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Podger L, Serrano D, Li L, Zhan L, Tang B, Barnes G. Psychometric validation of the EORTC QLQ-OES18 in patients with advanced or metastatic esophageal squamous cell carcinoma. J Patient Rep Outcomes 2025; 9:56. [PMID: 40397297 PMCID: PMC12095746 DOI: 10.1186/s41687-025-00891-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 05/02/2025] [Indexed: 05/22/2025] Open
Abstract
BACKGROUND The EORTC QLQ-OES18 has previously demonstrated clinical validity; however, there are limited published psychometric data for patients with advanced esophageal squamous cell carcinoma (ESCC). We evaluated the measurement properties of the QLQ-OES18 in a clinical trial population of patients with advanced or metastatic ESCC. METHODOLOGY Analyses used data from RATIONALE 302 (NCT03430843), a randomized phase 3 study of tislelizumab versus investigator-chosen chemotherapy as second-line treatment for patients with advanced or metastatic ESCC. Psychometric validation of the QLQ-OES18 included tests of reliability, construct validity, ability to detect change, and estimation of anchor-based meaningful within-patient change (MWPC) thresholds-the latter two being exploratory given that the trial was not powered to detect efficacy in patient-reported outcome endpoints. RESULTS In total, 512 patients were randomized to either tislelizumab or chemotherapy; the average age was 61.5 years, and 84.4% were male. Three of the 4 QLQ-OES18 multi-item scales (dysphagia, eating, and pain) and the index scale met the prespecified criterion for acceptable internal consistency as well as acceptable test-retest reliability. Associations between baseline QLQ-OES18 scores and convergent/discriminant validators were generally as expected (i.e., the QLQ-OES18 pain score had a strong positive correlation with the QLQ-C30 pain score). For known-groups validity, 88.6% of analyses demonstrated the hypothesized direction of effect, suggesting that the expected differences in baseline QLQ-OES18 scores between prespecified groups were observed. Ability to detect change analyses indicated that several QLQ-OES18 domain scores demonstrated sensitivity in detecting possible treatment effects, although many patients reported minimal symptoms at baseline, which limited the ability to detect significant improvement. CONCLUSION Overall, a collection of psychometric evidence indicated that the EORTC QLQ-OES18 reliably and validly measured symptom severity in the RATIONALE 302 population. Specifically, the dysphagia domain consistently demonstrated robust psychometric properties. Limitations in data reduced the interpretability of MWPC thresholds and are discussed in detail.
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Affiliation(s)
| | | | - Liyun Li
- BeOne Medicines Ltd, San Carlos, CA, USA
| | - Lin Zhan
- BeOne Medicines Ltd, San Carlos, CA, USA
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Cocks K, King-Kallimanis BL, Sims J, Worthy G, Stein J, Ayala-Nunes L, Achra M, Cui ZL, Payakachat N. Time to deterioration of patient-reported outcome endpoints in cancer clinical trials: targeted literature review and best practice recommendations. J Patient Rep Outcomes 2024; 8:150. [PMID: 39694990 DOI: 10.1186/s41687-024-00824-7] [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: 04/19/2024] [Accepted: 12/06/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Time to deterioration (TTD) endpoints are often utilized in the analysis of patient-reported outcome (PRO) data in oncology clinical trials but different endpoint definitions and analysis frameworks exist that can impact result interpretation. This review examined the analysis, reporting and heterogeneity of TTD endpoints in the literature, the impact of analysis methods on results, and provides recommendations for future trials. METHODS A targeted literature review of articles published between 2017 and 2022 was performed to collate TTD endpoints reported in oncology randomized controlled trials (RCTs). Details of endpoints and results were extracted including; deterioration definition, PRO assessment schedule, methods for handling intercurrent events, statistical analysis methods, main trial results (overall survival and/or progression-free survival) and TTD endpoint results. RESULTS Seventy RCTs were included covering 849 individual TTD endpoints. There were 17 primary cancer types, with lung (26%), breast (11%), and prostate (7%) cancers the most common. Most trials (71%) were for people with advanced cancer. Full definitions of TTD endpoints were often missing. There were no clear trends for a specific TTD definition within cancer types or stages. However, statistical analysis methods were consistent among trials. CONCLUSION The TTD definition can vary and is ultimately driven by the research question. Points to consider for successfully implementing PRO TTD endpoints in oncology include consideration of the trial setting (e.g., early vs. advanced cancer), expected treatment effect (e.g., improvement vs. worsening), likely adverse event profile (including early vs. delayed) and PRO data collection frequency in order to improve utility of these endpoints.
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Affiliation(s)
- Kim Cocks
- Adelphi Values Ltd, Patient-Centered Outcomes, Adelphi Mill, Grimshaw Lane, Bollington, Macclesfield, SK10 5JB, UK.
| | | | - Joel Sims
- Adelphi Values Ltd, Patient-Centered Outcomes, Adelphi Mill, Grimshaw Lane, Bollington, Macclesfield, SK10 5JB, UK
| | - Gill Worthy
- Adelphi Values Ltd, Patient-Centered Outcomes, Adelphi Mill, Grimshaw Lane, Bollington, Macclesfield, SK10 5JB, UK
| | - Julia Stein
- Adelphi Values Ltd, Patient-Centered Outcomes, Adelphi Mill, Grimshaw Lane, Bollington, Macclesfield, SK10 5JB, UK
| | - Lara Ayala-Nunes
- Adelphi Values Ltd, Patient-Centered Outcomes, Adelphi Mill, Grimshaw Lane, Bollington, Macclesfield, SK10 5JB, UK
| | - Monika Achra
- Eli Lilly and Company, 639 S. Delaware St, Indianapolis, Indiana, 46285, USA
| | - Zhanglin Lin Cui
- Eli Lilly and Company, 639 S. Delaware St, Indianapolis, Indiana, 46285, USA
| | - Nalin Payakachat
- Eli Lilly and Company, 639 S. Delaware St, Indianapolis, Indiana, 46285, USA
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Zhou Z, Zhang H, Du J, Yang J, Pan W, Zhang Q, Wang H, Tang P, Ba Y, Zhang H. A spatiotemporal comparative analysis on tumor immune microenvironment characteristics between neoadjuvant chemotherapy and preoperative immunotherapy for ESCC. Cell Death Dis 2024; 15:663. [PMID: 39256364 PMCID: PMC11387609 DOI: 10.1038/s41419-024-06986-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 08/02/2024] [Accepted: 08/07/2024] [Indexed: 09/12/2024]
Abstract
The average five-year survival rate for esophageal cancer, a common malignant tumor of the digestive system, is barely 20%. The majority of esophageal squamous cell carcinoma (ESCC) patients had already progressed to a locally advanced or even advanced stage at initial diagnosis, making routine surgery ineffective. Chemotherapy and immunotherapy are important neoadjuvant treatments for ESCC, however, it remains unknown how treatment will affect the immunological microenvironment, especially at the spatial level. Here, we presented the TME characters of ESCC from the temporal and spatial dimensions using scRNA-seq and ST, investigated the changes of immune cell clusters in the TME under neoadjuvant chemotherapy and preoperative immunotherapy, and explored the potential mechanisms. It was found that compared with chemotherapy, immunotherapy combined with chemotherapy increased the level of T cell proliferation, partially restored the function of exhausted T cells, induced the expansion of specific exhausted CD8 T cells, increased the production of dendritic cells (DCs), and supported the immune hot microenvironment of the tumor. We also found that CD52 and ID3 have potential as biomarkers of ESCC. Particularly, CD52 may be served as a predictor of the efficacy to screen the advantaged population of different regimens. Through multiple pathways, CAF2 and CAF5's antigen-presenting role affected the other fibroblast clusters, resulting in malignant transformation. We analyzed the immune microenvironment differences between the two regimens to provide a more thorough description of the ESCC microenvironment profile and serve as a foundation for customized neoadjuvant treatment of ESCC.
