|
1
|
Dong D, Yu X, Liu H, Xu J, Guo J, Guo W, Li X, Wang F, Zhang D, Liu K, Sun Y. Study of immunosenescence in the occurrence and immunotherapy of gastrointestinal malignancies. Semin Cancer Biol 2025; 111:16-35. [PMID: 39929408 DOI: 10.1016/j.semcancer.2025.01.007] [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: 12/15/2024] [Revised: 01/18/2025] [Accepted: 01/26/2025] [Indexed: 02/25/2025]
Abstract
In human beings heterogenous, pervasive and lethal malignancies of different parts of the gastrointestinal (GI) tract viz., tumours of the oesophagus, stomach, small intestine, colon, and rectum, represent gastrointestinal malignancies. Primary treatment modality for gastric cancer includes chemotherapy, surgical interventions, radiotherapy, monoclonal antibodies and inhibitors of angiogenesis. However, there is a need to improve upon the existing treatment modality due to associated adverse events and the development of resistance towards treatment. Additionally, age has been found to contribute to increasing the incidence of tumours due to immunosenescence-associated immunosuppression. Immunosenescence is the natural process of ageing, wherein immune cells as well as organs begin to deteriorate resulting in a dysfunctional or malfunctioning immune system. Accretion of senescent cells in immunosenescence results in the creation of a persistent inflammatory environment or inflammaging, marked with elevated expression of pro-inflammatory and immunosuppressive cytokines and chemokines. Perturbation in the T-cell pools and persistent stimulation by the antigens facilitate premature senility of the immune cells, and senile immune cells exacerbate inflammaging conditions and the inefficiency of the immune system to identify the tumour antigen. Collectively, these conditions contribute positively towards tumour generation, growth and eventually proliferation. Thus, activating the immune cells to distinguish the tumour cells from normal cells and invade them seems to be a logical strategy for the treatment of cancer. Consequently, various approaches to immunotherapy, viz., programmed death ligand-1 (PD-1) inhibitors, Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors etc are being extensively evaluated for their efficiency in gastric cancer. In fact, PD-1 inhibitors have been sanctioned as late late-line therapy modality for gastric cancer. The present review will focus on deciphering the link between the immune system and gastric cancer, and the alterations in the immune system that incur during the development of gastrointestinal malignancies. Also, the mechanism of evasion by tumour cells and immune checkpoints involved along with different approaches of immunotherapy being evaluated in different clinical trials will be discussed.
Collapse
Affiliation(s)
- Daosong Dong
- Department of Pain, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Xue Yu
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Molecular Pathology and Epidemiology of Gastric Cancer in the Universities of Liaoning Province, Shenyang, Liaoning 110001, China
| | - Haoran Liu
- Department of Breast Surgery, The First Hospital of China Medical University, Shenyang 110001, China
| | - Jingjing Xu
- Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Jiayan Guo
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang 110001, China
| | - Wei Guo
- Department of Pancreatic-Biliary Surgery, The First Hospital of China Medical University, Shenyang 110001, China
| | - Xiang Li
- Department of Pancreatic-Biliary Surgery, The First Hospital of China Medical University, Shenyang 110001, China
| | - Fei Wang
- Department of Otolaryngology, The First Hospital of China Medical University, Shenyang 110001, China.
| | - Dongyong Zhang
- Department of Neurosurgery, The First Hospital of China Medical University, Shenyang 110001, China.
| | - Kaiwei Liu
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Yanbin Sun
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang 110001, China.
