新辅助化疗、靶向治疗联合手术治疗临床Ⅲ期EGFR阳性肺腺癌

doi:10.3877/cma.j.issn.2095-8773.2021.01.04

中华胸部外科电子杂志 ›› 2021, Vol. 08 ›› Issue (01) : 16 -20. doi: 10.3877/cma.j.issn.2095-8773.2021.01.04

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论著

新辅助化疗、靶向治疗联合手术治疗临床Ⅲ期EGFR阳性肺腺癌

赵晨¹, 张辉¹, 刘冬¹, 张淼¹, 武文斌¹, 周悦²^,^†(

)

^1. 221009　徐州，徐州市中心医院胸外科
^2. 210029　南京，南京医科大学第一附属医院胸外科

收稿日期:2020-12-30 修回日期:2021-01-26 接受日期:2021-02-17 出版日期:2021-02-28
通信作者: 周悦

Neoadjuvant chemotherapy, targeted therapy combined with surgery for clinical stage Ⅲ lung adenocarcinoma with EGFR mutation

Chen Zhao¹, Hui Zhang¹, Dong Liu¹, Miao Zhang¹, Wenbin Wu¹, Yue Zhou²^,^†()

^1. Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou 221009, China
^2. Department of Cardiothoracic Surgery, The First Affiliated Hospital of NJMU, Nanjing 210029, China

Received:2020-12-30 Revised:2021-01-26 Accepted:2021-02-17 Published:2021-02-28
Corresponding author: Yue Zhou

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引用本文：

赵晨, 张辉, 刘冬, 张淼, 武文斌, 周悦. 新辅助化疗、靶向治疗联合手术治疗临床Ⅲ期EGFR阳性肺腺癌[J/OL]. 中华胸部外科电子杂志, 2021, 08(01): 16-20.

Chen Zhao, Hui Zhang, Dong Liu, Miao Zhang, Wenbin Wu, Yue Zhou. Neoadjuvant chemotherapy, targeted therapy combined with surgery for clinical stage Ⅲ lung adenocarcinoma with EGFR mutation[J/OL]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2021, 08(01): 16-20.

目的

探讨临床Ⅲ（cⅢ）期且EGFR阳性的肺腺癌患者术前行新辅助化疗、靶向治疗后再手术这一新的综合治疗模式的安全性及有效性。

方法

选取2019年9月至2020年9月12例行新辅助治疗、靶向治疗cⅢ期EGFR阳性的肺腺癌患者为观察组，其中10例完成手术，作为A组；筛选同期单纯手术的20例cⅢ期患者为对照组（B组）。回顾性分析两组的病历资料。

结果

观察组中1例患者行新辅助化疗联合靶向治疗后出现疾病进展（PD），1例病灶稳定（SD）且PS 3分未进行手术，余10例患者肿瘤部分缓解（PR），均于化疗后3~4周接受手术治疗。术后病理证实辅助治疗降期效果明显（9/12）。A、B两组患者的性别、年龄、淋巴结清扫枚数、严重并发症发生率等差异均无统计学意义（P>0.05）；A组术中平均出血量较B组多，术后住院时间延长，但差异无统计学意义（P>0.05）；两组肿瘤分化程度差异有统计学意义（P<0.05）。

结论

经病理证实为cⅢ期肺腺癌，如EGFR阳性、健康状态较好（PS 0~2）的患者，术前行新辅助化疗、靶向治疗后再行外科手术可达到术前降期的效果，这一新的综合治疗模式安全且有效。

关键词: 新辅助化疗, 靶向治疗, 肺腺癌, 手术治疗

Objective

To investigate the safety and efficacy of neoadjuvant chemotherapy and targeted therapy combined with surgery in patients with clinical stage Ⅲ (cⅢ) lung adenocarcinoma with EGFR mutation.

Methods

Twelve patients with cⅢ lung adenocarcinoma with EGFR mutation treated with neoadjuvant therapy and targeted therapy from September 2019 to September 2020 were selected, 10 patients completed surgery was group A, and 20 patients with cⅢ lung adenocarcinoma with EGFR mutation treated with surgery alone at the same period were selected as the control group (group B) . The clinical data were retrospectively reviewed.

