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Nie GL, Geng L, Zhang H, Chu S, Jiang H. Nomograms of risk prediction and prognosis for the T1-T2 stage gastric cancer with lymph node metastasis: a population-based study. Front Med (Lausanne) 2025; 12:1492041. [PMID: 40070650 PMCID: PMC11893835 DOI: 10.3389/fmed.2025.1492041] [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: 09/06/2024] [Accepted: 01/03/2025] [Indexed: 03/14/2025] Open
Abstract
Background and aims Lymph node metastasis plays a crucial role in determining the appropriate treatment approach for patients with gastric cancer (GC), particularly those in the T1-T2 stage. Currently available diagnostic strategies for GC with lymph nodes have limited accuracy. The present research aimed to create and validate diagnostic and prognostic nomograms specifically tailored for the T1-T2 stage GC patients with LNM. Methods We derived clinicopathological characteristics of patients diagnosed with GC from the Surveillance, Epidemiology, and End Results (SEER) database. We utilized univariate and multivariate logistic analyses to examine the risk factors linked with the occurrence of lymph node metastasis (LNM) in GC patients within the T1-T2 stage. Furthermore, the prognostic factors related to the T1-T2 stage GC patients with LNM were explored by univariate and multivariate cox analyses. Two nomograms were built by the risk factors screened above. Results Ultimately, our study included 5,350 patients with T1-T2 stage GC. After identifying age, T stage, tumor size, primary site, grade, and histological type as risk factors for the LNM occurrence, we successfully developed a diagnostic nomogram utilizing these variables. Age, T stage, M stage, tumor size, primary site, grade, radiation, surgery, and chemotherapy were all independent prognostic factors that related to the T1 - T2 GC patients with LNM. The results of the AUC, calibration curve and decision curve analysis (DCA) showed excellent calibration performance and clinical applicability of the two nomograms. The Kaplan-Meier (K-M) curves clearly demonstrated a notable distinction in overall survival between low-risk and high-risk groups, highlighting the prognostic significance of the nomogram. Conclusion The establishment and validation of the two nomograms for T1-T2 GC patients with LNM were successful, serving as valuable tools for clinical decision-making and the formulation of personalized treatment approaches.
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Affiliation(s)
- Guo-Le Nie
- Department of Colorectal Hernia Surgery, Binzhou Medical University Hospital, Binzhou, China
- The First School of Clinical Medicine of Binzhou Medical University, Binzhou, China
| | - Longlong Geng
- Department of Colorectal Hernia Surgery, Binzhou Medical University Hospital, Binzhou, China
- The First School of Clinical Medicine of Binzhou Medical University, Binzhou, China
| | - Hao Zhang
- Department of Colorectal Hernia Surgery, Binzhou Medical University Hospital, Binzhou, China
- The First School of Clinical Medicine of Binzhou Medical University, Binzhou, China
| | - Shicheng Chu
- Department of Colorectal Hernia Surgery, Binzhou Medical University Hospital, Binzhou, China
- The First School of Clinical Medicine of Binzhou Medical University, Binzhou, China
| | - Hong Jiang
- Department of Colorectal Hernia Surgery, Binzhou Medical University Hospital, Binzhou, China
- The First School of Clinical Medicine of Binzhou Medical University, Binzhou, China
- Department of Major Surgery, Binzhou Medical University Hospital, Binzhou, China
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Nakabayashi Y, Ohashi T, Kubota T, Nishibeppu K, Yubakami M, Konishi H, Shiozaki A, Fujiwara H, Otsuji E. The impact of preoperative skeletal muscle loss on the completion of S-1 adjuvant chemotherapy for gastric cancer. Surg Today 2025; 55:238-246. [PMID: 39080037 DOI: 10.1007/s00595-024-02902-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 06/24/2024] [Indexed: 01/24/2025]
Abstract
PURPOSE Body weight loss after surgery for gastric cancer is related to S-1 compliance and it also affects the prognosis. However, it is unclear whether the preoperative skeletal muscle mass affects S-1 completion for gastric cancer. We investigated the impact of preoperative skeletal muscle mass loss on the completion of S-1 adjuvant chemotherapy for gastric cancer. METHODS We retrospectively analyzed data from 53 patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy for pStage II-III gastric cancer between 2012 and 2021 at our hospital. The psoas muscle mass index (PMI) was used as the index for preoperative skeletal muscle mass. RESULTS Thirty-six patients completed S-1 treatment and 17 discontinued treatment. The patients who completed S-1 treatment had a longer overall survival than those who discontinued treatment (log-rank test, p = 0.043). According to a univariate analysis, the patients in the discontinuation group had a significantly lower preoperative body mass index (< 22.9 kg/m2, p = 0.005) and a higher rate of adverse events (grade 2 or higher, p < 0.001) than those in the completion group. According to a multivariate analysis, preoperative PMI (HR 3.563, p = 0.030) was an independent predictive factor for S-1 completion. CONCLUSION Preoperative skeletal muscle loss might therefore prevent the completion of adjuvant chemotherapy S-1 in patients with gastric cancer.
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Affiliation(s)
- Yudai Nakabayashi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Takuma Ohashi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Takeshi Kubota
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Keiji Nishibeppu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Masayuki Yubakami
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hitoshi Fujiwara
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
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Pracucho EM, Zanatto RM, Oliveira JCD, Lopes LR. PERIOPERATIVE CHEMOTHERAPY, ADJUVANT CHEMOTHERAPY AND ADJUVANT CHEMORADIOTHERAPY IN THE SURGICAL TREATMENT OF GASTRIC CANCER IN A HOSPITAL OF THE BRAZILIAN UNIFIED HEALTH SYSTEM. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2024; 37:e1810. [PMID: 38958346 PMCID: PMC11216411 DOI: 10.1590/0102-6720202400017e1810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 04/08/2024] [Indexed: 07/04/2024]
Abstract
BACKGROUND Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor. AIMS To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting. METHODS The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded. RESULTS Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%). CONCLUSIONS The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.
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Affiliation(s)
| | - Renato Morato Zanatto
- Hospital Amaral Carvalho, Department of Abdominal and Pelvic Surgery - Jaú (SP), Brazil
| | | | - Luiz Roberto Lopes
- Universidade Estadual de Campinas, Faculty of Medical Sciences, Department of Surgery - Campinas (SP), Brazil
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Lee G, Strickland MR, Wo JY. Role of Preoperative Radiation Therapy for Resectable Gastric Cancer. J Gastrointest Cancer 2024; 55:584-598. [PMID: 38353901 DOI: 10.1007/s12029-023-00985-6] [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] [Accepted: 11/11/2023] [Indexed: 06/20/2024]
Abstract
PURPOSE While surgery is the primary curative treatment for resectable gastric and gastroesophageal junction (GEJ) cancer, rates of locoregional and distant recurrence remain high with surgery alone, especially in more advanced disease. Multimodal approaches with perioperative therapy including chemotherapy and/or radiation therapy (RT) have thus evolved as ways to reduce the rates of disease recurrence and improve survival outcomes. This review article provides a comprehensive literature review on the role of preoperative RT for resectable gastric and GEJ cancer. METHODS A literature review on the role of preoperative RT for resectable gastric and GEJ cancer was conducted. RESULTS Preoperative RT has the potential to facilitate tumor downstaging and improved R0 resection, allowing for better locoregional control and thereby survival. For resectable locally advanced GEJ cancer, preoperative chemoradiotherapy (CRT) is currently a standard of care option along with perioperative chemotherapy, based on evidence from randomized trials. In resectable gastric cancer, however, the role of preoperative CRT is less defined with no randomized data to date, although phase II single-arm studies have shown promising results. Current standard of care for gastric cancer remains perioperative chemotherapy, with consideration for preoperative CRT in select cases. CONCLUSION Results from ongoing and future randomized controlled trials are expected to help define the role of preoperative CRT compared to perioperative chemotherapy alone as well as postoperative CRT for gastric and GEJ cancer.
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Affiliation(s)
- Grace Lee
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Matthew R Strickland
- Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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Wang X, Zhang L. The systemic oxidative stress score has a prognostic value on gastric cancer patients undergoing surgery. Front Oncol 2024; 14:1307662. [PMID: 38525419 PMCID: PMC10957578 DOI: 10.3389/fonc.2024.1307662] [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: 10/06/2023] [Accepted: 02/26/2024] [Indexed: 03/26/2024] Open
Abstract
Background Oxidative stress is strongly associated with the development, recurrence metastasis, and treatment of gastric cancer. It is yet unknown, though, how systemic oxidative stress levels relate to the surgically treated gastric cancer patients' clinical results. This research aims to investigate the prognostic effect of systemic oxidative stress score, also known as systematic oxidative stress score (SOS), on gastric cancer patients undergoing surgical treatment. Methods Development of the SOS Formula through Least Absolute Shrinkage and Selection Operator LASSO Cox Regression. By using optimal cut-off values, the 466 patients included in the study had been split into high SOS and low SOS groups. Utilizing Chi-square test and the Wilcoxon rank sum test, this research examined the relationship between SOS and clinical traits. With the aid of Kaplan-Meier and COX regression analysis, the prognosis of patients with gastric cancer was examined. Results SOS consisted of four oxidative stress-related laboratory indices. Univariate and multivariate COX regression analyses revealed that SOS, Age, CA724, Radical resection and TNM stage were crucial prognostic factors for OS, and the independent prognostic factors for PFS included Age, CA724, TNM stage and SOS. They could have their prognosis correctly predicted using a nomogram built around SOS and independent prognostic variables. Conclusion SOS is a practical and reasonably priced tool for determining a patient's prognosis for gastric cancer. More notably, SOS is an accurate prognostic factor for patients with advanced gastric cancer who has undergone radical surgery.
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Affiliation(s)
| | - Limin Zhang
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China
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Qu T, Zhang S, Yang S, Li S, Wang D. Utilizing serum metabolomics for assessing postoperative efficacy and monitoring recurrence in gastric cancer patients. BMC Cancer 2024; 24:27. [PMID: 38166693 PMCID: PMC10763142 DOI: 10.1186/s12885-023-11786-2] [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: 08/12/2023] [Accepted: 12/21/2023] [Indexed: 01/05/2024] Open
Abstract
OBJECTIVE (1) This study aims to identify distinct serum metabolites in gastric cancer patients compared to healthy individuals, providing valuable insights into postoperative efficacy evaluation and monitoring of gastric cancer recurrence; (2) Methods: Serum samples were collected from 15 healthy individuals, 16 gastric cancer patients before surgery, 3 months after surgery, 6 months after surgery, and 15 gastric cancer recurrence patients. T-test and analysis of variance (ANOVA) were performed to screen 489 differential metabolites between the preoperative group and the healthy control group. Based on the level of the above metabolites in the recurrence, preoperative, three-month postoperative, and six-month postoperative groups, we further selected 18 significant differential metabolites by ANOVA and partial least squares discriminant analysis (PLS-DA). The result of hierarchical clustering analysis about the above metabolites showed that the samples were regrouped into the tumor-bearing group (comprising the original recurrence and preoperative groups) and the tumor-free group (comprising the original three-month postoperative and six-month postoperative groups). Based on the results of PLS-DA, 7 differential metabolites (VIP > 1.0) were further selected to distinguish the tumor-bearing group and the tumor-free group. Finally, the results of hierarchical clustering analysis showed that these 7 metabolites could well identify gastric cancer recurrence; (3) Results: Lysophosphatidic acids, triglycerides, lysine, and sphingosine-1-phosphate were significantly elevated in the three-month postoperative, six-month postoperative, and healthy control groups, compared to the preoperative and recurrence groups. Conversely, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol were significantly reduced in the three-month postoperative, six-month postoperative, and healthy control groups compared to the preoperative and recurrence groups. However, these substances did not show significant differences between the preoperative and recurrence groups, nor between the three-month postoperative, six-month postoperative, and healthy control groups; (4) Conclusions: Our findings demonstrate the presence of distinct metabolites in the serum of gastric cancer patients compared to healthy individuals. Lysophosphatidic acid, triglycerides, lysine, sphingosine-1-phosphate, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol hold potential as biomarkers for evaluating postoperative efficacy and monitoring recurrence in gastric cancer patients. These metabolites exhibit varying concentrations across different sample categories.
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Affiliation(s)
- Tong Qu
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, 71 Xinmin Street, 130021, Changchun, Jilin, P.R. China
| | - Shaopeng Zhang
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, 71 Xinmin Street, 130021, Changchun, Jilin, P.R. China
| | - Shaokang Yang
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, 71 Xinmin Street, 130021, Changchun, Jilin, P.R. China
| | - Shuang Li
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, 71 Xinmin Street, 130021, Changchun, Jilin, P.R. China
| | - Daguang Wang
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, 71 Xinmin Street, 130021, Changchun, Jilin, P.R. China.
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Pang T, Nie M, Yin K. The correlation between the margin of resection and prognosis in esophagogastric junction adenocarcinoma. World J Surg Oncol 2023; 21:316. [PMID: 37814242 PMCID: PMC10561513 DOI: 10.1186/s12957-023-03202-7] [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: 08/08/2023] [Accepted: 09/30/2023] [Indexed: 10/11/2023] Open
Abstract
Adenocarcinoma of the gastroesophageal junction (AEG) has become increasingly common in Western and Asian populations. Surgical resection is the mainstay of treatment for AEG; however, determining the distance from the upper edge of the tumor to the esophageal margin (PM) is essential for accurate prognosis. Despite the relevance of these studies, most have been retrospective and vary widely in their conclusions. The PM is now widely accepted to have an impact on patient outcomes but can be masked by TNM at later stages. Extended PM is associated with improved outcomes, but the optimal PM is uncertain. Academics continue to debate the surgical route, extent of lymphadenectomy, preoperative tumor size assessment, intraoperative cryosection, neoadjuvant therapy, and other aspects to further ensure a negative margin in patients with gastroesophageal adenocarcinoma. This review summarizes and evaluates the findings from these studies and suggests that the choice of approach for patients with adenocarcinoma of the esophagogastric junction should take into account the extent of esophagectomy and lymphadenectomy. Although several guidelines and reviews recommend the routine use of intraoperative cryosections to evaluate surgical margins, its generalizability is limited. Furthermore, neoadjuvant chemotherapy and radiotherapy are more likely to increase the R0 resection rate. In particular, intraoperative cryosections and neoadjuvant chemoradiotherapy were found to be more effective for achieving negative resection margins in signet ring cell carcinoma.
