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Han S, Zhang T, Deng W, Han S, Wu H, Jiang B, Xie W, Chen Y, Deng T, Wen X, Liu N, Fan J. Deep learning progressive distill for predicting clinical response to conversion therapy from preoperative CT images of advanced gastric cancer patients. Sci Rep 2025; 15:17092. [PMID: 40379665 PMCID: PMC12084415 DOI: 10.1038/s41598-025-01063-6] [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: 01/25/2025] [Accepted: 05/02/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND AND OBJECTIVE Identifying patients suitable for conversion therapy through early non-invasive screening is crucial for tailoring treatment in advanced gastric cancer (AGC). This study aimed to develop and validate a deep learning method, utilizing preoperative computed tomography (CT) images, to predict the response to conversion therapy in AGC patients. This retrospective study involved 140 patients. We utilized Progressive Distill (PD) methodology to construct a deep learning model for predicting clinical response to conversion therapy based on preoperative CT images. Patients in the training set (n = 112) and in the test set (n = 28) were sourced from The First Affiliated Hospital of Wenzhou Medical University between September 2017 and November 2023. Our PD models' performance was compared with baseline models and those utilizing Knowledge Distillation (KD), with evaluation metrics including accuracy, sensitivity, specificity, receiver operating characteristic curves, areas under the receiver operating characteristic curve (AUCs), and heat maps. The PD model exhibited the best performance, demonstrating robust discrimination of clinical response to conversion therapy with an AUC of 0.99 and accuracy of 99.11% in the training set, and 0.87 AUC and 85.71% accuracy in the test set. Sensitivity and specificity were 97.44% and 100% respectively in the training set, 85.71% and 85.71% each in the test set, suggesting absence of discernible bias. The deep learning model of PD method accurately predicts clinical response to conversion therapy in AGC patients. Further investigation is warranted to assess its clinical utility alongside clinicopathological parameters.
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Grants
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
- 2023D007, 2023D015, 2023D033, 2023D034, 2023D035 Municipal Government of Quzhou
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Affiliation(s)
- Saiyi Han
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China
| | - Tong Zhang
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China
- Yangtze Delta Region Institute(Quzhou), University of Electronic Science and Technology of China, Quzhou, Zhejiang, China
- School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan, PR China
| | - Wenzhuo Deng
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China
- Yangtze Delta Region Institute(Quzhou), University of Electronic Science and Technology of China, Quzhou, Zhejiang, China
- School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan, PR China
| | - Shaoliang Han
- Department of The Gastrointestinal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Honghao Wu
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China
- Yangtze Delta Region Institute(Quzhou), University of Electronic Science and Technology of China, Quzhou, Zhejiang, China
- School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan, PR China
| | - Beier Jiang
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China
| | - Weidong Xie
- Department of The Gastrointestinal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Yide Chen
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China
- Yangtze Delta Region Institute(Quzhou), University of Electronic Science and Technology of China, Quzhou, Zhejiang, China
- School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan, PR China
| | - Tao Deng
- Department of The Gastrointestinal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Xuewen Wen
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China
- Yangtze Delta Region Institute(Quzhou), University of Electronic Science and Technology of China, Quzhou, Zhejiang, China
- School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan, PR China
| | - Nianbo Liu
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China
- Yangtze Delta Region Institute(Quzhou), University of Electronic Science and Technology of China, Quzhou, Zhejiang, China
- School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan, PR China
| | - Jianping Fan
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China.
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Chen Y, Jiang J, Yan C, Jiang J, Shi B, Xu Z, Yuan F, Zhang H, Zhang J. Prediction of tumor regression grade in far-advanced gastric cancer after preoperative immuno-chemotherapy using dual-energy CT-derived extracellular volume fraction. Eur Radiol 2025; 35:93-104. [PMID: 38981889 DOI: 10.1007/s00330-024-10737-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 02/29/2024] [Accepted: 03/17/2024] [Indexed: 07/11/2024]
Abstract
OBJECTIVES This study examines the effectiveness of dual-energy CT (DECT) delayed-phase extracellular volume (ECV) fraction in predicting tumor regression grade (TRG) in far-advanced gastric cancer (FAGC) patients receiving preoperative immuno-chemotherapy. MATERIALS AND METHODS A retrospective analysis was performed on far-advanced gastric adenocarcinoma patients treated with preoperative immuno-chemotherapy at our institution from August 2019 to March 2023. Patients were categorized based on their TRG into pathological complete response (pCR) and non-pCR groups. ECV was determined using the delayed-phase iodine maps. In addition, tumor iodine densities and standardized iodine ratios were meticulously analyzed using the triple-phase enhanced iodine maps. Univariate analysis with five-fold cross-validation and Spearman correlation determined DECT parameters and clinical indicators association with pCR. The predictive accuracy of these parameters for pCR was evaluated using a weighted logistic regression model with five-fold cross-validation. RESULTS Of the 88 patients enrolled (mean age 60.8 ± 11.1 years, 63 males), 21 (23.9%) achieved pCR. Univariate analysis indicated ECV's significant role in differentiating between pCR and non-pCR groups (average p value = 0.021). In the logistic regression model, ECV independently predicted pCR with an average odds ratio of 0.911 (95% confidence interval, 0.798-0.994). The model, incorporating ECV, tumor area, and IDAV (the relative change rate of iodine density from venous phase to arterial phase), showed an average area under curves (AUCs) of 0.780 (0.770-0.791) and 0.766 (0.731-0.800) for the training and validation sets, respectively, in predicting pCR. CONCLUSION DECT-derived ECV fraction is a valuable predictor of TRG in FAGC patients undergoing preoperative immuno-chemotherapy. CLINICAL RELEVANCE STATEMENT This study demonstrates that DECT-derived extracellular volume fraction is a reliable predictor for pathological complete response in far-advanced gastric cancer patients receiving preoperative immuno-chemotherapy, offering a noninvasive tool for identifying potential treatment beneficiaries.
