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Gao X, Overtoom HCG, Eyck BM, Huang SH, Nieboer D, van der Sluis PC, Lagarde SM, Wijnhoven BPL, Chao YK, van Lanschot JJB. Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma in Eastern versus Western countries: meta-analysis. Br J Surg 2024; 111:znae083. [PMID: 38721902 DOI: 10.1093/bjs/znae083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 02/23/2024] [Accepted: 03/05/2024] [Indexed: 05/15/2024]
Abstract
OBJECTIVE Locally advanced oesophageal squamous cell carcinoma can be treated with neoadjuvant chemoradiotherapy or chemotherapy followed by oesophagectomy. Discrepancies in pathological response rates have been reported between studies from Eastern versus Western countries. The aim of this study was to compare the pathological response to neoadjuvant chemoradiotherapy in Eastern versus Western countries. METHODS Databases were searched until November 2022 for studies reporting pCR rates after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. Multi-level meta-analyses were performed to pool pCR rates separately for cohorts from studies performed in centres in the Sinosphere (East) or in Europe and the Anglosphere (West). RESULTS For neoadjuvant chemoradiotherapy, 51 Eastern cohorts (5636 patients) and 20 Western cohorts (3039 patients) were included. Studies from Eastern countries included more men, younger patients, more proximal tumours, and more cT4 and cN+ disease. Patients in the West were more often treated with high-dose radiotherapy, whereas patients in the East were more often treated with a platinum + fluoropyrimidine regimen. The pooled pCR rate after neoadjuvant chemoradiotherapy was 31.7% (95% c.i. 29.5% to 34.1%) in Eastern cohorts versus 40.4% (95% c.i. 35.0% to 45.9%) in Western cohorts (fixed-effect P = 0.003). For cohorts with similar cTNM stages, pooled pCR rates for the East and the West were 32.5% and 41.9% respectively (fixed-effect P = 0.003). CONCLUSION The pathological response to neoadjuvant chemoradiotherapy is less favourable in patients treated in Eastern countries compared with Western countries. Despite efforts to investigate accounting factors, the discrepancy in pCR rate cannot be entirely explained by differences in patient, tumour, or treatment characteristics.
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Affiliation(s)
- Xing Gao
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
- Division of Thoracic Surgery, Chang Gung Memorial Hospital-Linkou, Chang Gung University, Taoyuan, Taiwan
| | - Hidde C G Overtoom
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Ben M Eyck
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Shi-Han Huang
- Division of Thoracic Surgery, Chang Gung Memorial Hospital-Linkou, Chang Gung University, Taoyuan, Taiwan
| | - Daan Nieboer
- Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands
| | | | - Sjoerd M Lagarde
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Bas P L Wijnhoven
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Yin-Kai Chao
- Division of Thoracic Surgery, Chang Gung Memorial Hospital-Linkou, Chang Gung University, Taoyuan, Taiwan
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Kawahara D, Murakami Y, Awane S, Emoto Y, Iwashita K, Kubota H, Sasaki R, Nagata Y. Radiomics and dosiomics for predicting complete response to definitive chemoradiotherapy patients with oesophageal squamous cell cancer using the hybrid institution model. Eur Radiol 2024; 34:1200-1209. [PMID: 37589902 DOI: 10.1007/s00330-023-10020-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 05/08/2023] [Accepted: 06/12/2023] [Indexed: 08/18/2023]
Abstract
OBJECTIVES To develop a multi-institutional prediction model to estimate the local response to oesophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy based on radiomics and dosiomics features. METHODS The local responses were categorised into two groups (incomplete and complete). An external validation model and a hybrid model that the patients from two institutions were mixed randomly were proposed. The ESCC patients at stages I-IV who underwent chemoradiotherapy from 2012 to 2017 and had follow-up duration of more than 5 years were included. The patients who received palliative or pre-operable radiotherapy and had no FDG PET images were excluded. The segmentations included the GTV, CTV, and PTV which are used in treatment planning. In addition, shrinkage, expansion, and shell regions were created. Radiomic and dosiomic features were extracted from CT, FDG PET images, and dose distribution. Machine learning-based prediction models were developed using decision tree, support vector machine, k-nearest neighbour (kNN) algorithm, and neural network (NN) classifiers. RESULTS A total of 116 and 26 patients enrolled at Centre 1 and Centre 2, respectively. The external validation model exhibited the highest accuracy with 65.4% for CT-based radiomics, 77.9% for PET-based radiomics, and 72.1% for dosiomics based on the NN classifiers. The hybrid model exhibited the highest accuracy of 84.4% for CT-based radiomics based on the kNN classifier, 86.0% for PET-based radiomics, and 79.0% for dosiomics based on the NN classifiers. CONCLUSION The proposed hybrid model exhibited promising predictive performance for the local response to definitive radiotherapy in ESCC patients. CLINICAL RELEVANCE STATEMENT The prediction of the complete response for oesophageal cancer patients may contribute to improving overall survival. The hybrid model has the potential to improve prediction performance than the external validation model that was conventionally proposed. KEY POINTS • Radiomics and dosiomics used to predict response in patients with oesophageal cancer receiving definitive radiotherapy. • Hybrid model with neural network classifier of PET-based radiomics improved prediction accuracy by 8.1%. • The hybrid model has the potential to improve prediction performance.
