|
1
|
Akkus E, Lamarca A. Adjuvant chemotherapy compared to observation in resected biliary tract cancers: Survival meta-analysis of phase-III randomized controlled trials. Eur J Cancer 2025; 220:115342. [PMID: 40101432 DOI: 10.1016/j.ejca.2025.115342] [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: 01/22/2025] [Revised: 02/23/2025] [Accepted: 03/03/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND A limited number of randomized controlled trials (RCTs) investigated adjuvant chemotherapy in biliary tract cancers (BTCs). Recurrences and deaths are common in the first 2 years and survival remains poor despite adjuvant treatment. METHODS Phase-III RCTs were included comparing adjuvant chemotherapy and observation in resected BTCs. The primary endpoints were recurrence-free (RFS) and overall survival (OS). Proportional hazard results were used for trial-based analyses. Patient data was curated from published Kaplan-Meier curves to analyze short-term (2-year) hazards. The Parmar and generic inverse variance methods were used. RESULTS 1308 patients in 4 trials (BILCAP, ASCOT, BCAT, PRODIGE-12) were included. Capecitabine (BILCAP) and S-1 (ASCOT) were grouped as 5-FU-based, gemcitabine (BCAT) and gemcitabine-oxaliplatin (PRODIGE-12) were grouped as gemcitabine-based chemotherapy. Adjuvant 5FU-based chemotherapy improved RFS [HR: 0.80 (95 % CI:0.68-0.95), p = 0.012] and OS [HR: 0.78 (95 % CI:0.65-0.94), p = 0.009]. However, gemcitabine-based chemotherapy did not provide benefit in RFS [HR: 0.90 (95 % CI:0.70-1.15), p = 0.428] and OS [HR: 1.03 (95 % CI:0.78-1.36), p = 0.794]. The benefit of 5-FU-based chemotherapy was more apparent in the short-term (2-year hazards) (RFS: [HR: 0.67 (95 %CI:57-0.79), p < 0.001] and OS: [HR: 0.61 (95 % CI:59-0.64), p < 0.001]). However, gemcitabine-based chemotherapy did not provide RFS benefit in the short term either [HR: 0.80 (95 % CI:0.64-0.1.01), p = 0.067] and seemed to be even detrimental for OS [HR: 1.22 (95 % CI:1.14-1.31), p < 0.001] in the first 2 years. CONCLUSION This study confirms using 5FU-based monotherapy in the adjuvant treatment of resected BTCs. The more prominent benefit in the first 2 years emphasizes that more effective adjuvant treatments with sustained long-term benefits are needed. Two-year proportional hazards OS and RFS are proposed here as an additional secondary end-point to consider in future clinical trials. in this setting. Registration ID (PROSPERO): CRD42024614444.
Collapse
Affiliation(s)
- Erman Akkus
- Ankara University Faculty of Medicine, Department of Medical Oncology, Ankara, Türkiye; Ankara University Cancer Research Institute, Ankara, Türkiye
| | - Angela Lamarca
- Department of Oncology, OncoHealth Institute, Instituto de Investigaciones Sanitarias FJD, Fundación Jiménez Díaz University Hospital, Madrid, Spain.
| |
Collapse
|
|
2
|
Puhr HC, Berchtold L, Zingerle L, Felfernig M, Weissenbacher L, Jomrich G, Asari R, Schoppmann SF, Prager GW, Bergen ES, Berghoff AS, Preusser M, Ilhan-Mutlu A. Association of family history with patient characteristics and prognosis in a large European gastroesophageal cancer cohort. Wien Klin Wochenschr 2025; 137:214-223. [PMID: 39235615 PMCID: PMC12006227 DOI: 10.1007/s00508-024-02432-3] [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: 06/04/2024] [Accepted: 08/10/2024] [Indexed: 09/06/2024]
Abstract
INTRODUCTION The role of the family history in the development and prognosis of gastroesophageal cancer is a controversially discussed topic as appropriate data from western cohorts are lacking. This study aims to explore its associations with disease and outcome parameters in a large European cohort. METHODS We retrospectively analyzed self-reported family history in patients with gastroesophageal cancer treated between 1 January 1990 and 31 December 2021 at the Medical University of Vienna. Association analyses with patient characteristics, tumor characteristics, symptoms and overall survival (OS) were performed. RESULTS In our cohort of 1762 gastroesophageal cancer patients, 592 (34%) reported a positive family history of cancer (159, 9%, gastroesophageal cancer). No associations were found with histopathological parameters or initial symptoms; however, a positive family history correlated with female gender (cancer in general: p = 0.011; gastroesophageal cancer: p = 0.015). Family history of cancer in general was associated with earlier cancer stages (p = 0.04), higher BMI (p = 0.005), and alcohol consumption (p = 0.010), while a positive history for gastroesophageal cancer was associated with higher age at diagnosis (p = 0.002) and stomach cancer (p = 0.002). There was no statistically significant association of positive family history with OS (p = 0.1, p = 0.45), also not in subgroups for histology (adeno and squamous cell), number of family members and degree of relative. CONCLUSION Our results emphasize that a positive family history is neither statistically significantly associated with prognosis nor with specific histopathological features in patients with gastroesophageal cancer. Yet, associations with distinct patient characteristics and positive family history indicate that specific subgroups might profit from endoscopic surveillance. Prospective studies are warranted to investigate these findings further.
Collapse
Affiliation(s)
- Hannah C Puhr
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Luzia Berchtold
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
- Institute for Medical Statistics, Center for Medical Data Science, Medical University of Vienna, Vienna, Austria
| | - Linda Zingerle
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Melanie Felfernig
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Lisa Weissenbacher
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Gerd Jomrich
- Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Reza Asari
- Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Sebastian F Schoppmann
- Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Gerald W Prager
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Elisabeth S Bergen
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Anna S Berghoff
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Matthias Preusser
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Aysegül Ilhan-Mutlu
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
| |
Collapse
|
|
3
|
Salehi N, Alqamish M, Zarnegar R. Perioperative chemotherapy strategies in diffuse gastric cancer. World J Gastrointest Surg 2025; 17:101326. [PMID: 39872775 PMCID: PMC11757181 DOI: 10.4240/wjgs.v17.i1.101326] [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: 09/14/2024] [Revised: 11/22/2024] [Accepted: 12/02/2024] [Indexed: 12/27/2024] Open
Abstract
This study reviews the findings of a recent study by Li et al, which demonstrated that perioperative chemotherapy benefits patients with diffuse-type gastric cancer compared to surgery alone. Despite potential biases, the study supports the inclusion of perioperative chemotherapy in treatment guidelines. Neoadjuvant and adjuvant chemotherapy may also provide similar survival outcomes, allowing for flexible treatment planning.
Collapse
Affiliation(s)
- Niloufar Salehi
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10128, United States
| | - Maria Alqamish
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10128, United States
| | - Rasa Zarnegar
- Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10128, United States
| |
Collapse
|
|
4
|
Puhr HC, Winkler EC, Preusser M. Ethnic origin in cancer clinical trials: overrated or understated? A comprehensive analysis of cancer clinical trials leading to FDA and EMA approvals between 2020 and 2022. ESMO Open 2025; 10:104093. [PMID: 39754982 PMCID: PMC11758121 DOI: 10.1016/j.esmoop.2024.104093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 11/11/2024] [Accepted: 11/25/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Ethnic diversity in cancer clinical trials is essential to ensure that therapeutic advances are equitable and broadly applicable in multicultural societies. Yet, missing consensus on the documentation of ethnic origin, partially based on the complexity of the terminology and fear of discrimination, leads to suboptimal patient management of minority populations. Additionally, eligibility criteria, such as stringent laboratory cut-offs, often fail to account for variations across ethnic groups, potentially excluding patients without evidence-based justification. PATIENTS AND METHODS This analysis addresses this issue by investigating ethnic diversity in clinical trials that led to European Medicines Agency (EMA) and Food and Drug Administration (FDA) approvals between 2020 and 2022. Trials were identified from FDA and EMA databases, and available protocols and full-text publications were reviewed for documentation of ethnic background and eligibility criteria for organ function (bone marrow, liver, and renal). Descriptive statistics were applied to summarize the findings. RESULTS Of the 56 trials analyzed, only two-thirds of primary result publications included information on ethnic origin. Caucasian and Asian groups were documented in most of those trials and also had the highest percentages of participants across trials, while other ethnic subgroups were less frequently documented and only made up a small proportion of trial participants. Eligibility criteria often set strict organ function cut-offs that did not consider variations among ethnic groups, potentially excluding minorities. The Cockcroft-Gault formula was frequently used to assess kidney function, despite its known limitations for multiethnic cohorts. CONCLUSIONS Ethnic homogenous participants and eligibility criteria that favor majority groups limit the applicability of findings in diverse populations, leading to inadequate patient management. While United States guidelines encourage inclusivity, similar recommendations are lacking in Europe. Thus European regulatory authorities, research organizations, and patient advocates should establish guidelines to improve ethnic diversity in cancer clinical trials, aligning research practices with the increasingly multicultural composition of European societies.
Collapse
Affiliation(s)
- H C Puhr
- Division of Oncology, Department of Medicine I, Medical University Vienna, Vienna, Austria. https://twitter.com/Hannah_C_Puhr
| | - E C Winkler
- Section for Translational Medical Ethics, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
| | - M Preusser
- Division of Oncology, Department of Medicine I, Medical University Vienna, Vienna, Austria.
| |
Collapse
|
|
5
|
Lew R, Cheng S, Chun I, Ishikawa K, Ahn HJ, Wai C. Gastric adenocarcinoma location and postoperative complication rates in Asian patients: A 2014-2019 NSQIP analysis. Am J Surg 2024; 227:208-212. [PMID: 38587050 DOI: 10.1016/j.amjsurg.2023.10.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 10/01/2023] [Accepted: 10/04/2023] [Indexed: 04/09/2024]
Abstract
BACKGROUND Asian gastric cancer patients have higher long-term survival rates post-gastrectomy. This study compares 30-day post-gastrectomy outcomes between Asians and non-Asians. METHODS Gastric cancer patients undergoing elective gastrectomies were identified in 2014-2019 NSQIP datasets (n = 1,438). Demographics, comorbidities, and postoperative outcomes were analyzed. RESULTS Asians had lower odds of total gastrectomy (AOR = 0.52, p = 0.003), age ≥65 (AOR = 0.60, p = 0.006), smoking history (AOR = 0.35, p < 0.001), dyspnea (AOR = 0.25, p = 0.01), and hypoalbuminemia (AOR = 0.62, p = 0.025); they also had lower BMI (p < 0.001). Postoperative outcomes were not significantly different aside from a shorter median length of hospital stay in days (LOS) (Asians: 7 (6, 11); non-Asians: 8 (6, 11); p < 0.001). CONCLUSIONS Asian gastric cancer patients have significantly lower odds of having select preoperative comorbidities and have shorter hospital LOS.
