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Shen LL, Zheng HL, Zheng ZW, Xu BB, Xue Z, Jia-Lin, Chen QY, Xie JW, Li P, Huang CM, Lin JX, Zheng CH. Paradoxical effects of adiposity and inflammation on immunotherapy efficacy in gastric cancer: novel insights from real-world data. Gastric Cancer 2025:10.1007/s10120-025-01622-w. [PMID: 40350511 DOI: 10.1007/s10120-025-01622-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Accepted: 04/29/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND Emerging studies suggest obesity may improve PD-1/PD-L1 inhibitor efficacy, correlating with prolonged survival, known as the 'obesity paradox'. However, the impact of this paradox and obesity-related chronic inflammation on immunotherapy for advanced gastric cancer (AGC) has not received sufficient research. METHODS Between January 2018 and December 2021, patients receiving neoadjuvant therapy were categorized into two groups: combined immunotherapy (ICIs, n = 173) and neoadjuvant chemotherapy (NAC, n = 126). Visceral (VATI) and subcutaneous adipose tissue index (SATI) were obtained from pre-treatment CT images. The systemic immune-inflammation index (SII) was calculated as platelet count multiplied by the neutrophil-to-lymphocyte ratio. RESULTS The median age of patients was 64 years (IQR 56-69), with 219 (73.2%) males and 80 (26.8%) females. In the ICIs group, the VATI-High group showed significantly higher 3-year overall survival (OS) (p = 0.010) and disease-free survival (DFS) (p = 0.029). Similar results were observed in the SATI analysis (p < 0.05). Conversely, OS (p = 0.040) and DFS (p = 0.039) were significantly lower in the SII-High group. Both VATI and SATI were independent protective factors for OS and DFS, but the effect disappeared after adjustment for SII. SII was associated with poorer OS and DFS, even after adjustment for VATI and SATI. No significant differences were observed in the analysis of the NAC group. CONCLUSIONS Elevated adiposity indices (VATI/SATI) and low SII correlate with survival benefit in ICI-treated AGC patients, and importantly, this paradoxical survival benefit is dependent on SII status. In contrast, no such benefit is observed in chemotherapy-alone cohorts.
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Affiliation(s)
- Li-Li Shen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Zhi-Wei Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Bin-Bin Xu
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
- Department of Digestive Endoscopy, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Zhen Xue
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jia-Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin Quan Road, 59, Fuzhou, 350001, Fujian, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
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Bahardoust M, Torabi S, Yarahmadi D, Kakoienejad MM, Abbasi F, Shamohammadi M, Haghmoradi M, Goodarzy B, Tizmaghz A. Impact of negative lymph node removal on survival in esophageal cancer: a systematic review and meta-analysis. BMC Surg 2025; 25:124. [PMID: 40155975 PMCID: PMC11951649 DOI: 10.1186/s12893-025-02858-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 03/18/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND Recent studies have reported that a high number of negative lymph nodes (NLNs) removed can be associated with improved survival in esophageal cancer( EC) after surgery; however, the effect size of a high number of removed NLNs on survival rates has been reported to vary, which may be due to the small sample size of early studies. This meta-analysis aimed to evaluate the effect of the high number of NLNs removed on the survival rate of patients with EC after surgery. METHODS We searched PubMed, Embase, Scopus, Web of Science, and Google Scholar databases with relevant Mesh terms to find studies that investigated the effect of the number of NLNs resected on the survival of EC patients after surgery until February 17, 2025. This systematic review was conducted based on the PRISMA 2020 checklist. Cochran's I2 was used to evaluate heterogeneity between studies. Publication bias was evaluated using the Egger test. Heterogeneity between studies was controlled by meta-regression. Finally, eight studies involving 5,521 EC patients were included. RESULTS The survival rate in patients whose number of removed NLNs ≥ 19 was significantly better than those with removed NLNs < 19 (HR: 0.88, 95% CI: 0.81, 0.95, I2 = 84.4). Subgroup analysis of 8 studies showed that the protective effect of the high number of removed NLNs) ≥ 19 (was greater in adenocarcinoma patients than in SCC (Pooled HR: 0.63 vs. 0.88). CONCLUSION The high number of NLNs removed (≥ 19) during surgery was associated with improved survival after surgery, especially in patients with adenocarcinoma. Removing ≥ 19 NLNs significantly improves survival in EC patients, particularly those with adenocarcinoma. This threshold should be incorporated into surgical guidelines.
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Affiliation(s)
- Mansour Bahardoust
- Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Danyal Yarahmadi
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Fatemeh Abbasi
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Meisam Haghmoradi
- Department of Orthopedic Surgery, Urmia University of Medical Sciences, Urmia, Iran
| | - Babak Goodarzy
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Adnan Tizmaghz
- Firoozabadi Clinical Research Development Unit (F A CRD U), Iran University of Medical Sciences (IUMS), Tehran, Iran.
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Namikawa K, Sverrisdottir M, Fridgeirsson HF, Hjaltason HD, Sigmundsson HK, Jonasson JG, Bjornsson ES, Konradsson M. Characteristics and Neoplastic Progression in Barrett's Esophagus: A Large Population-Based Study from Iceland. Diagnostics (Basel) 2025; 15:684. [PMID: 40150027 PMCID: PMC11941158 DOI: 10.3390/diagnostics15060684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 02/28/2025] [Accepted: 03/04/2025] [Indexed: 03/29/2025] Open
Abstract
Background: Barrett's esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC). However, reports on incidence and progression-to-neoplasm rates have been very variable and conflicting. The aims of the study were to evaluate the characteristics of BE and its progression to neoplasm in a large homogeneous population. Methods: This was a retrospective population-based study with patients identified from 11 institutions through the databases in two centralized pathology laboratories. Demographics and relevant clinicopathological features were obtained from medical records among patients with a pathologically confirmed BE by the presence of intestinal metaplasia between 2003 and 2022. Results: A total of 1388 patients were identified with BE: 948 were men (69%); the median age at diagnosis was 62 years (IQR, 53-72). The ratio of long-segment BE to short-segment BE was significantly higher in patients ≥ 60 years (1.15, 284/248) than those ≤ 60 years (0.77, 205/265) (p = 0.0025). At BE diagnosis, 9.4% had neoplasms: LGD (n = 65), HGD (n = 16), and EAC (n = 49). Among 1258 non-dysplastic BE (NDBE) patients, 4.6% developed a neoplasm-LGD (n = 35), HGD (n = 8), and EAC (n = 15)-with a median observation-period of 5 years (IQR, 3-7). Overall, 160 cases with neoplasms were diagnosed in this BE cohort; 130 (74%) were present at initial BE diagnosis, and 58 (26%) progressed to neoplasms from NDBE. Conclusions: The ratio of long-segment BE was found to be significantly higher in patients ≥ 60 years. Around 9% of the patients were diagnosed as harboring a neoplasm concomitantly with BE, accounting for approximately 74% of all neoplasms. After a median follow-up of 5 years, about 5% of BE showed dysplastic or malignant progression.
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Affiliation(s)
- Ken Namikawa
- Department of Gastroenterology, Landspitali—The National University Hospital of Iceland, 101 Reykjavik, Iceland
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | | | | | | | | | - Jon Gunnlaugur Jonasson
- Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
- Department of Pathology, Landspitali—The National University Hospital of Iceland, 101 Reykjavik, Iceland
| | - Einar Stefan Bjornsson
- Department of Gastroenterology, Landspitali—The National University Hospital of Iceland, 101 Reykjavik, Iceland
- Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
| | - Magnus Konradsson
- Department of Gastroenterology, Landspitali—The National University Hospital of Iceland, 101 Reykjavik, Iceland
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Dong C, Li Z. Circ_0096710 facilitates tumor growth via controlling ADAM10 expression in esophageal squamous cell carcinoma. Thorac Cancer 2025; 16:e15483. [PMID: 39620490 PMCID: PMC11729450 DOI: 10.1111/1759-7714.15483] [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: 07/02/2024] [Revised: 09/26/2024] [Accepted: 10/20/2024] [Indexed: 01/15/2025] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a global cancer related to the sixth largest cause of death. Circular RNAs (circRNAs) have affected the progress of ESCC during recent years, but the mechanism is not completely clear. So here we probed the effects of hsa_circ_0096710 (circ_0096710) in ESCC. METHODS Relative levels of circ_0096710, miR-1294, and ADAM10 were quantified by the quantitative real-time reverse transcription-polymerase chain reaction in ESCC tissues. Western blot assessed ADAM10, PCNA, MMP2, VEGFA, and OCT4 protein levels. Cell proliferative capacity was assessed by cell counting and cell colony-forming assays. Transwell assays assessed cell migration and invasion. Angiogenesis was detected by tube formation assays. Stemness of cancer cells was estimated by sphere formation assays. Dual-luciferin reporter and RNA immunoprecipitation assays determined the targeting relationship between miR-1294 and circ_0096710 or ADAM10. RESULTS Relative levels of circ_0096710 and ADAM10 mRNA were upregulated in ESCC cells, yet miR-1294 was downregulated. Circ_0096710 silencing repressed ESCC cell proliferation, migration, invasion, angiogenesis, and stem-like properties. Moreover, circ_0096710 was an upstream target of miR-1294, and miR-1294 inhibition reversed the role of circ_0096710 downregulation in ESCC cells. Furthermore, ADAM10 was a downstream target of miR-1294, and miR-1294 overexpression suppressed ESCC cell proliferation, migration, invasion, angiogenesis, and stem-like properties by targeting ADAM10. Meanwhile, circ_0096710 upgraded ADAM10 expression through sponging miR-1294. Also, circ_0096710 downregulation restrained tumor growth in mouse models. CONCLUSION Circ_0096710 upregulates ADAM10 via mediating miR-1294 expression so as to accelerate the occurrence of ESCC, suggesting that circ_0096710 may be a potential therapeutic target for ESCC.
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Affiliation(s)
- Chaoqun Dong
- Department of Thoracic SurgeryShanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan CityChina
| | - Zhilong Li
- Department of Thoracic SurgeryShanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan CityChina
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Caccialanza R, Da Prat V, De Luca R, Weindelmayer J, Casirati A, De Manzoni G. Nutritional support via feeding jejunostomy in esophago-gastric cancers: proposal of a common working strategy based on the available evidence. Updates Surg 2025; 77:153-164. [PMID: 39482454 DOI: 10.1007/s13304-024-02022-y] [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: 02/02/2024] [Accepted: 10/16/2024] [Indexed: 11/03/2024]
Abstract
Malnutrition is common in patients affected by esophago-gastric cancers and has a negative impact on both clinical and economic outcomes. Yet not all patients at risk of malnutrition are routinely assessed and receive appropriate support. Further, available research does not provide a mean for standardization of timing, route, and dosage for nutritional support, and this is particularly true for enteral nutrition via feeding jejunostomy. Herein, we provide an overview of the current evidence and use the gathered knowledge as a starting point for a consensus proposal. As a result, we aim to facilitate the development of appropriate and uniformed interventions, thus fulfilling the need for a multimodal therapeutic approach in these set of cancer patients.
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Affiliation(s)
- Riccardo Caccialanza
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Valentina Da Prat
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Raffaele De Luca
- Department of Surgical Oncology, IRCCS-Istituto Tumori "Giovanni Paolo II, Bari, Italy
| | - Jacopo Weindelmayer
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124, Verona, Italy
| | - Amanda Casirati
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Giovanni De Manzoni
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Borgo Trento Hospital, Piazzale Stefani 1, 37124, Verona, Italy.
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6
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Qureshi S, Abbasi WA, Qureshi MA, Jalil HA, Quraishy MS. Identification of PGC as a Potential Biomarker for Progression from Barrett's Esophagus to Esophageal Adenocarcinoma: A Comprehensive Bioinformatic Analysis. Diagnostics (Basel) 2024; 14:2863. [PMID: 39767224 PMCID: PMC11675858 DOI: 10.3390/diagnostics14242863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 11/28/2024] [Accepted: 12/04/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Barrett's esophagus (BE), with metaplastic columnar epithelium in the lower esophagus, predisposes patients to esophageal adenocarcinoma (EAC). Despite extensive research, mechanisms underlying BE progression to EAC remain unclear, and no validated biomarkers are available for clinical use. Progastricsin/Pepsinogen-C (PGC), an aspartic proteinase linked to maintaining normal epithelial morphology, is often absent in advanced gastrointestinal malignancies. This study comprehensively investigates PGC expression across cancers, particularly in esophageal cancer (ESCA), to clarify its role in BE progression to EAC. Methods: We utilized multiple bioinformatic platforms (TIMER, UALCAN, cBioPortal, GEPIA, STRING, Metascape, and GEO database) to assess PGC expression, genomic alterations, and correlations with clinicopathological features, survival, and immune infiltration. Additionally, using the GEO dataset, we compared non-dysplastic Barrett's esophagus (NDBE) patients with those who progressed to malignancy, identifying differentially expressed genes (DEGs), their interactions, and potential roles in progression. Results: PGC was notably upregulated in various cancers, especially in adjacent normal tissues of ESCA. Genomic amplifications of PGC were linked to improved survival in EAC patients, particularly those with high PGC expression, suggesting a protective role. Moreover, PGC expression positively correlated with favorable immune infiltration, notably B cells and CD8+ T cells. Enrichment analysis of downregulated DEGs revealed significant involvement in key biological processes, specifically in extracellular matrix organization. Among the downregulated DEGs, we identified PGC among the top 10 hub genes, underscoring its role in tissue homeostasis. Conclusions: These findings suggest that PGC could serve as a promising biomarker for predicting the high-risk transformation from BE to EAC, offering new insights into EAC progression and future therapeutic targets.
