Application of high-throughput drug sensitivity screening system in the treatment of non-small cell lung cancer with malignant pleural effusion

doi:10.3969/j.issn.1674-8115.2022.01.012

Abstract

Abstract: Objective

·To explore the feasibility of individualized treatment of malignant pleural effusion (MPE) patients with non-small cell lung cancer (NSCLC) guided by in vitro high-throughput drug sensitivity screening system.

Methods

·Thirty NSCLC patients with MPE treated in Nanjing Chest Hospital from January 2019 to May 2020 were included. The tumor cells in MPE were collected and isolated, and primary cells were cultured. The ex vivo drug sensitivity of primary cells was assessed for 30 chemotherapeutical and molecular targeted drugs by using the high-throughput drug sensitivity screening system of automated digital fluorescence imager. The consistency between the drug sensitivity assay results and the clinical efficacy of patients was evaluated.

Results

·The ex vivo drug sensitivity results of primary tumor cells cultured from MPE revealed considerable heterogeneity in drug response. Most of the primary cells were sensitive to Epirubicin, Lobaplatin, Gemcitabine and Irinotecan. Clinical efficacy of 23 patients can be evaluated. For patients with previously untreated, epidermal growth factor receptor (EGFR) mutation-positive advanced NSCLC, the consistency between the efficacy of targeted therapy and the high-throughput drug sensitivity assay results was 44.4% (4/9). For the EGFR negative untreated patients and EGFR mutation-positive advanced NSCLC patients with acquired resistance to targeted treatment, the consistency between the therapeutic effect of chemotherapy and the high-throughput drug sensitivity assay results was 85.7% (12/14).

Conclusion

·The high-throughput drug sensitivity assay based on MPE primary cell culture in NSCLC patients has a high consistency with the clinical efficacy of chemotherapy, which is helpful for decision-making of personalized chemotherapy.

Key words: non-small cell lung cancer, pleural effusion, in vitro chemosensitivity assay, individualized treatment

CLC Number:

R734.2

Yu ZHANG, Xiaoyuan WU, Lihua GUAN, Yiyuan LIU, Xingyue PENG, Haiyan XIE, Wei HU, Keke HAO, Ning XIA, Guojun LU, Zhibo HOU. Application of high-throughput drug sensitivity screening system in the treatment of non-small cell lung cancer with malignant pleural effusion[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2022, 42(1): 82-89.

Figures/Tables 5

TrendMD

References 30

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Sample	Gender	Age /year	Therapy line	Histology	EGFR/ALK/ ROS1 testing	Treatment	Clinical efficacy	High-throughput drug sensitivity test in vitro	Consistency analysis
S1	Male	72	1	Adenocarcinoma	EGFR19DEL	Gefitinib	PR	Gefitinib resistance	Inconsistent
S3	Female	48	1	Adenocarcinoma	EGFR19DEL	Gefitinib	PR	Gefitinib resistance	Inconsistent
S4	Female	78	1	Adenocarcinoma	Negative	Pemetrexed + Carboplatin	SD	Low sensitive to Pemetrexed and Carboplatin	Consistent
S5	Female	48	1	Adenocarcinoma	EGFR19DEL	Gefitinib	PR	Low sensitive to Gefitinib	Consistent
S7	Female	48	1	Adenocarcinoma	Negative	Pemetrexed + Cisplatin + Bevacizumab	PR	Low sensitive to Pemetrexed and Cisplatin	Consistent
S10	Female	60	1	Adenocarcinoma	Negative	Pemetrexed + Carboplatin	SD	Low sensitive to Pemetrexed and Carboplatin	Consistent
S15	Female	67	1	Adenocarcinoma	Negative	Pemetrexed + Cisplatin	PR	Resistant to Pemetrexed and Cisplatin	Inconsistent
S16	Male	63	1	Adenocarcinoma	EGFR21L858R	Gefitinib	SD	Low sensitive to Gefitinib	Consistent
S19	Male	74	1	Adenosquamous	Negative	Docetaxel + Nedaplatin	SD	Low sensitive to Docetaxel and Nedaplatin	Consistent
S20	Female	57	1	Adenocarcinoma	EGFR19DEL	Afatinib	PR	Afatinib resistance	Inconsistent
S23	Male	65	1	Adenocarcinoma	EGFR19DEL	Gefitinib	PR	Gefitinib resistance	Inconsistent
S24	Male	77	1	Adenocarcinoma	Negative	Pemetrexed + Carboplatin	SD	Resistant to Pemetrexed and Carboplatin	Inconsistent
S25	Male	74	1	Adenocarcinoma	EGFR21L858R	Gefitinib	PR	Moderate sensitive to Gefitinib	Consistent
S26	Female	66	1	Adenocarcinoma	EGFR21L861Q	Afatinib	PR	Low sensitive to Afatinib	Consistent
S27	Male	92	1	Adenocarcinoma	EGFR19DEL	Gefitinib	SD	Gefitinib resistance	Inconsistent
S8	Male	45	3	Adenocarcinoma	Negative	Vinorelbine + Lobaplatin	SD	Low sensitive to Vinorelbine， moderate sensitive to Lobaplatin	Consistent
S11	Female	48	3	Adenocarcinoma	EGFR19DEL	Pemetrexed + Carboplatin + Bevacizumab	PR	Moderate sensitive to Pemetrexed and Carboplatin	Consistent
S13	Male	55	2	Squamous	Negative	Gemcitabine + Nedaplatin	SD	Moderate sensitive to Gemcitabine， low sensitive to Nedaplatin	Consistent
S14	Female	82	3	Adenocarcinoma	EGFR21L858R/T790M/C797S（trans）	S1+Anlotinib	SD	Low sensitive to Tegafur and Nintedanib	Consistent
S18	Male	72	3	Squamous	Negative	S1	SD	Low sensitive to Tegafur	Consistent
S21	Male	45	5	Adenocarcinoma	EGFR19DEL/ T790M/C797S（trans）	Gemcitabine + Lobaplatin	PR	High sensitive to Gemcitabine， moderate sensitive to Lobaplatin	Consistent
S22	Female	71	3	Adenocarcinoma	EGFR21L858R/T790M/C797S（trans）	Pemetrexed + Carboplatin +Bevacizumab	PR	Moderate sensitive to Pemetrexed and Carboplatin	Consistent
S29	Female	60	3	Adenocarcinoma	EGFR21L858R+BRAF V600E	Pemetrexed + Carboplatin	PD	Resistant to Pemetrexed and Carboplatin	Consistent