Collapse
Affiliation(s)
- Rachel Lew
- University of Hawaii at Manoa John A. Burns School of Medicine, 651 Ilalo St, Honolulu, HI, 96813, United States.
| | - Shirley Cheng
- University of Hawaii at Manoa John A. Burns School of Medicine, 651 Ilalo St, Honolulu, HI, 96813, United States
| | - Ian Chun
- University of Hawaii at Manoa John A. Burns School of Medicine, 651 Ilalo St, Honolulu, HI, 96813, United States
| | - Kyle Ishikawa
- Department of Quantitative Health Sciences, University of Hawaii John A. Burns School of Medicine, 651 Ilalo Street, Medical Education Building Suite 411, Honolulu, HI, 96813, United States
| | - Hyeong Jun Ahn
- Department of Quantitative Health Sciences, University of Hawaii John A. Burns School of Medicine, 651 Ilalo Street, Medical Education Building Suite 411, Honolulu, HI, 96813, United States
| | - Christina Wai
- Department of Surgery, University of Hawaii John A. Burns School of Medicine, 1356 Lusitana Street, Queen's University Tower, Honolulu, HI, 96813, United States
| |
Collapse
|
|
6
|
Díaz del Arco C, Ortega Medina L, Estrada Muñoz L, Molina Roldán E, García Gómez de las Heras S, Fernández Aceñero MJ. Impact of Age at Diagnosis on Clinicopathological Features, Prognosis, and Management of Gastric Cancer: A Retrospective Single-Center Experience from Spain. Cancers (Basel) 2023; 15:4241. [PMID: 37686517 PMCID: PMC10486869 DOI: 10.3390/cancers15174241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 08/18/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
The impact of age on various aspects of gastric cancer (GC) remains controversial. Clarifying this issue can improve our understanding of the disease, refine risk stratification models, and aid in personalized therapeutic approaches. This study aimed to evaluate the influence of age at diagnosis on the clinicopathological features, prognosis, and management of a specific cohort of Spanish patients with resected GC. The study encompassed 315 patients treated at a single tertiary hospital in Spain, divided into two age-based subgroups: ≤65 years and >65 years. The mean and median ages at diagnosis were 72 and 76 years. Most tumors were diagnosed at pT3 stage (49.2%), and 59.6% of patients had lymph node metastases. 21.3% of cases were diagnosed with GC at age ≤ 65 years. Younger patients showed a significantly higher prevalence of flat, diffuse, high-grade tumors, signet-ring cells, perineural infiltration, D2 lymphadenectomies, and adjuvant therapy. They also exhibited a higher rate of recurrences, but had a significantly longer follow-up. Kaplan-Meier curves indicated no significant prognostic differences based on age. Finally, age did not independently predict overall survival or disease-free survival. Our results suggest that younger patients may require more aggressive treatment due to adverse clinicopathologic features, but the lack of prognostic differences among age groups in our cohort indicates the need for further investigation into the complex interplay between age, clinicopathologic factors, and long-term outcomes in GC.
Collapse
Affiliation(s)
- Cristina Díaz del Arco
- Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; (L.O.M.); (M.J.F.A.)
- Department of Pathology, Hospital Clínico San Carlos, Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain;
| | - Luis Ortega Medina
- Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; (L.O.M.); (M.J.F.A.)
- Department of Pathology, Hospital Clínico San Carlos, Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain;
| | - Lourdes Estrada Muñoz
- Department of Basic Medical Sciences, School of Medicine, Rey Juan Carlos University, Móstoles, 28933 Madrid, Spain; (L.E.M.); (S.G.G.d.l.H.)
- Department of Pathology, Rey Juan Carlos Hospital, Móstoles, 28933 Madrid, Spain
| | - Elena Molina Roldán
- Department of Pathology, Hospital Clínico San Carlos, Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain;
- Biobank, Hospital Clínico San Carlos, 28040 Madrid, Spain
| | - Soledad García Gómez de las Heras
- Department of Basic Medical Sciences, School of Medicine, Rey Juan Carlos University, Móstoles, 28933 Madrid, Spain; (L.E.M.); (S.G.G.d.l.H.)
| | - María Jesús Fernández Aceñero
- Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; (L.O.M.); (M.J.F.A.)
- Department of Pathology, Hospital Clínico San Carlos, Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain;
| |
Collapse
|
|
7
|
Van Cutsem E, di Bartolomeo M, Smyth E, Chau I, Park H, Siena S, Lonardi S, Wainberg ZA, Ajani J, Chao J, Janjigian Y, Qin A, Singh J, Barlaskar F, Kawaguchi Y, Ku G. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study. Lancet Oncol 2023; 24:744-756. [PMID: 37329891 PMCID: PMC11298287 DOI: 10.1016/s1470-2045(23)00215-2] [Citation(s) in RCA: 95] [Impact Index Per Article: 47.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/20/2023] [Accepted: 04/25/2023] [Indexed: 06/19/2023]
Abstract
BACKGROUND Approximately 15-20% of advanced gastric and gastro-oesophageal junction cancers overexpress HER2. In DESTINY-Gastric01, the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan improved response and overall survival versus chemotherapy in patients from Japan and South Korea with locally advanced or metastatic HER2-positive gastric or gastro-oesophageal junction cancer whose disease progressed after two lines of previous therapy including trastuzumab. Here, we report primary and updated analyses of the single-arm, phase 2 DESTINY-Gastric02 trial, which aimed to examine trastuzumab deruxtecan in patients living in the USA and Europe. METHODS DESTINY-Gastric02 is a single-arm, phase 2 study in adult patients from 24 study sites in the USA and Europe (Belgium, Spain, Italy, and the UK). Eligible patients were aged at least 18 years and had an Eastern Cooperative Oncology Group performance status of 0 or 1, pathologically documented unresectable or metastatic gastric or gastro-oesophageal junction cancer, progressive disease on or after first-line therapy with a trastuzumab-containing regimen, with at least one measurable lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and centrally confirmed HER2-positive disease on a postprogression biopsy. Patients were given 6·4 mg/kg of trastuzumab deruxtecan intravenously every 3 weeks until disease progression, withdrawal by patient, physician decision, or death. The primary endpoint was confirmed objective response rate by independent central review. The primary endpoint and safety were assessed in the full analysis set (ie, participants who received at least one dose of study drug). Here, we report the primary analysis of this study, with a data cutoff of April 9, 2021, and an updated analysis, with a data cutoff of Nov 8, 2021. This trial is registered with ClinicalTrials.gov, NCT04014075, and is ongoing. FINDINGS Between Nov 26, 2019, and Dec 2, 2020, 89 patients were screened and 79 were enrolled and subsequently treated with trastuzumab deruxtecan (median age 60·7 years [IQR 52·0-68·3], 57 [72%] of 79 were male, 22 [28%] were female, 69 [87%] were White, four [5%] were Asian, one [1%] was Black or African American, one [1%] was Native Hawaiian or Pacific Islander, one had missing race, and three [4%] were other races). At the primary analysis (median follow-up 5·9 months [IQR 4·6-8·6 months]), confirmed objective response was reported in 30 (38% [95% CI 27·3-49·6]) of 79 patients, including three (4%) complete responses and 27 (34%) partial responses, as assessed by independent central review. As of data cutoff for the updated analysis (median follow-up 10·2 months [IQR 5·6-12·9]), a confirmed objective response was reported in 33 (42% [95% CI 30·8-53·4]) of 79 patients, including four (5%) complete responses and 29 (37%) partial responses, as assessed by independent central review. The most common grade 3 or worse treatment-emergent adverse events were anaemia (11 [14%]), nausea (six [8%]), decreased neutrophil count (six [8%]), and decreased white blood cell count (five [6%]). Drug-related serious treatment-emergent adverse events occurred in ten patients (13%). Deaths determined to be associated with study treatment occurred in two patients (3%) and were due to interstitial lung disease or pneumonitis. INTERPRETATION These clinically meaningful results support the use of trastuzumab deruxtecan as second-line therapy in patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer. FUNDING Daiichi Sankyo and AstraZeneca.
Collapse
Affiliation(s)
- Eric Van Cutsem
- University Hospitals Gasthuisberg, Leuven, University of Leuven, Leuven, Belgium.
| | | | - Elizabeth Smyth
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Ian Chau
- The Royal Marsden Hospital, Sutton, UK
| | - Haeseong Park
- Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA
| | - Salvatore Siena
- Università degli Studi di Milano and Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Sara Lonardi
- Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - Zev A Wainberg
- Department of Medicine-Hematology-Oncology, University of California Los Angeles, Los Angeles, CA, USA
| | - Jaffer Ajani
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Joseph Chao
- City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | | | - Amy Qin
- Daiichi Sankyo, Basking Ridge, NJ, USA
| | | | | | | | - Geoffrey Ku
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| |
Collapse
|
|
8
|
Puhr HC, Reiter TJ, Preusser M, Prager GW, Ilhan-Mutlu A. Recent Advances in the Systemic Treatment of Localized Gastroesophageal Cancer. Cancers (Basel) 2023; 15:1900. [PMID: 36980786 PMCID: PMC10047169 DOI: 10.3390/cancers15061900] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/30/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
The overall survival expectancy of localized gastroesophageal cancer patients still remains under 5 years despite advances in neoadjuvant and adjuvant treatment strategies in recent years. For almost a decade, immunotherapy has been successfully implemented as a first-line treatment for various oncological diseases in advanced stages. In the case of advanced gastroesophageal cancer, 2021 witnessed several approvals of immune checkpoint inhibitor therapies by different authorities. Although it is still a debate whether this treatment should be restricted to a certain subgroup of patients based on biomarker selection, immunotherapy agents are making remarkable steps in resectable settings as well. The Checkmate-577 study demonstrated significant benefits of nivolumab as an adjuvant treatment for resectable esophageal and gastroesophageal junction tumors and thereby obtained approvals both from U.S. American and European authorities. First results of further potential practice-changing clinical trials are expected in 2023, which might change the treatment armamentarium for resectable gastroesophageal cancers significantly. This review aims to demonstrate the advances of immunotherapy and targeted therapies in treatment of localized gastric, gastroesophageal junction and esophageal tumors and gives a short summary on promising ongoing clinical trials.