Results

Among the observation group, 1 patient had disease progression (PD) after neoadjuvant chemotherapy combined with targeted therapy, 1 patient had stable lesion (SD) and PS 3 score without surgery, and the remaining 10 patients with partial remission (PR) received surgery after chemotherapy 3-4 weeks. Postoperative pathology confirmed that the effect of adjuvant therapy was obvious (9/12) . There was no significant difference in gender, age, number of lymph node dissection and incidence of serious complications between the two groups (P>0.05) ; the average intraoperative bleeding in group A was more than that in group B, and the postoperative hospital stay was longer, but there was no significant difference (P>0.05) ; there was significant difference in tumor differentiation between the two groups (P<0.05) .

Conclusion

For patients with cⅢ lung adenocarcinoma confirmed by pathology, and with EGFR positive with good health (PS 0-2) , preoperative neoadjuvant chemotherapy and targeted therapy followed with surgery can reduce the preoperative clinical stage, and this new comprehensive treatment mode is safe and effective.

Key words: Neoadjuvant chemotherapy, Targeted therapy, Lung adenocarcinoma, Surgery

表1 两组患者临床病例资料情况比较

项目		A组（n＝10）	B组（n＝20）	P
性别（例）				1.00
	男	2	4
	女	8	16
年龄（岁）				0.548
	≤65	6	13
	>65	4	7
吸烟史（例）				0.548
	是	3	5
	否	7	15
肺叶切除手术方式（例）				0.551
	胸腔镜	8	17
	开放手术	2	3
cTNM（例）				1.00
	ⅢA	8	16
	ⅢB	2	4

表1 两组患者临床病例资料情况比较

项目		A组（n＝10）	B组（n＝20）	P
性别（例）				1.00
	男	2	4
	女	8	16
年龄（岁）				0.548
	≤65	6	13
	>65	4	7
吸烟史（例）				0.548
	是	3	5
	否	7	15
肺叶切除手术方式（例）				0.551
	胸腔镜	8	17
	开放手术	2	3
cTNM（例）				1.00
	ⅢA	8	16
	ⅢB	2	4

表2 两组患者术中、术后临床指标比较

项目		A组（n＝10）	B组（n＝20）	P
淋巴结切除数（枚）		11.7±3.4	12.2±3.7	0.783
术中出血量（mL）		152.9±35.8	130±29.4	0.206
并发症数（例）		1	3	0.593
	乳糜胸	0	1
	神经损伤	0	1
	肺部感染	1	1
	30 d死亡病例	0	0
术后住院时间（天）		8.1±1.5	7.3±1.4	0.434
肿瘤分化（例）				0.048
	Ⅰ	3	1
	Ⅰ~Ⅱ	4	3
	Ⅱ	2	7
	Ⅱ~Ⅲ/Ⅲ	1	9

表2 两组患者术中、术后临床指标比较

项目		A组（n＝10）	B组（n＝20）	P
淋巴结切除数（枚）		11.7±3.4	12.2±3.7	0.783
术中出血量（mL）		152.9±35.8	130±29.4	0.206
并发症数（例）		1	3	0.593
	乳糜胸	0	1
	神经损伤	0	1
	肺部感染	1	1
	30 d死亡病例	0	0
术后住院时间（天）		8.1±1.5	7.3±1.4	0.434
肿瘤分化（例）				0.048
	Ⅰ	3	1
	Ⅰ~Ⅱ	4	3
	Ⅱ	2	7
	Ⅱ~Ⅲ/Ⅲ	1	9