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Wheless MC, Comer M, Gibson MK. Evolving Treatment Landscape for Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma. Curr Oncol Rep 2024; 26:1469-1488. [PMID: 39441479 PMCID: PMC11579124 DOI: 10.1007/s11912-024-01607-5] [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] [Accepted: 09/05/2024] [Indexed: 10/25/2024]
Abstract
PURPOSE OF REVIEW This review highlights advances and recent changes in the treatment paradigm for advanced esophageal adenocarcinoma (EAC) and gastroesophageal junction adenocarcinoma (GEJAC). RECENT FINDINGS Chemotherapy remains the backbone of treatment for advanced EAC/GEJAC. New targets/agents include immunotherapy, HER-2, claudin18.2, and FGFR2b, with various mechanisms (CAR-T, bispecific mAB, ADCs) altering the treatment landscape against these targets. The approaches to these targets may act together, in sequence, and even synergistically to improve outcomes. Herein, we review the state of the field, including highlighting ongoing clinical trials and additional emerging agents and approaches.
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Affiliation(s)
- Margaret C Wheless
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Margaret Comer
- Vanderbilt University Medical School, Nashville, TN, USA
| | - Michael K Gibson
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
- Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN, 37232, USA.
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Zhang WY, Chang YJ, Shi RH. Artificial intelligence enhances the management of esophageal squamous cell carcinoma in the precision oncology era. World J Gastroenterol 2024; 30:4267-4280. [PMID: 39492825 PMCID: PMC11525855 DOI: 10.3748/wjg.v30.i39.4267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 08/31/2024] [Accepted: 09/19/2024] [Indexed: 10/12/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer with a poor prognosis. Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients. With the advancement of artificial intelligence (AI) technology and the proliferation of medical digital information, AI has demonstrated promising sensitivity and accuracy in assisting precise detection, treatment decision-making, and prognosis assessment of ESCC. It has become a unique opportunity to enhance comprehensive clinical management of ESCC in the era of precision oncology. This review examines how AI is applied to the diagnosis, treatment, and prognosis assessment of ESCC in the era of precision oncology, and analyzes the challenges and potential opportunities that AI faces in clinical translation. Through insights into future prospects, it is hoped that this review will contribute to the real-world application of AI in future clinical settings, ultimately alleviating the disease burden caused by ESCC.
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Affiliation(s)
- Wan-Yue Zhang
- School of Medicine, Southeast University, Nanjing 221000, Jiangsu Province, China
| | - Yong-Jian Chang
- School of Cyber Science and Engineering, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Rui-Hua Shi
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
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Tran P, Ancha A, Tjahja M, Shell M, Naumann C. Poor adherence to proper Barrett's esophagus screening and surveillance guidelines in patients with newly diagnosed esophageal adenocarcinoma. Proc AMIA Symp 2024; 37:922-926. [PMID: 39440080 PMCID: PMC11492693 DOI: 10.1080/08998280.2024.2397936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 08/02/2024] [Accepted: 08/10/2024] [Indexed: 10/25/2024] Open
Abstract
Background Screening for Barrett's esophagus (BE) remains controversial, even for high-risk populations. Our study aimed to evaluate the proportion of patients diagnosed with esophageal adenocarcinoma (EAC) who were not screened for BE or did not receive recommended BE surveillance screening. We then evaluated the relationship between cancer staging and screening/surveillance opportunities. Methods This single-center retrospective study included 187 patients from January 2016 to January 2022 with newly diagnosed EAC. Data extracted from patient charts included BE risk factors, and BE, endoscopic, and histologic history. Results A total of 187 patients had a new diagnosis of EAC. Among this group, 44% had appropriate BE surveillance adherence, and 47% of patients met the criteria for BE screening but had not been screened prior to EAC diagnosis. Adherence to BE surveillance was associated with earlier stages of cancer on biopsy. No significant difference in cancer staging was found in those with missed BE screening opportunities. Discussion Patients with a diagnosis of BE who adhered to surveillance guidelines had earlier stage EAC at diagnosis, which emphasizes the importance of surveillance. Most of those with an initial diagnosis of EAC had not received any BE screening.
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Affiliation(s)
- Phi Tran
- Department of Internal Medicine, Baylor Scott and White Medical Center, Temple, Texas, USA
| | - Anupama Ancha
- Department of Internal Medicine, Baylor Scott and White Medical Center, Temple, Texas, USA
| | - Matthew Tjahja
- Department of Internal Medicine, Baylor Scott and White Medical Center, Temple, Texas, USA
| | - Mark Shell
- Division of Gastroenterology, Baylor Scott and White Medical Center, Temple, Texas, USA
| | - Christopher Naumann
- Division of Gastroenterology, Baylor Scott and White Medical Center, Temple, Texas, USA
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10
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Khan IR, Sadida HQ, Hashem S, Singh M, Macha MA, Al-Shabeeb Akil AS, Khurshid I, Bhat AA. Therapeutic implications of signaling pathways and tumor microenvironment interactions in esophageal cancer. Biomed Pharmacother 2024; 176:116873. [PMID: 38843587 DOI: 10.1016/j.biopha.2024.116873] [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: 03/24/2024] [Revised: 05/21/2024] [Accepted: 06/03/2024] [Indexed: 06/20/2024] Open
Abstract
Esophageal cancer (EC) is significantly influenced by the tumor microenvironment (TME) and altered signaling pathways. Downregulating these pathways in EC is essential for suppressing tumor development, preventing metastasis, and enhancing therapeutic outcomes. This approach can increase tumor sensitivity to treatments, enhance patient outcomes, and inhibit cancer cell proliferation and spread. The TME, comprising cellular and non-cellular elements surrounding the tumor, significantly influences EC's development, course, and treatment responsiveness. Understanding the complex relationships within the TME is crucial for developing successful EC treatments. Immunotherapy is a vital TME treatment for EC. However, the heterogeneity within the TME limits the application of anticancer drugs outside clinical settings. Therefore, identifying reliable microenvironmental biomarkers that can detect therapeutic responses before initiating therapy is crucial. Combining approaches focusing on EC signaling pathways with TME can enhance treatment outcomes. This integrated strategy aims to interfere with essential signaling pathways promoting cancer spread while disrupting factors encouraging tumor development. Unraveling aberrant signaling pathways and TME components can lead to more focused and efficient treatment approaches, identifying specific cellular targets for treatments. Targeting the TME and signaling pathways may reduce metastasis risk by interfering with mechanisms facilitating cancer cell invasion and dissemination. In conclusion, this integrative strategy has significant potential for improving patient outcomes and advancing EC research and therapy. This review discusses the altered signaling pathways and TME in EC, focusing on potential future therapeutics.
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Affiliation(s)
- Inamu Rashid Khan
- Department of Zoology, Central University of Kashmir, Ganderbal, Jammu and Kashmir 191201, India
| | - Hana Q Sadida
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha 26999, Qatar
| | - Sheema Hashem
- Department of Human Genetics, Sidra Medicine Doha 26999, Qatar
| | - Mayank Singh
- Department of Medical Oncology (Lab), Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Muzafar A Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Jammu and Kashmir 192122, India
| | - Ammira S Al-Shabeeb Akil
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha 26999, Qatar
| | - Ibraq Khurshid
- Department of Zoology, Central University of Kashmir, Ganderbal, Jammu and Kashmir 191201, India.
| | - Ajaz A Bhat
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha 26999, Qatar.
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Inoue J, Morishita S, Okayama T, Suzuki K, Tanaka T, Nakano J, Fukushima T. Impact of quality of life on mortality risk in patients with esophageal cancer: a systematic review and meta-analysis. Esophagus 2024; 21:270-282. [PMID: 38772959 DOI: 10.1007/s10388-024-01064-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 05/14/2024] [Indexed: 05/23/2024]
Abstract
This systematic review and meta-analysis investigated the impact of quality of life (QoL) on mortality risk in patients with esophageal cancer. A literature search was conducted using the CINAHL, PubMed/MEDLINE, and Scopus databases for articles published from inception to December 2022. Observational studies that examined the association between QoL and mortality risk in patients with esophageal cancer were included. Subgroup analyses were performed for time points of QoL assessment and for types of treatment. Seven studies were included in the final analysis. Overall, global QoL was significantly associated with mortality risk (hazard ratio 1.02, 95% confidence interval 1.01-1.04; p < 0.00004). Among the QoL subscales of QoL, physical, emotional, role, cognitive, and social QoL were significantly associated with mortality risk. A subgroup analysis by timepoints of QoL assessment demonstrated that pre- and posttreatment global and physical, pretreatment role, and posttreatment cognitive QoL were significantly associated with mortality risk. Moreover, another subgroup analysis by types of treatment demonstrated that the role QoL in patients with surgery, and the global, physical, role, and social QoL in those with other treatments were significantly associated with mortality risk. These findings indicate that the assessment of QoL in patients with esophageal cancer before and after treatment not only provides information on patients' condition at the time of treatment but may also serve as an outcome for predicting life expectancy. Therefore, it is important to conduct regular QoL assessments and take a proactive approach to improve QoL based on the results of these assessments.
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Affiliation(s)
- Junichiro Inoue
- Division of Rehabilitation Medicine, Kobe University Hospital International Clinical Cancer Research Center, 1-5-1 Minatojimaminamimachi, Chuo-ku, Kobe, 650-0047, Japan.
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12
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Wang Y, Dai M, Chen X. Prognostic and clinicopathological value of Ki-67 in patients with oesophageal squamous cell carcinoma: a systematic review and meta-analysis. BMJ Open 2024; 14:e083637. [PMID: 38839387 PMCID: PMC11163609 DOI: 10.1136/bmjopen-2023-083637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Accepted: 05/28/2024] [Indexed: 06/07/2024] Open
Abstract
OBJECTIVES The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their findings were inconsistent. Consequently, the present meta-analysis was performed to identify the precise value of Ki-67 in predicting the prognosis of ESCC. DESIGN The current meta-analysis was carried out in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. DATA SOURCES Electronic databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched until 26 September 2023. STATISTICAL METHODS Pooled HRs and corresponding 95% CIs were calculated to estimate the role of Ki-67 in predicting overall survival (OS) and disease-free survival (DFS) in ESCC. Between-study heterogeneity was evaluated using Cochrane's Q test and I2 statistics. Specifically, significant heterogeneities were identified based on p<0.10 on the Q statistic test or I2>50% so the random-effects model should be used; otherwise, the fixed-effects model should be used. The relationship between Ki-67 and clinicopathological characteristics of ESCC was evaluated by combining ORs with their corresponding 95% CIs. RESULTS 11 articles with 1124 patients were included in the present meta-analysis. Based on our analysis, increased Ki-67 expression was markedly associated with poor OS (HR 1.62, 95% CI 1.15 to 2.28, p=0.006) and DFS (HR 1.72, 95% CI 1.22 to 2.43, p=0.002) in ESCC. Moreover, subgroup analysis revealed that Ki-67 upregulation significantly predicted OS and DFS when a Ki-67 threshold of >30% was used. Nonetheless, Ki-67 was not significantly associated with sex, T stage, N stage, TNM stage, tumour differentiation or tumour location. CONCLUSIONS In the present meta-analysis, high Ki-67 expression significantly predicted OS and DFS in patients with ESCC, especially when Ki-67>30% was used as the threshold. These results suggest that Ki-67 could serve as an effective and reliable prognostic indicator for ESCC.
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Affiliation(s)
- Yanyan Wang
- Department of Pathology, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China
| | - Menglu Dai
- Clinical Laboratory, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China
| | - Xu Chen
- Department of Pathology, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China
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13
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Mager LF, Krause T, McCoy KD. Interaction of microbiota, mucosal malignancies, and immunotherapy-Mechanistic insights. Mucosal Immunol 2024; 17:402-415. [PMID: 38521413 DOI: 10.1016/j.mucimm.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 03/09/2024] [Accepted: 03/17/2024] [Indexed: 03/25/2024]
Abstract
The microbiome has emerged as a crucial modulator of host-immune interactions and clearly impacts tumor development and therapy efficacy. The microbiome is a double-edged sword in cancer development and therapy as both pro-tumorigenic and anti-tumorigenic bacterial taxa have been identified. The staggering number of association-based studies in various tumor types has led to an enormous amount of data that makes it difficult to identify bacteria that promote tumor development or modulate therapy efficacy from bystander bacteria. Here we aim to comprehensively summarize the current knowledge of microbiome-host immunity interactions and cancer therapy in various mucosal tissues to find commonalities and thus identify potential functionally relevant bacterial taxa. Moreover, we also review recent studies identifying specific bacteria and mechanisms through which the microbiome modulates cancer development and therapy efficacy.
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Affiliation(s)
- Lukas F Mager
- Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada; Department of Internal Medicine I, Faculty of Medicine, University of Tübingen, Germany; M3 Research Center for Malignom, Metabolome and Microbiome, Faculty of Medicine University Tübingen, Germany
| | - Tim Krause
- Department of Internal Medicine I, Faculty of Medicine, University of Tübingen, Germany; M3 Research Center for Malignom, Metabolome and Microbiome, Faculty of Medicine University Tübingen, Germany
| | - Kathy D McCoy
- Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada.