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Affiliation(s)
- Tao Pang
- Department of Gastrointestinal Tract Surgery, First Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Mingming Nie
- Department of Gastrointestinal Tract Surgery, First Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Kai Yin
- Department of Gastrointestinal Tract Surgery, First Affiliated Hospital of Naval Military Medical University, Shanghai, China.
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Shih YH, Lin HC, Liao PW, Chou CW, Lin CH, Hsu CY, Teng CLJ, Wu FH, Luo SC, Kao SH. The efficacy of adjuvant chemotherapy for older adults with stage II/III gastric cancer: a retrospective cohort study. BMC Cancer 2023; 23:770. [PMID: 37596599 PMCID: PMC10436551 DOI: 10.1186/s12885-023-11244-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 08/01/2023] [Indexed: 08/20/2023] Open
Abstract
BACKGROUND Adjuvant chemotherapy is recommended as the standard treatment for patients with stage II/III resected gastric cancer. However, it is unclear whether older patients also benefit from an adjuvant chemotherapy strategy. This study aimed to investigate the clinical impact of adjuvant chemotherapy in older patients with stage II/III gastric cancer. METHODS This retrospective, real-world study analyzed 404 patients with stage II/III gastric cancer visited at our institute between January 2009 and December 2019. The clinical characteristics and outcomes of patients aged 70 years or older who received adjuvant chemotherapy were compared with those who did not receive this type of treatment. Propensity score analysis was performed to mitigate selection bias. RESULTS Of the 404 patients analyzed, 179 were aged 70 years or older. Fewer older patients received adjuvant chemotherapy than did younger patients (60.9% vs. 94.7%, respectively; P < 0.001). Among patients aged 70 years or older, those who received adjuvant chemotherapy had improved disease-free survival (DFS) (5-year DFS rate, 53.1% vs. 30.4%; P < 0.001) and overall survival (OS) (5-year OS rate, 68.7% vs. 52.1%; P = 0.002) compared to those who did not receive adjuvant chemotherapy. A similar survival benefit was observed in the propensity-matched cohort. Multivariate analysis showed that more advanced stage was associated with poorer OS. Receipt of adjuvant chemotherapy was independently associated with a decreased hazard of death (hazard ratio (HR), 0.37; 95% confidence intervals (CI), 0.20-0.68; P = 0.002). CONCLUSIONS Adjuvant chemotherapy may benefit older stage II/III gastric cancer patients aged ≥ 70 years. Further prospective studies are needed to confirm these findings.
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Affiliation(s)
- Yu-Hsuan Shih
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Institute of Medicine, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, 402, Taichung, Taiwan
| | - Hsin-Chen Lin
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Po-Wei Liao
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Cheng-Wei Chou
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Cheng-Hsien Lin
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chiann-Yi Hsu
- Biostatistics Task Force, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chieh-Lin Jerry Teng
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Life Science, Tunghai University, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Feng-Hsu Wu
- Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Division of General Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Nursing, HungKuang University, Taichung, Taiwan
| | - Shao-Ciao Luo
- Institute of Medicine, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, 402, Taichung, Taiwan
- Division of General Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shao-Hsuan Kao
- Institute of Medicine, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, 402, Taichung, Taiwan.
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
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Schizas D, Mylonas KS, Syllaios A, Kapetanakis EI, Hasemaki N, Ntomi V, Michalinos A, Theochari NA, Theochari CA, Krivan S, Mpoura M, Bakopoulos A, Karavokyros I, Liakakos T. Gastrectomy for Cancer: A 15-Year Analysis of Real-World Data from the University of Athens. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58121792. [PMID: 36556994 PMCID: PMC9787625 DOI: 10.3390/medicina58121792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/19/2022] [Accepted: 11/30/2022] [Indexed: 12/09/2022]
Abstract
Background and Objectives: Encouraging data have been reported from referral centers following gastrointestinal cancer surgery. Our goal was to retrospectively review patient outcomes following gastrectomy for gastric or gastroesophageal junction (GEJ) cancer at a high-volume unit of the University of Athens. Methods: The enrollment period was from June 2003 to September 2018. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were constructed to identify variables independently associated with time-to-event outcomes. Results: A total of 205 patients were analyzed. R0 resection was achieved in 183 (89.3%) patients and was more likely to occur following neoadjuvant chemotherapy (p = 0.008). Recurrence developed in 46.6% of our cohort and the median disease-free survival was 31.2 months. On multivariate analysis, only staging (HR = 2.15; 95% CI: 1.06-4.36) was independently associated with increased risk of recurrence. All-cause mortality was 57.2% and the median time of death was 40.9 months. On multivariate regression, staging (HR: 1.35; 95% CI: 1.11-1.65) and recurrence (HR: 2.87; 95% CI: 1.32-6.22) predicted inferior prognosis. Conclusions: Gastrectomy at the University of Athens has yielded favorable outcomes for patients with GEJ cancer.
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Affiliation(s)
- Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Konstantinos S. Mylonas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Athanasios Syllaios
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Emmanouil I. Kapetanakis
- Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece
- Correspondence: ; Tel.: +30-6909200780
| | - Natasha Hasemaki
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Vasileia Ntomi
- Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece
| | | | - Nikoletta A. Theochari
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Christina A. Theochari
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Sylvia Krivan
- Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece
| | - Maria Mpoura
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Anargyros Bakopoulos
- Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece
| | - Ioannis Karavokyros
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
| | - Theodoros Liakakos
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece
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van Amelsfoort RM, Walraven I, Kieffer J, Jansen EPM, Cats A, van Grieken NCT, Meershoek-Klein Kranenbarg E, Putter H, van Sandick JW, Sikorska K, van de Velde CJH, Aaronson NK, Verheij M. Quality of Life Is Associated With Survival in Patients With Gastric Cancer: Results From the Randomized CRITICS Trial. J Natl Compr Canc Netw 2022; 20:261-267. [PMID: 35276669 DOI: 10.6004/jnccn.2021.7057] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 05/03/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND The evaluation of health-related quality of life (HRQoL) in clinical trials has become increasingly important because it addresses the impact of treatment from the patient's perspective. The primary aim of this study was to investigate the effect of postoperative chemotherapy and chemoradiotherapy (CRT) after neoadjuvant chemotherapy and surgery with extended (D2) lymphadenectomy on HRQoL in the CRITICS trial. Second, we investigated the potential prognostic value of pretreatment HRQoL on event-free survival (EFS) and overall survival (OS). PATIENTS AND METHODS Patients in the CRITICS trial were asked to complete HRQoL questionnaires (EORTC Quality-of-Life Questionnaire-Core 30 and Quality-of-Life Questionnaire gastric cancer-specific module) at baseline, after preoperative chemotherapy, after surgery, after postoperative chemotherapy or CRT, and at 12 months follow-up. Patients with at least 1 evaluable questionnaire (645 of 788 randomized patients) were included in the HRQoL analyses. The predefined endpoints included dysphagia, pain, physical functioning, fatigue, and Quality-of-Life Questionnaire-Core 30 summary score. Linear mixed modeling was used to assess differences over time and at each time point. Associations of baseline HRQoL with EFS and OS were investigated using multivariate Cox proportional hazards analyses. RESULTS At completion of postoperative chemo(radio)therapy, the chemotherapy group had significantly better physical functioning (P=.02; Cohen's effect size = 0.42) and less dysphagia (P=.01; Cohen's effect size = 0.38) compared with the CRT group. At baseline, worse social functioning (hazard ratio [HR], 2.20; 95% CI, 1.36-3.55; P=.001), nausea (HR, 1.89; 95% CI, 1.39-2.56; P<.001), worse WHO performance status (HR, 1.55; 95% CI, 1.13-2.13; P=.007), and histologic subtype (diffuse vs intestinal: HR, 1.94; 95% CI, 1.42-2.67; P<.001; mixed vs intestinal: HR, 2.35; 95% CI, 1.35-4.12; P=.003) were significantly associated with worse EFS and OS. CONCLUSIONS In the CRITICS trial, the chemotherapy group had significantly better physical functioning and less dysphagia after postoperative treatment. HRQoL scales at baseline were significantly associated with EFS and OS.
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Affiliation(s)
| | - Iris Walraven
- 1Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam.,2Department for Health Evidence, Radboud University Medical Center, Nijmegen
| | | | - Edwin P M Jansen
- 1Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam
| | - Annemieke Cats
- 4Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam
| | | | | | - Hein Putter
- 6Department of Surgical Oncology, Leiden University Medical Center, Leiden
| | | | - Karolina Sikorska
- 8Department of Biostatistics, Netherlands Cancer Institute, Amsterdam; and
| | | | - Neil K Aaronson
- 2Department for Health Evidence, Radboud University Medical Center, Nijmegen
| | - Marcel Verheij
- 1Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam.,9Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
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11
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Health-Related Quality of Life in Locally Advanced Gastric Cancer: A Systematic Review. Cancers (Basel) 2021; 13:cancers13235934. [PMID: 34885043 PMCID: PMC8657098 DOI: 10.3390/cancers13235934] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/19/2021] [Accepted: 11/23/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Current treatment strategies have been designed to improve survival in locally advanced gastric cancer patients. Besides its impact on survival, treatment also affects health-related quality of life (HRQOL), but an overview of reported studies is currently lacking. The aim of this systematic review was therefore to determine the short- and long-term impact of chemotherapy, surgery, and (chemo)radiotherapy on HRQOL in locally advanced, non-metastatic gastric cancer patients. METHODS A systematic review was performed including studies published between January 2000 and February 2021. We extracted studies published in Medline, Embase, and Scopus databases that assessed HRQOL in patients with locally advanced, non-metastatic gastric cancer treated with curative intent. Studies using non-validated HRQOL questionnaires were excluded. Short-term and long-term HRQOL were defined as HRQOL scores within and beyond 6 months after treatment, respectively. RESULTS Initially, we identified 8705 articles (4037 of which were duplicates, i.e., 46%) and ultimately included 10 articles. Most studies reported that short-term HRQOL worsened in the follow-up period from 6 weeks to 3 months after surgery. However, recovery of HRQOL to preoperative levels occurred after 6 months. After completion of chemoradiotherapy, the same pattern was seen with worse HRQOL after treatment and a recovery of HRQOL after 6-12 months. CONCLUSIONS In patients with locally advanced, non-metastatic gastric cancer, HRQOL deteriorated during the first 3 months after surgery and chemoradiotherapy. However, the long-term data showed a recovery of HRQOL after 6-12 months. To implement HRQOL in clinical decision making in current clinical practice, more research is needed.
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12
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Huang M, Li J, Yu X, Xu Q, Zhang X, Dai X, Li S, Sheng L, Huang K, Liu L. Comparison of Efficacy and Safety of Third-Line Treatments for Advanced Gastric Cancer: A Systematic Review With Bayesian Network Meta-Analysis. Front Oncol 2021; 11:734323. [PMID: 34745955 PMCID: PMC8570109 DOI: 10.3389/fonc.2021.734323] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 10/07/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Although various third-line treatments of advanced gastric cancer (AGC) significantly improved the overall survival, the optimal regimen has not been determined by now. This study aims to evaluate the efficacy and safety of multiple third-line treatments of AGC via integrated analysis and network meta-analysis (NMA) to provide valuable evidence for the optimal third-line systemic therapy for AGC. METHODS By searching the databases of PubMed, Embase and the Cochrane Central Register of Controlled Trials from Jan 01, 2005 to Dec 31, 2020, we included phase II/III randomized clinical trials (RCTs) of the third-line treatments for AGC to perform NMA. The main outcomes for NMA were median overall survival (mOS), median progression-free survival (mPFS), disease control rate (DCR) and adverse events (AEs). We also included phase IB/II non-RCTs and II/III RCTs of the third-line immune checkpoint inhibitors (ICIs) for integrated analysis for pooled mOS (POS), pooled mPFS (PPFS) and other outcomes. RESULTS Eight phase II/III RCTs and 2 ICIs-related phase IB/II non-RCTs were included for analysis, involving 9 treatment regimens and 3012 AGC patients. In terms of mOS, apatinib (hazard ratio [HR] 0.61, 95% credible interval [CrI] 0.48-0.78) and nivolumab (HR 0.62, 95% CrI 0.51-0.76) were the most effective treatments compared with placebo. Apatinib also significantly improved mPFS versus placebo (HR 0.38, 95% CrI 0.29-0.49). Nivolumab ranked first among all regimens for 1-year OS rate and achieved the best OS in patients with HER-2 positive tumor, patients with gastroesophageal junction (GEJ) cancer and patients without gastrectomy history. TAS-102 (OR 7.46, 95% CrI 4.61-12.51) was the most toxic treatment in terms of AEs of grade 3 and higher (≥3 AEs). Pembrolizumab was more likely to cause immune related adverse event. Finally, the POS, pooled 1-year OS rate, pooled ORR and PPFS of AGC patients treated with third-line ICIs were 5.1 months, 25%, 10% and 1.71 months respectively. CONCLUSIONS Apatinib and nivolumab are the most effective treatments for the third-line treatment of AGC in contrast to the third-line chemotherapy. For AGC patients with HER-2 positive tumor, patients with GEJ cancer and patients without gastrectomy history, ICIs could be the optimal third-line treatment choice.