Collapse
Affiliation(s)
| | | | | | | | - Aysegül Ilhan-Mutlu
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
| |
Collapse
|
|
9
|
Satake H, Lee KW, Chung HC, Lee J, Yamaguchi K, Chen JS, Yoshikawa T, Amagai K, Yeh KH, Goto M, Chao Y, Lam KO, Han SR, Shiratori S, Shah S, Shitara K. Pembrolizumab or pembrolizumab plus chemotherapy versus standard of care chemotherapy in patients with advanced gastric or gastroesophageal junction adenocarcinoma: Asian subgroup analysis of KEYNOTE-062. Jpn J Clin Oncol 2023; 53:221-229. [PMID: 36533429 PMCID: PMC9991501 DOI: 10.1093/jjco/hyac188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 11/15/2022] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVE First-line pembrolizumab with/without chemotherapy versus chemotherapy was evaluated in programmed death ligand 1 combined positive score ≥1, locally advanced/unresectable or metastatic gastric cancer/gastrooesophageal junction cancer in the KEYNOTE-062 study. We present results for patients enrolled in Asia. METHODS Eligible patients were randomly assigned 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin + 5-fluorouracil or capecitabine) or placebo plus chemotherapy Q3W. End points included overall survival (primary) in combined positive score ≥1 and combined positive score ≥10 populations and safety and tolerability (secondary). RESULTS A total of 187 patients were enrolled in Asia (pembrolizumab, n = 62; pembrolizumab plus chemotherapy, n = 64; chemotherapy, n = 61). Compared with the global population, higher proportions of patients had Eastern Cooperative Oncology Group performance status 0 and a diagnosis of stomach cancer. In the programmed death ligand 1 combined positive score ≥1 population, median overall survival was numerically longer with pembrolizumab versus chemotherapy (22.7 vs 13.8 months; hazard ratio, 0.54; 95% confidence interval, 0.35-0.82) and pembrolizumab plus chemotherapy versus chemotherapy (16.5 vs 13.8 months; hazard ratio, 0.78; 95% confidence interval, 0.53-1.16). In the programmed death ligand 1 combined positive score ≥10 population, median overall survival was also numerically longer with pembrolizumab versus chemotherapy (28.5 vs 14.8 months; hazard ratio, 0.43; 95% confidence interval, 0.21-0.89) and pembrolizumab plus chemotherapy versus chemotherapy (17.5 vs 14.8 months; hazard ratio, 0.86; 95% confidence interval, 0.45-1.64). The grade 3-5 treatment-related adverse event rate was 19.4%, 75.8% and 64.9% for patients receiving pembrolizumab, pembrolizumab plus chemotherapy and chemotherapy, respectively. CONCLUSIONS This post hoc analysis showed pembrolizumab monotherapy was associated with numerically improved overall survival and a favourable tolerability profile versus chemotherapy in Asians with programmed death ligand 1-positive advanced gastric cancer/gastrooesophageal junction cancer.This study is registered with ClinicalTrials.gov, NCT02494583.
Collapse
Affiliation(s)
- Hironaga Satake
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe City, Japan and Department of Medical Oncology, Kochi Medical School, Kochi, Japan
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Hyun Cheol Chung
- Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
| | - Jeeyun Lee
- Division of Hematology/Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of JFCR, Tokyo, Japan
| | - Jen-Shi Chen
- Division of Hematology-Oncology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan and College of Medicine, Chang Gung University, Tao-Yuan, Taiwan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Kenji Amagai
- Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Hospital and Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Masahiro Goto
- Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan
| | - Yee Chao
- Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan
| | - Ka-On Lam
- Department of Clinical Oncology, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Shi Rong Han
- Department of Medical Oncology, MSD K.K., Tokyo, Japan
| | | | - Sukrut Shah
- Department of Medical Oncology, Merck & Co., Inc., Rahway, NJ, USA
| | - Kohei Shitara
- Department of Gastrointestinal Oncology, National Cancer Center Hospital, Kashiwa, Japan.,Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| |
Collapse
|
|
10
|
Farley JH, Brady WE, O'Malley D, Fujiwara K, Yonemori K, Bonebrake A, Secord AA, Stephan JM, Walker JL, Nam JH, Birrer MJ, Gershenson DM. A phase II evaluation of temsirolimus with carboplatin and paclitaxel followed by temsirolimus consolidation in clear cell ovarian cancer: An NRG oncology trial. Gynecol Oncol 2022; 167:423-428. [PMID: 36244829 PMCID: PMC9789681 DOI: 10.1016/j.ygyno.2022.10.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/06/2022] [Accepted: 10/07/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVE The primary objective of the study was to estimate the 12-month progression-free survival (PFS) for carboplatin/paclitaxel + temsirolimus in women with newly diagnosed clear cell ovarian cancer (CCOC), compared to historical controls in this patient population. METHODS Patients with Stage III or IV CCOC were treated with Paclitaxel 175 mg/m2 on Day 1, Carboplatin AUC 6 Day 1, and temsirolimus (CCI-779) 25 mg IV Days 1 and 8 every 3 weeks for Cycles 1-6 or disease progression, followed by consolidation therapy with temsirolimus 25 mg Days 1, 8, and 15 every 3 weeks cycles 7-17 or until disease progression. RESULTS Ninety patients were accrued to the study: 45 in the US and Korea (US/Korea) and 45 in Japan. Twenty-two percent received ≤6 cycles of therapy while 28% completed all 17 cycles of chemotherapy. Median PFS (OS) was 11 (23) months for US/Korea and 12 (26) months for Japan. In the US, none of suboptimally debulked patients had PFS >12 months, and 49% of optimal patients did, compared to 25% and 59% in Japan. Most common grade 3-4 adverse events were neutropenia, leukopenia, anemia, thrombocytopenia, hypertension, hypertriglyceridemia, and oral mucositis. CONCLUSION The carboplatin/paclitaxel + temsirolimus regimen was well tolerated. In optimally debulked patients, 54% had a PFS >12 months. This regimen did not statistically significantly increase PFS at 12 months compared to historical controls. No statistically significant differences in PFS or OS were observed between US/Korea vs Japan, or Asians vs non-Asians.
Collapse
Affiliation(s)
- John H Farley
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
| | - William E Brady
- NRG Oncology, Clinical Trial Development Division, Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | | | | | - Kan Yonemori
- National Cancer Center Hospital, 5 Chome-1 - 1 Tsukiji, Chuo City, Tokyo 104-0045, Japan.
| | - Albert Bonebrake
- Cancer Research for the Ozarks-Cox Health, Springfield, MO, USA.
| | | | | | - Joan L Walker
- University of Oklahoma, Oklahoma City, OK 73104, USA.
| | - Joo-Hyun Nam
- Asan Medical Center, University of Ulsan, Seoul 13876 05505, KR, Republic of Korea.
| | | | - David M Gershenson
- Dept. of Gynecologic Oncology, University of Texas, MD, USA; Anderson Cancer Center, Unit 1362, PO Box 301439, Houston, TX 77230-1439, USA.
| |
Collapse
|
|
11
|
Liu H, Li Z, Zhang Q, Li Q, Zhong H, Wang Y, Yang H, Li H, Wang X, Li K, Wang D, Kong X, He Z, Wang W, Wang L, Zhang D, Xu H, Yang L, Chen Y, Zhou Y, Xu Z. Multi‑institutional development and validation of a nomogram to predict prognosis of early-onset gastric cancer patients. Front Immunol 2022; 13:1007176. [PMID: 36148218 PMCID: PMC9488636 DOI: 10.3389/fimmu.2022.1007176] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 08/19/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Early-onset gastric cancer (EOGC, ≤45 years old) is characterized with increasing incidence and more malignant phenotypes compared with late-onset gastric cancer, which exhibits remarkable immune cell infiltration and is potential immunotherapeutic population. Till now, restricted survival information of EOGC is available due to limited case numbers. This study established a novel nomogram to help evaluate cancer-specific survival (CSS) of EOGC patients who underwent gastrectomy, and may provide evidence for predicting patients' survival. METHODS We retrospectively enrolled a cohort containing 555 EOGC cases from five independent medical centers in China, among which 388 cases were randomly selected into a training set while the other 167 cases were assigned into the internal validation set. Asian or Pacific Islander (API) patients diagnosed with EOGC during 1975-2016 were retrieved from the SEER database (n=299) and utilized as the external validation cohort. Univariate and multivariate analyses were conducted to test prognostic significances of clinicopathological factors in the training set. Accordingly, two survival nomogram models were established and compared by concordance index (C-index), calibration curve, receiver operating characteristics (ROC) curves and decision curve analyses (DCA). RESULTS The 5-year CSS rate of training cohort was 61.3% with a median survival time as 97.2 months. High consistency was observed on calibration curves in all three cohorts. Preferred nomogram was selected due to its better performance on ROC and DCA results. Accordingly, a novel predicative risk model was introduced to better stratify high-risk EOGC patients with low-risk patients. In brief, the 5-year CSS rates for low-risk groups were 92.9% in training set, 83.1% in internal validation set, 89.9% in combined NQSQS cohort, and 85.3% in SEER-API cohort. In contrast, the 5-year CSS rates decreased to 38.5%, 44.3%, 40.5%, and 36.9% in the high-risk groups of the four cohorts above, respectively. The significant survival difference between high-risk group (HRG) and low-risk group (LRG) indicated the precise accuracy of our risk model. Furthermore, the risk model was validated in patients with different TNM stages, respectively. Finally, an EOGC web-based survival calculator was established with public access, which can help predict prognosis. CONCLUSIONS Our data provided a precise nomogram on predicting CSS of EOGC patients with potential clinical applicability.
