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Huang FL, Luo M, He ZM, Shen YQ, Liu GD. Diagnosis and treatment of pulmonary lymphoepithelioma-like carcinoma: A case report. World J Clin Oncol 2025; 16:104413. [PMID: 40290685 PMCID: PMC12019266 DOI: 10.5306/wjco.v16.i4.104413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/15/2025] [Accepted: 02/25/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare primary epithelial lung cancer associated with the Epstein-Barr virus. Standard treatment guideline for PLELC is yet not to be established, surgery remains the primary treatment for early-stage PLELC, and platinum chemotherapy is the most common first-line treatment for advanced PLELC. While targeted therapy and immunotherapy has emerged as effective way to treat various malignant tumors, including lung cancer, reports on PLELC are relatively scarce. CASE SUMMARY A 38-year-old man was diagnosed with right PLELC. Chest computed tomography (CT) revealed a mass in the medial segment of the middle lobe of the right lung, with lymph node metastasis in the mediastinum and right hilum of the lung. CT-guided lung tumor biopsy was performed and the postoperative pathological examination combined with immune phenotype analysis and in situ hybridization confirmed PLELC. Standard molecular testing for patients with non-small cell lung cancer was negative and programmed cell death ligand-1 expression was about 2%. The patient declined radiotherapy and chemotherapy. Consequently, immunotherapy was administered, which included toripalimab 240 mg on day 1 and anlotinib 10 mg on days 1-14 for 10 cycles, followed by a maintenance dose of anlotinib 10 mg daily every 3 weeks. As a result, his progression-free survival reached 48 months. CONCLUSION A combination of toripalimab and anlotinib may benefit patients with advanced diseases who have not received systematic antitumor therapy.
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Affiliation(s)
- Feng-Ling Huang
- Department of Pharmacology and Clinical Pharmacy, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Min Luo
- Department of Pharmacology and Clinical Pharmacy, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Zhen-Mei He
- Department of Pharmacology and Clinical Pharmacy, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Yong-Qi Shen
- Department of Oncology, The Third Affiliated Hospital of Guangxi College Traditional Chinese Medicine, Liuzhou 545007, Guangxi Zhuang Autonomous Region, China
| | - Guan-Da Liu
- Department of Pharmacology and Clinical Pharmacy, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
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FANG Y, WANG A, SHEN L, YUAN X, KONG Y. [Clinicopathological Analysis of 14 Cases of Primary Pulmonary Lymphoepithelial Carcinoma]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2024; 27:840-848. [PMID: 39800479 PMCID: PMC11732381 DOI: 10.3779/j.issn.1009-3419.2024.101.29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Primary pulmonary lymphoepithelial carcinoma (PPLEC) is a rare form of lung malignancy, accounting for only 0.7% of all lung cancers. It is currently classified as a distinct subtype within squamous cell carcinomas. This study aims to explore the clinicopathological characteristics of PPLEC and its subtypes, with the objective of enhancing understanding and improving diagnostic accuracy for this disease. METHODS A retrospective analysis was conducted on the clinical, pathological, imaging, and prognostic data of 14 patients diagnosed with PPLEC at the First Affiliated Hospital of Soochow University between February 2019 and June 2023. RESULTS A total of 14 cases of PPLEC were identified, including 5 cases of the Regaud type, with ages ranging from 33 to 73 years, comprising 2 males and 3 females; and 9 cases of the Schmincke type, with ages ranging from 36 to 79 years, including 4 males and 5 females. Computed tomography (CT) scans consistently demonstrated soft tissue masses or nodular shadows. Reagud type mainly showed peripheral masses and Schmincke type mainly showed central masses. Pathological examination revealed tumor cells exhibiting syncytial-like growth, accompanied by lymphocytic infiltration and stromal fibrosis, with the Regaud type showing well-defined borders combined with granulomatous inflammation, while the Schmincke type exhibited indistinct tumor margins. Immunohistochemistry showed that CK, CK5/6, P40 and P63 were positive, and the Ki-67 index of Regaud type was lower than that of Schmincke type; notably, all 8 cases tested for programmed death-ligand 1 (PD-L1) were positive. Epstein-Barr virus-encoded RNA (EBER) in situ hybridization was positive in all instances. Among these cases, 6 underwent surgical treatment, and 8 received comprehensive therapy; by the end of the follow-up period, all 14 patients remained alive. CONCLUSIONS PPLEC is a rare form of malignant lung tumor associated with Epstein-Barr virus (EBV) infection. The Regaud and Schmincke subtypes display distinct imaging and pathological characteristics. In the early stages of the disease, surgical intervention is the primary treatment method; however, for advanced stages, a multimodal treatment approach is utilized, resulting in a relatively favorable prognosis. Immunotherapy represents a promising and effective treatment modality for patients with middle to advanced stage disease exhibiting high PD-L1 expression levels.