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Affiliation(s)
- Miao Huang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jisheng Li
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xuejun Yu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Qian Xu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xue Zhang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xin Dai
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Medical Oncology, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, China
| | - Song Li
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lei Sheng
- Department of Thyroid Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Kai Huang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lian Liu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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13
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Takashima Y, Komatsu S, Nishibeppu K, Kiuchi J, Ohashi T, Shimizu H, Arita T, Yamamoto Y, Konishi H, Morimura R, Shiozaki A, Kuriu Y, Ikoma H, Kubota T, Fujiwara H, Okamoto K, Otsuji E. Clinical impact of postoperative interval until adjuvant chemotherapy following curative gastrectomy for advanced gastric cancer. J Cancer 2021; 12:5960-5966. [PMID: 34476010 PMCID: PMC8408116 DOI: 10.7150/jca.58154] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 08/03/2021] [Indexed: 11/17/2022] Open
Abstract
Background: Adjuvant chemotherapy (AC) following curative gastrectomy for stage II/III gastric cancer (GC) is recommended in Japan. However, for various reasons, patients cannot always start AC at the appropriate time. This study was designed to investigate the effect of the postoperative interval until adjuvant chemotherapy (PIAC) and cumulative S-1 dose on prognosis. Methods: Between 2008 and 2014, consecutive 81 GC patients who underwent postoperative S-1 monotherapy were enrolled in this study. Results: Postoperative complications of Clavien-Dindo grade II or higher and postoperative peak C-reactive protein of 8.1 mg/dl or higher were significantly associated with delayed AC. The cut-off value of PIAC selected to most effectively stratify prognosis was 7 weeks. For relapse-free survival (RFS), patients with PIAC ≥ 7 weeks had an insignificantly poorer prognosis than those with PIAC < 7 weeks. A multivariate analysis showed that PIAC ≥ 7 weeks [p = 0.024; hazard ratio (HR) 2.45] and the cumulative S-1 dose/body surface area (BSA) ≥ 12,000 mg/m2 [p = 0.004; HR 3.27] were independent prognostic factors. In patients with the cumulative S-1 dose/BSA ≥ 12,000 mg/m2, there were no prognostic differences between patients with and without PIAC ≥ 7 weeks. Conclusions: Seven weeks after surgery could be a limit indicator starting AC. A cumulative S-1 dose/BSA of more than 12,000 mg/m2 might be a key dose for diminishing the poor prognostic effects of delaying AC.
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Affiliation(s)
- Yusuke Takashima
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Shuhei Komatsu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Keiji Nishibeppu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Jun Kiuchi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Takuma Ohashi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Hiroki Shimizu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Tomohiro Arita
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Yusuke Yamamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Ryo Morimura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Yoshiaki Kuriu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Hisashi Ikoma
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Takeshi Kubota
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Hitoshi Fujiwara
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Kazuma Okamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan
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14
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Hua D, Harizaj A, Wels M, Brans T, Stremersch S, De Keersmaecker H, Bolea-Fernandez E, Vanhaecke F, Roels D, Braeckmans K, Xiong R, Huang C, De Smedt SC, Sauvage F. Bubble Forming Films for Spatial Selective Cell Killing. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2021; 33:e2008379. [PMID: 34050986 DOI: 10.1002/adma.202008379] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 03/22/2021] [Indexed: 06/12/2023]
Abstract
Photodynamic and photothermal cell killing at the surface of tissues finds applications in medicine. However, a lack of control over heat dissipation following a treatment with light might damage surrounding tissues. A new strategy to kill cells at the surface of tissues is reported. Polymeric films are designed in which iron oxide nanoparticles are embedded as photosensitizers. Irradiation of the films with pulsed laser light generates water vapor bubbles at the surface of the films. It is found that "bubble-films" can kill cells in close proximity to the films due to mechanical forces which arise when the bubbles collapse. Local irradiation of bubble-films allows for spatial selective single cell killing. As nanosurgery becomes attractive in ophthalmology to remove superficial tumors, bubble-films are applied on the cornea and it is found that irradiation of the bubble-films allows spatial and selective killing of corneal cells. As i) the photosensitizer is embedded in the films, which reduces its uptake by cells and spreading into tissues and ii) the bubble-films can be removed from the tissue after laser treatment, while iii) a low laser fluence is sufficient to generate vapor bubbles, it is foreseen that bubble-films might become promising for safe resection of superficial tumors.
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Affiliation(s)
- Dawei Hua
- Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), College of Chemical Engineering, Nanjing Forestry University (NFU), Nanjing, 210037, P. R. China
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Aranit Harizaj
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Mike Wels
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Toon Brans
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Stephan Stremersch
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Herlinde De Keersmaecker
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Eduardo Bolea-Fernandez
- Department of Chemistry, Ghent University, Atomic & Mass Spectrometry - A&MS research group, Campus Sterre, Krijgslaan 281-S12, Ghent, 9000, Belgium
| | - Frank Vanhaecke
- Department of Chemistry, Ghent University, Atomic & Mass Spectrometry - A&MS research group, Campus Sterre, Krijgslaan 281-S12, Ghent, 9000, Belgium
| | - Dimitri Roels
- Department of Ophthalmology, Ghent University Hospital, Corneel Heymanslaan 10, Ghent, 9000, Belgium
| | - Kevin Braeckmans
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Ranhua Xiong
- Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), College of Chemical Engineering, Nanjing Forestry University (NFU), Nanjing, 210037, P. R. China
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Chaobo Huang
- Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), College of Chemical Engineering, Nanjing Forestry University (NFU), Nanjing, 210037, P. R. China
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Stefaan C De Smedt
- Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), College of Chemical Engineering, Nanjing Forestry University (NFU), Nanjing, 210037, P. R. China
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
| | - Félix Sauvage
- Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, 9000, Belgium
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15
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Liang L, Kang H, Jia J. HCP5 contributes to cisplatin resistance in gastric cancer through miR-128/HMGA2 axis. Cell Cycle 2021; 20:1080-1090. [PMID: 33993846 PMCID: PMC8208113 DOI: 10.1080/15384101.2021.1924948] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/26/2021] [Accepted: 04/28/2021] [Indexed: 12/24/2022] Open
Abstract
The long non-coding RNA HLA complex P5 (HCP5) is extensively related to cancer chemoresistance, while its function in gastric cancer (GC) has not been well elucidated yet. Here, the role and mechanism of HCP5 in regulating the chemoresistance of GC to cisplatin (DDP) was investigated. Our results revealed that HCP5 was increased in GC patients and indicated a poor prognosis. HCP5 knockdown weakens DDP resistance and reduced apoptosis of GC cells. miR-128 was decreased in GC patients and sponged by HCP5. HMGA2 was targeted by miR-128 and was increased in GC patients. HCP5 aggravated the resistance of GC cells to DDP in vitro by elevating HMGA2 expression via sponging miR-128. HCP5 silencing inhibited GC cells growth, resistance to DDP, and Ki-67 expression in vivo. In summary, HCP5 contributed to DDP resistance in GC cells through miR-128/HMGA2 axis, providing a promising therapeutic target for GC chemoresistance.
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Affiliation(s)
- Liqun Liang
- Department of Oncology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Hongchun Kang
- Department of Oncology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Junmei Jia
- Department of Oncology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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16
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Kapoor R, Dracham CB, G Y S, Khosla D, Dey T, Elangovan A, Madan R, Yadav BS, Kumar N. Clinical Outcomes and Prognostic Factors in Gastric Carcinoma Patients with Curative Surgery Followed by Adjuvant Treatment: Real-World Scenario. J Gastrointest Cancer 2021; 52:616-624. [PMID: 32535755 DOI: 10.1007/s12029-020-00440-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
BACKGROUND A wide range of adjuvant treatment regimens exist in gastric carcinoma patients which include chemotherapy, radiotherapy, and/or both either sequential or concurrent. The study aimed to assess the benefit of adjuvant sequential chemotherapy followed by radiotherapy for operable gastric cancers and evaluate the prognostic factors associated with clinical outcomes. METHODS Patients of stage IB-III gastric carcinoma who underwent radical surgery followed by adjuvant treatment from January 2013 to December 2016 were analyzed retrospectively. Survival was computed using Kaplan-Meier method and prognostic factors were analyzed in multivariate analysis using Cox progression hazard model. A P value < 0.05 was taken as statistically significant. RESULTS A total of 108 patients were identified with a median follow-up of 31.7 months (range: 6-96). Seventy-two percent of the patients received adjuvant sequential chemoradiation (N = 77) and 28% of patients received chemotherapy alone. The median survival was 26 months (95% CI: 23.09-28.90). Overall survival (OS) rates for 1, 2, 3, 4, and 5 years were 88.9%, 57.4%, 40.7%, 28.8%, and 20.4%, respectively. Five-year OS for stage-IB, II, and III was 75%, 45%, and 8.3%, respectively (p = 0.023). Surgical margin positivity (9.5% vs. 26.9%, p = 0.042), signet-ring cell histology (6.5% vs. 25.8%, p = 0.00), and adjuvant sequential chemoradiation (p = 0.002) showed a significant impact on survival outcomes and proved as independent prognostic factors. CONCLUSION The present study demonstrated that survival in gastric carcinoma is influenced by the stage of disease and surgical margins. In locally advanced patients, radical surgery followed by sequential chemoradiation based on a doublet/triplet regimen was an independent prognostic factor for survival. Majority of patients in our set-up presented in locally advanced stage, curative resection followed by adjuvant sequential chemoradiation was an independent prognostic factor for survival.
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Affiliation(s)
- Rakesh Kapoor
- Department of Radiotherapy and Oncology, PGIMER, Chandigarh, 160012, India
| | | | - Srinivasa G Y
- Department of Radiotherapy and Oncology, PGIMER, Chandigarh, 160012, India
| | - Divya Khosla
- Department of Radiotherapy and Oncology, PGIMER, Chandigarh, 160012, India
| | - Treshita Dey
- Department of Radiotherapy and Oncology, PGIMER, Chandigarh, 160012, India
| | - Arun Elangovan
- Department of Radiotherapy and Oncology, PGIMER, Chandigarh, 160012, India
| | - Renu Madan
- Department of Radiotherapy and Oncology, PGIMER, Chandigarh, 160012, India
| | - Budhi Singh Yadav
- Department of Radiotherapy and Oncology, PGIMER, Chandigarh, 160012, India
| | - Narendra Kumar
- Department of Radiotherapy and Oncology, PGIMER, Chandigarh, 160012, India
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17
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Liu ZN, Wang YK, Li ZY. Neoadjuvant chemoradiotherapy followed by laparoscopic distal gastrectomy in advanced gastric cancer: A case report and review of literature. World J Clin Cases 2021; 9:2542-2554. [PMID: 33889619 PMCID: PMC8040168 DOI: 10.12998/wjcc.v9.i11.2542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 12/03/2020] [Accepted: 02/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The laparoscopic technique has been widely applied for early gastric cancer, with the advantages of minimal invasion and quick recovery. However, there is no report about the safety and oncological outcome of laparoscopic gastrectomy with D2 lymph node dissection for patients after neoadjuvant chemoradiotherapy.
CASE SUMMARY A 60-year-old man was diagnosed with advanced distal gastric cancer, cT4aN1M0 stage III. The neoadjuvant chemoradiotherapy was performed based on the regimen of gross tumor volume 50G y/25 f and clinical target volume 45 Gy/25 f, as well as concurrent S-1 60 mg Bid. Then laparoscopic distal gastrectomy with D2 lymph node dissection was undertaken successfully for him after achieving partial response evaluated by radiological examination. The patient recovered smoothly without moderate or severe postoperative complications. The postoperative pathological stage was ypT3N0M0 with American Joint Committee on Cancer tumor regression grade 1. He was still in good condition after 5 years of follow-up.
CONCLUSION Neoadjuvant chemoradiotherapy followed by laparoscopic technique could be applicable and may achieve satisfactory oncological outcomes. Our finding requires further validation by cohort studies.
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Affiliation(s)
- Zi-Ning Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yin-Kui Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zi-Yu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
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18
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Mansouri H, Zemni I, Achouri L, Mahjoub N, Ayedi MA, Ben Safta I, Ben Dhiab T, Chargui R, Rahal K. Chemoradiotherapy or chemotherapy as adjuvant treatment for resected gastric cancer: should we use selection criteria? ACTA ACUST UNITED AC 2021; 26:266-280. [PMID: 34211778 DOI: 10.5603/rpor.a2021.0040] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 02/08/2021] [Indexed: 12/24/2022]
Abstract
Background The management of gastric adenocarcinoma is essentially based on surgery followed by adjuvant treatment. Adjuvant chemotherapy (CT) as well as chemoradiotherapy (CTRT) have proven their effectiveness in survival outcomes compared to surgery alone. However, there is little data comparing the two adjuvant approaches. This study aimed to compare the prognosis and survival outcomes of patients with gastric adenocarcinoma operated and treated by adjuvant radio-chemotherapy or chemotherapy. Materials and methods We retrospectively evaluated 80 patients with locally advanced gastric cancer (LGC) who received adjuvant treatment. We compared survival outcomes and patterns of recurrence of 53 patients treated by CTRT and those of 27 patients treated by CT. Results After a median follow-up of 38.48 months, CTRT resulted in a significant improvement of the 5-year PFS (60.9% vs. 36%, p = 0.03) and the 5-year OS (55.9% vs. 33%, p = 0.015) compared to adjuvant CT. The 5-year OS was significantly increased by adjuvant CTRT (p = 0.046) in patients with lymph node metastasis, and particularly those with advanced pN stage (p = 0.0078) and high lymph node ratio (LNR) exceeding 25% (p = 0.012). Also, there was a significant improvement of the PFS of patients classified pN2-N3 (p = 0.022) with a high LNR (p = 0.018). CTRT was also associated with improved OS and PFS in patients with lymphovascular and perineural invasion (LVI and PNI) compared to chemotherapy. Conclusion There is a particular survival benefit of adding radiotherapy to chemotherapy in patients with selected criteria such as lymph node involvement, high LNR LVI, and PNI.
