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Mechahougui H, Chevallay M, Cauchy F, Chaveau N, Puppa G, Koessler T, Monig S. Complete response of a metastatic microsatellite-stable gastric cancer after neoadjuvant chemoimmunotherapy: should we still operate? A case report and review of the literature. Front Oncol 2024; 14:1440046. [PMID: 39634260 PMCID: PMC11614720 DOI: 10.3389/fonc.2024.1440046] [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: 05/28/2024] [Accepted: 10/16/2024] [Indexed: 12/07/2024] Open
Abstract
Gastric cancer often presents at an advanced stage in Western populations due to a lack of screening programs, leading to poor prognoses. Historically, palliative chemotherapy resulted in a median survival of 9.9 months. However, the introduction of the FLOT regimen and immunotherapy has significantly altered treatment outcomes. Oligometastatic gastric cancer, defined as metastasis limited to a single organ or a few sites, has emerged as a distinct subgroup with improved survival when treated with a combination of systemic and local therapies. We present the case of a 54-year-old male patient diagnosed with microsatellite-stable (MSS) oligometastatic gastric adenocarcinoma, including liver and peritoneal metastases, who achieved a complete pathological response following neoadjuvant chemoimmunotherapy with FOLFOX and nivolumab. Despite unfavorable prognostic factors, such as liver involvement and positive peritoneal cytology, the patient responded well to the treatment, allowing curative surgery. Postoperative histology confirmed complete regression of both the primary tumor and metastases, with no recurrence observed at the 1-year follow-up. This case shows the potential of combined chemoimmunotherapy to convert previously inoperable MSS gastric cancer to surgical candidates. Further research is needed to better define patient selection criteria and assess long-term outcomes for these patients.
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Affiliation(s)
- Hiba Mechahougui
- Department of Oncology, Geneva University Hospital, Geneva, Switzerland
| | - Mickael Chevallay
- Department of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland
| | - François Cauchy
- Department of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland
| | - Nicolas Chaveau
- Division of Pathology, Geneva University Hospital, Geneva, Switzerland
| | - Giacomo Puppa
- Division of Pathology, Geneva University Hospital, Geneva, Switzerland
| | - Thibaud Koessler
- Department of Oncology, Geneva University Hospital, Geneva, Switzerland
| | - Stefan Monig
- Department of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland
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Kumagai H, Baba S, Nikai H, Fujisawa R, Shimooki M, Sasaki A. Stage IV gastric cancer with microsatellite instability-high achieving long-term survival by gastrectomy after nivolumab as third-line therapy: a case report and literature review. Surg Case Rep 2024; 10:221. [PMID: 39294523 PMCID: PMC11411035 DOI: 10.1186/s40792-024-02022-5] [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: 06/27/2024] [Accepted: 09/10/2024] [Indexed: 09/20/2024] Open
Abstract
BACKGROUND The prognosis for stage IV gastric cancer remains poor; however, the advent of immune checkpoint inhibitors (ICIs) such as nivolumab has increased the number of patients with long-term survival. Patients with microsatellite instability (MSI)-high gastric cancer have been recognized as a highly effective population for ICIs. Herein, we report a patient with MSI-high advanced gastric cancer treated with gastrectomy after the administration of nivolumab as third-line therapy. CASE PRESENTATION A 73-year-old woman presented with a type 3 tumor in the lower part of the gastric body, which was diagnosed as gastric cancer through biopsy. Staging laparoscopy revealed that the tumor had invaded the pancreas and the posterior lobe of the transverse mesocolon, and disseminated nodules were found near the ligament of Treitz. After 4 courses of S-1 plus cisplatin therapy, laparoscopic gastrojejunal bypass was performed because of difficulty in oral intake. She received S-1 plus oxaliplatin therapy after a gastrojejunal bypass; however, her regional lymph nodes were enlarged. After six courses of paclitaxel plus ramucirumab as second-line chemotherapy, computed tomography (CT) showed exacerbation of peritoneal dissemination; thus, nivolumab was selected as the third-line therapy. The tumor was characterized by MSI-high. At 24 courses, CT and gastroscopy revealed a complete clinical response of the tumor; however, re-growth of the primary tumor was observed at 36 courses. The patient underwent distal gastrectomy with D1 + lymph node dissection, and received S-1 monotherapy as adjuvant therapy for 1 year. No recurrence was noted at 39 months after the surgery. CONCLUSIONS We report a patient with highly advanced gastric cancer with peritoneal dissemination, which worsened during second-line therapy and was successfully treated with gastrectomy after nivolumab administration as a third-line therapy. MSI-high gastric cancer is a target that should be actively considered for the administration of ICIs, such as nivolumab, and multidisciplinary treatment combined with chemotherapy and gastrectomy, including conversion surgery, can lead to patients' long-term survival.
