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Du XY, Xia RJ, Shen LW, Ma JG, Yao WQ, Xu W, Lin ZP, Ma LB, Niu GQ, Fan RF, Xu SM, Yan L. Quadruple therapy with immunotherapy and chemotherapy as first-line conversion treatment for unresectable advanced gastric adenocarcinoma: A case report. World J Gastrointest Oncol 2025; 17:102258. [DOI: 10.4251/wjgo.v17.i4.102258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/20/2025] [Accepted: 02/24/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND The treatment of gastric cancer remains highly challenging, particularly in cases of unresectable locally advanced or metastatic disease. Although chemotherapy and immunotherapy have shown some efficacy in such patients, significant limitations persist in extending survival and enhancing safety. To address these challenges, we designed an innovative first-line quadruple conversion therapy regimen that integrates a programmed cell death protein 1 (PD-1) inhibitor with chemotherapy, and we successfully implemented this therapy regimen in the treatment of a patient with unresectable locally advanced gastric adenocarcinoma.
CASE SUMMARY We report the case of a 55-year-old male who was diagnosed with unresectable locally advanced gastric adenocarcinoma and presented with intermittent epigastric pain and multiple lymph node metastases in the abdominal cavity, with the metastasis being notably large in size. The tumor tissue was negative for human epidermal growth factor receptor 2 by immunohistochemistry. Considering the patient's status, the multidisciplinary team decided to administer sintilimab in combination with albumin-bound paclitaxel (nab-paclitaxel), S-1, and oxaliplatin as a quadruple drug conversion therapy. After 4 cycles of conversion therapy, the patient's epigastric pain was significantly alleviated, his stool color normalized, the volume of the primary tumor and lymph node metastases was markedly reduced, and the tumor marker levels decreased to within the normal range. The patient subsequently underwent laparoscopic total gastrectomy with abdominal lymph node dissection, and postoperative pathological biopsy revealed a pathological complete response and R0 resection, after which the patient recovered to an excellent physical status.
CONCLUSION To the best of our knowledge, this is the first reported case of unresectable locally advanced gastric adenocarcinoma successfully treated with quadruple therapy with a PD-1 inhibitor and chemotherapy as a first-line conversion regimen. This first-line conversion therapy with the quadruple regimen may be effective and safe for unresectable locally advanced gastric adenocarcinoma.
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Affiliation(s)
- Xiao-Yu Du
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Ren-Jie Xia
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Li-Wen Shen
- Department of Medical Support Center, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Jian-Guo Ma
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Wei-Qing Yao
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Wei Xu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Zhi-Peng Lin
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Liang-Bin Ma
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Guo-Qiang Niu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Rui-Fang Fan
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Shu-Mei Xu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Long Yan
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
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Baba K, Suzuki N, Imamura CK, Booka E, Takeuchi M, Takahari D, Kawakami T, Kawakubo H, Kitagawa C, Kono Y, Ogura K, Kito Y, Saito K, Yamamoto S, Takeuchi H, Kudo T, Tsunoda T, Mizukami T, Yamaguchi T, Shoji H, Saito K, Tanoue K, Baba E, Nagashima K, Boku N. A phase I/II trial evaluating the safety of increased-dose S- 1 with oxaliplatin and nivolumab in HER2-negative advanced gastric cancer. BMC Cancer 2025; 25:675. [PMID: 40221699 PMCID: PMC11993961 DOI: 10.1186/s12885-025-14084-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 04/03/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND We developed and refined an S-1 dosage formula based on renal function, sex, and body surface area (BSA) to achieve the target area under the concentration-time curve of 5-fluorouracil in two prospective pharmacokinetic studies. The clinical validity of the refined formula (BBT formula) was evaluated using data from the two phase III trials of fist-line chemotherapy including S-1 for advanced gastric cancer, which demonstrated that overall survival and progression-free survival tended to be shorter in patients whose S-1 standard dose, based on BSA alone, was lower than that determined using the BBT formula. METHODS Chemo-naïve patients with HER2-negative advanced gastric or gastroesophageal junction cancer, whose standard S-1 dose is lower than that determined using the BBT formula, receive S-1 at an increased dose based on the BBT formula plus oxaliplatin (130 mg/m2) and nivolumab (360 mg/body). The primary endpoint is the incidence of dose-limiting toxicity in six patients in the phase I part and the proportion of patients requiring S-1 dose reduction in a total of 20 patients, expecting 30% and rejecting 50% with an alpha error of 0.1 and beta error of 0.2. The secondary endpoints are adverse events, relative dose intensity, response rate, disease control rate, progression-free survival, and overall survival. A correlation study is conducted to investigate the immune profiles associated with efficacy. DISCUSSION This phase I/II trial evaluates the safety and efficacy of S-1 at increased doses, determined by the BBT formula, in combination with oxaliplatin and nivolumab in patients with HER2-negative advanced gastric cancer, whose standard dose of S- 1 is lower than the dose recommended dose by the BBT formula. TRIAL REGISTRATION This study was approved by the University of Tokyo Clinical Research Review Board (URL: https://www.ut-crescent.jp/patients/chiken_jisshi/ , review number: 2022529SP) and was initiated at 19 institutions in June 2023 (registered as jRCTs031230127).
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Affiliation(s)
- Keisuke Baba
- Department of Oncology and General Medicine, IMSUT Hospital, the Institute of Medical Science Hospital, the University of Tokyo, Tokyo, Japan
| | - Nobumi Suzuki
- Department of Gastroenterology Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Chiyo K Imamura
- Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan
| | - Eisuke Booka
- Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Masashi Takeuchi
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Daisuke Takahari
- Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Kawakami
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Chiyoe Kitagawa
- Medical Oncology and Respiratory Medicine, NHO Nagoya Medical Center, Aichi, Japan
| | - Yoshiyasu Kono
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Keiji Ogura
- Department of Gastroenterology, Tokyo Metropolitan Police Hospital, Tokyo, Japan
| | - Yosuke Kito
- Department of Medical Oncology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Kei Saito
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Shinzo Yamamoto
- Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Toshihiro Kudo
- Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Takuya Tsunoda
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Takuro Mizukami
- Department of Medical Oncology, NTT Medical Center Tokyo, Tokyo, Japan
| | - Toshifumi Yamaguchi
- Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan
| | - Hirokazu Shoji
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kanako Saito
- Department of Medical Oncology, Mie University Hospital, Mie, Japan
| | - Kenro Tanoue
- Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eishi Baba
- Department of Comprehensive Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kengo Nagashima
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Narikazu Boku
- Department of Oncology and General Medicine, IMSUT Hospital, the Institute of Medical Science Hospital, the University of Tokyo, Tokyo, Japan.
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Ishida H, Sunakawa Y, Kodera Y, Yoshida K, Kochi M, Kakeji Y, Sano T, Takeuchi M, Ichikawa W, Fujii M. Post-recurrence survival in patients with stage III gastric cancer who received adjuvant chemotherapy; post-hoc analysis of the JACCRO GC-07 study. Eur J Cancer 2025; 219:115322. [PMID: 39999670 DOI: 10.1016/j.ejca.2025.115322] [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: 07/22/2024] [Revised: 02/06/2025] [Accepted: 02/16/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND As adjuvant chemotherapy for stage III gastric cancer, the phase III (JACCRO GC-07) trial showed that docetaxel plus S-1 (DS) was superior to S-1 in terms of recurrence-free and overall survival. However, whether adding docetaxel to S-1 in the adjuvant setting affects survival after recurrence remains unclear. The optimal treatment strategy for patients who develop recurrence during or after DS has also been controversial. METHODS We used results from JACCRO GC-07 to investigate post-recurrence survival (PRS) in patients who developed recurrence during or after completing adjuvant chemotherapy. PRS was compared between adjuvant groups and among post-recurrence chemotherapeutic regimens. RESULTS During 5 years of follow-up after surgery, 161 of 441 patients in the DS group and 216 of 452 patients in the S-1 group developed recurrence, with median PRS of 12.6 and 11.4 months, respectively (hazard ratio [HR] 0.98, 95 % confidence interval [CI] 0.79-1.22; p = 0.84). Among patients with recurrence, 115 patients in the DS group and 165 patients in the S-1 group received chemotherapy, and median PRS was 14.5 and 13.7 months, respectively (HR 1.04, 95 %CI 0.81-1.34; p = 0.76). Platinum-based chemotherapy resulted in longer PRS than non-platinum chemotherapy, regardless of the adjuvant chemotherapeutic regimen or time of recurrence. CONCLUSIONS PRS was similar between patients who received adjuvant chemotherapy with DS or with S-1 alone. PRS was also similar between groups of patients who received chemotherapy after recurrence. Platinum-based chemotherapy might be the optimal treatment for patients who develop recurrence after completing adjuvant DS, regardless of the time of recurrence.
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Affiliation(s)
- Hiroo Ishida
- Division of Medical Oncology, Showa University Fujigaoka Hospital, Japan.
| | - Yu Sunakawa
- Department of Clinical Oncology, St. Marianna University School of Medicine, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Japan
| | | | - Mitsugu Kochi
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare, School of Medicine, Japan
| | - Yoshihiro Kakeji
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan
| | - Takeshi Sano
- Gastroenterological Surgery, Cancer Institute Hospital, Japan
| | - Masahiro Takeuchi
- The University of Tokyo Graduate School of Mathematical Science, Japan
| | - Wataru Ichikawa
- Division of Medical Oncology, Showa University Fujigaoka Hospital, Japan
| | - Masashi Fujii
- Department of Digestive Surgery, Nihon University School of Medicine, Japan
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Liu Y, Zhao JG, Zhao GY. Impact of the SOX Regimen on Immune Function and Tumor Markers in Advanced Gastric Cancer. Int J Gen Med 2025; 18:1415-1422. [PMID: 40092456 PMCID: PMC11910057 DOI: 10.2147/ijgm.s509902] [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: 12/02/2024] [Accepted: 02/13/2025] [Indexed: 03/19/2025] Open
Abstract
Background Locally advanced gastric cancer presents significant challenges in treatment, often limiting the effectiveness of surgical interventions. Chemotherapy, especially the SOX regimen (combining oxaliplatin and tegafur/gimeracil/oteracil), has been explored as a potential alternative in the management of advanced gastric cancer. While studies on SOX have been conducted in other regions, its impact on immune function and tumor markers remains inadequately evaluated, particularly in China. Objective This study aimed to assess the toxicological profile, immune function modulation, and tumor marker reduction of the SOX regimen in patients with advanced gastric cancer. Methods A retrospective analysis was conducted on 100 patients diagnosed with advanced gastric cancer, excluding eight ineligible cases. Based on clinical records, patients were grouped into either the oxaliplatin monotherapy group (reference group) or the SOX regimen group (observation group), with 50 patients in each group. The primary endpoint was clinical effectiveness, while secondary endpoints included immune function, tumor marker levels, and chemotherapy-related toxicity. Results The SOX regimen demonstrated significantly higher disease control and objective remission rates compared to oxaliplatin monotherapy (P<0.05). In the SOX group, immune function was enhanced, with increased levels of immunoglobulins (IgA, IgG, IgM) and lymphocyte subsets (CD3+, CD4+, NK cells), and a decrease in CD8+ levels (P<0.05). Additionally, tumor markers such as CA125, CEA, MRP14, SDF-1, FSP-1, and CXCR4 showed a significant reduction (P<0.05). The SOX regimen also exhibited a more favorable safety profile, with lower incidences of chemotherapy-related nausea, vomiting, and leukopenia (P<0.05). Conclusion The SOX regimen is an effective and promising treatment option for advanced gastric cancer, offering significant improvements in clinical outcomes, immune function, and tumor marker reduction, with fewer chemotherapy-related toxicities. This study provides valuable insights into the application of the SOX regimen in Chinese patients with advanced gastric cancer.
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Affiliation(s)
- Yifen Liu
- Department of Gastrointestinal Surgery, Hengshui People's Hospital, Hengshui, People's Republic of China
| | - Jian-Gang Zhao
- Department of Gastrointestinal Surgery, Hengshui People's Hospital, Hengshui, People's Republic of China
| | - Guang-Yuan Zhao
- Department of Gastrointestinal Surgery, Hengshui People's Hospital, Hengshui, People's Republic of China
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Li Z, Aliseda D, Jones O, Rajendran L, Magyar C, Grant R, O’Kane GM, Saborowski A, Sapisochin G, Vogel A. Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis using reconstructed RCT survival data. JHEP Rep 2025; 7:101290. [PMID: 39980751 PMCID: PMC11840543 DOI: 10.1016/j.jhepr.2024.101290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/14/2024] [Accepted: 11/20/2024] [Indexed: 02/22/2025] Open
Abstract
Background & Aims Gemcitabine/cisplatin (GemCis) was the long-standing first-line treatment for advanced biliary tract cancers (BTCs). Following positive results from the TOPAZ-01 and KEYNOTE-966 trials, immune checkpoint inhibitors (ICIs) combined with chemotherapy are now the standard of care. We aim to compare the efficacy of first-line therapies for advanced BTCs. Methods Our systematic review included studies from five databases focusing on English-language articles published between January 2010 and June 2024. We included randomized clinical trials (RCTs) that featured GemCis in a treatment arm for treatment-naive adults with advanced BTCs. The primary endpoints were overall survival (OS) and progression-free survival. We conducted a one-stage meta-analysis using reconstructed survival data, Cox-based models, and restricted mean survival time (RMST). Results After screening 8,797 studies, 17 RCTs were selected, involving a total of 4,584 patients. Of these, 2,140 (46.7%) received GemCis. The majority (68.9%) were diagnosed with intrahepatic or extrahepatic cholangiocarcinoma, and 80% had metastatic disease at the time of treatment. The pooled median OS in the GemCis group was 11.6 months (95% CI 11.3-12.2 months). GemCis plus pembrolizumab (hazard ratio [HR] 0.99, 95% CI 0.98-0.99; p <0.001), GemCis plus durvalumab (HR 0.98, 95% CI 0.97-0.99; p = 0.015), GemCis plus S-1 (HR 0.97 95% CI 0.95-0.99; p <0.001), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.98-0.99; p <0.001) demonstrated superior OS compared with GemCis alone. These combinations also showed increases in RMST by +1.1, +2.5, +2.8, and +2.1 months, respectively. In terms of progression-free survival, GemCis with ICIs (HR 0.91, 95% CI 0.78-0.94; p <0.001), GemCis plus S-1 (HR 0.98, 95% CI 0.96-0.99; p = 0.003), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.97-0.99; p <0.001) also demonstrated superiority, with corresponding RMST increases of +0.7, +1.9, and +2.5 months, respectively. Conclusions Despite incremental advancements, a breakthrough in advanced BTC treatment remains elusive. Further improvements in treatment efficacy may require biomarker identification to optimize combinational therapies for better patient selection. Impact and implications This study analyzed recent RCTs, including KEYNOTE-966, TOPAZ-1, NIFE, and SWOG 1815, involving 4,584 patients with advanced biliary tract cancer. A meta-analysis of 17 treatment arms, using reconstructed survival data, confirmed the modest survival benefit of GemCis plus ICIs, supporting its guideline adoption. The findings, however, highlight the need for biomarker identification and better patient selection.
