Fowler Jack F
Emeritus of Medical School of Wisconsin University, Department of Human Oncology, University of Wisconsin-Madison, USA.
Acta Oncol. 2005;44(3):265-76. doi: 10.1080/02841860410002824.
Total radiation dose is not a reliable measure of biological effect when dose-per-fraction or dose-rate is changed. Large differences in biological effectiveness (per gray) are seen between the 2 Gy doses of external beam radiotherapy and the large boost doses given at high dose-rate from afterloading sources. The effects are profoundly different in rapidly or slowly proliferating tissues, that is for most tumors versus late complications. These differences work the opposite way round for prostate tumors versus late complications compared with most other types of tumor. Using the Linear-Quadratic formula it is aimed to explain these differences, especially for treatments of prostate cancer. The unusually slow growth rate of prostate cancers is associated with their high sensitivity to increased fraction size, so a large number of small fractions, such as 35 or 40 "daily" doses of 2 Gy, is not an optimum treatment. Theoretical modeling shows a stronger enhancement of tumor effect than of late complications for larger (and fewer) fractions, in prostate tumors uniquely. Biologically Effective Doses and Normalized Total Doses (in 2 Gy fraction equivalents) are given for prostate tumor, late rectal reactions, and--a new development--acute rectal mucosa. Tables showing the change of fraction-size sensitivity (the alpha/beta ratio) with proliferation rates of tissues lead to the association of slow cell doubling times in prostate tumors with small alpha/beta ratios. Clinical evidence to confirm this biological expectation is reviewed. The alpha/beta ratios of prostate tumors appear to be as low as 1.5 Gy (95% confidence interval 1.3-1.8 Gy), in contrast with the value of about 10 Gy for most other types of tumor. The important point is that alpha/beta =1.5 Gy appears to be significantly less than the alpha/beta =3 Gy for late complications in rectal tissues. Such differences are also emerging from recent clinical results. From this important difference stems the superior schedules of, for example, 20 fractions of 3 Gy, or 10 fractions of 4.7 Gy, or 5 fractions of 7 Gy, which can all give tumor results equivalent to 80-90 Gy in 2 Gy fractions, while keeping late complications equivalent to only 72 Gy in 2 Gy fractions. Combination treatments of external beam (EBRT) and brachytherapy boost doses (25F x 2 Gy plus 2 x 10 Gy) can give higher biological tumor effects than any EBRT using daily 2 Gy doses, and with acceptable late complications. Monotherapy by brachytherapy for low-risk cancer prostate using two to four fractions in a few days can give even higher biological effects on the tumors.
当每次分割剂量或剂量率发生变化时，总辐射剂量并非生物效应的可靠衡量指标。外照射放疗的2 Gy剂量与后装源高剂量率下给予的大剂量推量之间，（每格雷的）生物有效性存在巨大差异。在快速或缓慢增殖的组织中，即对于大多数肿瘤与晚期并发症而言，这些效应截然不同。与大多数其他类型的肿瘤相比，前列腺肿瘤与晚期并发症的情况则相反。旨在使用线性二次方程来解释这些差异，尤其是对于前列腺癌的治疗。前列腺癌异常缓慢的生长速度与其对增加分割剂量的高敏感性相关，因此大量小分割剂量，如35或40次“每日”2 Gy剂量，并非最佳治疗方案。理论模型显示，对于较大（且较少）分割次数，前列腺肿瘤中肿瘤效应的增强比晚期并发症更为显著。给出了前列腺肿瘤、直肠晚期反应以及——一项新进展——急性直肠黏膜的生物等效剂量和归一化总剂量（以2 Gy分割等效剂量表示）。显示分割剂量敏感性变化（α/β比值）与组织增殖率关系的表格表明，前列腺肿瘤中细胞倍增时间缓慢与较小的α/β比值相关。对证实这一生物学预期的临床证据进行了综述。前列腺肿瘤的α/β比值似乎低至1.5 Gy（95%置信区间1.3 - 1.8 Gy），而大多数其他类型肿瘤的值约为10 Gy。重要的是，α/β = 1.5 Gy似乎显著低于直肠组织晚期并发症的α/β = 3 Gy。近期临床结果也显示出此类差异。由此重要差异产生了诸如3 Gy的20次分割、4.7 Gy的10次分割或7 Gy的5次分割等更优方案，这些方案均可使肿瘤治疗效果等同于80 - 90 Gy的2 Gy分割剂量，同时将晚期并发症控制在等同于仅72 Gy的2 Gy分割剂量。外照射（EBRT）与近距离放疗推量剂量（25F x 2 Gy加2 x 10 Gy）的联合治疗可产生比任何每日2 Gy剂量的EBRT更高的肿瘤生物学效应，且晚期并发症可接受。对于低危前列腺癌，在几天内采用2至4次分割的近距离放疗单药治疗可对肿瘤产生更高的生物学效应。
