Endo Masahiro, Johkoh Takeshi, Kimura Kazuhiko, Yamamoto Nobuyuki
Division of Diagnostic Radiology, Shizuoka City Hospital, Shizuoka, Japan.
Lung Cancer. 2006 May;52(2):135-40. doi: 10.1016/j.lungcan.2006.02.002. Epub 2006 Mar 29.
Gefitinib (Iressatrade mark) is an epidermal growth factor receptor tyrosine kinase inhibitor that has been approved for the treatment of lung cancer in Japan, however, after marketing several cases of severe pulmonary toxicity were reported. The West Japan Thoracic Oncology Group conducted an independent survey of acute pulmonary toxicity and interstitial lung disease (ILD) caused by gefitinib in its member's institutions. The purpose of this study was to clarify the image characteristics of ILD caused by the molecular-targeting drug gefitinib. A total of 1976 patients had been treated with gefitinib between August and December 2002, and 102 of them were suspected of having acute pulmonary toxicity and ILD. A final definite diagnosis of gefitinib-induced ILD was made by at least three radiologists based on a review and analysis of the chest radiography and CT findings plus the clinical data in the medical records. The imaging findings were classified into four patterns: (A) a nonspecific area with ground-glass attenuation, (B) a multifocal area of airspace consolidations, (C) patchy distribution of ground-glass attenuation accompanied by interlobar septal thickening, and (D) extensive bilateral ground-glass attenuation or airspace consolidations with traction bronchiectasis. CT as well as chest radiography had been performed in 65 of the 102 patients at the onset of ILD, and chest radiography alone had been performed in 26. After excluding 11 cases with insufficient data and 21 cases concluded to be other pulmonary diseases, 70 patients were diagnosed with gefitinib-induced ILD. Finally, the diagnostic image findings were classified as pattern A in 29 cases, pattern B in 7 cases, pattern C in 3 cases, pattern D in 20 cases and others in 11 cases. The CT images were classified as pattern A, B, C, and D in 24, 7, 1, and 12 cases, respectively. The mortality rate was significantly higher in the patients with pattern D than the other patterns. Pattern D were thought to represent the features of diffuse alveolar damage. In conclusion, the molecular-targeting drug gefitinib induces pulmonary toxicity at a certain rate and the imaging findings of ILD induced by gefitinib are similar to those of pulmonary toxicity induced by conventional antineoplastic agents.
吉非替尼（易瑞沙商标）是一种表皮生长因子受体酪氨酸激酶抑制剂，在日本已被批准用于治疗肺癌，然而，上市后有几例严重肺部毒性的报告。日本西部胸部肿瘤学组在其成员机构中对吉非替尼引起的急性肺部毒性和间质性肺病（ILD）进行了独立调查。本研究的目的是阐明分子靶向药物吉非替尼引起的ILD的影像特征。2002年8月至12月期间共有1976例患者接受了吉非替尼治疗，其中102例怀疑有急性肺部毒性和ILD。至少三名放射科医生根据胸部X线片和CT表现以及病历中的临床资料进行回顾和分析，最终明确诊断为吉非替尼诱发的ILD。影像表现分为四种类型：（A）磨玻璃样衰减的非特异性区域；（B）气腔实变的多灶性区域；（C）伴有叶间间隔增厚的磨玻璃样衰减的斑片状分布；（D）广泛的双侧磨玻璃样衰减或气腔实变伴牵拉性支气管扩张。102例ILD发病时65例同时进行了CT和胸部X线检查，26例仅进行了胸部X线检查。排除11例资料不足和21例诊断为其他肺部疾病的病例后，70例患者被诊断为吉非替尼诱发的ILD。最后，诊断影像表现分类为：A类29例，B类7例，C类3例，D类20例，其他11例。CT图像分类为：A类24例，B类7例，C类1例，D类12例。D类患者的死亡率显著高于其他类型。D类被认为代表弥漫性肺泡损伤的特征。总之，分子靶向药物吉非替尼会以一定比例诱发肺部毒性，吉非替尼诱发的ILD的影像表现与传统抗肿瘤药物诱发的肺部毒性的影像表现相似。
