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Long B, Zhou H, Yu Z, Zhu J, Yang H, Huang Z, Wei D, Chen S, Yang X, Zhao X, Zhang W, Yan H, Guan X, Li L, Zhang G, Yu H, Che S, Gao Z, Jiang X, Luo C, Mao J, Zhao D, Li Y, Jiang Z, Jiao Z. Neoadjuvant cadonilimab plus FLOT chemotherapy in locally advanced gastric/gastroesophageal junction adenocarcinoma: A multicenter, phase 2 study. MED 2025; 6:100531. [PMID: 39536755 DOI: 10.1016/j.medj.2024.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 08/06/2024] [Accepted: 10/10/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Treatment with cadonilimab and chemotherapy has shown promise as a first-line treatment for gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, its application in neoadjuvant settings has not yet been documented. METHODS This multicenter, phase 2 trial (ChiCTR2200066893) was conducted at four hospitals across China. Treatment-naive patients with locally advanced G/GEJ adenocarcinoma (cT3/4, N+, M0) and who were human epidermal growth factor receptor 2 negative received 3-cycle or 4-cycle neoadjuvant treatment of cadonilimab plus FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy, followed by gastrectomy and 4-cycle adjuvant FLOT chemotherapy. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included major pathological response (MPR), overall response rate (ORR), disease control rate (DCR), R0 resection rate, downstaging rate, and safety. FINDINGS Between December 23, 2022, and December 15, 2023, 32 of 38 patients completed the scheduled treatment, achieving an R0 resection rate of 100% (32/32). The pCR rate was 21.1% (8/38, 90% confidence interval [CI]: 9.7-32.4), and the MPR rate was 44.7% (17/38, 90% CI: 30.9-58.5). Radiological evaluations were available for 28 of 38 patients by blinded independent central review. The ORR was 60.7% (17/28, 90% CI: 44.7-76.7), and the DCR was 100.0% (28/28, 90% CI: 100.0-100.0). Tumor downstaging occurred in 71.9% of patients (23/32), with consistent efficacy across all populations observed in the subgroup analysis. Grade 3 adverse events occurred in 31.6% of patients without severe safety issues. CONCLUSIONS Neoadjuvant cadonilimab plus FLOT chemotherapy treatment exhibits promising efficacy with manageable toxicities in locally advanced G/GEJ adenocarcinoma, providing preliminary evidence for further investigation. FUNDING This study was funded by Akeso Biopharma.
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Affiliation(s)
- Bo Long
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Huinian Zhou
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Zeyuan Yu
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Junmin Zhu
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Hanteng Yang
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Zeping Huang
- Lanzhou University Second Hospital, The Oncological Surgery Department, Lanzhou, China
| | - Dengwen Wei
- Sun Yat-sen University Cancer Center Gansu Provincial Cancer Hospital, The Gastrointestinal Surgery Department, Lanzhou, China
| | - Shigong Chen
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Xiaojun Yang
- Gansu Provincial Hospital, The General Surgery Department, Lanzhou, China
| | - Xiaoning Zhao
- Sun Yat-sen University Cancer Center Gansu Provincial Cancer Hospital, The Gastrointestinal Surgery Department, Lanzhou, China
| | - Wenjuan Zhang
- Lanzhou University Second Hospital, The Radiology Department, Lanzhou, China
| | - Hong Yan
- Lanzhou University Second Hospital, The Pathology Department, Lanzhou, China
| | - Xiaoying Guan
- Lanzhou University Second Hospital, The Pathology Department, Lanzhou, China
| | - Long Li
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Gengyuan Zhang
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Hongwei Yu
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Shengfu Che
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Zhongti Gao
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Xiangyan Jiang
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Changjiang Luo
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Jie Mao
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China
| | - Da Zhao
- The First Hospital of Lanzhou University, The Oncology Department, Lanzhou, China
| | - Yumin Li
- Lanzhou University Second Hospital, The Oncological Surgery Department, Lanzhou, China
| | - Zebin Jiang
- Gansu Provincial Hospital, The General Surgery Department, Lanzhou, China
| | - Zuoyi Jiao
- Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China; Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China.
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Majewska O, Pach R, Brzewski P, Kulig J, Kulig P. Impact of Clinicopathological Features on Gastric Cancer Stage According to TNM Classification. In Vivo 2025; 39:1112-1121. [PMID: 40010943 PMCID: PMC11884451 DOI: 10.21873/invivo.13916] [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: 12/08/2024] [Revised: 12/20/2024] [Accepted: 12/30/2024] [Indexed: 02/28/2025]
Abstract
BACKGROUND/AIM TNM stage is crucial for patients with gastric cancer because curative resection and treatment are only possible in early TNM stages. Therefore, our objective was to assess the association of clinicopathological features with TNM stage in such patients. PATIENTS AND METHODS The association of age, sex, tumor location and Lauren type with TNM stage was analyzed in 910 patients with gastric cancer. RESULTS Age, sex, and tumor location did not have any association with TNM stage in univariate nor multivariate analyses (p>0.05). However, compared to the diffuse and mixed types, the intestinal type (as defined by the Lauren classification) presented lower T stage of gastric cancer in the chi-squared test (p<0.001) and this association was confirmed in the multinominal log normal model (p=0.001). CONCLUSION The histological Lauren type of gastric cancer is associated with lower TNM T stage.
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Affiliation(s)
- Oliwia Majewska
- Andrzej Frycz Modrzewski Krakow University Faculty of Medicine and Health Sciences, Krakow, Poland
| | - Radosław Pach
- Jagiellonian University Medical College, Krakow, Poland
| | - Paweł Brzewski
- Andrzej Frycz Modrzewski Krakow University Faculty of Medicine and Health Sciences, Krakow, Poland
- Jagiellonian University Medical College, Krakow, Poland
| | - Jan Kulig
- Jagiellonian University Medical College, Krakow, Poland
| | - Piotr Kulig
- Andrzej Frycz Modrzewski Krakow University Faculty of Medicine and Health Sciences, Krakow, Poland;
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Semenova Y, Kerimkulov A, Uskenbayev T, Zharlyganova D, Shatkovskaya O, Sarina T, Manatova A, Yessenbayeva G, Adylkhanov T. Chemotherapy Options for Locally Advanced Gastric Cancer: A Review. Cancers (Basel) 2025; 17:809. [PMID: 40075656 PMCID: PMC11899121 DOI: 10.3390/cancers17050809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 02/20/2025] [Accepted: 02/24/2025] [Indexed: 03/14/2025] Open
Abstract
Cancers represent a significant global health burden, affecting millions of individuals each year [...].
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Affiliation(s)
- Yuliya Semenova
- Department of Surgery, School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan;
| | - Altay Kerimkulov
- Department of Multidisciplinary Surgery, National Research Oncology Center, Astana 020000, Kazakhstan; (A.K.); (T.U.); (T.S.); (T.A.)
| | - Talgat Uskenbayev
- Department of Multidisciplinary Surgery, National Research Oncology Center, Astana 020000, Kazakhstan; (A.K.); (T.U.); (T.S.); (T.A.)
| | - Dinara Zharlyganova
- Department of Scientific Management, National Research Oncology Center, Astana 020000, Kazakhstan; (D.Z.); (G.Y.)
| | - Oxana Shatkovskaya
- Board for Strategic Development, Scientific and Educational Activities, National Research Oncology Center, Astana 020000, Kazakhstan;
| | - Tomiris Sarina
- Department of Multidisciplinary Surgery, National Research Oncology Center, Astana 020000, Kazakhstan; (A.K.); (T.U.); (T.S.); (T.A.)
| | - Almira Manatova
- Department of Scientific Management, National Research Oncology Center, Astana 020000, Kazakhstan; (D.Z.); (G.Y.)
| | - Gulfairus Yessenbayeva
- Department of Scientific Management, National Research Oncology Center, Astana 020000, Kazakhstan; (D.Z.); (G.Y.)
| | - Tasbolat Adylkhanov
- Department of Multidisciplinary Surgery, National Research Oncology Center, Astana 020000, Kazakhstan; (A.K.); (T.U.); (T.S.); (T.A.)