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Affiliation(s)
- Zhihao Li
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Daniel Aliseda
- HBP and Liver Transplant Unit, Clinica Universidad de Navarra, University of Navarra, Pamplona-Madrid, Spain
| | - Owen Jones
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Luckshi Rajendran
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Christian Magyar
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Robert Grant
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Grainne M. O’Kane
- Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Hospital, Toronto, ON, Canada
- Department of Medical Oncology, St Vincent’s University Hospital and University College Dublin, Dublin, Ireland
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Gonzalo Sapisochin
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- Division of Gastroenterology and Hepatology, University Health Network, Toronto, ON, Canada
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Yamada Y, Seto Y, Yoshikawa T, Takeuchi H, Kitagawa Y, Kodera Y, Doki Y, Yoshida K, Muro K, Kabeya Y, Kamada A, Nagashima K, Kumamaru H, Tachimori H, Sasako M, Katai H, Konno H, Kakeji Y. Postoperative adjuvant chemotherapy in patients with gastric cancer based on the Nationwide Gastric Cancer Registry in Japan. Glob Health Med 2025; 7:13-27. [PMID: 40026857 PMCID: PMC11866910 DOI: 10.35772/ghm.2024.01080] [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: 10/23/2024] [Revised: 01/06/2025] [Accepted: 01/14/2025] [Indexed: 03/05/2025]
Abstract
The nationwide registry of the Japanese Gastric Cancer Association contains data related to the efficacy of adjuvant chemotherapy and prognostic factors across this patient population; elderly patients with advanced resectable gastric cancer are especially prevalent. Here, we analyzed data from 34,931 patients, who were treated between 2011 and 2013 at 421 hospitals in Japan. Although adjuvant chemotherapy was effective overall, 75 years or older elderly patients had a worse prognosis compared to younger patients. The most administered adjuvant chemotherapy was S-1 monotherapy. Adjuvant S-1 monotherapy was also effective for patients with pT1N2, pT1N3, and pT3N0 stage II tumors, as well as patients with other stage II and III malignancies. Independent prognostic factors for poor overall and relapse-free survival in patients at both stage II and stage III were age 75 or older, male, preoperative Eastern Cooperative Oncology Group performance status (ECOG-PS) 1 or more, preoperative renal dysfunction, undifferentiated adenocarcinoma, undergoing total gastrectomy, open laparotomy, no adjuvant chemotherapy, D1 lymphadenectomy, residual tumor R1 or R2, and Clavien-Dindo classification grade II or higher. Age 75 or older, renal dysfunction, ECOG-PS 1 and total gastrectomy were also significant risk factors for postoperative complications and lower compliance with adjuvant chemotherapy. Our analysis also revealed that adjuvant chemotherapy after resection of cancer of gastric remnant and postoperative chemotherapy against CY1 gastric cancer were also effective. We conclude that adjuvant chemotherapy is effective for all stage II and III patients including age 75 or older gastric cancer patients, in addition to distal gastrectomy, proximal gastrectomy, and pylorus-preserving surgery to avoid total gastrectomy may improve surgical outcomes and quality of life for elderly patients.
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Affiliation(s)
- Yasuhide Yamada
- Department of Medical Research, National Center for Global Health and Medicine, Tokyo, Japan
| | | | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University, School of Medicine, Hamamatsu, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University, School of Medicine, Tokyo, Japan
| | | | | | | | - Kei Muro
- Department of Pharmacotherapy, Aichi Cancer Center, Nagoya, Japan
| | | | - Ami Kamada
- Healthcare & Life Sciences, IBM Japan, Ltd, Tokyo, Japan
| | - Kengo Nagashima
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Hiraku Kumamaru
- Department of Healthcare Quality Assessment, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Hisateru Tachimori
- Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan
| | | | | | - Hiroyuki Konno
- Hamamatsu University, School of Medicine, Hamamatsu, Japan
| | - Yoshihiro Kakeji
- Database Committee, The Japanese Society of Gastroenterological Surgery, Tokyo, Japan
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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Hayano K, Kurata Y, Matsumoto Y, Otsuka R, Sekino N, Toyozumi T, Nakano A, Shiraishi T, Uesato M, Ohira G, Matsubara H. Improvement of Oral Intake after Treatment Using Enteral Feeding Tube for Large Advanced Gastric Cancer Invading Proximal Stomach: A Case Series of 20 Patients. Surg Case Rep 2025; 11:24-0143. [PMID: 39991496 PMCID: PMC11842876 DOI: 10.70352/scrj.cr.24-0143] [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: 12/16/2024] [Accepted: 01/08/2025] [Indexed: 02/25/2025] Open
Abstract
INTRODUCTION Patients with large Stage IV gastric cancer (GC) invading the proximal stomach find it difficult to receive not only bypass surgery but also S-1-based chemotherapy. This study aimed to show our treatment results for those GC patients using elementary diet (ED) tubes, which enabled S-1-based chemotherapy and nutrition support. CASE PRESENTATION We evaluated 20 patients (13 men and 7 women; median age 70 years) with large Stage IV GCs (8.7-21.9 cm) invading the proximal stomach, who were admitted due to inability to eat, treated with S-1-based chemotherapy using an ED tube. The duration from the initiation of the chemotherapy to the improvement of oral intake, changes in nutritional status, and disease-specific survival (DSS) were retrospectively investigated. Two of the 20 patients failed to complete even one cycle of chemotherapy due to severe nausea or diarrhea. The other 18 patients improved oral liquid intake after 47.5 ± 18.8 days, and 17 patients improved oral solid food intake after 54.5 ± 19.6 days from the start of chemotherapy. In addition, three patients (16.7%) could receive conversion surgery after improvement of oral intake. The median DSS of those 18 patients was 13.1 months. Serum albumin level and prognostic nutritional index (PNI) were significantly improved after about 1 month of the treatment (both P <0.0001). Improvement of serum albumin level and PNI during the first 1 month of the treatment significantly correlated with better DSS (P = 0.006, 0.01, respectively). CONCLUSIONS Given a high oral intake success rate, S-1-based chemotherapy using an ED tube can be a promising treatment option for large Stage IV GC with poor oral intake.
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Affiliation(s)
- Koichi Hayano
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Yoshihiro Kurata
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Yasunori Matsumoto
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Ryota Otsuka
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Nobufumi Sekino
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Takeshi Toyozumi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Akira Nakano
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Tadashi Shiraishi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Masaya Uesato
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Gaku Ohira
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan
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Eom SS, Ryu KW, Han HS, Kong SH. A Comprehensive and Comparative Review of Global Gastric Cancer Treatment Guidelines: 2024 Update. J Gastric Cancer 2025; 25:153-176. [PMID: 39822173 PMCID: PMC11739642 DOI: 10.5230/jgc.2025.25.e10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 12/19/2024] [Accepted: 12/20/2024] [Indexed: 01/19/2025] Open
Abstract
Differences in demographics, medical expertise, and patient healthcare resources across countries have led to significant variations in guidelines. In light of these differences, in this review, we aimed to explore and compare the most recent updates to gastric cancer treatment from five guidelines that are available in English. These English-version guidelines, which have been recently published and updated for journal publication, include those published in South Korea in 2024, Japan in 2021, China in 2023, the United States in 2024, and Europe in 2024. The South Korean and Japanese guidelines provide a higher proportion of content to endoscopic and surgical treatments, reflecting their focus on minimally invasive techniques, function-preserving surgeries, and systemic therapy. The Chinese guidelines provide recommendations addressing not only surgical approaches but also perioperative chemotherapy and palliative systemic therapy. Meanwhile, in the United States and European guidelines, a higher proportion of the content is dedicated to perioperative and palliative systemic therapy, aligning with their approaches to advanced-stage disease management. All guidelines address surgical and systemic chemotherapy treatments; however, the proportion and emphasis of content vary based on the patient distribution and treatment approaches specific to each country. With emerging research findings on gastric cancer treatment worldwide, the national guidelines are being progressively revised and updated. Understanding the commonalities and differences among national guidelines, along with the underlying evidence, can provide valuable insights into the treatment of gastric cancer.
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Affiliation(s)
- Sang Soo Eom
- Department of Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Keun Won Ryu
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Hye Sook Han
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea.
| | - Seong-Ho Kong
- Department of Surgery, Seoul National University Hospital and Seoul National University College of Medicine Cancer Research Institute, Seoul, Korea.
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9
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Wang C, Lv T, Song Y, Fan Z. SOX chemotherapy is effective treatment for gastric cancer with liver metastases. Asian J Surg 2024:S1015-9584(24)02805-7. [PMID: 39668031 DOI: 10.1016/j.asjsur.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 12/02/2024] [Indexed: 12/14/2024] Open
Affiliation(s)
- Cong Wang
- Department of General Surgery, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, 116033, China
| | - Tingcong Lv
- Department of General Surgery, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, 116033, China
| | - Yongwei Song
- Department of General Surgery, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, 116033, China.
| | - Zhe Fan
- Department of General Surgery, The Third People's Hospital of Dalian, Dalian Medical University, Dalian, 116033, China.
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10
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Latimer NR, Taylor K, Hatswell AJ, Ho S, Okorogheye G, Chen C, Kim I, Borrill J, Bertwistle D. An Evaluation of an Algorithm for the Selection of Flexible Survival Models for Cancer Immunotherapies: Pass or Fail? PHARMACOECONOMICS 2024; 42:1395-1412. [PMID: 39302594 PMCID: PMC11564353 DOI: 10.1007/s40273-024-01429-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/12/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND AND OBJECTIVE Accurately extrapolating survival beyond trial follow-up is essential in a health technology assessment where model choice often substantially impacts estimates of clinical and cost effectiveness. Evidence suggests standard parametric models often provide poor fits to long-term data from immuno-oncology trials. Palmer et al. developed an algorithm to aid the selection of more flexible survival models for these interventions. We assess the usability of the algorithm, identify areas for improvement and evaluate whether it effectively identifies models capable of accurate extrapolation. METHODS We applied the Palmer algorithm to the CheckMate-649 trial, which investigated nivolumab plus chemotherapy versus chemotherapy alone in patients with gastroesophageal adenocarcinoma. We evaluated the algorithm's performance by comparing survival estimates from identified models using the 12-month data cut to survival observed in the 48-month data cut. RESULTS The Palmer algorithm offers a systematic procedure for model selection, encouraging detailed analyses and ensuring that crucial stages in the selection process are not overlooked. In our study, a range of models were identified as potentially appropriate for extrapolating survival, but only flexible parametric non-mixture cure models provided extrapolations that were plausible and accurately predicted subsequently observed survival. The algorithm could be improved with minor additions around the specification of hazard plots and setting out plausibility criteria. CONCLUSIONS The Palmer algorithm provides a systematic framework for identifying suitable survival models, and for defining plausibility criteria for extrapolation validity. Using the algorithm ensures that model selection is based on explicit justification and evidence, which could reduce discordance in health technology appraisals.
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Affiliation(s)
- Nicholas R Latimer
- Delta Hat Limited, Bramley House, Bramley Road, Nottingham, NG10 3SX, UK.
- University of Sheffield, Sheffield, UK.
| | - Kurt Taylor
- Delta Hat Limited, Bramley House, Bramley Road, Nottingham, NG10 3SX, UK
| | - Anthony J Hatswell
- Delta Hat Limited, Bramley House, Bramley Road, Nottingham, NG10 3SX, UK
- Department of Statistical Science, University College London, London, UK
| | - Sophia Ho
- Bristol Myers Squibb, Uxbridge, London, UK
| | | | - Clara Chen
- Bristol Myers Squibb, Lawrenceville, NJ, USA
| | - Inkyu Kim
- Bristol Myers Squibb, Lawrenceville, NJ, USA
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11
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Sun W, Li X. Surgical Resection Enhances Survival in Patients With Liver Metastases From Gastric Cancer: A Population-Based, Case-Control Study. Health Sci Rep 2024; 7:e70220. [PMID: 39669188 PMCID: PMC11635178 DOI: 10.1002/hsr2.70220] [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: 06/17/2024] [Revised: 10/25/2024] [Accepted: 11/04/2024] [Indexed: 12/14/2024] Open
Abstract
Background and Aims Gastric cancer with liver metastases (GCLM) is a challenging condition that significantly reduces long-term survival rates, but recent advancements in surgical techniques have shown promise. This study aims to comprehensively evaluate the impact of surgical resection on survival rates in GCLM patients. Methods We conducted a population-based analysis utilizing the SEER database for patients diagnosed with GCLM between 2010 and 2015. Overall survival (OS) was compared between patients who underwent cancer-directed surgery (CDS) and those who did not. The overlap weighting method based on lasso regression with penalty factors was employed to minimize selection bias. Survival outcomes were compared using Kaplan-Meier curves and Cox proportional hazards models, with subgroup analyses to further explore the effects of surgery among patients. Results A total of 3694 patients with GCLM were identified. Of those, 354 (9.58%) patients underwent CDS. After propensity score adjustment, The median OS was significantly higher in the surgical resection group (12 months, 95% confidence interval (CI) 11-16) compared to the nonresection group (6 months, 95% CI: 5-6). Cox regression analysis revealed a substantial improvement in OS for the surgical resection group, with a hazard ratio (HR) of 0.562 (95% CI: 0.482-0.656), including patients with adverse conditions. Conclusions The analysis demonstrated a clear association between surgical resection and enhanced OS in GCLM patients. Nevertheless, further research endeavors should be undertaken to identify specific prognostic factors that aid in the selection of optimal candidates for surgical resection.
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Affiliation(s)
- Wuhui Sun
- Department of Thyroid SurgerySecond Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
| | - Xiawei Li
- Department of SurgerySecond Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer InstituteSecond Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
- Cancer CenterZhejiang UniversityHangzhouChina
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12
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Fujitani K, Kurokawa Y, Wada R, Takeno A, Kawabata R, Omori T, Imamura H, Hirao M, Endo S, Kawada J, Moon JH, Takiguchi S, Mori M, Eguchi H, Doki Y. Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival. Eur J Cancer 2024; 213:115080. [PMID: 39461056 DOI: 10.1016/j.ejca.2024.115080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 10/08/2024] [Accepted: 10/15/2024] [Indexed: 10/29/2024]
Abstract
OBJECTIVE Potential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study. METHODS Patients with synchronous or metachronous LMGC received 2-4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis. RESULTS Seventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1-71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9-34.0) and 34.9 % (95 % CI 22.2-50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1-3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16-6.35), P = 0.022; pN1-3: HR 9.11 (95 % CI, 1.22-68.2), P = 0.031). CONCLUSION R0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. CLINICAL TRIAL REGISTRATION NUMBER UMIN 000011445 (https://www.umin.ac.jp/ctr/).
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Affiliation(s)
- Kazumasa Fujitani
- Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan.
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryohei Wada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Atsushi Takeno
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | | | - Takeshi Omori
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Hiroshi Imamura
- Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Motohiro Hirao
- Department of Surgery, Osaka National Hospital, Osaka, Japan
| | - Shunji Endo
- Department of Surgery, Higashi-Osaka Medical Center, Higashi-Osaka, Japan
| | - Junji Kawada
- Department of Surgery, Kaizuka Municipal Hospital, Kaizuka, Japan
| | - Jeong Ho Moon
- Department of Surgery, Osaka 2nd Police Hospital, Osaka, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medicine, Nagoya, Japan
| | - Masaki Mori
- Tokai University School of Medicine, Isehara, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
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13
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Kawazoe Y, Shimamoto K, Seki T, Tsuchiya M, Shinohara E, Yada S, Wakamiya S, Imai S, Hori S, Aramaki E. Post-marketing surveillance of anticancer drugs using natural language processing of electronic medical records. NPJ Digit Med 2024; 7:315. [PMID: 39521935 PMCID: PMC11550814 DOI: 10.1038/s41746-024-01323-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024] Open
Abstract
This study demonstrates that adverse events (AEs) extracted using natural language processing (NLP) from clinical texts reflect the known frequencies of AEs associated with anticancer drugs. Using data from 44,502 cancer patients at a single hospital, we identified cases prescribed anticancer drugs (platinum, PLT; taxane, TAX; pyrimidine, PYA) and compared them to non-treatment (NTx) group using propensity score matching. Over 365 days, AEs (peripheral neuropathy, PN; oral mucositis, OM; taste abnormality, TA; appetite loss, AL) were extracted from clinical text using an NLP tool. The hazard ratios (HRs) for the anticancer drugs were: PN, 1.15-1.95; OM, 3.11-3.85; TA, 3.48-4.71; and AL, 1.98-3.84; the HRs were significantly higher than that of the NTx group. Sensitivity analysis revealed that the HR for TA may have been underestimated; however, the remaining three types of AEs extracted from clinical text by NLP were consistently associated with the three anticancer drugs.