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Affiliation(s)
- Zhengyang Zhou
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Hongdian Zhang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Jian Du
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Jiayu Yang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Wen Pan
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Qiumo Zhang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Huiya Wang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China
| | - Peng Tang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300202, China.
| | - Yi Ba
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dongcheng District, Beijing, 100032, China.
| | - Haiyang Zhang
- Tianjin Institute of Coloproctology, Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin, 300121, China.
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Yu Y, Wu T, Gan W, Liu C, Zhang R, Zheng J, Xiong J, Chen J, Li J. Clinical features and treatment outcomes of PD-1 inhibitor therapy in elderly patients (≥ 65 years) with advanced esophageal squamous cell carcinoma: a real-world study. Clin Transl Oncol 2024; 26:2360-2368. [PMID: 38602642 DOI: 10.1007/s12094-024-03453-0] [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: 02/28/2024] [Accepted: 03/05/2024] [Indexed: 04/12/2024]
Abstract
PURPOSE This study aims to determine the clinical features and outcomes of PD-1 inhibitor therapy as the initial treatment in patients aged 65 years or older with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS The retrospective study conducted a comprehensive analysis of elder patients diagnosed with locally advanced or metastatic ESCC who underwent combined immunochemotherapy in the first affiliated hospital of Nanchang University from January 2019 to January 2023. The main efficacy measures were the objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR) and overall survival (OS). The evaluation of safety was based on the assessment of adverse events (AEs). RESULTS A total of 88 patients were enrolled in the study. All patients received PD-1 inhibitors combined with chemotherapy including taxane and platinum as the first-line treatment. The median PFS was 6.2 months (95% CI: 5.1-7.3), and the median OS was 15.3 months (95% CI: 12.9-17.7). The ORR and DCR were 42.0% and 72.7%, correspondingly. 68 (77.3%) patients experienced treatment-related adverse events (TRAEs) of various degrees, with neutrophil count decreased (21, 23.9%) being the most frequent. TRAEs of grade 3 or 4 occurred in 13 (14.8%) patients. CONCLUSION The study demonstrated that individuals older than 65 years with locally advanced or metastatic ESCC have a survival benefit from the first-line treatment of PD-1 inhibitors combined therapy, with a manageable safety profile.
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Affiliation(s)
- Yi Yu
- Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Tao Wu
- Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Wei Gan
- Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China
| | - Can Liu
- Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Ran Zhang
- Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jinxiu Zheng
- Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jianping Xiong
- Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
| | - Jun Chen
- Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
| | - Junhe Li
- Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
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Qin S, Fang W, Ren Z, Ou S, Lim HY, Zhang F, Lee KC, Choi HJ, Tong J, Tao M, Xu A, Cheng A, Lu CH, Chiu CF, Abdul Wahid MI, Kamble S, Norquist JM, Zhong W, Li C, Chen Z. A Phase 3 Study of Pembrolizumab versus Placebo for Previously Treated Patients from Asia with Hepatocellular Carcinoma: Health-Related Quality of Life Analysis from KEYNOTE-394. Liver Cancer 2024; 13:389-400. [PMID: 39114760 PMCID: PMC11305669 DOI: 10.1159/000535338] [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: 03/08/2023] [Accepted: 09/13/2023] [Indexed: 08/10/2024] Open
Abstract
Introduction KEYNOTE-394 showed pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate with manageable safety versus placebo for patients from Asia with previously treated advanced hepatocellular carcinoma. We present results on health-related quality of life (HRQoL). Methods HRQoL was evaluated using the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EuroQol-5D-3L (EQ-5D-3L) questionnaires. Key HRQoL endpoints were least squares mean (LSM) score changes from baseline to week 12 and time to deterioration (TTD) for EORTC QLQ-C30 global health status (GHS)/QoL. p values were one-sided and nominal without adjustment for multiplicity. Results The HRQoL population included patients randomly assigned to pembrolizumab (n = 298) and placebo (n = 152). From baseline to week 12, a greater decline in EORTC QLQ-C30 GHS/QoL score was observed with placebo (LSM, -8.4; 95% CI: -11.7 to -5.1) versus pembrolizumab (-4.0; 95% CI: -6.4 to -1.6; difference vs. placebo: 4.4; 95% CI: 0.5-8.4; nominal p = 0.0142). Similarly, a greater decline in the EQ-5D-3L visual analog scale score was observed with placebo (-6.9; 95% CI: -9.4 to -4.5) versus pembrolizumab (-2.7; 95% CI: -4.5 to -1.0; difference vs. placebo: 4.2; 95% CI: 1.2-7.2; nominal p = 0.0030). TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (hazard ratio, 0.85; 95% CI: 0.58-1.25; nominal p = 0.1993). Conclusion Patients receiving placebo showed a greater decline in HRQoL than those receiving pembrolizumab. Combined with efficacy and safety data from KEYNOTE-394 and the global KEYNOTE-240 and KEYNOTE-224 trials, our data support the clinically meaningful benefit and manageable tolerability of pembrolizumab as second-line therapy for patients with advanced hepatocellular carcinoma.
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Affiliation(s)
- Shukui Qin
- GI Cancer Center, Nanjing Tianyinshan Hospital, Nanjing, China
| | - Weijia Fang
- The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhenggang Ren
- Zhongshan Hospital, Fudan University, Shanghai, China
| | | | - Ho Yeong Lim
- Samsung Medical Center, Seoul, Republic of Korea
| | | | - Kin Chung Lee
- Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong SAR
| | - Hye Jin Choi
- Severance Hospital Yonsei University Health System, Seoul, Republic of Korea
| | | | - Min Tao
- The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Aibing Xu
- Nantong Tumor Hospital, Nantong, China
| | - Ashley Cheng
- Princess Margaret Hospital, Kwai Chung, Hong Kong SAR
| | | | | | | | | | | | | | | | - Zhendong Chen
- The Second Affiliated Hospital of Anhui Medical University, Hefei, China
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Zhang Y, Li Z, Huang Y, Xu Y, Zou B. Advancements in immunotherapy for advanced esophageal squamous cell carcinoma: a comprehensive review of current strategies and future directions. Expert Rev Clin Immunol 2024; 20:971-984. [PMID: 38884604 DOI: 10.1080/1744666x.2024.2368194] [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: 12/19/2023] [Accepted: 06/10/2024] [Indexed: 06/18/2024]
Abstract
INTRODUCTION Esophageal cancer (EC), particularly esophageal squamous cell carcinoma (ESCC), is characterized by high incidence and poor prognosis worldwide, necessitating novel therapeutic approaches like immunotherapy. This review explores the impact of immune checkpoint inhibitors (ICIs) on ESCC, especially focusing on PD-1/PD-L1 and CTLA-4 inhibitors. Our literature search, conducted across databases including PubMed, Web of Science, and EMBASE, from January 2010 to December 2023, aimed at identifying advancements, challenges, and future directions in the use of immunotherapy for ESCC. AREAS COVERED We provide a detailed analysis of clinical trials evaluating the efficacy of ICIs as monotherapy and in combination with chemotherapy, radiotherapy, and targeted therapy for locally advanced ESCC. Our findings highlight the significant survival benefits offered by ICIs, albeit with varying efficacy across patient populations, emphasizing the need for precise biomarkers to tailor treatment strategies. EXPERT OPINION The integration of immunotherapy into the ESCC treatment paradigm represents a significant shift, improving survival outcomes. Future research should focus on optimizing combination therapies and novel immunotherapeutic agents, incorporating genetic and tumor microenvironment analyses to enhance patient selection and treatment efficacy.