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Dawood T, Rashid YA, Khan SR, Jabbar AA, Zahir MN, Moosajee MS. Outcomes of locally advanced gastric and gastroesophageal adenocarcinoma cancers treated with neoadjuvant FLOT in a tertiary care hospital in Pakistan. Ecancermedicalscience 2024; 18:1705. [PMID: 39021541 PMCID: PMC11254397 DOI: 10.3332/ecancer.2024.1705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Indexed: 07/20/2024] Open
Abstract
Background and aim Docetaxel, oxaliplatin, leucovorin and 5-fluorouracil (FLOT) may improve overall survival (OS) in patients with locally advanced gastric and gastroesophageal cancer. Our study aims to determine the pathological response in these patients with the FLOT chemotherapy in the Neoadjuvant setting. This is the first study conducted in our country. Methods We conducted a retrospective cross-sectional study from March 2018 to December 2020. After ethical review committee approval, all patients who fulfilled the inclusion criteria and received treatment at our tertiary care center were included in the study. SPSS version 22 was used for data analysis. Frequencies and percentages were calculated for categorical. Values were presented as mean ± standard deviation (SD) for continuous variables. The chi-square test was used to determine the difference between categorical variables. A p-value of ≤0.05 was considered the level of significance. Kaplan-Meier curves were used to calculate survival analysis. Results Out of 41, 35 patients with locally advanced resectable gastric or gastroesophageal adenocarcinoma were included in our study analysis. The entire cohort had a male predominance, with a mean age of 59. All patients received neoadjuvant FLOT. Pathological treatment response achieved was 77%, of which 66% had partial and 11% had complete response. There is a significant association of pathological response with age, gender, stage, grade, co-morbid and number of chemotherapy cycles received (p-value =<0.05). The OS was 80% with the mean OS was 2.6 years (31 months). Conclusion Our study shows comparable response rates to other studies conducted internationally. Our findings confirm that FLOT is an effective and well-tolerated perioperative regimen with reasonable response rates in the Pakistani population. A more extensive longitudinal study would ensure these preliminary results in the local patient population.
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Affiliation(s)
- Tasneem Dawood
- Department of Medical Oncology, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Yasmin Abdul Rashid
- Department of Medical Oncology, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Saqib Raza Khan
- Department of Medical Oncology, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Adnan Abdul Jabbar
- Department of Medical Oncology, Dr. Ziauddin Hospital, Karachi 74700, Pakistan
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Tian Y, Yang P, Guo H, Liu Y, Zhang Z, Ding P, Zheng T, Deng H, Ma W, Li Y, Fan L, Zhang Z, Wang D, Zhao X, Tan B, Liu Y, Zhao Q. Neoadjuvant docetaxel, oxaliplatin plus capecitabine versus oxaliplatin plus capecitabine for patients with locally advanced gastric adenocarcinoma: long-term results of a phase III randomized controlled trial. Int J Surg 2023; 109:4000-4008. [PMID: 37678277 PMCID: PMC10720837 DOI: 10.1097/js9.0000000000000692] [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: 05/16/2023] [Accepted: 08/04/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Neoadjuvant chemotherapy with docetaxel, oxaliplatin, and capecitabine (DOX regimen) is rarely used in Eastern countries and its efficacy and safety in advanced gastric cancer have not been reported. In this open-label, randomized, controlled trial, the authors aimed to assess the clinical efficacy of neoadjuvant chemotherapy using the DOX and oxaliplatin plus capecitabine (XELOX) regimens, in comparison to surgery alone. MATERIALS AND METHODS Three hundred patients younger than 60 years with potentially resectable advanced gastric cancer (cT3-4, Nany, M0) were enrolled in this randomized controlled clinical trial between November 2014 and June 2018. The primary endpoint of the study was the pathological complete response (pCR) rate. Secondary endpoints included 3-year overall survival (OS), 3-year disease-free survival. RESULTS In total, 280 patients (93 in the DOX group, 92 in the XELOX group, and 95 in the surgery group) were included in the per-protocol analysis. The DOX group demonstrated a significantly higher pCR rate compared to the XELOX group (16.1 vs. 4.3%, P =0.008). For patients with intestinal type, the DOX group exhibited significantly higher rates of both pCR and major pathological response compared to the XELOX group ( P =0.007, P <0.001). The 3-year OS rates of the DOX group, the XELOX group and the surgery group were 56.9, 44.6, and 34.7%, respectively. The 3-year disease-free survival rates were 45.2, 40.2, and 28.4%, respectively. The neoadjuvant DOX regimen demonstrated a significant improvement in the 3-year OS of patients compared to the neoadjuvant XELOX regimen ( P =0.037). CONCLUSION The neoadjuvant DOX regimen has shown the potential to increase the pCR rate and improve the prognosis of patients with advanced gastric cancer who are under 60 years old.
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Affiliation(s)
- Yuan Tian
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Peigang Yang
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Honghai Guo
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Yang Liu
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Ze Zhang
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Pingan Ding
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Tao Zheng
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Huiyan Deng
- Department of Pathology, The Fourth Hospital of Hebei Medical University
| | | | - Yong Li
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Liqiao Fan
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Zhidong Zhang
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Dong Wang
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Xuefeng Zhao
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Bibo Tan
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Yu Liu
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
| | - Qun Zhao
- The Third Department of Surgery
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, People’s Republic of China
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Forouhari A, Moghaddas A, Darakhshandeh A. Outcome evaluation of ECF, DCF, FOLFOX, and FLOT chemotherapy regimens as perioperative treatment in elderly patients with resectable gastric cancer; A retrospective comparative study. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2023; 28:79. [PMID: 38292337 PMCID: PMC10826847 DOI: 10.4103/jrms.jrms_417_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/18/2023] [Accepted: 08/07/2023] [Indexed: 02/01/2024]
Abstract
Background The incidence of gastric cancer is known to be high in the elderly population. Identification of the best perioperative chemotherapy regimen is challenging in patients with resectable gastric cancer. In this study, we aimed to evaluate and compare the outcomes and safety of epirubicin, cisplatin, and 5-fluorouracil (ECF), docetaxel, cisplatin, and 5-fluorouracil (DCF), oxaliplatin plus 5-Fluorouracil and leucovorin (FOLFOX), and docetaxel, oxaliplatin, leucovorin, and 5-Fluorouracil (FLOT) chemotherapy regimens to identify the most appropriate treatment option for elderly patients with resectable gastric cancer. Materials and Methods In this retrospective observational cohort study, data were extracted from the medical archives (2017-2021) of Omid Hospital, which is a tertiary oncology referral hospital in Isfahan, Iran. Patients with resectable gastric cancer, above 60 years of age, who were perioperatively treated with one of the mentioned chemotherapy regimens and met the inclusion criteria, were enrolled in this study. The survival parameters and safety profile of the regimens were evaluated and compared in this population. Results A total of 63 patients were included in this study. The median follow-up period of the patients was 24 months (range, 7-51 months). The results of survival analysis revealed that the FLOT and DCF regimens were significantly associated with longer overall survival (OS) as compared to the other regimens (median OS: 38 and 33 months, respectively). Based on the results, the progression-free survival was longer in the DCF regimen (median: 24 months) compared to the other regimens; however, only the difference with the ECF regimen (median: 14 months) was significant. The results of Cox regression analysis showed no significant difference in the overall adjusted hazard ratio of mortality between the FLOT and DCF regimens (P = 0.802). The DCF and FOLFOX regimens accounted for the highest and lowest rates of adverse events (e.g., neutropenia and mucositis), respectively. Conclusion Considering the higher rate of adverse events in the DCF group, besides the significant improvement of OS and the acceptable adverse event profile of patients treated with the FLOT regimen, it can be proposed that this chemotherapy regimen is the most appropriate treatment option for elderly patients with resectable gastric cancer.