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Oshima K, Tsushima T, Ito Y, Kato K. Recent progress in chemoradiotherapy for oesophageal squamous cell carcinoma. Jpn J Clin Oncol 2024; 54:395-402. [PMID: 38342589 PMCID: PMC10999767 DOI: 10.1093/jjco/hyae005] [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: 12/14/2023] [Accepted: 01/11/2024] [Indexed: 02/13/2024] Open
Abstract
Oesophageal squamous cell carcinoma is a common malignancy worldwide. Definitive chemoradiotherapy is the standard treatment for patients with resectable stage oesophageal squamous cell carcinoma who cannot undergo surgery, as well as those with locally advanced unresectable oesophageal squamous cell carcinoma. However, it has several disadvantages such as poor survival, radiation-related toxicities and severe and lethal complications related to salvage treatment for residual or recurrent disease. Numerous clinical trials on chemoradiotherapy have been conducted to confirm the optimal combination of irradiation and chemotherapy. For advanced disease, multimodal treatment strategies including salvage surgery are essential. Palliative chemoradiotherapy is also crucial for dysphagia in locally advanced oesophageal squamous cell carcinoma with or without metastatic lesions. Recently, the synergistic mechanism of radiotherapy combined with immunotherapy has been reported. Early phase clinical trials suggest that a combination of immunotherapy and chemoradiotherapy can improve clinical outcomes with manageable side effects, but further investigations are needed. Here, we reviewed the existing clinical data and current development of chemoradiotherapy combined with immunotherapy in patients with oesophageal squamous cell carcinoma.
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Affiliation(s)
- Kotoe Oshima
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Takahiro Tsushima
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Yoshinori Ito
- Department of Radiation Oncology, Showa University School of Medicine, Tokyo, Japan
| | - Ken Kato
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
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15
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Eisner DC. Esophageal cancer: Treatment advances and need for screening. JAAPA 2024; 37:19-24. [PMID: 38484297 DOI: 10.1097/01.jaa.0001007328.84376.da] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2024]
Abstract
ABSTRACT Esophageal cancer is a challenging malignancy that often is diagnosed in advanced stages, resulting in a poor prognosis. This article provides a comprehensive review of the two main types of esophageal cancer, esophageal squamous cell carcinoma and esophageal adenocarcinoma, and reviews epidemiology, risk factors, pathogenesis, diagnostic modalities, staging systems, and established and emerging treatments. Recent advancements in treatment for resectable and unresectable esophageal cancer also are explored. These include immunotherapy, targeted therapy, sentinel lymph node mapping, radiogenomics, palliative measures, and screening measures.
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Affiliation(s)
- Daniel C Eisner
- Daniel C. Eisner is the owner of Systolica LLC, consulting and medical supplies, based in Bel Air, Md. The author has disclosed no potential conflicts of interest, financial or otherwise
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Chen Z, Zhang X, Zhai J, Fan J, Cai Y, Ye T, Wang Z, Cai K. Global burden of esophageal cancer attributable to high BMI in 204 countries and territories: 1990-2019. Thorac Cancer 2024; 15:681-692. [PMID: 38316627 PMCID: PMC10961222 DOI: 10.1111/1759-7714.15239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/20/2024] [Indexed: 02/07/2024] Open
Abstract
BACKGROUND Esophageal cancer (EC), a common and fatal disease, includes two histological subtypes; esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (ECA). To aid policymakers in the allocation of resources for the prevention and treatment of EC, updated data on EC deaths and disability-adjusted life years (DALYs) attributable to high body mass index (BMI) are necessary. The objective of this study was to identify trends in EC associated with high BMI between 1990 and 2019 using 2019 Global Burden of Disease data. METHODS In this observational population-based study, epidemiological data on the association between high BMI and EC were obtained from GBD 2019. The age-standardized mortality rate (ASMRs) and disability-adjusted life year rate (ASDRs) attributable to high BMI-related EC were stratified by year, age, country, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of the ASMRs and ASDRs between 1990 and 2019. RESULTS In 2019, the proportion of EC deaths and DALYs attributed to high BMI was 18.1% and 18.9%, respectively, resulting in 89 904 (95% confidence interval [CI]: 27 879-171 255) deaths and 2 202 314 (95% CI: 681 901-4 173 080) DALYs. High BMI-related deaths and DALYs showed a strong upward trend, increasing by more than two-fold since 1990. East Asia and Western Europe showed the highest risk of EC mortality and DALYs attributable to high BMI; China and the USA bear the greatest burden. The ASMR and ASDR increased in five SDI regions. CONCLUSIONS The incidence of EC is increasing, particularly in developing nations, which may be attributed to the prevalence of high BMI. To mitigate the impact of high BMI on the incidence of EC, it is important to increase awareness of its deleterious effects, which may alleviate the burden of this disease.
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Affiliation(s)
- Zhiming Chen
- Department of Thoracic Surgery, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Xingxing Zhang
- Department of General Surgery, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Jianxue Zhai
- Department of Thoracic Surgery, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Jiayang Fan
- Department of Thoracic Surgery, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Yikuan Cai
- Department of Thoracic Surgery, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Tianlan Ye
- Department of Thoracic Surgery, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Zhizhi Wang
- Department of Thoracic Surgery, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Kaican Cai
- Department of Thoracic Surgery, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
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Liu S, Dou L, Li S. Immune checkpoint inhibitors versus chemotherapy as second-line therapy for advanced oesophageal squamous cell carcinoma: a systematic review and economic evaluation. Therap Adv Gastroenterol 2024; 17:17562848241233134. [PMID: 38425370 PMCID: PMC10903196 DOI: 10.1177/17562848241233134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/20/2024] [Indexed: 03/02/2024] Open
Abstract
Background Recently, several novel programmed cell death protein 1 (PD-1) inhibitors have been approved for second-line treating advanced or metastatic oesophageal squamous cell carcinoma (OSCC), including camrelizumab, nivolumab, pembrolizumab, sintilimab and tislelizumab. However, the optimal treatment regimen remained ambiguous. Objectives The purpose of this study was to investigate the efficacy, safety and economy of available PD-1 inhibitors to determine the optimal treatment from the Chinese healthcare system perspective. Design A systematic review and economic evaluation. Data sources and methods A systematic review was undertaken utilizing PubMed, Web of Science, Cochrane Library, Embase and Scopus databases to identify eligible studies until 31 August 2023. Primary outcomes were progression-free survival (PFS), overall survival (OS) and adverse events (AEs). We also developed a partitioned survival model at 3-week intervals based on five clinical trials to predict long-term costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios for various treatment options. Direct medical costs and utility values were obtained from public drug bidding databases, clinical trials or published literature. The parameter uncertainties within the model were determined via one-way and probabilistic sensitivity analyses. Results Five randomized controlled trials involving 2837 patients were included in the analysis. Compared with other treatments examined, camrelizumab provided the best PFS benefits [hazard ratio (HR): 0.69, 95% confidence interval (CI): 0.56-0.86], and pembrolizumab provided the best OS benefits (HR: 0.55, 95% CI: 0.37-0.82). Nivolumab caused a relatively lower incidence of treatment-related AEs (HR: 0.10, 95% CI: 0.05-0.20) and grade 3-5 AEs (HR: 0.13, 95% CI: 0.08-0.21) than other immunotherapy regimens. In the economic evaluation, average 10-year costs ranged from $5,433.86 (chemotherapy) to $50,617.95 (nivolumab) and mean QALYs ranged from 0.55 (chemotherapy) to 0.82 (camrelizumab). Pembrolizumab was eliminated because of dominance. Of the remaining strategies, when the willingness-to-pay thresholds were 1, 2 and 3 times GDP per capita in 2022, sintilimab, tislelizumab and camrelizumab were the most cost-effective treatment options, respectively. Conclusion Sintilimab might be the optimal treatment alternative for second-line therapy of advanced OSCC in China, followed by tislelizumab and camrelizumab. Trial registration This study has been registered on the PROSPERO database with the registration number CRD42023495204.
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Affiliation(s)
- Shixian Liu
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- NHC Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, China
- Center for Health Preference Research, Shandong University, Jinan, China
| | - Lei Dou
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- NHC Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, China
- Center for Health Preference Research, Shandong University, Jinan, China
| | - Shunping Li
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- NHC Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, China
- Center for Health Preference Research, Shandong University, Jinan, China
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18
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Yoshimoto T, Oshima T, Fukada T, Imamura N, Nakanishi T, Ebisutani N, Morishita D, Mieno M, Nakai K, Sei H, Kitayama Y, Eda H, Okugawa T, Tomita T, Fukui H, Shinzaki S. Pegfilgrastim for the management of neutropenia during neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in esophageal cancer patients. Int J Clin Oncol 2024; 29:142-148. [PMID: 38063978 DOI: 10.1007/s10147-023-02438-3] [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: 06/06/2023] [Accepted: 11/08/2023] [Indexed: 01/26/2024]
Abstract
BACKGROUND Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. METHODS All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. RESULTS Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7 days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. CONCLUSION Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.
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Affiliation(s)
- Takanori Yoshimoto
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Tadayuki Oshima
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan.
| | - Takashi Fukada
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Nobuko Imamura
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Takashi Nakanishi
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Nobuhiko Ebisutani
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Daisuke Morishita
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Masatoshi Mieno
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Keisuke Nakai
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hiroo Sei
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Yoshitaka Kitayama
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hirotsugu Eda
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Takuya Okugawa
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Toshihiko Tomita
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hirokazu Fukui
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Shinichiro Shinzaki
- Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
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Chew DCH, Yim CHH, Ali RA, El‐Omar EM. Epidemiology, Microbiome, and Risk Factors Involved in Carcinogenesis of Esophagus, Gastric, and Intestine. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:2-22. [DOI: 10.1002/9781119756422.ch1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Liao M, Kang S. Economic evaluation of sintilimab versus docetaxel as second-line treatment for patients with advanced or metastatic squamous non-small-cell lung cancer in China: a model-based cost-effectiveness analysis. Expert Rev Pharmacoecon Outcomes Res 2024; 24:161-166. [PMID: 37789675 DOI: 10.1080/14737167.2023.2267177] [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: 07/05/2023] [Accepted: 10/01/2023] [Indexed: 10/05/2023]
Abstract
OBJECTIVES The current study aimed to evaluate the cost-effectiveness of sintilimab versus docetaxel as second-line treatment for patients with advanced or metastatic squamous non-small-cell lung cancer (NSCLC) in China. METHODS A partitioned survival model was established to track 3-week patients' transition and project the health and economic outputs in 15-year horizon of the two competing options among sintilimab and docetaxel. Clinical data were obtained from the ORIENT-3 trial, and cost and utility values were gathered from the local charges and published studies. Total costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were evaluated. Sensitivity analyses were conducted to assess the robustness of the model outcomes. RESULTS Base-case results revealed that sintilimab yield marginal cost of $4,700.53 and additional 0.32 QALYs, resulting in an ICER of $14,615.31 per QALY gained, which is lower than the willingness-to-pay threshold of $38,224/QALY in China. One-way sensitivity analyses showed that the cost of best supportive care was the main driver of the ICER, and probabilistic sensitivity analyses demonstrated that the model outputs were robust. CONCLUSIONS Sintilimab could be considered the cost-effective second-line strategy for patients with advanced or metastatic squamous NSCLC compared with docetaxel in China.
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Affiliation(s)
- Mochong Liao
- Department of Ophthalmology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China
| | - Shuo Kang
- Medical Insurance Office, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China
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Abstract
Obesity has been recognized to be increasing globally and is designated a disease with adverse consequences requiring early detection and appropriate care. In addition to being related to metabolic syndrome disorders such as type 2 diabetes, hypertension, stroke, and premature coronary artery disease. Obesity is also etiologically linked to several cancers. The non-gastrointestinal cancers are breast, uterus, kidneys, ovaries, thyroid, meningioma, and thyroid. Gastrointestinal (GI) cancers are adenocarcinoma of the esophagus, liver, pancreas, gallbladder, and colorectal. The brighter side of the problem is that being overweight and obese and cigarette smoking are mostly preventable causes of cancers. Epidemiology and clinical studies have revealed that obesity is heterogeneous in clinical manifestations. In clinical practice, BMI is calculated by dividing a person's weight in kilograms by the square of the person's height in square meters (kg/m2). A BMI above 30 kg/m2 (defining obesity in many guidelines) is considered obesity. However, obesity is heterogeneous. There are subdivisions for obesity, and not all obesities are equally pathogenic. Adipose tissue, in particular, visceral adipose tissue (VAT), is endocrine and abdominal obesity (a surrogate for VAT) is evaluated by waist-hip measurements or just waist measures. Visceral Obesity, through several hormonal mechanisms, induces a low-grade chronic inflammatory state, insulin resistance, components of metabolic syndrome, and cancers. Metabolically obese, normal-weight (MONW) individuals in several Asian countries may have BMI below normal levels to diagnose obesity but suffer from many obesity-related complications. Conversely, some people have high BMI but are generally healthy with no features of metabolic syndrome. Many clinicians advise weight loss by dieting and exercise to metabolically healthy obese with large body habitus than to individuals with metabolic obesity but normal BMI. The GI cancers (esophagus, pancreas, gallbladder, liver, and colorectal) are individually discussed, emphasizing the incidence, possible pathogenesis, and preventive measures. From 2005 to 2014, most cancers associated with overweight and Obesity increased in the United States, while cancers related to other factors decreased. The standard recommendation is to offer or refer adults with a body mass index (BMI) of 30 or more to intensive, multicomponent behavioral interventions. However, the clinicians have to go beyond. They should critically evaluate BMI with due consideration for ethnicity, body habitus, and other factors that influence the type of obesity and obesity-related risks. In 2001, the Surgeon General's ``Call to Action to Prevent and Decrease Overweight and Obesity'' identified obesity as a critical public health priority for the United States. At government levels reducing obesity requires policy changes that improve the food and physical activity for all. However, implementing some policies with the most significant potential benefit to public health is politically tricky. The primary care physician, as well as subspecialists, should identify overweight and Obesity based on all the variable factors in the diagnosis. The medical community should address the prevention of overweight and Obesity as an essential part of medical care as much as vaccination in preventing infectious diseases at all levels- from childhood, to adolescence, and adults.