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Affiliation(s)
- Houyem Mansouri
- Department of Surgical Oncology, Salah Azaiez institute of oncology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia
| | - Ines Zemni
- Department of Surgical Oncology, Salah Azaiez institute of oncology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia.,Laboratory of Microorganisms and Active Biomolecules, Faculty of sciences, University of Tunis El Manar, Tunisia
| | - Leila Achouri
- Department of surgical oncology, Regional Hospital of Jendouba, Tunisia
| | - Najet Mahjoub
- Department of medical oncology, Regional Hospital of Jendouba, Tunisia
| | - Mohamed Ali Ayedi
- Department of Surgical Oncology, Salah Azaiez institute of oncology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia.,Laboratory of Microorganisms and Active Biomolecules, Faculty of sciences, University of Tunis El Manar, Tunisia
| | - Ines Ben Safta
- Department of Surgical Oncology, Salah Azaiez institute of oncology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia.,Laboratory of Microorganisms and Active Biomolecules, Faculty of sciences, University of Tunis El Manar, Tunisia
| | - Tarek Ben Dhiab
- Department of Surgical Oncology, Salah Azaiez institute of oncology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia
| | - Riadh Chargui
- Department of Surgical Oncology, Salah Azaiez institute of oncology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia
| | - Khaled Rahal
- Department of Surgical Oncology, Salah Azaiez institute of oncology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia
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19
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Ahn GT, Baek SK, Han JJ, Kim HJ, Jeong SJ, Maeng CH. Optimal time interval from surgery to adjuvant chemotherapy in gastric cancer. Oncol Lett 2020; 20:32. [PMID: 32774505 PMCID: PMC7406879 DOI: 10.3892/ol.2020.11893] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 07/01/2020] [Indexed: 12/19/2022] Open
Abstract
The effect of adjuvant chemotherapy (AC) for resected gastric cancer is well established; however, delays in treatment and its impact on clinical outcomes have not yet been determined. The current study analyzed the survival rates based on time interval (TI) between surgery and AC administration to evaluate a potential association between the two variables. Patients diagnosed with stage II-III gastric adenocarcinoma between 2009 and 2016 at the Kyung Hee University Hospital were included. Patients' data including demographics, TNM stage, types of AC, and TI retrospectively collected from surgery to the start of AC. Patients were dichotomized based on the TI, which was predetermined at 3, 4, 5, 6, 7 or 8 weeks. Median disease-free survival (DFS) and overall survival (OS) were analyzed according to TI. In total, 172 patients were identified. The median follow-up duration was 40.8 (3-109) months. The median TI was 4.1 (2.1-9.8) weeks. DFS in patients with TI ≥4 weeks (n=106, 61.6%) was significantly lower compared with patients with TI <4 weeks (n=66, 38.4%), with a median DFS of TI < vs. ≥4 weeks of 8.1 vs. 6.0 years [hazard ratio (HR)=1.80, 95% confidence interval (CI): 1.067-3.045, P=0.0277]. OS was also significantly reduced in patients with TI ≥4 weeks, favoring TI <4 weeks [median OS of TI < vs. ≥4 weeks: Not reached (NR) vs. 7.0 years, HR=2.15, 95% CI: 1.173-3.939, P=0.0133]. Other predetermined TIs were not associated with survival outcomes. The current study demonstrated that AC within 4 weeks of surgery should be recommended for gastric cancer, and delays of >4 weeks may be detrimental to patients' survival.
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Affiliation(s)
- Geon Tae Ahn
- Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea
| | - Sun Kyung Baek
- Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea
- Division of Medical Oncology and Hematology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea
| | - Jae Joon Han
- Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea
- Division of Medical Oncology and Hematology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea
| | - Hong Jun Kim
- Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea
- Division of Medical Oncology and Hematology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea
| | - Su Jin Jeong
- Statistics Support Department, Medical Science Research Institute, Kyung Hee University Hospital, Seoul 02447, Korea
| | - Chi Hoon Maeng
- Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea
- Division of Medical Oncology and Hematology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea
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20
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Jin L, Ma XM, Wang TT, Yang Y, Zhang N, Zeng N, Bai ZG, Yin J, Zhang J, Ding GQ, Zhang ZT. Psoralen Suppresses Cisplatin-Mediated Resistance and Induces Apoptosis of Gastric Adenocarcinoma by Disruption of the miR196a-HOXB7-HER2 Axis. Cancer Manag Res 2020; 12:2803-2827. [PMID: 32368152 PMCID: PMC7185648 DOI: 10.2147/cmar.s248094] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 04/02/2020] [Indexed: 12/19/2022] Open
Abstract
Purpose The present study aimed to investigate the impact of psoralen on miR-196a-5p expression and function, and to reveal the mechanism underlying miR-196a-5p-mediated inhibition and the reversal of cisplatin (DDP) resistance. Methods Serum samples were collected from 50 patients with gastric cancer (GC), and the association between miR-196a-5p expression and the response to chemotherapy was assessed. A DDP-resistant GC cell line was also established to determine the effects of miR-196a-5p and psoralen on DDP resistance. MGC803 cells were transfected with miR-196a-5p mimic and inhibitor vectors for the overexpression and downregulation of miR-196a-5p, respectively. Results Clinical data analysis showed that the lower expression levels of miR-196a-5p were significantly associated with chemoresistance in patients with GC. Upregulation of miR-196a-5p significantly enhanced the anti-proliferative effect, apoptosis and sensitivity to DDP by regulating the protein expression levels of HOXB7, HER2, Bcl-2 and G1/S-specific cyclin-D1 (CCND1). Furthermore, psoralen reversed miR-196a-5p-induced DDP resistance and reduced the expression levels of HOXB7, HER2, Bcl-2 and CCND1. Conclusion miR-196a-5p may be a novel biomarker of chemotherapeutic success in patients with GC and may also influence the sensitivity of GC cells to DDP. Moreover, psoralen can increase chemotherapeutic sensitivity by upregulating miR-196a-5p and then downregulating HOXB7-HER2 signaling axis.
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Affiliation(s)
- Lei Jin
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.,National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China
| | - Xue-Mei Ma
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.,National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China
| | - Ting-Ting Wang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.,National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China
| | - Yao Yang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.,National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China
| | - Nan Zhang
- National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China.,Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Na Zeng
- National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China.,Clinical Epidemiology and EBM Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Zhi-Gang Bai
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.,National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China
| | - Jie Yin
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.,National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China
| | - Jun Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.,National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China
| | - Guo-Qian Ding
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.,National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China
| | - Zhong-Tao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.,National Clinical Research Center for Digestive Diseases, Beijing, People's Republic of China
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21
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Prognostic factors for survival in patients with gastric cancer: Single-centre experience. North Clin Istanb 2020; 7:146-152. [PMID: 32259036 PMCID: PMC7117626 DOI: 10.14744/nci.2019.73549] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 09/05/2019] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE: We aimed to investigate survival outcomes and survival-related prognostic factors in gastric cancer patients who were followed-up or received adjuvant therapy in our center. METHODS: Patients with gastric cancer treated between 2005 and 2016 were evaluated retrospectively. We included 345 non-metastatic (stage I-III) gastric cancer patients in the study. The clinical, demographic, histologic data of the patients and treatment characteristics were obtained from the patient’s files. RESULTS: While 50 patients were stage I, 94 patients were stage II, 201 patients were stage III. While 221 patients (64%) presenting with serosal or adjacent visceral organ invasion or with involved lymph nodes were treated with adjuvant chemoradiotherapy, 124 patients presenting with early-stage disease were followed after surgery. Median follow up time was 34 months (4–156 months). While the median overall survival (OS) was 51 months, median disease-free survival (DFS) was 35 months. Overall survival and disease-free survival rates for 1st, 3rd and 5th years were 85%, 55%, 45% and 72%, 49%, 38%, respectively. According to univariate analysis, tumor size, T stage (p<0.001), N stage (p<0.001), TNM stage (p<0.001), grade (p<0.001) and presence of lymphovascular invasion (p=0.005) were determined as prognostic factors that affect overall survival significantly. According to the multivariate analysis, only T and N stage (p<0.001) were determined as independent prognostic factors for overall survival. CONCLUSION: Many different prognostic factors have been defined for gastric cancer. In concordance with the literature, we found T and N stages as prognostic factors in univariate and multivariate analysis.
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22
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Effect of Hospital Volume With Respect to Performing Gastric Cancer Resection on Recurrence and Survival: Results From the CRITICS Trial. Ann Surg 2020; 270:1096-1102. [PMID: 29995679 DOI: 10.1097/sla.0000000000002940] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVE We examined the association between surgical hospital volume and both overall survival (OS) and disease-free survival (DFS) using data obtained from the international CRITICS (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) trial. SUMMARY BACKGROUND DATA In the CRITICS trial, patients with resectable gastric cancer were randomized to receive preoperative chemotherapy followed by adequate gastrectomy and either chemotherapy or chemoradiotherapy. METHODS Patients in the CRITICS trial who underwent a gastrectomy with curative intent in a Dutch hospital were included in the analysis. The annual number of gastric cancer surgeries performed at the participating hospitals was obtained from the Netherlands Cancer Registry; the hospitals were then classified as low-volume (1-20 surgeries/year) or high-volume (≥21 surgeries/year) and matched with the CRITICS trial data. Univariate and multivariate analyses were then performed to evaluate the hazard ratio (HR) between hospital volume and both OS and DFS. RESULTS From 2007 through 2015, 788 patients were included in the CRITICS trial. Among these 788 patients, 494 were eligible for our study; the median follow-up was 5.0 years. Five-year OS was 59.2% and 46.1% in the high-volume and low-volume hospitals, respectively. Multivariate analysis revealed that undergoing surgery in a high-volume hospital was associated with higher OS [HR = 0.69, 95% confidence interval (CI) = 0.50-0.94, P = 0.020] and DFS (HR = 0.73, 95% CI: 0.54-0.99, P = 0.040). CONCLUSIONS In the CRITICS trial, hospitals with a high annual volume of gastric cancer surgery were associated with higher overall and DFS. These findings emphasize the value of centralizing gastric cancer surgeries in the Western world.
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23
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Nishibeppu K, Komatsu S, Imamura T, Kiuchi J, Kishimoto T, Arita T, Kosuga T, Konishi H, Kubota T, Shiozaki A, Fujiwara H, Okamoto K, Otsuji E. Plasma microRNA profiles: identification of miR-1229-3p as a novel chemoresistant and prognostic biomarker in gastric cancer. Sci Rep 2020; 10:3161. [PMID: 32081926 PMCID: PMC7035283 DOI: 10.1038/s41598-020-59939-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 02/05/2020] [Indexed: 02/06/2023] Open
Abstract
This study aimed to explore novel microRNAs in plasma for predicting chemoresistance in adjuvant chemotherapy for patients with gastric cancer (GC). We used the Toray 3D-Gene microRNA array-based approach to compare preoperative plasma microRNA levels between GC patients with and without recurrences after curative gastrectomy. All patients underwent adjuvant chemotherapy with S-1, an oral fluoropyrimidine. Of 2566 candidates, six candidate microRNAs (miR-1229-3p, 1249-5p, 762, 711, 1268a and 1260b), which were highly expressed in the preoperative plasma of patients with subsequent recurrences, were selected. In a large-scale validation analysis by quantitative RT-PCR, we focused on high plasma levels of miR-1229-3p, which was an independent poor prognostic factor for recurrence free survival (P = 0.009, HR = 3.71). Overexpression of miR-1229-3p in GC cells induced significant chemoresistance to 5-fluorouracil (5-FU), up-regulation of thymidylate synthase (TS) and dihydroprimidine dehydrogenase (DPD) and down-regulation of SLC22A7 both in vitro and in vivo. Intraperitoneal injection of miR-1229-3p in mice induced significant chemoresistance to 5-FU, accompanied by high levels of miR-1229-3p in plasma and tumor tissue. These findings suggest that plasma miR-1229-3p might be a clinically useful biomarker for predicting chemoresistance to S-1 and selecting other or combined intensive chemotherapy regimens in GC patients.
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Affiliation(s)
- Keiji Nishibeppu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Shuhei Komatsu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Taisuke Imamura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Jun Kiuchi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Takuma Kishimoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Tomohiro Arita
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Toshiyuki Kosuga
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Takeshi Kubota
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hitoshi Fujiwara
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Kazuma Okamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
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24
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Shin K, Park SJ, Lee J, Park CH, Song KY, Lee HH, Seo HS, Jung YJ, Park JM, Lee SH, Roh SY, Kim IH. Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection according to lymph node ratio and N stage. BMC Cancer 2019; 19:1232. [PMID: 31852475 PMCID: PMC6921502 DOI: 10.1186/s12885-019-6433-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 12/04/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND We sought to assess the prognostic significance of lymph node ratio (LNR) and N stage in patients undergoing D2 gastrectomy and adjuvant chemotherapy, S-1, and XELOX and to compare the efficacy of them according to LNRs and N stages to evaluate the clinical impact of using LNRs compared with using N staging. METHODS Patients undergoing D2 gastrectomy with adequate lymph node dissection and adjuvant chemotherapy for stage II/III gastric cancer between Mar 2011 and Dec 2016 were analysed. Of the 477 patients enrolled, 331 received S-1 and 146 received XELOX. LNR groups were segregated as 0, 0-0.1, 0.1-0.25, and > 0.25 (LNR0, 1, 2, and 3, respectively). Propensity score matching (PSM) was used to minimise potential selection bias and compare DFS and OS stratified by LNRs and N stages in the two treatment groups. RESULTS After PSM, the sample size of each group was 110 patients, and variables were well balanced. All patients had more than 15 examined lymph nodes (median 51, range 16~124). In multivariate analysis, LNR (> 0.25) and N stage (N3) showed independent prognostic value in OS and DFS, but LNR (> 0.25) showed better prognostic value. In subgroup analysis, the LNR3 group showed better 5-year DFS (20% vs 54%; HR 0.29; p = 0.004) and 5-year OS (26% vs 67%; HR 0.28; p = 0.020) in the XELOX group. The N3 group showed better 5-year DFS (38% vs 66%; HR 0.40; p = 0.004) and 5-year OS (47% vs 71%; HR 0.45; p = 0.019) in the XELOX group. Stage IIIC showed better 5-year DFS (22% vs 57%; HR 0.32; p = 0.004) and 5-year OS (27% vs 68%; HR 0.32; p = 0.009) in the XELOX group. The LNR3 group within N3 patients showed better 5-year DFS (21% vs 55%; HR 0.31; p = 0.004) and 5-year OS (27% vs 68%; HR 0.34; p = 0.018) in the XELOX group. CONCLUSIONS LNR showed better prognostic value than N staging. LNR3, N3 and stage IIIC groups showed the superior efficacy of XELOX to that of S-1. And the LNR3 group within N3 patients showed more survival benefit from XELOX. LNR > 0.25, N3 stage and stage IIIC were the discriminant factors for selecting XELOX over S-1. TRIAL REGISTRATION Not applicable (retrospective study).
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Affiliation(s)
- Kabsoo Shin
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea
| | - Se Jun Park
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea
| | - Jinsoo Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea
| | - Cho Hyun Park
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
- Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Kyo Young Song
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
- Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Han Hong Lee
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
- Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Ho Seok Seo
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
- Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Yoon Ju Jung
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
- Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jae Myung Park
- Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Sung Hak Lee
- Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
- Department of Clinical Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Sang Young Roh
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea.