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Affiliation(s)
- Yong Chen
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinling Jiang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chao Yan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiang Jiang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Bowen Shi
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhihan Xu
- Siemens Healthineers Ltd, Shanghai, China
| | - Fei Yuan
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Huan Zhang
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Jun Zhang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Tanioka N, Kuwahara M, Sakai T, Nokubo Y, Shimizu S, Hiroi M, Akimori T. Minimally Invasive Conversion Surgery for Unresectable Gastric Cancer with Splenic Metastasis and Splenic Vein Tumor Thrombus: A Case Report. Curr Oncol 2024; 31:2662-2669. [PMID: 38785482 PMCID: PMC11119725 DOI: 10.3390/curroncol31050201] [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: 04/15/2024] [Revised: 05/02/2024] [Accepted: 05/06/2024] [Indexed: 05/25/2024] Open
Abstract
While the importance of conversion surgery has increased with the development of systemic chemotherapy for gastric cancer (GC), reports of conversion surgery for patients with GC with distant metastasis and tumor thrombus are extremely scarce, and a definitive surgical strategy has yet to be established. Herein, we report a 67-year-old man with left abdominal pain referred to our hospital following a diagnosis of unresectable GC. Esophagogastroduodenoscopy and contrast-enhanced abdominal computed tomography (CT) revealed advanced GC with splenic metastasis. A splenic vein tumor thrombus (SVTT) and a continuous thrombus to the main trunk of the portal vein were detected. The patient was treated with anticoagulation therapy and systemic chemotherapy comprising S-1 and oxaliplatin. One year following chemotherapy initiation, a CT scan revealed progressive disease (PD); therefore, the chemotherapy regimen was switched to ramucirumab with paclitaxel. After 10 courses of chemotherapy resulting in primary tumor and SVTT shrinkage, the patient underwent laparoscopic total gastrectomy (LTG) and distal pancreaticosplenectomy (DPS). He was discharged without complications and remained alive 6 months postoperatively without recurrence. In summary, the wait-and-see approach was effective in a patient with GC with splenic metastasis and SVTT, ultimately leading to an R0 resection performed via LTG and DPS.
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Affiliation(s)
- Nobuhisa Tanioka
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City 788-0785, Kochi, Japan; (M.K.); (T.S.); (Y.N.); (S.S.); (T.A.)
| | - Michio Kuwahara
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City 788-0785, Kochi, Japan; (M.K.); (T.S.); (Y.N.); (S.S.); (T.A.)
| | - Takashi Sakai
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City 788-0785, Kochi, Japan; (M.K.); (T.S.); (Y.N.); (S.S.); (T.A.)
| | - Yuzuko Nokubo
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City 788-0785, Kochi, Japan; (M.K.); (T.S.); (Y.N.); (S.S.); (T.A.)
| | - Shigeto Shimizu
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City 788-0785, Kochi, Japan; (M.K.); (T.S.); (Y.N.); (S.S.); (T.A.)
| | - Makoto Hiroi
- Department of Pathology, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City 788-0785, Kochi, Japan;
| | - Toyokazu Akimori
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City 788-0785, Kochi, Japan; (M.K.); (T.S.); (Y.N.); (S.S.); (T.A.)
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Takeno A, Motoori M, Kishi K, Omori T, Hirao M, Masuzawa T, Fujitani K, Yamamato K, Kurokawa Y, Doki Y. Prognostic factors of conversion surgery for stage IV gastric cancer: A multi-institutional retrospective analysis. Ann Gastroenterol Surg 2024; 8:431-442. [PMID: 38707233 PMCID: PMC11066490 DOI: 10.1002/ags3.12778] [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: 09/28/2023] [Revised: 01/06/2024] [Accepted: 01/13/2024] [Indexed: 05/07/2024] Open
Abstract
Background Conversion surgery (CS) is a highly anticipated strategy for stage IV advanced gastric cancer (AGC) with a good response to chemotherapy. However, prognostic factors limiting R0 resection remain unclear. In this multi-institutional study, we investigated the clinical outcomes of CS for stage IV AGC and the prognostic factors of CS-limiting R0 resection and analyzed them according to metastatic patterns. Methods Clinical data on 210 patients who underwent CS for stage IV AGC at six institutions between 2007 and 2017 were retrospectively retrieved. The patient background, preoperative treatment, operative outcomes, and survival times were recorded. Prognostic factors for overall and recurrence-free survival were investigated using univariate and multivariate analyses for patients who underwent R0 resection. Results R0 resection was achieved in 146 (70%) patients. The median survival time was 32 months, and the 3-year survival rate was 45%. Patients who achieved R0 resection had significantly longer survival than those with R1/2 resection (median survival time: 41.5 months vs. 20.7 months). Multivariate analysis identified pathological N positivity for overall and relapse-free survival and pathological T4 for relapse-free survival as significant independent poor prognostic factors of R0 resected patients. There was no significant difference in survival among the peritoneum, liver, and lymph node groups regarding the initial metastatic sites. Conclusions CS with R0 resection for patients with stage IV AGC can lead to longer survival. Patients with pathological T4 and pathological N positivity were eligible for intensive adjuvant therapy after CS with R0 resection.
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Affiliation(s)
- Atsushi Takeno
- Department of Surgery, National Hospital OrganizationOsaka National HospitalOsakaJapan
| | | | - Kentaro Kishi
- Department of SurgeryOsaka Police HospitalOsakaJapan
| | - Takeshi Omori
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Motohiro Hirao
- Department of Surgery, National Hospital OrganizationOsaka National HospitalOsakaJapan
| | - Toru Masuzawa
- Department of SurgeryKansai Rosai HospitalAmagasakiHyogoJapan
| | | | - Kazuyoshi Yamamato
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaOsakaJapan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaOsakaJapan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaOsakaJapan
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Hojo Y, Ishida Y, Tomita T, Kurahashi Y, Nakamura T, Kitayama Y, Nakao E, Kohno S, Murakami M, Takeuchi J, Takagawa T, Hirota S, Shinohara H. Treatment strategy for successful conversion surgery in clinical stage IVB gastric cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107314. [PMID: 38101115 DOI: 10.1016/j.ejso.2023.107314] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 11/13/2023] [Accepted: 12/02/2023] [Indexed: 12/17/2023]
Abstract
INTRODUCTION Recent advances in chemotherapy have resulted in successful conversion surgery (CS) for clinical stage (cStage) IVB gastric cancer (GC). This study aimed to evaluate the success rate of CS in clinical practice and determine optimal treatment strategies. METHODS Totally, 166 patients with cStage IVB gastric and gastroesophageal junction adenocarcinoma, who underwent chemotherapy at Hyogo Medical University Hospital between January 2017 and June 2022, were included. CS was performed after confirming tumor to be M0 based on imaging and/or staging laparoscopy, except for resectable liver metastases. Preoperative chemotherapy was continued for at least 6 months provided that adverse events were manageable. RESULTS Of 125 eligible patients, 23 were treated with CS, achieving a conversion rate of 18.4% and an R0 resection rate of 91.3%. The median duration of preoperative chemotherapy was 8.5 months; the median number of cycles was eight. The highest conversion rate was observed in patients receiving first-line treatment (14.4%), followed by those receiving second and third lines (5.8% and 2.3%, respectively). The median survival time in patients who received CS was significantly longer than that in patients who continued chemotherapy alone (56.7 versus 16 months, respectively, P < 0.0001). There was no significant difference in the 3-year overall survival between the patients who achieved CS after first-line treatment (63.2%, n = 18) and those who achieved CS after second- or third-line treatment (66.7%, n = 5). CONCLUSION Consistent chemotherapy strategies could lead to successful CS and improved prognosis in a greater number of patients with cStage IVB GC, regardless of line of treatment.
