Adaptive radiotherapy for locally advanced non-small cell lung cancer, can we predict when and for whom?

<b>Background.</b> Adaptive radiotherapy (ART) could be a tool to reduce toxicity and to facilitate dose escalation in stage III NSCLC. Our aim was to identify the most appropriate time and potential benefit of ART.<b>Material and methods.</b> We analyzed volume reduction and dosimetric consequences of 41 patients who were treated with concurrent (cCRT) (n = 21) or sequential (sCRT) chemoradiotherapy to a median dose of 70 Gy, 2 Gy/F. At every treatment fraction a cone-beam CT (CBCT) was performed. The gross tumor volume (GTV-T) was adapted (exclusion of lymph nodes) to create the GTV-T-F1. Every fifth fraction (F5–F30), the GTV-T-F1 was adapted on the CBCT to create a GTV-T-Fx. Dose volume histograms were recalculated for every GTV-T-Fx, enabling to create lookup tables to predict the theoretical dosimetric advantage on common lung dose constraints.<b>Results.</b> The average GTV reduction was 42.1% (range 4.0–69.3%); 50.1% and 33.7% for the cCRT and sCRT patients, respectively. A linear relationship between GTV-T-F1 volume and absolute volume decrease was found for both groups. The mean V5, V20, V30 and mean lung dose increased by 0.8, 3.1, 5.2 and 3.4%, respectively. A larger increase (p &lt; 0.05) was observed for peripheral tumors and cCRT. Lookup tables were generated. <i>Conclusion.</i> ART offers the most beneficial dosimetric effects when performed around fraction 15, especially for patients with a large initial GTV-T treated by cCRT.

<b>研究背景。</b> 自适应放疗（Adaptive Radiotherapy, ART）可作为降低毒性反应、实现III期非小细胞肺癌（Non-Small Cell Lung Cancer, NSCLC）剂量递增的治疗工具。本研究旨在明确自适应放疗最适宜的实施时机及其潜在获益。<b>材料与方法。</b> 本研究分析了41例接受同步放化疗（concurrent chemoradiotherapy, cCRT，n=21）或序贯放化疗（sequential chemoradiotherapy, sCRT）的患者的肿瘤体积变化与剂量学效应，所有患者的中位总照射剂量为70 Gy，分割剂量为2 Gy/次。每次治疗分割均行锥形束CT（Cone-Beam CT, CBCT）扫描。对大体肿瘤体积（Gross Tumor Volume, GTV-T，不含淋巴结区域）进行适配调整，得到初始适配大体肿瘤体积GTV-T-F1。每间隔5个治疗分割（F5至F30），基于本次CBCT扫描结果对GTV-T-F1进行再次适配，得到各时间点的大体肿瘤体积GTV-T-Fx。针对每一例GTV-T-Fx重新计算剂量体积直方图（Dose Volume Histogram, DVH），进而构建查找表以预测常见肺组织剂量限制条件下的理论剂量学优势。<b>研究结果。</b> 所有患者的大体肿瘤体积平均缩小42.1%（范围4.0%~69.3%）；其中同步放化疗组与序贯放化疗组分别缩小50.1%与33.7%。两组均观察到初始GTV-T-F1体积与绝对体积缩小量之间存在线性相关关系。平均V5、V20、V30及平均肺剂量分别升高0.8%、3.1%、5.2%与3.4%。外周型肿瘤患者及同步放化疗组的上述指标升高更为显著（p<0.05）。本研究成功构建了上述剂量学预测查找表。<i>结论。</i> 自适应放疗在治疗分割第15次左右实施时可获得最优剂量学获益，尤其适用于初始GTV-T体积较大且接受同步放化疗的患者。