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Affiliation(s)
- Yuntao Zou
- Department of Medicine, Saint Peter's University Hospital, 125 Andover DR, Kendall Park, New Brunswick, NJ 08901, USA
| | - Capecomorin S Pitchumoni
- Department of Medicine, Saint Peter's University Hospital, 125 Andover DR, Kendall Park, New Brunswick, NJ 08901, USA.
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Akhtar J, Imran M, Wang G. CRISPR/Cas9-Mediated CtBP1 Gene Editing Enhances Chemosensitivity and Inhibits Metastatic Potential in Esophageal Squamous Cell Carcinoma Cells. Int J Mol Sci 2023; 24:14030. [PMID: 37762332 PMCID: PMC10530806 DOI: 10.3390/ijms241814030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 09/05/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
Innovative therapeutic strategies for esophageal squamous cell carcinoma (ESCC) are urgently required due to the limited effectiveness of standard chemotherapies. C-Terminal Binding Protein 1 (CtBP1) has been implicated in various cancers, including ESCC. However, the precise expression patterns and functional roles of CtBP1 in ESCC remain inadequately characterized. In this study, we aimed to investigate CtBP1 expression and its role in the resistance of ESCC to paclitaxel, an effective chemotherapeutic agent. Western blotting and immunofluorescence were applied to assess CtBP1 expression in the TE-1 and KYSE-50 cell lines. We observed the marked expression of CtBP1, which was associated with enhanced proliferation, invasion, and metastasis in these cell lines. Further, we successfully generated paclitaxel resistant ESCC cell lines and conducted cell viability assays. We employed the CRISPR/Cas9 genome editing system to disable the CtBP1 gene in ESCC cell lines. Through the analysis of the drug dose-response curve, we assessed the sensitivity of these cell lines in different treatment groups. Remarkably, CtBP1-disabled cell lines displayed not only improved sensitivity but also a remarkable inhibition of proliferation, invasion, and metastasis. This demonstrates that CtBP1 may promote ESCC cell malignancy and confer paclitaxel resistance. In summary, our study opens a promising avenue for targeted therapies, revealing the potential of CtBP1 inhibition to enhance the effectiveness of paclitaxel treatment for the personalized management of ESCC.
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Affiliation(s)
- Javed Akhtar
- Futian Biomedical Innovation R&D Center, The Chinese University of Hong Kong, Shenzhen 518172, China;
- Biomedical Science and Engineering, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China
- Ciechanover Institute of Precision and Regenerative Medicine, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China
- Center for Endocrinology and Metabolic Diseases, Second Affiliated Hospital, The Chinese University of Hong Kong, Shenzhen 518172, China
| | - Muhammad Imran
- Department of Computer Science & IT, Institute of Southern Punjab, Multan 60800, Pakistan;
| | - Guanyu Wang
- Futian Biomedical Innovation R&D Center, The Chinese University of Hong Kong, Shenzhen 518172, China;
- Biomedical Science and Engineering, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China
- Ciechanover Institute of Precision and Regenerative Medicine, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China
- Center for Endocrinology and Metabolic Diseases, Second Affiliated Hospital, The Chinese University of Hong Kong, Shenzhen 518172, China
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23
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Taj S, Hussain A, Sanekommu H, Miller B, Austin C, Kilada C, Dandu S, Ahsan E, Erler BS. Metachronous Squamous Cell Carcinoma of the Esophagus After Resolution of Previous Adenocarcinoma. ACG Case Rep J 2023; 10:e01097. [PMID: 37434661 PMCID: PMC10332822 DOI: 10.14309/crj.0000000000001097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 06/08/2023] [Indexed: 07/13/2023] Open
Abstract
Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Metachronous malignancies refer to multiple independent primary cancers diagnosed at least 6 months apart. The incidence of metachronous esophageal cancers with different histologic subtypes is extremely rare. This case presents an unprecedented occurrence of esophageal adenocarcinoma, followed by metachronous squamous cell carcinoma.
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Affiliation(s)
- Sobaan Taj
- Jersey Shore University Medical Center, Department of Medicine, Neptune City, NJ
| | | | | | - Brett Miller
- Jersey Shore University Medical Center, Department of Medicine, Neptune City, NJ
| | | | | | - Sowmya Dandu
- Jersey Shore University Medical Center, Department of Medicine, Neptune City, NJ
| | - Eram Ahsan
- Jersey Shore University Medical Center, Department of Medicine, Neptune City, NJ
| | - Brian S. Erler
- Jersey Shore University Medical Center, Department of Pathology, Neptune City, NJ
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24
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Mejza M, Małecka-Wojciesko E. Diagnosis and Management of Barrett's Esophagus. J Clin Med 2023; 12:jcm12062141. [PMID: 36983142 PMCID: PMC10057256 DOI: 10.3390/jcm12062141] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/07/2023] [Accepted: 03/07/2023] [Indexed: 03/30/2023] Open
Abstract
Barrett's esophagus is a metaplastic change of esophageal mucosa, which can be characterized by its salmon-colored lining and the presence of columnar epithelium with goblet cells. It is a well-established precancerous state of esophageal adenocarcinoma, a tumor with very poor survival rates, which incidence is rapidly growing. Despite numerous research, the debate about its diagnosis and management is still ongoing. This article aims to provide an overview of the current recommendations and new discoveries regarding the subject.
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Affiliation(s)
- Maja Mejza
- Department of Digestive Tract Diseases, Medical University, 90-153 Lodz, Poland
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25
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Zhang Y, Chen X, Qiao Y, Yang S, Wang Z, Ji M, Yin K, Zhao J, Liu K, Yuan B. DNA Aptamer Selected against Esophageal Squamous Cell Carcinoma for Tissue Imaging and Targeted Therapy with Integrin β1 as a Molecular Target. Anal Chem 2022; 94:17212-17222. [PMID: 36459499 DOI: 10.1021/acs.analchem.2c03863] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), poses a serious threat to human health. It is urgently needed to develop recognition tools and discover molecular targets for early diagnosis and targeted therapy of esophageal cancer. Here, we developed several DNA aptamers that can bind to ESCC KYSE410 cells with a nanomolar range of dissociation constants by using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). The selected A2 aptamer is found to strongly bind with multiple cancer cells, including several ESCC cell lines. Tissue imaging displayed that the A2 aptamer can specifically recognize clinical ESCC tissues but not the adjacent tissues. Moreover, we identified integrin β1 as the binding target of A2 through pull-down and RNA interference assays. Meanwhile, molecular docking and mutation assays suggested that A2 probably binds to integrin β1 through the nucleotides of DA16-DG21, and competitive binding and structural alignment assays indicated that A2 shares the overlapped binding sites with laminin and arginine-glycine-aspartate ligands. Furthermore, we engineered A2-induced targeted therapy for ESCC. By constructing A2-tethered DNA nanoassemblies carrying multiple doxorubicin (Dox) molecules as antitumor agents, inhibition of tumor cell growth in vitro and in vivo was achieved. This work provides a useful targeting tool and a potential molecular target for cancer diagnosis and targeted therapy and is helpful for understanding the integrin mechanism and developing integrin inhibitors.
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Affiliation(s)
- Yangyang Zhang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China
| | - Xinhuan Chen
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan 450000, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan 450001, China
| | - Yan Qiao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan 450000, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan 450001, China
| | - Shuang Yang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China
| | - Zhaoting Wang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China
| | - Mengmeng Ji
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China
| | - Kai Yin
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China
| | - Jimin Zhao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan 450000, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan 450001, China
| | - Kangdong Liu
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan 450000, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan 450001, China.,China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan 450003, China.,Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan 450000, China
| | - Baoyin Yuan
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan 450000, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan 450001, China
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26
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Liu C, Ma Y, Qin Q, Wang P, Luo Y, Xu P, Cui Y. Epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040. Thorac Cancer 2022; 14:3-11. [PMID: 36482832 PMCID: PMC9807450 DOI: 10.1111/1759-7714.14745] [Citation(s) in RCA: 133] [Impact Index Per Article: 44.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 11/05/2022] [Accepted: 11/09/2022] [Indexed: 12/14/2022] Open
Abstract
Esophageal cancer is a familiar malignancy with high incidence and mortality, and the overall prognosis is poor. The numbers of cases of and deaths from esophageal cancer have risen rapidly in recent decades. It is one of the most malignant cancers, with more than 0.6 million new cases and 0.54 million deaths worldwide in 2020. Here, we present the global epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040 at different geographical levels of continents, regions and countries, and analyze them by gender, race, geographic region and human development index. We summarize the prospects for the esophageal cancer burden and risk factors in different areas, which will be useful for global esophageal cancer clinical therapy and cancer control planning.
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Affiliation(s)
- Chun‐Quan Liu
- Department of Thoracic SurgeryBeijing Friendship Hospital, Capital Medical UniversityBeijingChina
| | - Yun‐Lei Ma
- Department of Thoracic SurgeryBeijing Friendship Hospital, Capital Medical UniversityBeijingChina
| | - Qi Qin
- Department of Thoracic SurgeryBeijing Friendship Hospital, Capital Medical UniversityBeijingChina
| | - Pei‐Hao Wang
- Department of Thoracic SurgeryBeijing Friendship Hospital, Capital Medical UniversityBeijingChina
| | - Yi Luo
- Department of Thoracic SurgeryBeijing Friendship Hospital, Capital Medical UniversityBeijingChina
| | - Peng‐Fei Xu
- School of Pharmaceutical SciencesWuhan UniversityWuhanChina,Center for Pharmacogenetics and Department of Pharmaceutical SciencesUniversity of PittsburghPittsburghPennsylvaniaUSA
| | - Yong Cui
- Department of Thoracic SurgeryBeijing Friendship Hospital, Capital Medical UniversityBeijingChina
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27
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Islam MM, Poly TN, Walther BA, Yeh CY, Seyed-Abdul S, Li YC(J, Lin MC. Deep Learning for the Diagnosis of Esophageal Cancer in Endoscopic Images: A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:cancers14235996. [PMID: 36497480 PMCID: PMC9736434 DOI: 10.3390/cancers14235996] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/17/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
Esophageal cancer, one of the most common cancers with a poor prognosis, is the sixth leading cause of cancer-related mortality worldwide. Early and accurate diagnosis of esophageal cancer, thus, plays a vital role in choosing the appropriate treatment plan for patients and increasing their survival rate. However, an accurate diagnosis of esophageal cancer requires substantial expertise and experience. Nowadays, the deep learning (DL) model for the diagnosis of esophageal cancer has shown promising performance. Therefore, we conducted an updated meta-analysis to determine the diagnostic accuracy of the DL model for the diagnosis of esophageal cancer. A search of PubMed, EMBASE, Scopus, and Web of Science, between 1 January 2012 and 1 August 2022, was conducted to identify potential studies evaluating the diagnostic performance of the DL model for esophageal cancer using endoscopic images. The study was performed in accordance with PRISMA guidelines. Two reviewers independently assessed potential studies for inclusion and extracted data from retrieved studies. Methodological quality was assessed by using the QUADAS-2 guidelines. The pooled accuracy, sensitivity, specificity, positive and negative predictive value, and the area under the receiver operating curve (AUROC) were calculated using a random effect model. A total of 28 potential studies involving a total of 703,006 images were included. The pooled accuracy, sensitivity, specificity, and positive and negative predictive value of DL for the diagnosis of esophageal cancer were 92.90%, 93.80%, 91.73%, 93.62%, and 91.97%, respectively. The pooled AUROC of DL for the diagnosis of esophageal cancer was 0.96. Furthermore, there was no publication bias among the studies. The findings of our study show that the DL model has great potential to accurately and quickly diagnose esophageal cancer. However, most studies developed their model using endoscopic data from the Asian population. Therefore, we recommend further validation through studies of other populations as well.