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Affiliation(s)
- Yi Zhang
- Department of Radiation Oncology, Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Zheng Li
- Department of Radiation Oncology, Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Ying Huang
- College of Management, Sichuan Agricultural University, Chengdu, P.R. China
| | - Yong Xu
- Department of Radiation Oncology, Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Bingwen Zou
- Department of Radiation Oncology, Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, P.R. China
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Gupta K, Roy AM, Attwood K, Nipp RD, Mukherjee S. Effects of Immunotherapy on Quality-of-Life Outcomes in Patients with Gastroesophageal Cancers: A Meta-Analysis of Randomized Controlled Trials. Healthcare (Basel) 2024; 12:1496. [PMID: 39120199 PMCID: PMC11311609 DOI: 10.3390/healthcare12151496] [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: 06/11/2024] [Revised: 07/16/2024] [Accepted: 07/23/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) have revolutionized cancer care, with increasing data demonstrating improved survival outcomes using ICIs among patients with advanced gastroesophageal cancer (GEC). ICIs are also associated with a lower incidence of grade ≥ 3 adverse events (AEs) compared to chemotherapy, suggesting that ICIs may have favorable effects on health-related quality of life (HRQoL). This meta-analysis sought to evaluate the effects of ICIs on the HRQoL of patients with advanced GEC. METHODS We conducted an online bibliographic search on Medline via PubMed using MeSH-based terms to retrieve randomized controlled trials (RCTs) that evaluated the effects of ICIs on HRQoL in patients with advanced GEC (we searched for all studies between 2018 and 2021). We included RCTs that incorporated ICIs as part of the intervention arm either as monotherapy (first or second line) or as a combination therapy (first-line) with another ICI or chemotherapy. We combined the HRQoL measures into a meta-analysis using standard random effects models, from which estimates of the average mean difference (MD) were obtained with 95% confidence intervals. We assessed the heterogeneity of the study outcomes using the Q and I2 statistics. RESULTS We identified 11 phase 3 RCTs that met the inclusion criteria, with a mean enrollment of 820 patients. Eight RCTs used an ICI plus chemotherapy combination in the intervention arm, three had ICIs as monotherapy, and one had doublet ICI therapy in the intervention arm. All RCTs used chemotherapy for the control arm. Collectively, the trials reported 37 HRQoL measures using five different HRQoL tools. The pooled analysis favored the intervention over the control arm in terms of the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) scores [MD 2.7 (95% CI 0.1 to 5.3), p < 0.041]. In a subgroup analysis of eight RCTs comparing combination therapy with ICIs plus chemotherapy versus chemotherapy alone, the effect estimates favored the ICI arm regarding the FACT-E [MD 2.7 (95% CI 0.1 to 5.3), p < 0.041] and the EORTC QLQ-OES18 pain scale [MD -2.2 (95% CI -4.3 to -0.2), p < 0.030]. Likewise, the effect estimates favored the ICI monotherapy arm over the chemotherapy arm regarding the QLQ-STO22 hair loss subscale [MD -23.2 (95% CI -29.7 to -16.7), p < 0.001], QLQ-STO22 dysphagia subscale [MD 6.7 (95% CI 1.7 to 11.7), p = 0.009], EQ-5D pain scale [MD 6.9 (95% CI 2.9 to 10.9), p < 0.001], and QLQ-OES18 saliva subscale [MD 5.8 (95% CI 0.1 to 11.6), p = 0.046]. CONCLUSIONS In this meta-analysis, we found that the inclusion of ICIs as a first-line treatment for advanced GEC yielded better HRQoL outcomes than chemotherapy alone. Further research on the impact of ICIs on HRQoL is needed, with increasing evidence that ICIs improve the survival outcomes in patients with advanced GEC.
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Affiliation(s)
- Kush Gupta
- Department of Internal Medicine, University of Massachusetts Chan Medical School-Baystate, Springfield, MA 01109, USA;
| | - Arya Mariam Roy
- Department of Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA; (A.M.R.); (K.A.)
| | - Kristopher Attwood
- Department of Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA; (A.M.R.); (K.A.)
| | - Ryan David Nipp
- OU Health Stephenson Cancer Center, Oklahoma City, OK 73104, USA;
| | - Sarbajit Mukherjee
- Department of Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA; (A.M.R.); (K.A.)
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Yang J, Luo W, Ma X, Cui Y, Xie J, Pan C, Chen Z, Yang S. Meta-Analysis of the Efficacy and Safety of Pembrolizumab in the Treatment of Advanced Gastric Cancer and Gastroesophageal Junction Cancer. Chemotherapy 2024; 70:37-52. [PMID: 38972303 DOI: 10.1159/000540071] [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: 11/13/2023] [Accepted: 06/08/2024] [Indexed: 07/09/2024]
Abstract
INTRODUCTION Pembrolizumab has been approved for the first-line treatment of patients with advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer. However, the results of several clinical trials are not entirely consistent, and the dominant population of first-line immunotherapy for advanced GC/GEJ still needs to be precisely determined. PURPOSE The aim of this meta-analysis was to assess the efficacy and safety of pembrolizumab in the treatment of advanced GC/GEJ. METHODS We conducted computerized searches across multiple databases, including PubMed, Cochrane Library, Web of Science, and Embase. We established the inclusion criteria to comprise randomized clinical trials examining the efficacy of pembrolizumab in late-stage GC/GCJ cancer. We conducted a meta-analysis of outcome measures using STATA 14.0 software. RESULTS A total of six studies involving 1,448 cases were included in this analysis. The results of the meta-analysis indicate that, when compared to chemotherapy, patients in the pembrolizumab group experienced a significant reduction in the risk of mortality in terms of overall survival (OS) (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.65-0.79, p < 0.01). In terms of progression-free survival (PFS), pembrolizumab was associated with a similar PFS as compared to chemotherapy (HR = 0.88, 95% CI: 0.73-1.07, p = 0.206). Subgroup analyses based on PD-L1 expression levels indicated a significantly longer PFS with pembrolizumab in subgroups of patients with PD-L1 CPS ≥10 but not in those with PD-L1 CPS ≥1 and PD-L1 CPS ≥5. Subgroup analyses based on distinct geographical regions revealed a comparable effect of PFS in patients residing in Asia or the USA Subgroup analysis based on tumor sites consistently demonstrated a similar effect of PFS in patients with EC/GEJ tumors and GC patients. CONCLUSION Our findings demonstrated that pembrolizumab led to a significant extension in OS and objective response rate, along with a favorable tolerability profile compared to chemotherapy. Furthermore, the observed survival benefits were particularly pronounced in subgroup patients with a CPS of ≥10. Given the potential limitations inherent in our study, it is imperative to underscore the necessity for further large-scale RCTs to corroborate our results.