Collapse
Affiliation(s)
- Hongda Liu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zequn Li
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qun Zhang
- Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qingya Li
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Zhong
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yawen Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Hui Yang
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Qianfoshan Hospital, Jinan, China
| | - Hui Li
- Department of Pathology, The Second Hospital Affiliated to Shandong University, Jinan, China
| | - Xiao Wang
- Department of Plastic Surgery, The Second Hospital Affiliated to Shandong University, Jinan, China
| | - Kangshuai Li
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Dehai Wang
- Department of Gastrointestinal Surgery, The Second Hospital Affiliated to Shandong University, Jinan, China
| | - Xiangrong Kong
- Qingdao Urban Planning and Design Research Institute, Qingdao, China
| | - Zhongyuan He
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Weizhi Wang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Linjun Wang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Diancai Zhang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Li Yang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yuxin Chen
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Yanbing Zhou
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zekuan Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
12
|
Variation in Treatment Patterns of Patients with Early-Onset Gastric Cancer. Cancers (Basel) 2022; 14:cancers14153633. [PMID: 35892891 PMCID: PMC9332417 DOI: 10.3390/cancers14153633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/19/2022] [Accepted: 07/19/2022] [Indexed: 02/04/2023] Open
Abstract
Background: Early-onset gastric cancer (EOGC), or gastric cancer in patients younger than 45 years old, is poorly understood and relatively uncommon. Similar to other gastrointestinal malignancies, the incidence of EOGC is rising in Western countries. It is unclear which populations experience a disproportionate burden of EOGC and what factors influence how patients with EOGC are treated. Methods: We conducted a retrospective, population-based study of patients diagnosed with gastric cancer from 2004 to 2018 using the National Cancer Database (NCDB). In addition to identifying unique demographic characteristics of patients with EOGC, we evaluated (using multivariable logistic regression controlling for year of diagnoses, primary site, and stage) how gender/sex, race/ethnicity, treatment facility type, payor status, and location of residence influenced the receipt of surgery, chemotherapy, and radiation. Results: Compared to patients 45−70 and >70 years of age with gastric cancer, patients with EOGC were more likely to be female, Asian/Pacific Islander (PI), African American (AA), Hispanic, uninsured, and present with stage IV disease. On multivariable analysis, several differences among subsets of patients with EOGC were identified. Female patients with EOGC were less likely to receive surgery and chemotherapy than male patients with EOGC. Asian/Pacific Islander patients with EOGC were more likely to receive chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. African American patients were more likely to receive chemotherapy than Caucasian patients with EOGC. Hispanic patients were more likely to receive surgery and chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. Patients with EOGC treated at community cancer centers were more likely to receive surgery and less likely to receive chemotherapy than patients with EOGC treated at academic centers. Uninsured patients with EOGC were more likely to receive surgery and less likely to receive chemotherapy than privately insured patients with EOGC. Patients with EOGC living in locations not adjacent to metropolitan areas were less likely to receive surgery compared to patients with EOGC who resided in metropolitan areas, Conclusions: Patients with EOGC are a demographically distinct population. Treatment of these patients varies significantly based on several demographic factors. Additional analysis is needed to elucidate why particular groups are more affected by EOGC and how treatment decisions are made for, and by, these patients.
Collapse
|
|
13
|
Puhr HC, Puhr R, Kuchling DA, Jahic L, Takats J, Reiter TJ, Paireder M, Jomrich G, Schoppmann SF, Berghoff AS, Preusser M, Ilhan-Mutlu A. Development of an alarm symptom-based risk prediction score for localized oesophagogastric adenocarcinoma (VIOLA score). ESMO Open 2022; 7:100519. [PMID: 35759854 PMCID: PMC9434169 DOI: 10.1016/j.esmoop.2022.100519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/19/2022] [Accepted: 05/22/2022] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND Gastroesophageal adenocarcinoma is a major contributor to global disease burden with poor prognosis even in resectable, regionally limited stages. Feasible prognostic tools are crucial to improve patient management, yet scarce. PATIENTS AND METHODS Disease-related symptoms, patient, tumour, treatment as well as laboratory parameters at initial diagnosis and overall survival (OS) of patients with stage II and III gastroesophageal adenocarcinoma, who were treated between 1990 and 2020 at the Medical University of Vienna, were evaluated in a cross-validation model to develop a feasible risk prediction score. RESULTS In total, 628 patients were included in this single-centre analysis. The final score ranked from 0 to 10 and included the factors sex (female +1), age, years (30-59 +1, >60 +2), underweight classified by body mass index (+2), location of the tumour (stomach +1), stage (III +2), stenosis in endoscopy (+1) and weight loss (+1). The score was grouped into low- (0-3), medium- (4-6) and high-risk (7+) subgroups. The median OS were 70.3 [95% confidence interval (CI) 51.2-111.8], 23.4 (95% CI 21.2-26.7) and 12.6 (7.0-16.1) months, respectively. The 1-year survival probabilities were 0.88 (95% CI 0.83-0.93), 0.75 (95% CI 0.70-0.79) and 0.54 (95% CI 0.39-0.74), whereas the 5-year survival probabilities were 0.57 (95% CI 0.49-0.66), 0.24 (95% CI 0.20-0.28) and 0.09 (95% CI 0.03-0.28), respectively. CONCLUSIONS The VIennese risk prediction score for Oesophagogastric Localized Adenocarcinoma (VIOLA) risk prediction score poses a feasible tool for the estimation of OS in patients with regionally limited gastroesophageal adenocarcinoma and, thus, may improve patient management in clinical routine. Prospective analyses should be carried out to confirm our findings.
Collapse
Affiliation(s)
- H C Puhr
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - R Puhr
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria; Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - D A Kuchling
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - L Jahic
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - J Takats
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - T J Reiter
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - M Paireder
- Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - G Jomrich
- Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - S F Schoppmann
- Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - A S Berghoff
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - M Preusser
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - A Ilhan-Mutlu
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
| |
Collapse
|
|
14
|
Amirmoezi F, Geramizadeh B. Molecular Classification of Gastric Cancer With Emphasis on PDL-1 Expression: The First Report From Iran. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2022; 15:2632010X221096378. [PMID: 35651850 PMCID: PMC9149623 DOI: 10.1177/2632010x221096378] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 03/25/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Gastric cancer is one of the lethal cancers and there is no effective treatment for these patients and still, 5-year survival rate is about 25% to 30%. Finding reliable biomarkers for early-stage diagnosis, targeted therapy, and survival prediction is a priority in this cancer. OBJECTIVES In this study we were trying to know about the molecular classification of gastric cancers in a group of patients from the South of Iran. PATIENTS AND METHODS In a cross sectional study, 50 specimens of gastric cancer were selected that have enough tissue to be stained by immunohistochemistry (IHC). IHC was performed for Her-2, mismatch repair genes (MLH-1, MSH-2, MSH-6, and PMS-2), and PDL-1. Frequency of positive makers was compared with survival and outcome. RESULTS AND CONCLUSION In our study, deficient MMR (dMMR) was detected in 4 patients (8.0%). PD-L1 expression in tumor cells (TC) was observed in 1 of 4 cases (25%) with PMS2 loss. However, PD-L1 in TCs and TILs (tumor infiltrating lymphocytes) was negative in 1 case with MLH1 loss and in 3 of 4 cases with PMS2 loss, which was not statistically significant. All of our 50 cases were positive for MSH2 and MSH6, 24% of which showed TCs with PDL-1 expression and 32% of them in TIL. HER2 was positive in 2 (2/50, 4.0%) cases, among which all of the cases were positive for PD-L1 expression in TCs and TILs, respectively. However, in HER2-negative group, 26.2% (11/42) and 28.6% (12/42) of tumors were positive for PD-L1 in TCs and TILs, respectively. The expression rate of PD-L1 in HER2 negative TCs was significantly higher than that in HER2 positive TCs (P = .033). Immunohistochemistry for Her-2 was equivocal in 6 cases (12.0%) none of which expressed PD-L1 in tumor cells. In our study minimum and maximum survival times from detection of gastric cancer were 1 and 87 months, respectively. The mean ± SD and median ± SD of overall survival time were 30.69 ± 4.88 and 18 ± 1.45 months, respectively. One and 3-year survival rates of 40% and 24%, respectively. PD-L1 expression was not associated with survival, but its expression was associated with intestinal type Lauren classification and negative HER-2. PD-L1 positivity in tumor cells or tumor infiltrating lymphocytes was not an independent prognostic factor in gastric cancer.