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Affiliation(s)
- Hideki Kumagai
- Department of Surgery, Iwate Medical University, 2-1-1 Idaidori, Yahaba, Iwate, 028-3695, Japan.
| | - Shigeaki Baba
- Department of Surgery, Iwate Medical University, 2-1-1 Idaidori, Yahaba, Iwate, 028-3695, Japan
| | - Haruka Nikai
- Department of Surgery, Iwate Medical University, 2-1-1 Idaidori, Yahaba, Iwate, 028-3695, Japan
| | - Ryosuke Fujisawa
- Department of Surgery, Iwate Medical University, 2-1-1 Idaidori, Yahaba, Iwate, 028-3695, Japan
| | - Misato Shimooki
- Department of Surgery, Iwate Medical University, 2-1-1 Idaidori, Yahaba, Iwate, 028-3695, Japan
| | - Akira Sasaki
- Department of Surgery, Iwate Medical University, 2-1-1 Idaidori, Yahaba, Iwate, 028-3695, Japan
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Rawicz-Pruszyński K, Erodotou M, Pelc Z, Sędłak K, Polkowski W, Pawlik TM, Wijnhoven BP. Techniques of staging laparoscopy and peritoneal fluid assessment in gastric cancer: a systematic review. Int J Surg 2023; 109:3578-3589. [PMID: 37581636 PMCID: PMC10651295 DOI: 10.1097/js9.0000000000000632] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 07/13/2023] [Indexed: 08/16/2023]
Abstract
BACKGROUND Staging laparoscopy for gastric cancer is recommended to assess the tumor's locoregional extension and exclude peritoneal disease. As there is no consensus on optimizing the procedure's diagnostic accuracy, we aimed to systematically review the literature on operative techniques, followed by peritoneal lavage fluid assessment in gastric cancer patients. Specifically, we sought to indicate the most common characteristics of the procedure and cytological evaluation. METHODS This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol for this systematic review was registered on PROSPERO database (CRD: 42022306746). On September 2022, a search was carried out using Embase, Medline ALL, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection. RESULTS The search identified 1632 studies on staging laparoscopy and 2190 studies on peritoneal fluid assessment. Some 212 studies were included. Open Hasson was the method of choice in accessing the peritoneal cavity in 65% of the studies, followed by establishing a pneumoperitoneum at 10-12 mmHg in 52% of reports. Most frequently, the patient was positioned supine (70%), while a 30° scope and three ports were used to assess the peritoneal cavity clockwise (72%, 77%, and 85%, respectively). Right and left upper abdomen quadrants were the predominant area of laparoscopic exploration (both 65%), followed by the primary tumor region (54%), liver and pelvis (both 30%), and small bowel and spleen (19% and 17%, respectively). Regions of peritoneal lavage and aspiration were limited to the pelvis (50%), followed by right and left upper abdomen quadrants (37.5% and 50%, respectively). No studies compared different methods of operative techniques or analysis of ascites/fluid. CONCLUSIONS This study indicates a high heterogeneity in the technique of staging laparoscopy and peritoneal fluid assessment in gastric cancer patients. Further research and initiatives to reach a consensus on the standardization of the procedure are warranted.
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Affiliation(s)
- Karol Rawicz-Pruszyński
- Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Maria Erodotou
- Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Zuzanna Pelc
- Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland
| | - Katarzyna Sędłak
- Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland
| | - Wojciech Polkowski
- Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland
| | - Timothy M. Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Bas P.L. Wijnhoven
- Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
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Lewis CR, Dadgar N, Yellin SA, Donnenberg VS, Donnenberg AD, Bartlett DL, Allen CJ, Wagner PL. Regional Immunotherapy for Peritoneal Carcinomatosis in Gastroesophageal Cancer: Emerging Strategies to Re-Condition a Maladaptive Tumor Environment. Cancers (Basel) 2023; 15:5107. [PMID: 37894473 PMCID: PMC10605802 DOI: 10.3390/cancers15205107] [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: 08/24/2023] [Revised: 10/04/2023] [Accepted: 10/20/2023] [Indexed: 10/29/2023] Open
Abstract
Peritoneal carcinomatosis originating from gastric/gastroesophageal junction cancer (GC-PC) occurs in a defined subset of gastric cancer patients with unique clinical, pathologic, molecular and immunologic characteristics that create significant obstacles to effective treatment with modern therapy. Although systemic chemo- and immuno- therapy have yielded disappointing results in GC-PC, recent advances in the characterization of GC-PC and peritoneal immune biology present new opportunities for targeted therapeutics. In this review article, we discuss the distinct properties of GC-PC and the peritoneal immune environment as they pertain to current and investigative treatment strategies. We discuss pre-clinical studies and clinical trials relevant to the modulation of the peritoneal environment as a therapeutic intervention in GC-PC. Finally, we present a road map for future combinatorial strategies based on the conception of the peritoneal cavity as a bioreactor. Within this isolated compartment, prevailing immunosuppressive conditions can be altered through regional interventions toward an adaptive phenotype that would support the effectiveness of regionally delivered cellular therapy products. It is hoped that novel combination strategies would promote efficacy not only in the sequestered peritoneal environment, but also via migration into the circulation of tumor-reactive lymphocytes to produce durable systemic disease control, thereby improving oncologic outcome and quality of life in patients with GC-PC.