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Affiliation(s)
- Yoshimasa Kawazoe
- Artificial Intelligence and Digital Twin in Healthcare, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Kiminori Shimamoto
- Artificial Intelligence and Digital Twin in Healthcare, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomohisa Seki
- Department of Healthcare Information Management, The University of Tokyo Hospital, Tokyo, Japan
| | - Masami Tsuchiya
- Division of Drug Informatics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Emiko Shinohara
- Artificial Intelligence and Digital Twin in Healthcare, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shuntaro Yada
- Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan
| | - Shoko Wakamiya
- Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan
| | - Shungo Imai
- Division of Drug Informatics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Satoko Hori
- Division of Drug Informatics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Eiji Aramaki
- Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan
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14
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Boku N, Omori T, Shitara K, Sakuramoto S, Yamaguchi K, Kato K, Kadowaki S, Tsuji K, Ryu MH, Oh DY, Oh SC, Rha SY, Lee KW, Chung IJ, Sym SJ, Chen LT, Chen JS, Bai LY, Nakada T, Hagihara S, Makino R, Nishiyama E, Kang YK. Nivolumab plus chemotherapy in patients with HER2-negative, previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: 3-year follow-up of the ATTRACTION-4 randomized, double-blind, placebo-controlled, phase 3 trial. Gastric Cancer 2024; 27:1287-1301. [PMID: 39162872 PMCID: PMC11513732 DOI: 10.1007/s10120-024-01535-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 06/30/2024] [Indexed: 08/21/2024]
Abstract
BACKGROUND Nivolumab + chemotherapy is now a standard of care for HER2-negative, previously untreated, unresectable or recurrent gastric/gastroesophageal junction cancer (advanced gastric cancer), but long-term follow-up data of clinical trials are limited. METHODS ATTRACTON-4 was a phase 3, double-blind, placebo-controlled trial in Japan, South Korea, and Taiwan. Patients were randomized to either nivolumab or placebo, both combined with the physician's choice of SOX (oral S-1 [tegafur-gimeracil-oteracil potassium] + oxaliplatin) or CAPOX (capecitabine + oxaliplatin). We report the primary endpoints-centrally assessed progression-free survival (PFS) and overall survival (OS)-and landmark analyses of OS among patients alive using 3-year follow-up data. RESULTS At the cutoff date (May 10, 2021), 17/359 patients in the nivolumab + chemotherapy group and 6/358 in the placebo + chemotherapy group were continuing study treatment. PFS (centrally assessed) was longer in the nivolumab + chemotherapy group (median 10.94 vs. 8.48 months; hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.55-0.82). Although OS did not differ between the two groups (median 17.45 vs. 17.15 months; HR 0.89, 95% CI 0.75-1.05), the landmark analysis of OS, calculating HRs at each landmark time point (every month), was getting numerically better in the nivolumab + chemotherapy group over time. Approximately 80% of patients who achieved complete response in the nivolumab + chemotherapy group were alive at 3 years. No new safety signals or major late-onset select treatment-related adverse events were observed for nivolumab + chemotherapy. CONCLUSION This 3-year follow-up of ATTRACTION-4 confirmed the long-term clinical benefit and manageable safety of nivolumab + chemotherapy in patients with previously untreated advanced gastric cancer. TRIAL REGISTRATION NCT02746796.
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Affiliation(s)
- Narikazu Boku
- Department of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Takeshi Omori
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kohei Shitara
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | | | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Ken Kato
- Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Shigenori Kadowaki
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kunihiro Tsuji
- Department of Medical Oncology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Min-Hee Ryu
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Do-Youn Oh
- Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sang Cheul Oh
- Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, South Korea
| | - Sun Young Rha
- Division of Medical Oncology, Yonsei Cancer Center, Yonsei University Health System, Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Keun-Wook Lee
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Ik-Joo Chung
- Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University College of Medicine, Hwasun, South Korea
| | - Sun Jin Sym
- Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, and National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
- Kaohsiung Medical University Hospital, and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jen-Shi Chen
- Division of Hematology and Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan
| | - Li-Yuan Bai
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, and China Medical University, Taichung, Taiwan
| | - Takashi Nakada
- Department of Oncology Clinical Development Planning, Ono Pharmaceutical Co., Ltd., Osaka, Japan
| | - Shunsuke Hagihara
- Department of Statistical Analysis, Ono Pharmaceutical Co., Ltd., Osaka, Japan
| | - Reina Makino
- Department of Medical Affairs, Ono Pharmaceutical Co., Ltd., Osaka, Japan
| | - Eiji Nishiyama
- Department of Medical Affairs, Ono Pharmaceutical Co., Ltd., Osaka, Japan
| | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro, 43-gil, Songpa-gu, Seoul, 05505, South Korea.
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15
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Ichikawa H, Aizawa M, Kano Y, Hanyu T, Muneoka Y, Hiroi S, Ueki H, Moro K, Hirose Y, Miura K, Shimada Y, Sakata J, Yabusaki H, Nakagawa S, Kawasaki T, Okuda S, Wakai T. Landscape of homologous recombination deficiency in gastric cancer and clinical implications for first-line chemotherapy. Gastric Cancer 2024; 27:1273-1286. [PMID: 39110344 DOI: 10.1007/s10120-024-01542-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 07/25/2024] [Indexed: 10/29/2024]
Abstract
BACKGROUND Homologous recombination deficiency (HRD) is one of the crucial hallmarks of cancer. It is associated with a favorable response to platinum-based chemotherapy. We explored the distinctive clinicopathological features of gastric cancer (GC) with HRD and the clinical significance of HRD in platinum-based first-line chemotherapy for unresectable metastatic GC. METHODS We enrolled 160 patients with GC in this study. Their tumor samples were subjected to genomic profiling utilizing targeted tumor sequencing. HRD was defined as the presence of alterations in any of 16 HR genes (BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, PARP1, POLD1, RAD50, RAD51, RAD51C, RAD51D, WRN, and XRCC2). The clinicopathological features and treatment outcomes of first-line chemotherapy for unresectable metastatic GC were compared between HRD and non-HRD groups. RESULTS Forty-seven patients (29.4%) were classified into the HRD group. This group had a significantly lower proportion of macroscopic type 3 or 4 tumors and higher TMB than the non-HRD group. Among patients who underwent platinum-based first-line chemotherapy, the HRD group had a greater response rate and longer progression-free survival after treatment (median 8.0 months vs. 3.0 months, P = 0.010), with an adjusted hazard ratio of 0.337 (95% confidence interval 0.151-0.753). HRD status was not associated with treatment outcomes in patients who did not undergo platinum-based chemotherapy. CONCLUSIONS Low proportion of macroscopic type 3 or 4 tumors and a high TMB are distinctive features of GC with HRD. HRD status is a potential predictive marker in platinum-based first-line chemotherapy for unresectable metastatic GC.
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Affiliation(s)
- Hiroshi Ichikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan.
| | - Masaki Aizawa
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata City, Niigata, 951-8566, Japan
| | - Yosuke Kano
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Takaaki Hanyu
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Yusuke Muneoka
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Sou Hiroi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Hiroto Ueki
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Kazuki Moro
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Yuki Hirose
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Kohei Miura
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Yoshifumi Shimada
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Hiroshi Yabusaki
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata City, Niigata, 951-8566, Japan
| | - Satoru Nakagawa
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata City, Niigata, 951-8566, Japan
| | - Takashi Kawasaki
- Department of Pathology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata City, Niigata, 951-8566, Japan
| | - Shujiro Okuda
- Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-dori, Chuo-ku, Niigata City, Niigata, 951-8514, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
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Chalkoo M, Bhat MY, Wani YH. Impact of liver metastasis on immunotherapy in gastric carcinoma. World J Gastrointest Surg 2024; 16:3084-3086. [PMID: 39575288 PMCID: PMC11577416 DOI: 10.4240/wjgs.v16.i10.3084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/24/2024] [Accepted: 06/28/2024] [Indexed: 09/27/2024] Open
Abstract
The editorial discusses the impact of liver metastasis on immunotherapy efficacy in gastric cancer (GC) patients. Liver metastasis can hinder the effectiveness of immunotherapy by altering the immune microenvironment, leading to systemic loss of T-cells and reduced treatment response. Studies suggest that liver metastases serve as a negative baseline factor for immunotherapy efficacy, resulting in poorer progression-free survival and objective response rates. Strategies such as liver-mediated radiotherapy may help improve treatment outcomes by reshaping the liver's immune microenvironment and reducing T-cell depletion. Understanding the complex interplay between liver metastasis and immunotherapy response is crucial for optimising patient care in GC.
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Affiliation(s)
- Mushtaq Chalkoo
- Department of Surgery, Government Medical College, Srinagar 190014, Jammu and Kashmir, India
| | - Mohd Yaqoob Bhat
- Department of General Surgery, Government Medical College Srinagar, Srinagar 190010, Jammu and Kashmir, India
| | - Yaser Hussain Wani
- Post Graduate Department of Minimal Access and General Surgery, Government Medical College Srinagar, Srinagar 190010, Jammu and Kashmīr, India
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Yang Y, Wang Z, Xin D, Guan L, Yue B, Zhang Q, Wang F. Analysis of the treatment efficacy and prognostic factors of PD-1/PD-L1 inhibitors for advanced gastric or gastroesophageal junction cancer: a multicenter, retrospective clinical study. Front Immunol 2024; 15:1468342. [PMID: 39512347 PMCID: PMC11540680 DOI: 10.3389/fimmu.2024.1468342] [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: 07/21/2024] [Accepted: 10/08/2024] [Indexed: 11/15/2024] Open
Abstract
Introduction Immune checkpoint inhibitors (ICIs) have transformed advanced gastric cancer treatment, yet patient responses vary, highlighting the need for effective biomarkers. Common markers, such as programmed cell death ligand-1 (PD-L1), microsatellite instability/mismatch repair (MSI/MMR), tumor mutational burden, tumor-infiltrating lymphocytes, and Epstein-Barr virus, face sampling challenges and high costs. This study seeks practical, minimally invasive biomarkers to enhance patient selection and improve outcomes. Methods This multicenter retrospective study analyzed 617 patients with advanced gastric or gastroesophageal junction cancer treated with programmed cell death protein-1 (PD-1)/PD-L1 inhibitors from January 2019 to March 2023. Clinical data and peripheral blood marker data were collected before and after treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included the objective response rate (ORR) and disease control rate (DCR). Least absolute shrinkage and selection operator (LASSO)-Cox and LASSO logistic regression analyses identified independent factors for OS, PFS, and ORR. Predictive nomograms were validated using receiver operating characteristic (ROC) curves, areas under the curve (AUCs), C-indices, and calibration curves, with clinical utility assessed via decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results OS-related factors included treatment line, T stage, ascites, pretreatment indirect bilirubin (pre-IBIL), posttreatment CA125, CA199, CA724, and the PLR. PFS-related factors included treatment lines, T stage, metastatic sites, pre-IBIL, posttreatment globulin (GLOB), CA125, and CA199 changes. ORR-related factors included treatment line, T stage, N stage, liver metastasis, pretreatment red cell distribution width-to-platelet ratio (RPR), CA125, and CA724 changes. The nomograms showed strong predictive performance and clinical utility. Conclusions Early treatment, lower T stage, the absence of ascites, and lower pre-IBIL, post-CA125, CA199, CA724, and PLR correlate with better OS. Factors for improved PFS include early treatment, lower T stage, fewer metastatic sites, and lower pre-IBIL, post-GLOB, and post-CA125 levels. Nomogram models can help identify patients who may benefit from immunotherapy, providing valuable clinical guidance.
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Affiliation(s)
- Yuanyuan Yang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhe Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Clinical Medicine, The First Clinical Medical College, Zhengzhou University, Zhengzhou, China
| | - Dao Xin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lulu Guan
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bingtong Yue
- Department of Clinical Medicine, The First Clinical Medical College, Zhengzhou University, Zhengzhou, China
| | - Qifan Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Clinical Medicine, The First Clinical Medical College, Zhengzhou University, Zhengzhou, China
| | - Feng Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Chronic Disease Prevention and Therapy & Intelligent Health Management, Zhengzhou, China
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18
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Nishina T, Boku N, Kurokawa Y, Sasaki K, Machida R, Yoshikawa T. A real-world survey on expensive drugs used as first-line chemotherapy in patients with HER2-negative unresectable advanced/recurrent gastric cancer in the stomach cancer study group of the Japan clinical oncology group. Jpn J Clin Oncol 2024; 54:1100-1106. [PMID: 39180720 DOI: 10.1093/jjco/hyae104] [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: 04/17/2024] [Accepted: 08/08/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND Molecular-targeted drugs and immune checkpoint inhibitors have been developed for various malignant diseases, thereby improving clinical outcomes. However, these drugs are expensive, and few studies have assessed their actual use and costs in Japan. This study aimed to survey the use and costs of first-line chemotherapy for advanced/recurrent gastric cancer (AGC) in real-world settings. METHODS The survey included patients with human epidermal growth factor receptor type2 (HER2)-negative AGC who initiated first-line chemotherapy from January 2022 to December 2022 at the participating 92 institutions in the Japan Clinical Oncology Group. Data on the regimens were collected using Google Forms. A regimen that costs >500 000 Japanese yen (JPY) per month was defined as expensive. RESULTS Data on chemotherapy regimens were collected from 2173 patients at all 92 institutions between March 2023 and May 2023. We analyzed 2113 patients who underwent the chemotherapy with recommended regimens and conditionally recommended regimens according to the Japanese Gastric Cancer Treatment Guidelines sixth edition. The expensive regimens were triplet chemotherapy with fluoropyrimidine (S-1 or capecitabine or 5-fluorouracil/levofolinate), oxaliplatin, and nivolumab. Their monthly costs ranged from 767 648 to 771 046 JPY. Nivolumab-containing regimens cost more than 20 times the price of conventional chemotherapy with fluoropyrimidine and oxaliplatin. These regimens were used in 1416 (67%) of 2113 patients: in 71% of patients aged ≤74 years and in 59% of patients aged ≥75 years. CONCLUSION The regimens with >20-fold cost of conventional chemotherapy were used as first-line chemotherapy in two-thirds of patients and more than half even in the elderly population with HER2-negative AGC. This finding is important for future health economic studies on drug cost-efficacy.