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Affiliation(s)
- Jingyun Yang
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China,
| | - Weisheng Luo
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Xiaocong Ma
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Yinhang Cui
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Jiacheng Xie
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Chengzhen Pan
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Ziyao Chen
- Department of Gastroenterology, Ruikang Hospital Affliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Shuang Yang
- Department of Gastroenterology, Ruikang Hospital Affliated to Guangxi University of Chinese Medicine, Nanning, China
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Sasahara Y, Takumoto Y, Watanabe K, Takeda H, Umemoto K, Sunakawa Y, Suzuki N, Yoshioka T, Kobayashi S, Ueno M, Nakamura S, Akazawa M, Narimatsu H. Quality-of-life survey of pancreatic cancer patients: a comparison between general public and physicians. FRONTIERS IN HEALTH SERVICES 2024; 4:1275496. [PMID: 39071080 PMCID: PMC11272646 DOI: 10.3389/frhs.2024.1275496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 06/28/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, conducting a QOL survey with patients is difficult. Therefore, we conducted a QOL survey with physicians. Specifically, this study aimed to clarify how physicians assess QOL in patients with pancreatic cancer by conducting a survey and comparing the results between physicians and the general public. METHODS A survey was conducted by interviewing physicians administering chemotherapy to patients for recurrent/metastatic pancreatic cancer. This method is similar to that of the QOL survey conducted among the general public. Responses were evaluated using the composite time trade-off (cTTO) and the visual analog scale (VAS) for 11 pancreatic cancer status scenarios (survey scenarios). These scenarios consisted of patients' health states as well as the types and grades of adverse events (AEs). Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). In addition, we conducted a survey using the EuroQol 5 Dimensions 5-Level (EQ-5D-5l) as reference values. RESULTS Twenty physicians responded to the survey. SD had the highest mean QOL value for both assessment methods (Physicians: 0.78, General public: 0.63), whereas PD had the lowest mean QOL value (Physicians: 0.15, General public: -0.12). The physicians assigned higher QOL values on both the VAS and cTTO than the general public did in all survey scenarios. CONCLUSIONS The QOL values obtained from physicians were consistent with the degree of status in any assessment scenarios. Based on the differences in the QOL survey results between physicians and the general public, physicians tended to assign higher QOL values than the general public in cTTO and VAS assessments.
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Affiliation(s)
- Yuriko Sasahara
- Department of Medical Oncology, Yamagata Prefectural Central Hospital, Yamagata, Japan
| | - Yuki Takumoto
- Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Tokyo, Japan
| | - Kaname Watanabe
- Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan
- Department of Genetic Medicine, Kanagawa Cancer Center, Yokohama, Japan
| | - Hiroyuki Takeda
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Kumiko Umemoto
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Yu Sunakawa
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Naoki Suzuki
- Department of Clinical Oncology, Yamagata University, Yamagata, Japan
| | - Takashi Yoshioka
- Department of Clinical Oncology, Yamagata University, Yamagata, Japan
| | - Satoshi Kobayashi
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Makoto Ueno
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Sho Nakamura
- Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan
- Graduate School of Health Innovation, Kanagawa University of Human Services, Kawasaki, Japan
| | - Manabu Akazawa
- Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Tokyo, Japan
| | - Hiroto Narimatsu
- Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan
- Department of Genetic Medicine, Kanagawa Cancer Center, Yokohama, Japan
- Graduate School of Health Innovation, Kanagawa University of Human Services, Kawasaki, Japan
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10
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Yan S, Wang W, Feng Z, Xue J, Liang W, Wu X, Tan Z, Zhang X, Zhang S, Li X, Zhang C. Immune checkpoint inhibitors in colorectal cancer: limitation and challenges. Front Immunol 2024; 15:1403533. [PMID: 38919624 PMCID: PMC11196401 DOI: 10.3389/fimmu.2024.1403533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 05/23/2024] [Indexed: 06/27/2024] Open
Abstract
Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded suboptimal results. ICIs can decrease tumor development by preventing the tumor's immune evasion, presenting cancer patients with a new treatment alternative. The increased use of immune checkpoint inhibitors (ICIs) in CRC has brought several issues. In particular, ICIs have demonstrated significant clinical effectiveness in patients with MSI-H CRC, whereas their efficacy is limited in MSS. Acquired resistance can still occur in patients with a positive response to ICIs. This paper describes the efficacy of ICIs currently in the clinical treatment of CRC, discusses the mechanisms by which acquired resistance occurs, primarily related to loss and impaired presentation of tumor antigens, reduced response of IFN-λ and cytokine or metabolic dysregulation, and summarizes the incidence of adverse effects. We posit that the future of ICIs hinges upon the advancement of precise prediction biomarkers and the implementation of combination therapies. This study aims to elucidate the constraints associated with ICIs in CRC and foster targeted problem-solving approaches, thereby enhancing the potential benefits for more patients.
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Affiliation(s)
- Suying Yan
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wanting Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhiqiang Feng
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jun Xue
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Weizheng Liang
- Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Xueliang Wu
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
- Institute of Cancer, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Zhiquan Tan
- Department of Scientific and Technical Information, Tianjin Union Medical Center, Tianjin, China
| | - Xipeng Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- Tianjin Institute of Coloproctology, Tianjin, China
| | - Shuai Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xichuan Li
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Chunze Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China
- The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- Tianjin Institute of Coloproctology, Tianjin, China
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11
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Lu Z, Kong L, Wang B, Wang J, Liu L, Shu Y, Yang L, Sun G, Cao G, Ji Y, Cui T, Liu H, Qiu W, Li N, Li G, Luo H, Hou X, Zhang Y, Yue W, Xue L, Liu Z, Pan Y, Gao S, Wang X, Pan Z, Zhang S, Lin G, Xie Y, Gu K, Ren T, Li W, Li T, Wang S, He W, Fan Y, Liang J, Xia B, Zhao L, Wang S, Shen L. Effects of sintilimab plus chemotherapy as first-line treatment on health-related quality of life in patients with advanced esophageal squamous cell carcinoma: results from the randomized phase 3 ORIENT-15 study. EClinicalMedicine 2024; 72:102623. [PMID: 38800802 PMCID: PMC11127225 DOI: 10.1016/j.eclinm.2024.102623] [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: 01/10/2024] [Revised: 03/24/2024] [Accepted: 04/16/2024] [Indexed: 05/29/2024] Open
Abstract
Background In ORIENT-15 study, sintilimab plus chemotherapy demonstrated significant improvement on overall survival (OS) versus placebo plus chemotherapy in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Here, we report effect of sintilimab plus chemotherapy on health-related quality of life (HRQoL) in patients with advanced ESCC. Methods From December 14, 2018 to August 28, 2022, HRQoL was evaluated in all randomized patients using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and visual analogue scale (VAS) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L). Mean scores of each scale were described by treatment group through week 60. Least-squares mean (LSM) score change from baseline through week 24 were analyzed using the mixed-model repeated-measures method. Time to the first onset of deterioration (TTD) and OS for each scale were estimated. Clinical Trials Registration: NCT03748134. Findings As of August 28, 2022, 689 of 690 enrolled patients were assessed for HRQoL analysis (sintilimab group: 340, placebo group: 349). Median follow-up was 32.2 months. Differences in LSM favored sintilimab over placebo for QLQ-C30 social functioning (LSM difference: 3.06, 95% CI: 0.55 to 5.57; P = 0.0170), pain (-2.24, 95% CI: -4.30 to -0.17; P = 0.0337), fatigue (-2.24, 95% CI: -4.46 to -0.02; P = 0.0479), constipation (-3.27, 95% CI -5.49 to -1.05; P = 0.0039), QLQ-OES18 pain (-1.77, 95% CI -3.11 to -0.43; P = 0.0097), trouble swallowing saliva (-2.09, 95% CI: -3.77 to -0.42; P = 0.0146), and choked when swallowing (-3.23, 95% CI: -5.60 to -0.86; P = 0.0076). TTD favored sintilimab over placebo for QLQ-OES18 dysphagia (Hazard ratio [HR]: 0.76, 95% CI: 0.61-0.94, P = 0.0104), and trouble swallowing saliva (HR: 0.48, 95% CI: 0.35-0.67, P < 0.0001). Improved OS were observed in patients with better performance in several functioning and symptom scales of QLQ-C30 and QLQ-QES18. Interpretation The statistically significant differences of several HRQoL scales and improvements in delayed deterioration observed in our study further support the use of sintilimab plus chemotherapy as first-line treatment for advanced ESCC. Funding This study was funded by Innovent Biologics and was co-funded by Eli Lilly.