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Zhong Y, Chen J, Jiang J, Zhou W, Gao L, Zhang S, Yan W, Chen Y, Zhang D, Lu D, Lv Z, Xie Z, Huang Y, Guo W, Wang B, Yang J, Yang X, Wu Y, Zhang X. Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma. Clin Transl Immunology 2024; 13:e1515. [PMID: 38835955 PMCID: PMC11147665 DOI: 10.1002/cti2.1515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 04/24/2024] [Accepted: 05/15/2024] [Indexed: 06/06/2024] Open
Abstract
Objectives Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral EBNA-1 and BamHI-W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results Progression-free survival (PFS) was significantly longer in EBNA-1 high or BamHI-W high groups. A longer PFS was also observed in patients with both high plasma EBNA-1 or BamHI-W and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA-1 and BamHI-W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.
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Affiliation(s)
- Yu‐Min Zhong
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Ji Chen
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Jie Jiang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- School of Medicine, South China University of TechnologyGuangzhouChina
| | - Wen‐Bin Zhou
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- School of Medicine, South China University of TechnologyGuangzhouChina
| | - Ling‐Ling Gao
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Shui‐Lian Zhang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Wen‐Qing Yan
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Yu Chen
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Dong‐Kun Zhang
- Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Dan‐Xia Lu
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Zhi‐Yi Lv
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Zhi Xie
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Ying Huang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Wei‐Bang Guo
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Bin‐Chao Wang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Jin‐Ji Yang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Xue‐Ning Yang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Yi‐Long Wu
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
| | - Xu‐Chao Zhang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Medical Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- School of Medicine, South China University of TechnologyGuangzhouChina
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Chen GF, Wang J, Yan Y, Xu S, Chen J. Metastatic stomach lymphoepithelioma-like carcinoma and immune checkpoint inhibitor therapy: A case report. World J Gastrointest Surg 2024; 16:1436-1442. [PMID: 38817283 PMCID: PMC11135303 DOI: 10.4240/wjgs.v16.i5.1436] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 04/10/2024] [Accepted: 04/22/2024] [Indexed: 05/23/2024] Open
Abstract
BACKGROUND Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare type of non-small-cell lung cancer. Stomach lymphoepithelioma-like carcinoma (LELC) metastasis secondary to PLELC has not been reported recently. CASE SUMMARY A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC. Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region. Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus. Immunohistochemistry (IHC) of the biopsy suggested metastatic stomach LELC. Proximal gastrectomy showed that this 6.5 cm × 5.0 cm mass was located in the stomach fundus near the cardia. Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration. IHC demonstrated that the tumor was positive for CK (AE1/AE3), p63, p40, p53, Ki-67 (70%), and EGFR (3+) and negative for CK7, CK20, Her2, and CD10. In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA. Tumor programmed cell death ligand 1 (PD-L1) expression score was 98%, and the combined positive score was 100, with no evidence of microsatellite instability. Thus, the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC. After discharge, this patient underwent PD-1 inhibitor treatment (toripalimab, 240 mg) every 3 wk for ten cycles, and she has had no tumor recurrence. CONCLUSION For gastric LELC metastasis, PD-1 inhibitor therapy could become a new therapeutic approach, though there is still no evidence from large data sets to support this.
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Affiliation(s)
- Guo-Feng Chen
- Department of Gastroenterology Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Jun Wang
- Department of Gastroenterology Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
- Cancer Center, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
| | - Yu Yan
- Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Song Xu
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Jian Chen
- Department of Gastroenterology Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
- Cancer Center, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
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Low YH, Loh CJL, Peh DYY, Chu AJM, Han S, Toh HC. Pathogenesis and therapeutic implications of EBV-associated epithelial cancers. Front Oncol 2023; 13:1202117. [PMID: 37901329 PMCID: PMC10600384 DOI: 10.3389/fonc.2023.1202117] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 09/07/2023] [Indexed: 10/31/2023] Open
Abstract
Epstein-Barr virus (EBV), one of the most common human viruses, has been associated with both lymphoid and epithelial cancers. Undifferentiated nasopharyngeal carcinoma (NPC), EBV associated gastric cancer (EBVaGC) and lymphoepithelioma-like carcinoma (LELC) are amongst the few common epithelial cancers that EBV has been associated with. The pathogenesis of EBV-associated NPC has been well described, however, the same cannot be said for primary pulmonary LELC (PPLELC) owing to the rarity of the cancer. In this review, we outline the pathogenesis of EBV-associated NPC and EBVaGCs and their recent advances. By drawing on similarities between NPC and PPLELC, we then also postulated the pathogenesis of PPLELC. A deeper understanding about the pathogenesis of EBV enables us to postulate the pathogenesis of other EBV associated cancers such as PPLELC.