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Affiliation(s)
- Tomohiro Nishina
- Department of Gastrointestinal Medical Oncology, NHO Shikoku Cancer Center, Ehime, Japan
| | - Narikazu Boku
- Department of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Keita Sasaki
- Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Ryunosuke Machida
- Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
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Tsai HJ, Yang SH, Hsiao CF, Kao HF, Su YY, Shan YS, Yen CJ, Du JS, Hsu C, Wu IC, Chen LT. A phase 1 study of biweekly nab-paclitaxel/oxaliplatin/S-1/LV for advanced upper gastrointestinal cancers: TCOG T1216 study. Oncologist 2024; 29:e1396-e1405. [PMID: 38902994 PMCID: PMC11449045 DOI: 10.1093/oncolo/oyae109] [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: 09/29/2023] [Accepted: 04/19/2024] [Indexed: 06/22/2024] Open
Abstract
BACKGROUND Oxaliplatin- and fluoropyrimidine-based triplet regimens have demonstrated feasibility and efficacy in the treatment of upper gastrointestinal (UGI) cancers. Herein, we evaluate the feasibility and preliminary efficacy of biweekly nab-paclitaxel plus oxaliplatin and S-1/leucovorin (SOLAR) in chemonaïve UGI cancers. METHODS A 3 + 3 phase 1 study was conducted to determine the maximal tolerated dose (MTD) of oxaliplatin in SOLAR (nab-paclitaxel [150 mg/m2 in D1], oxaliplatin [60, 75, or 85 mg/m2 in D1], and oral S-1/leucovorin [35 mg/m2 and 30 mg bid from D1 to D7]). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Thirteen and 6 accruals were in the dose-escalation and MTD expansion cohorts, respectively. One of 6 patients at level III experienced dose-limiting toxicity (grade 3 diarrhea), which revealed that the MTD of oxaliplatin was 85 mg/m2. After a mean of 15.9 cycles of treatment, the most common treatment-related grade 3/4 toxicities were neutropenia (57.9%) and diarrhea (21.1%). The ORR was 63.2%. The median PFS and OS were 12.5 and 24.7 months, respectively. CONCLUSION The current study revealed the MTD of oxaliplatin and demonstrated the preliminary efficacy of SOLAR in UGI cancers, which deserves further investigation. CLINICALTRIALS.GOV IDENTIFIER NCT03162510.
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Affiliation(s)
- Hui-Jen Tsai
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shih-Hung Yang
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chin-Fu Hsiao
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
| | - Hsiang-Fong Kao
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- National Taiwan University Cancer Center, Taipei, Taiwan
| | - Yung-Yeh Su
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yan-Shen Shan
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Jui Yen
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jeng-Shiun Du
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chiun Hsu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - I-Chen Wu
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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20
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Zhang Z, Wu C, Liu N, Wang Z, Pan Z, Jiang Y, Tian J, Sun M. Modified Banxiaxiexin decoction benefitted chemotherapy in treating gastric cancer by regulating multiple targets and pathways. JOURNAL OF ETHNOPHARMACOLOGY 2024; 331:118277. [PMID: 38697407 DOI: 10.1016/j.jep.2024.118277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 04/19/2024] [Accepted: 04/29/2024] [Indexed: 05/05/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chemotherapy tolerance weakened efficacy of chemotherapy drugs in the treating gastric cancer (GC). Banxiaxiexin decoction (BXXXD) was widely used in digestive diseases for thousands of years in Traditional Chinese medicine (TCM). In order to better treat GC, three other herbs were added to BXXXD to create a new prescription named Modified Banxiaxiexin decoction (MBXXXD). Although MBXXXD potentially treated GC by improving chemotherapy tolerance, the possible mechanisms were still unknown. AIM OF THE STUDY To explore the therapeutic effect of MBXXXD on GC patients and explore the possible anti-cancer mechanism. MATERIALS AND METHODS A randomized controlled trial (n = 146) was conducted to evaluate the clinical efficacy between MBXXXD + chemotherapy (n = 73) and placebo + chemotherapy (n = 73) in GC patients by testing overall survival, progression free survival, clinical symptoms, quality of life score, tumor markers, T cell subpopulation, and adverse reactions. Network pharmacology was conducted to discover the potential mechanism of MBXXXD in treating GC. Metabolic activity assay, cell clone colony formation and mitochondrial apoptosis were detected in human GC cell lines including AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD. Multiple pathways including P53, AKT, IκB, P65, P38, ERK, JNK p-AKT, p-P65, p-P38, p-ERK and p-JNK in AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy were also detected. RESULTS MBXXXD + chemotherapy promoted overall survival and progression free survival, improved clinical symptoms and quality of life score, increased T4 lymphocyte ratio and T8 lymphocyte ratio as well as T4/T8 lymphocyte ratio, and alleviated adverse reactions in GC patients. Network pharmacology predicted multiple targets and pathways of MBXXXD in treating GC including apoptosis, P53 pathway, AKT pathway, MAPK pathway. MBXXXD inhibited cell viability, decreased cell clone colony formation, and promoted mitochondrial apoptosis by producing reactive oxygen species (ROS), promoting mitochondrial permeability transition pore (MPTP) and the cleavage of pro-caspase-3 and pro-caspase-9, and decreasing mito-tracker red Chloromethyl-X-rosamine (CMXRos) in AGS cell, KNM-45 cell and SGC7901 cell. MBXXXD up-regulated the expression of P53 and IκB, and down-regulated the expression of p-AKT, p-P65, p-P38, p-ERK, p-JNK, AKT, P65, P38, ERK and JNK AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy. CONCLUSION MBXXXD benefitted chemotherapy for GC by regulating multiple targets and pathways.
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Affiliation(s)
- Zhipeng Zhang
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, 200071, China; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Chao Wu
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Ningning Liu
- Department of Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Cancer Institute of Integrative Medicine, Shanghai, 201203, China; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Ziyuan Wang
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Pathology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Ziyang Pan
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Yulang Jiang
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Jianhui Tian
- Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, 200071, China; Clinical Oncology Center, Shanghai Municipal Hospital of TCM, Shanghai University of TCM, Shanghai, 200071, China; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Mingyu Sun
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
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21
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Chu Y, He X, Xue Y, Jiang H, Zhu C, Qi C, Zhang X, Chen D, Dai H, Xian Q, Zhu W. An exploratory clinical study of β-glucan combined with camrelizumab and SOX chemotherapy as first-line treatment for advanced gastric adenocarcinoma. Front Immunol 2024; 15:1448485. [PMID: 39253086 PMCID: PMC11381272 DOI: 10.3389/fimmu.2024.1448485] [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: 06/13/2024] [Accepted: 08/07/2024] [Indexed: 09/11/2024] Open
Abstract
Background β-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. We aimed to evaluate the efficacy and safety of β-glucan plus immunotherapy and chemotherapy in the first-line treatment of advanced gastric adenocarcinoma. Methods This is a phase IB, prospective, single-arm, investigator-initiated trail. Advanced gastric adenocarcinoma patients received β-glucan, camrelizumab, oxaliplatin, oral S-1 every 3 weeks. The curative effect was evaluated every 2 cycles. The primary endpoints were objective response rate (ORR) and safety, with secondary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). The exploratory endpoint explored biomarkers of response to treatment efficacy. Results A total of 30 patients had been enrolled, including 20 (66.7%) males and all patients with an ECOG PS score of ≥1. The ORR was 60%, the mPFS was 10.4 months (95% confidence interval [CI], 9.52-11.27), the mOS was 14.0 months (95% CI, 11.09-16.91). A total of 19 patients (63.3%) had TRAEs, with 9 patients (30%) with grade ≥ 3. The most common TRAEs were nausea (53.3%). After 2 cycles of treatment, the levels of IL-2, IFN-γ and CD4+ T cells significantly increased (P < 0.05). Furthermore, biomarker analysis indicated that patient with better response and longer OS exhibited lower GZMA expression at baseline serum. Conclusions This preliminary study demonstrates that β-glucan plus camrelizumab and SOX chemotherapy offers favorable efficacy and a manageable safety profile in patients with advanced gastric adenocarcinoma, and further studies are needed to verify its efficacy and safety. Clinical Trial Registration Chinese Clinical Trials Registry, identifier ChiCTR2100044088.
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Affiliation(s)
- Yunqian Chu
- Department of Oncology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Xuan He
- West China Hospital, Sichuan University, Chengdu, China
| | - Ya Xue
- Department of Oncology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Hua Jiang
- Department of Oncology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Chan Zhu
- Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China
| | - Chunjian Qi
- Medical Research Center, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Xing Zhang
- Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China
| | - Dongsheng Chen
- Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China
| | - Hanjue Dai
- Department of Oncology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Qingying Xian
- Department of Oncology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Wenyu Zhu
- Department of Oncology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China
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22
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Lim SH, Kim MJ, Lee J, Lim HY, Kang WK, Kim ST. The Impact of Pembrolizumab as a Salvage Therapy Based on HER2 Expression in Advanced Gastric Cancer. Cancers (Basel) 2024; 16:2969. [PMID: 39272827 PMCID: PMC11393848 DOI: 10.3390/cancers16172969] [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: 06/22/2024] [Revised: 08/22/2024] [Accepted: 08/23/2024] [Indexed: 09/15/2024] Open
Abstract
Immune checkpoint inhibitors (ICIs) are used as salvage treatments for advanced gastric cancer (AGC) regardless of HER2 status. This study assessed the efficacy of ICIs based on HER2 expression in AGC patients who received pembrolizumab as salvage monotherapy at Samsung Medical Center from November 2017 to March 2023. HER2 status was determined via immunohistochemistry, and tumor response and survival outcomes were compared accordingly. Among the 113 patients analyzed, with a median age of 61 years and 64.6% being male, 12 patients (10.6%) were HER2-positive, and 101 patients (89.4%) were HER2-negative. Of 92 evaluable patients, none had a complete response. However, 50% of HER2-positive patients had a partial response, compared to 4.9% of HER2-negative patients (p < 0.001). The disease control rate was 70% in HER2-positive and 37.8% in HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). Pembrolizumab as a salvage chemotherapy for the treatment of AGC demonstrated superior effectiveness in HER2-positive patients compared with HER2-negative patients.
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Affiliation(s)
- Sung Hee Lim
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Min Jung Kim
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Jeeyun Lee
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Ho Yeong Lim
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Won Ki Kang
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Seung Tae Kim
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
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23
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Suto H, Inui Y, Okamura A. Long-term survival of a patient with gastric cancer with bone marrow metastasis receiving S-1 plus oxaliplatin beyond three years: a case report and literature review. Front Oncol 2024; 14:1449212. [PMID: 39165681 PMCID: PMC11333263 DOI: 10.3389/fonc.2024.1449212] [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: 06/14/2024] [Accepted: 07/22/2024] [Indexed: 08/22/2024] Open
Abstract
Background Bone marrow metastasis (BMM) of gastric cancer (GC), which is the most common cause of disseminated intravascular coagulation (DIC) among solid tumors, has a poor prognosis. Studies on prognostic improvement beyond one year in patients with GC with BMM are limited. This is the first report of a patient who survived over three years after 30 months of S-1 plus oxaliplatin (SOX) therapy for GC with BMM. Case Report The patient was a 72-year-old woman who presented with anemia and high levels of alkaline phosphatase (ALP) and carbohydrate antigen 19-9 (CA19-9). Detailed examination led to the diagnosis with BMM of GC uncomplicated by DIC and the SOX regimen was initiated in November 2018. After six cycles, she was switched to S-1 monotherapy, and both ALP and CA19-9 levels reached normal by November 2019. However, computed tomography in April 2021 showed multiple bone metastases. Therefore, she was switched to paclitaxel-based therapy. In November 2021, the patient was further switched to nivolumab monotherapy, but she succumbed due to DIC in March 2022. Conclusion GCs with BMM are prone to DIC, and the SOX regimen, which includes S-1 with efficacy against micrometastases, may constitute a safe and effective treatment modality.
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Affiliation(s)
- Hirotaka Suto
- Department of Medical Oncology, Hyogo Cancer Center, Hyogo, Japan
- Department of Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
| | - Yumiko Inui
- Department of Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
| | - Atsuo Okamura
- Department of Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
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24
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Naher SK, Mercieca-Bebber R, Siu D, Stockler MR, Kiely BE, Grimison P. Estimating survival scenarios in advanced or metastatic gastric and oesophageal adenocarcinoma: a systematic review of randomized-controlled trials. Curr Med Res Opin 2024; 40:1357-1367. [PMID: 38961804 DOI: 10.1080/03007995.2024.2376129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 06/24/2024] [Accepted: 07/01/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUND We aimed to summarize survival data from RCTs in patients with GO adenocarcinoma; estimate and explain worst-, typical-, and best-case-scenarios of survival time; and determine if simple multiples of median overall survival (mOS) could estimate these percentiles. METHODS We systematically searched RCTs of systemic therapies for GO adenocarcinoma published 2000-2022. The following key percentiles were extracted from overall survival curves: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). We tested if these percentiles could be estimated by simple multiples of mOS: 0.25 of the median for the 90th percentile, 0.5 for the 75th, 2 for the 25th, and 3 for the 10th. RESULTS We identified 44 trials (22,447 participants). For first line chemotherapy and immunotherapy combined (CI) trials (n = 3) worst-to-best case survival time ranged from 4 months to not reached, compared to 3-30 months for other trials (n = 27) and 1-23 months for subsequent lines (n = 14). Simple multiples of mOS accurately estimated the following survival percentiles: 90th (n = 3/3 trials), 75th (n = 3/3), and 25th (n = 2/3) in first line CI trials. In other first line trials, the mOS accurately estimated the 90th survival percentile in n = 22/27 trials, 75th percentile in n = 26/27, 25th percentile in 27/27 trials, and 10th percentile in 22/27 trials. Simple multiples of the mOS accurately predicted the 90th, 75th, 25th, and 10th survival percentiles in the majority of trials of second and subsequent lines apart from chemotherapy and immunotherapy only trials. CONCLUSION We provide realistic, evidence-based prognostic information as scenarios for survival time which can inform clinical decision-making. Simple multiples of the mOS accurately estimated the percentiles for most groups.
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Affiliation(s)
- Sayeda K Naher
- National Health and Medical Research Council (NHMRC) Clinical Trials Centre (CTC), University of Sydney, Camperdown, NSW, Australia
- Illawarra and Shoalhaven Local Health District, Warrawong, NSW, Australia
| | - Rebecca Mercieca-Bebber
- National Health and Medical Research Council (NHMRC) Clinical Trials Centre (CTC), University of Sydney, Camperdown, NSW, Australia
| | - Derrick Siu
- National Health and Medical Research Council (NHMRC) Clinical Trials Centre (CTC), University of Sydney, Camperdown, NSW, Australia
| | - Martin R Stockler
- National Health and Medical Research Council (NHMRC) Clinical Trials Centre (CTC), University of Sydney, Camperdown, NSW, Australia
| | - Belinda E Kiely
- National Health and Medical Research Council (NHMRC) Clinical Trials Centre (CTC), University of Sydney, Camperdown, NSW, Australia
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Mao C, He Y, Xu N, Yan H, Zhang N, Cheng G, Jiang H, Chen M, Chen Y, Wang X, Gu Y, Shen P, Zhang G, Yan J, Yang Z, Ding L, Han Z, Wang Z, Zhang J, Zheng W, Wang J, Qin S. A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer. Immun Inflamm Dis 2024; 12:e1348. [PMID: 39105572 PMCID: PMC11301656 DOI: 10.1002/iid3.1348] [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: 01/08/2024] [Revised: 06/12/2024] [Accepted: 07/06/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND Mecapegfilgrastim, a long-acting granulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. OBJECTIVE We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. METHOD Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. RESULTS The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. CONCLUSION In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.