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Affiliation(s)
- Zhihao Lu
- Beijing University Cancer Hospital and Institute, Beijing, China
| | - Li Kong
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Buhai Wang
- Northern Jiangsu People's Hospital, Affiliated Hospital to Yangzhou University, Yangzhou, China
| | - Junye Wang
- The Affiliated Hospital of Jining Medical College, Jining, China
| | - Lianke Liu
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yongqian Shu
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lei Yang
- Nantong Tumor Hospital, Nantong, China
| | - Guogui Sun
- Tangshan People's Hospital, Tangshan, China
| | - Guochun Cao
- Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, China
| | - Yinghua Ji
- The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | | | - Hu Liu
- Anhui Provincial Cancer Hospital, University of Science and Technology of China, Hefei, China
| | - Wensheng Qiu
- The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Na Li
- Suining Central Hospital, Suining, China
| | | | - Hui Luo
- Jiangxi Cancer Hospital, Nanchang, China
| | | | - Yanqiao Zhang
- Harbin Medical University Cancer Hospital, Harbin, China
| | - Wenbin Yue
- Puyang Oilfield General Hospital, Puyang, China
| | - Liying Xue
- Inner Mongolia People's Hospital, Hohhot, China
| | - Zheng Liu
- Handan Central Hospital, Handan, China
| | | | - Shegan Gao
- The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
| | - Xiuwen Wang
- Qilu Hospital of Shandong University, Jinan, China
| | | | - Shuqun Zhang
- The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Gen Lin
- Fujian Cancer Hospital, Fuzhou, China
| | - Yanru Xie
- Lishui Central Hospital, Lishui, China
| | - Kangsheng Gu
- The First Affiliated Hospital of Anhui First University, Hefei, China
| | - Tiejun Ren
- Luoyang City Center Hospital, Luoyang, China
| | - Weidong Li
- Cancer Hospital Affiliated to Guangzhou Medical University, Guangzhou, China
| | - Tao Li
- Sichuan Cancer Hospital, Chengdu, China
| | | | - Wei He
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yun Fan
- Zhejiang Cancer Hospital, Hangzhou, China
| | - Jun Liang
- Beijing University International Hospital, Beijing, China
| | - Bing Xia
- Hangzhou First People's Hospital, Hangzhou, China
| | - Li Zhao
- Innovent Biologics, Inc., Suzhou, China
| | | | - Lin Shen
- Beijing University Cancer Hospital and Institute, Beijing, China
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12
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Xia Y, Tang Y, Huang Z, Ke N, Zheng Y, Zhuang W, Zhang Y, Yin X, Tu M, Chen J, Wang Y, Huang Y. Artesunate-loaded solid lipid nanoparticles resist esophageal squamous cell carcinoma by inducing Ferroptosis through inhibiting the AKT/mTOR signaling. Cell Signal 2024; 117:111108. [PMID: 38369266 DOI: 10.1016/j.cellsig.2024.111108] [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: 11/29/2023] [Revised: 02/02/2024] [Accepted: 02/15/2024] [Indexed: 02/20/2024]
Abstract
Esophageal squamous cell carcinoma (ESCC) is a severe malignancy with high incidence and mortality rate in China, while the application of standard chemotherapeutic drugs for ESCC meets the barriers of high toxicity and multiple drug resistance (MDR). In recent years, the anticancer effects of artesunate (ART), a Chinese medicine monomer have gained extensive attentions due to its characteristics of low toxicity, high potency, and reversal of MDR. In this study, we develop the artesunate-loaded solid lipid nanoparticles (SLNART) to overcome the poor water solubility and bioavailability of ART, further improving the efficiency of ART on ESCC treatment. Especially mentioned, SLNART is shown to present marked inhibitory effects on ESCC development based on the induction of ferroptosis by two pathways included upregulating TFR to increase Fe2+ ions and inhibiting the AKT/mTOR signaling to downregulate GPX4. Collectively, this study is the first to pave a promising approach for ESCC therapy based on a strategy of developing SLNART to induce ferroptosis by mediating Fe2+ ions and AKT/mTOR signaling.
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Affiliation(s)
- Yu Xia
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350000, China; Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China
| | - Yixin Tang
- College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China; Engineering Research Center of Advanced Manufacturing Technology for Fine Chemicals, College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China
| | - Zhixin Huang
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350000, China; Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China
| | - Nantian Ke
- Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China; Department of Clinical Laboratory, Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350001, China
| | - Yue Zheng
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China; Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China
| | - Wanzhen Zhuang
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China; Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China
| | - Yi Zhang
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China; Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China
| | - Xiaoqing Yin
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350000, China; Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China
| | - Mingshu Tu
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China; Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China
| | - Jianlin Chen
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China; Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China
| | - Yingshu Wang
- College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China; Engineering Research Center of Advanced Manufacturing Technology for Fine Chemicals, College of Chemical Engineering, Fuzhou University, Fuzhou 350108, China
| | - Yi Huang
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350000, China; Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, China; Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China; Central Laboratory, Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou 350001, China; Fujian Provincial Key Laboratory of Critical Care Medicine, Fujian Provincial Key Laboratory of Cardiovascular Disease, Fuzhou 350001, China.
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13
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Csontos A, Fazekas A, Szakó L, Farkas N, Papp C, Ferenczi S, Bellyei S, Hegyi P, Papp A. Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma: A systematic review and meta-analysis. World J Gastroenterol 2024; 30:1621-1635. [PMID: 38617451 PMCID: PMC11008422 DOI: 10.3748/wjg.v30.i11.1621] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 01/18/2024] [Accepted: 03/04/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) is unclear. Therefore, a discussion of these two modalities is necessary. AIM To investigate the benefits and complications of neoadjuvant modalities. METHODS To address this concern, predefined criteria were established using the PICO protocol. Two independent authors performed comprehensive searches using predetermined keywords. Statistical analyses were performed to identify significant differences between groups. Potential publication bias was visualized using funnel plots. The quality of the data was evaluated using the Risk of Bias Tool 2 (RoB2) and the GRADE approach. RESULTS Ten articles, including 1928 patients, were included for the analysis. Significant difference was detected in pathological complete response (pCR) [P < 0.001; odds ratio (OR): 0.27; 95%CI: 0.16-0.46], 30-d mortality (P = 0.015; OR: 0.4; 95%CI: 0.22-0.71) favoring the nCRT, and renal failure (P = 0.039; OR: 1.04; 95%CI: 0.66-1.64) favoring the nCT. No significant differences were observed in terms of survival, local or distal recurrence, or other clinical or surgical complications. The result of RoB2 was moderate, and that of the GRADE approach was low or very low in almost all cases. CONCLUSION Although nCRT may have a higher pCR rate, it does not translate to greater long-term survival. Moreover, nCRT is associated with higher 30-d mortality, although the specific cause for postoperative complications could not be identified. In the case of nCT, toxic side effects are suspected, which can reduce the quality of life. Given the quality of available studies, further randomized trials are required.