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Affiliation(s)
- Daisuke Kawahara
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
| | - Yuji Murakami
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Shota Awane
- School of Medicine, Hiroshima University, Hiroshima, 734-8551, Japan
| | - Yuki Emoto
- Department of Radiation Oncology, Hyogo Cancer Center, 70, Kitaoji-Cho 13, Akashi-Shi, Hyogo, Japan
| | - Kazuma Iwashita
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan
| | - Hikaru Kubota
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan
| | - Ryohei Sasaki
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan
| | - Yasushi Nagata
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
- Hiroshima High-Precision Radiotherapy Cancer Center, Hiroshima, 732-0057, Japan
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Gaber CE, Sarker J, Abdelaziz AI, Okpara E, Lee TA, Klempner SJ, Nipp RD. Pathologic complete response in patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A systematic review and meta-analysis. Cancer Med 2024; 13:e7076. [PMID: 38457244 PMCID: PMC10923050 DOI: 10.1002/cam4.7076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 02/11/2024] [Accepted: 02/20/2024] [Indexed: 03/10/2024] Open
Abstract
BACKGROUND Neoadjuvant chemoradiation and chemotherapy are recommended for the treatment of nonmetastatic esophageal cancer. The benefit of neoadjuvant treatment is mostly limited to patients who exhibit pathologic complete response (pCR). Existing estimates of pCR rates among patients receiving neoadjuvant therapy have not been synthesized and lack precision. METHODS We conducted an independently funded systematic review and meta-analysis (PROSPERO CRD42023397402) of pCR rates among patients diagnosed with esophageal cancer treated with neoadjuvant chemo(radiation). Studies were identified from Medline, EMBASE, and CENTRAL database searches. Eligible studies included trials published from 1992 to 2022 that focused on nonmetastatic esophageal cancer, including the gastroesophageal junction. Histology-specific pooled pCR prevalence was determined using the Freeman-Tukey transformation and a random effects model. RESULTS After eligibility assessment, 84 studies with 6451 patients were included. The pooled prevalence of pCR after neoadjuvant chemotherapy in squamous cell carcinomas was 9% (95% CI: 6%-14%), ranging from 0% to 32%. The pooled prevalence of pCR after neoadjuvant chemoradiation in squamous cell carcinomas was 32% (95% CI: 26%-39%), ranging from 8% to 66%. For adenocarcinoma, the pooled prevalence of pCR was 6% (95% CI: 1%-12%) after neoadjuvant chemotherapy, and 22% (18%-26%) after neoadjuvant chemoradiation. CONCLUSIONS Under one-third of patients with esophageal cancer who receive neoadjuvant chemo(radiation) experience pCR. Patients diagnosed with squamous cell carcinomas had higher rates of pCR than those with adenocarcinomas. As pCR represents an increasingly utilized endpoint in neoadjuvant trials, these estimates of pooled pCR rates may serve as an important benchmark for future trial design.