Sample	Gender	Age /year	Therapy line	Histology	EGFR/ALK/ ROS1 testing	Treatment	Clinical efficacy	High-throughput drug sensitivity test in vitro	Consistency analysis
S1	Male	72	1	Adenocarcinoma	EGFR19DEL	Gefitinib	PR	Gefitinib resistance	Inconsistent
S3	Female	48	1	Adenocarcinoma	EGFR19DEL	Gefitinib	PR	Gefitinib resistance	Inconsistent
S4	Female	78	1	Adenocarcinoma	Negative	Pemetrexed + Carboplatin	SD	Low sensitive to Pemetrexed and Carboplatin	Consistent
S5	Female	48	1	Adenocarcinoma	EGFR19DEL	Gefitinib	PR	Low sensitive to Gefitinib	Consistent
S7	Female	48	1	Adenocarcinoma	Negative	Pemetrexed + Cisplatin + Bevacizumab	PR	Low sensitive to Pemetrexed and Cisplatin	Consistent
S10	Female	60	1	Adenocarcinoma	Negative	Pemetrexed + Carboplatin	SD	Low sensitive to Pemetrexed and Carboplatin	Consistent
S15	Female	67	1	Adenocarcinoma	Negative	Pemetrexed + Cisplatin	PR	Resistant to Pemetrexed and Cisplatin	Inconsistent
S16	Male	63	1	Adenocarcinoma	EGFR21L858R	Gefitinib	SD	Low sensitive to Gefitinib	Consistent
S19	Male	74	1	Adenosquamous	Negative	Docetaxel + Nedaplatin	SD	Low sensitive to Docetaxel and Nedaplatin	Consistent
S20	Female	57	1	Adenocarcinoma	EGFR19DEL	Afatinib	PR	Afatinib resistance	Inconsistent
S23	Male	65	1	Adenocarcinoma	EGFR19DEL	Gefitinib	PR	Gefitinib resistance	Inconsistent
S24	Male	77	1	Adenocarcinoma	Negative	Pemetrexed + Carboplatin	SD	Resistant to Pemetrexed and Carboplatin	Inconsistent
S25	Male	74	1	Adenocarcinoma	EGFR21L858R	Gefitinib	PR	Moderate sensitive to Gefitinib	Consistent
S26	Female	66	1	Adenocarcinoma	EGFR21L861Q	Afatinib	PR	Low sensitive to Afatinib	Consistent
S27	Male	92	1	Adenocarcinoma	EGFR19DEL	Gefitinib	SD	Gefitinib resistance	Inconsistent
S8	Male	45	3	Adenocarcinoma	Negative	Vinorelbine + Lobaplatin	SD	Low sensitive to Vinorelbine， moderate sensitive to Lobaplatin	Consistent
S11	Female	48	3	Adenocarcinoma	EGFR19DEL	Pemetrexed + Carboplatin + Bevacizumab	PR	Moderate sensitive to Pemetrexed and Carboplatin	Consistent
S13	Male	55	2	Squamous	Negative	Gemcitabine + Nedaplatin	SD	Moderate sensitive to Gemcitabine， low sensitive to Nedaplatin	Consistent
S14	Female	82	3	Adenocarcinoma	EGFR21L858R/T790M/C797S（trans）	S1+Anlotinib	SD	Low sensitive to Tegafur and Nintedanib	Consistent
S18	Male	72	3	Squamous	Negative	S1	SD	Low sensitive to Tegafur	Consistent
S21	Male	45	5	Adenocarcinoma	EGFR19DEL/ T790M/C797S（trans）	Gemcitabine + Lobaplatin	PR	High sensitive to Gemcitabine， moderate sensitive to Lobaplatin	Consistent
S22	Female	71	3	Adenocarcinoma	EGFR21L858R/T790M/C797S（trans）	Pemetrexed + Carboplatin +Bevacizumab	PR	Moderate sensitive to Pemetrexed and Carboplatin	Consistent
S29	Female	60	3	Adenocarcinoma	EGFR21L858R+BRAF V600E	Pemetrexed + Carboplatin	PD	Resistant to Pemetrexed and Carboplatin	Consistent

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