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Affiliation(s)
- Md. Mohaimenul Islam
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
- International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei 110, Taiwan
- Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
| | - Tahmina Nasrin Poly
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
- International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei 110, Taiwan
- Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
| | - Bruno Andreas Walther
- Deep Sea Ecology and Technology, Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung, Am Handelshafen 12, D-27570 Bremerhaven, Germany
| | - Chih-Yang Yeh
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
| | - Shabbir Seyed-Abdul
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
| | - Yu-Chuan (Jack) Li
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
- International Center for Health Information Technology (ICHIT), Taipei Medical University, Taipei 110, Taiwan
- Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Department of Dermatology, Wan Fang Hospital, Taipei 116, Taiwan
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Ming-Chin Lin
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
- Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan
- Correspondence:
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28
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Ye ZM, Xu Z, Zeng FY, Tang ZQ, Zhou Q. Cost-Effectiveness Analysis of Sintilimab Combined with Chemotherapy Versus Chemotherapy Alone as the First-Line Treatment for Advanced Esophageal Cancer. Front Pharmacol 2022; 13:934275. [PMID: 36518659 PMCID: PMC9742528 DOI: 10.3389/fphar.2022.934275] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 05/24/2022] [Indexed: 09/15/2023] Open
Abstract
Background: Esophageal cancer has a poor prognosis and currently ranks sixth in global cancer mortality rates. The ORIENT-15 trial showed sintilimab plus chemotherapy significantly improved survival when compared to chemotherapy alone. This study aimed to evaluate the cost-effectiveness of sintilimab, a programmed death-ligand 1 (PD-L1) inhibitor, plus chemotherapy in treating patients with esophageal cancer compared with chemotherapy alone. Methods: A Markov model with a 10-year horizon was developed based on the perspective of the Chinese healthcare payers. We conducted a cost-effectiveness analysis for sintilimab combined with chemotherapy based on a questionnaire. Patients were grouped into the sintilimab group based on a positive score of 10 or more (combined positive score (CPS) ≥ 10 groups), and those with any other PD-L1 expression were randomized into patient groups. We estimated the cost and the effectiveness of sintilimab on the quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) was computed. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness results. Results: In the base-case analysis, compared with chemotherapy alone, the ICER of sintilimab plus chemotherapy for all patients was $21024.05 per QALY, and in the CPS≥10 group, it was $20974.23 per QALY. This was lower than $37653 per QALY. One-way sensitivity analysis demonstrated that ICERs were most sensitive to the price of sintilimab. Conclusion: The study demonstrated that sintilimab plus chemotherapy for advanced esophageal cancer as its first-line treatment would be more cost-effective than chemotherapy alone in Chinese patients.
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Affiliation(s)
- Zhuo-Miao Ye
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zhe Xu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
| | - Fan-Yuan Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
| | - Zi-Qing Tang
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
| | - Qin Zhou
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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29
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Zhang Q, Lin X, Jiang K, Deng J, Ke L, Wu Z, Xia P, Li Q, Yu L, Ni P, Lv W, Hu J. PD0166285 sensitizes esophageal squamous cell carcinoma to radiotherapy by dual inhibition of WEE1 and PKMYT1. Front Oncol 2022. [DOI: 10.3389/fonc.2022.1061988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
BackgroundEsophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a 5-year survival rate of only 20%. More than 80% of ESCC patients possess TP53 mutation, which abolishes the G1/S checkpoint and accelerates the cell cycle. Thus, WEE1 and PKMYT1, regulators of G2/M phase in cell cycle, play essential roles in TP53-mutated cancer cells. PD0166285(PD) is a pyridopyrimidine compound that can inhibit WEE1 and PKMYT1 simultaneously, however, the effects of PD on ESCC, either as monotherapy or in combination therapy with radiotherapy, remain unclear.MethodsTo measure the anti-tumor efficacy of PD in ESCC cells, cell viability, cell cycle and cell apoptosis assays were examined in KYSE150 and TE1 cells with PD treatment. The combination therapy of PD and irradiation was also performed in ESCC cells to find whether PD can sensitize ESCC cells to irradiation. Vivo assays were also performed to investigate the efficacy of PD.ResultsWe found that the IC50 values of PD among ESCC cells ranged from 234 to 694 nM, PD can regulate cell cycle and induce cell apoptosis in ESCC cells in a dose-dependent manner. When combined with irradiation, PD sensitized ESCC cells to irradiation by abolishing G2/M phase arrest, inducing a high ratio of mitosis catastrophe, eventually leading to cell death. We also demonstrated that PD can attenuate DNA damage repair by inhibiting Rad51, further research also found the interaction of WEE1 and Rad51. In vivo assays, PD inhibited the tumor growth in mice, combination therapy showed better therapeutic efficacy.ConclusionPD0166285 can exert antitumor effect by inhibiting the function of WEE1 and PKMYT1 in ESCC cells, and also sensitize ESCC cells to irradiation not only by abolishing G2/M arrest but also attenuating DNA repair directly. We believe PD0166285 can be a potent treatment option for ESCC in the future.
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30
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Xie P, Xia W, Lowe S, Zhou Z, Ding P, Cheng C, Bentley R, Li Y, Wang Y, Zhou Q, Wu B, Gao J, Feng L, Ma S, Liu H, Sun C. High spicy food intake may increase the risk of esophageal cancer: A meta-analysis and systematic review. Nutr Res 2022; 107:139-151. [PMID: 36215887 DOI: 10.1016/j.nutres.2022.09.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 09/02/2022] [Accepted: 09/03/2022] [Indexed: 12/27/2022]
Abstract
Spicy food is popular with people around the world and reports on the association between spicy food intake and esophageal cancer (EC) risk have been controversial. Therefore, we conducted a meta-analysis of 25 studies to provide the latest evidence for this uncertainty. We hypothesized that high spicy food intake is associated with an increased risk of EC. A database was searched to identify case-control or cohort studies of spicy food intake associated with EC through March 2022. Combined odds ratios (ORs) and their 95% CIs were used to estimate the effect of spicy food intake on EC. Subgroup analyses and sensitivity analyses were also performed. All data were analyzed using STATA 15.1 software. Twenty-five studies from 22 articles met the inclusion criteria for the meta-analysis (7810 patients with EC and 515,397 controls). Despite significant heterogeneity (P < .001), the comparison of highest versus lowest spicy food intake in each study showed a significant OR of 1.70 (95% CI, 1.30-2.22). In subgroup analyses, this positive association was found among the Chinese population, different sample sizes of EC, different sources of the control group, and different quality of articles. However, for India, as well as for other countries, esophageal squamous cell carcinoma and esophageal adenocarcinoma showed no statistically significant association. This meta-analysis suggests that high levels of spicy food intake may be associated with an increased risk of EC, although 1 prospective study found an inverse association. Additional studies are necessary to confirm the relationship between spicy food and EC risk.
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Affiliation(s)
- Peng Xie
- Department of Epidemiology and Health Statistics, School of Public Health Anhui Medical University, Hefei 230032, Anhui, P.R. China
| | - Weihang Xia
- Department of Epidemiology and Health Statistics, School of Public Health Anhui Medical University, Hefei 230032, Anhui, P.R. China
| | - Scott Lowe
- College of Osteopathic Medicine, Kansas City University, Kansas City, MO 64106, USA
| | - Zhen Zhou
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Tasmania, Australia
| | - Ping'an Ding
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China
| | - Ce Cheng
- The University of Arizona College of Medicine, Tucson, AZ 85724; Banner-University Medical Center South, Tucson, AZ 85713
| | - Rachel Bentley
- College of Osteopathic Medicine, Kansas City University, Kansas City, MO 64106, USA
| | - Yaru Li
- College of Osteopathic Medicine, Des Moines University, Des Moines, IA, 50312, USA; Internal Medicine, Swedish Hospital, Chicago, IL 60625, USA
| | - Yichen Wang
- Mercy Internal Medicine Service, Trinity Health of New England, Springfield, MA 01104, USA
| | - Qin Zhou
- Mayo Clinic, Rochester, MN 55905, USA
| | - Birong Wu
- Department of Epidemiology and Health Statistics, School of Public Health Anhui Medical University, Hefei 230032, Anhui, P.R. China
| | - Juan Gao
- Department of Epidemiology and Health Statistics, School of Public Health Anhui Medical University, Hefei 230032, Anhui, P.R. China
| | - Linya Feng
- Department of Epidemiology and Health Statistics, School of Public Health Anhui Medical University, Hefei 230032, Anhui, P.R. China
| | - Shaodi Ma
- Department of Epidemiology and Health Statistics, School of Public Health Anhui Medical University, Hefei 230032, Anhui, P.R. China
| | - Haixia Liu
- Department of Epidemiology and Health Statistics, School of Public Health Anhui Medical University, Hefei 230032, Anhui, P.R. China
| | - Chenyu Sun
- AMITA Health Saint Joseph Hospital Chicago, Chicago 60657, Illinois, USA.
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31
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Teng C, Kong F, Mo J, Lin W, Jin C, Wang K, Wang Y. The roles of RNA N6-methyladenosine in esophageal cancer. Heliyon 2022; 8:e11430. [DOI: 10.1016/j.heliyon.2022.e11430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 07/15/2022] [Accepted: 10/31/2022] [Indexed: 11/08/2022] Open
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32
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Chen W, Li D, Bian X, Wu Y, Xu M, Wu M, Tao M. Peripheral Blood Markers Predictive of Progression-Free Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Treated With PD-1 Inhibitors Plus Chemotherapy as First-Line Therapy. Nutr Cancer 2022; 75:207-218. [PMID: 36190755 DOI: 10.1080/01635581.2022.2123533] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Aim: To determine the prognostic value of peripheral blood markers in advanced esophageal squamous cell carcinoma (ESCC) patients receiving programmed cell death protein 1 inhibitors plus chemotherapy as first-line therapy. Methods: A retrospective analysis of 54 patients with advanced ESCC was performed to assess 12 blood markers involving inflammation, nutrition, and tumor burden. Analysis of variance or Kruskal-Wallis tests were used to explore the difference in markers among different response to therapy. Survival curves were constructed using the Kaplan-Meier method. Multivariate Cox models were applied to identify independent predictors of outcome. Results: Patients who achieved response had significantly higher prealbumin, increased BMI, and lower hs-CRP levels at baseline compared with those who experienced disease progression. In the univariate analysis, ALI > 23.55, PNI > 45.175, NLR ≤ 5, and hs-CRP ≤ 6.7 mg/L were significantly associated with a better progression-free survival. Cox regression analysis revealed that ALI >23.55 (P = 0.037) and hs-CRP ≤6.7 mg/L (P = 0.043) were independently associated with superior PFS. Increased tumor abnormal protein (TAP) levels post two cycles was significantly associated with a worse prognosis (P = 0.004). Conclusions: A baseline signature of low ALI and high hs-CRP as well as an early increase in TAP in ESCC appear to be predictive of inferior PFS.
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Affiliation(s)
- Wei Chen
- Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Dapeng Li
- Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xuyu Bian
- Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yan Wu
- Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Mengdan Xu
- Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Mengyao Wu
- Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Min Tao
- Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China.,Department of Oncology, DuShu Lake Hospital Affiliated to Soochow University, Suzhou, China
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Hu H, Zhang J, Yan H, Qin C, Guo H, Liu T, Tang S, Zhou H. Development and validation of a novel prognostic model for patients with surgically resected esophageal squamous cell carcinoma. Front Oncol 2022; 12:955353. [PMID: 36059713 PMCID: PMC9435602 DOI: 10.3389/fonc.2022.955353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 07/18/2022] [Indexed: 01/17/2023] Open
Abstract
Background and objectives Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal malignancy in most regions of the world. The study aimed to identify risk factors and develop a predictive model for ESCC following surgical resection. Patients and methods A total of 533 ESCC patients who underwent surgical resection from Suining Central Hospital were enrolled in the study. Cox proportional hazards regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to identify significant prognostic factors. A prognostic model was constructed, and the receiver operating characteristic (ROC) curve, concordance index (C-index), and decision cure analysis (DCA) were used to evaluate the discrimination and calibration of the prognostic model. Subsequently, we built a nomogram for overall survival (OS) incorporating the prognostic factors, and a calibration plot was employed to assess the consistency between the predicted survival and the observed survival. Based on the model risk score, we split the patients into two subgroups, low-risk and high-risk, and we analyzed the survival time of these two groups using Kaplan–Meier (K-M) survival plots. Results Five independent prognosis factors were identified as independent risk factors for OS in ESCC patients who underwent surgical resection. The C-index, ROC curve, and DCA showed that the prognostic model had good predictive accuracy and discriminatory power in the training cohort and validation cohort than other clinical features. A nomogram consisting of prognosis factors showed some superior net benefit. K-M survival plots showed significant differences in OS between the low-risk and high-risk groups. Similar results were observed in the subgroup analysis based on age, grade, and stage. Univariate and multivariate Cox regression analyses revealed that both risk score and risk group are independent prognostic factors in the patient cohort. Conclusions This study put forward a novel prognostic model based on clinical features; biopsy data and blood biomarkers may represent a promising tool for estimating OS in ESCC patients.