| |
Collapse
|
|
2
|
Huang JB, Zhou ZY, Lu J, Zhu JY, Lai B, Mao SX, Cao JQ. Inflammatory burden index as a prognostic marker in patients with advanced gastric cancer treated with neoadjuvant chemotherapy and immunotherapy. Front Immunol 2025; 15:1471399. [PMID: 39906738 PMCID: PMC11790653 DOI: 10.3389/fimmu.2024.1471399] [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: 07/27/2024] [Accepted: 12/23/2024] [Indexed: 02/06/2025] Open
Abstract
Background Blood inflammation index has been shown to correlate with the prognosis of patients with gastric cancer. However, few studies have compared the efficacy of existing blood inflammatory markers in predicting the prognosis of patients with locally advanced gastric cancer in combination with neoadjuvant chemotherapy and immunotherapy. Objective The objective of this study was to compare the prognostic value of existing commonly used blood inflammatory index in patients with advanced gastric cancer treated with neoadjuvant chemotherapy combined with immunotherapy. Methods The clinicopathological data of patients with advanced gastric cancer from three centers in China were analyzed retrospectively. Univariate COX regression analysis was used to analyze the independent risk factors of poor tumor regression and overall survival (OS) in this part of patients, and the predictive value of different inflammatory indexes on prognosis was compared by C-index index. Finally, Inflammatory burden index(IBI) was grouped by X-tile software, and Kaplan-Meier method was used to compare the survival difference between groups. Results A total of 163 patients were enrolled in this study. The median age was 63 years(56-68). The median cycle of neoadjuvant therapy was 4(3-4). The median survival time was 85.1%(1 years), 65.6%(2 years), and 47.4%(3 years).Univariate analysis showed that IBI was an independent risk factor for non-TR(residual tumor cells>50%) (HR=1.08,95%CI:1.00-1.45,p<0.001)and OS(HR=1.04,95%CI:1.03-1.05,p<0.001). IBI is the best predictor of OS (C-index: 0.82, 95% CI: 0.78-0.87) among all inflammatory indexes. The IBI cutoff value was 52.1. It was found that the high IBI group had a higher incidence of postoperative complications(32.1%vs14.3%, p=0.001), the proportion of non-TR patients was significantly higher than that of the low IBI group(64.3%vs35.7%, p =0.001), and the high IBI group had a significantly lower OS((47.6% vs 87.6%, p < 0.001). Conclusion IBI is the best inflammatory index to predict the prognosis of advanced gastric cancer treated with neoadjuvant chemotherapy combined with immunotherapy, which will help guide patients' treatment decisions. This result still needs to be verified by large prospective studies.
Collapse
Affiliation(s)
- Jiao-Bao Huang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhi-Yong Zhou
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ji-Yun Zhu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Bin Lai
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Sheng-Xun Mao
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jia-Qing Cao
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| |
Collapse
|
|
3
|
Sun X, Lyu J, Yang M, Lin Y, Wu K, Liu K, Li A, Shuai X, Cai K, Wang Z, Wang G, Zhang P, Yin Y, Tao K. Two-Year Outcomes and Biomarker Analysis of Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma After Neoadjuvant Chemotherapy and Immunotherapy from the Phase II WuhanUHGI001 Trial. Ann Surg Oncol 2024; 31:8157-8169. [PMID: 39154154 DOI: 10.1245/s10434-024-16041-x] [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: 04/08/2024] [Accepted: 07/31/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND This study reports the 2-year outcomes and biomarker analysis results of patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma who received neoadjuvant chemotherapy and immunotherapy in a phase II WuhanUHGI001 trial. METHODS Eligible patients with cT3/4aN+M0 locally advanced G/GEJ adenocarcinoma were screened, enrolled, and treated with 3 cycles of neoadjuvant tislelizumab and SOX followed by D2 gastrectomy and another 5 cycles of postoperative adjuvant SOX. The primary endpoint was major pathological response. RESULTS Of the 49 included patients, 24 (49.0%) achieved major pathological response and 13 (26.5%) achieved pathological complete response. During a median follow-up of 26.8 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 69.4% and 81.2%, respectively. Grade 3-4 adverse events occurred in six patients (12.2%) during the neoadjuvant period, eight patients (17.0%) during the postoperative period, and seven patients (15.2%) during the adjuvant period. Biomarker analysis revealed that the pathological complete response showed no association with 2-year PFS and OS. Major pathological response showed a potentially strong association with improved 2-year PFS and OS rates. In addition, preoperative circulating tumor cells combined with pathological responses are helpful in prognosis assessment. In addition, our results showed that T downstaging, lymphocyte-to-monocyte ratio, and CD3+ T cells were independent factors that affect PFS. The signet ring cell component (SRCC), T downstaging, and neutrophil-to-lymphocyte ratio were independent factors affecting OS. Prognostic nomograms of PFS and OS constructed based on the multivariate Cox regression results demonstrated suitable calibration and discrimination ability. CONCLUSIONS Neoadjuvant tislelizumab plus SOX exhibits promising efficacy and acceptable toxicity in patients with locally advanced G/GEJ adenocarcinoma. In addition, our study established a prognostic risk signature and nomograms based on clinicopathological characteristics, which can accurately predict patient outcomes and aid in personalized treatment planning.