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Affiliation(s)
- Yi Hua Low
- Duke-NUS Medical School, Singapore, Singapore
| | | | - Daniel Yang Yao Peh
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Axel Jun Ming Chu
- Singapore Health Services Internal Medicine Residency Programme, Singapore, Singapore
| | - Shuting Han
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Han Chong Toh
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
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Zhang Q, Dai Y, Jin L, Shi S, Liu C, Rong R, Sun W, Dai S, Kong H, Xie W. Clinicopathological characteristics and cancer-specific prognosis of primary pulmonary lymphoepithelioma-like carcinoma: a population study of the US SEER database and a Chinese hospital. Front Oncol 2023; 13:1103169. [PMID: 37274245 PMCID: PMC10235615 DOI: 10.3389/fonc.2023.1103169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 04/17/2023] [Indexed: 06/06/2023] Open
Abstract
Introduction Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare histological type of non-small cell lung cancer (NSCLC), which accounts for less than 1% of NSCLC. Currently, there is no well-recognized treatment guideline for PPLELC. Methods We identified PPLELC patients from the Surveillance, Epidemiology, and End Results (SEER) dataset between 2000 and 2015 (n = 72) as well as from our medical center between 2014 and 2020 (n = 16). All diagnoses were confirmed by pathological testing, and the clinicopathological characteristics of patients were retrieved and summarized. Survival analyses were conducted using the Kaplan-Meier analysis and log-rank tests. Multivariate survival analysis was performed with the Cox regression hazards model. Results The median age at diagnosis of the PPLELC cohort was 64 years, ranging from 15 to 86 years. The percentages of patients with TNM stages I, II, III, and IV were 52.3%, 10.2%, 20.5%, and 17.0%, respectively. Among the 88 cases, lesion resection was performed in 69 cases (78.4%), 16 cases (18.1%) received beam radiation, and 40 cases (45.5%) underwent chemotherapy. In the SEER dataset of lung cancer, the percentage of PPLELC in the Asian race (0.528‰) was almost 10 times higher than that in the white (0.065‰) and black (0.056‰) races. Patients with TNM stage III-IV exhibited a worse prognosis than those with TNM stage I-II (p = 0.008), with a 5-year cancer-specific survival (CSS) rate of 81.8% for TNM stage I-II and 56.2% for TNM stage III-IV. Specifically, the N stage and M stage were the leading prognostic factors, not the T stage and tumor size. Moreover, patients who underwent surgery had significantly better outcomes than those who did not (p = 0.014). Additional multivariate analysis indicated that the TNM stage was an independent prognosis factor for CSS (HR, 3.31; 95% CI, 1.08-10.14). Conclusion PPLELC is a rare tumor with Asian susceptibility. Although the prognosis of PPLELC is better than that of other subtypes of NSCLC, it remains unsatisfactory for advanced-stage disease. The current treatment options for PPLELC include surgical resection, chemotherapy, radiotherapy, and immune therapy. Among these options, patients with surgical resection have better survival rates in this study. However, large-scale clinical research trials will be necessary to develop effective treatment guidelines for PPLELC.