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Affiliation(s)
- Armand Csontos
- Department of Surgery, University of Pécs, Medical School, Clinical Center, Pécs H-7624, Baranya, Hungary
| | - Alíz Fazekas
- Institute of Bioanalysis, University of Pécs, Medical School, Pécs H-7624, Baranya, Hungary
- Institute for Translational Medicine, University of Pécs, Medical School, Pécs H-7624, Baranya, Hungary
| | - Lajos Szakó
- Department of Emergency Medicine, Clinical Center, University of Pécs, Medical School, Pécs 7624, Baranya, Hungary
| | - Nelli Farkas
- Institute of Bioanalysis, University of Pécs, Medical School, Pécs H-7624, Baranya, Hungary
- Institute for Translational Medicine, University of Pécs, Medical School, Pécs H-7624, Baranya, Hungary
| | - Csenge Papp
- Department of Surgery, University of Pécs, Medical School, Clinical Center, Pécs H-7624, Baranya, Hungary
| | - Szilárd Ferenczi
- Department of Surgery, University of Pécs, Medical School, Clinical Center, Pécs H-7624, Baranya, Hungary
| | - Szabolcs Bellyei
- Department of Oncotherapy, University of Pécs, Medical School, Clinical Center, Pécs H-7624, Baranya, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine, University of Pécs, Medical School, Pécs H-7624, Baranya, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest 1085, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest H-1083, Hungary
| | - András Papp
- Department of Surgery, University of Pécs, Medical School, Clinical Center, Pécs H-7624, Baranya, Hungary
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14
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Kim SB, Van Cutsem E, Ajani J, Shen L, Barnes G, Ding N, Tao A, Xia T, Zhan L, Kato K. Tislelizumab in advanced/metastatic esophageal squamous cell carcinoma: health-related quality of life in Asian patients. Curr Med Res Opin 2024; 40:69-75. [PMID: 37846080 DOI: 10.1080/03007995.2023.2270894] [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: 06/12/2023] [Accepted: 10/11/2023] [Indexed: 10/18/2023]
Abstract
OBJECTIVE Post-hoc analysis examined health-related quality of life and esophageal squamous cell carcinoma (ESCC) symptoms in the Asian subgroup of patients in RATIONALE-302 (NCT03430843). METHODS Patients were randomized 1:1 to either tislelizumab or investigator-chosen chemotherapy (paclitaxel, docetaxel, or irinotecan). Health-related quality of life was measured using the EORTC QLQ-C30 and the QLQ-OES18. Least-squares mean score changes from baseline to weeks 12 and 18 in health-related quality-of-life scores were assessed using a mixed model for repeated measurements. Reported nominal p-values are for descriptive purposes only. RESULTS Of the 512 patients, this analysis was conducted in 392 Asian patients (tislelizumab, n = 192; investigator-chosen chemotherapy, n = 200). The tislelizumab arm had stable global health status/quality of life, but fatigue scores worsened in both arms. The change from baseline was similar for physical functioning in both arms at weeks 12 and 18. Eating and dysphagia scores remained stable in the tislelizumab arm. Reflux improved at week 12 in the tislelizumab arm and worsened in the investigator-chosen chemotherapy arm. CONCLUSIONS Overall, the health-related quality of life and ESCC-related symptoms of patients receiving tislelizumab in the Asian subgroup remained stable or improved, while patients receiving investigator-chosen chemotherapy experienced worsening. These results in Asian patients corroborate the findings in the intent-to-treat population, suggesting tislelizumab is a potential new second-line treatment option for patients with advanced or metastatic ESCC. TRIAL REGISTRATION The RATIONALE-302 study is registered on clinicaltrials.gov as NCT03430843.
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Affiliation(s)
- Sung-Bae Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Eric Van Cutsem
- University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
| | - Jaffer Ajani
- University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | | | | | | | | | - Lin Zhan
- BeiGene, Ltd, Emeryville, CA, USA
| | - Ken Kato
- National Cancer Center Hospital, Tokyo, Japan
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15
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Zhao T, Jia W, Zhao C, Wu Z. Survival benefit of surgery for second primary esophageal cancer following gastrointestinal cancer: a population-based study. J Gastrointest Surg 2024; 28:1-9. [PMID: 38353068 DOI: 10.1016/j.gassur.2023.11.016] [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: 10/09/2023] [Accepted: 11/14/2023] [Indexed: 02/16/2024]
Abstract
BACKGROUND The incidence of second primary malignancy is increasing. However, although there is some information on second primary esophageal cancer (SPEC) itself, there is no study or guideline on the use of surgery for SPEC after gastrointestinal cancer (SPEC-GC). Thus, this study aimed to gather evidence for the benefits of surgery by analyzing a national cohort and determining the prognostic factors and clinical treatment decisions for SPEC-GC. METHODS Data for patients with SPEC-GC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The prognostic factors of SPEC-GC were investigated by stepwise Cox proportional hazards regression and Kaplan-Meier analyses for overall survival and cancer-specific survival. RESULTS A total of 8308 patients with SPEC were selected, including 582 patients with SPEC-GC. Multivariate analysis revealed that surgery, year of diagnosis, scope of regional lymph node surgery, tumor differentiation grade, SEER historic stage, and triple therapy were significant predictors of survival outcomes (P < .05). Surgery seemed to improve the prognosis of patients with SPEC-GC significantly compared with no surgery and chemoradiotherapy (P < .001). CONCLUSIONS Surgery should be considered as the main treatment for SPEC-GC. Surgery, year of diagnosis, scope of regional lymph node surgery, tumor differentiation grade, SEER historic stage, and triple therapy were found to be independent prognostic factors for these patients. These factors should be considered in the clinical diagnosis and treatment of SPEC-GC.
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Affiliation(s)
- Tianhao Zhao
- Department of Cardiothoracic Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, China
| | - Wenxin Jia
- Department of Mental Health, The Second People's Hospital of Lishui, Lishui, Zhejiang, China
| | - Chun Zhao
- Department of Cardiothoracic Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, China
| | - Zhijun Wu
- Department of Cardiothoracic Surgery, Lishui Municipal Central Hospital, Lishui, Zhejiang, China.
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16
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Wang Y, Wang Y, Zhang J, Shi Z, Liu J. LncRNA NONHSAT227443.1 Confers Esophageal Squamous Cell Carcinoma Chemotherapy Resistance by Activating PI3K/AKT Signaling via Targeting MRTFB. Technol Cancer Res Treat 2024; 23:15330338241274369. [PMID: 39150441 PMCID: PMC11329966 DOI: 10.1177/15330338241274369] [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: 02/20/2024] [Revised: 06/04/2024] [Accepted: 07/08/2024] [Indexed: 08/17/2024] Open
Abstract
INTRODUCTION Esophageal cancer presents significant challenges due to limited treatment options and poor prognosis, particularly in advanced stages. Dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. This study investigated the roles of dysregulated lncRNA NONHSAT227443.1, identified through lncRNA-seq, and its downstream target gene MRTFB in esophageal squamous cell carcinoma (ESCC). METHODS Dysregulated lncRNAs were identified through lncRNA-seq in esophageal cancer tissues with varying chemotherapy response. The regulatory interaction of overexpressed NONHSAT227443.1 was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Functional assays, including cell viability, cell proliferation, and flow cytometry analyses, were performed to comprehensively investigate the influence of NONHSAT227443.1 and its downstream molecules on ESCC. RESULTS NONHSAT227443.1 was significantly overexpressed in paclitaxel plus platinum chemotherapy non-responders and esophageal cancer cell lines. Chemotherapy exposure led to diminished NONHSAT227443.1 expression. NONHSAT227443.1 negatively regulated MRTFB expression, and their combined dysregulation correlated with increased cancer activity, proliferation, and suppressed apoptosis. Diminished MRTFB expression was associated with PI3K/AKT pathway activation. CONCLUSION Our study provides insights into NONHSAT227443.1 and MRTFB roles in esophageal cancer, contributing to aggressive traits and treatment resistance. NONHSAT227443.1 and MRTFB may serve as potential therapeutic targets to enhance the response to paclitaxel plus platinum chemotherapy in non-responsive cases.