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Affiliation(s)
- Yudai Hojo
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Yoshinori Ishida
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Toshihiko Tomita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Yasunori Kurahashi
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Tatsuro Nakamura
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Yoshitaka Kitayama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Eiichiro Nakao
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Shugo Kohno
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Motoki Murakami
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Jiro Takeuchi
- Department of Clinical Epidemiology, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Tetsuya Takagawa
- Center for Clinical Research and Education, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Seiichi Hirota
- Department of Surgical Pathology, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hisashi Shinohara
- Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
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Ministrini S, Bencivenga M, Filippini F, Mura G, Milandri C, Mazzei MA, Bagnacci G, Berselli M, Monti M, Morgagni P, Solaini L, Marrelli D, Piccioni S, De Pascale S, Graziosi L, Reddavid R, Rosa F, Belluco C, Tiberio G. A pragmatic approach improves the clinical management of stage IV gastric cancer: Comparison between the Meta-Gastro results and the GIRCG's retrospective series. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107275. [PMID: 37995604 DOI: 10.1016/j.ejso.2023.107275] [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: 08/14/2023] [Revised: 10/29/2023] [Accepted: 11/10/2023] [Indexed: 11/25/2023]
Abstract
INTRODUCTION The Italian Research Group for Gastric Cancer developed a prospective database about stage IV gastric cancer, to evaluate how a pragmatic attitude impacts the management of these patients. MATERIALS AND METHODS We prospectively collected data about metastatic gastric cancer patients thanks to cooperation between radiologists, oncologists and surgeons and we analyzed survival and prognostic factors, comparing the results to those obtained in our retrospective study. RESULTS Three-hundred and eighty-three patients were enrolled from 2018 to September 2022. We observed a higher percentage of laparoscopic exploration with peritoneal lavage in the prospective cohort. In the registry only 3.6 % of patients was submitted to surgery without associated chemotherapy, while in the retrospective population 44.3 % of patients were operated on without any chemotherapy. At univariate and multivariate analyses, the different metastatic sites did not show any survival differences among each other (OS 20.0 vs 16.10 vs 16.7 months for lymphnodal, peritoneal and hepatic metastases, respectively), while the number of metastatic sites and the type of treatment showed a statistical significance (OS 16,7 vs 13,0 vs 4,5 months for 1, 2 and 3 different metastatic sites respectively, p < 0.001; 24,2 vs 12,0 vs 2,5 months for surgery with/without chemotherapy, chemotherapy alone and best supportive treatment respectively, p < 0.001). CONCLUSIONS Our data highlight that the different metastatic sites did not show different survivals, but survival is worse in case of multiple localization. In patients where a curative resection can be achieved, acceptable survival rates are possible. A better diagnostic workup and a more accurate staging impact favorably upon survival.
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Affiliation(s)
- Silvia Ministrini
- Surgical Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123, Brescia, Italy.
| | - Maria Bencivenga
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Verona, Italy
| | - Federica Filippini
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Verona, Italy
| | - Gianni Mura
- Department of Surgery, San Donato Hospital, Arezzo, Italy
| | - Carlo Milandri
- Department of Oncology, San Donato Hospital, 52100, Arezzo, Italy
| | - Maria Antonietta Mazzei
- Unit of Diagnostic Imaging, Department of Medical, Surgical and Neuro Sciences and of Radiological Sciences, University of Siena, Azienda Ospedaliero-Universitaria Senese, 53100, Siena, Italy
| | - Giulio Bagnacci
- Unit of Diagnostic Imaging, Department of Medical, Surgical and Neuro Sciences and of Radiological Sciences, University of Siena, Azienda Ospedaliero-Universitaria Senese, 53100, Siena, Italy
| | - Mattia Berselli
- General Surgical Unit I, Department of Surgery, ASST Settelaghi-Varese, Italy
| | - Manlio Monti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Paolo Morgagni
- General and Oncologic Surgery, "Morgagni-Pierantoni" Hospital, Forlì, Italy
| | - Leonardo Solaini
- General and Oncologic Surgery, "Morgagni-Pierantoni" Hospital, Forlì, Italy
| | - Daniele Marrelli
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, Strada delle Scotte, 4, 53100, Siena, Italy
| | - Stefania Piccioni
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, Strada delle Scotte, 4, 53100, Siena, Italy
| | - Stefano De Pascale
- Digestive Surgery Unit, European Institute of Oncology IRCCS, 20141, Milan, Italy
| | - Luigina Graziosi
- SC di Chirurgia Generale e d'Urgenza, Azienda Ospedaliera di Perugia, Perugia, Italy
| | - Rossella Reddavid
- University of Turin, Department of Oncology, Division of Surgical Oncology and Digestive Surgery, San Luigi University Hospital, Orbassano, Turin, Italy
| | - Fausto Rosa
- Department of Digestive Surgery, Catholic University, A. Gemelli Hospital, Rome, Italy
| | - Claudio Belluco
- Department of Surgical Oncology, Surgical Oncology Unit, National Cancer institute-Centro di Riferimento Oncologico IRCCS, Aviano, PN, Italy
| | - Guido Tiberio
- Surgical Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123, Brescia, Italy
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Abstract
The prognosis of advanced gastric cancer (AGC) is extremely poor, and the therapeutic effect of traditional palliative chemotherapy is far from satisfactory. To overcome this bottleneck, palliative surgery resection, perioperative chemotherapy combined with surgical resection, hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), radiation therapy, molecular-targeted therapy have been explored in AGC. Although considerable progress has been achieved, there is still no overwhelming therapeutic method. Due to the high heterogeneity of AGC, it is particularly vital to reshaped the paradigm of gastric cancer therapy according to the characteristics of clinical classifications and molecular subtypes.
