The radiobiology of prostate cancer including new aspects of fractionatedradiotherapy
The radiobiology of prostate cancer including new aspects of fractionatedradiotherapy
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DOI：
10.1080/02841860410002824
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发表时间：
2005-05-01
期刊：
影响因子：
3.1
通讯作者：
Fowler, JF
中科院分区：
文献类型：
--
作者：
Fowler, JF
当每部分剂量或剂量率发生变化时，总辐射剂量不是衡量生物效应的可靠方法。在2 Gy剂量的外部放射治疗和从后负荷源以高剂量率给予的大增强剂量之间，可以看到生物有效性（每灰色）的巨大差异。在快速或缓慢增殖的组织中，效果是截然不同的，这是对大多数肿瘤和晚期并发症的影响。与大多数其他类型的肿瘤相比，这些差异在前列腺肿瘤和晚期并发症方面的作用正好相反。使用线性二次公式的目的是解释这些差异，特别是前列腺癌的治疗。前列腺癌异常缓慢的生长速度与它们对增加的颗粒大小的高度敏感性有关，因此大量的小颗粒，如每天35或40次的2 Gy剂量，并不是最佳的治疗方法。理论模型显示，在前列腺肿瘤中，对于较大（和较少）分数的晚期并发症，肿瘤效应的增强比晚期并发症更强。生物有效剂量和标准化总剂量（2gy分数当量）给予前列腺肿瘤，直肠晚期反应，和一个新的发展-急性直肠粘膜。图表显示了分数大小敏感性（α / β比）随组织增殖率的变化，导致小α / β比前列腺肿瘤中缓慢细胞倍增时间的关联。本文回顾了证实这一生物学预期的临床证据。前列腺肿瘤的α / β比值似乎低至1.5 Gy(95%可信区间1.3-1.8 Gy)，而大多数其他类型的肿瘤的α / β比值约为10 Gy。重要的一点是，对于直肠组织晚期并发症，α / β = 1.5 Gy似乎明显小于α / β = 3 Gy。这些差异也出现在最近的临床结果中。从这一重要差异中产生了优越的治疗方案，例如，20次3 Gy， 10次4.7 Gy，或5次7 Gy，这些方案在2 Gy组中都能产生相当于80-90 Gy的肿瘤结果，而在2 Gy组中，晚期并发症仅相当于72 Gy。外束治疗（EBRT）和近距离治疗增强剂量（25F x 2gy + 2 x 10gy）的联合治疗比任何使用每日2gy剂量的EBRT具有更高的生物肿瘤效应，并且具有可接受的晚期并发症。对低风险前列腺癌进行近距离放射治疗，在几天内使用两到四个部分，可以对肿瘤产生更高的生物效应。
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.