放疗期间肿瘤缩小使缺氧细胞再氧合。计算机模拟。

Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer simulation.

作者信息

Kocher M, Treuer H

机构信息

Department of Radiotherapy, University of Cologne.

出版信息

Strahlenther Onkol. 1995 Apr;171(4):219-30.

PMID:7740410

Abstract

PURPOSE

A 3-dimensional computer simulation was developed in order to estimate the impact of tumor shrinkage on reoxygenation of chronic hypoxic tumor cells during a full course of fractionated irradiation.

MATERIAL AND METHODS

The growth of a small tumor situated in a vascularized stroma with 350 capillary cross-sections/mm3 which were displaced by the growing tumor was simulated. Tumors contained 10(4) cells when irradiation started, intrinsic radiosensitivity was set to either low (alpha = 0.3 Gy-1, beta = 0.03 Gy-2) or high (alpha = 0.4 Gy-1, beta = 0.04 Gy-2) values. Oxygen enhancement ratio was 3.0, potential tumor doubling time Tpot = 1.2 or 5 days. A simulated fractionated radiotherapy was carried out with daily fractions of 2.0 Gy, total dose 50 to 70 Gy. The presence or absence of factors preventing tumor cord shrinkage was also included.

RESULTS

During the growth phase, all tumors developed a necrotic core with a hypoxic cell fraction of 25% under these conditions. During irradiation, the slower growing tumors (Tpot = 2 to 5 days) showed complete reoxygenation of the hypoxic cells after 30 to 40 Gy independent from radiosensitivity, undisturbed tumor shrinkage provided. If shrinkage was prevented, the hypoxic fraction rose to 100% after 30 to 50 Gy. Local tumor control, defined as the destruction of all clonogenic and hypoxic tumor cells increased by 20 to 100% due to reoxygenation and 50 Gy were enough in order to sterilize the tumors in these cases. In the fast growing tumors (Tpot = 1 day), reoxygenation was only observed in the case of high radiosensitivity and undisturbed tumor shrinkage. In these tumors reoxygenation increased the control rates by up to 60%.

CONCLUSION

The simulation results suggests that shrinking of a homogeneous tumor during irradiation with restoration of the normal vascular architecture can contribute significantly to reoxygenation, which in turn has a major effect on tumor control.

摘要

目的

开发一种三维计算机模拟，以评估肿瘤缩小对分次照射全过程中慢性缺氧肿瘤细胞再氧合的影响。

材料与方法

模拟一个位于血管化基质中的小肿瘤的生长，该基质具有350个毛细血管横截面积/mm³，随着肿瘤生长而移位。照射开始时肿瘤含有10⁴个细胞，内在放射敏感性设定为低（α = 0.3 Gy⁻¹，β = 0.03 Gy⁻²）或高（α = 0.4 Gy⁻¹，β = 0.04 Gy⁻²）值。氧增强比为3.0，潜在肿瘤倍增时间Tpot = 1.2或5天。进行模拟分次放射治疗，每日分次剂量为2.0 Gy，总剂量为50至70 Gy。还考虑了是否存在阻止肿瘤缩小的因素。

结果

在生长阶段，在这些条件下，所有肿瘤都形成了一个坏死核心，缺氧细胞比例为25%。在照射期间，生长较慢的肿瘤（Tpot = 2至5天）在30至40 Gy后显示缺氧细胞完全再氧合，与放射敏感性无关，前提是肿瘤缩小不受干扰。如果阻止缩小，缺氧比例在30至50 Gy后升至100%。局部肿瘤控制定义为所有克隆源性和缺氧肿瘤细胞的破坏，由于再氧合增加了20%至100%，在这些情况下50 Gy足以使肿瘤灭菌。在快速生长的肿瘤（Tpot = 1天）中，仅在高放射敏感性和肿瘤缩小不受干扰的情况下观察到再氧合。在这些肿瘤中，再氧合使控制率提高了高达60%。