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Affiliation(s)
- Tao Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yufang He
- The First Clinical Medical School, Southern Medical University, Guangzhou, Guangdong, China
| | - Qinglei Zhong
- The First Clinical Medical School, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiang Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xinhua Chen
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
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8
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Namikawa T, Marui A, Yokota K, Fujieda Y, Munekage M, Uemura S, Maeda H, Kitagawa H, Kobayashi M, Hanazaki K. Successful Conversion Surgery for Advanced Gastric Cancer With Multiple Liver Metastases Following Ramucirumab Plus Paclitaxel Combination Treatment. In Vivo 2021; 35:2929-2935. [PMID: 34410989 PMCID: PMC8408704 DOI: 10.21873/invivo.12584] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/11/2021] [Accepted: 06/15/2021] [Indexed: 02/07/2023]
Abstract
AIM To present the case of a patient with unresectable gastric cancer showing a remarkable effect by second-line drug treatment with ramucirumab plus paclitaxel and conversion surgery. CASE REPORT A 68-year-old woman who was diagnosed with gastric cancer was referred to us. Esophagogastroduodenoscopy showed an ulcerated lesion with an irregular nodulated border in the lower third of the stomach, and histology of biopsied specimens indicated a poorly differentiated adenocarcinoma. Enhanced computed tomography revealed extensive invasion of the liver, and the patients was treated using S-1 plus oxaliplatin as first-line chemotherapy. Because she developed liver metastases, the treatment regimen was changed to ramucirumab plus paclitaxel as the second-line treatment. After four cycles of weekly paclitaxel with ramucirumab treatment, the liver metastases had completely disappeared. Because no other metastatic lesions in other organs were detected, we performed total gastrectomy with D2 lymphadenectomy. The macroscopic findings of the surgically resected specimen revealed an ulcerated lesion with an irregularly modulated lesion measuring 9.5×4.5 cm. Pathological analysis demonstrated a poorly differentiated adenocarcinoma in the stomach, with invasion to the liver through the serosal layer, and seven lymph node metastases. The postoperative course was unremarkable, and she received ramucirumab in combination with paclitaxel treatment. However, liver metastasis appeared at 4 months after the operation, for which she was treated with irinotecan. Although the patient continued to receive irinotecan chemotherapy for 10 months, her general condition gradually deteriorated, and she was started on best supportive care 13 months after conversion surgery. CONCLUSION Conversion surgery may prolong survival not only through first-line but also second-line treatments in selected patients with unresectable advanced gastric cancer; however, assessments of additional cases and further studies are required to establish this treatment strategy.
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Affiliation(s)
| | - Akira Marui
- Department of Surgery, Kochi Medical School, Kochi, Japan
| | | | - Yuki Fujieda
- Department of Surgery, Kochi Medical School, Kochi, Japan
| | | | - Sunao Uemura
- Department of Surgery, Kochi Medical School, Kochi, Japan
| | | | | | - Michiya Kobayashi
- Department of Human Health and Medical Sciences, Kochi Medical School, Kochi, Japan
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9
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Yamashita K, Hosoda K, Niihara M, Hiki N. History and emerging trends in chemotherapy for gastric cancer. Ann Gastroenterol Surg 2021; 5:446-456. [PMID: 34337293 PMCID: PMC8316740 DOI: 10.1002/ags3.12439] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/29/2020] [Accepted: 01/15/2021] [Indexed: 12/24/2022] Open
Abstract
Chemotherapy is indispensable for gastric cancer. For unresectable and/or recurrent gastric cancer, first-line chemotherapy consists of multidrug regimens including oral 5-FU agents such as S1/Xeloda and platinum preparations, as well as Trastuzumab, which is effective in HER2-positive cases. Second- and third-line chemotherapy regimens include taxanes, Ramucirumab (R-mab), and Nivolumab (N-mab), which have different mechanisms of action from first-line chemotherapy. R-mab is molecularly targeted to vascular endothelial growth factor receptor 2 in the host cells, but its indication is not conditional. For resectable gastric cancer, in Eastern countries, postoperative adjuvant chemotherapy has been successful, including S1, Docetaxel/S1 (DS), and Xeloda/Oxaliplatin (Xelox) regimens, whereas, in Western countries, the 5-FU/Leucovorin/Oxaliplatin/Docetaxel (FLOT) regimen was recently shown to be effective in the perioperative chemotherapy setting. Most recently, however, in Eastern countries, perioperative SOX was demonstrated to be effective in specific advanced gastric cancer. For stage IV gastric cancer, new therapeutic strategies have been proposed such as neoadjuvant chemotherapy and conversion surgery, and cures can be conditionally obtained. Recent genomic understanding of gastric cancer proposed a diversity of molecular targets by molecular profiling. Such optimized chemotherapy regimens, according to the specific clinical situations, have been rigorously established for the best survival of advanced gastric cancer.
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Affiliation(s)
- Keishi Yamashita
- Division of Advanced Surgical Oncology, Research and Development Center for New Medical FrontiersKitasato University School of MedicineSagamiharaJapan
- Department of Upper Gastrointestinal SurgeryKitasato University School of MedicineSagamiharaJapan
| | - Kei Hosoda
- Department of Upper Gastrointestinal SurgeryKitasato University School of MedicineSagamiharaJapan
| | - Masahiro Niihara
- Department of Upper Gastrointestinal SurgeryKitasato University School of MedicineSagamiharaJapan
| | - Naoki Hiki
- Department of Upper Gastrointestinal SurgeryKitasato University School of MedicineSagamiharaJapan
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10
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Preoperative chemotherapy could modify recurrence patterns through postoperative complications in patients with gastric cancer. Langenbecks Arch Surg 2021; 406:1045-1055. [PMID: 33745003 DOI: 10.1007/s00423-021-02153-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 03/16/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE Postoperative infectious complications have a negative impact on survival outcomes in patients with gastric cancer. It is recently reported that preoperative chemotherapy may eliminate this negative impact. This study aimed to confirm whether preoperative chemotherapy can eliminate the negative impact of postoperative infectious complications (IC) on survival outcomes and elucidate the association between postoperative infectious complications and recurrence patterns. METHODS We retrospectively reviewed data of 86 patients who received preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by R0 gastrectomy at the Kitasato University between 2006 and 2016. Patients who developed grade II or higher infectious complications during hospitalization were grouped into the IC group, while others were grouped into the non-IC (NIC) group. Survival outcomes and recurrence patterns were analyzed between the two groups. RESULTS Infectious complications with Clavien-Dindo classification of grade II or higher were found in 12 patients (14.0%, IC group). The median observational period was 61 months. Overall survival and progression-free survival were similar in the IC and NIC groups. Recurrence occurred in 39 patients. The proportions of peritoneal and lymph node recurrences were not significantly different between the two groups. However, the proportion of distant metastasis in the IC group was significantly higher than that in NIC group (3/4 [75%] vs. 9/35 [17%], p = 0.04). CONCLUSIONS Pathological stage after neoadjuvant therapy plays a stronger role in recurrence than postoperative complications. Lymph node and peritoneal metastasis may be suppressed by preoperative chemotherapy.