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Affiliation(s)
- Chenyu Mao
- Department of Medical Oncology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouChina
| | - Ye He
- Department of Medical Oncology, Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐sen UniversityGuangzhouChina
| | - Nong Xu
- Department of Medical Oncology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouChina
| | - Haijiao Yan
- Department of OncologyThe First People's Hospital of ChangzhouChangzhouChina
| | - Ningling Zhang
- Department of OncologyAffiliated Hospital of North Sichuan Medical CollegeNanchongChina
| | - Gang Cheng
- Department of OncologyBozhou People's HospitalBozhouChina
| | - Hua Jiang
- Department of OncologyThe Second People's Hospital of ChangzhoChangzhouChina
| | - Minbin Chen
- Department of OncologyThe First People's Hospital of KunshanKunshanChina
| | - Yong Chen
- Department of Radiology, The First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Xiaoguang Wang
- Department of Hepatobiliary and Pancreatic SurgeryThe Second Hospital of JiaxingJiaxingChina
| | - Yulan Gu
- Department of OncologyChangshu No 2 People's HospitalChangshuChina
| | - Peng Shen
- Department of Medical Oncology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouChina
| | - Guifang Zhang
- Department of Medical OncologyXinxiang Central HospitalXinxiangChina
| | - Jun Yan
- Department of OncologyThe Central Hospital of JiadingShanghaiChina
| | - Zhe Yang
- Department of RadiologyShandong Provincial HospitalJinanChina
| | - Lifang Ding
- Department of OncologyThe People's Hospital of DanyangDanyangChina
| | - Zhengxiang Han
- Depatment of Integrated Traditional Chinese and Western MedicineThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina
| | - Zhanggui Wang
- Department of RadiologyThe Second People's Hospital of Anhui ProvinceHefeiChina
| | - Junqi Zhang
- Department of OncologyThe Central Hospital of BazhongBazhongChina
| | - Weie Zheng
- Department of Medical OncologyThe People's Hospital of Rui'anRui'anChina
| | - Jufeng Wang
- Depatment of GastroenterologyHenan Cancer HospitalZhengzhouChina
| | - Shukui Qin
- Chief of HospitalNanjing Tianyinshan HospitalNanjingChina
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Cai J, Tan X, Hu Q, Pan H, Zhao M, Guo C, Zeng J, Ma X, Zhao Y. Flavonoids and Gastric Cancer Therapy: From Signaling Pathway to Therapeutic Significance. Drug Des Devel Ther 2024; 18:3233-3253. [PMID: 39081701 PMCID: PMC11287762 DOI: 10.2147/dddt.s466470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 07/01/2024] [Indexed: 08/02/2024] Open
Abstract
Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances and develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink and other databases to find the relevant literature in the last two decades. Using "gastric cancer", "stomach cancers", "flavonoid", "bioflavonoid", "2-Phenyl-Chromene" as keywords, were searched, then analyzed and summarized the mechanism of flavonoids in the treatment of GC. It was revealed that the anti-tumor mechanism of flavonoids involves inhibiting tumor growth, proliferation, invasion, and metastasis, as well as inducing cell death through various processes such as apoptosis, autophagy, ferroptosis, and pyroptosis. Additionally, combining flavonoids with other chemotherapeutic agents like 5-FU and platinum compounds can potentially reduce chemoresistance. Flavonoids have also demonstrated enhanced biological activity when used in combination with other natural products. Consequently, this review proposes innovative perspectives for the development of flavonoids as new anti-GC agents.
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Affiliation(s)
- Jiaying Cai
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Xiyue Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Qichao Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Huafeng Pan
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Maoyuan Zhao
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Cui Guo
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Jinhao Zeng
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Yanling Zhao
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, People’s Republic of China
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Okuno K, Watanabe S, Hur H, Lee J, Park JO, Tokunaga M, Tanabe M, Kinugasa Y, Goel A. An exosome-based liquid biopsy signature for therapeutic response prediction in metastatic gastric cancer. Clin Transl Med 2024; 14:e1629. [PMID: 39031975 PMCID: PMC11259598 DOI: 10.1002/ctm2.1629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/26/2024] [Accepted: 02/28/2024] [Indexed: 07/22/2024] Open
Affiliation(s)
- Keisuke Okuno
- Department of Molecular Diagnostics and Experimental TherapeuticsBeckman Research Institute of City of HopeBiomedical Research CenterMonroviaCaliforniaUSA
- Department of Gastrointestinal SurgeryTokyo Medical and Dental UniversityTokyoJapan
| | - Shuichi Watanabe
- Department of Hepatobiliary and Pancreatic SurgeryTokyo Medical and Dental UniversityTokyoJapan
| | - Hoon Hur
- Department of SurgeryAjou University School of MedicineSuwonSouth Korea
| | - Jeeyun Lee
- Division of Hematology‐OncologyDepartment of MedicineSamsung Medical CenterSeoulSouth Korea
| | - Joon Oh Park
- Division of Hematology‐OncologyDepartment of MedicineSamsung Medical CenterSeoulSouth Korea
| | - Masanori Tokunaga
- Department of Gastrointestinal SurgeryTokyo Medical and Dental UniversityTokyoJapan
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic SurgeryTokyo Medical and Dental UniversityTokyoJapan
| | - Yusuke Kinugasa
- Department of Gastrointestinal SurgeryTokyo Medical and Dental UniversityTokyoJapan
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental TherapeuticsBeckman Research Institute of City of HopeBiomedical Research CenterMonroviaCaliforniaUSA
- City of Hope Comprehensive Cancer CenterDuarteCaliforniaUSA
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28
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Fujise Y, Hazama S, Fujii T, Inoue M, Takahashi S, Yoshida K, Ikeda A, Hashiyada H, Nakamoto K, Yamashita A, Hino K, Okita K. Rectal squamous cell carcinoma treated with neoadjuvant fluorouracil, oxaliplatin, cetuximab, and radiation: A case report of pathological complete response. Medicine (Baltimore) 2024; 103:e38627. [PMID: 38905362 PMCID: PMC11191886 DOI: 10.1097/md.0000000000038627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 05/29/2024] [Indexed: 06/23/2024] Open
Abstract
RATIONALE Treatment strategies for rectal squamous cell carcinoma (rSCC) are yet to be established, given its rarity. Although squamous cell carcinoma has been reported to be highly sensitive to cetuximab and radiation, there is no report of combination therapy of cetuximab and radiation for rSCC. In this study, we firstly reported a case of rSCC in which a complete response was achieved with the original chemoradiotherapy comprising oxaliplatin, S-1, cetuximab, and simultaneous radiation. PATIENT CONCERNS A 46-year-old women presented to our hospital with lower abdominal pain and fatigue. DIAGNOSES Based on tumor marker analyses, histological examination of biopsy specimens, and comprehensive imaging, the patient was diagnosed with rSCC. INTERVENTIONS Neoadjuvant chemoradiotherapy (50.4 Gy) was administered in 28 fractions, along with concurrent chemotherapy comprising SOX (S-1: 80 mg/m2, days 1-5 and 8-12, oxaliplatin: 85 mg/m2, day 1) and cetuximab (400 mg/m2, day 1, 250 mg/m2, after day 8). OUTCOMES Five weeks after chemoradiation, the patient underwent laparoscopic partial intersphincteric resection, achieving a complete pathological response. LESSONS This case firstly highlights the usefulness of SOX plus cetuximab combined with radiation in the treatment of locally advanced rSCC. However, a large-scale study is required to establish safe and effective treatment regimens.
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Affiliation(s)
- Yuta Fujise
- Department of Surgery, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Shoichi Hazama
- Department of Surgery, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Toshiyuki Fujii
- Department of Surgery, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Motoshige Inoue
- Department of Internal Medicine, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | | | - Kazuya Yoshida
- Department of Surgery, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Akihiko Ikeda
- Department of Surgery, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Hiroshi Hashiyada
- Department of Surgery, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Kembu Nakamoto
- Department of Surgery, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Aogu Yamashita
- Department of Internal Medicine, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Keisuke Hino
- Department of Internal Medicine, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Kiwamu Okita
- Department of Internal Medicine, Gastroenterological Center, Shunan Memorial Hospital, Kudamatsu, Japan
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29
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Yamada E, Iwasaki K, Barroga E, Sakurai T, Enomoto M, Shimoda Y, Mazaki J, Kuwabara H, Hoshino A, Hayashi Y, Ishizaki T, Nagakawa Y. Clinical complete response after trastuzumab deruxtecan 6th-line treatment for postoperative gastric cancer recurrence: a case report. Surg Case Rep 2024; 10:149. [PMID: 38886285 PMCID: PMC11182999 DOI: 10.1186/s40792-024-01954-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 06/13/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND Despite the recent developments in the treatment of advanced or recurrent gastric cancer, the median survival time remains shorter than 15 months. Herein, we report a case of postoperative gastric cancer recurrence in which a complete clinical response was achieved with trastuzumab deruxtecan as 6th-line treatment. CASE PRESENTATION A 70-year-old man underwent abdominal contrast-enhanced computed tomography (CT) during follow-up after rectal cancer surgery. The CT revealed an enlarged perigastric lymph node. After further examination, the patient's condition was diagnosed as gastric cancer cT2N1H0P0M0 cStage IIA. The patient underwent distal gastrectomy and D2 lymph node dissection. The resulting pathological diagnosis was pT1bN3aH0P0 pStageIIB, HER2 score 3+. Abdominal contrast-enhanced CT 19 months postoperatively revealed para-aortic lymph node recurrence, thus systemic chemotherapy courses were planned. The primary treatment was a combination of S-1, cisplatin, and trastuzumab administered in 11 courses. However, there was an enlargement of the para-aortic lymph node which was evaluated as progressive disease. Systematic chemotherapy with various regimens was continued until the 5th-line treatment. However, therapeutic benefits were not achieved and lung metastasis was observed. Trastuzumab deruxtecan (TDXD) was initiated as 6th-line treatment. Abdominal contrast-enhanced CT at 4 months after the start of treatment showed marked shrinkage of the enlarged para-aortic lymph node and disappearance of the lung metastasis in the right upper lung lobe, which was evaluated as partial response (PR). The para-aortic lymph node metastasis was evaluated as PR with only a slight accumulation of SUV-Max 2.66 with a shrinking trend by positron emission tomography-computed tomography (PET-CT) performed after 1 year. Tumor markers CEA, CA19-9, and CA125 also improved significantly. PET-CT after 1 year and 4 months showed no lymph node enlargement or accumulation, indicating a complete response (CR). All tumor markers also normalized. The patient has maintained clinical CR without additional treatment to date. CONCLUSIONS We report the apparent first case of postoperative gastric cancer recurrence successfully treated with TDXD, achieving clinical CR with TDXD as a 6th-line treatment.
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Affiliation(s)
- Erika Yamada
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Kenichi Iwasaki
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan.
| | - Edward Barroga
- Medical English Education Center, Showa University School of Medicine, Tokyo, Japan
| | - Toru Sakurai
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Masaya Enomoto
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Yota Shimoda
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Junichi Mazaki
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Hiroshi Kuwabara
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Akihiro Hoshino
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Yutaka Hayashi
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Tetsuo Ishizaki
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Yuichi Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
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Kawai J, Yasufuku I, Fukada M, Asai R, Sato Y, Tajima YJ, Saigo C, Kiyama S, Makiyama A, Tanaka Y, Okumura N, Murase K, Miyazaki T, Matsuhashi N. Successful R0 resection after chemotherapy, including nivolumab, for gastric cancer with liver metastases: three case reports. Surg Case Rep 2024; 10:138. [PMID: 38837046 PMCID: PMC11153382 DOI: 10.1186/s40792-024-01929-3] [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: 03/22/2024] [Accepted: 05/10/2024] [Indexed: 06/06/2024] Open
Abstract
BACKGROUND Advances in chemotherapy have increased clinical experience with conversion surgery for inoperable advanced gastric cancer. This report describes three patients with unresectable gastric cancer accompanied by multiple liver metastases. In all three patients, nivolumab resolved the liver metastases and subsequent conversion surgery achieved a pathological complete response. CASE PRESENTATION In Case 1, a 68-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX plus nivolumab. The patient completed 13 cycles; however, only nivolumab was continued for 3 cycles because of adverse events. Distal gastrectomy and partial hepatic resection were performed because of a significant reduction in the size of the liver metastases as observed on magnetic resonance imaging (MRI). In Case 2, a 72-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX. Because of the subsequent emergence of new liver metastases, the patient transitioned to ramucirumab plus paclitaxel as second-line therapy. Third-line therapy with nivolumab was initiated because of side effects. MRI revealed necrosis within the liver metastasis, and the patient underwent proximal gastrectomy and partial hepatectomy. In Case 3, a 51-year-old woman with clinical Stage IVB gastric cancer accompanied by multiple metastases of the liver and para-aortic lymph nodes began first-line therapy with SOX plus nivolumab. The patient completed 10 cycles; however, only nivolumab was continued for 5 cycles because of adverse events. Computed tomography showed a significant decrease in the size of the para-aortic lymph nodes, while MRI indicated the presence of a singular liver metastasis. Distal gastrectomy and partial hepatic resection were subsequently performed. In all three cases, MRI revealed the presence of liver metastases; however, pathological examination showed no viable tumor cells. CONCLUSIONS We herein present three cases in which chemotherapy, including nivolumab, elicited a response in patients with multiple unresectable liver metastases, ultimately culminating in R0 resection through conversion surgery. Although MRI showed liver metastases, pathological analysis revealed no cancer, underscoring the beneficial impact of chemotherapy.
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Affiliation(s)
- Junpei Kawai
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Itaru Yasufuku
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Masahiro Fukada
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Ryuichi Asai
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Yuta Sato
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Yu Jesse Tajima
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Chiemi Saigo
- Department of Pathology, Gifu University Hospital, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Shigeru Kiyama
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Akitaka Makiyama
- Cancer Center, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Yoshihiro Tanaka
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Naoki Okumura
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Katsutoshi Murase
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Tatsuhiko Miyazaki
- Department of Pathology, Gifu University Hospital, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Nobuhisa Matsuhashi
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
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Sakoh T, Eto K, Iwagami S, Yoshida N, Kosumi K, Iwatsuki M, Baba Y, Miyamoto Y, Yoshii D, Baba H. Conversion surgery for stage IV gastric cancer with multiple liver metastases with a complete pathological response to S-1 plus oxaliplatin therapy. Clin J Gastroenterol 2024; 17:419-424. [PMID: 38466470 DOI: 10.1007/s12328-024-01933-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 01/29/2024] [Indexed: 03/13/2024]
Abstract
Although patients with stage IV gastric cancer who respond well to systemic chemotherapy can be treated with gastrectomy, the prognosis of patients with multiple liver metastases is poor. We herein describe a patient with stage IV gastric cancer with multiple liver metastases who underwent conversion surgery after systemic treatment with S-1 plus oxaliplatin. The patient was a 62-year-old man. Upper gastrointestinal endoscopy revealed a 30-mm type 2 tumor in the greater curvature of the stomach at the anterior wall, and biopsy revealed a poorly differentiated adenocarcinoma. Imaging showed three suspected liver metastases in liver segment S8. The patient was judged to have gastric cancer, cStage IV (cT3N1M1(H)), and systemic chemotherapy was administered. He was treated with a total of six courses of chemotherapy. After re-evaluation, the primary tumor had shrunk significantly, and liver metastases could not be detected. Confirming no signs of seeding by laparoscopy, robot-assisted pylorus-preserving gastrectomy with D2 dissection and laparoscopic partial hepatic (S8) resection were performed. The patient was diagnosed with a complete pathological response. Conversion surgery is an option for stage IV gastric cancer when distant metastases are controlled with chemotherapy and when R0 resection is possible.