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Affiliation(s)
- Yuchen Wang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
- Graduate School, Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Yingying Wang
- Department of Functional Region of Diagnosis, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jinze Zhang
- Department of Thoracic Endoscopy Room, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhihua Shi
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Junfeng Liu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
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17
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Fang Q, Shen G, Xie Q, Guan Y, Liu X, Ren D, Zhao F, Liu Z, Ma F, Zhao J. Development of Tumor Markers for Breast Cancer Immunotherapy. Curr Mol Med 2024; 24:547-564. [PMID: 37157196 DOI: 10.2174/1566524023666230508152817] [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: 01/02/2023] [Revised: 03/08/2023] [Accepted: 03/16/2023] [Indexed: 05/10/2023]
Abstract
Although breast cancer treatment has been developed remarkably in recent years, it remains the primary cause of death among women. Immune checkpoint blockade therapy has significantly altered the way breast cancer is treated, although not all patients benefit from the changes. At present, the most effective mechanism of immune checkpoint blockade application in malignant tumors is not clear and efficacy may be influenced by many factors, including host, tumor, and tumor microenvironment dynamics. Therefore, there is a pressing need for tumor immunomarkers that can be used to screen patients and help determine which of them would benefit from breast cancer immunotherapy. At present, no single tumor marker can predict treatment efficacy with sufficient accuracy. Multiple markers may be combined to more accurately pinpoint patients who will respond favorably to immune checkpoint blockade medication. In this review, we have examined the breast cancer treatments, developments in research on the role of tumor markers in maximizing the clinical efficacy of immune checkpoint inhibitors, prospects for the identification of novel therapeutic targets, and the creation of individualized treatment plans. We also discuss how tumor markers can provide guidance for clinical practice.
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Affiliation(s)
- Qianqian Fang
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Guoshuang Shen
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Qiqi Xie
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Yumei Guan
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Xinlan Liu
- Department of Oncology, General Hospital of Ningxia Medical University, No. 804 Shengli Road, Xingqing District, Yinchuan, 750004, China
| | - Dengfeng Ren
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Fuxing Zhao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Zhilin Liu
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Fei Ma
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Jiuda Zhao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
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18
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Ou SL, Luo J, Wei H, Qin XL, Jiang Q. Value assessment of PD-1/PD-L1 inhibitors in the treatment of oesophageal and gastrointestinal cancers. Front Pharmacol 2023; 14:1106961. [PMID: 37153768 PMCID: PMC10160363 DOI: 10.3389/fphar.2023.1106961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 04/10/2023] [Indexed: 05/10/2023] Open
Abstract
Background: Evidence of efficacy and safety of programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) checkpoint inhibitors in oesophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC) was inconsistent, obscuring their clinical application and decision-making. The aim of this study was to comprehensively evaluate the value of PD-1/PD-L1 inhibitors in EC, GC and CRC to select valuable PD-1/PD-L1 inhibitors, and to assess the association between the value and cost of PD-1/PD-L1 inhibitors. Methods: A comprehensive search of trials of PD-1/PD-L1 inhibitors in EC, GC and CRC was performed in Chinese and English medical databases with a cut-off date of 1 July 2022. Two authors independently applied the ASCO-VF and ESMO-MCBS to assess the value of PD-1/PD-L1 inhibitors. A receiver operating characteristic (ROC) curve was generated to establish the predictive value of the ASCO-VF score to meet the threshold of the ESMO-MCBS grade. Spearman's correlation was used to calculate the relationship between the cost and value of drugs. Results: Twenty-three randomized controlled trials were identified: ten (43.48%) in EC, five (21.74%) in CRC, and eight (34.78%) in GC or gastroesophageal junction cancer (GEJC). For advanced diseases, ASCO-VF scores ranged from -12.5 to 69, with a mean score of 26.5 (95% CI 18.4-34.6). Six (42.9%) therapeutic regimens met the ESMO-MCBS benefit threshold grade. The area under the ROC curve was 1.0 (p = 0.002). ASCO-VF scores and incremental monthly cost were negatively correlated (Spearman's ρ = -0.465, p = 0.034). ESMO-MCBS grades and incremental monthly cost were negatively correlated (Spearman's ρ = -0.211, p = 0.489). Conclusion: PD-1/PD-L1 inhibitors did not meet valuable threshold in GC/GEJC. Pembrolizumab met valuable threshold in advanced microsatellite instability-high CRC. The value of camrelizumab and toripalimab may be more worth paying in EC.
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Affiliation(s)
- Shun-Long Ou
- Department of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Jing Luo
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Hua Wei
- Department of Pharmacy, Chengdu Second People’s Hospital, Chengdu, China
| | - Xiao-Li Qin
- Department of Pharmacy, The Third People’s Hospital of Chengdu, Chengdu, China
| | - Qian Jiang
- Department of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
- *Correspondence: Qian Jiang,
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19
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Wang H, Xu Y, Zuo F, Liu J, Yang J. Immune-based combination therapy for esophageal cancer. Front Immunol 2022; 13:1020290. [PMID: 36591219 PMCID: PMC9797857 DOI: 10.3389/fimmu.2022.1020290] [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: 08/16/2022] [Accepted: 11/30/2022] [Indexed: 12/23/2022] Open
Abstract
Esophageal cancer (EC) is an aggressive malignancy raising a healthcare concern worldwide. Standard treatment options include surgical resection, chemotherapy, radiation therapy, and targeted molecular therapy. The five-year survival rate for all stages of EC is approximately 20%, ranging from 5% to 47%, with a high recurrence rate and poor prognosis after treatment. Immunotherapy has shown better efficacy and tolerance than conventional therapies for several malignancies. Immunotherapy of EC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapy, has shown clinical advantages. In particular, monoclonal antibodies against PD-1 have a satisfactory role in combination therapy and are recommended for first- or second-line treatments. Here, we present a systematic summary and analysis of immunotherapy-based combination therapies for EC.