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11
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Ohnuma H, Sato Y, Onoyama N, Hamaguchi K, Hayasaka N, Sato M, Murase K, Takada K, Miyanishi K, Murakami T, Ito T, Nobuoka T, Takemasa I, Kato J. Survival benefit of conversion surgery after intensive chemotherapy for unresectable metastatic gastric cancer: a propensity score-matching analysis. J Cancer Res Clin Oncol 2021; 147:2385-2396. [PMID: 33534051 DOI: 10.1007/s00432-021-03516-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 01/09/2021] [Indexed: 12/23/2022]
Abstract
PURPOSE The clinical benefit of conversion surgery (CS) for unresectable gastric cancer (GC), whereby unresectable GC responds to chemotherapy and subsequently receives curative-intent surgery, remains unclear. Here, we aimed to clarify the clinical value of CS. METHODS In this retrospective cohort study, we analyzed 175 unresectable GC, who received triple combined chemotherapy between 2004 and 2019. We divided patients into two groups: those who underwent CS and those receiving chemotherapy only (CS and C groups, respectively). Propensity score matching was used to minimize confounding bias. RESULTS Of 175 cases, 61 (34.9%) underwent CS. R0 resection was obtained in 85.2%. After matching, 44 pairs were selected; there were no significant differences in baseline covariants. Group CS had a significantly better median overall survival (OS) (18.8 vs. 46.0 months, p < 0.001), and prolonged progression-free survival (7.4 vs. 25.8 months, p < 0.001). Subgroup analysis of OS showed a favorable trend for CS for almost all subgroups. Multivariate analysis revealed that good ECOG performance status and CS were associated with a longer OS. CONCLUSION The survival benefit of CS was consistently demonstrated in the univariate and multivariate analysis, even in the matched cohort. Additional large-scale trials are needed for further validation.
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Affiliation(s)
- Hiroyuki Ohnuma
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Yasushi Sato
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Naoki Onoyama
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kota Hamaguchi
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Naotaka Hayasaka
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Masanori Sato
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kazuyuki Murase
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kohichi Takada
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Koji Miyanishi
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Takeshi Murakami
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tatsuya Ito
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Takayuki Nobuoka
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Junji Kato
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan.
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12
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Kinoshita J, Yamaguchi T, Moriyama H, Fushida S. Current status of conversion surgery for stage IV gastric cancer. Surg Today 2021; 51:1736-1754. [PMID: 33486610 DOI: 10.1007/s00595-020-02222-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 11/02/2020] [Indexed: 12/23/2022]
Abstract
Palliative chemotherapy with best supportive care is a mainstay for patients with gastric cancer (GC) and distant metastasis. However, with advances in GC chemotherapy, multimodal treatment, including perioperative chemotherapy plus conversion surgery, has attracted attention as a new strategy to improve the outcome of patients with stage IV disease. Conversion surgery is defined as surgical treatment aimed at R0 resection after a good response to induction chemotherapy for tumors originally considered unresectable or marginally resectable for technical and/or oncological reasons. Various biological characteristics differ, depending on each metastatic condition in stage IV GC. The main metastatic pathways of GC can be divided into three categories: lymphatic, hematogenous, and peritoneal. In each category, considerable historical data on conversion surgery have demonstrated the benefits of individualized approaches. However, owing to the diversity of these conditions, a common definition, including the choice of induction chemotherapy, optimal timing of resection, and eligibility for conversion surgery, has not been established among surgical oncologists. Thus, we explore the current and future treatment options by reviewing the literature on this controversial topic comprehensively.
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Affiliation(s)
- Jun Kinoshita
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Takahisa Yamaguchi
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Hideki Moriyama
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Sachio Fushida
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
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13
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Sun G, Wang S, Liu G. Preoperative neoadjuvant chemotherapy on surgical condition and oncogene expression in advanced gastric cancer. Pak J Med Sci 2020; 36:485-489. [PMID: 32292457 PMCID: PMC7150411 DOI: 10.12669/pjms.36.3.1608] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Objective To evaluate the effect of preoperative neoadjuvant chemotherapy regimen of XELOX (capecitabine combined with oxaliplatin) on surgical condition and oncogene expression in advanced gastric cancer. Methods From January 2015 to July 2016, 124 patients with advanced gastric cancer who were admitted to our hospital were selected. Random number table method was used to divide them into an observation group and a control group, 62 each group. The observation group received two courses of neoadjuvant chemotherapy (XELOX) before operation, and the control group received surgery. The operation condition, expression of oncogenes in gastric cancer lesions, occurrence of adverse reactions and the long-term prognosis were compared between the two groups. Results The R0 resection rate of the observation group was significantly higher than that of the control group, and the difference was statistically significant (P<0.05). The operation time of the observation group was shorter than that of the control group, the amount of intraoperative bleeding and the amount of postoperative drainage of the observation group were less than that of the control group, and the differences were statistically significant (P<0.05). The mRNA expression of gastrokine 1, multiple tumor suppressor protein, Wilms tumor gene on the X chromosome (WTX gene) and gene of phosphate and tension homology deleted on chromosome ten (PTEN gene) in the observation group after treatment was significantly higher than that in the control group before treatment, and the increase amplitude of the observation group was more obvious than that of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). In terms of long-term prognosis, the disease-free survival time and average survival time of the observation group during the two-year follow-up period were significantly better than those of the control group, and the recurrence rate of the observation group was significantly lower than that of the control group; the differences were statistically significant (P<0.05). Conclusion Preoperative XELOX for advanced gastric cancer patients can effectively increase the proportion of radical surgery, reduce the risk of surgery, and significantly regulate the expression of oncogene, thus improving the long-term prognosis of patients.
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Affiliation(s)
- Guangyu Sun
- Guangyu Sun, Department of Oncology, Binzhou People's Hospital, Shandong 256600, China
| | - Shuyan Wang
- Shuyan Wang, Department of Oncology, Binzhou People's Hospital, Shandong 256600, China
| | - Guangsheng Liu
- Guangsheng Liu, Department of Oncology, Binzhou People's Hospital, Shandong 256600, China
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14
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Conversion Surgery in Metastatic Gastric Cancer and Cancer Dormancy as a Prognostic Biomarker. Cancers (Basel) 2019; 12:cancers12010086. [PMID: 31905818 PMCID: PMC7016667 DOI: 10.3390/cancers12010086] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 12/23/2019] [Accepted: 12/24/2019] [Indexed: 12/24/2022] Open
Abstract
The role of conversion surgery in metastatic gastric cancer remains unclear. Cancer dormancy markers might have a role in predicting the survival in patients with conversion surgery. We identified 26 patients who went through conversion surgery, i.e., a curative-intent gastrectomy with metastasectomy after chemotherapy in initially metastatic gastric cancer. As controls, 114 potential candidates for conversion surgery who only received chemotherapy were included for the propensity score matching. Conversion surgery showed a significantly longer overall survival (OS) compared with only palliative chemotherapy (median-43.6 vs. 14.0 months, respectively, p < 0.001). This better survival in the conversion surgery group persisted even after propensity matching (p < 0.001), and also when compared to patients with tumor response over 5.1 months in the chemotherapy only group (p = 0.005). In the conversion surgery group, OS was longer in patients with R0 resection (22/26, 84.6%) than without R0 resection (4/26, 15.4%) (median-not reached vs 22.1 months, respectively, p = 0.005). Although it should be interpreted with caution due to the primitive analysis in a small population, the positive expression of NR2F1 showed a longer duration of disease-free survival (DFS) after conversion surgery (p = 0.016). In conclusion, conversion surgery showed a durable OS even in patients with initially metastatic gastric cancer when R0 resection was achieved after chemotherapy.