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Affiliation(s)
- Ali Forouhari
- Isfahan Eye Research Center, Department of Ophthalmology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azadeh Moghaddas
- Department of Clinical Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali Darakhshandeh
- Department of Medical Oncology and Hematology, Isfahan University of Medical Sciences, Isfahan, Iran
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Ye H, Shi W, Yang J, Wang L, Jiang X, Zhao H, Qin L, Qin J, Li L, Cai W, Guan J, Yang H, Zhou H, Yu Z, Sun H, Jiao Z. PICH Activates Cyclin A1 Transcription to Drive S-Phase Progression and Chemoresistance in Gastric Cancer. Cancer Res 2023; 83:3767-3782. [PMID: 37646571 DOI: 10.1158/0008-5472.can-23-1331] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 07/17/2023] [Accepted: 08/24/2023] [Indexed: 09/01/2023]
Abstract
The chemotherapeutic agent 5-fluorouracil (5-FU) remains the backbone of postoperative adjuvant treatment for gastric cancer. However, fewer than half of patients with gastric cancer benefit from 5-FU-based chemotherapies owing to chemoresistance and limited clinical biomarkers. Here, we identified the SNF2 protein Polo-like kinase 1-interacting checkpoint helicase (PICH) as a predictor of 5-FU chemosensitivity and characterized a transcriptional function of PICH distinct from its role in chromosome separation. PICH formed a transcriptional complex with RNA polymerase II (Pol II) and ATF4 at the CCNA1 promoter in an ATPase-dependent manner. Binding of the PICH complex promoted cyclin A1 transcription and accelerated S-phase progression. Overexpressed PICH impaired 5-FU chemosensitivity in human organoids and patient-derived xenografts. Furthermore, elevated PICH expression was negatively correlated with survival in postoperative patients receiving 5-FU chemotherapy. Together, these findings reveal an ATPase-dependent transcriptional function of PICH that promotes cyclin A1 transcription to drive 5-FU chemoresistance, providing a potential predictive biomarker of 5-FU chemosensitivity for postoperative patients with gastric cancer and prompting further investigation into the transcriptional activity of PICH. SIGNIFICANCE PICH binds Pol II and ATF4 in an ATPase-dependent manner to form a transcriptional complex that promotes cyclin A1 expression, accelerates S-phase progression, and impairs 5-FU chemosensitivity in gastric cancer.
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Affiliation(s)
- Huili Ye
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, P.R. China
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
- The Second Clinical Medical College, Lanzhou University, Lanzhou, P.R. China
| | - Wengui Shi
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, P.R. China
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
| | - Jing Yang
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, P.R. China
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
| | - Long Wang
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
- The Second Clinical Medical College, Lanzhou University, Lanzhou, P.R. China
| | - Xiangyan Jiang
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
- The Second Clinical Medical College, Lanzhou University, Lanzhou, P.R. China
| | - Huiming Zhao
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
- The Second Clinical Medical College, Lanzhou University, Lanzhou, P.R. China
| | - Long Qin
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, P.R. China
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
| | - Junjie Qin
- The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, P.R. China
| | - Lianshun Li
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
- The Second Clinical Medical College, Lanzhou University, Lanzhou, P.R. China
| | - Weiwen Cai
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
- The Second Clinical Medical College, Lanzhou University, Lanzhou, P.R. China
| | - Junhong Guan
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, P.R. China
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
| | - Hanteng Yang
- The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, P.R. China
| | - Huinian Zhou
- The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, P.R. China
| | - Zeyuan Yu
- The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, P.R. China
| | - Hui Sun
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, P.R. China
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
| | - Zuoyi Jiao
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, P.R. China
- Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P.R. China
- The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, P.R. China
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Zhang M, Yang H, Fu T, Meng M, Feng Y, Qu C, Li Z, Xing X, Li W, Ye M, Li S, Bu Z, Jia S. Liquid biopsy: circulating tumor DNA monitors neoadjuvant chemotherapy response and prognosis in stage II/III gastric cancer. Mol Oncol 2023; 17:1930-1942. [PMID: 37356061 PMCID: PMC10483607 DOI: 10.1002/1878-0261.13481] [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: 10/06/2022] [Revised: 03/09/2023] [Accepted: 06/23/2023] [Indexed: 06/27/2023] Open
Abstract
A good response to neoadjuvant chemotherapy (NACT) is strongly associated with a higher curative resection rate and favorable outcomes for patients with gastric cancer (GC). We examined the utility of serial circulating tumor DNA (ctDNA) testing for monitoring NACT response and prognosis in stage II-III GC. Seventy-nine patients were enrolled to receive two cycles of NACT following gastrectomy with D2-lymphadenectomy. Plasma at baseline, post-NACT, and after surgery, and tissue at pretreatment and surgery were collected. We used a 425-gene panel to detect genomic alterations (GAs). Results show that the mean cell-free DNA concentration of patients with clinical stage III was significantly higher than patients with stage II (15.43 ng·mL-1 vs 14.40 ng·mL-1 ). After receiving NACT and surgery, the overall detection rate of ctDNA gradually reduced (59.5%, 50.8%, and 47.4% for baseline, post-NACT, and postsurgery). The maximum variant allele frequency (max-VAF) and the number of GAs decreased from 0.50% to 0.08% and from 2.9 to 1.7 after NACT. For patients with a partial response after NACT, the max-VAF and the number of GAs declined significantly, but they increased for patients with progressive disease. Patients with detectable ctDNA at baseline, after NACT, or after surgery have a worse overall survival (OS) than patients with undetectable ctDNA. The estimated 3-year OS was 73% for the post-NACT ctDNA-negative patients and 34% for ctDNA-positive. Patients with perpetual negative ctDNA before and after NACT have the best prognosis. In conclusion, ctDNA was proposed as a potential biomarker to predict prognosis and monitor the NACT response for stage II-III GC patients.
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Affiliation(s)
- Meng Zhang
- Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Heli Yang
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Tao Fu
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Meizhu Meng
- Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Yi Feng
- Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Changda Qu
- Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Zhongwu Li
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Xiaofang Xing
- Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Wenmei Li
- Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Meiying Ye
- Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Sisi Li
- Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Zhaode Bu
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
| | - Shuqin Jia
- Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing)Peking University Cancer Hospital & InstituteBeijingChina
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Fiflis S, Papakonstantinou M, Giakoustidis A, Christodoulidis G, Louri E, Papadopoulos VN, Giakoustidis D. Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer: A systematic review. World J Gastrointest Surg 2023; 15:1808-1818. [PMID: 37701690 PMCID: PMC10494580 DOI: 10.4240/wjgs.v15.i8.1808] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 06/07/2023] [Accepted: 06/27/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is a major health concern worldwide. Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma, however, the optimal approach remains unclear and should be different in each individual. Chemotherapy can be administered both pre- and postoperatively, but a multidisciplinary approach is preferred when possible. This is particularly relevant for locally advanced GC (LAGC), as neoadjuvant chemotherapy (NAT) could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent. Even though the recent progress has been impressive, European and International guidelines are still controversial, thus attenuating the need for a more standardized approach in the management of locally advanced cancer. AIM To investigate the effects of NAT on the overall survival (OS), the disease-free survival (DFS), the morbidity and the mortality of patients with LAGC in comparison to upfront surgery (US). METHODS For this systematic review, a literature search was conducted between November and February 2023 in PubMed, Cochrane Library and clinicaltrials.gov for studies including patients with LAGC. Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews. RESULTS Eighteen studies with 4839 patients with LAGC in total were included in our systematic review. Patients were separated into two groups; one receiving NAT before the gastrectomy (NAT group) and the other undergoing upfront surgery (US group). The OS ranged from 41.6% to 74.2% in the NAT group and from 30.9% to 74% in the US group. The DFS was also longer in the NAT group and reached up to 80% in certain patients. The complications related to the chemotherapy or the surgery ranged from 6.4% to 38.1% in the NAT group and from 5% to 40.5% in the US group. Even though in most of the studies the morbidity was lower in the NAT group, a general conclusion could not be drawn as it seems to depend on multiple factors. Finally, regarding the mortality, the reported rate was higher and up to 5.3% in the US group. CONCLUSION NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates. However, patients with different clinicopathological features respond differently to chemotherapy, therefore currently the treatment plan should be individualized in order to achieve optimal results.