Collapse
Affiliation(s)
- Xiong Sun
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Jianbo Lyu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Ming Yang
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yao Lin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Ke Wu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Ke Liu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Anshu Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Xiaoming Shuai
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Kailin Cai
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Zheng Wang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Guobin Wang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Peng Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yuping Yin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
| | - Kaixiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
| |
Collapse
|
|
4
|
Zhang X, Liu B, Wang R, Li X, Zhou W. Current status of neoadjuvant immunotherapy for the treatment of gastric cancer. Clin Transl Oncol 2024; 26:2097-2108. [PMID: 38504071 DOI: 10.1007/s12094-024-03437-0] [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: 01/07/2024] [Accepted: 03/01/2024] [Indexed: 03/21/2024]
Abstract
Gastric cancer is one of the most prevalent malignant tumors worldwide, characterized by high incidence and mortality rates. At present, comprehensive surgical treatment has enhanced the prognosis of locally advanced gastric cancer patients significantly. However, the postoperative recurrence rate remains high, and the long-term survival for patients is sub-optimal. In recent years, immunotherapy has garnered extensive attention as an innovative approach to the treatment of gastric cancer. Indeed, multiple studies have validated its therapeutic effects in advanced gastric cancer patients, leading to its incorporation into treatment guidelines. Currently, researchers are exploring the application of immunotherapy in the neoadjuvant setting globally in order to further adjust and refine neoadjuvant immunotherapy regimens for gastric cancer. This article summarizes the research progress and controversies associated with neoadjuvant immunotherapy in gastric cancer, aiming to optimize clinical benefits for gastric cancer patients undergoing this treatment approach. The retrieval methods of this study encompassed databases such as PubMed, Google Scholar, Web of Science, clinicaltrials.gov, etc. The retrieved articles included guidelines, consensus, meta-analyses, clinical trials, and reviews related to locally advanced gastric cancer published up to January 2024.
Collapse
Affiliation(s)
- Xijie Zhang
- The Second Clinical Medical School, Lanzhou University, Lanzhou, China
| | - Bo Liu
- The Second Clinical Medical School, Lanzhou University, Lanzhou, China
| | - Rui Wang
- The Second Clinical Medical School, Lanzhou University, Lanzhou, China
| | - Xin Li
- Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, China
| | - Wence Zhou
- The Second Clinical Medical School, Lanzhou University, Lanzhou, China.
- Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, China.
| |
Collapse
|
|
5
|
Lin JL, Lin M, Lin GT, Zhong Q, Lu J, Zheng CH, Xie JW, Wang JB, Huang CM, Li P. Oncological outcomes of sequential laparoscopic gastrectomy after treatment with camrelizumab combined with nab-paclitaxel plus S-1 for gastric cancer with serosal invasion. Front Immunol 2024; 15:1322152. [PMID: 38333217 PMCID: PMC10850348 DOI: 10.3389/fimmu.2024.1322152] [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: 10/15/2023] [Accepted: 01/11/2024] [Indexed: 02/10/2024] Open
Abstract
OBJECTIVE To explore the oncological outcomes of sequential laparoscopic gastrectomy after treatment with camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion. METHODS This study is a retrospective cohort study and retrospectively analyzed the clinicopathological data of 128 patients with serosal invasion gastric cancer (cT4NxM0) who received nab-paclitaxel + S-1(SAP) or camrelizumab + nab-paclitaxel + S-1 (C-SAP) regimen and underwent laparoscopy assisted gastrectomy in Fujian Union Hospital from March 2019 to December 2020. The patients were divided into SAP group and C-SAP group. The 2-years overall survival rate, 2-year recurrence free survival rate recurrence rate and initial recurrence time were compared between the two groups. RESULTS A total of 128 patients were included, including 90 cases in SAP group and 38 cases in C-SAP group. There were no significant differences in age, gender, gastrectomy method, surgical approach, R0 resection, nerve invasion, vascular invasion, total number of harvested lymph nodes, number of positive lymph nodes and major pathologic response (MPR) rate between the two groups (P>0.05). However, the proportion of ypT0, ypN0 and pCR rate in C-SAP group were significantly higher than those in SAP group (P<0.05). The 2-year OS of C-SAP group (80.7%) was higher than that of SAP group (67.8%), and the difference was not statistically significant (P = 0.112); At 2 years after operation, the recurrence rate of C-SAP group (44.3%) was lower than that of SAP group (55.8%) (P = 0.097); Further analysis showed that the average time to recurrence in the C-SAP group was 18.9 months, which was longer than that in SAP group 13.1 months (P = 0.004); The 2-year recurrence free survival rate in C-SAP group was higher than that in SAP group (P=0.076); There was no significant difference in the overall survival time after recurrence between the two groups (P= 0.097). CONCLUSION Camrelizumab combined with neoadjuvant chemotherapy can improve the proportion of ypT0, ypN0 and pCR in patients, while prolonging the initial recurrence time of patients in the C-SAP group, but did not increase the immunotherapy/chemotherapy related side effects and postoperative complications.
