Malinen Eirik, Søvik Aste, Hristov Dimitre, Bruland Øyvind S, Olsen Dag Rune
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
Phys Med Biol. 2006 Oct 7;51(19):4903-21. doi: 10.1088/0031-9155/51/19/012. Epub 2006 Sep 18.
In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO(2)-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO(2)-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO(2) Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO(2) values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields and step-and-shoot intensity levels). Simulated random and systematic errors in the pO(2)-related images reduced the TCP for the non-uniform dose prescription. In conclusion, improved tumour control of hypoxic tumours by dose redistribution may be expected following hypoxia imaging, tumour control predictions, inverse treatment planning and IMRT.
在当前工作中，提出了在包含功能性肿瘤成像、肿瘤控制预测、逆向治疗计划和调强放射治疗（IMRT）的框架内对缺氧肿瘤进行生物适应性放射治疗的概念。采用了对一只犬鼻区自发性肉瘤的动态对比增强磁共振成像（DCEMRI）。假设肿瘤中的示踪剂浓度与氧张力相关，并与Eppendorf组织血氧仪测量结果进行比较。基于磁共振分析得出的与pO₂相关的图像，通过分割程序将肿瘤分为四个区域。由此可以得出用于IMRT计划的DICOM结构集。为了展示非均匀肿瘤剂量的可能优势，引入了四个肿瘤区域之间的剂量重新分配。通过保持肿瘤的平均剂量等于传统目标剂量来限制剂量重新分配。产生最佳肿瘤控制概率（TCP）的区域剂量被用作逆向计划系统的输入，其中计划基础是来自磁共振分析的与pO₂相关的肿瘤图像。对均匀（传统）和非均匀IMRT计划进行了物理和生物学评分。评估了区域图像中随机和系统误差的后果。示踪剂浓度和pO₂ Eppendorf测量的归一化频率分布没有显著差异。根据磁共振分析，28%的肿瘤pO₂值小于5毫米汞柱。非均匀剂量处方后的最佳TCP比均匀剂量处方后的高出约四倍。逆向计划得出的非均匀IMRT剂量分布的TCP比均匀分布的高出三倍。TCP和基于剂量的计划质量取决于逆向计划程序中定义的IMRT参数（射野和步进式强度水平）。与pO₂相关图像中模拟的随机和系统误差降低了非均匀剂量处方的TCP。总之，在进行缺氧成像、肿瘤控制预测、逆向治疗计划和IMRT后，通过剂量重新分配有望改善缺氧肿瘤的控制。