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Affiliation(s)
- Charles E. Gaber
- Department of Pharmacy Systems, Outcomes and Policy, College of PharmacyUniversity of Illinois ChicagoChicagoIllinoisUSA
- Center for Pharmacoepidemiology and Pharmacoeconomic Research, College of PharmacyUniversity of Illinois ChicagoChicagoIllinoisUSA
| | - Jyotirmoy Sarker
- Department of Pharmacy Systems, Outcomes and Policy, College of PharmacyUniversity of Illinois ChicagoChicagoIllinoisUSA
| | - Abdullah I. Abdelaziz
- Department of Pharmacy Systems, Outcomes and Policy, College of PharmacyUniversity of Illinois ChicagoChicagoIllinoisUSA
| | - Ebere Okpara
- Department of Pharmacy Systems, Outcomes and Policy, College of PharmacyUniversity of Illinois ChicagoChicagoIllinoisUSA
| | - Todd A. Lee
- Department of Pharmacy Systems, Outcomes and Policy, College of PharmacyUniversity of Illinois ChicagoChicagoIllinoisUSA
- Center for Pharmacoepidemiology and Pharmacoeconomic Research, College of PharmacyUniversity of Illinois ChicagoChicagoIllinoisUSA
| | | | - Ryan D. Nipp
- OU Health Stephenson Cancer CenterOklahoma UniversityOklahoma CityOklahomaUSA
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Zhou RQ, Luo J, Li LJ, Du M, Wu QC. Neoadjuvant camrelizumab plus chemotherapy in locally advanced oesophageal squamous cell carcinoma: a retrospective cohort study. BMC Surg 2023; 23:114. [PMID: 37161374 PMCID: PMC10170768 DOI: 10.1186/s12893-023-02023-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 04/30/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Neoadjuvant therapy is recommended to improve the prognosis of oesophageal squamous cell carcinoma (ESCC). As a PD-1 inhibitor developed in China, camrelizumab is more accessible and available for Chinese ESCC patients. Camrelizumab plus neoadjuvant chemotherapy has shown promising efficacy with acceptable toxicity for resectable ESCC in the NIC-ESCC2019 trial. However, this was a single-arm trial, so we conducted a retrospective cohort study to compare neoadjuvant camrelizumab plus chemotherapy with neoadjuvant chemotherapy alone in terms of the safety and efficacy in patients with locally advanced ESCC. METHODS Between January 2017 and December 2021, patients with stage II-IVa ESCC who received neoadjuvant therapy at the First Affiliated Hospital of Chongqing Medical University and underwent radical oesophagectomy were enrolled in our study. These included 19 patients who received neoadjuvant chemotherapy plus camrelizumab (group 1) and 40 patients who only received neoadjuvant chemotherapy (group 2). RESULTS The baseline characteristics of the patients were comparable between the two groups. The pathological complete response (pCR) rate in group 1 was significantly higher than that in group 2 (26.3% vs. 2.5%, P = 0.018). All patients in group 1 achieved complete resection (R0), compared with 39 (97.5%) patients in group 2. Adverse events occurred in 16 (84%) patients in group 1 versus 35 (87.5%) patients in group 2. No grade ≥ 4 adverse events occurred in either group. No significant difference was found in surgical outcomes or postoperative complications. The 90-day mortality rate was comparable between the two groups (1 patient died in group 1 versus 2 patients in group 2). CONCLUSIONS Neoadjuvant camrelizumab plus chemotherapy followed by surgery was associated with a promising pCR rate and a manageable safety profile for patients with locally advanced ESCC.
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Affiliation(s)
- Rui-Qin Zhou
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Jun Luo
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Lin-Jun Li
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Ming Du
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Qing-Chen Wu
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
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Du QC, Wang XY, Hu CK, Zhou L, Fu Z, Liu S, Wang J, Ma YY, Liu MY, Yu H. Integrative analysis of platelet-related genes for the prognosis of esophageal cancer. World J Clin Cases 2022; 10:12077-12088. [PMID: 36483802 PMCID: PMC9724514 DOI: 10.12998/wjcc.v10.i33.12077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 08/15/2022] [Accepted: 10/11/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Every year, esophageal cancer is responsible for 509000 deaths and around 572000 new cases worldwide. Although esophageal cancer treatment options have advanced, patients still have a dismal 5-year survival rate.
AIM To investigate the relationship between genes associated to platelets and the prognosis of esophageal cancer.
METHODS We searched differentially expressed genes for changes between 151 tumor tissues and 653 normal, healthy tissues using the “limma” package. To develop a prediction model of platelet-related genes, a univariate Cox regression analysis and least absolute shrinkage and selection operator Cox regression analysis were carried out. Based on a median risk score, patients were divided into high-risk and low-risk categories. A nomogram was created to predict the 1-, 2-, and 3-year overall survival (OS) of esophageal cancer patients using four platelet-related gene signatures, TNM stages, and pathological type. Additionally, the concordance index, receiver operating characteristic curve, and calibration curve were used to validate the nomogram.
RESULTS The prognosis of esophageal cancer was associated to APOOL, EP300, PLA2G6, and VAMP7 according to univariate Cox regression analysis and least absolute shrinkage and selection operator regression analysis. Patients with esophageal cancer at high risk had substantially shorter OS than those with cancer at low risk, according to a Kaplan-Meier analysis (P < 0.05). TNM stage (hazard ratio: 2.187, 95% confidence interval: 1.242-3.852, P = 0.007) in both univariate and multivariate Cox regression and risk score were independently correlated with OS (hazard ratio: 2.451, 95% confidence interval: 1.599-3.756, P < 0.001).
CONCLUSION A survival risk score model and independent prognostic variables for esophageal cancer have been developed using APOOL, EP300, PLA2G6, and VAMP7. OS for esophageal cancer might be predicted using the nomogram based on TNM stage, pathological type, and risk score. The nomogram demonstrated strong predictive ability, as shown by the concordance index, receiver operating characteristic curve, and calibration curve.