- Department of Gastric Cancer Centre, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
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Zhang X, Yang J, Huang Q, Lyu J. Prognostic factors in patients with gastric adenocarcinoma using competing-risk analysis: a study of cases in the SEER database. Scand J Gastroenterol 2019; 54:1015-1021. [PMID: 31382800 DOI: 10.1080/00365521.2019.1649456] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background: Accurate prognostic factors for gastric adenocarcinoma are still lacking in clinical practice, which contributes to inappropriate treatment. Applying the widely used Cox-proportional hazards model to describe survival trends and identify prognostic factors has limitations that result in a risk of bias. A competing-risk model was therefore adopted in this study to identify the significant prognostic factors and evaluate the cumulative incidence of cause-specific death for gastric adenocarcinoma, which can be used to guide clinical treatments. Methods: All of the cases analyzed in this study were extracted from the SEER (Surveillance, Epidemiology, and End Results) database. Using the competing risk approach, we calculated the cumulative incidence function (CIF) for cause-specific death and death from other causes at each time point. The Fine and Gray's proportional subdistribution hazard model was then applied in the univariate analysis and multivariate analysis to test the differences in CIF between different groups and obtain independent prognostic factors. Results: The univariate analysis showed that patients with characteristics of advanced pathology grade, lymph node involvement, and metastasis, were at risk of increasing cancer-specific mortality. Primary-site surgery, radiation with surgery, and chemotherapy, were associated with decreased cancer-specific mortality. The multivariate analysis showed that pathology grade, primary-site surgery, radiation with surgery, and chemotherapy, could significantly affect the cancer-specific mortality and were independent prognostic factors in patients with gastric adenocarcinoma. Conclusions: Using a competing-risk model, this study obtained more-accurate estimates for the cumulative incidence of cancer-specific death and identified the prognostic factors more accurately for gastric adenocarcinoma.
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Affiliation(s)
- Xu Zhang
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.,School of Public Health, Xi'an Jiaotong University Health Science Center , Xi'an , China
| | - Jin Yang
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.,School of Public Health, Xi'an Jiaotong University Health Science Center , Xi'an , China
| | - Qiao Huang
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University , Wuhan , China
| | - Jun Lyu
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.,School of Public Health, Xi'an Jiaotong University Health Science Center , Xi'an , China
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Zhang D, Wu JR, Duan XJ, Wang KH, Zhao Y, Ni MW, Liu SY, Zhang XM, Zhang B. A Bayesian Network Meta-Analysis for Identifying the Optimal Taxane-Based Chemotherapy Regimens for Treating Gastric Cancer. Front Pharmacol 2019; 10:717. [PMID: 31333452 PMCID: PMC6624233 DOI: 10.3389/fphar.2019.00717] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 06/05/2019] [Indexed: 01/30/2023] Open
Abstract
Background: Several taxane-based chemotherapy regimens are effective in the treatment of gastric cancer; nevertheless, their comparative efficacy and safety remain disputed. This network meta-analysis (NMA) was designed to compare the efficacy and safety of different taxane-based chemotherapy regimens against gastric cancer. Methods: A comprehensive search was conducted to identify all relevant randomized controlled trials (RCTs) in multiple electronic databases. A Bayesian NMA was performed to combine the direct and indirect evidence and estimate the comparative efficacy and safety of different taxane-based chemotherapy regimens simultaneously by utilizing WinBUGS 1.4.3 and Stata 13.1 software. The efficacy outcomes included overall survival rate (OS), progression-free survival (PFS), and overall response rate (ORR), and the safety outcomes were adverse reactions (ADRs), namely, neutropenia, leucopenia, vomiting, and fatigue. Results: A total of 37 RCTs were identified involving 7,178 patients with gastric cancer, and 10 taxane-based chemotherapy regimens (RT, T, TC, TCF, TF, TO, TOF, mTCF, mTF, and mTOF) were collected in gastric cancer therapy. According to the results of cluster analysis, compared with other taxane-based chemotherapy regimens, the regimens of TOF, mTCF, and TF were associated with the most favorable clinical efficacy in improving OS, PFS, and ORR. On the other hand, the regimens of T and mTF had the potential to be the most tolerable and acceptable therapeutic alternative in terms of ADRs. Conclusions: The current NMA provides the evidence that the combination of taxanes (paclitaxel or docetaxel) and fluorouracil is associated with the most preferable and beneficial option for patients with gastric cancer, although additional results from multicenter trials and high-quality studies will be pivotal for supporting our findings.
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Affiliation(s)
- Dan Zhang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Jia-Rui Wu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiao-Jiao Duan
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Kai-Huan Wang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yi Zhao
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Meng-Wei Ni
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Shu-Yu Liu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiao-Meng Zhang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Bing Zhang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
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Chan WL, Lam KO, So TH, Lee VHF, Kwong LWD. Third-line systemic treatment in advanced/metastatic gastric cancer: a comprehensive review. Ther Adv Med Oncol 2019; 11:1758835919859990. [PMID: 31285759 PMCID: PMC6600493 DOI: 10.1177/1758835919859990] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Accepted: 06/06/2019] [Indexed: 12/11/2022] Open
Abstract
The management of advanced gastric cancer has improved over the past decade.
There is more evidence to support the efficacy of systemic treatment in
refractory gastric cancer beyond second-line treatment. Important randomized
controlled trials of chemotherapies, targeted agents and immunotherapies have
been reported. With the development of these novel therapies, clinicians can
better individualize treatment for patients beyond progression on second-line
therapy. However, there is no guideline on third-line therapy available for
clinicians. This review discussed the efficacy and safety data from the pivotal
trials of the agents proven to be effective in third-line settings, including
the quality of study design, level of evidence and subgroup analysis, and how
the data can help to guide clinicians on selecting the most appropriate
third-line therapy for their patients.
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Affiliation(s)
- Wing-Lok Chan
- Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, 1/F Professorial Block, 102 Pokfulam Road, Hong Kong
| | - Ka-On Lam
- Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, 1/F Professorial Block, 102 Pokfulam Road, Hong Kong
| | - Tsz-Him So
- Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Victor Ho-Fun Lee
- Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Lai-Wan Dora Kwong
- Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, Hong Kong
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Struller F, Horvath P, Solass W, Weinreich FJ, Strumberg D, Kokkalis MK, Fischer I, Meisner C, Königsrainer A, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis: a phase II study. Ther Adv Med Oncol 2019; 11:1758835919846402. [PMID: 31205501 PMCID: PMC6535725 DOI: 10.1177/1758835919846402] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 04/04/2019] [Indexed: 01/11/2023] Open
Abstract
Background: Efficacy of second-line systemic chemotherapy in recurrent gastric cancer with peritoneal metastasis (RGCPM) is limited. We assessed the feasibility, safety and possible efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with RGCPM after ⩾1 line of palliative intravenous chemotherapy. Methods: In this open-label, single-arm, monocentric phase II ICH-GCP clinical trial, patients were scheduled for three courses of PIPAC with cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 (PIPAC C/D) every 6 weeks. Patients with bowel obstruction or extraperitoneal metastasis were ineligible. The primary endpoint was clinical benefit rate (CBR) by Response Evaluation Criteria in Solid Tumors based on clinical records. Secondary endpoints included overall survival (OS), median time to progression (TTP), peritoneal carcinomatosis index (PCI), histological regression and ascites volume. Safety and tolerability were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4, quality of life (QoL) by EORTC-QLQ30 questionnaire. Results: A total of 25 patients were enrolled and available for the analysis of the primary endpoint. Of those 25 patients, 10 (40%) had a radiological complete, partial response or stable disease. Median OS [intention to treat (ITT)] was 6.7 months, median TTP was 2.7 months. Complete or major regression on histology were observed in 9/25 patients (36%, ITT) or 6/6 [100%, per protocol (PP)] patients. There were no suspected unexpected serious adverse reactions, no treatment-related deaths, no CTCAE grade 4 toxicity and three (12%) grade 3 toxicities. Changes in the QLQ-C30 scores during PIPAC C/D therapy were small and not significant. Conclusions: PIPAC C/D was well tolerated and active in patients with RGCPM. Survival was encouraging. Randomized controlled trials should now be designed in this indication.
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Affiliation(s)
- Florian Struller
- Department of General and Transplant Surgery, Tübingen, University Hospital, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany
| | - Philipp Horvath
- Department of General and Transplant Surgery, University Hospital Tübingen, Germany
| | - Wiebke Solass
- Department of Pathology, University Hospital Tübingen, Germany
| | | | - Dirk Strumberg
- Department of Medical Oncology, Marien Hospital, Ruhr University Bochum, Germany
| | - Marios K Kokkalis
- Department of General and Transplant Surgery, University Hospital Tübingen, Germany
| | - Imma Fischer
- Institute for Clinical Epidemiology and Applied Biometrics, University Hospital Tübingen, Germany
| | - Christoph Meisner
- Institute for Clinical Epidemiology and Applied Biometrics, University Hospital Tübingen, Germany
| | - Alfred Königsrainer
- Department of General and Transplant Surgery, University Hospital Tübingen, Germany
| | - Marc A Reymond
- Department of General and Transplant Surgery, University Hospital Tübingen, Germany National Center for Pleura and Peritoneum, University Hospital, Tübingen, Germany
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Li Z, Wang Y, Ying X, Shan F, Wu Z, Zhang L, Li S, Jia Y, Ren H, Ji J. Different prognostic implication of ypTNM stage and pTNM stage for gastric cancer: a propensity score-matched analysis. BMC Cancer 2019; 19:80. [PMID: 30651085 PMCID: PMC6335703 DOI: 10.1186/s12885-019-5283-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 01/07/2019] [Indexed: 01/19/2023] Open
Abstract
Background Pathological stage is considered as the best prognosis indicator for gastric cancer. With the increasing use of neoadjuvant chemotherapy (NACT), the latest TNM staging included a new pathological stage of ypTNM for patients with NACT. However, no study has investigated if ypTNM stage has the same prognostic implication as pTNM stage for gastric cancer. Methods We retrospectively selected eligible patients within a prospectively maintained database containing all patients treated with gastric cancer in Peking University Cancer Hospital from 2007 to 2015 using overall survival as the outcome. Patients using ypTNM and pTNM were 1:1 matched by propensity scores (PS) calculated from a model containing variables associated with ypTNM use or survival. Overall survival was compared by unconditional Cox regression. Conventional multivariate analysis was conducted to corroborate PS matching results. Results 1441 patients were included in the analysis with a median follow-up of 37 months (range = 2–106). The matched sample contained 756 patients. After PS matching, patients with specific ypTNM stage were 1.34 (95%CI = 1.05–1.72, P = 0.019) times more likely to die than patients with the same pTNM stage. Similar to the results of PS matching, multivariate Cox regression yielded a hazard ratio (HR) of 1.35 (95%CI = 1.09–1.67, P = 0.006). Subgroup analysis indicated this survival difference between ypTNM and pTNM stage varied by the specific TNM stage of patients. The HR was 3.44 (95%CI = 1.06–11.18, P = 0.040) and 1.28 (95%CI = 1.00–1.62, P = 0.048) for patients in stage I and III, respectively; whereas for stage II patients, no significant difference was observed (HR = 1.37, 95%CI = 0.78–2.38, P = 0.27). Conclusion Gastric cancer patients with specific ypTNM stage had worse prognosis compared to those at the same stage defined by pTNM. Electronic supplementary material The online version of this article (10.1186/s12885-019-5283-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ziyu Li
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China
| | - Yinkui Wang
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China
| | - Xiangji Ying
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China
| | - Fei Shan
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China
| | - Zhouqiao Wu
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China
| | - Lianhai Zhang
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China
| | - Shuangxi Li
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China
| | - Yongning Jia
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China
| | - Hui Ren
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China
| | - Jiafu Ji
- Department of Gastrointestinal Cancer Center Surgery, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People's Republic of China.
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Yepuri N, Bahary N, Jain A, Dhir M. Review and Update on the Role of Peritoneal Cytology in the Treatment of Gastric Cancer. J Surg Res 2018; 235:607-614. [PMID: 30691849 DOI: 10.1016/j.jss.2018.10.049] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 08/12/2018] [Accepted: 10/26/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Positive peritoneal cytology (Cyt+) even in the absence of macroscopic disease is associated with poor prognosis in patients with gastric cancer and deemed as M1 disease. Recent years have seen advancements in the evaluation strategies for peritoneal washings and management of patients with Cyt+. The aim of this review was to describe the newest paradigms in the management of patients with gastric cancer who have Cyt+ without macroscopic peritoneal metastases. METHODS A comprehensive literature review was performed to identify studies on the management of gastric cancer and thereby to summarize relevant information on the accuracy of various diagnostic tests and controversies involved in the treatment of patients with Cyt+. RESULTS Although conventional cytology remains the standard technique for assessment of peritoneal washings, it is limited by low sensitivity. The role of immunohistochemistry and molecular techniques for the assessment of peritoneal washings is evolving. Although systemic chemotherapy remains the standard of care for patients with Cyt+ disease, the role of gastrectomy, intraperitoneal chemotherapy, extensive intraperitoneal saline lavage, and hyperthermic intraperitoneal chemotherapy is being evaluated. CONCLUSIONS Clinical decision-making in patients with Cyt+ remains controversial given the seemingly technical resectable albeit biologically unresectable or aggressive disease that portends an overall poor prognosis. Current management strategies are evolving, and further studies are needed to develop an optimal treatment strategy for these patients.
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Affiliation(s)
- Natesh Yepuri
- Division of Surgical Oncology, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York
| | - Nathan Bahary
- Division of Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Ajay Jain
- Division of Surgical Oncology, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York
| | - Mashaal Dhir
- Division of Surgical Oncology, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York.