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Affiliation(s)
- Stylianos Fiflis
- A’ Department of Surgery, General Hospital Papageorgiou, Thessaloniki 56429, Greece
| | | | | | | | - Eleni Louri
- A’ Department of Surgery, General Hospital Papageorgiou, Thessaloniki 56429, Greece
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Arefpour AM, Hosseini S, Basi A, Novin K, Foroughi A, Garousi M. Evaluation of Pathological Response Rate and Complications of FOLFOX versus FLOT Regimen in Perioperative Chemotherapy for Resectable Gastric Cancer: A Prospective Study. Asian Pac J Cancer Prev 2023; 24:2791-2797. [PMID: 37642066 PMCID: PMC10685210 DOI: 10.31557/apjcp.2023.24.8.2791] [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: 04/07/2023] [Accepted: 08/14/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Previous studies have shown that the perioperative and postoperative chemotherapy can lead to an improvement in the prognosis of patients with resectable gastric cancer (GC). There is no preference for postoperative chemotherapy with the two common treatment regimens, FLOT and FOLFOX, in these patients. The aim of this study was to compare FOLFOX and FLOT regimens in perioperative chemotherapy in resectable GC based on pathological response and complications. METHODS This prospective cohort study was conducted on 112 patients with resectable GC who were admitted to Firozgar Hospital affiliated with Iran University of Medical Sciences, Tehran, Iran between 2021 to 2022. Given the inclusion criteria, 80 patients were enrolled in the present study. Patients were divided into 2 groups based on the type of treatment regimen, FOLFOX (40 patients) and FLOT (40 patients). Tumor response was classified using Mandard Tumor regression grading system criteria into five categories of TRG1 to 5. Also, the side effects were classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. RESULTS The rate of complete pathological response in FOLT group was significantly higher than FOLFOX group (35.0% vs 2.5%, p: 0.001). The frequency of neurological complications and hair loss in the FOLT group was significantly higher than the FOLFOX group (P<0.05). While no significant difference was observed in the frequency of hematological, Gastroenterological, hepatic, renal and stomatitis complications in the both groups (p>0.05). CONCLUSION Our study showed that perioperative FLOT regimen has a better pathological response than FOLFOX regimen. The frequency of neurological complications and hair loss was significantly higher in patients treated with FLOT regimen. Thus, perioperative FLOT regimen may be recommended for treating GC patients.
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Affiliation(s)
- Amir Mohammad Arefpour
- Department of Radiotherapy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Saeed Hosseini
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Ali Basi
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Kambiz Novin
- Department of Radiotherapy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Ahmad Foroughi
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Maryam Garousi
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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11
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Kianersi S, Salari S, Rezvani H, Araskhan MA, Shirangi A, Fathi MR, Ghorbi MD. Neoadjuvant chemotherapy outcome with taxane-based versus non-taxane protocols in gastric cancer. JOURNAL OF EDUCATION AND HEALTH PROMOTION 2023; 12:205. [PMID: 37545995 PMCID: PMC10402764 DOI: 10.4103/jehp.jehp_786_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 08/24/2022] [Indexed: 08/08/2023]
Abstract
BACKGROUND Gastric cancer is the fifth most common cancer worldwide. One of the chemotherapy agents, taxanes is important in increasing patients' survival. The purpose of this study is to assess the efficacy of taxane-based drugs versus non-taxanes in neoadjuvant chemotherapy in non-metastatic gastric adenocarcinoma (GA) in Iranian patients. MATERIALS AND METHODS In a historical cohort method, 65 patients between 18 and 75 years old who suffered from non-metastatic GA were included. Nineteen and 21 and 25 patients, had undergone DCF (docetaxel, cisplatin, 5fluorouracil) and FLOT (5fluorouracil, leucovorin, oxaliplatin, docetaxel) and FOLFOX6 (oxaliplatin, leucovorin, 5fluorouracil) regimens, respectively, between 2018 and 2021. Survival criteria consisting of progression-free survival (PFS), overall survival (OS), progression rate, and mortality rate were evaluated using the Kaplan-Meier method, in a three-year follow-up period. RESULTS The majority of patients were male (72.3%), with a median age of 65 years. Most of the patients had lesions with tumor, node, metastasis (TNM) stage IIIb (27.7%) and poor differentiated pathological grade (49.2%). OS time had a significant correlation with the low TNM stage (P = 0.01), well-differentiated pathological grade (P = 0.005), and FLOT vs. FOLFOX protocol (20.3 vs. 12.2 months, respectively. P =0.04). FLOT regimen had significantly better OS survival vs. DCF regimen (20.3 vs. 15.4 months, respectively, P = 0.03). No significant correlation was observed between survival criteria and other factors like gender, age, past medical history, Karnofsky scale, and tumor location in the stomach. The taxane-based arm (sum of DSF and FLOT) had no superiority over the non-taxane arm in survival criteria. CONCLUSION FLOT protocol, as a taxane-based regimen had better survival compared to FOLFOX protocol in neoadjuvant chemotherapy in gastric non-metastatic adenocarcinoma.
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Affiliation(s)
- Shirin Kianersi
- Department of Medical Oncology and Hematology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sina Salari
- Department of Medical Oncology and Hematology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Rezvani
- Department of Medical Oncology and Hematology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad A. Araskhan
- Department of Medical Oncology and Hematology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Shirangi
- Firoozgar Clinical Research Development Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad R. Fathi
- Department of Neurosurgery, Rajaii Hospital,Qazvin University of Medical Sciences, Qazvin, Iran
| | - Mahmoud D. Ghorbi
- Department of Medical Oncology and Hematology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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12
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Oganyan KA, Musaelyan AA, Lapin SV, Kupenskaya TV, Sveсhkova AA, Belyaev MA, Zakharenko AA, Orlov SV. Molecular markers as predictors of response to perioperative chemotherapy in locally advanced gastric cancer. ADVANCES IN MOLECULAR ONCOLOGY 2023. [DOI: 10.17650/2313-805x-2023-10-1-40-48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Introduction. Perioperative FLOT chemotherapy has improved prognosis in patients with locally advanced resectable gastric cancer (GC). However, in 80 % of cases, the tumor is resistant to the therapy, resulting in unnecessary toxicity and delayed surgical treatment.Aim. Evaluation of clinico-morphological patterns of microsatellite instability, HER2 gene amplification, changes in gene copy number and their relationship with the response to perioperative FLOT chemotherapy in patients with locally advanced resectable GC.Materials and methods. The retrospective study included 185 patients. All tumor samples were assessed for HER2 and microsatellite instability status. Among all cases there were 45 patients with locally advanced T2–4N1–2 M0 GC, who underwent a total or subtotal gastrectomy with D2 lymphadenectomy and perioperative chemotherapy with FLOT. Microsatellite instability detection was performed using fragment analysis, HER2 gene amplification testing – fluorescent in situ hybridization. Also 19 patients were tested for copy number changes of the FGFR1, FGFR2, KRAS, MET, EGFR, CCND1, MYC genes using Multiplex ligation-dependent probe amplification. The endpoints were progression-free survival and objective response rate.Results. Microsatellite instability was detected in 4.8 % (9/185) of GC cases. Microsatellite instability was associated with advanced age (p = 0.005), low grade of differentiation (p = 0.011), presence of tumor-infiltrating lymphocytes (p = 0.0004), and high preoperative CA 72–4 levels (p = 0.025). Prevalence of HER2 amplification was 7.5 % (14/185). It was associated with low grade of differentiation (p = 0.048) and metastasis in regional lymph nodes (p = 0.037). PFS in patients with HER2-positive (HER2 – human epidermal growth factor receptor 2) GC treated with perioperative FLOT chemotherapy (4/45) was significantly lower than in patients with HER2-negative GC: the median was 156 and 317 days, respectively (hazard ratio 0.49; 95 % confidence interval 0.16–1.47; p = 0.0006). There was no correlation between the presence of the alteration and ORR (p = 1.0). Progression-free survival in GC patients with KRAS amplification (3/19) was significantly lower comparing with patients without it: the median was 98 and 327 days, respectively (hazard ratio 0.29; 95 % confidence interval 0.07–1.19; p <0.0001). There was no association between an increase in KRAS copy number and objective response rate (p = 1.0). For microsatellite instability and other studied markers no statistically significant correlation with progression-free survival and objective response rate was found (p >0.05).Conclusion. The presence of HER2 and KRAS amplification have been shown as promising predictive markers of the treatment failure in patients treated with perioperative FLOT chemotherapy for locally advanced resectable GC.