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Affiliation(s)
- Huiling Wang
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China
| | - Yufei Xu
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China
| | - Fengli Zuo
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China
| | - Junzhi Liu
- West China School of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Jiqiao Yang
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China,Breast Center, West China Hospital of Sichuan University, Chengdu, China,*Correspondence: Jiqiao Yang,
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20
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Lin N, Dai T, Zhou J, Huang H, Yun H, Ding Z, Ma X. Evaluation of the nutritional index and immunological function of a fermented vegetable for esophageal cancer patients undergoing immunotherapy plus chemotherapy: A randomized controlled trial. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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21
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Chen M, Li C, Sun M, Li Y, Sun X. Recent developments in PD-1/PD-L1 blockade research for gastroesophageal malignancies. Front Immunol 2022; 13:1043517. [PMID: 36505480 PMCID: PMC9731511 DOI: 10.3389/fimmu.2022.1043517] [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: 09/13/2022] [Accepted: 11/03/2022] [Indexed: 11/25/2022] Open
Abstract
Gastroesophageal cancers (GECs) comprise malignancies in the stomach, esophagus, and gastroesophageal junction. Despite ongoing improvements in chemoradiotherapy, the clinical outcomes of GEC have not significantly improved over the years, and treatment remains challenging. Immune checkpoint inhibitors (ICIs) have been the subject of clinical trials worldwide for several years. Encouraging results have been reported in different countries, but further research is required to apply ICIs in the clinical care of patients with GEC. This review summarizes completed and ongoing clinical trials with programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway blockers in GEC and current biomarkers used for predicting PD-1/PD-L1 blockade efficacy. This review captures the main findings of PD-1/PD-L1 antibodies combined with chemotherapy as an effective first-line treatment and a monotherapy in second-line or more treatment and in maintenance therapy. This review aims to provide insight that will help guide future research and clinical trials, thereby improving the outcomes of patients with GEC.
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Affiliation(s)
- Meng Chen
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Chenyan Li
- Department of Endocrinology and Metabolism, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Mingjun Sun
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yiling Li
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xuren Sun
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China,*Correspondence: Xuren Sun,
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22
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Kuo CL, Ponneri Babuharisankar A, Lin YC, Lien HW, Lo YK, Chou HY, Tangeda V, Cheng LC, Cheng AN, Lee AYL. Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend? J Biomed Sci 2022; 29:74. [PMID: 36154922 PMCID: PMC9511749 DOI: 10.1186/s12929-022-00859-2] [Citation(s) in RCA: 151] [Impact Index Per Article: 50.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 09/19/2022] [Indexed: 12/07/2022] Open
Abstract
The major concept of "oxidative stress" is an excess elevated level of reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption of oxygen. The precise harmonization of oxidative stresses between mitochondria and other organelles in the cell is absolutely vital to cell survival. Under oxidative stress, ROS produced from mitochondria and are the major mediator for tumorigenesis in different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, and immunoescape to allow cancer cells to adapt to the rigorous environment. Accordingly, the dynamic balance of oxidative stresses not only orchestrate complex cell signaling events in cancer cells but also affect other components in the tumor microenvironment (TME). Immune cells, such as M2 macrophages, dendritic cells, and T cells are the major components of the immunosuppressive TME from the ROS-induced inflammation. Based on this notion, numerous strategies to mitigate oxidative stresses in tumors have been tested for cancer prevention or therapies; however, these manipulations are devised from different sources and mechanisms without established effectiveness. Herein, we integrate current progress regarding the impact of mitochondrial ROS in the TME, not only in cancer cells but also in immune cells, and discuss the combination of emerging ROS-modulating strategies with immunotherapies to achieve antitumor effects.
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Affiliation(s)
- Cheng-Liang Kuo
- National Institute of Cancer Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan
| | - Ananth Ponneri Babuharisankar
- National Institute of Cancer Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan.,Joint PhD Program in Molecular Medicine, NHRI & NCU, Zhunan, Miaoli, 35053, Taiwan
| | - Ying-Chen Lin
- National Institute of Cancer Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan
| | - Hui-Wen Lien
- National Institute of Cancer Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan
| | - Yu Kang Lo
- National Institute of Cancer Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan
| | - Han-Yu Chou
- National Institute of Cancer Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan
| | - Vidhya Tangeda
- National Institute of Cancer Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan.,Joint PhD Program in Molecular Medicine, NHRI & NCU, Zhunan, Miaoli, 35053, Taiwan
| | - Li-Chun Cheng
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan
| | - An Ning Cheng
- Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan
| | - Alan Yueh-Luen Lee
- National Institute of Cancer Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan. .,Joint PhD Program in Molecular Medicine, NHRI & NCU, Zhunan, Miaoli, 35053, Taiwan. .,Department of Life Sciences, College of Health Sciences and Technology, National Central University, Zhongli, Taoyuan, 32001, Taiwan. .,Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 40402, Taiwan. .,Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
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23
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Van Cutsem E, Kato K, Ajani J, Shen L, Xia T, Ding N, Zhan L, Barnes G, Kim SB. Tislelizumab versus chemotherapy as second-line treatment of advanced or metastatic esophageal squamous cell carcinoma (RATIONALE 302): impact on health-related quality of life. ESMO Open 2022; 7:100517. [PMID: 35785595 PMCID: PMC9434166 DOI: 10.1016/j.esmoop.2022.100517] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/20/2022] [Accepted: 05/23/2022] [Indexed: 12/05/2022] Open
Abstract
Background RATIONALE 302 (NCT03430843) an open-label, phase III study of second-line treatment of advanced/metastatic esophageal squamous cell carcinoma (ESCC), reported that tislelizumab, relative to investigator-chosen chemotherapy (ICC), was associated with improvements in overall survival and a favorable safety profile. This study assessed the health-related quality of life (HRQoL) and ESCC-related symptoms of patients in RATIONALE 302. Methods Adults with advanced/metastatic ESCC whose disease progressed following prior systemic therapy were randomized 1 : 1 to receive either tislelizumab or ICC (paclitaxel, docetaxel, or irinotecan). HRQoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and the EuroQoL Five-Dimensions Five-Levels (EQ-5D-5L) visual analogue scale. Mixed effect modeling for repeated measurements examined changes from baseline to weeks 12 and 18. The Kaplan–Meier method was used to examine time to deterioration. Results Overall, 512 patients were randomized to tislelizumab (n = 256) or ICC (n = 256). The tislelizumab arm maintained QLQ-C30 global health status/quality whereas the ICC arm worsened at week 12 {difference in least square (LS) mean change: 5.8 [95% confidence interval (CI): 2.0-9.5], P = 0.0028} and week 18 [difference in LS mean change: 8.1 (95% CI: 3.4-12.8), P = 0.0008]. Physical functioning (week 18) and fatigue (weeks 12 and 18) worsened less in the tislelizumab compared with the ICC arm. The tislelizumab arm improved in reflux symptoms, whereas the ICC worsened at week 12 [difference in LS mean change: −4.1 (95% CI: −7.6 to −0.6), P = 0.0229]. The visual analogue scale remained consistent in the tislelizumab arm whereas it worsened in the ICC arm. The hazard of time to deterioration was lower in tislelizumab patients compared with ICC for physical functioning and reflux. Conclusions HRQoL, including fatigue symptoms and physical functioning, was maintained in patients with advanced or metastatic ESCC receiving tislelizumab compared with ICC-treated patients. These results provide additional support for the benefits of tislelizumab in this patient population.
Global health status and HRQoL remained consistent in the tislelizumab arm whereas the ICC arm experienced worsening. Fatigue and physical functioning worsened in both arms; however, the worsening was greater in the ICC arm. The tislelizumab arm was at lower risk of reaching the threshold for worsening in physical functioning and reflux.
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Affiliation(s)
- E Van Cutsem
- University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium.
| | - K Kato
- National Cancer Center Hospital, Tokyo, Japan
| | - J Ajani
- University of Texas MD Anderson Cancer Center, Houston, USA
| | - L Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - T Xia
- BeiGene, Ltd., Cambridge, USA
| | - N Ding
- BeiGene (Shanghai) Co., Ltd., Shanghai, China
| | - L Zhan
- BeiGene, Ltd., Emeryville, USA
| | | | - S-B Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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