EXPLORATORY STUDY OF THE PROGNOSTIC VALUE OF MICROENVIRONMENTAL PARAMETERS DURING FRACTIONATED IRRADIATION IN HUMAN SQUAMOUS CELL CARCINOMA XENOGRAFTS
EXPLORATORY STUDY OF THE PROGNOSTIC VALUE OF MICROENVIRONMENTAL PARAMETERS DURING FRACTIONATED IRRADIATION IN HUMAN SQUAMOUS CELL CARCINOMA XENOGRAFTS
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DOI：
10.1016/j.ijrobp.2011.02.015
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发表时间：
2011-07-15
影响因子：
7
通讯作者：
Zips, Daniel
中科院分区：
文献类型：
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作者：
Yaromina, Ala;Kroeber, Theresa;Zips, Daniel
目的：探讨分次照射前和照射中微环境参数对局部肿瘤控制的预后价值。方法与材料：将6株人鳞状细胞癌(HSCC)细胞株移植到裸鼠右后肢皮下。在6周内对肿瘤进行30次照射。照射后120天测定肿瘤局部控制率。放射反应被量化为治愈50%肿瘤的剂量(TCD(50))。同时，注射低氧标志物匹莫硝唑和灌注标志物Hoechst 33342后，切除未治疗和照射的肿瘤，进行组织学评价。结果：在分次照射过程中，大多数肿瘤细胞的乏氧减少。在分次照射过程中，血流灌注分数和血管面积变化不大。治疗前、照射后3次和5次后的组织学参数与照射后6周内30次照射后的TCD50无显著相关性(p>；0.05)。低氧体积和10次分割后的灌流血管与分割后局部肿瘤控制显著相关(分别为p=0.018和p=0.019)。结论：这项探索性研究的结果表明，与治疗前参数相比，在治疗过程中测定微环境参数可以提供更好的预后信息，这值得在实验和临床研究中进一步研究和证实。(C)2011年爱思唯尔公司。
Purpose: To explore the prognostic value of microenvironmental parameters for local tumor control determined before and during fractionated irradiation.Methods and Materials: 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.Results: 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 TCD50 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.Conclusions: 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. (C) 2011 Elsevier Inc.