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Affiliation(s)
- Qun Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yuan Dai
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Linling Jin
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Shuangshuang Shi
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chang Liu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Rong Rong
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wenkui Sun
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Shanlin Dai
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hui Kong
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Weiping Xie
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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Zou QH, Liu H, Huang CW, Kang LP, Qiu B, Mai JL, Lin YB, Liang Y. Efficacy and safety of gemcitabine and capecitabine combination for patients with previously treated advanced primary pulmonary lymphoepithelioma-like carcinoma: a retrospective single-arm cohort study. Transl Lung Cancer Res 2023; 12:96-108. [PMID: 36762055 PMCID: PMC9903090 DOI: 10.21037/tlcr-22-256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 12/02/2022] [Indexed: 01/17/2023]
Abstract
Background Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of non-small cell lung cancer (NSCLC). Studies reporting on salvage treatment for pretreated PLELC are limited. Positive interactions between gemcitabine (GEM) and capecitabine (CAP) have been demonstrated in preclinical studies. In addition, the clinical benefit of the combination has been reported for other malignancies. However, the efficacy and safety of the combination for pretreated PLELC remain unclear. Therefore, we conducted this retrospective study to examine the activity and safety of gemcitabine plus capecitabine (GEM/CAP) combination for previously treated PLELC. Methods Patients with PLELC at Sun Yat-sen University Cancer Center who received GEM combined with CAP between May 2013 and January 2021 as the second-line therapy or beyond were retrospectively enrolled. Treatment consisted of intravenous GEM (1,000 mg/m2 on days 1 and 8) and oral CAP (1,000 mg/m2 twice daily on days 1-14) every 3 weeks. Evaluation of response was performed every 2 cycles in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Safety was assessed in accordance with Common Terminology Criteria for Adverse Events version 5.0. Clinical characteristics were collected from medical records. The survival data were obtained by medical records or telephone. Follow-ups were performed until February 3rd, 2021. Results A total of 16 patients were enrolled in this study. There were 5, 4, 4, and 3 patients treated with GEM/CAP combination as the second-, third-, fourth-, and fifth-line settings, respectively. There were 8 patients with partial response (PR) (50.00%), 6 with stable disease (SD) (37.50%), 2 with progressive disease (PD) (12.50%), and none with complete response (CR). The objective response rate and disease control rate (DCR) were 50.00% and 87.50%, respectively. The most common hematological and nonhematological adverse events (AEs) at any grade were neutropenia (31.25%) and hand-foot syndrome (43.75%). At a median follow-up of 29.3 months with 95% confidence interval (CI) of 20.3 to 38.3 months, the median progression-free survival (PFS) was 9.3 months (95% CI: 6.5-12.1 months). The median overall survival (OS) was 41.5 months (95% CI: 3.1-79.8 months). Conclusions This retrospective study demonstrated the potential clinical benefit of GEM in combination with CAP for pretreated PLELC. Future multicenter large-scale, prospective studies are warranted.
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Affiliation(s)
- Qi-Hua Zou
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China;,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Hui Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China;,Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Cai-Wen Huang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China;,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China;,Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Li-Ping Kang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China;,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Bo Qiu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China;,Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jian-Liang Mai
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China;,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yong-Bin Lin
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China;,Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ying Liang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China;,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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Pang LL, Liao J, Huang YH, Gan JD, Zhuang WT, Lv Y, Liang WT, Zhang L, Fang WF. Exploration of immunotherapy in advanced pulmonary lymphoepithelioma-like carcinoma. Int J Cancer 2023; 152:2338-2350. [PMID: 36631999 DOI: 10.1002/ijc.34426] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 12/08/2022] [Accepted: 12/13/2022] [Indexed: 01/13/2023]
Abstract
Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and histologically distinctive subtype of nonsmall cell lung cancer (NSCLC). High expression of programmed death ligand 1 (PD-L1) and scarcity of druggable driver mutations raise the potential of immunotherapy for advanced PELEC. However, evidence on the clinical impact of immune-checkpoint inhibitors (ICIs) remained limited and unconvincing. The present study retrospectively enrolled advanced PLELC patients who received ICIs either as up-front or salvage therapy in SYSUCC between March 15, 2017 and March 15, 2022. The comparative efficacy of chemoimmunotherapy vs chemotherapy in the first-line setting and chemoimmunotherapy vs ICIs monotherapy in the ≥2 line setting was investigated. A total of 96 patients were finally enrolled; 49 PLELC patients received immunotherapy plus platinum-based chemotherapy, while 45 patients received platinum-based chemotherapy as first-line treatment. Patients with chemoimmunotherapy significantly obtain more survival benefits than those receiving chemotherapy (median progression-free survival [PFS]: 15.6 vs 8.6 months, P = .0015). Additionally, patients with chemoimmunotherapy obtained more PFS benefits than those with ICIs monotherapy in the ≥2 line of therapy (median PFS: 21.7 months vs 7.8 months, P = .094). A significant correlation was observed between prognostic nutritional index (PNI) and favorable treatment outcomes in patients receiving first-line chemoimmunotherapy (median PFS: 17.8 months vs 7.6 months, P < .0001). Likewise, patients in the monocyte-to-lymphocyte ratio (MLR)-high group had significantly shorter PFS than the MLR-low group (median PFS: 11.2 months vs not reached, P = .0009). Our study elucidated the superior efficacy of ICIs therapy, especially chemoimmunotherapy in advanced PLELC, which may provide new insight into the role of immunotherapy in advanced PLELC.