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Affiliation(s)
- K. A. Oganyan
- Pavlov First Saint Petersburg State Medical University
| | - A. A. Musaelyan
- Pavlov First Saint Petersburg State Medical University; Research Institute of Medical Primatology
| | - S. V. Lapin
- Pavlov First Saint Petersburg State Medical University
| | | | | | - M. A. Belyaev
- Pavlov First Saint Petersburg State Medical University
| | | | - S. V. Orlov
- Pavlov First Saint Petersburg State Medical University; Research Institute of Medical Primatology
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Gastric adenocarcinoma: A review of the TNM classification system and ways of spreading. RADIOLOGIA 2023; 65:66-80. [PMID: 36842787 DOI: 10.1016/j.rxeng.2022.10.011] [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: 09/01/2022] [Accepted: 10/12/2022] [Indexed: 02/28/2023]
Abstract
Gastric cancer is the fifth most common cancer in the world. The most common histologic subtype is adenocarcinoma. Gastric adenocarcinomas are staged using the American Joint Committee on Cancer's 8th TNM classification. The perigastric ligaments, mesentery, omentum, and potential spaces between the parietal and visceral peritoneal linings play are important structures for staging. The spread of disease is influenced by the location of the tumor within the stomach, as well as by the anatomy related to the ligaments and lymph vessels. CT is the imaging modality of choice for the preoperative clinical staging of gastric cancer, and it is essential for planning treatment. To be able to do an adequate imaging workup, radiologists need to know the different pathways through which gastric cancer can spread: lymphatic, subperitoneal, direct invasion, transperitoneal, hematogenous, and extramural venous invasion.
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Textbook outcome in gastric surgery, what implications does it have on survival? Cir Esp 2023; 101:20-28. [PMID: 35787475 DOI: 10.1016/j.cireng.2022.06.047] [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: 06/23/2021] [Accepted: 09/25/2021] [Indexed: 01/17/2023]
Abstract
INTRODUCTION The textbook outcome (TO) is a multidimensional measure to assess the quality of healthcare practice. This is reflected as the "ideal" surgical result, attending to a series of indicators or established reference points that are adapted depending on the surgical disease that we want to analyze. There are few references and series published about TO, all of them very recent. OBJECTIVE We present a series of gastric surgery from the TO perspective and we analyze its impact on survival. METHOD Retrospective observational study of all gastric neoplasms operated on in our center. PERIOD January 2015-December 2020. The criteria for TO were: margins R0, >15 lymph nodes in the histological study, no Clavien-Dindo complications > IIIa, hospital stay < 21 days, no mortality or readmission in the 30 postoperative days. A comparative analysis was performed between the TO group versus the non-TO group. RESULTS 91 patients were operated on. We reached the TO in 34.1% of the patients. The variable >15 lymph nodes was the one that most affected to achieve a TO. When performing the survival analysis, we obtained that the group in which the TO was obtained had a greater survival (p < 0.008). CONCLUSION In our series, obtaining the TO has an impact on survival which 34,1% of degree of compliance.
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15
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Adenocarcinoma gástrico: revisión del TNM y de las vías de diseminación. RADIOLOGIA 2022. [DOI: 10.1016/j.rx.2022.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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16
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Farrokhi P, Sadeghi A, Sharifi M, Riechelmann R, Moghaddas A. Efficacy and safety of FLOT regimen vs DCF, FOLFOX, and ECF regimens as perioperative chemotherapy treatments for resectable gastric cancer patients; a report from the middle east. Res Pharm Sci 2022; 17:621-634. [PMID: 36704436 PMCID: PMC9872182 DOI: 10.4103/1735-5362.359430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 08/13/2022] [Accepted: 08/23/2022] [Indexed: 01/28/2023] Open
Abstract
Background and purpose This study aimed to compare the efficacy and toxicity of perioperative chemotherapy regimens including epirubicin, cisplatin, 5-fluorouracil (ECF), docetaxel, cisplatin, 5-fluorouracil (DCF), leucovorin, 5-fluorouracil, oxaliplatin (FOLFOX), and 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) to identify the most effective chemotherapy regimen with less toxicity. Experimental approach This retrospective cohort study (2014-2021) was based on 152 eligible resectable gastric cancer patients who had received one of the perioperative mentioned chemotherapy regimens and followed for at least two years. The primary endpoint of this study was overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and R0 resection. Findings / Results Of included patients, 21%, 33.7%, 24.3%, and 21% had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 30-month follow-ups, OS was higher with the FLOT regimen in comparison with other regimens (hazard ratio = 0. 276). The median OS of the FLOT regimen was 39 months. Besides, the median OS was 28, 25, and 21 months for DCF, FOLOFX, and ECF regimens, respectively. Moreover, a median PFS of 24, 18, 17, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank < 0.001). FLOT regimen showed 84. 4% ORR which was notably higher than other groups. Conclusions and implications For resectable gastric cancer patients, the perioperative FLOT regimen led to a significant improvement in patients' OS and PFS versus ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered the optimal option for managing resectable gastric cancer patients.
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Affiliation(s)
- Pegah Farrokhi
- Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Minneapolis, USA
| | - Alireza Sadeghi
- Department of Internal Medicine-Haematology-Oncology Section, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Mehran Sharifi
- Department of Internal Medicine-Haematology-Oncology Section, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran,Corresponding authors: A. Moghaddas, Tel: +98-3137927074, Fax: +98-3136680011 M. Sharifi, Tel: +98-3132368005, Fax: +98-3132350210
| | - Rachel Riechelmann
- Department of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil
| | - Azadeh Moghaddas
- Department of Clinical Pharmacy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran,Corresponding authors: A. Moghaddas, Tel: +98-3137927074, Fax: +98-3136680011 M. Sharifi, Tel: +98-3132368005, Fax: +98-3132350210
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Carbonell Morote S, Gracia Alegría E, Ruiz de la Cuesta Tapia E, Llopis Torremocha C, Ortiz Sebastián S, Estrada Caballero JL, Villodre C, Ramia JM. Textbook outcome en cirugía gástrica oncológica, ¿qué implicaciones tiene sobre la supervivencia? Cir Esp 2021. [DOI: 10.1016/j.ciresp.2021.09.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Mittal SK, Abdo J, Adrien MP, Bayu BA, Kline JR, Sullivan MM, Agrawal DK. Current state of prognostication, therapy and prospective innovations for Barrett's-related esophageal adenocarcinoma: a literature review. J Gastrointest Oncol 2021; 12:1197-1214. [PMID: 34532080 DOI: 10.21037/jgo-21-117] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 06/30/2021] [Indexed: 12/11/2022] Open
Abstract
Objective Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), which has one of the lowest 5-year survival rates in oncology. The reasons for poor survival are twofold: the large majority of diagnoses are in advanced stages (~80%) and limited treatment options, with a deficit of biology-guided therapies. As a rapidly growing public health concern with poor prognosis, research into the molecular progression for BE and novel therapeutics for EAC currently has high clinical utility. Review of the literature reveals that innovative analysis of metaplastic progression from BE to EAC at a molecular level can shed light on the underlying transformative probabilities of BE into malignant pathologies and may impact current of future therapeutic modalities for management of these diseases. Background EAC is the fastest increasing cancer in the United States with a 600% increase over the past 25 years. This cancer arises from dysplastic tissue of BE, a complication of gastroesophageal reflux disease (GERD). Chronic acid and bile reflux in the distal esophagus initiates a metaplastic conversion of normal squamous epithelium to premalignant intestinalized columnar epithelium. Patients with BE have a 125-fold higher risk of cancer compared to the general population. Methods We critically reviewed the current status of BE monitoring, and subsequent therapeutic strategies being used in patients who have progressed to cancer. Also, new diagnostic tools and therapeutic candidates for BE-related EAC are discussed. Highly-targeted searches of databases containing recent original peer-reviewed papers were utilized for this review. Conclusions Novel and well-described biomarkers analyzed in the patient's diseased tissue will provide for more powerful diagnostics, but also possess the potential to develop strategies for personalized management and identify targets for intervention to either cease disease progression or treat BE and/or EAC. Since millions of Americans develop BE without progressing to cancer, there is a critical need to identify the small percentage of Barrett's patients who possess hallmarks of disease progression or carcinogenesis with novel screening techniques. Incorporation of such tools into standard screening protocols for BE surveillance and/or therapy would be critical to detect malignant transformations before clinically obvious cancer ever develops.