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Min JS, Lee CM, Choi SI, Seo KW, Park DJ, Baik YH, Son MW, Choi WH, Kim S, Pak KH, Kim MG, Park JM, Jeong SH, Lee MS, Park S. Who Can Perform Adjuvant Chemotherapy Treatment for Gastric Cancer? A Multicenter Retrospective Overview of the Current Status in Korea. J Gastric Cancer 2018; 18:264-273. [PMID: 30276003 PMCID: PMC6160523 DOI: 10.5230/jgc.2018.18.e29] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 08/28/2018] [Accepted: 09/02/2018] [Indexed: 12/18/2022] Open
Abstract
Purpose To investigate the current status of adjuvant chemotherapy (AC) regimens in Korea and the difference in efficacy of AC administered by surgical and medical oncologists in patients with stage II or III gastric cancers. Materials and Methods We performed a retrospective observational study among 1,049 patients who underwent curative resection and received AC for stage II and III gastric cancers between February 2012 and December 2013 at 29 tertiary referral university hospitals in Korea. To minimize the influence of potential confounders on selection bias, propensity score matching (PSM) was used based on binary logistic regression analysis. The 3-year disease-free survival (DFS) rates were compared between patients who received AC administered by medical oncologists or surgical oncologists. Results Between February 2012 and December 2013 in Korea, the most commonly prescribed AC by medical oncologists was tegafur/gimeracil/oteracil (S-1, 47.72%), followed by capecitabine with oxaliplatin (XELOX, 16.33%). After performing PSM, surgical oncologists (82.74%) completed AC as planned more often than medical oncologists (75.9%), with statistical significance (P=0.036). No difference in the 3-year DFS rates of stage II (P=0.567) or stage III (P=0.545) gastric cancer was found between the medical and surgical oncologist groups. Conclusions S-1 monotherapy and XELOX are a main stay of AC, regardless of whether the prescribing physician is a medical or surgical oncologist. The better compliance with AC by surgical oncologists is a valid reason to advocate that surgical oncologists perform the treatment of AC for stage II or III gastric cancers.
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Affiliation(s)
- Jae-Seok Min
- Department of Surgery, Dongnam Institute of Radiological and Medical Sciences, Cancer Center, Busan, Korea
| | - Chang Min Lee
- Department of Surgery, Korea University Medical Center, Korea University College of Medicine, Seoul, Korea
| | - Sung Il Choi
- Department of Surgery, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Kyung Won Seo
- Department of Surgery, Kosin University College of Medicine, Busan, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yong Hae Baik
- Department of Surgery, Dongguk University Hospital, Goyang, Korea
| | - Myoung-Won Son
- Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Won Hyuk Choi
- Department of Surgery, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea
| | - Sungsoo Kim
- Department of Surgery, Chosun University College of Medicine, Gwangju, Korea
| | - Kyung Ho Pak
- Department of Surgery, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Min Gyu Kim
- Department of Surgery, Hanyang University Guri Hospital, Guri, Korea
| | - Joong-Min Park
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea
| | - Sang Ho Jeong
- Department of Surgery, Gyeongsang National University Hospital, Changwon, Korea
| | - Moon-Soo Lee
- Department of Surgery, Eulji University Hospital, Daejeon, Korea
| | - Sungsoo Park
- Department of Surgery, Korea University Medical Center, Korea University College of Medicine, Seoul, Korea
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Celli R, Barbieri AL, Colunga M, Sinard J, Gibson JA. Optimal Intraoperative Assessment of Gastric Margins. Am J Clin Pathol 2018; 150:353-363. [PMID: 30020407 DOI: 10.1093/ajcp/aqy062] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES Intraoperative pathology consultation (IOC) to assess margins is frequently requested during surgery of the stomach and gastroesophageal junction. METHODS We studied 110 consecutive patients undergoing gastrectomy with IOC margin assessment. RESULTS Gastric margins at IOC utilized the most blocks but were least often positive. In 64% of patients, the entire gastric margin was examined using average six blocks; representative sections were examined in 25% of patients using two blocks. There was no difference in patient outcome between those who had entire vs representative sections of margin examined. Gross variables showing strongest associations with positive margins were tumor size and tumor distance to margin. Tumors sized greater than 2.3 cm had significantly increased risk of positive margin, and tumor distance greater than 4.5 cm to margin was associated with negative margins. CONCLUSIONS We conclude representative sections of the closest gastric margin are sufficient to ensure R0 resection in the majority of cases.
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Affiliation(s)
- Romulo Celli
- Department of Pathology, Yale University School of Medicine, New Haven, CT
| | - Andrea L Barbieri
- Department of Pathology, Yale University School of Medicine, New Haven, CT
| | | | - John Sinard
- Department of Pathology, Yale University School of Medicine, New Haven, CT
| | - Joanna A Gibson
- Department of Pathology, Yale University School of Medicine, New Haven, CT
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Wongsirisin P, Limpakan Yamada S, Yodkeeree S, Punfa W, Limtrakul P. Association of DNA Repair and Drug Transporter in Relation to Chemosensitivity in Primary Culture of Thai Gastric Cancer Patients. Biol Pharm Bull 2018; 41:360-367. [PMID: 29491212 DOI: 10.1248/bpb.b17-00688] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Acquired resistance is a major reason for poor clinical outcomes in cancer chemotherapy patients. The aim of this study was to determine the sensitivity to anticancer drugs and to identify the alterations of DNA repair and drug transporter in a model of primary culture obtained from pre- and post-platinum-based anticancer treatments in nine Thai gastric cancer patients. Ex vivo sensitivity to anti-cancer drugs (cisplatin, oxaliplatin, 5-fluorouracil (5-FU) and irinotecan) was analysed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of the drug transporter (multidrug resistance-associated protein 1 (MRP1), P-glycoprotein (P-gp)) and DNA repair (X-ray cross-complementing gene 1 (XRCC1) and excision repair cross-complementing 1 (ERCC1)) were examined by RT-PCR. The IC50 to cisplatin and oxaliplatin of the cells obtained from gastric cancer patients after clinical drug treatments were administered to five patients (55.5%) revealed a significant increase when compared with prior treatments. The basal expression values of XRCC1, ERCC1 and MRP1 obtained from the treated patients were in correlation with those of IC50. Ex vivo platinum drug treatment of the primary culture obtained from naïve patients over seven days also revealed a significant increase in MRP1 (7/9), XRCC1 (4/9) and ERCC1 (4/9). These observations have also been observed in the KATOIII cell line. Clinical treatment by platinum-based anti-cancer drug can develop acquired drug resistance in Thai gastric cancer patients through upregulation in the expression of drug transporter MRP1 and DNA repair XRCC1 and ERCC1. In cell culture model, cisplatin-resistant gastric cancer cell line KATOIII/diamminedichloroplatinum (KATOIII/DDP) significantly increased the expression level of these genes when compared to its parental cells (KATOIII).
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Affiliation(s)
| | - Sirikan Limpakan Yamada
- Division of Gastrointestinal Surgery and Endoscopy, Department of Surgery, Faculty of Medicine
| | | | - Wanisa Punfa
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University
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Abbas M, Ahmed A, Khan GJ, Baig MMFA, Naveed M, Mikrani R, Cao T, Naeem S, Shi M, Dingding C. Clinical evaluation of carcinoembryonic and carbohydrate antigens as cancer biomarkers to monitor palliative chemotherapy in advanced stage gastric cancer. Curr Probl Cancer 2018; 43:5-17. [PMID: 30172422 DOI: 10.1016/j.currproblcancer.2018.08.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Revised: 07/19/2018] [Accepted: 08/01/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-125, CA19-9, and CA72-4 are often found modulated parameters in gastric cancer. OBJECTIVE Our present study is focused to evaluate the synchronization of these biomarkers in response to palliative chemotherapy. METHOD A retrospective study was conducted on 216 gastric cancer patients undergoing first-line cisplatin chemotherapy along with antiangiogenic regimen. Blood samples were taken and analyzed biochemically and statistically. RESULTS Progression occurred in 78 of 216 patients and the median progression-free survival (PFS) was 5 months. For serum CEA, the median PFS was 4 versus 7 months for elevated and normal groups respectively (P = 0.01). The median PFS for normal and elevated CA19-9 and CA72-4 was 6 vs 4 months respectively (P = 0.001). In the multivariate Cox regression model, elevated pretreatment level of CEA, CA19-9, and distant metastases were independent factors associated with increased risk of progression (P = 0.021, P = 0.000, P = 0.006, respectively). CONCLUSIONS Conclusively, elevated pretreatment level of CEA and CA19-9 is correlated with high risk of progression and worse prognosis. Moreover, an additional antiangiogenic therapy is more effective in decreasing cancer biomarker level after palliative chemotherapy that may be correlated with therapeutic triumph.
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Affiliation(s)
- Muhammad Abbas
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Jiangsu Province, Nanjing, PR China; Department of Oncology, Jiangsu Cancer Hospital, Jiangsu institute of cancer research, Nanjing medical university affiliated cancer hospital Nanjing 210009, Jiangsu, PR China
| | - Abrar Ahmed
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Jiangsu Province, Nanjing, PR China; Department of Oncology, Jiangsu Cancer Hospital, Jiangsu institute of cancer research, Nanjing medical university affiliated cancer hospital Nanjing 210009, Jiangsu, PR China
| | - Ghulam Jilany Khan
- Jiangsu key laboratory of Drug Screening, Evaluation and Pharmacodynamics Research, China Pharmaceutical University, Nanjing, PR China; Department of Pharmacology and Therapeutics, Faculty of Pharmacy (FOP), University of Central Punjab, Lahore, Pakistan; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, PR China.
| | - Mirza Muhammad Faran Ashraf Baig
- State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, PR China
| | - Muhammad Naveed
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Jiangsu Province, Nanjing, PR China
| | - Reyaj Mikrani
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Jiangsu Province, Nanjing, PR China
| | - Tengli Cao
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Jiangsu Province, Nanjing, PR China
| | - Shagufta Naeem
- Department of Pathology, Ayub Medical College, Abbottabad, Pakistan.
| | - Meiqi Shi
- Department of Oncology, Jiangsu Cancer Hospital, Jiangsu institute of cancer research, Nanjing medical university affiliated cancer hospital Nanjing 210009, Jiangsu, PR China.
| | - Chen Dingding
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Jiangsu Province, Nanjing, PR China.
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Park CJ, Seo N, Hyung WJ, Koom WS, Kim HS, Kim MJ, Lim JS. Prognostic significance of preoperative CT findings in patients with advanced gastric cancer who underwent curative gastrectomy. PLoS One 2018; 13:e0202207. [PMID: 30092078 PMCID: PMC6084995 DOI: 10.1371/journal.pone.0202207] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 06/14/2018] [Indexed: 12/23/2022] Open
Abstract
Background Preoperative therapy has gained wide interest in advanced gastric cancer patients due to its potential advantages of improved disease control. Selection of high risk patients based on preoperative staging is crucial to choose the candidates for neoadjuvant therapy. Methods Our institutional review board approved this retrospective study and waived the requirement for patient consent. We searched 394 advanced gastric cancer patients (pT2-4) who underwent curative resection in 2010 without neoadjuvant therapies. Two abdominal radiologists independently reviewed the preoperative CT including tumor depth on CT (CT-tumor depth), which was categorized as follows: intramural, minimal extramural(<1mm), spiculated extramural(≥1mm) and nodular extramural infiltration. The impact of clinicoradiologic factors on disease recurrence and disease free survival (DFS) was evaluated. Recursive partitioning analysis was performed to suggest prediction models for recurrence. Results Of total 394 patients, 86 patients (21.8%) experienced recurrence. Spiculated (≥1mm) and nodular extramural tumor infiltration and CT size of 5-10cm were independent predictors of disease recurrence and significantly associated with worse DFS. Lymph node involvement on CT was not significantly associated with patient outcome. Among patients with same pT4a stage, the recurrence rate rises and DFS gets worse as the extramural tumor infiltration progresses (P < 0.001). The prediction model for recurrence revealed that size and CT-tumor depth were the two major discriminating factors. Conclusion CT-tumor depth and size could be used as independent predictors for prognosis. Preoperative CT can be used for prognostic stratification to select high risk patients for whom neoadjuvant therapies might be considered.
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Affiliation(s)
- Chae Jung Park
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Nieun Seo
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Woo Jin Hyung
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Hyo Song Kim
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Myeong-Jin Kim
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Joon Seok Lim
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- * E-mail:
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Liu Y, Zhao G, Xu Y, Zhang T, Chen Z, Yan G, Tu W, Hu Y, Chen Y, He X, Li X, Chen H, Yao S, Hu Z, Chen X, Chen T. Phase II Study of Adjuvant Chemoradiotherapy Using Docetaxel/Cisplatin/5-Fluorouracil Before and After Intensity-modulated Radiotherapy With Concurrent Docetaxel in Patients With Completely (R0) Resected Gastric Carcinoma. Am J Clin Oncol 2018; 41:619-625. [PMID: 28263232 PMCID: PMC6023597 DOI: 10.1097/coc.0000000000000373] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVES The Intergroup 0116 study has demonstrated a significant survival benefit for completely resected (R0) gastric cancer patients treated with a fluorouracil/leucovorin chemoradiotherapy regimen. However, this regimen is also toxic and less effective in terms of distant disease control. Therefore, a more efficacious and safer regimen is urgently needed. METHODS Patients with R0 resected gastric carcinoma received up to two 21-day cycles of postoperative adjuvant preradiation and postradiation DCF chemotherapy (docetaxel 37.5 mg/m on days 1 and 8, cisplatin 25 mg/m on days 1 to 3, and a continuous infusion of fluorouracil 750 mg/m on days 1 to 5), respectively. Chemoradiotherapy between preradiation and postradiation chemotherapy was initiated on day 43 and consisted of intensity-modulated radiotherapy (45 Gy) plus concurrent docetaxel 20 mg/m weekly for 5 weeks. RESULTS A total of 55 patients were evaluated and 76% (42) of patients completed the prescribed therapy. With a median follow-up of 61 months, the 3- and 5-year progression-free survival rates were 67% (95% confidence interval [CI], 54%-80%) and 59% (95% CI, 46%-72%), respectively; and the 3- and 5-year overall survival rates were 72% (95% CI, 60%-84%) and 61% (95% CI, 48%-74%), respectively. The most common grade 3 or greater toxicity, during the chemotherapy phase, was neutropenia (24%). Common grade 3/4 toxicities during concurrent chemoradiotherapy were nausea (32%), vomiting (26%), fatigue (15%), and anorexia (19%). CONCLUSIONS These results demonstrate that this adjuvant regimen is active with an acceptable toxicity profile. A randomized phase 3 trial comparing the Intergroup 0116 chemoradiotherapy regimen with this regimen is underway.
