OncoRay-National Centre for Radiation Research in Oncology, Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Int J Radiat Oncol Biol Phys. 2011 Jul 15;80(4):1205-13. doi: 10.1016/j.ijrobp.2011.02.015. Epub 2011 Apr 12.
To explore the prognostic value of microenvironmental parameters for local tumor control determined before and during fractionated irradiation.
Six human squamous cell carcinoma (hSCC) lines were transplanted subcutaneously into the right hind leg of nude mice. Tumors were irradiated with 30 fractions within 6 weeks. Local tumor control was determined 120 days after irradiation. Radiation response was quantified as dose to cure 50% of tumors (TCD(50)). In parallel, untreated and irradiated tumors were excised after injection of pimonidazole (hypoxia marker) and Hoechst 33342 (perfusion marker) for histological evaluation.
Pimonidazole hypoxia decreased during fractionated irradiation in the majority of tumor lines. Fraction of perfused vessels and vascular area showed modest changes during fractionated irradiation. Histological parameters before treatment and after three and five fractions did not significantly correlate with TCD(50) after irradiation with 30 fractions within 6 weeks (p > 0.05). Hypoxic volume and perfused vessels after 10 fractions showed a significant association with local tumor control after fractionated irradiation (p = 0.018 and p = 0.019, respectively). None of these parameters remained statistically significant when the p value was adjusted for multiple comparisons.
The results from this exploratory study suggest that determination of microenvironmental parameters during treatment provides better prognostic information for the outcome after fractionated radiotherapy than pretreatment parameters, which warrants further investigation and confirmation in experimental and clinical studies.
探讨在分次照射前后确定的微环境参数对局部肿瘤控制的预后价值。
将 6 个人鳞状细胞癌（hSCC）系皮下移植到裸鼠的右后腿。肿瘤在 6 周内接受 30 次分割照射。照射后 120 天确定局部肿瘤控制。将辐射反应量化为治愈 50%肿瘤的剂量（TCD(50)）。平行地，在未处理和照射的肿瘤中注射 pimonidazole（缺氧标志物）和 Hoechst 33342（灌注标志物）后切除，用于组织学评估。
在大多数肿瘤系中，pimonidazole 缺氧在分次照射期间减少。在分次照射期间，灌注血管的比例和血管面积略有变化。在治疗前和治疗后 3 次和 5 次时的组织学参数与 6 周内接受 30 次分割照射后的 TCD(50)没有显著相关性（p > 0.05）。在 10 次分割后，缺氧体积和灌注血管与分次照射后的局部肿瘤控制有显著相关性（p = 0.018 和 p = 0.019）。当调整 p 值以进行多次比较时，这些参数中没有一个具有统计学意义。
这项探索性研究的结果表明，在治疗期间确定微环境参数比预处理参数提供了更好的预后信息，可用于进一步的实验和临床研究。