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Affiliation(s)
- Sumeet K Mittal
- Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Dignity Health, Phoenix, AZ, USA
| | - Joe Abdo
- Stella Diagnostics, Inc., Salt Lake City, UT, USA
| | - Malika P Adrien
- Department of Biochemistry, Georgetown University Medical Center, Washington, DC, USA
| | - Binyam A Bayu
- Department of Biochemistry, Georgetown University Medical Center, Washington, DC, USA
| | - Jay R Kline
- Department of Biochemistry, Georgetown University Medical Center, Washington, DC, USA
| | - Molly M Sullivan
- Department of Biochemistry, Georgetown University Medical Center, Washington, DC, USA
| | - Devendra K Agrawal
- Department of Translational Research, Western University of Health Sciences, Pomona, CA, USA
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Tseng J, Miller JP, Johnson J, Waters K, Gangi A, Gong J, Burch M. Disparities and survival in newly diagnosed gastric cancer in Hispanic patients in the United States: a propensity score matched analysis. J Gastrointest Oncol 2021; 12:1308-1325. [PMID: 34532090 DOI: 10.21037/jgo-21-207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 06/30/2021] [Indexed: 11/06/2022] Open
Abstract
Background The burden of gastric cancer involving Hispanic patients in the United States is growing as both the population and the incidence of gastric cancer in this group increases. This burden is compounded by presentation with advanced disease and socioeconomic challenges shaping cancer care. We sought to describe the demographics, socioeconomic factors, treatment, and survival experience of Hispanic patients with gastric adenocarcinoma. Methods Patients with gastric adenocarcinoma diagnosed between 2004 and 2015 (n=90,737) in the National Cancer Database were retrospectively identified. Patients of Hispanic ethnicity were compared against non-Hispanic white patients. Surgical cohort was further analyzed, and 1:1 propensity score matching was used to balance covariates between Hispanic and non-Hispanic white surgical patients. Survival was compared using Kaplan-Meier method. Cox regression was used to determine prognostic factors for survival. Results Compared to non-Hispanic white patients, Hispanic patients are more likely to be younger, female, and healthier. They were more likely to be uninsured, reside in poorer neighborhoods and reside in areas with lower rates of education. Hispanic patients were more likely to live in a metropolitan area, travel shorter distances for healthcare, and receive treatment at an academic and high volume centers. Hispanic patients were more likely to have higher stage disease presentation, higher grade tumors, lymphovascular invasion, and poorly cohesive adenocarcinoma. Hispanic patients were more likely to receive surgery, but less likely to receive adjuvant therapy. In Cox regression of all patients, unmatched surgical patients, and matched surgical patients, Hispanic ethnicity was an independent prognostic factor of improved survival. Conclusions Hispanic patients with gastric adenocarcinoma present with several unfavorable clinicopathologic and socioeconomic factors. Paradoxically, these patients demonstrate improved survival. Further study is warranted to characterize disease biology in this population.
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Affiliation(s)
- Joshua Tseng
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - James P Miller
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Jeffrey Johnson
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Kevin Waters
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Alexandra Gangi
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Jun Gong
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Miguel Burch
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Chen X, Lu J, Yao Y, Huang Z, Liu K, Jiang W, Li C. Effects of bevacizumab combined with oxaliplatin intrathoracic injection on tumor markers and survival rate in patients with malignant pleural effusion of lung cancer. Am J Transl Res 2021; 13:2899-2906. [PMID: 34017454 PMCID: PMC8129278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/21/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVE This study aims to explore the therapeutic effects of bevacizumab combined with oxaliplatin on patients with malignant pleural effusion of lung cancer. METHODS A total of 109 patients with malignant pleural effusion of lung cancer admitted to our hospital from March 2015 to April 2017 were selected as research objects. Among them, 59 patients treated with bevacizumab combined with oxaliplatin intrathoracic injection were enrolled in the observation group, and another 50 patients treated with oxaliplatin intrathoracic injection were enrolled in the regular group. Clinical efficacy and safety of the two groups were compared, as well as the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR) and tumor markers before and after treatment. The two groups of patients were followed up for 3 years to compare their prognosis, survival and quality of life. RESULTS The cure rate of the observation group was higher than that of the regular group (P < 0.05), but there was no difference in the incidence of adverse reactions (P > 0.05). After treatment, VEGF, VEGFR and tumor markers in the observation group were significantly lower than those in the regular group (P < 0.05), while the survival rate and quality of life of the observation group were significantly higher than those in the regular group (P < 0.05). CONCLUSION Bevacizumab combined with oxaliplatin intrathoracic injection is effective in treating malignant pleural effusion of lung cancer.
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Affiliation(s)
- Xiaoju Chen
- Department of General Internal Medicine, Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, China
- Department of Respiratory Medicine, First Affiliated Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, China
| | - Jiali Lu
- Department of Respiratory Medicine, First Affiliated Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, China
| | - Yien Yao
- Department of Respiratory Medicine, First Affiliated Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, China
| | - Zhongchen Huang
- Department of Respiratory Medicine, First Affiliated Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, China
| | - Ke Liu
- Department of Respiratory Medicine, First Affiliated Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, China
| | - Wenxin Jiang
- Department of General Internal Medicine, Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, China
| | - Chaoqian Li
- Department of Respiratory Medicine, First Affiliated Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, China
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21
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Zhang LY, Ma JJ, Zang L, Hong HJ, Lu AG, He ZR, Jiang TY, Zhao X, Fingerhut A, Zheng MH. Staged laparoscopic management of locally advanced gastric cancer with outlet obstruction. J Surg Oncol 2021; 123 Suppl 1:S8-S14. [PMID: 33818776 DOI: 10.1002/jso.26342] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 11/23/2020] [Accepted: 11/23/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND The prognosis of patients with locally advanced gastric cancer with outlet obstruction is poor. Gastrectomy with curative intent is often initially impossible or difficult. OBJECTIVE We report our experience of curative distal gastrectomy after laparoscopic gastrojejunostomy and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy to examine the feasibility and safety of this modified strategy for locally advanced gastric cancer with outlet obstruction, initially deemed unresectable. METHODS Between October 2017 and June 2019, 15 patients diagnosed with locally advanced gastric cancer with outlet obstruction sequentially underwent gastrojejunostomy, received four cycles of FLOT chemotherapy, and underwent laparoscopic distal gastrectomy with curative intent (R0 resection + D2 lymphadenectomy). Clinical data were retrospectively collected and analyzed. RESULTS R0 resection was possible in 12/15 patients, laparoscopically in 11, and one conversion to laparotomy was necessary. There was no perioperative mortality in the 12 patients. Pathologic evaluation of the resected specimens revealed that complete tumor grade regression 1a (TRG1a), TRG1b, TRG2, and TRG3 occurred in 3, 2, 4, and 3 patients, respectively. CONCLUSION This case series showed that curative surgical resection was feasible as a staged approach for patients with locally advanced gastric cancer with outlet obstruction, after initial staged gastrojejunostomy and chemotherapy.