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15
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Zhang F, Huang X, Song Y, Gao P, Zhou C, Guo Z, Shi J, Wu Z, Wang Z. Conversion Surgery for Stage IV Gastric Cancer. Front Oncol 2019; 9:1158. [PMID: 31788445 PMCID: PMC6854003 DOI: 10.3389/fonc.2019.01158] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 10/17/2019] [Indexed: 12/24/2022] Open
Abstract
The prognosis of stage IV gastric cancer (GC) is poor, with palliative chemotherapy remaining the main therapeutic option. Studies increasingly indicate that patients with unresectable stage IV GC, who undergo gastrectomy with radical intention after responding to several regimens of combined chemotherapy, can achieve good survival outcomes. Thus, surgery aiming at radical resection for unresectable stage IV GC after combined chemotherapy has received increasing attention in recent years. This novel therapeutic strategy was defined as conversion surgery in patients with unresectable stage IV GC and it can associate with significant improved survival when R0 resection can be achieved. Despite the recent advances in conversion surgery for patients with unresectable stage IV GC, selection criteria for combination chemotherapy regimens, indications for conversion surgery, optimal timing to surgery, and postoperative chemotherapy all remain controversial. This article reviews the current state of conversion surgery for unresectable stage IV GC.
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Affiliation(s)
- Fei Zhang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xuanzhang Huang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yongxi Song
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Peng Gao
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Cen Zhou
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhexu Guo
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jinxin Shi
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhonghua Wu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhenning Wang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
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16
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Solaini L, Ministrini S, Bencivenga M, D'Ignazio A, Marino E, Cipollari C, Molteni B, Mura G, Marrelli D, Graziosi L, Roviello F, De Manzoni G, Tiberio GAM, Morgagni P. Conversion gastrectomy for stage IV unresectable gastric cancer: a GIRCG retrospective cohort study. Gastric Cancer 2019; 22:1285-1293. [PMID: 31065878 DOI: 10.1007/s10120-019-00968-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 04/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. METHODS A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. RESULTS Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI > 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25 months (IQR 9-50). Median overall survival from surgery was 15 months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12 months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72-11.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04-31.4, p = 0.045). CONCLUSIONS Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement.
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Affiliation(s)
- Leonardo Solaini
- General and Oncologic Surgery, Department of Surgery, Morgagni-Pierantoni Hospital, Via Forlanini 34, Forlì, Italy
| | - Silvia Ministrini
- Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy
| | - Maria Bencivenga
- General and Upper GI Surgery Division, University of Verona, Verona, Italy
| | - Alessia D'Ignazio
- Department of Surgery, Policlinico le Scotte- University of Siena, Siena, Italy
| | - Elisabetta Marino
- Department of Surgery, Santa Maria della Misericordia Hospital University of Perugia, Perugia, Italy
| | - Chiara Cipollari
- General and Upper GI Surgery Division, University of Verona, Verona, Italy
| | - Beatrice Molteni
- Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy
| | - Gianni Mura
- Department of Surgery, Azienda USl Toscana SudEst- Arezzo, Arezzo, Italy
| | - Daniele Marrelli
- Department of Surgery, Policlinico le Scotte- University of Siena, Siena, Italy
| | - Luigina Graziosi
- Department of Surgery, Santa Maria della Misericordia Hospital University of Perugia, Perugia, Italy
| | - Franco Roviello
- Department of Surgery, Policlinico le Scotte- University of Siena, Siena, Italy
| | | | - Guido A M Tiberio
- Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy
| | - Paolo Morgagni
- General and Oncologic Surgery, Department of Surgery, Morgagni-Pierantoni Hospital, Via Forlanini 34, Forlì, Italy.
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Wang T, Wang N, Ren H, Zhou H, Zhou A, Jin J, Chen Y, Zhao D. Long-term Results of Conversion Therapy for Initially Unresectable Gastric Cancer: Analysis of 122 Patients at the National Cancer Center in China. J Cancer 2019; 10:5975-5985. [PMID: 31762807 PMCID: PMC6856572 DOI: 10.7150/jca.35527] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Accepted: 08/18/2019] [Indexed: 02/07/2023] Open
Abstract
Purpose: To assess the long-term survival and prognostic factors of conversion therapy in patients with initially unresectable gastric cancer. Patients and methods: We conducted a retrospective study of clinicopathological and survival data of 122 consecutive patients who were diagnosed with initially unresectable gastric cancer and underwent the conversion surgery after systemic chemotherapy at the China National Cancer Center between May 2006 and May 2017. Results: For all the 122 patients, the 3- and 5-year overall survival (OS) rates from the date of chemotherapy initiation were 61.0% and 52.0%, respectively, with a median OS of 63.6 months. During follow-up, the recurrence was observed in 49 (40.1%) patients who underwent conversion surgery. According to the multivariate COX regression analysis, receipt of postoperative adjuvant chemotherapy (POAC) was the only significant independent predictor of a favorable OS (HR 0.40; 95% CI 0.18-0.85, P=0.017). Log-rank analysis showed that POAC group experienced a survival advantage in terms of PFS when compared with observation group (HR 0.53, 95%CI 0.31-0.92, P=0.009). Conclusions: Conversion therapy may provide long-term survival for patients with initially unresectable gastric cancer. Postoperative adjuvant chemotherapy might be recommended for patients who underwent conversion therapy.
