Guerrero M, Li X Allen
Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Phys Med Biol. 2003 Oct 21;48(20):3307-26. doi: 10.1088/0031-9155/48/20/004.
Numerous studies of early-stage breast cancer treated with breast conserving surgery (BCS) and radiotherapy (RT) have been published in recent years. Both external beam radiotherapy (EBRT) and/or brachytherapy (BT) with different fractionation schemes are currently used. The present RT practice is largely based on empirical experience and it lacks a reliable modelling tool to compare different RT modalities or to design new treatment strategies. The purpose of this work is to derive a plausible set of radiobiological parameters that can be used for RT treatment planning. The derivation is based on existing clinical data and is consistent with the analysis of a large number of published clinical studies on early-stage breast cancer. A large number of published clinical studies on the treatment of early breast cancer with BCS plus RT (including whole breast EBRT with or without a boost to the tumour bed, whole breast EBRT alone, brachytherapy alone) and RT alone are compiled and analysed. The linear quadratic (LQ) model is used in the analysis. Three of these clinical studies are selected to derive a plausible set of LQ parameters. The potential doubling time is set a priori in the derivation according to in vitro measurements from the literature. The impact of considering lower or higher T(pot) is investigated. The effects of inhomogeneous dose distributions are considered using clinically representative dose volume histograms. The derived LQ parameters are used to compare a large number of clinical studies using different regimes (e.g., RT modality and/or different fractionation schemes with different prescribed dose) in order to validate their applicability. The values of the equivalent uniform dose (EUD) and biologically effective dose (BED) are used as a common metric to compare the biological effectiveness of each treatment regime. We have obtained a plausible set of radiobiological parameters for breast cancer: alpha = 0.3 Gy(-1), alpha/beta = 10 Gy and sub-lethal damage repair time T(rep) = 1 h (mono-exponential behaviour is assumed). This set of parameters is consistent with in vitro experiments and with previously reported analyses. Using this set of parameters, we have found that most of the studies, using BCS plus whole breast RT and a boost to the tumour bed, have EUDs ranging from 60-70 Gy. No correlation is found between BED and the local recurrence rate. The treatments of BCS plus brachytherapy alone have a wide range of EUD (30-50 Gy), which is significantly lower than the treatments with whole breast EBRT plus a boost of the tumour bed. The studies with different fractionation schemes for whole breast EBRT also show a significant variation of EUD. Carefully designed clinical studies with large numbers of patients are required to determine clinically the relative effectiveness of these treatment variations. The derived LQ parameter set based on clinical data is consistent with in vitro experiments and previous studies. As demonstrated in the present work, these radiobiological parameters can be potentially useful in radiotherapy treatment planning for early breast cancer, e.g., in comparing biological effectiveness of different radiotherapy modalities, different fractionation schemes and in designing new treatment strategies.
近年来，发表了许多关于早期乳腺癌保乳手术（BCS）和放疗（RT）的研究。目前使用的是具有不同分割方案的外照射放疗（EBRT）和/或近距离放疗（BT）。目前的放疗实践很大程度上基于经验，缺乏可靠的建模工具来比较不同的放疗方式或设计新的治疗策略。这项工作的目的是推导一组合理的放射生物学参数，可用于放疗治疗计划。该推导基于现有临床数据，并与对大量已发表的早期乳腺癌临床研究的分析一致。收集并分析了大量关于BCS加RT（包括对瘤床进行或不进行增量照射的全乳EBRT、单纯全乳EBRT、单纯近距离放疗）和单纯RT治疗早期乳腺癌的已发表临床研究。分析中使用线性二次（LQ）模型。选择其中三项临床研究来推导一组合理的LQ参数。在推导过程中，根据文献中的体外测量结果预先设定潜在倍增时间。研究了考虑较低或较高T(pot)的影响。使用具有临床代表性的剂量体积直方图来考虑非均匀剂量分布的影响。所推导的LQ参数用于比较大量使用不同方案（例如，放疗方式和/或具有不同处方剂量的不同分割方案）的临床研究，以验证其适用性。等效均匀剂量（EUD）和生物有效剂量（BED）的值用作比较各治疗方案生物有效性的通用指标。我们获得了一组合理的乳腺癌放射生物学参数：α = 0.3 Gy(-1)，α/β = 10 Gy，亚致死损伤修复时间T(rep) = 1 h（假设为单指数行为）。这组参数与体外实验以及先前报道的分析一致。使用这组参数，我们发现大多数采用BCS加全乳RT并对瘤床进行增量照射的研究，其EUD范围为60 - 70 Gy。未发现BED与局部复发率之间存在相关性。单纯BCS加近距离放疗的治疗方案EUD范围较宽（30 - 50 Gy），明显低于全乳EBRT加瘤床增量照射的治疗方案。全乳EBRT不同分割方案的研究也显示EUD有显著差异。需要精心设计的、纳入大量患者的临床研究来临床确定这些治疗差异的相对有效性。基于临床数据推导的LQ参数集与体外实验和先前研究一致。如本研究所示，这些放射生物学参数在早期乳腺癌的放疗治疗计划中可能有用，例如，在比较不同放疗方式、不同分割方案的生物有效性以及设计新的治疗策略方面。