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Affiliation(s)
- Lu-Yang Zhang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun-Jun Ma
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lu Zang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hi-Ju Hong
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ai-Guo Lu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zi-Rui He
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tian-Yu Jiang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuan Zhao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Abe Fingerhut
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Surgery, Section for Surgical Research, Medical University of Graz, Graz, Austria.,Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Min-Hua Zheng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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22
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Wu F, Hong J, Du N, Wang Y, Chen J, He Y, Chen P. Long-Term Outcomes of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer/Esophagogastric Junction Cancer: A Systematic Review and Meta-Analysis. Anticancer Agents Med Chem 2021; 22:143-151. [PMID: 33719964 DOI: 10.2174/1871520621666210315091932] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 01/31/2021] [Accepted: 02/01/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) has been defined as any preoperative chemotherapy scheme aiming to reduce tumor staging and to control preoperative micrometastasis, which has been extensively used as a treatment for resectable gastric cancer. However, its effect on the long-term survival of patients with locally advanced gastric cancer (AGC) or esophagogastric junction cancer (EGC) remains unknown. OBJECTIVE This study aimed at investigating the long-term efficacy of NAC in locally AGC/EGC. METHODS The following databases were searched for articles published from their inception up to April 2020: PubMed, Web of Science, EBSCO, and Cochrane library. The primary outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS A total of 19 articles were included in this meta-analysis, with a total of 4,446 patients. The results showed that NAC increased the patients' 3-year OS (HR, 0.56; 95%CI, 0.21-0.91; P<0.001), 3-year PFS (HR, 0.76; 95%CI, 0.66-0.87; P<0.001), 5-year OS (HR, 0.71; 95% CI, 0.64-0.78; P<0.001), and 5-year PFS (HR, 0.70; 95% CI, 0.61-0.79; P<0.001) respectively. Besides, subgroup analysis showed that Asian countries have benefited significantly from NAC (HR, 0.65; 95%CI, 0.55-0.74; P<0.001), and other countries have also benefited (HR, 0.79; 95%CI, 0.68-0.89; P<0.001). CONCLUSIONS Compared with adjuvant chemotherapy and surgery alone, NAC can improve the long-term survival outcomes (OS and PFS) of patients with resectable AGC or EGC.
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Affiliation(s)
- Feng Wu
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang. China
| | - Jiaze Hong
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Nannan Du
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Yiran Wang
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Juan Chen
- Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Yuanfang He
- Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Ping Chen
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang. China
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23
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Zhang Y, Zhang B, Yang J, Zhang J, Zhang W. Perioperative Safety and Effectiveness of Neoadjuvant Therapy with Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel Plus Apatinib in Locally Advanced Gastric Cancer. Cancer Manag Res 2021; 13:2279-2286. [PMID: 33732020 PMCID: PMC7956581 DOI: 10.2147/cmar.s304093] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 02/26/2021] [Indexed: 02/03/2023] Open
Abstract
Purpose The trend in neoadjuvant therapy for locally advanced gastric cancer (LAGC) is to use more drugs or therapies in combination. This study aimed to assess the safety and effectiveness of neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) plus apatinib in the treatment of LAGC. Patients and Methods We collected clinical data from patients with LAGC who received neoadjuvant FLOT and apatinib therapy and underwent surgery from January 2017 to December 2020. Patients were divided into either the FLOT group (in which patients received FLOT neoadjuvant therapy and surgery) or the FLOTA group (in which patients received FLOT plus apatinib neoadjuvant therapy and surgery). Results The FLOT and FLOTA groups contained 44 and 31 patients, respectively. There were significant differences between the FLOT and FLOTA groups in the objective response rate (50.00% vs. 80.65%, respectively, p = 0.008) and average change from baseline in the target lesion size (−26.16 ± 34.61 vs. −54.32 ± 36.11, respectively, p < 0.001). There were also significant differences in the pretreatment clinical tumor-node-metastasis (cTNM) and post treatment cTNM stages for the FLOT group (p = 0.001) and for the FLOTA group (p < 0.001). There were no significant differences between the FLOT and FLOTA groups in post neoadjuvant therapy cTNM stages (p = 0.525), R0 rate (p = 0.397), tumor regression grade (p = 0.397), or post treatment pathological TNM stage (p = 0.180). Some neoadjuvant therapy-related adverse events occurred significantly more frequently in the FLOTA group, including diarrhea (all grades), pain (all grades), oral mucositis (all grades), and hand-foot syndrome (all grades). Conclusion The FLOTA regimen can achieve better perioperative efficacy and acceptable toxicity compared with that of the FLOT regimen in neoadjuvant treatment of LAGC. The FLOTA regimen for neoadjuvant therapy for LAGC merits further study.
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Affiliation(s)
- Yonglei Zhang
- Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan Province, People's Republic of China
| | - Bin Zhang
- Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan Province, People's Republic of China
| | - Jinpo Yang
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan Province, People's Republic of China
| | - Jindai Zhang
- Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan Province, People's Republic of China
| | - Wei Zhang
- Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, Zhengzhou, 450008, Henan Province, People's Republic of China
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24
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Runkel M, Verst R, Spiegelberg J, Fichtner-Feigl S, Hoeppner J, Glatz T. Perioperative FLOT chemotherapy plus surgery for oligometastatic esophagogastric adenocarcinoma: surgical outcome and overall survival. BMC Surg 2021; 21:35. [PMID: 33435947 PMCID: PMC7805136 DOI: 10.1186/s12893-020-01035-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 12/27/2020] [Indexed: 10/25/2022] Open
Abstract
BACKGROUND Guidelines do not recommend surgery for patients with oligometastatic disease from esophagogastric adenocarcinoma (EGAC), although some studies suggest a more favorable survival. We analyzed the outcome of oligometastatic EGAC receiving FLOT chemotherapy followed by surgery. METHODS The data of patients with either pre-therapeutic, post-neoadjuvant or intraoperative clinical diagnosis of oligometastatic EGAC were extracted from a prospective database of the 2009-2018 treatment period. 48 consecutive patients were identified with oligometastatic disease, who underwent perioperative chemotherapy plus surgery. We retrospectively analyzed surgical outcome and overall survival. RESULTS The overall 5-year survival was 18%. 12 patients (25%) with pre-therapeutic oligometastatic EGAC, who had no histologic vital tumor evidence of metastases after surgery had a survival rate of 48% compared to an 11% 5-year survival rate of 36 patients (75%), who had histologic vital tumor metastatic evidence after FLOT chemotherapy and surgical resection (p = 0.012). The survival rates after R0, R1 and R2 (non-resected metastases) resection were 21% (n = 33), 0% (n = 4) and 17% (n = 11), respectively (p = 0.273). CONCLUSION Oligometastatic EGAC is associated with poor overall survival even after complete resection of all tumor manifestations. The subgroup of patients with a complete histologic response of metastatic lesions to neoadjuvant FLOT shows 5-year survival rates similar to non-metastatic EGAC. Trial registration Not applicable.