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Affiliation(s)
- Haiyang Hu
- Department of Thoracic Surgery, Suining Central Hospital, An Affiliated Hospital of Chongqing Medical University, Suining, China
- Institute of Surgery, Graduate School, Zunyi Medical University, Zunyi, China
| | - Jun Zhang
- Department of Thoracic Surgery, Suining Central Hospital, An Affiliated Hospital of Chongqing Medical University, Suining, China
- Institute of Surgery, Graduate School, Zunyi Medical University, Zunyi, China
| | - Hang Yan
- Department of Thoracic Surgery, Suining Central Hospital, An Affiliated Hospital of Chongqing Medical University, Suining, China
- Institute of Surgery, Graduate School, Zunyi Medical University, Zunyi, China
| | - Chao Qin
- Department of Thoracic Surgery, Suining Central Hospital, An Affiliated Hospital of Chongqing Medical University, Suining, China
- Institute of Surgery, Graduate School, Zunyi Medical University, Zunyi, China
| | - Haiyang Guo
- Department of Thoracic Surgery, Suining Central Hospital, An Affiliated Hospital of Chongqing Medical University, Suining, China
- Institute of Surgery, Graduate School, Chengdu University of TCM, Chengdu, China
| | - Tao Liu
- Department of Thoracic Surgery, Suining Central Hospital, An Affiliated Hospital of Chongqing Medical University, Suining, China
- Institute of Surgery, Graduate School, Zunyi Medical University, Zunyi, China
| | - Shengjie Tang
- Department of Thoracic Surgery, Suining Central Hospital, An Affiliated Hospital of Chongqing Medical University, Suining, China
| | - Haining Zhou
- Department of Thoracic Surgery, Suining Central Hospital, An Affiliated Hospital of Chongqing Medical University, Suining, China
- Institute of Surgery, Graduate School, Zunyi Medical University, Zunyi, China
- *Correspondence: Haining Zhou,
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Qiao Y, Zhao C, Li X, Zhao J, Huang Q, Ding Z, Zhang Y, Jiao J, Zhang G, Zhao S. Efficacy and safety of camrelizumab in combination with neoadjuvant chemotherapy for ESCC and its impact on esophagectomy. Front Immunol 2022; 13:953229. [PMID: 35911723 PMCID: PMC9329664 DOI: 10.3389/fimmu.2022.953229] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 06/27/2022] [Indexed: 12/12/2022] Open
Abstract
Background Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. The use of neoadjuvant immunotherapy for the treatment of ESCC is gradually increasing. Camrelizumab is one such immune checkpoint inhibitor (ICI) used for treatment. In this retrospective study, we explored the efficacy, safety, and short-term perioperative prognosis of camrelizumab in combination with neoadjuvant chemotherapy for ESCC. Materials and Methods A total of 254 Chinese patients with ESCC were enrolled in the study; 48 received camrelizumab in combination with neoadjuvant chemotherapy (C-NC group), and 206 received neoadjuvant chemotherapy (NC group). All patients underwent surgery after the completion of 2 cycles of neoadjuvant therapy. Results Twenty patients (20/48, 41.7%) in the C-NC group and 22 patients (22/206, 10.7%) in the NC group achieved a pathologic complete response (pCR) (p<0.001). Twenty-nine patients (29/48, 60.4%) in the C-NC group and 56 patients (56/206, 27.2%) in the NC group achieved major pathologic remission (MPR) (p<0.001). There was a lower incidence of myelosuppression during neoadjuvant therapy in patients in the C-NC group (33/48, 68.8%) than in the NC group (174/206, 84.5%, p=0.012). The total incidence of adverse reactions during neoadjuvant therapy was also lower in the C-NC group (37/48, 77.1%) than in the NC group (189/206, 91.7%, p=0.003). Patients in the C-NC group had more lymph nodes cleared during surgery than those in the NC group (34 vs.30, p<0.001). The logistic model showed that the treatment regimen, age, and presence of lymph node metastasis were influential factors for achieving a pCR in these patients (p<0.001). Regarding other adverse events and surgery-related data, there were no significant differences observed between the two groups. Conclusion Camrelizumab in combination with neoadjuvant chemotherapy is an efficacious neoadjuvant regimen with an acceptable safety profile and does not increase the difficulty of surgery or the incidence of complications. A pCR is more likely to be achieved in patients treated with camrelizumab in combination with neoadjuvant chemotherapy, in younger patients, or in those without lymph node metastases.
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Affiliation(s)
- Yujin Qiao
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Cong Zhao
- Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiangnan Li
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jia Zhao
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qi Huang
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zheng Ding
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Zhang
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jia Jiao
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guoqing Zhang
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Guoqing Zhang, ; Song Zhao,
| | - Song Zhao
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Guoqing Zhang, ; Song Zhao,
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Wu X, Zhang H, Sui Z, Gao Y, Gong L, Chen C, Ma Z, Tang P, Yu Z. CXCR4 promotes the growth and metastasis of esophageal squamous cell carcinoma as a critical downstream mediator of HIF-1α. Cancer Sci 2022; 113:926-939. [PMID: 34990040 PMCID: PMC8898735 DOI: 10.1111/cas.15265] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 12/16/2021] [Accepted: 12/27/2021] [Indexed: 11/28/2022] Open
Abstract
C–X–C motif chemokine receptor 4 (CXCR4) belongs to the CXC chemokine receptor family, which mediates the metastasis of tumor cells and promotes the malignant development of cancers. However, its biological role and regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we found that CXCR4 expression was associated with lymph node metastasis and a poor prognosis. In vitro and in vivo studies demonstrated that CXCR4 overexpression promoted ESCC cell proliferation, migration, invasion, and survival, whereas silencing CXCR4 induced the opposite effects. Mechanically, HIF‐1α transcriptionally regulates CXCR4 expression by binding to a hypoxia response element in its promoter. HIF‐1α‐induced ESCC cell migration and invasion were reversed by CXCR4 knockdown or treatment with MSX‐122, a CXCR4 antagonist. Collectively, these data revealed that the HIF‐1α/CXCR4 axis plays key roles in ESCC growth and metastasis and indicated CXCR4 as a potential target for ESCC treatment.
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Affiliation(s)
- Xianxian Wu
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.,Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and PeKing Union Medical College, Shenzhen, 518116, China
| | - Hongdian Zhang
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Zhilin Sui
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Yongyin Gao
- Department of Cardio-pulmonary Functions, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Lei Gong
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Chuangui Chen
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Zhao Ma
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Peng Tang
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Zhentao Yu
- Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.,Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and PeKing Union Medical College, Shenzhen, 518116, China
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Harriott CB, Angeramo CA, Casas MA, Schlottmann F. Open vs. Hybrid vs. Totally Minimally Invasive Ivor Lewis Esophagectomy: Systematic Review and Meta-analysis. J Thorac Cardiovasc Surg 2022; 164:e233-e254. [DOI: 10.1016/j.jtcvs.2021.12.051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 12/03/2021] [Accepted: 12/24/2021] [Indexed: 02/07/2023]
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37
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Muro K, Kojima T, Moriwaki T, Kato K, Nagashima F, Kawakami H, Ishihara R, Ogata T, Satoh T, Iwakami K, Han S, Yatsuzuka N, Takami T, Bhagia P, Doi T. Second-line pembrolizumab versus chemotherapy in Japanese patients with advanced esophageal cancer: subgroup analysis from KEYNOTE-181. Esophagus 2022; 19:137-145. [PMID: 34591237 PMCID: PMC8739314 DOI: 10.1007/s10388-021-00877-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 08/30/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Safe and effective treatments for advanced esophageal cancer are an unmet need in Japan. We report results of a subgroup analysis of Japanese patients enrolled in KEYNOTE-181, a randomized, open-label, phase 3 study of pembrolizumab versus chemotherapy as second-line therapy for patients with advanced or metastatic esophageal cancer whose disease progressed after standard first-line therapy. METHODS Patients were randomly assigned 1:1 to receive pembrolizumab 200 mg every 3 weeks or investigator's choice of paclitaxel, docetaxel, or irinotecan. Efficacy was evaluated in all Japanese patients and in those with programmed death ligand 1 combined positive score ≥ 10. RESULTS Of the 152 Japanese patients enrolled (pembrolizumab, n = 77; chemotherapy, n = 75), 150 (98.7%) had squamous cell carcinoma and 79 (52.0%) had combined positive score ≥ 10. At the final analysis, median overall survival was improved among all patients (12.4 vs 8.2 months with pembrolizumab and chemotherapy, respectively; hazard ratio, 0.68; 95% CI 0.48-0.97) and patients with combined positive score ≥ 10 (12.6 vs 8.4 months; hazard ratio, 0.68; 95% CI 0.42-1.10). Fewer patients had any-grade (74.0% vs 95.9%) or grade 3-5 (16.9 vs 50.0%) treatment-related adverse events with pembrolizumab than with chemotherapy. CONCLUSION Consistent with the global trial results, second-line pembrolizumab therapy showed a survival benefit and a favorable safety profile compared with chemotherapy in Japanese patients with advanced esophageal cancer.
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Affiliation(s)
- Kei Muro
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
| | - Takashi Kojima
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | | | - Ken Kato
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Fumio Nagashima
- Department of Medical Oncology, Faculty of Medicine, Kyorin University, Tokyo, Japan
| | - Hisato Kawakami
- Department of Medicine, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Ryu Ishihara
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Takashi Ogata
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Taroh Satoh
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Suita, Osaka, Japan
| | | | - Shirong Han
- Department of Medical Oncology, MSD K.K., Tokyo, Japan
| | | | - Tomoko Takami
- Department of Medical Oncology, MSD K.K., Tokyo, Japan
| | - Pooja Bhagia
- Department of Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA
| | - Toshihiko Doi
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
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38
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Yajima S, Sugawara K, Iwai M, Tanaka M, Seto Y, Todo T. Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma. Mol Ther Oncolytics 2021; 23:402-411. [PMID: 34853811 PMCID: PMC8605086 DOI: 10.1016/j.omto.2021.10.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 10/01/2021] [Accepted: 10/18/2021] [Indexed: 12/13/2022] Open
Abstract
Treatment options are limited for esophageal carcinoma (EC). G47Δ, a triple-mutated, conditionally replicating herpes simplex virus type 1 (HSV-1), exhibits enhanced killing of tumor cells with high safety features. Here, we studied the efficacy of G47Δ using preclinical models of human EC. In vitro, G47Δ showed efficient cytopathic effects and replication capabilities in all eight human esophageal cancer cell lines tested. In athymic mice harboring subcutaneous tumors of human EC (KYSE180, TE8, and OE19), two intratumoral injections with G47Δ significantly inhibited the tumor growth. To mimic the clinical treatment situations, we established an orthotopic EC model using luciferase-expressing TE8 cells (TE8-luc). An intratumoral injection with G47Δ markedly inhibited the growth of orthotopic TE8-luc tumors in athymic mice. Furthermore, we evaluated the safety of applying G47Δ to the esophagus in mice. A/J mice inoculated intraesophageally or administered orally with G47Δ (107 plaque-forming units [pfu]) survived for more than 2 months without remarkable symptoms, whereas the majority with wild-type HSV-1 (106 pfu) deteriorated within 10 days. PCR analyses showed that the G47Δ DNA was confined to the esophagus after intraesophageal inoculation and was not detected in major organs after oral administration. Our results provide a rationale for the clinical use of G47Δ for treating EC.
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Affiliation(s)
- Shoh Yajima
- Division of Innovative Cancer Therapy, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.,Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kotaro Sugawara
- Division of Innovative Cancer Therapy, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.,Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Miwako Iwai
- Division of Innovative Cancer Therapy, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Minoru Tanaka
- Division of Innovative Cancer Therapy, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomoki Todo
- Division of Innovative Cancer Therapy, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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39
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Zhu X, Chen D, Li S, Zhang W, Li Y, Wang X, Zhou J, Wen Z. Albumin-To-Alkaline Phosphatase Ratio as a Novel and Promising Prognostic Biomarker in Patients Undergoing Esophagectomy for Carcinoma: A Propensity Score Matching Study. Front Oncol 2021; 11:764076. [PMID: 34746006 PMCID: PMC8563791 DOI: 10.3389/fonc.2021.764076] [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: 08/25/2021] [Accepted: 10/04/2021] [Indexed: 01/06/2023] Open
Abstract
Background Albumin-to-alkaline phosphatase ratio (AAPR) has been reported as a novel prognostic predictor for numerous solid tumors. We aimed to assess the prognostic role of preoperative AAPR in surgically resectable esophageal squamous cell carcinoma (ESCC) by a propensity score matching (PSM) analysis with predictive nomograms. Methods Our study was conducted in a single-center prospective database between June 2009 and December 2012. Kaplan-Meier analysis was used to distinguish the difference in survival outcomes between patients stratified by an AAPR threshold. Multivariable Cox proportional hazards regression model was finally generated to specify independent prognostic markers for the entire and PSM cohorts. Results A total of 497 patients with ESCC were included in this study. An AAPR of 0.50 was determined as the optimal cutoff point for prognostic outcome stratification. Patients with AAPR<0.50 had significantly worse overall survival (OS), and progression-free survival (PFS) compared to those with AAPR≥0.50 (Log-rank P<0.001). This significant difference remained stable in the PSM analysis. Multivariable analyses based on the entire and PSM cohorts consistently showed that AAPR<0.50 might be one of the most predominant prognostic factors resulting in unfavorable OS and PFS of ESCC patients undergoing esophagectomy (P<0.001). The nomograms consisting of AAPR and other independent prognostic factors further demonstrated a plausible predictive accuracy of postoperative OS and PFS. Conclusion AAPR can be considered as a simple, convenient and noninvasive biomarker with a significant prognostic effect in surgically resected ESCC.