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Affiliation(s)
- Qian-Cheng Du
- Department of Thoracic Surgery, Shanghai Xuhui Central Hospital, Shanghai 200031, China
| | - Xin-Yu Wang
- Department of General Surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
| | - Cheng-Kai Hu
- Department of Thoracic Surgery, Shanghai Xuhui Central Hospital, Shanghai 200031, China
| | - Ling Zhou
- Department of General Surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
| | - Zheng Fu
- Department of Thoracic Surgery, Shanghai Xuhui Central Hospital, Shanghai 200031, China
| | - Shun Liu
- Department of Thoracic Surgery, Shanghai Xuhui Central Hospital, Shanghai 200031, China
| | - Jian Wang
- Department of Thoracic Surgery, Shanghai Xuhui Central Hospital, Shanghai 200031, China
| | - Ying-Ying Ma
- Department of Thoracic Surgery, Shanghai Xuhui Central Hospital, Shanghai 200031, China
| | - Meng-Yao Liu
- Department of Thoracic Surgery, Shanghai Xuhui Central Hospital, Shanghai 200031, China
| | - Hua Yu
- Department of General Surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
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Nuplazid suppresses esophageal squamous cell carcinoma growth in vitro and in vivo by targeting PAK4. Br J Cancer 2021; 126:1037-1046. [PMID: 34912075 PMCID: PMC8980085 DOI: 10.1038/s41416-021-01651-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 10/31/2021] [Accepted: 11/22/2021] [Indexed: 11/09/2022] Open
Abstract
Background Due to the high recurrence and low 5-year survival rates of esophageal squamous cell carcinoma (ESCC) after treatment, the discovery of novel drugs for recurrence chemoprevention is of particular importance. Methods We screened the FDA-approved drug library and found that Nuplazid, an atypical antipsychotic that acts as an effective 5-HT 2 A receptor inverse agonist, could potentially exert anticancer effects in vitro and in vivo on ESCC. Results Pull-down results indicated that Nuplazid binds with p21-activated kinase 4 (PAK4), and a kinase assay showed that Nuplazid strongly suppressed PAK4 kinase activity. Moreover, Nuplazid exhibited inhibitory effects on ESCC in vivo. Conclusions Our findings indicate that Nuplazid can suppress ESCC progression through targeting PAK4.
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Huang B, Shi H, Gong X, Yu J, Xiao C, Zhou B, Liang Z, Li X. Comparison of efficacy and safety between pembrolizumab combined with chemotherapy and simple chemotherapy in neoadjuvant therapy for esophageal squamous cell carcinoma. J Gastrointest Oncol 2021; 12:2013-2021. [PMID: 34790369 PMCID: PMC8576253 DOI: 10.21037/jgo-21-610] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/19/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Immunotherapy can activate the recognition of tumor antigen, build immune memory, and more and more clinical trials have taken the scheme of immunochemotherapy or immunoradiotherapy as a treatment strategy for esophageal squamous cell carcinoma (ESCC). Our objective was to compare the efficacy and safety between pembrolizumab combined with the chemotherapy group and simple chemotherapy in neoadjuvant therapy of ESCC. METHODS Fifty-four ESCC patients with stage II-IVa were enrolled at the Fifth Affiliated Hospital of Sun Yat-sen University between January 2018 and December 2020, including 23 in the pembrolizumab combined with chemotherapy group (combined group), and 31 in the simple chemotherapy group. All patients received radical surgical treatment after two cycles of neoadjuvant therapy. RESULTS The pathological complete response (pCR) and objective response rate (ORR) in the combined group were significantly higher than that of the simple chemotherapy group (30.4% vs. 9.7%, P=0.048; 86.9% vs. 95.7%, P=0.017) as well as the score of tumor regression ≥2 (80.7% vs. 50.0%, P=0.013). And the complete rate of esophagectomy and R0 /R1 resection rate in the two groups were not statistically significant. Otherwise, the incidence of adverse events in the combined group was similar compared with the simple chemotherapy group. CONCLUSIONS Pembrolizumab combined with chemotherapy showed promising activity with a manageable safety profile. And it could offer a potential new neoadjuvant treatment approach for patients with ESCC.
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Affiliation(s)
- Bingjiang Huang
- Department of Thoracic Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Haiyan Shi
- Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Xiaohua Gong
- Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jing Yu
- Department of Minimally Invasive Surgery, The Cancer Center of The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Caixia Xiao
- Department of Minimally Invasive Surgery, The Cancer Center of The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Bin Zhou
- Department of Minimally Invasive Surgery, The Cancer Center of The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Zibin Liang
- Department of Thoracic Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Xiaojian Li
- Department of Thoracic Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
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