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Affiliation(s)
- Lan-Lan Pang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jun Liao
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yi-Hua Huang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jia-Di Gan
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wei-Tao Zhuang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yi Lv
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Wei-Ting Liang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Li Zhang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Feng Fang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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9
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Zhou N, Tang H, Yu S, Lin Y, Wang Y, Wang Y. Anti-PD-1 antibodies, a novel treatment option for advanced chemoresistant pulmonary lymphoepithelioma carcinoma. Front Immunol 2022; 13:1001414. [PMID: 36561745 PMCID: PMC9763302 DOI: 10.3389/fimmu.2022.1001414] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 11/17/2022] [Indexed: 12/12/2022] Open
Abstract
Background Pulmonary lymphoepithelioma-like carcinoma (LELC) exhibits a unique immune microenvironment, including high PD-L1 expression and abundant infiltrating-immune cells. However, the availability of PD-1/PD-L1 inhibitors in patients with LELC is still not determined. Methods A total of 36 cases of pulmonary LELC treated with PD-1/PD-L1 inhibitors were reviewed, including 10 cases from our institute and 26 cases included from the literature. The Kaplan-Meier method and log-rank test were utilized to analyze the survival outcomes of LELC patients receiving immunotherapy, and the factors related to immunotherapy response were further examined. Results Of the 10 patients from our institute, the median age was 53.5 years, adrenal glands and distant lymph nodes were the most common metastatic sites, and 4 of 8 (50%) patients had a PD-L1 TPS ≥50%. The median progression-free survival and overall survival in patients from our institute and from the literature were 11.6 and 27.3 months, 17.2 months and not reached, respectively. In all 36 patients, the objective response rate was as high as 57.6%. Patients with higher PD-L1 expression were more likely to have a tumor response, but the association of PD-L1 expression with survival time remains to be determined. Conclusions PD-1/PD-L1 inhibitors in patients with pulmonary LELC demonstrated a promising efficacy in retrospective cohorts, and deserve further validation in prospective studies administrating in front-line setting.
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Affiliation(s)
- Na Zhou
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hui Tang
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuangni Yu
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Lin
- Department of oncology, Centro Hospitalar Conde de Sao Januario, Estrada do Visconde de S. Januario, Macau, China
| | - Yingyi Wang
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,*Correspondence: Yingyi Wang, ; Yuzhou Wang,
| | - Yuzhou Wang
- Department of oncology, Centro Hospitalar Conde de Sao Januario, Estrada do Visconde de S. Januario, Macau, China,*Correspondence: Yingyi Wang, ; Yuzhou Wang,
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10
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Shechter O, Sausen DG, Gallo ES, Dahari H, Borenstein R. Epstein-Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments. Int J Mol Sci 2022; 23:14389. [PMID: 36430864 PMCID: PMC9699474 DOI: 10.3390/ijms232214389] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/06/2022] [Accepted: 11/14/2022] [Indexed: 11/22/2022] Open
Abstract
Epstein-Barr virus (EBV) is one of eight known herpesviruses with the potential to infect humans. Globally, it is estimated that between 90-95% of the population has been infected with EBV. EBV is an oncogenic virus that has been strongly linked to various epithelial malignancies such as nasopharyngeal and gastric cancer. Recent evidence suggests a link between EBV and breast cancer. Additionally, there are other, rarer cancers with weaker evidence linking them to EBV. In this review, we discuss the currently known epithelial malignancies associated with EBV. Additionally, we discuss and establish which treatments and therapies are most recommended for each cancer associated with EBV.