1	Ettinger DS, WoodD E, Aggarwal C, et al. NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 1. 2020[J]. J Natl Compr Canc Netw, 2019, 17(12): 1464-1472.
2	Yang P, Allen MS, Aubry MC, et al. Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003[J]. Chest, 2005, 128(1): 452-462.
3	Watanabe SI, Nakagawa KZ, Suzuki KJ, et al. Neoadjuvant and adjuvant therapy for Stage III non-small cell lung cancer[J]. Jpn J Clin Oncol, 2017, 47(12): 1112-1118.
4	Berghmans T, Paesmans M, Sculier JP. Prognostic factors in stage III non-small cell lung cancer: a review of conventional, metabolic and new biological variables[J]. Ther Adv Med Oncol, 2011, 3(3): 127-138.
5	Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer[J]. N Engl J Med, 2005, 352(25): 2589-2597.
6	Zhong H, Yang W, Yan H, et al. Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on epidermal growth factor receptor mutation status[J]. J Hematol Oncol, 2015, 8: 54.
7	赫捷，毛友生，沈铿，等．临床肿瘤学[M]. 北京：人民卫生出版社，2016：43-44．
8	Matos I, Martin-Liberal J, García-Ruiz A, et al. Capturing Hyperprogressive Disease with Immune-Checkpoint Inhibitors Using RECIST 1.1 Criteria[J]. Clin Cancer Res, 2020, 26(8): 1846-1855.
9	徐瑞华，姜文奇，管忠震．临床肿瘤内科学[M]．北京：人民卫生出版社，2014：107-108．
10	Edwards JG, Chansky K, Van Schil P, et al. The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for Residual Tumor Descriptors for Non-Small Cell Lung Cancer[J]. J Thorac Oncol, 2020, 15(3): 344-359.
11	Wu F, Zhang S, Gao G, et al. Successful treatment using apatinib with or without docetaxel in heavily pretreated advanced non-squamous non-small cell lung cancer: A case report and literature review[J]. Cancer Biol Ther, 2018, 19(3): 141-144.
12	宁泽，陈睿，陈柯宏，等．两种新辅助治疗方案对ⅢA期EGFR突变肺腺癌疗效及安全性的影响[J]．临床肺科杂志，2019，24(5)：915-918．
13	子宜，邢镨元，马迪，等．可切除111a/N2期非小细胞肺癌治疗模式探讨[J]．中国肺癌杂志，2019，22(2)：111-117．
14	Sun JM, Noh JM, Oh D, et al. Randomized Phase II Trial Comparing Chemoradiotherapy with Chemotherapy for Completely Resected Unsuspected N2-Positive Non-Small Cell Lung Cancer[J]. J Thorac Oncol, 2017, 12(12): 1806-1813.
15	中国抗癌协会肺癌专业委员会，中华医学会肿瘤学分会肺癌学组．Ⅲ期非小细胞肺癌多学科诊疗专家共识(2019版)[J]．中华肿瘤杂志，2019，41(12)：881-890．
16	Van Meerbeeck JP, De Pooter C, Raskin J, et al. Local treatment of stage IIIA-N2 nonsmall cell lung cancer: surgery and/or radiotherapy[J]. Curr Opin Oncol, 2020, 32(1): 54-62.
17	NSCLC Meta-analysis Collaborative Group, Preoperative chemotherapy for non-small cell Lung cancer: a Systematic review and meta-analysis of individual participant data[J]. Lancet, 2014, 383(9928): 1561-1571.
18	Askoxylakis V, Tanner J, Kappes J, et a1. Trimodal therapy for stage III-N2 non-small-cell lung carcinoma: a single center retrospective analysis[J]. BMC Cancer, 2014, 14: 572.
19	Kim Y, Lee SH, Ahn JS, et al. Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib[J]. Cancer Res Treat, 2019, 51(2): 502-509.
20	Liu Y, Zhang Y, Feng G, et al. Comparison of effectiveness and adverse effects of gefitinib, erlotinib and icotinib among patients with non-small cell lung cancer: A network meta-analysis[J]. Exp Ther Med, 2017, 14(5): 4017-4032.
21	Takeda Y, Ishizuka N, Sano K, et al. Phase I/II Study of Erlotinib to Determine the Optimal Dose in Patients With Non-Small Cell Lung Cancer Harboring Only EGFR Mutations[J]. Clin Transl Sci, 2020, 13(6): 1150-1160.
22	Yukio H, Satoshi M, Shunichi S, et al. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study[J]. J Clin Oncol, 2020, 38(2): 115-123.
23	Rebuzzi SE, Alfieri R, La Monica S, et al. Combination of EGFR-TKIs and chemotherapy in advanced EGFR mutated NSCLC: Review of the literature and future perspectives[J]. Crit Rev Oncol Hematol, 2020, 146: 102820.
24	Hu L, Zhang P, Mei Q, et al. Podoplanin is a useful prognostic marker and indicates better differentiation in lung squamous cell cancer patients? A systematic review and meta-analysis[J]. BMC Cancer, 2020, 20(1): 424.
25	Rice JD, Heidel J, Trivedi JR, et al. Optimal Surgical Timing After Neoadjuvant Therapy for Stage IIIa Non-Small Cell Lung Cancer[J]. Ann Thorac Surg, 2020, 109(3): 842-847.

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