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Affiliation(s)
- Yong Liu
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Guoqi Zhao
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Yi Xu
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Tiening Zhang
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Zhixiao Chen
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Ge Yan
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Wenzhi Tu
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Ye Hu
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Ying Chen
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Xia He
- Department of Radiation Oncology, Jiangsu Cancer Hospital
| | - Xiaodong Li
- Department of Radiation Oncology, Nanjing BenQ Medical Center
| | - Hui Chen
- Department of Radiation Oncology, Nanjing Jiangning Hospital, Nanjing Medical University, Nanjing, P.R. China
| | - Shengyu Yao
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Zhekai Hu
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Xuming Chen
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
| | - Tingfeng Chen
- Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai
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Girardi DM, de Lima MA, Pereira GCB, Negrão MV, López RVM, Capareli FC, Sabbaga J, Hoff PMG. Chemoradiotherapy versus chemotherapy as adjuvant treatment for localized gastric cancer: a propensity score-matched analysis. BMC Cancer 2018; 18:378. [PMID: 29614980 PMCID: PMC5883367 DOI: 10.1186/s12885-018-4305-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 03/26/2018] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Treatment of localized gastric cancer (LGC) consists of surgical resection followed by adjuvant treatment. Both chemoradiation (CRT) and chemotherapy (CT) regimens have shown benefit in survival outcomes versus observation. However, there are few data comparing these approaches. METHODS This study included consecutive patients with LGC treated at Instituto do Cancer do Estado de Sao Paulo (ICESP) from 2012 to 2015. CRT was based on the INT-0116 regimen and CT consisted of a platinum and fluoropyrimidine doublet. Treatment choice was based on physician preference. Toxicity was evaluated for every cycle. Overall survival (OS) analysis was performed by Kaplan-Meier. A propensity score-matched analysis was performed to minimize selection bias. RESULTS A total of 309 patients were evaluated, 227 in CRT group and 82 in CT group. The most prevalent grade 3/4 toxicities in CRT and CT groups were: nausea/vomiting (9.25 vs 4.9%), fatigue (9.3% vs 2.4%), mucositis (4.4% vs 1.2%), neutropenia (37.8% vs 20.9%), febrile neutropenia (3.9% vs 0%), anemia (4.3% vs 6.1%), thrombocytopenia (2.6% vs 4.9%), neuropathy (0 vs 2.4%) and hand-foot syndrome (0.4% vs 2.4%). Two grade 5 toxicities (febrile neutropenia and anemia) occurred in CRT group. There was no difference in the pattern of recurrence. After a median follow-up of 23.5 months (CRT) and 20.6 months (CT), there was no difference in OS between groups. CONCLUSIONS CT and CRT present similar efficacy and tolerability as adjuvant treatment for LGC.
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Affiliation(s)
- Daniel M. Girardi
- Department of oncology, Hospital Sírio Libanês, SGAS 613, conjunto E lote 95, Asa Sul, Brasília, DF 70200-001 Brazil
| | - Mariana A. de Lima
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | | | - Marcelo V. Negrão
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Rossana V. M. López
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Fernanda C. Capareli
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Jorge Sabbaga
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Paulo Marcelo G. Hoff
- Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
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Peng Y, Shen X, Jiang H, Chen Z, Wu J, Zhu Y, Zhou Y, Li J. miR-188-5p Suppresses Gastric Cancer Cell Proliferation and Invasion via Targeting ZFP91. Oncol Res 2018; 27:65-71. [PMID: 29471891 PMCID: PMC7848256 DOI: 10.3727/096504018x15191223015016] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
MicroRNAs (miRNAs) have been demonstrated to be essential regulators in the development and progression of various cancers. The role of miR-188-5p in gastric cancer (GC) has not been determined. In this study, we found that the expression of miR-188-5p was downregulated in GC tissues compared with adjacent normal tissues. The lowly expressed miR-188-5p was significantly associated with lymph node metastasis and advanced TNM stage. Moreover, overexpression of miR-188-5p significantly inhibited GC cell proliferation, migration, and invasion but promoted cellular apoptosis. Mechanistically, we identified transcription factor ZFP91 as a target gene of miR-188-5p in GC. We found that miR-188-5p overexpression significantly inhibited the expression of ZFP91 in GC cell lines. There was an inverse correlation between the expression of miR-188-5p and ZFP91 in GC tissues. We found that restoration of ZFP91 in miR-188-5p-overexpressed MGC-803 and SGC-7901 cells promoted cell proliferation, migration, and invasion. Finally, we also showed that overexpression of miR-188-5p inhibited tumor growth in vivo. Taken together, our findings indicated that miR-188-5p serves as a tumor suppressor in human GC by targeting ZFP91, suggesting that miR-188-5p might be a promising therapeutic target for GC treatment.
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Affiliation(s)
- Yuping Peng
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Xuning Shen
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Honggang Jiang
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Zhiheng Chen
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Jiaming Wu
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Yi Zhu
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Yuan Zhou
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
| | - Jin Li
- Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China
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Kim IH, Park SS, Lee CM, Kim MC, Kwon IK, Min JS, Kim HI, Lee HH, Lee SI, Chae H. Efficacy of Adjuvant S-1 Versus XELOX Chemotherapy for Patients with Gastric Cancer After D2 Lymph Node Dissection: A Retrospective, Multi-Center Observational Study. Ann Surg Oncol 2018; 25:1176-1183. [PMID: 29450755 DOI: 10.1245/s10434-018-6375-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND After curative resection of gastric cancer with D2 lymph node dissection, postoperative adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin (XELOX) is considered to be standard therapy in Eastern countries. This study aimed to compare the efficacies of adjuvant S-1 and XELOX chemotherapy for gastric cancer patients after D2 dissection based on disease-free survival (DFS). METHODS This retrospective observational study was conducted at 29 tertiary hospitals in Korea. Of 1898 patients who underwent curative resection and received adjuvant chemotherapy for gastric cancer between February 2012 and December 2013, 1088 patients who met the eligibility criteria were enrolled in the study. After propensity score-matching, the 3-year disease-free survival rate (DFS) was used to compare efficacies directly between adjuvant XELOX and S-1 chemotherapies for patients with stage 2 or 3 gastric cancer after D2 gastrectomy. RESULTS The 3-year DFS rates for the S-1 and XELOX groups did not differ significantly among disease stages 2A, 2B, and 3A (all p > 0.05). However, the survival rates for the S-1 group were significantly lower than for the XELOX group for stage 3B (65.8% vs. 68.6%; p = 0.019) and stage 3C (48.4% vs. 66.7%; p = 0.002) gastric cancer. The hazard ratios (HRs) of S-1 chemotherapy for recurrence compared with XELOX for stages 3B and 3C were respectively 2.030 [95% confidence interval (CI), 1.110-3.715; p = 0.022] and 2.732 (95% CI 1.427-5.234; p = 0.002). CONCLUSIONS Adjuvant XELOX chemotherapy was more effective than S-1 for patients with stage 3B or 3C gastric cancer after D2 lymph node dissection.
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Affiliation(s)
- In-Hwan Kim
- Department of Surgery, Daegu Catholic University School of Medicine, Daegu, South Korea
| | - Sung-Soo Park
- Department of Surgery, Korea University College of Medicine and School of Medicine, Seoul, South Korea
| | - Chang-Min Lee
- Department of Surgery, Korea University College of Medicine and School of Medicine, Seoul, South Korea
| | - Min Chan Kim
- Department of Surgery, Dong-A University School of Medicine, Busan, South Korea
| | - In-Kyu Kwon
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
| | - Jae-Seok Min
- Department of Surgery, Dongnam Institute of Radiological and Medical Sciences, Busan, South Korea
| | - Hyoung-Il Kim
- Department of Surgery, Yonsei University School of Medicine, Seoul, South Korea
| | - Han Hong Lee
- Department of Surgery, Seoul St. Mary's Hospital, Seoul, South Korea
| | - Sang-Il Lee
- Department of Surgery, Chungnam National University School of Medicine, Daejeon, South Korea
| | - Hyundong Chae
- Department of Surgery, Daegu Catholic University School of Medicine, Daegu, South Korea.
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Nishibeppu K, Komatsu S, Ichikawa D, Imamura T, Kosuga T, Okamoto K, Konishi H, Shiozaki A, Fujiwara H, Otsuji E. Venous invasion as a risk factor for recurrence after gastrectomy followed by chemotherapy for stage III gastric cancer. BMC Cancer 2018; 18:108. [PMID: 29382310 PMCID: PMC5791734 DOI: 10.1186/s12885-018-4052-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 01/25/2018] [Indexed: 12/14/2022] Open
Abstract
Background Although adjuvant chemotherapy with S-1 after curative gastrectomy has been performed as a standard treatment for Stage II and III gastric cancer (GC) in Japan, patients with Stage III GC still have a high incidence of recurrence and a poor prognostic outcome. The aim of this study was to investigate risk factors for recurrence in patients with Stage III GC despite of curative gastrectomy followed by adjuvant chemotherapy, suggesting an indicator for more intensive management. Methods A total of 97 patients with pathological Stage III GC underwent adjuvant chemotherapy after curative gastrectomy between 2001 and 2014, were enrolled in this study. We retrospectively analyzed their hospital records from our hospital. Results The 5-year relapse-free survival (RFS) rates of patients with pStage III GC were 42.0%. Univariate and multivariate analyses for RFS revealed that venous invasion (v+) was an independent factor predicting a shorter RFS (v + vs. v-, 36.5% vs. 47.4%, P = 0.034, HR 1.82, 95% CI: 1.01–3.37). Venous invasion also predicted a shorter overall survival (OS) (v + vs. v-, 33.7% vs. 50.4%, P = 0.027). Regarding the patterns of recurrence, hematogenous recurrence was significantly occurred in patients with v + GC than those without (P = 0.022). Conclusions Stage III GC with venous invasion is a high-risk subgroup for hematogenous recurrence after curative surgery followed by adjuvant chemotherapy. More intensive and effective adjuvant chemo and/or molecular targeted therapy for Stage III GC patients with venous invasion should be considered to improve their outcomes. Electronic supplementary material The online version of this article (10.1186/s12885-018-4052-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Keiji Nishibeppu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Shuhei Komatsu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Daisuke Ichikawa
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Taisuke Imamura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Toshiyuki Kosuga
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Kazuma Okamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hitoshi Fujiwara
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
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Comparison of capecitabine and oxaliplatin with S-1 as adjuvant chemotherapy in stage III gastric cancer after D2 gastrectomy. PLoS One 2017; 12:e0186362. [PMID: 29040299 PMCID: PMC5645114 DOI: 10.1371/journal.pone.0186362] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 09/29/2017] [Indexed: 12/26/2022] Open
Abstract
Aim To compare capecitabine and oxaliplatin (XELOX) with S-1 as adjuvant chemotherapy in stage III gastric cancer after D2 gastrectomy. Methods Clinical data from 206 patients who received XELOX or S-1 regimens as adjuvant chemotherapy in stage III gastric cancer were collected. Patients were divided into 2 groups according to regimen; the groups were XELOX (n = 114) and S-1 monotherapy (n = 92). Results 3-year disease-free survival (DFS) was higher in the S-1 group than in the XELOX group (66.6% vs 59.1%; p = 0.636). 3-year overall survival (OS) was 75.6% in the S-1 group and 69.6% in the XELOX group (p = 0.495). But, the difference was not statistically significant. Especially, for patients with stage IIIC disease, 3-year overall survival was 55.2% in the XELOX group and 39.0% in the S-1 group (hazard ratio, HR 0.50, 95% confidence interval, CI 0.23–1.10; p = 0.075). In multivariate analysis, N stage (HR, 5.639; 95% CI, 1.297–24.522; p = 0.021) and cycle completion as planned (HR, 5.734; 95% CI, 3.007–10.936; p<0.001) were independent predictors of overall survival. Conclusion Adjuvant XELOX and S-1 regimen did not prove anything superior for stage III gastric cancer in this study. But, XELOX had a tendency to be superior to S-1 in stage IIIC gastric cancer after D2 gastrectomy although the difference was not statistically significant. N stage and cycle completion as planned were prognostic factors.
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Kim Y, Squires MH, Poultsides GA, Fields RC, Weber SM, Votanopoulos KI, Kooby DA, Worhunsky DJ, Jin LX, Hawkins WG, Acher AW, Cho CS, Saunders N, Levine EA, Schmidt CR, Maithel SK, Pawlik TM. Impact of lymph node ratio in selecting patients with resected gastric cancer for adjuvant therapy. Surgery 2017; 162:285-294. [PMID: 28578142 PMCID: PMC6036903 DOI: 10.1016/j.surg.2017.03.023] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 01/14/2017] [Accepted: 03/02/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND The impact of adjuvant chemotherapy and chemo-radiation therapy in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio on the relative benefit of adjuvant chemotherapy or chemo-radiation therapy among patients having undergone curative-intent resection for gastric cancer. METHODS Using the multi-institutional US Gastric Cancer Collaborative database, 719 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2013 were identified. Patients with metastasis or an R2 margin were excluded. The impact of lymph node ratio on overall survival among patients who received chemotherapy or chemo-radiation therapy was evaluated. RESULTS Median patient age was 65 years, and the majority of patients were male (56.2%). The majority of patients underwent either subtotal (40.6%) or total gastrectomy (41.0%), with the remainder undergoing distal gastrectomy or wedge resection (18.4%). On pathology, median tumor size was 4 cm; most patients had a T3 (33.0%) or T4 (27.9%) lesion with lymph node metastasis (59.7%). Margin status was R0 in 92.5% of patients. A total of 325 (45.2%) patients underwent resection alone, 253 (35.2%) patients received 5-FU or capecitabine-based chemo-radiation therapy, whereas the remaining 141 (19.6%) received chemotherapy. Median overall survival was 40.9 months, and 5-year overall survival was 40.3%. According to lymph node ratio categories, 5-year overall survival for patients with a lymph node ratio of 0, 0.01-0.10, >0.10-0.25, >0.25 were 54.1%, 53.1 %, 49.1 % and 19.8 %, respectively. Factors associated with worse overall survival included involvement of the gastroesophageal junction (hazard ratio 1.8), T-stage (3-4: hazard ratio 2.1), lymphovascular invasion (hazard ratio 1.4), and lymph node ratio (>0.25: hazard ratio 2.3; all P < .05). In contrast, receipt of adjuvant chemo-radiation therapy was associated with an improved overall survival in the multivariable model (versus resection alone: hazard ratio 0.40; versus chemotherapy: hazard ratio 0.45, both P < .001). The benefit of chemo-radiation therapy for resected gastric cancer was noted only among patients with lymph node ratio >0.25 (versus resection alone: hazard ratio R 0.34; versus chemotherapy: hazard ratio 0.45, both P < .001). In contrast, there was no noted overall survival benefit of chemotherapy or chemo-radiation therapy among patients with lymph node ratio ≤0.25 (all P > .05). CONCLUSION Adjuvant chemotherapy or chemo-radiation therapy was utilized in more than one-half of patients undergoing curative-intent resection for gastric cancer. Lymph node ratio may be a useful tool to select patients for adjuvant chemo-radiation therapy, because the benefit of chemo-radiation therapy was isolated to patients with greater degrees of lymphatic spread (ie, lymph node ratio >0.25).