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Affiliation(s)
- Oren Shechter
- Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23501, USA
| | - Daniel G. Sausen
- Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23501, USA
| | - Elisa S. Gallo
- Tel-Aviv Sourasky Medical Center, Division of Dermatology, Tel-Aviv 6423906, Israel
| | - Harel Dahari
- The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
| | - Ronen Borenstein
- The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
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11
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Zhong YM, Yin K, Chen Y, Xie Z, Lv ZY, Yang JJ, Yang XN, Zhou Q, Wang BC, Zhong WZ, Gao LL, Zhou WB, Chen J, Tu HY, Liao RQ, Zhang DK, Zhang SL, Lu DX, Zheng HB, Zhang HH, Wu YL, Zhang XC. PD-1/PD-L1 combined with LAG3 is associated with clinical activity of immune checkpoint inhibitors in metastatic primary pulmonary lymphoepithelioma-like carcinoma. Front Immunol 2022; 13:951817. [PMID: 36263036 PMCID: PMC9574915 DOI: 10.3389/fimmu.2022.951817] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 08/16/2022] [Indexed: 11/13/2022] Open
Abstract
Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is an Epstein–Barr virus (EBV)-related, rare subtype of non-small-cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) show durable responses in advanced NSCLC. However, their effects and predictive biomarkers in PLELC remain poorly understood. We retrospectively analyzed the data of 48 metastatic PLELC patients treated with ICI. Pretreated paraffin-embedded specimens (n = 19) were stained for PD-1, PD-L1, LAG3, TIM3, CD3, CD4, CD8, CD68, FOXP3, and cytokeratin (CK) by multiple immunohistochemistry (mIHC). Next-generation sequencing was performed for 33 PLELC samples. Among patients treated with ICI monotherapy (n = 30), the objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and overall survival (mOS) were 13.3%, 80.0%, 7.7 months, and 24.9 months, respectively. Patients with PD-L1 ≥1% showed a longer PFS (8.4 vs. 2.1 months, p = 0.015) relative to those with PD-L1 <1%. Among patients treated with ICI combination therapy (n = 18), ORR, DCR, mPFS, and mOS were 27.8%, 100.0%, 10.1 months, and 19.7 months, respectively. Patients with PD-L1 ≥1% showed a significantly superior OS than those with PD-L1 <1% (NA versus 11.7 months, p = 0.001). Among the 19 mIHC patients, those with high PD-1/PD-L1 and LAG3 expression showed a longer PFS (19.0 vs. 3.9 months, p = 0.003). ICI also showed promising efficacy for treating metastatic PLELC. PD-L1 may be both predictive of ICI treatment efficacy and prognostic for survival in PLELC. PD-1/PD-L1 combined with LAG3 may serve as a predictor of ICI treatment effectiveness in PLELC. Larger and prospective trials are warranted to validate both ICI activity and predictive biomarkers in PLELC.This study was partly presented as a poster at the IASLC 20th World Conference on Lung Cancer 2019, 7–10 September 2019, Barcelona, Spain.
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Affiliation(s)
- Yu-Min Zhong
- Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Kai Yin
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Yu Chen
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhi Xie
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhi-Yi Lv
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jin-Ji Yang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xue-Ning Yang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Qing Zhou
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Bin-Chao Wang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Wen-Zhao Zhong
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ling-Ling Gao
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Wen-Bin Zhou
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ji Chen
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Hai-Yan Tu
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ri-Qiang Liao
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Dong-Kun Zhang
- Department of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Shui-Lian Zhang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Dan-Xia Lu
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Hong-Bo Zheng
- Department of Medical Affairs, Genecast Biotechnology, Wuxi, China
| | - Heng-Hui Zhang
- Department of Medical Affairs, Genecast Biotechnology, Wuxi, China
| | - Yi-Long Wu
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xu-Chao Zhang
- Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- *Correspondence: Xu-Chao Zhang,
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12
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Archwamety A, Ruangchira-Urai R, Akewanlop C, Korphaisarn K. Primary pulmonary lymphoepithelioma-like carcinoma treated with immunotherapy: A case report and literature review. Thorac Cancer 2022; 13:2539-2541. [PMID: 35830974 PMCID: PMC9436678 DOI: 10.1111/1759-7714.14580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 12/02/2022] Open
Abstract
Here, we report a case of metastatic Epstein–Barr virus (EBV)‐related primary pulmonary lymphoepithelioma‐like carcinoma (PPLELC) in a young, nonsmoking female who responded well to treatment with two types of immune checkpoint inhibitors (ICIs). This is the first case report of a favorable outcome to ICIs in the late‐line treatment of advanced PPLELC patients with programmed cell death‐ligand 1 (PD‐L1) expression.
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Affiliation(s)
- Anita Archwamety
- Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Ruchira Ruangchira-Urai
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Charuwan Akewanlop
- Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Krittiya Korphaisarn
- Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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13
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Zhu Y, Dang Z, Xu H, Yuan Y, Chen Y, Li Z. High PD-L1 level of advanced hepatic lymphoepithelioma-like carcinoma response favorably to lenvatinib plus toripalimab. Cancer Sci 2022; 113:1880-1884. [PMID: 35298067 PMCID: PMC9128174 DOI: 10.1111/cas.15339] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/07/2022] [Accepted: 03/12/2022] [Indexed: 02/05/2023] Open
Abstract
Lymphoepithelioma-like carcinoma (LELC) is an uncommon subtype of primary liver cancer with predominant lymphocyte infiltration and a relatively favorable outcome. However, no standard treatment for advanced hepatic LELC has been established. Here, we give a first report of a 60-year-old man with advanced hepatic LELC who had a high expression of PD-L1 in tumor cells and a high level of tumor-infiltrating leukocytes (TILs) in the tumor microenvironment (TME). After receiving six cycles of multiple receptor tyrosine kinase inhibitor (rTKI) with lenvatinib plus PD-1 inhibitor toripalimab treatment, the patient achieved persistent partial response (PR). Our report indicates that advanced hepatic LELC with high expression of PD-L1 may benefit from the combination of rTKI and PD-L1/PD-1 blockade. Therefore, this potential strategy should be considered when treating those rare liver cancers.