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Affiliation(s)
- Tongbo Wang
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Nianchang Wang
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hu Ren
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hong Zhou
- Department of Pancreatic and Gastric Surgical Oncology, 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, Beijing 100021, China
| | - Jing Jin
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yingtai Chen
- Department of Pancreatic and Gastric Surgical Oncology, 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 Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Sato S, Kunisaki C, Tanaka Y, Sato K, Miyamoto H, Yukawa N, Kosaka T, Akiyama H, Endo I, Misumi T. Curative-Intent Surgery for Stage IV Advanced Gastric Cancer: Who Can Undergo Surgery and What Are the Prognostic Factors for Long-Term Survival? Ann Surg Oncol 2019; 26:4452-4463. [PMID: 31529308 DOI: 10.1245/s10434-019-07790-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND A retrospective study was performed to evaluate the predictive factors for performing curative-intent surgery and prognostic factors for long-term survival of patients undergoing surgery for stage IV gastric cancer. PATIENTS AND METHODS Between 2001 and 2017, 271 patients with stage IV gastric cancer with distant metastasis who underwent systemic chemotherapy were enrolled. Logistic regression analysis was performed to evaluate predictive factors for curative-intent surgery. Cox proportional hazards regression model was applied for patients who were subsequently treated with curative-intent surgery to identify prognostic factors for long-term survival. RESULTS Curative-intent surgery was performed in 48 patients (17.7%). Median survival time was significantly longer in the surgery group than in the nonsurgery group (53 vs. 11 months, p < 0.0001). R0 resection was performed in 35 patients (72.9%). The three-year overall survival (OS) rates of the R0, R1, and R2 surgery groups were 75.4%, 33.3%, and 25.0%, respectively (p = 0.0002). Logistic regression analysis revealed that lymphogenous distant metastasis alone (odds ratio = 3.276, p = 0.004), positive lavage cytology alone (6.394, 0.014), doublet or triplet chemotherapy (4.064, 0.034), and high Glasgow prognostic score (0.276, 0.001) were independent predictive factors for performing curative-intent surgery. Among patients undergoing surgery, the Cox proportional hazards regression model for OS showed that R0 surgery was an independent prognostic factor for favorable OS (hazard ratio 0.188, p = 0.022). CONCLUSIONS Patients with lymphogenous distant metastasis alone, P0CY1 alone, good immunonutritional status, and doublet/triplet chemotherapy are candidates for performing effective curative-intent surgery. R0 surgery is crucial for improving long-term survival after surgery.
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Affiliation(s)
- Sho Sato
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan.,Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Chikara Kunisaki
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan.
| | - Yusaku Tanaka
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Kei Sato
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Hiroshi Miyamoto
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Norio Yukawa
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Takashi Kosaka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Hirotoshi Akiyama
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Toshihiro Misumi
- Department of Biostatistics, School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
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19
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A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1, followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer: results of the KDOG1001 trial. Gastric Cancer 2019; 22:598-606. [PMID: 30284080 DOI: 10.1007/s10120-018-0884-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 09/29/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prognosis of patients with gastric cancer with bulky node metastasis, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) remains poor. We conducted a phase II study to evaluate the safety and efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS) for establishing a new treatment modality that improves prognosis. METHODS Patients received up to four 28-day cycles of DCS therapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 nodal dissection. S-1 chemotherapy was administered for 1 year after surgical resection. The primary endpoint was the percentage of complete resections of the primary tumor with clear margins (R0 resection). The planned sample size was 40; this was calculated based on an expected R0 rate of 85% and a threshold R0 rate of 65%, with a one-sided alpha of 5% and a power of 90%. RESULTS Between 2010 and 2017, 40 patients were enrolled. The R0 resection rate was 90%. The most common grade 3 or 4 adverse events during DCS therapy were leukocytopenia (27.5%), neutropenia (55.0%), and hyponatremia (22.5%). The most common grade 3 or 4 surgical morbidity was pancreatic fistula (12.5%); mortality was 0%. The pathological response rate was 57.5% with a grade 3 histological response rate of 8%. CONCLUSIONS Neoadjuvant chemotherapy with DCS was feasible and showed a sufficient R0 resection rate. A future study with a sufficient follow-up period should confirm survival outcomes.
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20
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Hosoda K, Watanabe M, Yamashita K. Re-emerging role of macroscopic appearance in treatment strategy for gastric cancer. Ann Gastroenterol Surg 2019; 3:122-129. [PMID: 30923781 PMCID: PMC6422795 DOI: 10.1002/ags3.12218] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 09/16/2018] [Accepted: 09/22/2018] [Indexed: 12/22/2022] Open
Abstract
Pathological outcomes are definitely the most important prognostic factors in gastric cancer, but they can be obtained only after surgical resection. Use of preoperative adjuvant chemotherapy is becoming widespread for aggressive human cancer, so clinical factors such as macroscopic features are important as they are highly predictive for patient prognosis. In gastric cancer, the macroscopic type represents a distinct prognosis; Type 0 represents early gastric cancer with excellent prognosis, but, among advanced tumors, giant Type III and Type IV tumors have a dismal prognosis. Japan Clinical Oncology Group (JCOG) Stomach Cancer Study Group adopted macroscopic features as high-risk entities in clinical trials. It makes sense for risk classification to use macroscopic phenotypes because The Cancer Genome Atlas (TCGA) Network has lately subcategorized different histologies associated with specific macroscopic types by the molecular features of the whole genome. Dismal prognosis of Type IV gastric cancer is notorious, but similar prognosis was seen in giant Type III gastric cancer defined as 8 cm or beyond, both of which are unique for their propensity of peritoneal dissemination. In this review, clinical relevance including prognosis of such macroscopic high-risk features will be separately debated in the context of precision medicine and updated prognostic outcomes will be presented under the present standard therapy of curative surgery followed by postoperative S-1 chemotherapy. Moreover, promising emerging novel therapeutic strategies including trimodal potent regimens or intraperitoneal chemotherapy will be described for such aggressive gastric cancer.
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Affiliation(s)
- Kei Hosoda
- Department of SurgeryKitasato University School of MedicineSagamiharaJapan
| | - Masahiko Watanabe
- Department of SurgeryKitasato University School of MedicineSagamiharaJapan
| | - Keishi Yamashita
- Department of SurgeryKitasato University School of MedicineSagamiharaJapan
- Division of Advanced Surgical Oncology, Research and Development Center for New Medical FrontiersKitasato University School of MedicineSagamiharaJapan
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21
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Zurleni T, Gjoni E, Altomare M, Rausei S. Conversion surgery for gastric cancer patients: A review. World J Gastrointest Oncol 2018; 10:398-409. [PMID: 30487951 PMCID: PMC6247102 DOI: 10.4251/wjgo.v10.i11.398] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 09/25/2018] [Accepted: 10/07/2018] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is the third most common cancer-related cause of death worldwide. In locally advanced tumors, neoadjuvant chemotherapy has recently been introduced in most international Western guidelines. For metastatic and unresectable disease, there is still debate regarding correct management and the role of surgery. The standard approach for stage IV GC is palliative chemotherapy. Over the last decade, an increasing number of M1 patients who responded to palliative regimens of induction chemotherapy have been subsequently undergone surgery with curative intent. The objective of the present review is to analyze the literature regarding this approach, known as “conversion surgery”, which has become one of the most commonly adopted therapeutic options. It is defined as a treatment aiming at an R0 resection after chemotherapy in initially unresectable tumors. The 13 retrospective studies analyzed, with a total of 411 patients treated with conversion therapy, clearly show that even if standardization of unresectable and metastatic criteria, post-chemotherapy resectability evaluation and timing of surgery has not yet been established, an R0 surgery after induction chemotherapy with partial or complete response seems to offer superior survival results than chemotherapy alone. Additional larger sample-size randomized control trials are needed to identify subgroups of well-stratified patients who could benefit from this multimodal approach.