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Affiliation(s)
- Yuhree Kim
- Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD
| | - Malcolm H Squires
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | | | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Sharon M Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | | | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - David J Worhunsky
- Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - Linda X Jin
- Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - William G Hawkins
- Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Alexandra W Acher
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Clifford S Cho
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Neil Saunders
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH
| | - Edward A Levine
- Department of Surgery, Wake Forest University, Winston-Salem, NC
| | - Carl R Schmidt
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD; Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH.
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Chan WL, Yuen KK, Siu SWK, Lam KO, Kwong DLW. Third-line systemic treatment versus best supportive care for advanced/metastatic gastric cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol 2017; 116:68-81. [DOI: 10.1016/j.critrevonc.2017.05.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 04/18/2017] [Accepted: 05/03/2017] [Indexed: 12/29/2022] Open
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Ghiassi-Nejad Z, Tarchi P, Moshier E, Ru M, Tabrizian P, Schwartz M, Buckstein M. Prognostic Factors and Patterns of Locoregional Failure After Surgical Resection in Patients With Cholangiocarcinoma Without Adjuvant Radiation Therapy: Optimal Field Design for Adjuvant Radiation Therapy. Int J Radiat Oncol Biol Phys 2017; 99:805-811. [PMID: 29063849 DOI: 10.1016/j.ijrobp.2017.06.2467] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 06/13/2017] [Accepted: 06/27/2017] [Indexed: 12/15/2022]
Abstract
PURPOSE To identify prognostic factors and patterns of local failure in patients with cholangiocarcinoma (CCA), after surgical resection in the absence of adjuvant radiation, for optimal definition of target volumes encompassing the majority of local recurrences. METHODS AND MATERIALS A chart review was performed in patients who underwent resection for primary CCA (intrahepatic, hilar, and distal) between 1999 and 2014. Local failure was defined as recurrence in a theoretical reasonable postoperative radiation volume. This includes the cut surface of liver, biliary anastomosis, hilum, portal nodes, celiac nodes, peri-pancreatic nodes, gastro-hepatic nodes, and retroperitoneal nodes. Patients who received adjuvant radiation were excluded. RESULTS A total of 189 patients underwent surgical resection for CCA, of whom 145 patients had sufficient follow-up. Median follow-up was 41.6 months (95% confidence interval 35.4-48.7 months). Of the 145 cases, 102 were intrahepatic and 43 were hilar/distal CCA. Adjuvant chemotherapy was given in 38 cases (26%), of which 20 (54%) were gemcitabine-based. Eighty-six patients (59%) had a documented recurrence, of whom 44 (51%) had a locoregional component. Among patients who had a recurrence, 23 (27%) had a recurrence at the biliary anastomosis and/or cut liver surface. Twenty-eight patients (32.6%) had a recurrence in the regional lymph nodes, most prevalent in the portal (16.3%) and retroperitoneal (17.4%) lymph nodes. Univariable analysis identified tumor size, any vascular invasion, presence of satellites, stage/nodal status, and receipt of chemotherapy as significant prognostic factors of overall recurrence among intrahepatic patients. Presence of satellites, and stage 3/Nx status remained statistically significant in multivariable modeling. CONCLUSIONS The areas at highest risk for locoregional recurrence after surgical resection for primary CCA are the biliary anastomosis/cut liver surface, portal lymph nodes, and retroperitoneal lymph nodes. Although these results need to be validated, adjuvant radiation should possibly cover these areas to maximize locoregional control.
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Affiliation(s)
- Zahra Ghiassi-Nejad
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Paola Tarchi
- Department of General Surgery, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy
| | - Erin Moshier
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Meng Ru
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Parissa Tabrizian
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Myron Schwartz
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Michael Buckstein
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.
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Pilar A, Gupta M, Ghosh Laskar S, Laskar S. Intraoperative radiotherapy: review of techniques and results. Ecancermedicalscience 2017; 11:750. [PMID: 28717396 PMCID: PMC5493441 DOI: 10.3332/ecancer.2017.750] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Indexed: 12/14/2022] Open
Abstract
Intraoperative radiotherapy (IORT) is a technique that involves precise delivery of a large dose of ionising radiation to the tumour or tumour bed during surgery. Direct visualisation of the tumour bed and ability to space out the normal tissues from the tumour bed allows maximisation of the dose to the tumour while minimising the dose to normal tissues. This results in an improved therapeutic ratio with IORT. Although it was introduced in the 1960s, it has seen a resurgence of popularity with the introduction of self-shielding mobile linear accelerators and low-kV IORT devices, which by eliminating the logistical issues of transport of the patient during surgery for radiotherapy or building a shielded operating room, has enabled its wider use in the community. Electrons, low-kV X-rays and HDR brachytherapy are all different methods of IORT in current clinical use. Each method has its own unique set of advantages and disadvantages, its own set of indications where one may be better suited than the other, and each requires a specific kind of expertise. IORT has demonstrated its efficacy in a wide variety of intra-abdominal tumours, recurrent colorectal cancers, recurrent gynaecological cancers, and soft-tissue tumours. Recently, it has emerged as an attractive treatment option for selected, early-stage breast cancer, owing to the ability to complete the entire course of radiotherapy during surgery. IORT has been used in a multitude of roles across these sites, for dose escalation (retroperitoneal sarcoma), EBRT dose de-escalation (paediatric tumours), as sole radiation modality (early breast cancers) and as a re-irradiation modality (recurrent rectal and gynaecological cancers). This article aims to provide a review of the rationale, techniques, and outcomes for IORT across different sites relevant to current clinical practice.
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Affiliation(s)
- Avinash Pilar
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| | - Meetakshi Gupta
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| | - Sarbani Ghosh Laskar
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
| | - Siddhartha Laskar
- Department of Radiation Oncology, Tata Memorial Hospital, Dr Ernest Borges' Marg, Parel, Mumbai, MS, India 400012
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Monitoring with sensitive tumor markers contributes to decision-making and better prognosis in gastric cancer patients with peritoneal recurrence. Int J Clin Oncol 2017; 22:897-904. [PMID: 28488013 DOI: 10.1007/s10147-017-1132-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 05/02/2017] [Indexed: 01/01/2023]
Abstract
BACKGROUND There is no evidence that monitoring tumor dynamics using sensitive tumor markers contributes to treatment decision-making and prognosis in gastric cancer patients with tumor recurrence. This study was designed to investigate the significance of tumor markers in monitoring peritoneal recurrence of gastric cancer. METHODS We retrospectively analysed 102 consecutive patients who developed recurrence after curative gastrectomy for gastric cancer at our institute between 2002 and 2011. They were followed intensively using tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen. RESULTS Of 102 patients who exhibited recurrence, 51 had peritoneal recurrence. These patients were divided into three groups according to the status of tumor markers at the time of recurrence. Each tumor marker was re-elevated in 28 patients (58%) (re-elevation group; REG), was continuously elevated since initial surgery in 13 patients (22%) (continuous elevation group; CEG) and was not elevated in 10 patients (20%) (non-elevation group; NEG). With regard to survival after recurrence and total postoperative survival, patients in the REG were significantly better than those in the other groups ( p = 0.001, p = 0.018, respectively). REG patients received more different types of chemotherapy regimens than NEG patients because of monitoring (p = 0.018). Multivariate analysis revealed that re-elevation of tumor markers at the time of recurrence was an independent and better prognostic factor for peritoneal recurrence (p = 0.003, hazard ratio 0.29). CONCLUSION Monitoring of tumor dynamics with sensitive tumor markers may contribute to the decision-making process for more promising chemotherapeutic regimens by avoiding subsequent ileus and lead to better prognosis in gastric cancer patients with peritoneal recurrence.
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Chang JS, Kim KH, Yoon HI, Hyung WJ, Rha SY, Kim HS, Lee YC, Lim JS, Noh SH, Koom WS. Locoregional relapse after gastrectomy with D2 lymphadenectomy for gastric cancer. Br J Surg 2017; 104:877-884. [PMID: 28245053 DOI: 10.1002/bjs.10502] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 10/09/2016] [Accepted: 01/09/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Risk for and site of locoregional relapse have not been well studied in patients undergoing gastrectomy with D2 lymphadenectomy for gastric cancer. METHODS Patients who had undergone gastrectomy with D2 lymphadenectomy for gastric cancer between 2004 and 2007 were identified from an institutional database. The locoregional relapse rate was estimated by competing risk analysis, and risk groups were derived according to locoregional relapse risk using recursive partitioning analysis (RPA). The locations of nodal relapses were evaluated according to Japanese Classification of Gastric Carcinoma criteria. RESULTS Some 2618 patients were included. With a median follow-up of 78·0 (range 28·5-122·6) months, relapse was diagnosed in 471 of 2618 patients (18·0 per cent). The cumulative incidence of locoregional relapse at 5 years was 8·5 (95 per cent c.i. 7·4 to 9·6) per cent. The 5-year locoregional recurrence rates for high-risk (N3), intermediate-risk (N1-2) and low-risk (N0) groups were 32·4, 12·3 and 1·7 per cent respectively (P < 0·001). Among patients with regional relapse, 90·4 per cent had involvement outside the D2 dissected area, and the most commonly involved site was station 16b1. This pattern was maintained in the RPA risk groups (P = 0·329). CONCLUSION Locoregional relapse at 5 years after gastrectomy with D2 lymphadenectomy was 8·5 per cent, and was most often seen outside the D2 dissected area.
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Affiliation(s)
- J S Chang
- Department of Radiation Oncology, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
| | - K H Kim
- Department of Radiation Oncology, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
| | - H I Yoon
- Department of Radiation Oncology, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
| | - W J Hyung
- Department of Surgery, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
| | - S Y Rha
- Division of Medical Oncology, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
| | - H S Kim
- Division of Medical Oncology, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
| | - Y C Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
| | - J S Lim
- Department of Radiology, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
| | - S H Noh
- Department of Surgery, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
| | - W S Koom
- Department of Radiation Oncology, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, Korea
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Nanovesicle-mediated systemic delivery of microRNA-34a for CD44 overexpressing gastric cancer stem cell therapy. Biomaterials 2016; 105:12-24. [DOI: 10.1016/j.biomaterials.2016.07.036] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Revised: 07/24/2016] [Accepted: 07/29/2016] [Indexed: 12/22/2022]
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Goody RB, MacKay H, Pitcher B, Oza A, Siu LL, Kim J, Wong RKS, Chen E, Swallow C, Knox J, Kassam Z, Cummings B, Feld R, Hedley D, Liu G, Krzyzanowska MK, Dinniwell R, Brade AM, Dawson LA, Pintilie M, Ringash J. Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer. Int J Radiat Oncol Biol Phys 2016; 96:994-1002. [PMID: 27745984 DOI: 10.1016/j.ijrobp.2016.08.034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 08/16/2016] [Accepted: 08/23/2016] [Indexed: 01/07/2023]
Abstract
PURPOSE Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. METHODS AND MATERIALS Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m2/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m2) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. RESULTS Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m2 cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. CONCLUSION Cisplatin can be safely delivered with 5-FU-based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.
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Affiliation(s)
- Rebecca B Goody
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Helen MacKay
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Bethany Pitcher
- Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Amit Oza
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Lillian L Siu
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - John Kim
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Rebecca K S Wong
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Eric Chen
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Carol Swallow
- Department of Surgical Oncology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Jennifer Knox
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Zahra Kassam
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket, Ontario, Canada
| | - Bernard Cummings
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Ron Feld
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - David Hedley
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Geoffrey Liu
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Monika K Krzyzanowska
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Robert Dinniwell
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Anthony M Brade
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Laura A Dawson
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Melania Pintilie
- Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Jolie Ringash
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
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Zhang Z, Kong Y, Yang W, Ma F, Zhang Y, Ji S, Ma EM, Liu H, Chen Y, Hua Y. Upregulation of microRNA-34a enhances the DDP sensitivity of gastric cancer cells by modulating proliferation and apoptosis via targeting MET. Oncol Rep 2016; 36:2391-7. [PMID: 27513895 DOI: 10.3892/or.2016.5016] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 07/14/2016] [Indexed: 12/15/2022] Open
Abstract
Cisplatin (DDP) based chemotherapy is still the main strategy of human gastric cancer (GC) treatment. However, drug resistance is a major obstacle for DDP chemotherapy. Recent studies indicated that the resistance could be modulated by the regulation of dysregulated microRNAs (miRs). Previous study also found miR-34a was associated with cell proliferation and apoptosis in human GC; however, the relationship between miR-34a and DDP resistance still remains unexplored. The purpose of this study was to investigate whether miR-34a is associated with DDP resistance in human GC cells. Our study found that the expression of miR-34a was significantly decreased in DDP resistance human GC tissues and DDP resistance human GC SGC7901/DDP cells compared with normal GC tissues and cells. Upregulation of miR-34a enhanced the DDP sensitivity of SGC7901/DDP cells to DDP through the inhibition of cell proliferation and induction of cell apoptosis; on the other hand downregulation of miR-34a could weaken the DDP sensitivity of SGC7901 cells to DDP. Further study found that MET was a direct target of miR-34a and the regulation of MET could affect the DDP sensitivity of SGC7901/DDP cells. Moreover, our study also indicated that up-regulation of miR-34a could decrease the expression of MET in SGC7901/DDP cells. Therefore, our findings suggested miR-34a could modulate human gastric cancer cell DDP sensitivity by regulation of cell proliferation and apoptosis via targeting MET, potentially benefiting human GC treatment in the future.
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Affiliation(s)
- Zhandong Zhang
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Ye Kong
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Wei Yang
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Fei Ma
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Yonglei Zhang
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Sheqing Ji
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Er-Min Ma
- Surgical Oncology, The People Hospital of Zhengzhou, Zhengzhou, Henan 450000, P.R. China
| | - Hongxing Liu
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Yongshun Chen
- Department of Radiotherapy, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Yawei Hua
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
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