摘要
表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)已被批准用于非小细胞肺癌(NSCLC)治疗。本文报道1例42岁ⅢA期EGFR突变NSCLC男性患者,使用奥希替尼治疗4.5个月后切除肿瘤,术后继续奥希替尼辅助治疗,复查未见复发或转移,提示奥希替尼作为可切除Ⅲ期NSCLC的新辅助治疗可能有效。
肺癌的发病率和病死率均位于恶性肿瘤前
患者男性,42岁,无吸烟史或其他疾病史,2021年7月30日因咳嗽咳痰1年余入院。患者无痰中带血或咯血,无胸痛、胸闷、气短,无发热、盗汗、全身乏力症状。肿瘤标志物癌胚抗原(carcinoembryonic antigen, CEA)72.43 ng·m
图1 奥希替尼治疗前后患者胸部CT图
Fig.1 Chest CT images of the patient before and after osimertinib treatment
注: (A)奥希替尼治疗前(2021年7月30日)CT显示右肺下叶软组织密度肿块影,大小约15.2 cm×10.1 cm×14.8 cm;(B)奥希替尼治疗前(2021年7月30日)CT显示右肺下叶部分支气管闭塞,肿瘤与肺动脉、肺静脉关系密切;(C)奥希替尼治疗后(2022年1月5日)CT显示肿瘤明显缩小,横断面大小约6.2 cm×4.6 cm;(D)奥希替尼治疗后(2022年1月5日)CT显示肿瘤与肺动脉、肺静脉有明显间隙。
Note: (A) Before osimertinib treatment (July 30, 2021),CT showed the tumor in the lower lobe of the right lung, in a size of 15.2 cm×10.1 cm×14.8 cm; (B) Before osimertinib treatment (July 30, 2021), CT showed partial bronchial occlusion in the lower lobe of the right lung, and the tumor was closely related to the pulmonary artery and pulmonary vein; (C) After osimertinib treatment (January 5, 2022), CT showed significant shrinkage of the tumor, with a cross-sectional size of about 6.2 cm × 4.6 cm; (D) After osimertinib treatment (January 5, 2022), CT showed that the tumor had significant gaps with pulmonary arteries and pulmonary veins.
图2 穿刺活检组织苏木精-伊红染色和免疫组化检测结果及术后病理切片染色
Fig.2 The hematoxylin and eosin stained image and immunohistochemical results of lung biopsy specimen and the stained image of the resected lung tissue
注: (A)肺活检标本苏木精-伊红染色图像(×200);(B)肺活检标本免疫组化TTF-1图像(×200);(C)肺活检标本免疫组化CK7图像(×200);(D)肺活检标本免疫组化NapsinA图像(×200);(E)肺活检标本免疫组化Ki-67图像(×200);(F)术后切除肺组织苏木精-伊红染色切片(×200)。
Note: (A) Hematoxylin and eosin stained image of lung biopsy specimen (×200); (B) IHC image of TTF-1 in lung biopsy specimen (×200); (C) IHC image of CK7 in lung biopsy specimen (×200); (D)IHC image of NapsinA in lung biopsy specimen (×200); (E)IHC image of Ki-67 in lung biopsy specimen (×200); (F)Hematoxylin and eosin stained image of the resected lung tissue (×200).
检测内容 | 样本类型 | 检测结果 | 结果判读 | |
---|---|---|---|---|
EGFR Exon18 | 基因突变 | 肿瘤组织 | — | 无突变 |
EGFR Exon19 | 基因突变 | 肿瘤组织 | — | 无突变 |
EGFR Exon20 | 基因突变 | 肿瘤组织 | — | 无突变 |
EGFR Exon21 | 基因突变 | 肿瘤组织 |
c.2573T>G p.L858R | 突变 |
ALK | 基因重排 | 肿瘤组织 | — | 阴性 |
ROS1 | 基因重排 | 肿瘤组织 | — | 阴性 |
注: 病理诊断结果:肺浸润性腺癌;肿瘤细胞含量:35%;检测时间:2021年8月9日。
Note: Pathological diagnosis: lung invasive adenocarcinoma; Tumor cell content: 35%; Detection time: August 9, 2021.