Collapse
Affiliation(s)
- Ju-Li Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Guang-Tan Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Qing Zhong
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jia-bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China
| |
Collapse
|
|
6
|
Li S, Yu W, Xie F, Luo H, Liu Z, Lv W, Shi D, Yu D, Gao P, Chen C, Wei M, Zhou W, Wang J, Zhao Z, Dai X, Xu Q, Zhang X, Huang M, Huang K, Wang J, Li J, Sheng L, Liu L. Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer. Nat Commun 2023; 14:8. [PMID: 36596787 PMCID: PMC9810618 DOI: 10.1038/s41467-022-35431-x] [Citation(s) in RCA: 120] [Impact Index Per Article: 60.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 12/02/2022] [Indexed: 01/04/2023] Open
Abstract
Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers.
Collapse
Affiliation(s)
- Song Li
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Wenbin Yu
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Fei Xie
- Department of Pharmacy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Haitao Luo
- Shenzhen Yucebio Technology Co., Ltd., Shenzhen, 518000, Guangdong, China
| | - Zhimin Liu
- Department of General Surgery, Zibo Municipal Central Hospital, Binzhou Medical College, Zibo, 255036, Shandong, China
| | - Weiwei Lv
- Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Duanbo Shi
- Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Dexin Yu
- Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Peng Gao
- Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Cheng Chen
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Meng Wei
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Wenhao Zhou
- Shenzhen Yucebio Technology Co., Ltd., Shenzhen, 518000, Guangdong, China
| | - Jiaqian Wang
- Shenzhen Yucebio Technology Co., Ltd., Shenzhen, 518000, Guangdong, China
| | - Zhikun Zhao
- Shenzhen Yucebio Technology Co., Ltd., Shenzhen, 518000, Guangdong, China
| | - Xin Dai
- Department of Medical Oncology, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, 250012, China
| | - Qian Xu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Xue Zhang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Miao Huang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Kai Huang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Jian Wang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Jisheng Li
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Lei Sheng
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Lian Liu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
| |
Collapse
|
|
7
|
Haque E, Esmail A, Muhsen I, Salah H, Abdelrahim M. Recent Trends and Advancements in the Diagnosis and Management of Gastric Cancer. Cancers (Basel) 2022; 14:5615. [PMID: 36428707 PMCID: PMC9688354 DOI: 10.3390/cancers14225615] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/10/2022] [Accepted: 11/10/2022] [Indexed: 11/17/2022] Open
Abstract
Gastric cancer is an enigmatic malignancy that has recently been shown to be increasing in incidence globally. There has been recent progress in emerging technologies for the diagnosis and treatment of the disease. Improvements in non-invasive diagnostic techniques with serological tests and biomarkers have led to decreased use of invasive procedures such as endoscopy. A multidisciplinary approach is used to treat gastric cancer, with recent significant advancements in systemic therapies used in combination with cytotoxic chemotherapies. New therapeutic targets have been identified and clinical trials are taking place to assess their efficacy and safety. In this review, we provide an overview of the current and emerging treatment strategies and diagnostic techniques for gastric cancer.
Collapse
Affiliation(s)
- Emaan Haque
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
| | - Abdullah Esmail
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston, TX 77030, USA
| | - Ibrahim Muhsen
- Section of Hematology and Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Haneen Salah
- Department of Pathology, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Maen Abdelrahim
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston, TX 77030, USA
- Cockrell Center for Advanced Therapeutic Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA
| |
Collapse
|
|
8
|
Liu R, Wang X, Ji Z, Deng T, Li HL, Zhang YH, Yang YC, Ge SH, Zhang L, Bai M, Ning T, Ba Y. Toripalimab combined with targeted therapy and chemotherapy achieves pathologic complete response in gastric carcinoma: A case report. World J Clin Cases 2022; 10:6184-6191. [PMID: 35949814 PMCID: PMC9254214 DOI: 10.12998/wjcc.v10.i18.6184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 02/28/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma. Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/ adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy. Herein, we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab, Herceptin, and docetaxel, oxaliplatin, calcium folinate, and fluorouracil (FLOT) chemotherapy followed by surgery for human epidermal growth factor receptor 2 (HER2)- and programmed death-ligand 1 (PD-L1)-positive locally advanced gastric carcinoma. We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.
CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia. Immunohistochemistry of the baseline tissues suggested that the tissues were HER2- (fluorescent in situ hybridization) and PD-L1-positive (combined positive score = 1). The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin, toripalimab, and FLOT chemotherapy. The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation (proximal stomach), no clear residual tumor (tumor regression grade 0), no regional lymph node metastasis, and negative upper and lower cut ends. The levels of tumor markers were reduced to normal levels after re-examination. With good postoperative recovery, the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered. After the treatment, the patient was monitored every 3 mo with a follow-up of 12 mo (4 times). As of February 27, 2022, he was in a good condition without disease progression. The clinical trial registration number is E2019401.
CONCLUSION There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy; however, most of these studies are phase II studies with small cohorts. According to the results of some current studies, these combined regimens have shown promising results in terms of efficacy and safety. However, the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials, and further exploration of molecular markers for effective populations is required.
Collapse
Affiliation(s)
- Rui Liu
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Xia Wang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Zhi Ji
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Ting Deng
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Hong-Li Li
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Yan-Hui Zhang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Yu-Chong Yang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Shao-Hua Ge
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Le Zhang
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Ming Bai
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Tao Ning
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| | - Yi Ba
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, China
| |
Collapse
|
|
9
|
Lin JL, Lin JX, Lin JP, Zheng CH, Li P, Xie JW, Wang JB, Lu J, Chen QY, Huang CM. Safety and Efficacy of Camrelizumab in Combination With Nab-Paclitaxel Plus S-1 for the Treatment of Gastric Cancer With Serosal Invasion. Front Immunol 2022; 12:783243. [PMID: 35116023 PMCID: PMC8805791 DOI: 10.3389/fimmu.2021.783243] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 12/27/2021] [Indexed: 02/03/2023] Open
Abstract
OBJECTIVE To investigate the safety and efficacy of camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion. METHOD Two hundred patients with gastric cancer with serosal invasion who received neoadjuvant therapy from January 2012 to December 2020 were retrospectively analyzed. According to the different neoadjuvant therapy regimens, the patients were divided into the following three groups: the SOX group (S-1 + oxaliplatin) (72 patients), SAP group (S-1 + nab-paclitaxel) (95 patients) and C-SAP group (camrelizumab + S-1 + nab-paclitaxel) (33 patients). RESULT The pathological response (TRG 1a/1b) in the C-SAP group (39.4%) was not significantly different from that in the SAP group (26.3%) and was significantly higher than that in the SOX group (18.1%). The rate of ypT0 in the C-SAP group (24.2%) was higher than that in the SAP group (6.3%) and the SOX group (5.6%). The rate of ypN0 in the C-SAP group (66.7%) was also higher than that in the SAP group (38.9%) and the SOX group (36.1%). The rate of pCR in the C-SAP group (21.2%) was higher than that in the SAP group (5.3%) and the SOX group (2.8%). The use of an anti-PD-1 monoclonal antibody was an independent protective factor for TRG grade (1a/1b). The use of camrelizumab did not increase postoperative complications or the adverse effects of neoadjuvant therapy. CONCLUSION Camrelizumab combined with nab-paclitaxel plus S-1 could significantly improve the rate of tumor regression grade (TRG 1a/1b) and the rate of pCR in gastric cancer with serosal invasion.
Collapse
Affiliation(s)
- Ju-Li Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jun Peng Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jia-bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| |
Collapse
|
|
10
|
Kole C, Charalampakis N, Tsakatikas S, Kouris NI, Papaxoinis G, Karamouzis MV, Koumarianou A, Schizas D. Immunotherapy for gastric cancer: a 2021 update. Immunotherapy 2021; 14:41-64. [PMID: 34784774 DOI: 10.2217/imt-2021-0103] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Gastric cancer, the fifth most frequent cancer and the fourth leading cause of cancer deaths, accounts for a devastating death rate worldwide. Since the majority of patients with gastric cancer are diagnosed at advanced stages, they are not suitable for surgery and present with locally advanced or metastatic disease. Recent advances in immunotherapy have elicited a considerable amount of attention as viable therapeutic options for several cancer types. This work presents a summary of the currently ongoing clinical trials and critically addresses the efficacy of a large spectrum of immunotherapy approaches in the general population for gastric cancer as well as in relation to tumor genetic profiling.
