Amin A E, Wheldon T E, O'Donoghue J A, Barrett A
Department of Radiation Oncology, University of Glasgow, UK.
Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):323-30. doi: 10.1016/0360-3016(93)90244-p.
A model is presented for calculating combinations of targeted 131I and total body irradiation, followed by bone marrow rescue, in the treatment of tumors of different radiosensitivity. The model is used to evaluate the role of the total body irradiation component in the optimal combination regime as a function of the radiosensitivity of the tumor cells.
A microdosimetric model was used to calculate absorbed dose in small tumors and micrometastases when uniformly targeted by the radionuclide 131I. Cell kill was calculated from absorbed dose using an extended version of the linear quadratic model. The addition of varying total doses of total body irradiation, assuming 2 Gy fractions, was also calculated using the linear quadratic model. The net cell kill from combined modality (targeted 131I and total body irradiation) was computed for varying proportions of the two components, for a range of tumor sizes, restricting the total radiation dose to within tolerance for a full-course TBI regime (approximately 14 Gy total) in all cases. The calculations were repeated for a range of presumed tumor uptakes of the targeting agent and for a range of tumor radiosensitivities, typical of those reported for tumor cells of differing type in culture. Optimal regimes were identified as those predicted to yield a high probable tumor cure rate (evaluated using a Poisson statistical model) for all tumor sizes.
The analysis supports earlier model studies which predicted that systemic combination treatment with targeted 131I and total body irradiation would be superior to either component used alone. The intrinsic tumor radiosensitivity is found to be a factor which influences the optimal combination of the 131I and external beam total body irradiation components. The total body irradiation component is greater in optimal regimes treating radio-resistant than radiosensitive tumors. However, an obligatory total body irradiation component is also predicted for more radiosensitive tumors; the analysis suggests that the total body irradiation component should in no circumstances be less than 2 x 2 Gy, whilst practical arguments exist in favor of higher doses.
Total body irradiation is an obligatory component for effective systemic treatment of disseminated malignant tumors to which 131I can be selectively targeted. Clinical studies applying this strategy to the treatment of neuroblastoma by 131I targeted by meta-iodo-benguanidine (mIBG), total body irradiation and bone marrow rescue are now in progress.
提出一种模型，用于计算在不同放射敏感性肿瘤的治疗中，靶向131I与全身照射相结合并随后进行骨髓救援的组合方式。该模型用于评估全身照射部分在最佳组合方案中作为肿瘤细胞放射敏感性函数的作用。
使用微剂量模型计算放射性核素131I均匀靶向时小肿瘤和微转移灶中的吸收剂量。使用线性二次模型的扩展版本根据吸收剂量计算细胞杀伤情况。还使用线性二次模型计算了假设为2Gy分次剂量的不同全身照射总剂量的添加情况。针对不同大小的肿瘤，计算了两种成分不同比例下联合治疗方式（靶向131I和全身照射）的净细胞杀伤情况，在所有情况下将总辐射剂量限制在全疗程全身照射方案的耐受范围内（约14Gy总量）。针对一系列假定的靶向剂肿瘤摄取量和一系列肿瘤放射敏感性（典型的是培养中不同类型肿瘤细胞报道的放射敏感性）重复进行了计算。将最佳方案确定为预计对所有肿瘤大小都能产生高可能肿瘤治愈率（使用泊松统计模型评估）的方案。
该分析支持早期模型研究，该研究预测靶向131I与全身照射的全身联合治疗将优于单独使用的任何一种成分。发现肿瘤固有放射敏感性是影响131I和外照射全身照射成分最佳组合的一个因素。在治疗放射抗性肿瘤的最佳方案中，全身照射部分比放射敏感性肿瘤中的更大。然而，对于放射敏感性更高的肿瘤也预测有必要进行全身照射部分；分析表明，全身照射部分在任何情况下都不应小于2×2Gy，同时实际情况支持更高剂量。
全身照射是对可选择性靶向131I的播散性恶性肿瘤进行有效全身治疗的必要组成部分。目前正在进行将该策略应用于用间碘苄胍（mIBG）靶向的131I、全身照射和骨髓救援治疗神经母细胞瘤的临床研究。