Collapse
Affiliation(s)
- Fatemeh Amirmoezi
- Department of Pathology, Medical School
of Shiraz University, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bita Geramizadeh
- Department of Pathology, Medical School
of Shiraz University, Shiraz University of Medical Sciences, Shiraz, Iran
- Transplant Research Center, Shiraz
University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
15
|
Chung HC, Kang YK, Chen Z, Bai Y, Wan Ishak WZ, Shim BY, Park YL, Koo DH, Lu J, Xu J, Chon HJ, Bai LY, Zeng S, Yuan Y, Chen YY, Gu K, Zhong WY, Kuang S, Shih CS, Qin SK. Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. Cancer 2021; 128:995-1003. [PMID: 34878659 PMCID: PMC9299889 DOI: 10.1002/cncr.34019] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 08/23/2021] [Accepted: 08/24/2021] [Indexed: 01/05/2023]
Abstract
Background KEYNOTE‐063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second‐line therapy in Asian patients with advanced programmed death ligand 1 (PD‐L1)–positive (combined positive score ≥1) gastric/gastroesophageal junction (GEJ) cancer. Methods This randomized, open‐label, phase 3 study was conducted at 36 medical centers in China (mainland), Malaysia, South Korea, and Taiwan. Patients were randomly assigned 1:1 to 200 mg of pembrolizumab intravenously every 3 weeks for ≤2 years or 80 mg/m2 of paclitaxel intravenously every week. Primary end points were overall survival (OS) and progression‐free survival (PFS). Secondary end points were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 and safety. Results Between February 16, 2017, and March 12, 2018, 94 patients were randomly assigned (47 pembrolizumab/47 paclitaxel) after screening; enrollment was stopped on March 12, 2018, based on the results of the global KEYNOTE‐061 study, and patients were followed until the last patient's last visit. Median OS was 8 months (95% confidence interval [CI], 4‐10 months) with pembrolizumab versus 8 months (95% CI, 5‐11 months) with paclitaxel (hazard ratio [HR], 0.99; 95% CI, 0.63‐1.54). Median PFS was 2 months (95% CI, 1‐3 months) with pembrolizumab versus 4 months (95% CI, 3‐6 months) with paclitaxel (HR, 1.62; 95% CI, 1.04‐2.52). ORR was 13% for pembrolizumab versus 19% for paclitaxel. Any‐grade treatment‐related adverse events occurred in 28 pembrolizumab‐treated patients (60%) and 42 paclitaxel‐treated patients (96%); grades 3 to 5 events occurred in 5 patients (11%) and 28 patients (64%), respectively. Conclusions Definitive conclusions about the efficacy of second‐line pembrolizumab in Asian patients with advanced PD‐L1–positive gastric/GEJ cancer are limited because of insufficient power, but pembrolizumab was well tolerated in this patient population. Efficacy followed a trend similar to that observed in the phase 3 KEYNOTE‐061 trial. In this small sample of Asian patients with advanced PD‐L1–positive (combined positive score [CPS] ≥1) gastric/gastroesophageal junction (GEJ) cancer enrolled in the randomized, open‐label, phase 3 KEYNOTE‐063 study, definitive conclusions on clinical outcomes are limited; however, second‐line pembrolizumab monotherapy seems to be well tolerated in this patient population. These findings are consistent with those of the larger global KEYNOTE‐061 study in patients with CPS ≥1 gastric/GEJ cancer.
Collapse
Affiliation(s)
- Hyun Cheol Chung
- Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
| | - Yoon-Koo Kang
- Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | | | - Yuxian Bai
- Harbin Medical University Cancer Hospital, Harbin, China
| | | | - Byoung Yong Shim
- St. Vincent's Hospital, The Catholic University of Korea, Gyeonggi-Do, South Korea
| | | | - Dong-Hoe Koo
- Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jianwei Lu
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Jianming Xu
- The People's Liberation Army General Hospital, Beijing, China
| | | | - Li-Yuan Bai
- China Medical University Hospital and China Medical University, Taichung, Taiwan
| | - Shan Zeng
- Xiangya Hospital, Central South University, Changsha, China
| | - Ying Yuan
- Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yen-Yang Chen
- Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kangsheng Gu
- Hospital of Anhui Medical University, Hefei, China
| | | | | | | | - Shu-Kui Qin
- People's Liberation Army Cancer Centre of Nanjing Bayi Hospital, Nanjing, China
| |
Collapse
|
|
16
|
Abstract
Surgery is an essential component of curative-intent treatment strategies for gastric cancer. However, the care of each patient with gastric cancer must be individualized based on patient and tumor characteristics. It is important that all physicians who will be caring for patient with gastric cancer understand the current best practices of surgical management to provide patients with the highest quality of care. This article aims to provide this information while acknowledging areas of surgical management that are still controversial.
Collapse
Affiliation(s)
- Ian Solsky
- Department of Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue Block Building #112, New York, NY 10461, USA
| | - Haejin In
- Department of Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue Block Building #112, New York, NY 10461, USA; Department of Surgery, Albert Einstein College of Medicine, New York, NY, USA; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.
| |
Collapse
|
|
17
|
Zhao L, Niu P, Zhao D, Chen Y. Regional and racial disparity in proximal gastric cancer survival outcomes 1996-2016: Results from SEER and China National Cancer Center database. Cancer Med 2021; 10:4923-4938. [PMID: 34105890 PMCID: PMC8290239 DOI: 10.1002/cam4.4033] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 05/04/2021] [Accepted: 05/06/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Given the growing incidence and aggressive biological behavior of proximal gastric cancer (PGC) as reported, it is important to understand which regional or racial populations are at poor prognosis so that interventions can be treated appropriately. We sought to explore regional treatment differences as well as racial genes influence survival outcomes in China and the US patients with PGC. METHODS PGC patients defined as tumors with the epicenter located in cardia (C16.0) or fundus (C16.1) from 1996 to 2016 were identified from the Surveillance Epidemiology and End Results (SEER) in the United States as well as data from a high-volume National Cancer Center Database in China. Overall survival (OS) curves were plotted for different regional or racial groups, respectively, using the Kaplan-Meier method and compared statistically using the log-rank test. Differentially expressed genes (DEGs) analysis was performed using TCGA database. RESULTS Finally, the cohort consistent of 40973 PGC patients who enrolled in SEER database (n = 36305) or China National Cancer Center (n = 4668), and divided into 4 racial groups: Chinese (n = 5179), Black (n = 2429), White (n = 31185), and Others (n = 2096). After controlling for confounding variables, racial factors were independently associated with poor survival included Black ethnicity (HR = 1.376, 95% CI: 1.066-1.7760, p = 0.014) and White ethnicity (HR = 1.262, 95% CI: 1.005-1.583, p = 0.045) when compared to Chinese ethnicity in total PGC patients. Even in the same region for only US group, Chinese PGC patients also showed better prognosis. CONCLUSIONS In conclusion, we demonstrated the different survival outcomes of PGC patients in different regions or races from two high-volume database SEER and China National Cancer Center database. These survival differences are likely influenced by a number of factors (e.g., access to screening, quality of gastrectomy, neo/adjuvant therapy, and biological genes itself). More importantly, a better understanding of these disparities could lead to interventions that may help to abolish these disparities.
Collapse
Affiliation(s)
- Lulu Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Penghui Niu
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dongbing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yingtai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
18
|
Cowling J, Gorman B, Riaz A, Bundred JR, Kamarajah SK, Evans RPT, Singh P, Griffiths EA. Peri-operative Outcomes and Survival Following Palliative Gastrectomy for Gastric Cancer: a Systematic Review and Meta-analysis. J Gastrointest Cancer 2021; 52:41-56. [PMID: 32959118 PMCID: PMC7900337 DOI: 10.1007/s12029-020-00519-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/09/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND Many patients with gastric cancer present with late stage disease. Palliative gastrectomy remains a contentious intervention aiming to debulk tumour and prevent or treat complications such as gastric outlet obstruction, perforation and bleeding. METHODS We conducted a systematic review of the literature for all papers describing palliative resections for gastric cancer and reporting peri-operative or survival outcomes. Data from peri-operative and survival outcomes were meta-analysed using random effects modelling. Survival data from patients undergoing palliative resections, non-resective surgery and palliative chemotherapy were also combined. This study was registered with the PROSPERO database (CRD42019159136). RESULTS One hundred and twenty-eight papers which included 58,675 patients contributed data. At 1 year, there was a significantly improved survival in patients who underwent palliative gastrectomy when compared to non-resectional surgery and no treatment. At 2 years following treatment, palliative gastrectomy was associated with significantly improved survival compared to chemotherapy only; however, there was no significant improvement in survival compared to patients who underwent non-resectional surgery after 1 year. Palliative resections were associated with higher rates of overall complications versus non-resectional surgery (OR 2.14; 95% CI, 1.34, 3.46; p < 0.001). However, palliative resections were associated with similar peri-operative mortality rates to non-resectional surgery. CONCLUSION Palliative gastrectomy is associated with a small improvement in survival at 1 year when compared to non-resectional surgery and chemotherapy. However, at 2 and 3 years following treatment, survival benefits are less clear. Any survival benefits come at the expense of increased major and overall complications.
Collapse
Affiliation(s)
- Joseph Cowling
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Bethany Gorman
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Afrah Riaz
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - James R Bundred
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- College of Medical and Dental Sciences, University of Leeds, Leeds, UK
| | - Sivesh K Kamarajah
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Department of Upper GI surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS FT, Mindelsohn Way, Birmingham, B15 2TH, UK
| | - Richard P T Evans
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Pritam Singh
- Nottingham Oesophago-Gastric Unit, City Hospital, Hucknall Rd, Nottingham, NG5 1PB, UK
| | - Ewen A Griffiths
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
- Department of Upper GI surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS FT, Mindelsohn Way, Birmingham, B15 2TH, UK.
| |
Collapse
|
|
19
|
Multidisciplinary Approach in Improving Survival Outcome of Early-Stage Gastric Cancer. J Surg Res 2020; 255:285-296. [PMID: 32574755 DOI: 10.1016/j.jss.2020.05.058] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 02/06/2020] [Accepted: 05/03/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The necessity of extensive lymph node (LN) dissection/examination and adjuvant therapy for patients with early gastric cancer (EGC, Tis-T1, any N) remains controversial. We aim to refine treatment recommendations for patients with EGC through a reflective analysis for the survival gap between Eastern and Western countries. METHODS EGC patients diagnosed between 2004 and 2014 were identified from the National Cancer Database (NCDB) and a large medical center in China. Adequate LN yield was defined as ≥25 LNs examined. RESULTS In the US cohort, 14.4% of (1104/7641) patients with EGC had ≥25 LNs examined. The 5-y overall survival (OS) was significantly better than those with <25 LNs (78.9% versus 68.5%, P < 0.001). Examination of ≥25 LNs was an independent predictor of better OS after adjusting all known prognostic factors. Patients with ≥25 LNs examined had significantly higher chance of having LN-positive disease compared to patients with <25 LNs (14.9% versus 10.7%, P < 0.001). A similar stage migration phenomenon was observed in Chinese cohort (LN positive: 25.2% versus 18.4% in ≥25 LNs and <25 LNs examined group, respectively, P = 0.02). In the US cohort, adjuvant therapy was associated with a significant survival benefit for LN-positive patients (5-y OS: 71.0% versus 43.0% for with/without adjuvant therapy, respectively, P < 0.001) but not in LN-negative patients (5-y OS: 71.2% versus 71.5%, P = 0.90). CONCLUSIONS Adequate lymphadenectomy and LN examination are critical components of EGC management. Adjuvant therapy should be strongly encouraged for all EGC patients with LN-positive disease in the United States.