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Affiliation(s)
- Yueting Zhu
- Department of Biotherapy, Cancer CenterWest China HospitalSichuan UniversityChengduChina
| | - Zhuyi Dang
- Department of Radiotherapy, Cancer CenterWest China HospitalSichuan UniversityChengduChina
| | - Hang Xu
- Department of UrologyInstitute of UrologyWest China HospitalSichuan UniversityChengduChina
| | - Yunlong Yuan
- West China Medical SchoolSichuan UniversityChengduChina
| | - Ye Chen
- Department of Abdominal Cancer, Cancer CenterWest China HospitalSichuan UniversityChengduChina
| | - Zhiping Li
- Department of Radiotherapy, Cancer CenterWest China HospitalSichuan UniversityChengduChina
- Department of Abdominal Cancer, Cancer CenterWest China HospitalSichuan UniversityChengduChina
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14
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Xiao Y, He J, Luo S, Dong M, Li W, Liu G, Chen H, Yang X, Huang S. Comparison of Immunotherapy, Chemotherapy, and Chemoimmunotherapy in Advanced Pulmonary Lymphoepithelioma-Like Carcinoma： A Retrospective Study. Front Oncol 2022; 12:820302. [PMID: 35237520 PMCID: PMC8882604 DOI: 10.3389/fonc.2022.820302] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/24/2022] [Indexed: 12/25/2022] Open
Abstract
Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare subtype of lung cancer that is associated with the Epstein-Barr virus in Asia. Due to the lack of prospective studies, the best first-line treatment and survival outcomes remain unclear. Herein, This study investigated the efficacy and safety of different treatment regimens for advanced pLELC. This retrospective study included 68 patients with advanced pLELC from two centers in China. Patients were divided into three groups according to different first-line treatments: chemotherapy (n=49, 72.1%), immunotherapy (n=7, 10.3%), and chemoimmunotherapy (n=12,17.6%). The primary endpoint of this study was the 2-year progression-free survival (PFS) of each group. The results show that the median PFS was 6.9 months (range, 2.3–not estimable) in the chemotherapy group, 11.0 months (range, 2–not estimable) in the immunotherapy group, and 11.8 months (range, 6–not estimable) in the chemoimmunotherapy group. There was a significant difference in 2-year PFS between the chemoimmunotherapy group and the chemotherapy group (hazard ratio, 0.38, 95% confidence interval: 0.18-0.78, log-rank P=0.007). The most frequent grade 3-4 adverse event in the chemotherapy and chemoimmunotherapy groups was myelosuppression (10/49 [22.4%] and 4/12 [33.3%], respectively). The most frequent grade 3-4 adverse events in the immunotherapy group were diarrhea (1/7, 14.8%) and hepatotoxicity (1/7, 14.8%). Chemoimmunotherapy had the highest 2-year PFS as a first-line treatment for advanced pLELC compared to chemotherapy and immunotherapy. This study suggests that chemoimmunotherapy may be the best first-line treatment for patients with advanced pLELC.
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Affiliation(s)
- Yi Xiao
- Department of Thoracocardiac Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jinyuan He
- Department of Thoracocardiac Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shaoning Luo
- Department of Emergency Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Min Dong
- Department of Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wei Li
- Department of Thoracocardiac Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Urology, Affiliated Hospital of Xizang Minzu University, Xianyang, China
| | - Gaijiao Liu
- Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hongjie Chen
- Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, China
- *Correspondence: Shaohong Huang, ; Xiongwen Yang, ; Hongjie Chen,
| | - Xiongwen Yang
- Department of Surgical Oncology, The First People’s Hospital of ChenZhou City, Chenzhou, China
- College of Medicine, South China University of Technology, Guangzhou, China
- *Correspondence: Shaohong Huang, ; Xiongwen Yang, ; Hongjie Chen,
| | - Shaohong Huang
- Department of Thoracocardiac Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- *Correspondence: Shaohong Huang, ; Xiongwen Yang, ; Hongjie Chen,
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15
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Weng W, Sheng W, Wang L. Human Papillomavirus-Associated Lymphoepithelioma-Like Carcinoma of the Anal Canal: A Case Report and Literature Review. Front Med (Lausanne) 2021; 8:766960. [PMID: 34869478 PMCID: PMC8641443 DOI: 10.3389/fmed.2021.766960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 10/19/2021] [Indexed: 12/02/2022] Open
Abstract
Lymphoepithelioma-like carcinoma is a rare type of tumor that is histologically identical to lymphoepithelial carcinoma of the nasopharynx. Lymphoepithelioma-like carcinomas (LELCs) are closely associated with viral infections. Human papillomavirus (HPV)-associated LELCs have been reported in a variety of anatomic sites. We reported an extremely rare case of a 25-year-old woman with LELC derived from the anal canal, which is the second case reported at this site. The tumor was diffusely positive for p16 staining, and was correlated with high-risk HPV-16; Epstein-Barr virus-encoded small RNA was negative; PD-L1 positivity and abundant CD8+ T cell infiltration were observed, indicating a “hot” immune microenvironment. In reporting this case, we highlight the potential for misdiagnosis and suggested an association of HPV infection with LELC in the anal canal.
