Yang Yong, Xing Lei
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305-5847, USA.
Med Phys. 2005 Jun;32(6):1473-84. doi: 10.1118/1.1924312.
It is well known that the spatial biology distribution (e.g., clonogen density, radiosensitivity, tumor proliferation rate, functional importance) in most tumors and sensitive structures is heterogeneous. Recent progress in biological imaging is making the mapping of this distribution increasingly possible. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data into intensity modulated radiation therapy (IMRT) inverse planning. In order to implement this, we first derive a general formula for determining the desired dose to each tumor voxel for a known biology distribution of the tumor based on a linear-quadratic model. The desired target dose distribution is then used as the prescription for inverse planning. An objective function with the voxel-dependent prescription is constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered phenomenologically when constructing the objective function. Two cases with different hypothetical biology distributions are used to illustrate the new inverse planning formalism. For comparison, treatments with a few uniform dose prescriptions and a simultaneous integrated boost are also planned. The biological indices, tumor control probability (TCP) and normal tissue complication probability (NTCP), are calculated for both types of plans and the superiority of the proposed technique over the conventional dose escalation scheme is demonstrated. Our calculations revealed that it is technically feasible to produce deliberately nonuniform dose distributions with consideration of biological information. Compared with the conventional dose escalation schemes, the new technique is capable of generating biologically conformal IMRT plans that significantly improve the TCP while reducing or keeping the NTCPs at their current levels. Biologically conformal radiation therapy (BCRT) incorporates patient-specific biological information and provides an outstanding opportunity for us to truly individualize radiation treatment. The proposed formalism lays a technical foundation for BCRT and allows us to maximally exploit the technical capacity of IMRT to more intelligently escalate the radiation dose.
众所周知,大多数肿瘤和敏感结构中的生物学空间分布(如克隆原密度、放射敏感性、肿瘤增殖率、功能重要性)是不均匀的。生物成像技术的最新进展使得绘制这种分布情况越来越可行。这项工作的目的是建立一个理论框架,以便将空间生物学数据定量纳入调强放射治疗(IMRT)逆向计划中。为了实现这一点,我们首先基于线性二次模型推导出一个通用公式,用于确定已知肿瘤生物学分布情况下每个肿瘤体素的期望剂量。然后将期望的靶区剂量分布用作逆向计划的处方。通过纳入非均匀剂量处方,构建一个与体素相关处方的目标函数。在构建目标函数时,还从现象学角度考虑了敏感结构中的功能单元密度分布。使用两种具有不同假设生物学分布的情况来说明新的逆向计划形式。为了进行比较,还计划了几种均匀剂量处方和同步整合加量的治疗方案。计算了两种类型计划的生物学指标,即肿瘤控制概率(TCP)和正常组织并发症概率(NTCP),并证明了所提出技术相对于传统剂量递增方案的优越性。我们的计算表明,考虑生物学信息来产生故意不均匀的剂量分布在技术上是可行的。与传统剂量递增方案相比,新技术能够生成生物学适形的IMRT计划,显著提高TCP,同时将NTCP降低或保持在当前水平。生物学适形放射治疗(BCRT)纳入了患者特异性生物学信息,为我们真正实现放射治疗个体化提供了绝佳机会。所提出的形式为BCRT奠定了技术基础,使我们能够最大限度地利用IMRT的技术能力,更智能地提高放射剂量。