Collapse
|
|
20
|
Yoon SJ, Park J, Shin Y, Choi Y, Park SW, Kang SG, Son HY, Huh YM. Deconvolution of diffuse gastric cancer and the suppression of CD34 on the BALB/c nude mice model. BMC Cancer 2020; 20:314. [PMID: 32293340 PMCID: PMC7160933 DOI: 10.1186/s12885-020-06814-4] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 04/01/2020] [Indexed: 12/15/2022] Open
Abstract
Background Gastric cancer is a considerable burden for worldwide patients. And diffuse gastric cancer is the most insidious subgroup with poor survival. The phenotypic characterization of the diffuse gastric cancer cell line can be useful for gastric cancer researchers. In this article, we aimed to characterize the diffuse gastric cancer cells with MRI and transcriptomic data. We hypothesized that gene expression pattern is associated with the phenotype of the cells and that the heterogeneous enhancement pattern and the high tumorigenicity of SNU484 can be modulated by the perturbation of the highly expressed gene. Methods We evaluated the 9.4 T magnetic resonance imaging and transcriptomic data of the orthotopic mice models from diffuse gastric cancer cells such as SNU484, Hs746T, SNU668, and KATO III. We included MKN74 as an intestinal cancer control cell. After comprehensive analysis integrating MRI and transcriptomic data, we selected CD34 and validated the effect by shRNA in the BALB/c nude mice models. Results SNU484, SNU668, Hs746T, and MKN74 formed orthotopic tumors by the 5 weeks after cell injection. The diffuse phenotype was found in the SNU484 and Hs746T. SNU484 was the only tumor showing the heterogeneous enhancement pattern on T2 images with a high level of CD34 expression. Knockdown of CD34 decreased the round-void shape in the H&E staining (P = 0.028), the heterogeneous T2 enhancement, and orthotopic tumorigenicity (100% vs 66.7%). The RNAseq showed that the suppressed CD34 is associated with the downregulated gene-sets of the extracellular matrix remodeling. Conclusion Suppression of CD34 in the human-originated gastric cancer cell suggests that it is important for the round-void histologic shape, heterogeneous enhancement pattern on MRI, and the growth of gastric cancer cell line.
Collapse
Affiliation(s)
- Seon-Jin Yoon
- Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea.,Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea
| | - Jungmin Park
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Youngmin Shin
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuna Choi
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sahng Wook Park
- Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea.,Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea
| | - Seok-Gu Kang
- Departments of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.,Department of Medical Science, Yonsei University Graduate School, Seoul, South Korea
| | - Hye Young Son
- Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul, South Korea.
| | - Yong-Min Huh
- Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea. .,Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. .,Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul, South Korea. .,YUHS-KRIBB Medical Convergence Research Institute, Seoul, South Korea.
| |
Collapse
|
|
21
|
Jiang DM, Suzuki C, Espin-Garcia O, Lim CH, Ma LX, Sun P, Sim HW, Natori A, Chan BA, Moignard S, Chen EX, Liu G, Swallow CJ, Darling GE, Wong R, Jang RW, Elimova E. Surveillance and outcomes after curative resection for gastroesophageal adenocarcinoma. Cancer Med 2020; 9:3023-3032. [PMID: 32130793 PMCID: PMC7196047 DOI: 10.1002/cam4.2948] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 02/12/2020] [Accepted: 02/14/2020] [Indexed: 12/15/2022] Open
Abstract
Background The goal of surveillance testing is to enable curative salvage therapy through early disease detection, however supporting evidence in gastroesophageal adenocarcinoma is limited. We evaluated frequency of successful salvage therapy and outcomes in patients who underwent surveillance. Methods A single‐site, retrospective cohort study was conducted to identify all patients who received curative resection for gastroesophageal adenocarcinoma. Surveillance testing were those investigations not triggered by abnormal symptoms, physical examination, or blood tests. Successful salvage therapy was any potentially curative therapy for disease recurrence which resulted in postrecurrence disease‐free survival ≥2 years. Time‐to‐event data were analyzed using the Kaplan‐Meier method and log rank tests. Results Between 2011 and 2016, 210 consecutive patients were reviewed. Esophageal (14%), gastroesophageal junction (40%), and gastric adenocarcinomas (45%) were treated with surgery alone (29%) or multimodality therapy (71%). Adjuvant therapy was administered in 35%. At median follow‐up of 38.3 months, 5‐year overall survival (OS) rate was 56%. Among 97 recurrences, 53% were surveillance‐detected, and 46% were symptomatic. None was detected by surveillance endoscopy. Median time‐to‐recurrence (TTR) was 14.8 months. Recurrences included locoregional only (4%), distant (86%), and both (10%). Salvage therapy was attempted in 15 patients, 4 were successful. Compared to symptomatic recurrences, patients with surveillance‐detected recurrences had longer median OS (36.2 vs 23.7 months, P = .004) and postrecurrence survival (PRS, 16.5 vs 4.6 months, P < .001), but similar TTR (16.2 vs 13.3 months, P = .40) and duration of palliative chemotherapy (3.9 vs 3.3 months, P = .64). Conclusions Among patients surveyed, 96% of recurrences were distant, and salvage therapy was successful in only 1.9% of patients. Longer OS in patients with surveillance‐detected compared to symptomatic recurrences was not associated with significant earlier disease detection, and may be contributed by differences in disease biology. Further prospective data are warranted to establish the benefit of surveillance testing in gastroesophageal adenocarcinoma.
Collapse
Affiliation(s)
- Di M Jiang
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Chihiro Suzuki
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Osvaldo Espin-Garcia
- Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Charles H Lim
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Lucy X Ma
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Peiran Sun
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Hao-Wen Sim
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Akina Natori
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Bryan A Chan
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Stephanie Moignard
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Eric X Chen
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Geoffrey Liu
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Carol J Swallow
- Department of Surgical Oncology, Mount Sinai Hospital, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Gail E Darling
- Division of Thoracic Surgery, Department of Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Rebecca Wong
- Radiation Medicine Program, Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Raymond W Jang
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Elena Elimova
- Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| |
Collapse
|
|
22
|
Hacker UT, Hasenclever D, Linder N, Stocker G, Chung HC, Kang YK, Moehler M, Busse H, Lordick F. Prognostic role of body composition parameters in gastric/gastroesophageal junction cancer patients from the EXPAND trial. J Cachexia Sarcopenia Muscle 2020; 11:135-144. [PMID: 31464089 PMCID: PMC7015239 DOI: 10.1002/jcsm.12484] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 06/29/2019] [Accepted: 07/08/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Body fat and/or muscle composition influences prognosis in several cancer types. For advanced gastric and gastroesophageal junction cancer, we investigated which body composition parameters carry prognostic information beyond well-established clinical parameters using robust model selection strategy such that parameters identified can be expected to generalize and to be reproducible beyond our particular data set. Then we modelled how differences in these parameters translate into survival outcomes. METHODS Fat and muscle parameters were measured on baseline computed tomography scans in 761 patients with advanced gastric or gastroesophageal junction cancer from the phase III EXPAND trial, undergoing first-line chemotherapy. Cox regression analysis for overall survival (OS) and progression-free survival (PFS) included body composition parameters and clinical prognostic factors. All continuous variables were entered linearly into the model as there was no evidence of non-linear prognostic impact. For transferability, the final model included only parameters that were picked by Bayesian information criterion model selection followed by bootstrap analysis to identify the most robust model. RESULTS Muscle and fat parameters formed correlation clusters without relevant between-cluster correlation. Mean muscle attenuation (MA) clusters with the fat parameters. In multivariate analysis, MA was prognostic for OS (P < 0.0001) but not for PFS, while skeletal muscle index was prognostic for PFS (P = 0.02) but not for OS. Worse performance status Eastern Cooperative Oncology Group (ECOG 1/0), younger age (on a linear scale), and the number of metastatic sites were strong negative clinical prognostic factors for both OS and PFS. MA remained in the model for OS (P = 0.0001) following Bayesian information criterion model selection in contrast to skeletal muscle index that remained prognostic for PFS (P = 0.009). Applying stricter criteria for transferability, MA represented the only prognostic body composition parameter for OS, selected in >80% of bootstrap replicates. Finally, Cox model-derived survival curves indicated that large differences in MA translate into only moderate differences in expected OS in this cohort. CONCLUSIONS Among body composition parameters, only MA has robust prognostic impact for OS. Data suggest that treatment approaches targeting muscle quality are unlikely to prolong OS noticeably on their own in advanced gastric cancer patients, indicating that multimodal approaches should be pursued in the future.