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Affiliation(s)
- Weiwei Weng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Institute of Pathology, Fudan University, Shanghai, China
| | - Weiqi Sheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Institute of Pathology, Fudan University, Shanghai, China
| | - Lei Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Institute of Pathology, Fudan University, Shanghai, China
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16
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Novel Multimodal Management of Post-Partum Synchronous Metastatic Pulmonary EBV-Associated Lymphoepithelioma-Like Carcinoma (LELC)-A Case Report. Diagnostics (Basel) 2021; 11:diagnostics11112072. [PMID: 34829420 PMCID: PMC8624618 DOI: 10.3390/diagnostics11112072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/01/2021] [Accepted: 11/05/2021] [Indexed: 11/17/2022] Open
Abstract
Primary Epstein-Barr-Virus (EBV)-associated pulmonary lymphoepithelioma-like carcinoma (LELC) is an aggressive rare cancer. Higher incidences have been observed in Asian sub-populations. Multimodal treatment paradigms have emerged as promising novel strategies in the management of advanced NSCLC. In this report, we describe the case of a 34-year-old female patient of Asian origin with a post-partum initial diagnosis of pulmonary LELC. Multimodal treatment with chemoimmunotherapy and hypofractionated irradiation to the primary tumour and main metastatic sites led to a favourable response demonstrating that radiotherapy may potentially augment anti-tumour immunity. To the best of our knowledge, this is the first case report on this novel therapy strategy of multi-site hypofractionated radiotherapy and chemoimmunotherapy for metastatic pulmonary EBV-associated LELC.
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17
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Liu Y, Long L, Liu J, Zhu L, Luo F. Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification. Front Oncol 2021; 11:749682. [PMID: 34692530 PMCID: PMC8531585 DOI: 10.3389/fonc.2021.749682] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 09/16/2021] [Indexed: 02/05/2023] Open
Abstract
Background Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC). Currently, anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has become an important treatment for NSCLC. Anti-human PD-1 monoclonal antibodies, such as nivolumab, significantly prolong the survival time of patients with advanced lung adenocarcinoma and lung squamous cell carcinoma. However, there are few reports on the therapeutic effect, drug resistance mechanism, and strategies to overcome resistance to anti-PD-1/PD-L1 treatment in advanced pulmonary LELC. We report the case of a patient with advanced pulmonary LELC harboring fibroblast growth factor receptor (FGFR)3 gene amplification that showed resistance to nivolumab. After treatment with anlotinib, a multi-targeted small-molecule tyrosine kinase inhibitor, the patient’s resistance to nivolumab was reversed. She achieved long-term disease remission with a combination of anlotinib and nivolumab treatment. Case Presentation A 68-year-old woman was diagnosed with stage IVA pulmonary LELC. After multiple-line chemotherapy, her disease progressed. Since the PD-L1 expression rate of the patient was 90%, nivolumab was administered. However, the therapeutic effect of nivolumab was not ideal; the disease continued to progress, and a new cervical lymph node metastasis appeared. FGFR3 gene amplification was detected in lymph node metastasis. Based on this gene abnormality, we added anlotinib to the treatment. After two cycles of anlotinib and nivolumab, the metastatic focus of the patient was significantly reduced. The patient continued to receive this combined treatment and achieved remission for more than 15 months. Conclusion Pulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.
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Affiliation(s)
- Yanyang Liu
- Lung Cancer Center, Cancer Center, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Lang Long
- Lung Cancer Center, Cancer Center, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Jiewei Liu
- Lung Cancer Center, Cancer Center, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Lingling Zhu
- Lung Cancer Center, Cancer Center, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Feng Luo
- Lung Cancer Center, Cancer Center, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
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