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Affiliation(s)
- Tommaso Zurleni
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Elson Gjoni
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Michele Altomare
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Stefano Rausei
- Department of Surgery, ASST Valle Olona, Gallarate. 21013, Italy
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22
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Namikawa T, Tsuda S, Fujisawa K, Iwabu J, Uemura S, Tsujii S, Maeda H, Kitagawa H, Kobayashi M, Hanazaki K. Conversion surgery after S-1 plus oxaliplatin combination chemotherapy for advanced gastric cancer with multiple liver metastases. Clin J Gastroenterol 2018; 11:297-301. [PMID: 29500608 DOI: 10.1007/s12328-018-0842-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Accepted: 02/23/2018] [Indexed: 02/08/2023]
Abstract
Conversion therapy for gastric cancer is a new therapeutic concept. We report a case of a patient with advanced gastric cancer who underwent conversion surgery due to a remarkable regression of multiple liver metastases following chemotherapy. A 71-year-old man was referred to our hospital with gastric cancer. Esophagogastroduodenoscopy (EGD) revealed an irregular, nodular, ulcerated lesion in the lower third of the stomach. Analysis of biopsy specimens revealed a poorly differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography (CT) showed multiple liver mass lesions. The patient was clinically diagnosed with advanced gastric cancer with liver metastases and received S-1 plus oxaliplatin chemotherapy. After 6 cycles of chemotherapy, CT and magnetic resonance imaging showed complete resolution of the liver metastases, and EGD detected mucosal irregularities only. Since there was no evidence of further metastatic lesions in other organs, the patient underwent distal gastrectomy with D2 lymphadenectomy. The gross appearance of the surgically resected specimen showed a slightly elevated tumor measuring 4.5 × 3.5 cm. Pathological examination confirmed the diagnosis of a moderately differentiated gastric adenocarcinoma invading the muscularis propria with no lymph node metastases. The postoperative course was uneventful. The patient has continued to receive S-1 and oxaliplatin chemotherapy, and there has been no evidence of recurrence for 3 months following the operation. We propose that conversion therapy might be an effective treatment for patients with advanced gastric cancer; however, further studies and assessments are needed to confirm and establish this treatment strategy.
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Affiliation(s)
- Tsutomu Namikawa
- Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
| | - Sachi Tsuda
- Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| | - Kazune Fujisawa
- Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| | - Jun Iwabu
- Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| | - Sunao Uemura
- Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| | - Shigehiro Tsujii
- Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| | - Hiromichi Maeda
- Cancer Treatment Center, Kochi Medical School Hospital, Kochi, Japan
| | - Hiroyuki Kitagawa
- Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| | - Michiya Kobayashi
- Cancer Treatment Center, Kochi Medical School Hospital, Kochi, Japan
- Department of Human Health and Medical Sciences, Kochi Medical School, Kochi, Japan
| | - Kazuhiro Hanazaki
- Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
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23
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Morgagni P, Solaini L, Framarini M, Vittimberga G, Gardini A, Tringali D, Valgiusti M, Monti M, Ercolani G. Conversion surgery for gastric cancer: A cohort study from a western center. Int J Surg 2018; 53:360-365. [PMID: 29654967 DOI: 10.1016/j.ijsu.2018.04.016] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 03/15/2018] [Accepted: 04/08/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Advanced unresectable gastric cancer has a dismal prognosis. The aim of this study was to evaluate the short- and long-term outcomes of patients who underwent induction chemotherapy ± gastrectomy for advanced gastric cancer. MATERIAL AND METHODS All patients referred to our center with a clinical diagnosis of unresectable locally advanced or stage IV gastric adenocarcinoma between April 2005 and August 2016 were included in the study. Cox regression was performed to find independent prognostic factor among the considered variable. RESULTS The cohort included 73 patients: 16 had best supportive care, 35 chemotherapy alone and 22 chemotherapy plus radical surgery. Thirty-three patients underwent surgery after chemotherapy. Twenty-two patients had R0 surgery, while the remaining 11 had only an exploratory procedure. Nine patients (40.9%) underwent gastrectomy plus hyperthermic intraperitoneal chemotherapy. Three patients out of 22 developed postoperative complications with a Clavien-Dindo grade above 2. Median survival was 50 months for patients who had chemotherapy plus surgery while it was 14 and 3 for those who had chemotherapy alone and best supportive care, respectively (p < 0.0001). Cox regression analysis performed on the whole cohort identified only radical conversion surgery as an independent factor positively associated with survival (HR 0.12, 95% CI 0.05-0.29, p < 0.0001). CONCLUSION Conversion gastrectomy, when R0 could be achieved, is associated with long survivals and it is the most important prognostic factor in patients with advanced gastric cancer. Further studies are needed to define the ideal patient who can really benefit from this treatment.
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Affiliation(s)
- Paolo Morgagni
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Leonardo Solaini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
| | - Massimo Framarini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Giovanni Vittimberga
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Andrea Gardini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Domenico Tringali
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Martina Valgiusti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Manlio Monti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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24
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Abstract
PURPOSE Oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) is not inferior to standard weekly fluorouracil and folinate for stage II/III colon cancer. However, protein-bound polysaccharide K (PSK) has been evaluated as postoperative adjuvant therapy for colorectal cancer. This report is the first of MCSGO-CCTG, which compared UFT/LV to UFT/PSK as adjuvant chemotherapy for stage IIB or III colorectal cancer in patients who had undergone Japanese D2/D3 lymph node dissection. METHODS The primary endpoint was the 3-year disease-free survival (DFS). A randomized non-inferiority study compared UFT/LV to UFT/PSK. The overall survival, adverse events, compliance, and quality of life were also investigated as the secondary endpoints. RESULTS Between March 2006 and December 2010, 357 patients were randomized to UFT/PSK (n = 178) or UFT/LV (n = 179) (median age 65 years, colon/rectum 67.4/32.6%, stage IIB/IIIA/IIIB/IIIC 11.1/15.7/55.0/18.2%). The 3-year DFS rate was 82.3% in those receiving UFT/LV and 72.1% in those receiving UFT/PSK. The non-inferiority of UFT/PSK adjuvant therapy to UFT/LV therapy was not verified (-9.06%, 90% confidence interval -17.06 to -1.06%). The 3-year overall survival rate was 95.4% in those receiving UFT/LV and 90.7% in those receiving UFT/PSK. CONCLUSIONS As adjuvant chemotherapy for stage IIB and III colorectal cancer patients, UFT/PSK adjuvant therapy was not non-inferior to UFT/LV therapy with respect to the DFS.
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