Collapse
Affiliation(s)
- Ulrich T Hacker
- 1st Medical Department, University Cancer Center Leipzig (UCCL), University Leipzig Medical Center, Leipzig, Germany
| | - Dirk Hasenclever
- Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Medical Faculty of the University Leipzig, Leipzig, Germany
| | - Nicolas Linder
- Department of Radiology, University Leipzig Medical Center, Leipzig, Germany
| | - Gertraud Stocker
- 1st Medical Department, University Cancer Center Leipzig (UCCL), University Leipzig Medical Center, Leipzig, Germany
| | - Hyun-Cheol Chung
- Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
| | - Yoon-Koo Kang
- Division Oncology Department, Medical Center, Seoul, South Korea
| | - Markus Moehler
- First Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Harald Busse
- Department of Radiology, University Leipzig Medical Center, Leipzig, Germany
| | - Florian Lordick
- 1st Medical Department, University Cancer Center Leipzig (UCCL), University Leipzig Medical Center, Leipzig, Germany
| |
Collapse
|
|
23
|
Chau I, Ayers D, Goring S, Cope S, Korytowsky B, Abraham P. Comparative effectiveness of nivolumab versus clinical practice for advanced gastric or gastroesophageal junction cancer. J Comp Eff Res 2020; 9:103-114. [PMID: 31872771 DOI: 10.2217/cer-2019-0145] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To determine the effectiveness of nivolumab compared with routine clinical practice (RCP) for patients with gastric or gastroesophageal cancer refractory to, or intolerant of, two or more previous regimens, using real-world electronic patient records from a US population, a single-arm trial (CheckMate 032) and a randomized controlled trial in an Asian setting (ATTRACTION-2). Materials & methods: A simulated treatment comparison was conducted to predict overall survival for patients treated with nivolumab compared with RCP in the USA. Results: Results of the indirect simulated treatment comparison suggest that nivolumab is associated with a 50% reduction in the risk of all-cause mortality relative to RCP (Hazard ratio: 0.50; 95% CI: 0.36, 0.68). Conclusion: The survival benefit of nivolumab may extend more generally to the USA.
Collapse
Affiliation(s)
- Ian Chau
- Royal Marsden Hospital, London & Surrey, SM2 5PT, UK
| | - Dieter Ayers
- Precision Xtract, Vancouver, B.C., V6H 3Y4, Canada
| | - Sarah Goring
- Precision Xtract, Vancouver, B.C., V6H 3Y4, Canada
| | - Shannon Cope
- Precision Xtract, Vancouver, B.C., V6H 3Y4, Canada
| | | | | |
Collapse
|
|
24
|
Prophylactic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer-A Systematic Review. J Clin Med 2019; 8:jcm8101685. [PMID: 31618869 PMCID: PMC6832700 DOI: 10.3390/jcm8101685] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 10/10/2019] [Accepted: 10/11/2019] [Indexed: 02/07/2023] Open
Abstract
Survival after potentially curative treatment of gastric cancer remains low, mostly due to peritoneal recurrence. This descriptive review gives an overview of available comparative studies concerning prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with neither clinically evident metastases nor positive peritoneal cytology who undergo potentially curative gastrectomy. After searching the PubMed, Embase, CDSR, CENTRAL and ASCO meeting library, a total of 11 studies were included comparing surgery plus prophylactic HIPEC versus surgery alone (SA): three randomised controlled trials and eight non-randomised comparative studies, involving 1145 patients. Risk of bias was high in most of the studies. Morbidity after prophylactic HIPEC was 17-60% compared to 25-43% after SA. Overall survival was 32-35 months after prophylactic HIPEC and 22-28 months after SA. The 5-year survival rates were 39-87% after prophylactic HIPEC and 17-61% after SA, which was statistically significant in three studies. Peritoneal recurrence occurred in 7-27% in the HIPEC group, compared to 14-45% after SA. This review tends to demonstrate that prophylactic HIPEC for gastric cancer can be performed safely, may prevent peritoneal recurrence and may prolong survival. However, studies were heterogeneous and outdated, which emphasizes the need for well-designed trials conducted according to current standards.
Collapse
|
|
25
|
Chen QY, Zhong Q, Wang W, Chen S, Li P, Xie JW, Wang JB, Lin JX, Lu J, Cao LL, Lin M, Tu RH, Huang ZN, Lin JL, Zheng HL, Liu ZY, Zheng CH, Peng JS, Zhou ZW, Huang CM. Prognosis of Young Survivors of Gastric Cancer in China and the U.S.: Determining Long-Term Outcomes Based on Conditional Survival. Oncologist 2019; 24:e260-e274. [PMID: 30470692 PMCID: PMC6656502 DOI: 10.1634/theoncologist.2018-0220] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 09/05/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Young survivors of gastric cancer (GC) have better prognoses than elderly patients, yet their disease-specific survival (DSS) has received little attention. PATIENTS AND METHODS Data on young patients (aged ≤40 years) with GC undergoing resections at three Chinese institutions (n = 542) and from the SEER database (n = 533) were retrospectively analyzed. Three-year conditional disease-specific survival (CS3) was assessed. The effects of well-known prognostic factors over time were analyzed by time-dependent Cox regression. RESULTS Overall, young Chinese patients with GC had a better 5-year DSS than U.S. patients (62.8% vs. 54.1%; p < .05). The disease-specific mortality likelihood of the entire cohort was not constant over time, with most deaths occurring during the first 3 years after surgery but peaking at 1 and 2 years in China and the U.S., respectively. Based on 5-year survivorship, the CS3 rates of both groups were similar (90.9% [U.S.] vs. 91.5% [China]; p > .05). Cox regression showed that for Chinese patients, site, size, T stage, and N stage were independent prognostic factors at baseline (p < .05). For U.S. patients, grade, T stage. and N stage significantly affected DSS at baseline (p < .05). In both groups, only T stage continuously affected DSS within 3 years after gastrectomy. However, for both groups, the initial well-known prognostic factors lost prognostic significance after 5 years of survival (all p > .05). Although the 5-year DSS rates of young Chinese patients with T3 and T4a disease were significantly better than those of young U.S. patients, in each T stage, the CS3 of both regions trended toward consistency over time. CONCLUSION For young patients with GC, the factors that predict survival at baseline vary over time. Although the initial 5-year DSS is heterogeneous, insight into conditional survival will help clinicians evaluate the long-term prognoses of survivors while ignoring population differences. IMPLICATIONS FOR PRACTICE With the increasing number of young survivors of gastric cancer (GC), it is essential for clinicians to understand the dynamic prognosis of these patients. Based on large data sets from China and the U.S., this study found that the prognostic factors that predict survival for young patients with GC at baseline vary over time. Although the initial 5-year disease-specific survival is heterogeneous, insight into conditional survival will help clinicians evaluate the long-term prognoses of survivors while ignoring population differences. This knowledge may be more effective in helping young patients with GC to manage future uncertainties, especially when they need to make important life plans.
Collapse
Affiliation(s)
- Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Qing Zhong
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Wei Wang
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangdong, People's Republic of China
| | - Shi Chen
- Department of Esophageal and Gastrointestinal Surgery, The Sixth Hospital Affiliated to Sun Yat-Sen University, Sun Yat-Sen University Research Center of Diagnosis and Treatment of Gastric Cancer, Guangzhou, People's Republic of China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Jia-Bing Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Ju-Li Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Zhi-Yu Liu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| | - Jun-Sheng Peng
- Department of Esophageal and Gastrointestinal Surgery, The Sixth Hospital Affiliated to Sun Yat-Sen University, Sun Yat-Sen University Research Center of Diagnosis and Treatment of Gastric Cancer, Guangzhou, People's Republic of China
| | - Zhi-Wei Zhou
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangdong, People's Republic of China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China
| |
Collapse
|
|
26
|
Rhome RM, Ru M, Moshier E, Mazumdar M, Buckstein MH. Stage-matched survival differences by ethnicity among gastric cancer patients of Asian ancestry treated in the United States. J Surg Oncol 2019; 119:737-748. [PMID: 30694524 PMCID: PMC6458087 DOI: 10.1002/jso.25389] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 01/15/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND Differences have been noted in overall survival (OS) in gastric cancer (GC) between trials conducted in Western vs Asian countries. The National Cancer Database (NCDB) reports outcomes and patient/disease variables relevant to OS. METHODS Using NCDB, we identified 89 558 adult patients with GC diagnosed (2004-2012), where self-reported race/ethnicity was available. Cox proportional hazard model was used to calculate multivariable hazard ratio (HR) of death, adjusting for race/ethnicity, age, gender, insurance, histology, grade, location, stage, and treatment type. RESULTS After adjustment, Asian patients had improved OS (HR = 0.74, 95% confidence intervals [CI] = 0.71-0.77). There were differences in OS between Asian ethnicities compared with white patients (n = 69 945), notably with Korean (n = 1249, HR = 0.70, 95% CI = 0.64-0.75), Chinese (n = 1271, HR = 0.69, 95% CI = 0.64-0.75), and Indian/Pakistani patients (n = 492, HR = 0.68, 95% CI = 0.61-0.76). Japanese (n = 829, HR = 0.84, 95% CI = 0.77-0.91) and Vietnamese (n = 560, HR = 0.79, 95% CI = 0.71-0.88) OS was also improved (P < 0.0001), while Filipino patients showed no difference (n = 415, HR = 1.00). Black patients had slightly improved OS (n = 13 500, HR = 0.98, 95% CI = 0.95-1.00, P = 0.035). CONCLUSIONS This analysis supports improved OS in Asian patients independent of stage, treatment, and known patient or disease characteristics in this large US cohort, and is the largest to define OS differences between Asian ethnicities.
Collapse
Affiliation(s)
- Ryan M Rhome
- Department of Radiation Oncology, Indiana University, Indianapolis, Indiana
| | - Meng Ru
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Erin Moshier
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Madhu Mazumdar
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Michael H Buckstein
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| |
Collapse
|
|
27
|
Zou Y, Chen L, Wang X, Chen Y, Hu L, Zeng S, Wang P, Li G, Huang M, Wang L, He S, Li S, Jian L, Zhang S. Prognostic Threshold of Neuroendocrine Differentiation in Gastric Carcinoma: a Clinicopathological Study of 945 Cases. J Gastric Cancer 2019; 19:121-131. [PMID: 30944765 PMCID: PMC6441775 DOI: 10.5230/jgc.2019.19.e9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 02/02/2019] [Accepted: 03/12/2019] [Indexed: 12/22/2022] Open
Abstract
Purpose The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. Materials and Methods Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. Results In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. Conclusions GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.
