Armstrong J G, Zelefsky M J, Leibel S A, Burman C, Han C, Harrison L B, Kutcher G J, Fuks Z Y
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Ann Oncol. 1995 Sep;6(7):693-7. doi: 10.1093/oxfordjournals.annonc.a059286.
Local failure is a major obstacle to the cure of locally advanced non-small-cell lung cancer. 3-Dimensional conformal radiation therapy (3-DCRT) selects optimal treatment parameters to increase dose to tumor and reduce normal tissue dose, potentially permitting dose escalation. There are several ongoing trials of dose escalation using 3-Dimensional conformal radiation therapy for non-small-cell lung cancer. We performed this analysis to determine if data derived from dose volume histograms could be used as the basis for designing the method of dose escalation in these trials.
Between 1990 and 1993, 31 patients were treated with 3-DCRT and had complete normal tissue dose volume histograms created as part of the planning process. The stage distribution was stage I/II 13%, stage IIIa in 45%, and stage IIIb in 42%. The median radiation dose to gross disease was 70.2 Gy (52.2-72 Gy). Elective mediastinal irradiation (50.4 Gy) was administered to 52% (16/31) of patients.
The major toxicity encountered in this experience was pulmonary. Dose-volume-histogram data were used to analyze the predictors of toxicity and showed a correlation between risk of pulmonary toxicity and indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred in 38% (3/8) of pts with >30%of lung volume receiving > or =25 Gy, versus 4% (1/23) of pts. with < or = 30% lung receiving > or = 25 Gy (p=0.04). Grade 3 or higher pulmonary toxicity occurred in 29% (4/14) of patients with a predicted pulmonary normal tissue complication probability of 12% or higher versus 0% (0/17) in patients with a predicted probability of less than 12% (p=0.03). The single fatality occurred in a patient with a calculated pneumonitis probability of 85% and a high percent (49%) lung volume receiving >= 25 GY.
This preliminary experience demonstrates a correlation between lung dose-volume-histogram data and the risk of severe pulmonary toxicity. This provides an opportunity to modify the method of radiation dose escalation. Dose-volume-histogram data can allow escalation according to the risk to the lung parenchyma (which is the major organ of concern) rather than escalation according to tumor dose levels. Because of teh major inter-patient variability of intrathoracic tumor bulk and anatomic distribution, this strategy is intuitively appropriate. This approach may facilitate completion of dose escalation studies and identification of maximum tolerable pulmonary dose levels.
局部失败是局部晚期非小细胞肺癌治愈的主要障碍。三维适形放射治疗（3-DCRT）可选择最佳治疗参数，以增加肿瘤剂量并减少正常组织剂量，从而有可能实现剂量递增。目前有多项正在进行的关于使用三维适形放射治疗对非小细胞肺癌进行剂量递增的试验。我们进行这项分析是为了确定剂量体积直方图得出的数据是否可作为设计这些试验中剂量递增方法的基础。
1990年至1993年间，31例患者接受了3-DCRT治疗，并在计划过程中创建了完整的正常组织剂量体积直方图。分期分布为I/II期占13%，IIIa期占45%，IIIb期占42%。对大体肿瘤的中位放射剂量为70.2 Gy（52.2 - 72 Gy）。52%（16/31）的患者接受了选择性纵隔照射（50.4 Gy）。
该研究中遇到的主要毒性反应是肺部毒性。剂量体积直方图数据用于分析毒性预测因素，结果显示肺部毒性风险与肺实质剂量指标之间存在相关性。肺体积超过30%且接受≥25 Gy照射的患者中，38%（3/8）发生3级或更高等级的肺部毒性，而肺体积≤30%且接受≥25 Gy照射的患者中，这一比例为4%（1/23）（p = 0.04）。预测肺部正常组织并发症概率为12%或更高的患者中，29%（4/14）发生3级或更高等级的肺部毒性，而预测概率低于12%的患者中这一比例为0%（0/17）（p = 0.03）。唯一的死亡病例发生在一名计算得出肺炎概率为85%且肺体积接受≥25 Gy照射比例较高（49%）的患者身上。
这一初步研究表明肺剂量体积直方图数据与严重肺部毒性风险之间存在相关性。这为修改放射剂量递增方法提供了机会。剂量体积直方图数据可根据肺实质（主要关注器官）的风险进行递增，而不是根据肿瘤剂量水平递增。由于胸腔内肿瘤体积和解剖分布在患者之间存在较大差异，这种策略直观上是合适的。这种方法可能有助于完成剂量递增研究并确定最大可耐受肺部剂量水平。