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Affiliation(s)
- Teruki Sakoh
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Kojiro Eto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Shiro Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Keisuke Kosumi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Daiki Yoshii
- Department of Diagnostic Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
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Nakayama H, Ida T, Hasegawa Y, Sakamoto A, Umezawa Y, Inaba Y, Nakada H. Stage IV gastric adenocarcinoma with enteroblastic differentiation with 5-year relapse-free survival after D2 gastrectomy and chemotherapy: A case report. Surg Case Rep 2024; 10:123. [PMID: 38744791 PMCID: PMC11093955 DOI: 10.1186/s40792-024-01921-x] [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: 01/26/2024] [Accepted: 05/06/2024] [Indexed: 05/16/2024] Open
Abstract
BACKGROUND Gastric adenocarcinoma with enteroblastic differentiation (GACED), a rare subtype of gastric cancer, is associated with a more aggressive behavior than conventional gastric adenocarcinomas. We report a rare case of stage IV GACED treated with D2 gastrectomy and postoperative chemotherapy. CASE PRESENTATION A 39-year-old woman with acute upper abdominal pain immediately underwent surgery for gastric perforation. Afterward she was diagnosed with adenocarcinoma of the pylorus. D2 gastrectomy was performed and the final pathological diagnosis was stage IV GACED with positive peritoneal cytology. Postoperative chemotherapy was initiated with S1 plus oxaliplatin for 1 year, which was ceased thereafter to enhance her quality of life. The patient survived more than 5 years without relapse after gastrectomy. CONCLUSIONS Stage IV GACED, determined by positive spalt-like transcription factor 4, can be successfully treated with surgery and chemotherapy.
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Affiliation(s)
- Hiroshi Nakayama
- Department of Gastroenterological Surgery, Digestive Disease Center, NHO Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-shi, Tokyo, 204-8431, Japan.
- Department of Surgery, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan.
| | - Tomonori Ida
- Department of Gastroenterology, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
| | - Yui Hasegawa
- Department of Surgery, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
| | - Atsuhiko Sakamoto
- Department of Pathology and Laboratory Medicine, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
| | - Yoko Umezawa
- Department of Pathology and Laboratory Medicine, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
- Department of Pathology, Fukushima Medical University Hospital, 1 Hikariga-Oka, Fukushima, 960-1295, Japan
| | - Yuki Inaba
- Department of Surgery, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
| | - Hiroshi Nakada
- Department of Gastroenterological Surgery, Digestive Disease Center, NHO Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-shi, Tokyo, 204-8431, Japan
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Makinoya M, Miyatani K, Matsumi Y, Sakano Y, Shimizu S, Shishido Y, Hanaki T, Kihara K, Matsunaga T, Yamamoto M, Tokuyasu N, Takano S, Sakamoto T, Hasegawa T, Saito H, Nakayama Y, Osaki M, Okada F, Fujiwara Y. Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis. Sci Rep 2024; 14:10075. [PMID: 38698201 PMCID: PMC11065888 DOI: 10.1038/s41598-024-60967-x] [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: 12/25/2023] [Accepted: 04/29/2024] [Indexed: 05/05/2024] Open
Abstract
Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IPnon-respond group) exhibited resistance to PTX compared with exosomes from responding patients (IPrespond group) (p = 0.002). A comprehensive search for exo-miRNAs indicated that miR-493 was significantly up-regulated in exosomes from the IPnon-respond group compared with those collected from the IPrespond group. The expression of miR-493 in PTX-resistant MKN45 cells (MKN45PTX-res) was higher compared with that in MKN45. In addition, MKN45PTX-res cells exhibited lower MAD2L1 gene and protein expression compared with MKN45. Finally, miR-493 enhancement by transfection of miR-493 mimics significantly down-regulated MAD2L1 expression in MKN45 cells and reduced PTX sensitivity. Our results suggest that intra-peritoneal exo-miR-493 is involved in chemoresistance to PTX by downregulating MAD2L1 in GC with PM. Exo-miR-493 may be a biomarker for chemoresistance and prognosis of GC patients with PM and may also be a promising therapeutic target.
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Affiliation(s)
- Masahiro Makinoya
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Kozo Miyatani
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
| | - Yoshiaki Matsumi
- Division of Chemical Biology, Technical Department, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Yu Sakano
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Shota Shimizu
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Yuji Shishido
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Takehiko Hanaki
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Kyoichi Kihara
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Tomoyuki Matsunaga
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Manabu Yamamoto
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Naruo Tokuyasu
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Shuichi Takano
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Teruhisa Sakamoto
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Toshimichi Hasegawa
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Hiroaki Saito
- Department of Surgery, Japanese Red Cross Tottori Hospital, Tottori, 680‑8517, Japan
| | - Yuji Nakayama
- Division of Radioisotope Science, Research Initiative Center, Organization for Research Initiative and Promotion, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Mitsuhiko Osaki
- Division of Experimental Pathology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
- Chromosomal Engineering Research Center, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Futoshi Okada
- Division of Experimental Pathology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
- Chromosomal Engineering Research Center, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Yoshiyuki Fujiwara
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan
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Jiang Z, Xie Y, Zhang W, Du C, Zhong Y, Zhu Y, Jiang L, Dou L, Shao K, Sun Y, Xue Q, Tian Y, Gao S, Zhao D, Zhou A. Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for the treatment of locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): an open-label, randomized, phase 2 clinical trial. Gastric Cancer 2024; 27:571-579. [PMID: 38457083 PMCID: PMC11016518 DOI: 10.1007/s10120-024-01471-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 01/20/2024] [Indexed: 03/09/2024]
Abstract
BACKGROUND It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients. METHODS Patients with cT3-4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR). RESULTS From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX. CONCLUSIONS Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.
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Affiliation(s)
- Zhichao Jiang
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, No. 17, Panjiayuannanli Street, Chaoyang District, Beijing, 100021, China
| | - Yibin Xie
- Department of Pancreatic and Gastric Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Wen Zhang
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, No. 17, Panjiayuannanli Street, Chaoyang District, Beijing, 100021, China
| | - Chunxia Du
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, No. 17, Panjiayuannanli Street, Chaoyang District, Beijing, 100021, China
| | - Yuxin Zhong
- Department of Pancreatic and Gastric Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yuelu Zhu
- Department of Pathology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Liming Jiang
- Department of Imaging Diagnosis, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Lizhou Dou
- Department of Endoscopy, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Kang Shao
- Department of Thoracic Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yongkun Sun
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, No. 17, Panjiayuannanli Street, Chaoyang District, Beijing, 100021, China
| | - Qi Xue
- Department of Thoracic Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yantao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Shugeng Gao
- Department of Thoracic Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Dongbing Zhao
- Department of Pancreatic and Gastric Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Aiping Zhou
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, No. 17, Panjiayuannanli Street, Chaoyang District, Beijing, 100021, China.
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Fabbi M, Bali CD, Lianos GD, Rausei S. Treatment of Gastric Cancer Means Surgery, but Not Surgery Alone. Cancers (Basel) 2024; 16:1601. [PMID: 38672682 PMCID: PMC11049502 DOI: 10.3390/cancers16081601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 04/19/2024] [Indexed: 04/28/2024] Open
Abstract
Despite numerous studies, gastric cancer (GC) still presents a high mortality rate in Eastern and Western countries, increasing attention for new therapeutic strategies [...].
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Affiliation(s)
- Manrica Fabbi
- Department of General Surgery, Cittiglio-Angera Hospital, ASST Settelaghi, 21033 Varese, Italy;
| | - Christina D. Bali
- Department of Surgery, University Hospital of Ioannina, 45332 Ioannina, Greece; (C.D.B.); (G.D.L.)
| | - Georgios D. Lianos
- Department of Surgery, University Hospital of Ioannina, 45332 Ioannina, Greece; (C.D.B.); (G.D.L.)
| | - Stefano Rausei
- Department of General Surgery, Cittiglio-Angera Hospital, ASST Settelaghi, 21033 Varese, Italy;
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36
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Kuang ZY, Sun QH, Cao LC, Ma XY, Wang JX, Liu KX, Li J. Efficacy and safety of perioperative therapy for locally resectable gastric cancer: A network meta-analysis of randomized clinical trials. World J Gastrointest Oncol 2024; 16:1046-1058. [PMID: 38577462 PMCID: PMC10989386 DOI: 10.4251/wjgo.v16.i3.1046] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 01/14/2024] [Accepted: 02/04/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death. AIM To determine the optimal perioperative treatment regimen for patients with locally resectable GC. METHODS A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy. RESULTS Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen. CONCLUSION This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.
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Affiliation(s)
- Zi-Yu Kuang
- Graduate College, Beijing University of Traditional Chinese Medicine, Beijing 100029, China
| | - Qian-Hui Sun
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Lu-Chang Cao
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Xin-Yi Ma
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Jia-Xi Wang
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ke-Xin Liu
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Jie Li
- Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Yamada Y, Nagashima K, Azuma M, Masutani M, Ichikawa H, Iwasa S, Takahashi N, Hirano H, Kanato K, Machida N, Kinoshita T, Hata H, Kawakami H, Takahari D, Boku N, Kurokawa Y, Terashima M, Yoshikawa T, Sekine S, Hiraoka N. Predictive and prognostic value of excision repair cross-complementing group 1 in patients with advanced gastric cancer. BJC REPORTS 2024; 2:18. [PMID: 39516666 PMCID: PMC11523942 DOI: 10.1038/s44276-024-00046-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 01/29/2024] [Accepted: 01/31/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND To define the optimal chemotherapy regimen for each patient we therefore used tissue from patients to identify molecular prognostic or predictive biomarkers. METHODS Endoscopic biopsy specimens from primary lesions and surgical specimens on a phase III trial in patients with unresectable advanced or recurrent gastric cancer treated with docetaxel with cisplatin plus S-1 (DCS) or cisplatin plus S-1 (CS), were collected. We measured the mRNA expression of ERCC1 and analyzed SNPs in GSTP1 and ERCC1. RESULTS Low ERCC1 expression was associated with favorable prognosis for overall survival, OS by multivariable analysis (P = 0.001). There were significant interactions between the two treatment arms of DCS and CS, and ERCC1 mRNA expression. In patients with low ERCC1 expression of a favorable prognosis, DCS therapy was inferior to CS (P = 0.046). In addition to GSTP1 rs1695 (HR 1.728), ERCC1 rs3212980, ERCC1 rs2298881, ERCC1 rs3212964 with high expression of ERCC1 mRNA were associated with significantly worse prognosis with regard to OS. CONCLUSIONS ERCC1 mRNA is an independent prognostic factor and predictive marker that can be used to guide the addition of docetaxel. The SNPs of ERCC1 and GSTP1 could be also prognostic or predictive factors.
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Grants
- NCGM Intramural Reasearch Fund, 20A1014 National Center for Global Health and Medicine
- NCGM Intramural Reasearch Fund, 20A1014 National Center for Global Health and Medicine
- NCGM Intramural Reasearch Fund, 20A1014 National Center for Global Health and Medicine
- NCGM Intramural Reasearch Fund, 20A1014 National Center for Global Health and Medicine
- NCGM Intramural Reasearch Fund, 20A1014 National Center for Global Health and Medicine
- NCGM Intramural Reasearch Fund, 20A1014 National Center for Global Health and Medicine
- NCGM Intramural Reasearch Fund, 20A1014 National Center for Global Health and Medicine
- NCGM Intramural Reasearch Fund, 20A1014 National Center for Global Health and Medicine
- National Cancer Research and Development Fund, 2020-J-3, 2023-J-03 National Cancer Center Japan
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Affiliation(s)
- Yasuhide Yamada
- Department of Medical Research, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.
| | - Kengo Nagashima
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, 160-8582, Japan
| | - Mizutomo Azuma
- Department of Gastroenterology, Kitasato University Hospital, Sagamihara, 252-0329, Japan
| | - Mitsuko Masutani
- Molecular & Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School, Nagasaki, 852-8521, Japan
| | - Hitoshi Ichikawa
- Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, 104-0045, Japan
| | - Satoru Iwasa
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Naoki Takahashi
- Department of Gastroenterology, Saitama Cancer Center, Saitama, 362-0806, Japan
| | - Hidekazu Hirano
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Keisuke Kanato
- JCOG Data Center/ Operations Office, National Cancer Center, Tokyo, 104-0045, Japan
| | - Nozomu Machida
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, 241-8515, Japan
| | - Takahiro Kinoshita
- Department Gastric Surgery, National Cancer Center Hospital East, Chiba, 241-8515, Japan
| | - Hiroaki Hata
- Department of Surgery, Kyoto Medical Center, Kyoto, 612-0861, Japan
| | - Hisato Kawakami
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, 577-8502, Japan
| | - Daisuke Takahari
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of JFCR, Tokyo, 135-8550, Japan
| | - Narikazu Boku
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan
| | - Masanori Terashima
- Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Shigeki Sekine
- Department of Pathology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Nobuyoshi Hiraoka
- Department of Pathology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
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Hirase Y, Arigami T, Kawasaki Y, Matsushita D, Shimonosono M, Tsuruda Y, Sasaki K, Yamasaki Y, Hagihara T, Noma H, Higashi M, Kurahara H, Ohtsuka T. Successful subtotal gastrectomy and hepatectomy for HER2-positive gastric cancer with liver metastasis after trastuzumab-based chemotherapy: a case report. Surg Case Rep 2024; 10:51. [PMID: 38438775 PMCID: PMC10912058 DOI: 10.1186/s40792-024-01852-7] [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: 01/22/2024] [Accepted: 02/25/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND Conversion surgery (CS) after chemotherapy is weakly recommended as a promising tool for improving prognoses in patients with unresectable gastric cancer. Moreover, several investigators have demonstrated the clinical efficacy of subtotal gastrectomy (sTG) with a small remnant stomach for the nutritional status and surgical outcome compared with total gastrectomy. Here, we report a patient with liver metastasis from human epidermal growth factor receptor 2 (HER2)-positive gastric cancer who underwent sTG and hepatectomy after trastuzumab-based chemotherapy. CASE PRESENTATION An 84-year-old male patient was diagnosed with HER2-positive gastric cancer with a single liver metastasis. He was treated with eight courses of trastuzumab in combination with S-1 and oxaliplatin as first-line chemotherapy. The primary tumor and liver metastasis shrank significantly. The metastatic liver lesion's reduction rate was 65%. According to the Response Evaluation Criteria in Solid Tumors, the patient had a partial response. Therefore, he underwent an sTG with D2 lymphadenectomy and partial hepatectomy of segment 2. Histopathological examination revealed a grade 3 histological response without lymph node metastases from the primary tumor. No viable cancer cells were observed in the resected liver specimens. The patient received adjuvant chemotherapy with S-1. The postoperative quality of life (QOL) evaluated using the Postgastrectomy Syndrome Assessment Scale-45 was maintained, and the patient was still alive 8 months after the CS without recurrence. CONCLUSIONS An sTG with a small remnant stomach might be clinically useful for preventing a decline in QOL and improving prognoses in patients with stage IV gastric cancer after chemotherapy.