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Affiliation(s)
- Mira Runkel
- Department of General - and Visceral Surgery, Medical Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
| | - Rasmus Verst
- Department of General - and Visceral Surgery, Medical Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany
| | - Julia Spiegelberg
- Department of General - and Visceral Surgery, Medical Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany
| | - Stefan Fichtner-Feigl
- Department of General - and Visceral Surgery, Medical Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany
| | - Jens Hoeppner
- Department of General - and Visceral Surgery, Medical Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.,Department of Surgery, University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Torben Glatz
- Department of General - and Visceral Surgery, Medical Center, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.,Department of Surgery, Marien Hospital Herne, Ruhr-University Bochum, 44625, Herne, Germany
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25
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Sah BK, Zhang B, Zhang H, Li J, Yuan F, Ma T, Shi M, Xu W, Zhu Z, Liu W, Yan C, Li C, Liu B, Yan M, Zhu Z. Neoadjuvant FLOT versus SOX phase II randomized clinical trial for patients with locally advanced gastric cancer. Nat Commun 2020; 11:6093. [PMID: 33257672 PMCID: PMC7705676 DOI: 10.1038/s41467-020-19965-6] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 11/08/2020] [Indexed: 02/07/2023] Open
Abstract
Neoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (FLOT regimen) has shown promising results in terms of pathological response and survival rate in patients with locally advanced resectable gastric cancer (LAGC). However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (SOX regimen) is the preferred chemotherapy regimen in Eastern countries. Here, we conduct an open label, two-arm, phase II randomized interventional clinical trial (Dragon III; ClinicalTrials.gov: NCT03636893) to evaluate the safety and efficacy of both regimens. Patients with LAGC are randomly assigned to receive either 4 cycles of the neoadjuvant FLOT regimen (40 patients) or 3 cycles of the SOX regimen (34 patients) before gastrectomy. The primary endpoint is the comparison of complete (TRG1a) or subtotal (TRG1b) tumor regression grading in the primary tumor. There are no significant differences in adverse effects or postoperative morbidity and mortality between the two groups. No significant differences in the proportion of tumor regression grading between the FLOT group and the SOX group are found. Complete or subtotal TRG is 20.0% in the FLOT group versus 32.4% in the SOX group. Therefore, our study does not find statistically significant differences between neoadjuvant FLOT and SOX regimens for the primary outcomes reported here in locally advanced gastric cancer.
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Affiliation(s)
- Birendra Kumar Sah
- Department of General Surgery, Gastrointestinal Surgery Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai, China.
| | - Benyan Zhang
- Department of Pathology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huan Zhang
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian Li
- Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fei Yuan
- Department of Pathology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tao Ma
- Department of Medical Oncology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Shi
- Department of Medical Oncology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Xu
- Department of General Surgery, Gastrointestinal Surgery Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai, China
| | - Zhenglun Zhu
- Department of General Surgery, Gastrointestinal Surgery Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai, China
| | - Wentao Liu
- Department of General Surgery, Gastrointestinal Surgery Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai, China
| | - Chao Yan
- Department of General Surgery, Gastrointestinal Surgery Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai, China
| | - Chen Li
- Department of General Surgery, Gastrointestinal Surgery Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai, China.
| | - Bingya Liu
- Department of General Surgery, Gastrointestinal Surgery Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai, China
| | - Min Yan
- Department of General Surgery, Gastrointestinal Surgery Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai, China
| | - Zhenggang Zhu
- Department of General Surgery, Gastrointestinal Surgery Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai, China.
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26
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Sah BK, Zhang B, Zhang H, Li J, Yuan F, Ma T, Shi M, Xu W, Zhu Z, Liu W, Yan C, Li C, Liu B, Yan M, Zhu Z. Dragon III- Phase II Randomized Controlled Trial: Neoadjuvant FLOT versus SOX for Patients with Locally Advanced Gastric Cancer.. [DOI: 10.1101/2020.06.21.20136887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
AbstractBackgroundNeoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (the FLOT regimen) has shown promising results in terms of pathological response and survival rate. However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (the SOX regimen) is a more favorable chemotherapy regimen in Eastern countries. We conducted this study to evaluate the safety and efficacy of both regimens and to explore a suitable regimen for gastric cancer patients.MethodsPatients with locally advanced gastric cancer (LAGC) were 1:1 randomly assigned to receive either 4 cycles of the FLOT regimen or 3 cycles of the SOX regimen before curative gastrectomy. The primary endpoint was the comparison of complete or subtotal tumor regression grading (TRG1a+ TRG1b) in the primary tumor.ResultsAltogether, 74 patients were enrolled between August 2018 and March 2020. There was no significant difference in pretreatment clinicopathological parameters between the FLOT group and the SOX group (p>0.05). There was no significant difference in adverse effects or postoperative morbidity and mortality between the two groups (p>0.05). Similarly, there was no significant difference in the proportion of tumor regression grading between the FLOT group and the SOX group (p>0.05). In the ITT population, complete or subtotal TRG was 20.0% in the FLOT group versus 32.4% in the SOX group (p>0.05).ConclusionOur study demonstrates that the FLOT and SOX regimens are similarly effective for locally advanced gastric cancer patients in terms of clinical downstaging and pathological response. A large-scale phase III randomized controlled trial is necessary to validate this result.
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27
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Xu X, Chang X, Xu Y, Deng P, Wang J, Zhang C, Zhu X, Chen S, Dai D. SAMD14 promoter methylation is strongly associated with gene expression and poor prognosis in gastric cancer. Int J Clin Oncol 2020; 25:1105-1114. [PMID: 32206938 DOI: 10.1007/s10147-020-01647-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 02/20/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Gastric cancer (GC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related mortality. In recent years, SAMD14 has been studied in various malignant cancers; however, little is known about the exact mechanisms of SAMD14 involvement in carcinogenesis and malignant progression. METHODS 60 paired GC-normal gastric tissues were evaluated for their SAMD14 mRNA expression in relation to SAMD14 gene promoter methylation. GC patient survival was assessed by Kaplan-Meier analyses and a Cox's proportional hazard model was employed for multivariate analyses. RESULTS SAMD14 expression was significantly inversely correlated with the Borrmann type (P = 0.017), lymph node metastasis (P = 0.006) and tumor-node-metastasis (TNM) stage (P = 0.033). Methylation-specific PCR (MSP) revealed hyper-methylation of the SAMD14 promoter in 56.7% (34/60) of the primary GC tissues tested and in 10% (6/60) of matched non-malignant tissues. The SAMD14 promoter methylation status was also related to pathological differentiation, Borrmann type, TNM stage and lymph node metastasis. The results showed SAMD14 expression was significantly downregulated in Borrmann type, lymph node metastasis and TNM stage, which showed significantly higher methylation. SAMD14 promoter hyper-methylation was significantly associated with a poor prognosis and could serve as an independent marker for survival using multivariate Cox regression analysis. CONCLUSIONS Our results indicated that promoter methylation was a key mechanism contributing to the downregulation of SAMD14 in GC. SAMD14 may be an epigenetically silenced tumor suppressor gene, and hyper-methylation of the SAMD14 promoter may serve as a biomarker to predict the clinical outcome of GC.
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Affiliation(s)
- Xiaoyang Xu
- Department of Gastrointestinal Surgery and Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
- Department of Surgery, Fushun Mining Bureau General Hospital of Liaoning Health Industry Group (the Seventh Affiliated Hospital of China Medical University), Fushun, China
| | - Xiaojing Chang
- Department of Radiotherapy, The Second Hospital, Hebei Medical University, Shijiazhuang, China
| | - Yan Xu
- The First Department of Radiotherapy, Fushun Fourth Hospital, Fushun, China
| | - Peng Deng
- Department of Gastrointestinal Surgery and Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
| | - Jiang Wang
- Department of Surgery, Fushun Mining Bureau General Hospital of Liaoning Health Industry Group (the Seventh Affiliated Hospital of China Medical University), Fushun, China
| | - Chundong Zhang
- Department of Gastrointestinal Surgery and Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
| | - Xinjiang Zhu
- Department of Gastrointestinal Surgery and Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
| | - Shuchen Chen
- Department of Gastrointestinal Surgery and Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
| | - Dongqiu Dai
- Department of Gastrointestinal Surgery and Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China.
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