Schena Marina, La Rovere Erika, Solerio Dino, Bustreo Sara, Barone Carla, Daniele Lorenzo, Buffoni Lucio, Bironzo Paolo, Sapino Anna, Gasparri Guido, Ciuffreda Libero, Ricardi Umberto
Department of Onco-Hematology, Oncology Unit, San Giovanni Battista Hospital, Turin, Italy.
Tumori. 2012 Jul-Aug;98(4):451-7. doi: 10.1177/030089161209800409.
Multimodal therapy is a keystone of care in advanced esophageal cancer. Although neoadjuvant chemoradiotherapy is known to provide a survival advantage in selected cases, reliable prognostic and response predictive factors remain elusive. We report the outcome in a series of esophageal cancer patients treated at our center and the results of a retrospective analysis of epidermal growth factor receptor (EGFR) expression and EGFR/HER2 gene copy numbers taken as possible prognostic and predictive factors.
Between 2001 and 2009, a total of 40 consecutive patients (34 men and 6 women; median age, 59 years) were treated for esophageal cancer.
cisplatin, 80 mg/m² day 1, and 5-fluorouracil, 800 mg/m²/24 h on days 1-5, every 21 days, concomitant with 3D-conformal radiotherapy (54-59.4 in 30-33 fractions) for three up to four cycles. Surgery was performed in eligible patients 6-8 weeks after chemoradiation. EGFR expression and EGFR/HER2 amplification and gene copy number were studied by immunohistochemical analysis and fluorescence in situ hybridization, respectively.
Acceptable toxicity following chemoradiation was recorded, with G3-G4 hematological toxicity in 20% of patients and G3-G4 dysphagia in less than 10%; 14 (35%) patients achieved complete response and 19 (48%) partial response; 18 underwent surgery after chemoradiation, of which 8 (20%) achieved pathologic complete response. The median survival was 29 months (95% CI, 25.7-32.1): 42 months for the resected and 20 for the unresected patients. EGFR and HER2 analysis in 28 patients showed that 89% had immunohistochemical EGFR expression, with 5 cases of EGFR and 10 of HER2 gene gain without a significant difference in response rate and survival in these patient subgroups.
Our results suggest a better outcome in patients who underwent surgery after chemoradiation. A larger sample size is necessary to clarify the role of EGFR and HER2 gene gain in predict response and survival.
多模式治疗是晚期食管癌治疗的关键。尽管新辅助放化疗已知在特定病例中可提供生存优势,但可靠的预后和反应预测因素仍不明确。我们报告了在我们中心接受治疗的一系列食管癌患者的结果,以及对表皮生长因子受体(EGFR)表达和EGFR/HER2基因拷贝数进行回顾性分析的结果,将其作为可能的预后和预测因素。
2001年至2009年期间,共有40例连续的患者(34例男性和6例女性;中位年龄59岁)接受了食管癌治疗。
顺铂,80mg/m²,第1天;5-氟尿嘧啶,800mg/m²/24小时,第1 - 5天,每21天重复一次,同时进行三维适形放疗(54 - 59.4Gy,分30 - 33次),共三至四个周期。符合条件的患者在放化疗后6 - 8周进行手术。分别通过免疫组织化学分析和荧光原位杂交研究EGFR表达以及EGFR/HER2扩增和基因拷贝数。
放化疗后记录到可接受的毒性,20%的患者出现3 - 4级血液学毒性,不到10%的患者出现3 - 4级吞咽困难;14例(35%)患者达到完全缓解,19例(48%)部分缓解;18例患者在放化疗后接受了手术,其中8例(20%)达到病理完全缓解。中位生存期为29个月(95%CI,25.7 - 32.1):切除患者为42个月,未切除患者为20个月。对28例患者的EGFR和HER2分析显示,89%的患者免疫组织化学检测EGFR表达阳性,5例EGFR基因增加,10例HER2基因增加,这些患者亚组的反应率和生存率无显著差异。
我们的结果表明放化疗后接受手术的患者预后较好。需要更大样本量来阐明EGFR和HER2基因增加在预测反应和生存方面的作用。