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Affiliation(s)
- Catherine R. Lewis
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
| | - Neda Dadgar
- Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA;
| | - Samuel A. Yellin
- Department of Surgery, Lehigh Valley Health Network, Allentown, PA 18101, USA;
| | - Vera S. Donnenberg
- Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA;
- Hillman Cancer Centers, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Albert D. Donnenberg
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
| | - David L. Bartlett
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
| | - Casey J. Allen
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
| | - Patrick L. Wagner
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (C.R.L.); (A.D.D.); (D.L.B.); (C.J.A.)
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Successful second conversion surgery after trastuzumab deruxtecan for recurrent HER2-positive gastric cancer. Clin J Gastroenterol 2023; 16:330-335. [PMID: 36708503 DOI: 10.1007/s12328-023-01764-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 01/17/2023] [Indexed: 01/29/2023]
Abstract
A 65-year-old woman with HER2-positive gastric cancer with multiple liver metastases underwent first conversion surgery of gastrectomy with D2 lymph nodes dissection and three liver metastases after combination therapy with capecitabine, cisplatin, and trastuzumab. Two years later, she experienced multiple liver metastases that were refractory to combination therapy with paclitaxel albumin-bound nanoparticles and ramucirumab. She participated in the DESTINY-Gastric01 trial and received tri-weekly trastuzumab deruxtecan as third-line treatment for 26 cycles. The recurrent lesions markedly shrank, and this effect continued for 19 months. We then performed partial hepatectomy for the one remaining lesion. No adjuvant chemotherapy was given, and she remains alive without recurrence 18 months after the second conversion surgery. Trastuzumab deruxtecan may generate a notable tumor response and subsequent conversion surgery could be a treatment option for HER2-positive stage IV gastric cancer.
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Hidaka Y, Arigami T, Osako Y, Desaki R, Hamanoue M, Takao S, Kirishima M, Ohtsuka T. Conversion surgery for microsatellite instability-high gastric cancer with a complete pathological response to pembrolizumab: a case report. World J Surg Oncol 2022; 20:193. [PMID: 35689267 PMCID: PMC9185925 DOI: 10.1186/s12957-022-02661-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 05/28/2022] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Immune checkpoint inhibitors are reportedly effective in treating microsatellite instability (MSI)-high gastric cancer. There are a few case reports of conversion surgery (CS) with nivolumab but none with pembrolizumab. Herein, we describe a patient with MSI-high gastric cancer who was successfully treated with pembrolizumab and underwent CS with a pathological complete response. CASE PRESENTATION A 69-year-old man was diagnosed with stage III gastric cancer (T3N2M0) based on contrast-enhanced computed tomography, which revealed a neoplastic lesion and enlarged perigastric lymph nodes in the gastric lesser curvature. The anterior superior lymph node of the common hepatic artery (CHA) was determined to be unresectable due to invasion of the pancreatic head and CHA. Histopathologically, the biopsied tissue showed moderately differentiated adenocarcinoma, then determined to be MSI-high. After three courses of mFOLFOX6 therapy, the patient was diagnosed with progressive disease. Since one course of paclitaxel plus ramucirumab therapy caused grade 3 fatigue, his second-line therapy was switched to pembrolizumab monotherapy. After three courses, the primary tumor and perigastric lymph nodes had shrunk, and it was determined as a partial response. The anterior superior lymph node of the CHA became resectable based on the improvement of infiltration of the pancreatic head and CHA due to shrinkage of the lymph node. Tumor markers remained low; hence, distal gastrectomy plus D2 lymphadenectomy was performed at the end of six courses. Anterior superior lymph node of the CHA was confirmed by intraoperative ultrasonography, and the resection was completed safely. The gross examination of the resected specimen revealed an ulcer scar at the primary tumor site. The histopathological examination showed no viable tumor cell remnants in the primary tumor, which had a grade 3 histological response, and resection margins were negative. The lymph nodes showed mucus retention only in the anterior superior lymph node of the CHA, indicating the presence of metastasis, but no viable tumor cells remained. The patient commenced 6 months of adjuvant pembrolizumab monotherapy 3 months after surgery. Twenty months after surgery, there was no evidence of recurrence. CONCLUSIONS Conversion surgery following pembrolizumab monotherapy has a potential utility for the treatment of MSI-high gastric cancer.
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Affiliation(s)
- Yoshifumi Hidaka
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan.
| | - Takaaki Arigami
- Department of Onco-biological Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 9-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Yusaku Osako
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Ryosuke Desaki
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Masahiro Hamanoue
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Sonshin Takao
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Mari Kirishima
- Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Takao Ohtsuka
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
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Matsumura N. Strategies for the use of immune checkpoint inhibitors. Int Cancer Conf J 2021; 10:265. [PMID: 34567935 PMCID: PMC8421497 DOI: 10.1007/s13691-021-00508-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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