率最近已开始超过肺癌。尽管早期治疗后的生存率和局部肿瘤控制情况良好，但对于局部进展期的情况仍在寻求改善。剂量递增可能有益，可通过“三维”适形放疗或超分割放疗来实现。由于已知前列腺癌通常是生长缓慢的肿瘤，即使延长治疗时间以容纳更多非常小的分次剂量，极端超分割放疗可能仍有更大空间。本文仅从理论上探讨超分割放疗方法，以研究治疗何时可能变得过度超分割。
主要问题是如何假设人类腺癌的增殖率。文献检索得出标记指数（S期比例）通常平均约为1%，但个别情况下可高达6%或更高。对这些数据进行了综述，并为后续计算选择了三个局部控制丧失率范围：每周延长治疗时间导致局部控制丧失0.5%、1%和2%。使用线性二次模型进行计算，每次分割剂量分别为1.2、1.0、0.8和0.6 Gy，每天两次（bid），分别在7、9、12和17周内完成。将它们与“标准”的7周内36次分割、每次2 Gy = 72 Gy进行比较。假设晚期α/β为3 Gy，计算同等晚期效应的总剂量；假设肿瘤α/β值为30、10和5 Gy，计算肿瘤生物等效剂量。假设γ-37斜率为2%（总肿瘤剂量每增加1%），估计局部肿瘤控制的可能增加情况。
给出了估计的局部控制作为每次分割剂量（和总时间）的函数的图表，适用于晚期肿瘤（起始局部控制率为30%）和较早期肿瘤（起始局部控制率为70%）。最大的增加总是从每天一次2 Gy（qd）变为每天两次1.2 Gy。超分割放疗后局部控制的进一步变化取决于肿瘤增殖率和肿瘤细胞存活曲线的形状。最大的获益是对于更晚期的肿瘤。
没有很大的动力去采用比7 - 9周内每天两次给予1.2 - 1.0 Gy更超分割和更长疗程的方案。在考虑进一步超分割放疗之前，我们等待可能更可靠地常规确定个体肿瘤潜在倍增时间和细胞存活曲线形状的进展。在没有肿瘤动力学测量的情况下，我们可能会认为低级别肿瘤适合选择延长分割，而高级别肿瘤更适合每天两次1.2 Gy且不延长疗程，或使用常规分割剂量和适形放疗进行剂量递增。