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Affiliation(s)
- Xianying Zhu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Intensive Care Unit, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, China
| | - Dongni Chen
- Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shuangjiang Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Endoscopy and Laser, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, China
| | - Wenbiao Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Medical Imaging, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, China
| | - Yongjiang Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, China
| | - Xiaoyu Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Jian Zhou
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Medical Imaging, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, China
| | - Zhesheng Wen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Thoracic Oncology, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, China
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40
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Ding CZ, Wang GL, Wang HT, Wang WG, Wang L, Wang PF, Zhu RJ, Liu X, Wang JH, Wang J, Zhao S. Esophagectomy combined with off-pump coronary artery bypass grafting through left posterolateral incision is safe and feasible for esophageal cancer associated with coronary artery disease. Dis Esophagus 2021; 34:6095855. [PMID: 33442734 DOI: 10.1093/dote/doaa123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 05/08/2020] [Accepted: 10/28/2020] [Indexed: 12/11/2022]
Abstract
Controversy still exists as to whether surgical treatment has any impact on the long-term survival of esophageal cancer (EC) patients with coronary artery disease treated with curative esophagectomy combined with off-pump coronary artery bypass grafting (OPCABG). Therefore, the aim of this study was to introduce and assess the effect of esophagectomy combined with OPCABG on both short- and long-term outcomes. From January 2010 to January 2015, 1428 EC or esophagogastric junction cancer patients underwent surgical treatment at Henan Chest Hospital, Zhengzhou, China. The clinical data of 25 patients who underwent EC resection through a left thoracotomy following OPCABG and the perioperative characteristics and follow-up results were analyzed. The majority of the patients were male, and the EC stage was predominantly cT2N0-1M0 II. The most common pathological types were squamous cell carcinoma. The EC surgeries consisted of 15 chest anastomosis procedures and 10 cervical anastomosis procedures with aortocoronary graft implantation (mean: 2.36 grafts per patient). The mean total operative time was 330.8 ± 83.5 minutes. The median intensive care unit and hospital lengths of stay were 1.72 and 21.16 days, respectively. Resection without macroscopic residual disease (R0) was achieved in all of the patients. The most frequent complications included pulmonary infections (24%), arrhythmias (24%), pleural effusion (12%), and esophageal anastomotic leakage (8%). There were no postoperative deaths or myocardial infarctions within 30 days after the surgery. The overall 1-, 3-, and 5-year survival rates were 88%, 40%, and 24%, respectively, with a median survival time of 43 months. In the short-term, radical resection of EC following OPCABG is a safe and feasible treatment with low postoperative mortality rates. In the long-term, simultaneous surgery is acceptable and is associated with favorable overall and disease-free survival.
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Affiliation(s)
- C-Z Ding
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Department of Thoracic Oncology, Henan Chest Hospital, Zhengzhou, China
| | - G-L Wang
- Department of Thoracic Oncology, Henan Chest Hospital, Zhengzhou, China
| | - H-T Wang
- Department of Thoracic Oncology, Henan Chest Hospital, Zhengzhou, China
| | - W-G Wang
- Department of Thoracic Oncology, Henan Chest Hospital, Zhengzhou, China
| | - L Wang
- Department of Cardiac Surgery, Henan Chest Hospital, Zhengzhou, China
| | - P-F Wang
- Department of Cardiac Surgery, Henan Chest Hospital, Zhengzhou, China
| | - R-J Zhu
- Department of Cardiac Surgery, Henan Chest Hospital, Zhengzhou, China
| | - X Liu
- Department of Cardiology, Henan Chest Hospital, Zhengzhou, China
| | - J-H Wang
- Department of Radiotherapy, Henan Cancer Hospital Affiliated to Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - J Wang
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - S Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Zhou YX, Chen P, Sun YT, Zhang B, Qiu MZ. Comparison of PD-1 Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma in the Second-Line Setting. Front Oncol 2021; 11:698732. [PMID: 34621668 PMCID: PMC8490758 DOI: 10.3389/fonc.2021.698732] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/30/2021] [Indexed: 12/24/2022] Open
Abstract
Background KEYNOTE-181, ATTRACTION-3, and ESCORT trials have opened the era of programmed death 1 (PD-1) inhibitors in the second-line therapy for esophageal squamous cell carcinoma (ESCC). There is no head-to-head comparison of pembrolizumab vs. nivolumab vs. camrelizumab in the second-line setting for ESCC. We performed an indirect comparison to explore the optimal choice of immune checkpoint inhibitor (ICI) for advanced ESCC. Methods Patients in ATTRACTION-3 and ESCORT were all squamous carcinoma, while KEYNOTE-181 enrolled both adenocarcinoma and squamous carcinoma patients. We only extract information of patients with squamous carcinoma from KEYNOTE 181 study and all the patients from ATTRACTION-3 and ESCORT. The main clinical outcomes for this study were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Results Indirect analysis showed similar survival benefit among three PD-1 inhibitors. Nivolumab was comparable with pembrolizumab in most subgroups except that nivolumab was slightly better for patients with performance status (PS) score of 1 [HRnivo/pembro: 0.68 (95% confidence interval (CI): 0.45–1.02], p = 0.07). Compared with nivolumab indirectly, pembrolizumab and camrelizumab had better PFS [HRpembro/nivo: 0.85 (95% CI: 0.63–1.14), p = 0.29; HRcam/nivo: 0.64 (95% CI: 0.47–0.87), p = 0.004] and significantly higher ORR [RRpembro/nivo: 2.51 (95% CI: 1.22–5.15), p = 0.01; RRcam/nivo: 3.52 (95% CI: 1.73–7.18), p = 0.001]. Compared with camrelizumab indirectly, pembrolizumab had slightly worse PFS [HRpembro/cam: 1.33 (95% CI: 0.99–1.79), p = 0.057] and comparable ORR [RRpembro/cam: 0.71 (95% CI: 0.32–1.60; p = 0.41)]. Camrelizumab had a significantly higher rate of all grade TRAEs than both pembrolizumab and nivolumab. Conclusions Combining the safety and potential survival benefit, we recommend nivolumab for ESCC patients with PS score of 1 and pembrolizumab or camrelizumab for patients with better PS and seeking for higher efficacy or longer PFS.
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Affiliation(s)
- Yi-Xin Zhou
- Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Ping Chen
- Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yu-Ting Sun
- 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
| | - Bei Zhang
- Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Miao-Zhen Qiu
- 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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Yamamoto S, Kawakami H, Kii T, Hara H, Kawabata R, Kawada J, Takeno A, Matsuyama J, Ueda S, Okita Y, Endo S, Kimura Y, Yanagihara K, Okuno T, Kurokawa Y, Shimokawa T, Satoh T. Randomized phase II study of docetaxel versus paclitaxel in patients with esophageal squamous cell carcinoma refractory to fluoropyrimidine- and platinum-based chemotherapy: OGSG1201. Eur J Cancer 2021; 154:307-315. [PMID: 34311300 DOI: 10.1016/j.ejca.2021.06.035] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 06/09/2021] [Accepted: 06/20/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND There is no standard chemotherapy for esophageal squamous cell carcinoma (ESCC) refractory to first-line fluoropyrimidine- and platinum-based chemotherapy. We therefore performed a randomized, selection-design phase II trial to compare docetaxel (DTX) and paclitaxel (PTX) in this setting. PATIENTS AND METHODS Eligible patients were randomly assigned to receive either DTX (70 mg/m2 on day 1 of each 21-day cycle) or PTX (100 mg/m2 on days 1, 8, 15, 22, 29 and 36 of each 49-day cycle). The primary end-point was overall survival (OS), and secondary end-points included progression-free survival (PFS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS Seventy-eight eligible patients (N = 39 in each group) were included for efficacy analysis. OS was significantly longer in the PTX group than in the DTX group (median, 8.8 versus 7.3 months; hazard ratio [HR], 0.62; P = 0.047). A significant benefit of PTX over DTX was also apparent in PFS (median, 4.4 versus 2.1 months; HR, 0.49; P = 0.002) and TTF (median, 3.8 versus 2.1 months; HR, 0.45; P < 0.001). RR (25.6% versus 7.7%, P = 0.065) were higher in the PTX group than in the DTX group. Compared to the PTX group, neutropenia (28% versus 80%) and leukopenia (28% versus 76%) of grade ≥3 as well as febrile neutropenia (0% vs. 46%, P < 0.0001) occurred more frequently in the DTX group. CONCLUSION PTX showed a significantly better efficacy as well as a more manageable toxicity compared with DTX. CLINICAL TRIAL REGISTRATION UMIN000007940.
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Affiliation(s)
- Sachiko Yamamoto
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Osaka, 541-8567, Japan.
| | - Hisato Kawakami
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osakasayama, Osaka, 589-8511, Japan.
| | - Takayuki Kii
- Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, 569-0801, Japan.
| | - Hiroki Hara
- Department of Gastroenterology, Saitama Cancer Center, Kitaadachi-gun, Saitama, 362-0806, Japan.
| | - Ryohei Kawabata
- Department of Surgery, Osaka Rosai Hospital, Sakai, Osaka, 591-8025, Japan; Department of Surgery, Sakai City Medical Center, Sakai, Osaka, 593-8304, Japan.
| | - Junji Kawada
- Department of Surgery, Osaka General Medical Center, Osaka, Osaka, 558-8558, Japan.
| | - Atsushi Takeno
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, 660-8511, Japan.
| | - Jin Matsuyama
- Department of Surgery, Yao Municipal Hospital, Yao, Osaka, 581-0069, Japan.
| | - Shugo Ueda
- Department of Gastroenterological Surgery and Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Osaka, 530-8480, Japan.
| | - Yoshihiro Okita
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo, 650-0047, Japan; Department of Clinical Oncology, Kagawa University Faculty of Medicine, Kita-gun, Kagawa, 761-0793, Japan.
| | - Shunji Endo
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Higashiosaka, Osaka, 578-8588, Japan.
| | - Yutaka Kimura
- Department of Surgery, Sakai City Medical Center, Sakai, Osaka, 593-8304, Japan; Department of Surgery, Kindai University Faculty of Medicine, Osakasayama, Osaka, 589-8511, Japan.
| | - Kazuhiro Yanagihara
- Department of Medical Oncology, Kansai Electric Power Hospital, Osaka, Osaka, 553-0003, Japan.
| | - Tatsuya Okuno
- Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Hyogo, 650-0017, Japan.
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
| | - Toshio Shimokawa
- Department of Medical Data Science, Graduate School of Medicine, Wakayama Medical University, Wakayama, Wakayama, 641-8510, Japan.
| | - Taroh Satoh
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
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Chen X, Zhang Y, Shi Y, Niu T, Li B, Guo L, Qiao Y, Zhao J, Yuan B, Liu K. Evolution of DNA aptamers against esophageal squamous cell carcinoma using cell-SELEX. Analyst 2021; 146:4180-4187. [PMID: 34105524 DOI: 10.1039/d1an00634g] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Esophageal cancer is the ninth most common cancer and the sixth most common cause of cancer-related death worldwide, and the esophageal squamous cell carcinoma (ESCC) subtype accounts for about 90% of all cases of esophageal cancer globally. Currently, ESCC is usually diagnosed in late stages, and targeted therapy is lacking. Therefore, the development of ESCC-specific recognition molecules for an early detection and targeted treatment of ESCC is urgently needed. Aptamers are an excellent molecular recognition tool with unique advantages. In this manuscript, three aptamers (S2, S3, and S8) specific to ESCC cells were successfully screened via cell-SELEX. The experimental results displayed the high affinities of the three aptamers for target KYSE150 cells with dissociation constants in the nanomolar range. The specificity evaluation showed that S2 only bound target KYSE150 cells, but S3 and S8 were capable of targeting a series of ESCC cells. Moreover, several truncated aptamers were generated through sequence optimization. In particular, an ultrashort aptamer S3-2-3 with only 18 bases was successfully obtained; after labeling with Cy5 dyes, it was feasible for the specific imaging of ESCC tissues. Furthermore, the target types of the selected aptamers were preliminarily identified as membrane proteins, and target proteins could be captured by S3-2-3, which may be useful for biomarker discovery. Therefore, the selected aptamers hold great potential for clinical diagnosis, biomarker discovery, and the targeted therapy of ESCC.
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Affiliation(s)
- Xinhuan Chen
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. and Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, China and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China
| | - Yangyang Zhang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
| | - Yanli Shi
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
| | - Tingting Niu
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
| | - Bo Li
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. and Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, China and China-US Hormel (Henan) Cancer Institute, Zhengzhou, Henan, China
| | - Linyan Guo
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
| | - Yan Qiao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. and Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, China and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China
| | - Jimin Zhao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. and Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, China and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China
| | - Baoyin Yuan
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. and Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, China and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China
| | - Kangdong Liu
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. and Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, China and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China and China-US Hormel (Henan) Cancer Institute, Zhengzhou, Henan, China and Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China
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Yu G, Yu W, Xu X, Ye B, Yao L. Neoadjuvant immunotherapy for resectable esophageal cancer: A protocol of meta-analysis. PLoS One 2021; 16:e0252829. [PMID: 34086821 PMCID: PMC8177427 DOI: 10.1371/journal.pone.0252829] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 05/21/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Esophageal cancer is a highly malignant cancer with a very poor prognosis. For resectable esophageal cancer, neoadjuvant treatment could improve the prognosis of esophageal cancer. However, current clinical neoadjuvant treatment options for esophageal cancer are still limited. The application of immunotherapy is a potentially beneficial new neoadjuvant treatment option for esophageal cancer. The objective of this meta-analysis is to evaluate the efficacy and safety of immunotherapy for the neoadjuvant treatment of esophageal cancer. METHODS We will search Wanfang Database, SinoMed, China National Knowledge Infrastructure, Embase, Web of Science, Pubmed, and Cochrane Library for relevant articles published before July, 2021. We will also search the unpublished clinical trials of neoadjuvant immunotherapy in esophageal cancer in preprint website (such as bioRXiv and medRxiv) up to July, 2021. We will perform a meta-analysis to evaluate the efficacy and safety of neoadjuvant immunotherapy for resectable esophageal cancer. Randomized controlled trials (RCTs) will be included in this study. The risk of bias will be evaluated for each included study using the Cochrane Handbook for Systematic Reviews of Interventions. We will use RevMan 5.3 software for statistical analysis of the data. RESULTS The results of this study will provide evidence of immunotherapy using as neoadjuvant treatment for esophageal cancer. This meta-analysis will be submitted to a peer-reviewed journal seeking for publication. CONCLUSION The results of this study will provide a reliable basis for clinicians and patients to formulate the best pre-surgical treatment plan for resectable esophageal cancer. SYSTEMATIC REVIEW REGISTRATION INPLASY202120026.