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Affiliation(s)
- Yuki Hirase
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Takaaki Arigami
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
| | - Yota Kawasaki
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Daisuke Matsushita
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Masataka Shimonosono
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Yusuke Tsuruda
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Ken Sasaki
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Yoichi Yamasaki
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | | | - Hidetoshi Noma
- Department of Surgery, Terada Hospital, Kagoshima, Japan
| | - Michiyo Higashi
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Hiroshi Kurahara
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Takao Ohtsuka
- Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
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Saito M, Suzuki K, Tamaki S, Kimura Y, Abe I, Endo Y, Watanabe F, Rikiyama T. Efficacy of ramucirumab and subsequent nivolumab therapy in patients with advanced gastric cancer: A retrospective study. Mol Clin Oncol 2024; 20:17. [PMID: 38292013 PMCID: PMC10823313 DOI: 10.3892/mco.2024.2715] [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: 07/21/2023] [Accepted: 11/21/2023] [Indexed: 02/01/2024] Open
Abstract
Nivolumab monotherapy is a standard treatment of metastatic gastric cancer, and this type of cancer involves vascular endothelial growth factor (VEGF) signaling in the tumor immunological environment. The subgroup analysis of the ATTRACTION-2 trial revealed that prior treatment with ramucirumab (RAM), a VEGF inhibitor, affected the therapeutic effect of nivolumab. The present retrospective study aimed to review patients with metastatic gastric cancer who were treated with paclitaxel (PTX) and RAM followed by nivolumab. A total of 29 patients with metastatic gastric cancer were treated with PTX + RAM as second-line treatment, followed by nivolumab monotherapy as third-line treatment. The therapeutic efficacy of nivolumab was compared in 13 patients with progression-free survival (PFS) of <5 months and 16 patients with PFS ≥5 months after PTX + RAM therapy. The present study included 22 male and seven female patients, with a median age of 68 years (range, 45-82 years). Human epidermal growth factor receptor 2 positivity was observed in six patients. The disease control rate was 62.1%. The PFS and overall survival (OS) were 4.4 and 11.9 months, respectively. Patients with PFS ≥5 months after PTX + RAM therapy showed better outcome in both PFS (5.3 months vs. 2.8 months, P=0.039) and OS (6.9 months vs. 15.2 months, P=0.066) after nivolumab treatment than patients with PFS of <5 months after PTX + RAM therapy. However, no significant relationship was observed between the outcome of first-line treatment and nivolumab. The therapeutic effect of nivolumab was associated with prior PTX + RAM treatment in advanced gastric cancer.
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Affiliation(s)
- Masaaki Saito
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Koichi Suzuki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Sawako Tamaki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Yasuaki Kimura
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Iku Abe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Yuhei Endo
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Fumiaki Watanabe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Toshiki Rikiyama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
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Kurokawa Y, Doki Y, Kitabayashi R, Yoshikawa T, Nomura T, Tsuji K, Goto M, Cho H, Hihara J, Hiki N, Nunobe S, Mizusawa J, Boku N, Terashima M. Short-term outcomes of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (JCOG1704). Gastric Cancer 2024; 27:366-374. [PMID: 38180622 PMCID: PMC10896774 DOI: 10.1007/s10120-023-01453-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 11/19/2023] [Indexed: 01/06/2024]
Abstract
BACKGROUND The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. METHODS Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), and S-1 (80-120 mg/body, days 1-14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. RESULTS Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. CONCLUSIONS Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.
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Affiliation(s)
- Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Ryo Kitabayashi
- Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takashi Nomura
- Department of Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan
| | - Kunihiro Tsuji
- Department of Medical Oncology, Ishikawa Prefectural Chuo Hospital, Kanazawa, Japan
| | - Masahiro Goto
- Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan
| | - Haruhiko Cho
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Jun Hihara
- Department of Surgery, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Naoki Hiki
- Department of Upper Gastrointestinal Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Junki Mizusawa
- Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Narikazu Boku
- Department of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan
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Pichioni P, Kokkinovasilis D, Stylianou S, Kipouridis G, Kalogeropoulos A, Al Mogrampi S. Multiple Muscle Metastases as the First Presentation of Gastric Cancer: A Case Report and Review of Literature. Cureus 2024; 16:e55458. [PMID: 38571840 PMCID: PMC10988182 DOI: 10.7759/cureus.55458] [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] [Accepted: 03/03/2024] [Indexed: 04/05/2024] Open
Abstract
The presence of an abdominal wall mass may serve as the initial presentation of an unknown gastric malignancy. The invasion of the abdominal wall and the occurrence of multiple skeletal muscle metastases originating from gastric cancer are exceedingly uncommon. We present a case of a 45-year-old female patient exhibiting widespread abdominal wall infiltration and skeletal muscle metastases derived from gastric cancer. The primary presentation included a distressing diffuse abdominal mass in the left upper and lower quadrants. Abdominal computed tomography revealed extensive swelling of multiple skeletal muscles within the abdominal wall, raising suspicions of gastric malignancy. Biopsies of the affected muscles, along with upper gastrointestinal tract endoscopy and colonoscopy, were performed. The upper endoscopy examination unveiled a poorly differentiated diffuse-type gastric adenocarcinoma, while the subsequent muscle biopsy confirmed infiltration by the recently diagnosed malignancy. At this stage of the disease, systemic chemotherapy was deemed the optimal choice for our patient. Subsequent abdominal computed tomography showed a decrease in the dimensions of the abdominal wall and other skeletal muscle lesions. Seventeen months after the initial diagnosis, our patient continues to be alive. Additionally, we provide a comprehensive review of the existing literature on similar reported cases of gastric cancer patients with concurrent muscle metastases.
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Affiliation(s)
- Polyxeni Pichioni
- Department of Surgery, General Hospital of Imathia, Naousa Health Unit, Naousa, GRC
| | | | - Stylianos Stylianou
- Department of Surgery, General Hospital of Imathia, Naousa Health Unit, Naousa, GRC
| | - Georgios Kipouridis
- Department of Surgery, General Hospital of Imathia, Naousa Health Unit, Naousa, GRC
| | | | - Saant Al Mogrampi
- Department of Surgery, General Hospital of Imathia, Naousa Health Unit, Naousa, GRC
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Matsunaga T, Satio H, Sakano Y, Makinoya M, Shimizu S, Shishido Y, Miyatani K, Hanaki T, Kihara K, Yamamoto M, Tokuyasu N, Takano S, Sakamoto T, Hasegawa T, Fujiwara Y. Prognostic significance of the cachexia index in patients with unresectable advanced gastric cancer receiving palliative chemotherapy: a retrospective single-center study. Surg Today 2024; 54:231-239. [PMID: 37526733 DOI: 10.1007/s00595-023-02721-w] [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: 04/21/2023] [Accepted: 06/13/2023] [Indexed: 08/02/2023]
Abstract
PURPOSE To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). METHODS The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. RESULTS The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors. CONCLUSIONS Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment.
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Affiliation(s)
- Tomoyuki Matsunaga
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan.
| | - Hiroaki Satio
- Department of Surgery, Japanese Red Cross Tottori Hospital, 117 Shotoku-Cho, Tottori, 680-8517, Japan
| | - Yu Sakano
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Masahiro Makinoya
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Shota Shimizu
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Yuji Shishido
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Kozo Miyatani
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Takehiko Hanaki
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Kyoichi Kihara
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Manabu Yamamoto
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Naruo Tokuyasu
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Shuichi Takano
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Teruhisa Sakamoto
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Toshimichi Hasegawa
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Yoshiyuki Fujiwara
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
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Zhang J, Wang L, Zhang S, Cao R, Zhao Y, Zhao Y, Song Y, Guo Z. Alpha-fetoprotein predicts the treatment efficacy of immune checkpoint inhibitors for gastric cancer patients. BMC Cancer 2024; 24:266. [PMID: 38408930 PMCID: PMC10895833 DOI: 10.1186/s12885-024-11999-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 02/13/2024] [Indexed: 02/28/2024] Open
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) are commonly used in conjunction with chemotherapy to improve treatment outcomes for patients with gastric cancer. Since AFP could influence immunity by both inhibiting natural killer (NK) cells and regulating negatively the function of dendritic cells, we evaluated the influence of baseline serum alpha-fetoprotein (AFP) levels on the curative effect of ICIs in advanced gastric cancer (AGC) patients. METHODS A retrospective analysis was conducted on 158 AGC patients who underwent ICI treatment. The patients were divided into high and low groups based on the AFP threshold of 20 ng/ml. The efficacy of ICI treatment was assessed using objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS The higher levels of baseline AFP were found to be associated with a decrease in the effectiveness of ICIs, as evidenced by a DCR of 50.0% in the group with high AFP levels compared to 87.7% in the group with low AFP levels (P < 0.001). Further analysis using Kaplan-Meier survival techniques indicated that a high AFP level was linked to shorter progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) in AGC individuals receiving ICIs. After propensity score matching, a log rank test revealed that the high AFP group had a decrease in median PFS (P = 0.011) and median OS (P = 0.036) compared to the low AFP group. The high AFP levels also showed its association with shorter PFS and OS in the subgroup analysis of ICI plus chemotherapy patients. CONCLUSIONS Baseline AFP levels may predict immune checkpoint inhibitor treatment efficacy in AGC patients.
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Affiliation(s)
- Jingjing Zhang
- Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, 050011, Shijiazhuang, Hebei, P.R. China
| | - Lei Wang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, 050011, Shijiazhuang, Hebei, P.R. China
| | - Shasha Zhang
- Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, 050011, Shijiazhuang, Hebei, P.R. China
| | - Ruijie Cao
- Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, 050011, Shijiazhuang, Hebei, P.R. China
| | - Yufei Zhao
- Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, 050011, Shijiazhuang, Hebei, P.R. China
| | - Yue Zhao
- Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, 050011, Shijiazhuang, Hebei, P.R. China
| | - Yanrong Song
- Department of Medical Technology, Xingtai Medical College, 054000, Xingtai, Hebei, P.R. China
| | - Zhanjun Guo
- Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, 050011, Shijiazhuang, Hebei, P.R. China.
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Ueda A, Yuki S, Ando T, Hosokawa A, Nakada N, Kito Y, Motoo I, Ito K, Sakumura M, Nakayama Y, Ueda Y, Kajiura S, Nakashima K, Harada K, Kawamoto Y, Komatsu Y, Yasuda I. CA125 Kinetics as a Potential Biomarker for Peritoneal Metastasis Progression following Taxane-Plus-Ramucirumab Administration in Patients with Advanced Gastric Cancer. Cancers (Basel) 2024; 16:871. [PMID: 38473233 DOI: 10.3390/cancers16050871] [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: 01/06/2024] [Revised: 02/12/2024] [Accepted: 02/20/2024] [Indexed: 03/14/2024] Open
Abstract
Currently, no established marker exists for predicting peritoneal metastasis progression during chemotherapy, although they are major interruptive factors in sequential chemotherapy in patients with advanced gastric cancer (AGC). This multicenter retrospective study was conducted from June 2015 to July 2019, analyzing 73 patients with AGC who underwent taxane-plus-ramucirumab (TAX/RAM) therapy and had their serum carbohydrate antigen 125 (CA125) concentrations measured. Of 31 patients with elevated CA125 levels above a cutoff of 35 U/mL, 25 (80.6%) had peritoneal metastasis. The CA125 concentrations before TAX/RAM treatment were associated with ascites burden. The overall survival was significantly shorter in the CA125-elevated group. CA125 kinetics, measured at a median of 28 days after chemotherapy, were associated with the ascites response (complete or partial response: -1.86%/day; stable disease: 0.28%/day; progressive disease: 2.33%/day). Progression-free survival in the CA125-increased group, defined by an increase of 0.0067%/day using receiver operating characteristic curve analysis, was significantly poorer among patients with peritoneal metastases. In conclusion, this study highlights that CA125 kinetics can serve as an early predictor for the progression of peritoneal metastasis during TAX/RAM treatment.
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Affiliation(s)
- Akira Ueda
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Satoshi Yuki
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Kita14, Nishi 5, Kita-ku, Sapporo 060-8648, Japan
| | - Takayuki Ando
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Ayumu Hosokawa
- Department of Clinical Oncology, University of Miyazaki Hospital, 5200 Kihara, Kiyotake-cho, Miyazaki 889-1692, Japan
| | - Naokatsu Nakada
- Department of Internal Medicine, Itoigawa Sogo Hospital, 457-1 Takegahana, Itoigawa 941-8502, Japan
| | - Yosuke Kito
- Department of Medical Oncology, Ishikawa Prefectural Central Hospital, 2-1 Kuratuki Higashi, Kanazawa 920-8530, Japan
| | - Iori Motoo
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Ken Ito
- Department of Gastroenterology, Tomakomai City Hospital, 1-5-20 Shimizucho, Tomakomai 053-8567, Japan
| | - Miho Sakumura
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Yurika Nakayama
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Yuko Ueda
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Shinya Kajiura
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Koji Nakashima
- Department of Clinical Oncology, University of Miyazaki Hospital, 5200 Kihara, Kiyotake-cho, Miyazaki 889-1692, Japan
| | - Kazuaki Harada
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Kita14, Nishi 5, Kita-ku, Sapporo 060-8648, Japan
| | - Yasuyuki Kawamoto
- Division of Cancer Center, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo 060-8648, Japan
| | - Yoshito Komatsu
- Division of Cancer Center, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo 060-8648, Japan
| | - Ichiro Yasuda
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
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Zhong W, Lin J, Wu C, Wang J, Chen J, Zheng H, Ye K. Efficacy and safety of camrelizumab combined with oxaliplatin and S-1 as neoadjuvant treatment in locally advanced gastric or gastroesophageal junction cancer: A phase II, single-arm study. Cancer Med 2024; 13:e7006. [PMID: 38400680 PMCID: PMC10891470 DOI: 10.1002/cam4.7006] [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: 07/25/2023] [Revised: 11/02/2023] [Accepted: 01/31/2024] [Indexed: 02/25/2024] Open
Abstract
PURPOSE In the present study, we aimed to evaluate the efficacy and safety of camrelizumab combined with oxaliplatin plus S-1 in patients with resectable gastric or gastroesophageal junction cancer. METHODS In this single-arm, phase II clinical trial, patients with locally advanced gastric or gastroesophageal junction adenocarcinoma were enrolled to receive three cycles of neoadjuvant camrelizumab and oxaliplatin plus S-1 every 3 weeks, followed by surgical resection and adjuvant therapy with the same regimen. The primary endpoint was pathological complete response (pCR) (ypT0) rate and secondary endpoints were R0 resection rate, total pCR (tpCR, ypT0N0) rate, major pathological response (MPR) rate, downstaging, objective response rate (ORR), disease control rate (DCR), event-free survival (EFS), overall survival (OS), and safety. RESULTS Between September, 2020 and January, 2022, a total of 29 patients were enrolled in the present study, all of whom completed neoadjuvant therapy and underwent surgery. Three (10.3%) (95% CI: 2.2-27.4) patients achieved pCR as well as tpCR, 20 (69.0%) patients had MPR and 28 (96.6%) patients achieved R0 resection. Treatment-emergent adverse events (AEs) of any grade were observed in 24 (82.8%) patients. Immune-related adverse events of any grade were reported in 13 (44.8%) patients, whereas no grade 3 or higher adverse events occurred. CONCLUSION The neoadjuvant therapy with camrelizumab in combination with oxaliplatin and S-1 showed a modest pCR rate, and favorable MPR rate and safety profile in patients with gastric or gastroesophageal junction cancer.
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Affiliation(s)
- Wen‐Jin Zhong
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Jian‐An Lin
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Chu‐Ying Wu
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Jiantian Wang
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Jun‐Xing Chen
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Huida Zheng
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
| | - Kai Ye
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Fujian Medical UniversityQuanZhou CityFujianChina
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Kawase T, Imamura H, Kawabata R, Matsuyama J, Nishikawa K, Yanagihara K, Yamamoto K, Hoki N, Kawada J, Kawakami H, Sakai D, Kurokawa Y, Shimokawa T, Satoh T. Phase II study of S-1 plus docetaxel as first-line treatment for older patients with advanced gastric cancer (OGSG 0902). Int J Clin Oncol 2024; 29:134-141. [PMID: 38227090 DOI: 10.1007/s10147-023-02437-4] [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: 05/11/2023] [Accepted: 11/08/2023] [Indexed: 01/17/2024]
Abstract
BACKGROUND Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. METHODS Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m2, day 1; S-1: 80 mg/m2, days 1-14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. RESULTS From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%-64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). CONCLUSIONS These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer.