患者于2022年1月5日复查胸部强化CT提示右肺下叶肿物明显缩小,横断面大小约6.2 cm×4.6 cm(图
图3 切除的肺组织及肿物标本(肿瘤大小约6.0 cm×5.0 cm×4.5 cm)
Fig.3 The resected lung tissue and tumor specimen (size: 6.0 cm×5.0 cm×4.5 cm)
检测内容 | 样本类型 | 检测结果 | 结果判读 | |
---|---|---|---|---|
EGFR Exon18 | 基因突变 | 肿瘤组织 | — | 无突变 |
EGFR Exon19 | 基因突变 | 肿瘤组织 | — | 无突变 |
EGFR Exon20 | 基因突变 | 肿瘤组织 | — | 无突变 |
EGFR Exon21 | 基因突变 | 肿瘤组织 |
c.2573T>G p.L858R 45.80% | 突变 |
KRAS Exon2(codon12/13) | 基因突变 | 肿瘤组织 | — | 无突变 |
KRAS Exon3(codon61) | 基因突变 | 肿瘤组织 | — | 无突变 |
ALK | 基因重排 | 肿瘤组织 | — | 阴性 |
ROS1 | 基因重排 | 肿瘤组织 | — | 阴性 |
注: 病理诊断结果:肺浸润性腺癌;肿瘤细胞含量:20%;检测时间:2022年1月30日。
Note: Pathological diagnosis: lung invasive adenocarcinoma; Tumor cell content: 20%; Detection time: January 30, 2022.
图4 术后4个月复查胸部CT
Fig.4 The chest CT images at 4 months after surgery
注: (A) 2022年5月24日纵隔窗未见复发;(B) 2022年5月24日肺窗未见复发。
Note: (A)No recurrence was observed in mediastinal window on May 24, 2022;(B)No recurrence in the pulmonary window on May 24, 2022.
肺恶性肿瘤局部晚期患者行姑息性切除获益欠佳。针对潜在可接受手术的局部晚期NSCLC患者,临床医生可给予术前新辅助治疗后再行手术。新辅助治疗可降低肿瘤分期,增加根治手术的成功率,提高患者术后生活质量和生存
本例患者肿瘤巨大,且肿瘤与血管关系密切。经MDT讨论,肿瘤潜在可切除,需行术前新辅助治疗。患者拒绝化疗,且基因检测结果为EGFR 21外显子L858R阳性,因而直接选择第三代EGFR-TKI奥希替尼进行治疗。治疗4.5个月后,CT示肿瘤明显缩小。再次经MDT讨论,患者可以进行手术。肿瘤标志物水平可反映肿瘤细胞活性。本例患者肿瘤标志物CEA、CYFRA211及NSE水平在奥希替尼治疗后明显降低,也提示奥希替尼在本病例中有确切疗效。本例患者在新辅助治疗期间出现轻度皮疹及腹泻,对症治疗后好转。患者服用奥希替尼4.5个月后行胸部强化CT检查,与治疗前比较,肿瘤阴影较前缩小。但奥希替尼在治疗肿瘤有效的同时是否对肿瘤周围组织造成类似的影响暂无相关报道。本例患者术中血管、气管及周围组织解剖结构较清晰,组织间隙较为疏松,手术切除顺利。
在新辅助靶向治疗领域,目前已有多项研究正在进行。CTONG 1103研
本例患者使用奥希替尼术前新辅助治疗取得了较好的效果,为潜在不可切除的EGFR突变NSCLC患者提供了一定参考。奥希替尼用于EGFR敏感突变型NSCLC患者术前新辅助治疗尚有许多问题需要解决,例如术前新辅助治疗时长、术后辅助治疗方案及时间均有待确定,服用靶向药物是否对血管、气管及周围组织产生影响尚不确定。对于EGFR突变型患者,奥希替尼是否可替代新辅助化、放疗等,仍需更多循证医学证据的支持和验证。
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