Tang Xingni, Shen Yichao, Meng Yinnan, Hou Liqiao, Zhou Chao, Yu Changhui, Jia Haijian, Wang Wei, Ren Ge, Cai Jing, Li X Allen, Yang Haihua, Kong Feng-Ming Spring
Laboratory of Cellular and Molecular Radiation Oncology, Radiation Oncology Institute of Enze Medical Health Academy, Department of Radiation Oncology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, China.
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
Ann Palliat Med. 2021 Mar;10(3):2832-2842. doi: 10.21037/apm-20-1116. Epub 2021 Feb 5.
To quantitatively evaluate lung damage after treatment of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and stereotactic body radiotherapy (SBRT) in patients with nonsmall cell lung cancer (NSCLC), and compare that of SBRT only treatment.
Eligible patients from an IRB-approved prospective clinical trial had one month of EGFRTKIs treatment followed by SBRT (TKI + SBRT) and with 3-month follow-up high resolution CT. NSCLC patients treated with SBRT alone during the same time period without EGFR-TKIs or other systemic therapies were identified as controls. The lung damage was assessed clinically by pneumonitis and quantitatively using by CT intensity (Hounsfield unit, HU) changes. The mean HU values were extracted for regions of the lungs receiving the same dose range at 10 Gy intervals to generate dose-response curves (DRC). The relationship of HU changes and radiation dose was modeled using a Probit model.
Four out of 20 (25%) TKI + SBRT patients and none of 19 (0%) SBRT alone patients had developed grade 2 and above pneumonitis (P=0.053), respectively. Sixty percent of TKI + SBRT patients and 30% SBRT alone patients had HU changes of the normal lung density >200 HU, respectively. There were significant differences in the DRC and in lung HU changes between the two groups (all P<0.05). The physical dose for a 50% complication risk (TD50) of CT lung damage was 52 Gy (CI: 46-59) in TKI + SBRT group versus 72 Gy (CI: 58-107) in SBRT alone group (P<0.01).
Compared to patients treated with SBRT alone, patients treated with EGFR-TKIs followed by SBRT were more incline to develop radiation pneumonitis, and resulted in greater lung CT intensity changes and steeper dose-CT lung damage response relationship at 3 months post treatment. Future study with larger number of patients and longer follow-up period is warranted to validate this finding.
为了定量评估非小细胞肺癌（NSCLC）患者接受表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）和立体定向体部放疗（SBRT）治疗后的肺损伤情况，并与单纯SBRT治疗的情况进行比较。
从一项经机构审查委员会批准的前瞻性临床试验中选取符合条件的患者，先进行1个月的EGFR-TKIs治疗，随后进行SBRT（TKI + SBRT），并在治疗后3个月进行高分辨率CT随访。将同期接受单纯SBRT治疗且未使用EGFR-TKIs或其他全身治疗的NSCLC患者作为对照。通过肺炎临床评估肺损伤情况，并利用CT密度（亨氏单位，HU）变化进行定量评估。以10 Gy间隔提取接受相同剂量范围照射的肺区域的平均HU值，以生成剂量反应曲线（DRC）。使用概率模型对HU变化与辐射剂量之间的关系进行建模。
20例TKI + SBRT患者中有4例（25%）发生2级及以上肺炎，而19例单纯SBRT患者中无一例发生（0%）（P = 0.053）。TKI + SBRT患者中有60%、单纯SBRT患者中有30%的正常肺密度HU变化>200 HU。两组之间的DRC和肺HU变化存在显著差异（所有P < 0.05）。TKI + SBRT组CT肺损伤50%并发症风险（TD50）的物理剂量为52 Gy（CI：46 - 59），而单纯SBRT组为72 Gy（CI：58 - 107）（P < 0.01）。
与单纯接受SBRT治疗的患者相比，先接受EGFR-TKIs治疗后再接受SBRT治疗的患者更易发生放射性肺炎，且在治疗后3个月导致更大的肺CT密度变化以及更陡峭的剂量-CT肺损伤反应关系。有必要开展纳入更多患者且随访期更长的未来研究来验证这一发现。