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Affiliation(s)
- Tomono Kawase
- Department of Surgery, Toyonaka Municipal Hospital, 4-14-1 Shibahara-cho, Toyonaka-city, Japan
| | - Hiroshi Imamura
- Department of Surgery, Toyonaka Municipal Hospital, 4-14-1 Shibahara-cho, Toyonaka-city, Japan.
| | - Ryohei Kawabata
- Department of Surgery, Sakai City Medical Center, 1-1-1 Ebaraji-cho, Nishi-ku, Sakai-city, Japan
- Department of Surgery, Osaka Rosai Hospital, 1179-3 Nakasone-cho, Kita-ku, Sakai-city, Japan
| | - Jin Matsuyama
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka-city, Japan
| | - Kazuhiro Nishikawa
- Department of Surgery, Sakai City Medical Center, 1-1-1 Ebaraji-cho, Nishi-ku, Sakai-city, Japan
| | - Kazuhiro Yanagihara
- Department of Medical Oncology, Kansai Electric Power Hospital, 2-1-7 Fukushima, Fukushima-ku, Osaka-city, Japan
| | - Kazuyoshi Yamamoto
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita-city, Japan
| | - Noriyuki Hoki
- Department of Gastroenterology, Bellland General Hospital, 500-3 Higashiyama, Naka-ku, Sakai-city, Japan
| | - Junji Kawada
- Department of Surgery, Yao Municipal Hospital, 1-3-1 Ryuge-cho, Yao-city, Japan
| | - Hisato Kawakami
- Department of Medical Oncology, Faculty of Medicine, Kindai University, 377-2 Oonohigashi, Sayama-city, Japan
| | - Daisuke Sakai
- Department of Medical Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka-city, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita-city, Japan
| | - Toshio Shimokawa
- Clinical Study Support Center, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Japan
| | - Taroh Satoh
- Palliative and Supportive Care Center, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita-city, Japan
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Kobayashi D, Kodera Y, Fukushima R, Morita M, Fushida S, Yamashita N, Yoshikawa K, Ueda S, Yabusaki H, Kusumoto T, Arigami T, Hidemura A, Omori T, Yamaguchi H, Hirono Y, Tsuji Y, Moon JH, Tomita T, Imamura H, Nakanishi K, Shimizu D, Hirakawa A, Ishigami H, Kitayama J. Phase II Study of Intraperitoneal Administration of Paclitaxel Combined with S-1 and Cisplatin for Gastric Cancer with Peritoneal Metastasis. Ann Surg Oncol 2024; 31:735-743. [PMID: 37952018 DOI: 10.1245/s10434-023-14240-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 07/26/2023] [Indexed: 11/14/2023]
Abstract
BACKGROUND Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.
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Affiliation(s)
- Daisuke Kobayashi
- Department of Gastroenterological Surgery, Komaki City Hospital, Komaki, Japan.
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ryoji Fukushima
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Masaru Morita
- Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Sachio Fushida
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
| | | | - Kozo Yoshikawa
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Shugo Ueda
- Department of Gastroenterological Surgery and Oncology, Medical Research Institute Kitano Hospital, Osaka, Japan
| | - Hiroshi Yabusaki
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Tetsuya Kusumoto
- Department of Gastroenterological Surgery, Clinical Research Institute Cancer Research Division, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Takaaki Arigami
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Akio Hidemura
- Department of Surgery, Kanto Rosai Hospital, Kawasaki, Japan
| | - Takeshi Omori
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hironori Yamaguchi
- Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Japan
| | - Yasuo Hirono
- Cancer Care Promotion Center, University of Fukui Hospital, Fukui, Japan
| | - Yasushi Tsuji
- Department of Medical Oncology, Tonan Hospital, Sapporo, Japan
| | - Jeong Ho Moon
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Toshihiko Tomita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Japan
| | - Hiroshi Imamura
- Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Koki Nakanishi
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Dai Shimizu
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Akihiro Hirakawa
- Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | | | - Joji Kitayama
- Center for Clinical Research, Jichi Medical University Hospital, Shimotsuke, Japan
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Nakayama Y, Ando T, Takahashi N, Tsukada K, Takagi H, Goto Y, Nakaya A, Nakada N, Yoshita H, Motoo I, Ueda A, Ueda Y, Sakumura M, Kajiura S, Ogawa K, Hosokawa A, Yasuda I. The Efficacy and Safety of Nivolumab Plus mFOLFOX6 in Gastric Cancer with Severe Peritoneal Metastasis. J Clin Med 2024; 13:834. [PMID: 38337528 PMCID: PMC10856034 DOI: 10.3390/jcm13030834] [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: 12/27/2023] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/12/2024] Open
Abstract
(1) Background: Nivolumab plus chemotherapy is established as a first-line treatment for advanced gastric cancer (AGC). While mFOLFOX6 is commonly used for AGC with severe peritoneal metastasis, the efficacy of nivolumab combined with it remains uncertain. We evaluated the outcomes of nivolumab plus mFOLFOX6 for AGC with severe peritoneal metastasis in clinical practice. (2) Methods: This multicenter retrospective study was conducted between December 2021 and June 2023. We investigated AGC patients with massive ascites or inadequate oral intake due to severe peritoneal metastasis and who received nivolumab plus mFOLFOX6. (3) Results: Among 106 patients treated with nivolumab plus chemotherapy, 21 (19.8%) had severe peritoneal metastasis, with 14 receiving nivolumab plus mFOLFOX6. The median progression-free survival was 7.4 months (95%CI 1.9-10.1), and the median overall survival was 10.7 months (95%CI 5.3-NA), with four patients (28.5%) surviving more than 12 months. Improved ascites and oral intake were observed in 6/14 patients (42.8%) and 10/11 patients (90.9%), respectively. The major grade 3 or more adverse events included leukopenia (28.5%) and neutropenia (21.4%), with no severe immune-related adverse events reported. (4) Conclusions: The safety and moderate efficacy of nivolumab plus mFOLFOX6 were suggested even in AGC patients with severe peritoneal metastasis.
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Affiliation(s)
- Yurika Nakayama
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (A.U.); (Y.U.); (M.S.); (S.K.); (I.Y.)
| | - Takayuki Ando
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (A.U.); (Y.U.); (M.S.); (S.K.); (I.Y.)
| | - Naoki Takahashi
- Department of Gastroenterology, Kouseiren Takaoka Hospital, 5-10 Eirakumachi, Takaoka-shi 933-8555, Japan; (N.T.); (K.T.)
| | - Kenichiro Tsukada
- Department of Gastroenterology, Kouseiren Takaoka Hospital, 5-10 Eirakumachi, Takaoka-shi 933-8555, Japan; (N.T.); (K.T.)
| | - Hiroaki Takagi
- Department of Medical Oncology, Toyama Prefectural Central Hospital, 2-2-78 Nishinagae, Toyama-shi 930-8550, Japan; (H.T.); (K.O.)
| | - Yuno Goto
- Department of Gastroenterology, Takaoka City Hospital, 4-1 Takaramachi, Takaoka-shi 933-8550, Japan; (Y.G.); (A.N.)
| | - Atsuko Nakaya
- Department of Gastroenterology, Takaoka City Hospital, 4-1 Takaramachi, Takaoka-shi 933-8550, Japan; (Y.G.); (A.N.)
| | - Naokatsu Nakada
- Department of Gastroenterology, Itoigawa General Hospital, 457-1 Takegahana, Itoigawa-shi 941-8502, Japan;
| | - Hiroki Yoshita
- Department of Gastroenterology, Toyama Nishi General Hospital, 1019 Fuchumachi Shimokutsuwada, Toyama-shi 939-2716, Japan;
| | - Iori Motoo
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (A.U.); (Y.U.); (M.S.); (S.K.); (I.Y.)
| | - Akira Ueda
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (A.U.); (Y.U.); (M.S.); (S.K.); (I.Y.)
| | - Yuko Ueda
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (A.U.); (Y.U.); (M.S.); (S.K.); (I.Y.)
| | - Miho Sakumura
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (A.U.); (Y.U.); (M.S.); (S.K.); (I.Y.)
| | - Shinya Kajiura
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (A.U.); (Y.U.); (M.S.); (S.K.); (I.Y.)
| | - Kohei Ogawa
- Department of Medical Oncology, Toyama Prefectural Central Hospital, 2-2-78 Nishinagae, Toyama-shi 930-8550, Japan; (H.T.); (K.O.)
| | - Ayumu Hosokawa
- Department of Clinical Oncology, University of Miyazaki Hospital, Kihara-5200 Kiyotakecho, Miyazaki-shi 889-1692, Japan;
| | - Ichiro Yasuda
- Third Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.N.); (I.M.); (A.U.); (Y.U.); (M.S.); (S.K.); (I.Y.)
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Arai H, Takeuchi M, Ichikawa W, Shitara K, Sunakawa Y, Oba K, Koizumi W, Sakata Y, Furukawa H, Yamada Y, Takeuchi M, Fujii M. Correlation of multiple endpoints in the first-line chemotherapy of advanced gastric cancer: Pooled analysis of individual patient data from Japanese Phase III trials. Cancer Med 2024; 13:e6818. [PMID: 38140879 PMCID: PMC10807593 DOI: 10.1002/cam4.6818] [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: 07/09/2023] [Revised: 10/07/2023] [Accepted: 12/03/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Individual-level surrogates are important for management in patients treated for advanced gastric cancer (AGC). This study aimed to comprehensively investigate the correlation of multiple clinical endpoints in the first-line chemotherapy of AGC. METHODS Individual patient data (IPD) were collected from four Japanese Phase III trials comparing S-1-based first-line chemotherapies (SPIRITS, START, GC0301/TOP-002, and G-SOX trials). Patients without Response Evaluation Criteria in Solid Tumors (RECIST)-based radiological assessments were excluded. Spearman's rank correlation coefficient was tested for correlation among overall survival (OS), progression-free survival (PFS), and postprogression survival (PPS). OS, PFS, and PPS were compared between responders (best response: complete response or partial response) and nonresponders (best response: stable disease or progressive disease). RESULTS The study included a total of 1492 patients. Eighty percent of the patients (n = 1190) received subsequent chemotherapies after the failure of each trial's treatment protocol. PFS moderately correlated with OS (Spearman correlation coefficient = 0.66, p < 0.005), whereas the correlation between PPS and OS was strong (Spearman correlation coefficient = 0.87, p < 0.005). Responders had significantly longer OS (median, 17.7 vs. 9.1 months, p < 0.005), PFS (median, 6.9 vs. 2.8 months, p < 0.005), and PPS (median, 10.5 vs. 6.0 months, p < 0.005) than nonresponders. CONCLUSIONS Our results reacknowledged the mild surrogacy of PFS and importance of postprogression treatments in patients with AGC receiving first-line chemotherapy. Consistent longer survival outcomes in better RECIST categories suggested that tumor response might be a useful individual-level surrogate.
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Affiliation(s)
- Hiroyuki Arai
- Department of Clinical OncologySt. Marianna University School of MedicineKawasakiJapan
| | - Madoka Takeuchi
- Graduate School of Mathematical SciencesThe University of TokyoTokyoJapan
| | - Wataru Ichikawa
- Division of Medical OncologyShowa University Fujigaoka HospitalYokohamaJapan
| | - Kohei Shitara
- Department of Gastrointestinal OncologyNational Cancer Center Hospital EastKashiwaJapan
| | - Yu Sunakawa
- Department of Clinical OncologySt. Marianna University School of MedicineKawasakiJapan
| | - Koji Oba
- Department of Biostatistics, School of Public Health, Graduate School of MedicineThe University of TokyoTokyoJapan
| | - Wasaburo Koizumi
- Department of GastroenterologyKitasato University School of MedicineSagamiharaJapan
| | - Yuh Sakata
- Department of Internal MedicineMisawa City HospitalMisawaJapan
| | - Hiroshi Furukawa
- Department of SurgeryKindai University Faculty of MedicineOsaka‐SayamaJapan
| | - Yasuhide Yamada
- Comprehensive Cancer Center, National Center for Global Health and MedicineTokyoJapan
| | - Masahiro Takeuchi
- Department of Clinical Medicine, School of PharmacyKitasato UniversityTokyoJapan
| | - Masashi Fujii
- Department of Digestive SurgeryNihon University Itabashi HospitalTokyoJapan
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50
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Hara K, Cho H, Onodera A, Endo K, Maezawa Y, Aoyama T, Yamada T, Oshima T, Rino Y. Long-term treatment outcomes in gastric cancer with oligometastasis. Ann Gastroenterol Surg 2024; 8:60-70. [PMID: 38250694 PMCID: PMC10797816 DOI: 10.1002/ags3.12733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 07/24/2023] [Accepted: 08/10/2023] [Indexed: 01/23/2024] Open
Abstract
Aim While surgery is essential for curative treatment of gastric cancer with oligometastasis, its target, timing, and possibility of combination with other treatments are unclear. We herein investigated the clinical course and long-term outcomes of gastric cancer with oligometastasis in the real world setting to determine the optimal therapeutic strategy. Methods The present study retrospectively analyzed 992 patients who received any treatment for metastatic or recurrent gastric adenocarcinoma at Tokyo Metropolitan Komagome Hospital between 2007 and 2019. Oligometastasis was defined as any one of the following: liver metastases (HEP) <3; lung metastases (PUL) <3; unilateral adrenal gland metastasis (ADR); para-aortic lymph node metastasis (PALN); or one, distant, lymph node metastasis, excluding the regional lymph nodes (LYM). Overall survival was compared by the characteristics and treatments for the oligometastasis, and univariate and multivariate analyses were used to identify the prognostic factors of overall survival. Results Ninety-seven patients (9.8%) with the following metastasis sites were enrolled: HEP (n = 27), PUL (n = 2), ADR (n = 3), PALN (n = 55), and LYM (n = 10). The median survival time of the cohort was 22.8 months, and the five-year overall survival rate was 28.4%. On multivariate analysis, chemotherapy for the initial treatment (hazard ratio [HR]: 0.438; p = 0.048), distal gastrectomy and/or metastasectomy (HR: 0.290; p = 0.001), and R0 resection (HR: 0.373; p = 0.005) were identified as independent, positive factors of overall survival. Conclusion The long-term outcomes of gastric cancer in patients with oligometastasis may improve if treatment is begun with chemotherapy rather than surgery.
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Affiliation(s)
- Kentaro Hara
- Department of Gastric SurgeryTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
| | - Haruhiko Cho
- Department of Gastric SurgeryTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
| | - Atsushi Onodera
- Department of Gastric SurgeryTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
| | - Kazuya Endo
- Department of Gastric SurgeryTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
| | - Yukio Maezawa
- Department of SurgeryYokohama City UniversityYokohamaJapan
| | - Toru Aoyama
- Department of SurgeryYokohama City UniversityYokohamaJapan
| | - Takanobu Yamada
- Department of Gastrointestinal SurgeryKanagawa Cancer CenterYokohamaJapan
| | - Takashi Oshima
- Department of Gastrointestinal SurgeryKanagawa Cancer CenterYokohamaJapan
| | - Yasushi Rino
- Department of SurgeryYokohama City UniversityYokohamaJapan
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