Collapse
Affiliation(s)
- Christo Kole
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 115 27, Greece
| | | | - Sergios Tsakatikas
- Department of Medical Oncology, Metaxa Cancer Hospital, Athens, 185 37, Greece
| | - Nikolaos-Iasonas Kouris
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 115 27, Greece
| | - George Papaxoinis
- Second Department of Medical Oncology, Agios Savas Anticancer Hospital, Athens, 115 22, Greece
| | - Michalis V Karamouzis
- Molecular Oncology Unit, Department of Biological Chemistry, National & Kapodistrian University of Athens, Athens, 115 27, Greece
| | - Anna Koumarianou
- Hematology Oncology Unit, Fourth Department of Internal Medicine, National & Kapodistrian University of Athens, Attikon University Hospital, Athens, 124 62, Greece
| | - Dimitrios Schizas
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 115 27, Greece
| |
Collapse
|
|
11
|
Advances in clinical immunotherapy for gastric cancer. Biochim Biophys Acta Rev Cancer 2021; 1876:188615. [PMID: 34403771 DOI: 10.1016/j.bbcan.2021.188615] [Citation(s) in RCA: 216] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 07/14/2021] [Accepted: 08/12/2021] [Indexed: 12/26/2022]
Abstract
Gastric cancer (GC) is one of the most malignant human cancers with increasing incidence worldwide, ranking among the top five malignant tumors worldwide in terms of incidence and mortality. The clinical efficacy of conventional therapies is limited, and the median overall survival (mOS) for advanced-stage gastric cancer is only about 8 months. Emerging as one of breakthroughs for cancer therapy, immunotherapy has become an effective treatment modality after surgery, chemotherapy, radiotherapy, and targeted therapy. In this review, we have summarized the progresses of clinical development of immunotherapies for gastric cancer. Major advances with immune checkpoint inhibitors (ICIs) have started to change the clinical practice for gastric cancer treatment and prognosis. Additionally, combination therapies with other modalities, such as targeted therapies, are expected to push immunotherapies to front-line. In this review, the efficacy of ICIs and targeted therapy alone or combination with existing therapies gastric cancer treatment was described and the predictive value of biomarkers for immunotherapies in gastric cancer treatment is also discussed.
Collapse
|
|
12
|
Park R, Da Silva LL, Saeed A. Immunotherapy Predictive Molecular Markers in Advanced Gastroesophageal Cancer: MSI and Beyond. Cancers (Basel) 2021; 13:1715. [PMID: 33916348 PMCID: PMC8038572 DOI: 10.3390/cancers13071715] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 03/31/2021] [Accepted: 04/02/2021] [Indexed: 12/13/2022] Open
Abstract
Advanced gastroesophageal cancer (GEC) has a poor prognosis and limited treatment options. Immunotherapy including the anti-programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab have been approved for use in various treatment settings in GEC. Additionally, frontline chemoimmunotherapy regimens have recently demonstrated promising efficacy in large phase III trials and have the potential to be added to the therapeutic armamentarium in the near future. There are currently several immunotherapy biomarkers that are validated for use in the clinical setting for GEC including programmed death ligand-1 (PD-L1) expression as well as the tumor agnostic biomarkers such as mismatch repair or microsatellite instability (MMR/MSI) and tumor mutational burden (TMB). However, apart from MMR/MSI, these biomarkers are imperfect because none are highly sensitive nor specific. Therefore, there is an unmet need for immunotherapy biomarker development. To this end, several biomarkers are currently being evaluated in ongoing trials with some showing promising predictive potential. Here, we summarize the landscape of immunotherapy predictive biomarkers that are currently being evaluated in GEC.
Collapse
Affiliation(s)
- Robin Park
- Department of Medicine, MetroWest Medical Center/Tufts University School of Medicine, Framingham, MA 01702, USA; (R.P.); (L.L.D.S.)
| | - Laercio Lopes Da Silva
- Department of Medicine, MetroWest Medical Center/Tufts University School of Medicine, Framingham, MA 01702, USA; (R.P.); (L.L.D.S.)
| | - Anwaar Saeed
- Department of Medicine, Division of Medical Oncology, Kansas University Medical Center, Kansas City, KS 66205, USA
| |
Collapse
|