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Affiliation(s)
- Guocan Yu
- Department of Thoracic Surgery, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wenfeng Yu
- Department of Thoracic Surgery, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xudong Xu
- Department of Thoracic Surgery, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Bo Ye
- Department of Thoracic Surgery, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Liwei Yao
- Department of Nursing, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Wu X, Zhang H, Sui Z, Wang Y, Yu Z. The biological role of the CXCL12/CXCR4 axis in esophageal squamous cell carcinoma. Cancer Biol Med 2021; 18:j.issn.2095-3941.2020.0140. [PMID: 33710803 PMCID: PMC8185864 DOI: 10.20892/j.issn.2095-3941.2020.0140] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 07/30/2020] [Indexed: 12/12/2022] Open
Abstract
Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the main histological type of esophageal cancer, and accounts for 90% of all cancer cases. Despite the progress made in surgery, chemotherapy, and radiotherapy, the mortality rate from esophageal cancer remains high, and the overall 5-year survival rate is less than 20%, even in developed countries. The C-X-C motif chemokine ligand 12 (CXCL12) is a member of the CXC chemokine subgroup, which is widely expressed in a variety of tissues and cells. CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor, C-X-C motif chemokine receptor type 4 (CXCR4), where it causes embryonic development, immune response, and angiogenesis. In addition, increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells. Studies have shown that CXCL12 and its receptor, CXCR4, are highly expressed in ESCC. This abnormal expression contributes to tumor proliferation, lymph node and distant metastases, and worsening prognosis. At present, antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors. This article summarizes the structure, function, and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC. Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.
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Affiliation(s)
- Xianxian Wu
- Departments of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Hongdian Zhang
- Departments of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Zhilin Sui
- Departments of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Yang Wang
- Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Zhentao Yu
- Departments of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
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High Systemic Immune-Inflammation Index is an Adverse Prognostic Factor for Patients With Gastroesophageal Adenocarcinoma. Ann Surg 2021; 273:532-541. [PMID: 31425286 DOI: 10.1097/sla.0000000000003370] [Citation(s) in RCA: 112] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The aim of this study was to determine the clinical role of the systemic immune-inflammation index in patients with resectable adenocarcinoma of the gastroesophageal junction treated with or without neoadjuvant therapy. BACKGROUND Adenocarcinoma of the gastroesophageal junction is an aggressive disease, with less than 20% of overall patients surviving more than 5 years after diagnosis, while currently available clinical staging for esophageal cancer is lacking necessary accuracy. The systemic immune-inflammation index (SII) based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in various malignancies. METHODS Data of consecutive patients undergoing esophagectomy (n = 320, 1992 to 2016) were abstracted. The cut point for high and low SII before neoadjuvant treatment and before surgery was calculated for illustration of the Kaplan-Meier curves. SII was used for the correlation with patients' clinicopathological characteristics as a continuous variable. Survival was analyzed with Cox proportional hazards models using clinical or pathological staging, adjusting for other known survival predictors. RESULTS In both neoadjuvantly treated and primarily resected patients, high SII was significantly associated with diminished overall [hazard ratio (HR) 1.3, 95% confidence interval (95% CI) 1.2-1.4; HR 1.2, 95% CI 1.2-1.3, respectively] and disease-free survival (HR 1.3, 95% CI 1.2-1.3; HR 1.2, 95% CI 1.2-1.3, respectively). In multivariable survival analysis, SII remained an independent prognostic factor for overall survival (HR 1.3, 95% CI 1.2-1.4; HR 1.2, 95% CI 1.2-1.3, respectively) and disease-free survival (HR 1.3, 95% CI 1.2-1.3; HR 1.2, 95% CI 1.2-1.3, respectively) in primarily resected and neoadjuvantly treated patients. CONCLUSION Elevated SII is an independent adverse prognostic factor in patients with resectable gastroesophageal adenocarcinomas with and without neoadjuvant treatment.
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Mao C, Zeng X, Zhang C, Yang Y, Xiao X, Luan S, Zhang Y, Yuan Y. Mechanisms of Pharmaceutical Therapy and Drug Resistance in Esophageal Cancer. Front Cell Dev Biol 2021; 9:612451. [PMID: 33644048 PMCID: PMC7905099 DOI: 10.3389/fcell.2021.612451] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 01/04/2021] [Indexed: 02/05/2023] Open
Abstract
Pharmaceutical therapies are essential for esophageal cancer (EC). For the advanced EC, the neoadjuvant therapy regimen, including chemotherapy plus radiotherapy and/or immunotherapy, is effective to achieve clinical benefit, even pathological complete response. For the unresectable, recurrent, and metastatic EC, the pharmaceutical therapy is the limited effective regimen to alleviate the disease and prolong the progression-free survival and overall survival. In this review, we focus on the pharmaceutical applications in EC treatment including cytotoxic agents, molecular targeted antibodies, and immune checkpoint inhibitors (ICIs). The chemotherapy regimen is based on cytotoxic agents such as platinum-based complexes, fluorinated pyrimidines and taxenes. Although the cytotoxic agents have been developed in past decades, the standard chemotherapy regimen is still the cisplatin and 5-FU or paclitaxel because the derived drugs have no significant advantages of overcoming the shortcomings of side effects and drug resistance. The targeted molecular therapy is an essential supplement for chemotherapy; however, there are only a few targeted therapies available in clinical practice. Trastuzumab and ramucirumab are the only two molecular therapy drugs which are approved by the US Food and Drug Administration to treat advanced and/or metastatic EC. Although the targeted therapy usually achieves effective benefits in the early stage therapy of EC, the patients will always develop drug resistance during treatment. ICIs have had a significant impact on routine clinical practice in cancer treatment. The anti-programmed cell death-1 monoclonal antibodies pembrolizumab and nivolumab, as the ICIs, are recommended for advanced EC by several clinical trials. However, the significant issues of pharmaceutical treatment are still the dose-limiting side effects and primary or secondary drug resistance. These defects of pharmaceutical therapy restrain the clinical application and diminish the effectiveness of treatment.
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Affiliation(s)
- Chengyi Mao
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoxi Zeng
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
| | - Chao Zhang
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yushang Yang
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
| | - Xin Xiao
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
| | - Siyuan Luan
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
| | - Yonggang Zhang
- Department of Periodical Press, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
- Nursing Key Laboratory of Sichuan Province, Chengdu, China
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Yuan
- Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China
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Qian J, Tong Z, Zhang Y, Chen C. Platinum versus immunotherapy for unresectable esophageal cancer: A protocol for systematic review and meta analysis. Medicine (Baltimore) 2020; 99:e23537. [PMID: 33371077 PMCID: PMC7748184 DOI: 10.1097/md.0000000000023537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 11/06/2020] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND Esophageal cancer is one of the most common malignant tumors, with early metastasis, highly malignant characteristics. Morbidity ranks 7th among all malignant tumors, and mortality ranks 6th. Esophageal adjuvant therapy can significantly improve overall survival in unresectable esophageal cancer patients. With the breakthrough and progress of immunotherapy, the possibility of curing esophageal cancer has greatly increased. Some clinical trials have reported that compared with traditional platinum-based chemotherapy, the use of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors alone can benefit patients and effectively prolong their overall survival. We compare the efficacy of single immunotherapy with traditional platinum-based chemotherapy in a systematic review and meta-analysis to provide a reliable basis for clinicians. METHODS We will search PubMed, Medline, Embase, Web of Science, Cancerlit, Google Scholar, and the Cochrane Central Register of Controlled Trials for related studies published before December 1, 2019 without language restrictions. Two review authors will search and assess relevant studies independently. Randomized controlled trials (RCTs) or quasi-RCTs, and prospective cohort studies will be included. We will perform subgroup analysis in sex, age, ethnicity, and tumor stage of esophageal cancer patients. RESULTS The results of this study will be published in a peer-reviewed journal. CONCLUSION The results of this systematic review and meta-analysis will provide a basis for clinicians to formulate the best chemotherapy regimen for patients, as well as a research clue for clinical researchers in this field. The results of this study will expand the treatment options for esophageal patients, but due to the nature of the disease and intervention, large sample clinical trials are not abundant, so we will include some high-quality small sample trials, which may cause high heterogeneity. INPLASY REGISTRATION NUMBER INPLASY2020110012.
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Affiliation(s)
- Jiekun Qian
- Department of Thoracic Surgery, Fujian Medical University Union Hospital
| | - Zhangwei Tong
- Department of Thoracic Surgery, Fujian Medical University Union Hospital
| | - Yannan Zhang
- Department of Ophthalmology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Chun Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital
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Endoscopic Eradication Therapy for Barrett's Neoplasia: Where Do We Stand a Decade Later? Curr Gastroenterol Rep 2020; 22:61. [PMID: 33277663 DOI: 10.1007/s11894-020-00799-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), a cancer associated with increasing incidence and poor survival. Early identification and effective treatment of BE-related neoplasia prior to the development of invasive adenocarcinoma are essential to limiting the morbidity and mortality associated with this cancer. In this review, we summarized the recent evidence guiding endoscopic eradication therapies (EET) for neoplastic BE. RECENT FINDINGS New sampling technologies and the application of artificial intelligence (AI) systems have potential to revolutionize early neoplasia detection in BE. EET for BE are safe and effective in achieving complete eradication of intestinal metaplasia (CE-IM) and reducing the progression to EAC, a practice endorsed by all GI society guidelines. EET should be considered in patients with high-grade dysplasia (HGD), intramucosal carcinoma (IMC), and select cases with low-grade dysplasia (LGD). The increasing use of endoscopic submucosal dissection (ESD) in the West may allow EET of select cases with submucosal EAC. Post-EET surveillance strategies will continue to evolve as knowledge of specific risk factors and long-term neoplasia recurrence rates improve. In the last decade, major advancements in EET for neoplastic BE have been achieved. These now represent the standard of care in the management of BE-related dysplasia and intramucosal cancer.
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Chen J, Zhou L, Wang C, Sun Y, Lu Y, Li R, Hu X, Chen M, Chen L, Chai K, Yao T, Shi S, Dong C. A multifunctional SN38-conjugated nanosystem for defeating myelosuppression and diarrhea induced by irinotecan in esophageal cancer. NANOSCALE 2020; 12:21234-21247. [PMID: 33063070 DOI: 10.1039/d0nr06266a] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
A combination of chemotherapy and phototherapy has been proposed as a promising treatment for esophageal cancer (EC). Irinotecan as a first-line treatment option is widely prescribed for metastatic EC, however, its clinical application is extremely restricted by the low conversion rate to SN38, severe myelosuppression and diarrhea. As a more potent active metabolite of irinotecan, SN38 is a better substitution for irinotecan, but the poor water solubility and the difficulty of encapsulation hindered its medical application. Herein, a multifunctional SN38-conjugated nanosystem (FA-PDA@PZM/SN38@BSA-MnO2, denoted as FA-PPSM) is designed for overcoming the above-mentioned drawbacks and achieving collaborative chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT). The tumor acidic microenvironment induces decomposition of BSA-MnO2 nanoparticles into O2 and Mn2+, thus enhancing oxygen-dependent PDT efficacy; meanwhile, Mn2+ can be employed as a magnetic resonance imaging (MRI) contrast agent. Under 650 and 808 nm laser irradiation, the FA-PPSM nanocomposites exhibit superior antitumor efficacy in Eca-109-tumor bearing mice. Notably, there is low gastrointestinal toxicity and myelosuppression in the FA-PPSM treated mice compared with those treated with irinotecan (alone). Taken together, this work highlights the great potential of the FA-PPSM nanocomposites for MRI-guided chemotherapy in combination with endoscopic light therapy for esophageal cancer.
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Affiliation(s)
- Jinjin Chen
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Lulu Zhou
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Chunhui Wang
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Yunhao Sun
- Department of Thoracic surgery, The First People's Hospital of Yancheng, Affiliated Hospital of Nanjing University Medical School, Yancheng, Jiangsu, P. R. China
| | - Yonglin Lu
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Ruihao Li
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Xiaochun Hu
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Mengyao Chen
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Lv Chen
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Keke Chai
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Tianming Yao
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Shuo Shi
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
| | - Chunyan Dong
- Breast Cancer Center, Shanghai East Hospital, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.
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