Collapse
Affiliation(s)
- Yi Zou
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Linying Chen
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Xingfu Wang
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yupeng Chen
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Liwen Hu
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Saifan Zeng
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Pengcheng Wang
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Guoping Li
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Ming Huang
- Public Security Bureau of Changle City, Changle, China
| | - Liting Wang
- Department of Pathology, No. 2 Hospital, Xiamen, China
| | - Shi He
- Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, China
| | - Sanyan Li
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Lihui Jian
- Maternity and Child Care Hospital of Huli District, Xiamen, China
| | - Sheng Zhang
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| |
Collapse
|
|
28
|
Morgan R, Cassidy M, DeGeus SWL, Tseng J, McAneny D, Sachs T. Presentation and Survival of Gastric Cancer Patients at an Urban Academic Safety-Net Hospital. J Gastrointest Surg 2019; 23:239-246. [PMID: 30097966 DOI: 10.1007/s11605-018-3898-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 07/23/2018] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Gastric cancer is decreasing nationally but remains pervasive globally. We evaluated our experience with gastric cancer at a safety-net hospital with a substantial immigrant population. METHODS Demographics, pathology, and treatment were analyzed for gastric adenocarcinoma at our institution (2004-2017). Chi-square analyses were performed for dependence of staging on demographics. Survival was evaluated with Kaplan-Meier and Cox regression analyses. RESULTS We identified 249 patients (median age 65 years). Patients were predominantly born outside the USA or Canada (74.3%), non-white (70.7%), and federally insured (71.4%), and presented with late-stage disease (52.2%). Hispanic ethnicity, Central American birthplace, Medicaid insurance, and zip code poverty > 20% were associated with late-stage presentation (all p < 0.05). Univariate analyses showed decreased survival for patients with late-stage disease, highest zip code poverty, and age ≥ 65 (all p < 0.05). On multivariate analysis, survival was negatively associated with late-stage presentation (HR 4.45, p < 0.001), age ≥ 65 (1.80, p = 0.018), and H. pylori infection (2.02, p = 0.036). CONCLUSION Hispanic ethnicity, Central American birthplace, Medicaid insurance, and increased neighborhood poverty were associated with late-stage presentation of gastric cancer with poor outcomes. Further study of these populations may lead to screening protocols in order to increase earlier detection and improve survival.
Collapse
Affiliation(s)
- Ryan Morgan
- Department of Surgery, Boston Medical Center, Boston, MA, USA
| | - Michael Cassidy
- Department of Surgery, Boston Medical Center, Boston, MA, USA
| | | | - Jennifer Tseng
- Department of Surgery, Boston Medical Center, Boston, MA, USA
| | - David McAneny
- Department of Surgery, Boston Medical Center, Boston, MA, USA
| | - Teviah Sachs
- Department of Surgery, Boston Medical Center, Boston, MA, USA.
| |
Collapse
|
|
29
|
Wu C, Wang N, Zhou H, Wang T, Zhao D. Development and validation of a nomogram to individually predict survival of young patients with nonmetastatic gastric cancer: A retrospective cohort study. Saudi J Gastroenterol 2019; 25:236-244. [PMID: 30719999 PMCID: PMC6714466 DOI: 10.4103/sjg.sjg_378_18] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND/AIMS Evidence regarding gastric cancer (GC) patients <40 years old is limited. The aim of the study was to identify risk factors affecting overall survival (OS) of young patients with nonmetastatic GC and to establish a nomogram for prognostic prediction using data from the Surveillance, Epidemiology and End Results (SEER) database. Furthermore, this study sought to externally validate this nomogram in an independent patient cohort. PATIENTS AND METHODS In this retrospective cohort study, the records of patients aged <40 years with nonmetastatic GC (n = 559), from the SEER database, between 2006 and 2015, were examined. The nomogram was established based on the Cox proportional hazards regression model using the SEER dataset. Patients with nonmetastatic GC (n = 201) in our department between 2009 and 2015 were selected as an external validation set. Discrimination and calibration were performed in both cohorts. RESULTS The multivariate Cox model identified race, tumor subsites, tumor size, depth of invasion, lymph node metastasis, number of examined lymph nodes, and surgery as independent covariates associated with OS. The nomogram exhibited superior discriminative power than the eighth tumor, node, metastasis (TNM) staging system in both the training set [Harrell's concordance index (C index): 0.762 vs. 0.635,P < 0.001] and validation set (C index: 0.805 vs. 0.712,P= 0.176). Calibration of the nomogram was good in both cohorts. CONCLUSIONS We developed a nomogram predicting 3- and 5-year OS rates in young patients with nonmetastatic GC. Both the training set and validation set showed good discrimination and calibration, suggesting good clinical applicability.
Collapse
Affiliation(s)
- Chaorui Wu
- Department of Pancreatic and Gastric Surgery, National Cancer Centre/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nianchang Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Centre/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhou
- Department of Pancreatic and Gastric Surgery, National Cancer Centre/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tongbo Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Centre/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dongbing Zhao
- Department of Pancreatic and Gastric Surgery, National Cancer Centre/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,Address for correspondence: Dr. Dongbing Zhao, National Cancer Centre/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Pan-jia-yuan South Lane, Chaoyang District, Beijing - 100021, China. E-mail:
| |
Collapse
|
|
30
|
Ren J, Niu G, Wang X, Song T, Hu Z, Ke C. Effect of Age on Prognosis of Gastric Signet-Ring Cell Carcinoma: A SEER Database Analysis. Med Sci Monit 2018; 24:8524-8532. [PMID: 30473583 PMCID: PMC6278247 DOI: 10.12659/msm.911766] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Age is a prognostic factor for multiple malignancies. In this study, we aimed to assess the effect of age on the cancer-specific survival (CSS) of patients with gastric signet-ring cell carcinoma (SRC). Material/Methods Information on patients with gastric SRC was extracted from the Surveillance, Epidemiology, and End Results database. Chi-squared tests were used to demonstrate distribution differences, and Kaplan-Meier analysis and Cox regression models were used to analyze the impact of age on CSS. Results A total of 4596 patients were enrolled and divided into 3 subgroups according to age (<45, 45–74, and >74 years old). Higher percentages of T4, N2, and M1 disease were observed in the <45-year-old group (all P<0.001). Kaplan-Meier plots showed that the youngest group had the most favorable 5-year CSS rate (36.3%), which remained true after stratification according to tumor stage. Multivariate Cox regression models demonstrated a poorer survival outcome for >74-year-old than for <45-year-old patients (hazard ratio 1.841, 95% confidence interval 1.636–2.071; P<0.001). Conclusions Young age is associated with improved survival, even though younger patients generally present with a more advanced-stage disease.
Collapse
Affiliation(s)
- Jun Ren
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Gengming Niu
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Xin Wang
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Tao Song
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Zhiqing Hu
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| | - Chongwei Ke
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China (mainland)
| |
Collapse
|
|
31
|
Li P, Huang CM, Zheng CH, Russo A, Kasbekar P, Brennan MF, Coit DG, Strong VE. Comparison of gastric cancer survival after R0 resection in the US and China. J Surg Oncol 2018; 118:975-982. [PMID: 30332517 PMCID: PMC6319936 DOI: 10.1002/jso.25220] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 08/01/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND OBJECTIVES Gastric cancer (GC) outcomes differ between Asian and Western countries, even when controlling for contributing factors, but whether this difference holds true for China remains inadequately studied. We sought to compare the presentation, treatment, and outcomes of patients with GC undergoing curative intent (R0) resection between the US and China, and to ascertain whether geography/ institution is an independent predictor of disease-specific survival (DSS). METHODS Data were analyzed from patients with GC undergoing R0 resection at high-volume cancer centers in the US (Memorial Sloan Kettering Cancer Center [MSKCC], n = 1378) and China (Fujian Medical University Union Hospital [FMUUH], n = 4262) between 2000 and 2014. Factors associated with DSS were examined by multivariate analysis. RESULTS The 5-year DSS ( P < 0.001) for all patients was better at MSKCC than at FMUUH, even among patients not receiving preoperative chemotherapy ( P < 0.001), but stratification by substage eliminated this difference ( P > 0.05). Factors independently associated with DSS included age, histology, tumor size, T category, N category, gastrectomy type, and preoperative chemotherapy, but not institution. CONCLUSIONS Although the presentation of patients with GC between MSKCC and FMUUH differs, survival of patients with curatively resected GC, when matched for clinical stage, is comparable.
Collapse
Affiliation(s)
- Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Ashley Russo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Priyanka Kasbekar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Murray F. Brennan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Daniel G. Coit
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vivian E. Strong
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| |
Collapse
|
|
32
|
Shu Y, Zhang W, Hou Q, Zhao L, Zhang S, Zhou J, Song X, Zhang Y, Jiang D, Chen X, Wang P, Xia X, Liao F, Yin D, Chen X, Zhou X, Zhang D, Yin S, Yang K, Liu J, Fu L, Zhang L, Wang Y, Zhang J, An Y, Cheng H, Zheng B, Sun H, Zhao Y, Wang Y, Xie D, Ouyang L, Wang P, Zhang W, Qiu M, Fu X, Dai L, He G, Yang H, Cheng W, Yang L, Liu B, Li W, Dong B, Zhou Z, Wei Y, Peng Y, Xu H, Hu J. Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer. Nat Commun 2018; 9:2447. [PMID: 29961079 PMCID: PMC6026495 DOI: 10.1038/s41467-018-04907-0] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 05/31/2018] [Indexed: 02/05/2023] Open
Abstract
Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.
Collapse
Affiliation(s)
- Yang Shu
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Weihan Zhang
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Qianqian Hou
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Linyong Zhao
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Shouyue Zhang
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Jiankang Zhou
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Xiaohai Song
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yan Zhang
- Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Dan Jiang
- Department of Pathology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Xinzu Chen
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Peiqi Wang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 610041, Chengdu, China
| | - Xuyang Xia
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Fei Liao
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Dandan Yin
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Xiaolong Chen
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Xueyan Zhou
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Duyu Zhang
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Senlin Yin
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Kun Yang
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Jianping Liu
- Department of Pathology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Leilei Fu
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Lan Zhang
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yuelan Wang
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Junlong Zhang
- Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Yunfei An
- Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Hua Cheng
- WuxiNextCODE, 200131, Shanghai, China
| | - Bin Zheng
- WuxiNextCODE, 200131, Shanghai, China
| | | | - Yinglan Zhao
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yongsheng Wang
- Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Dan Xie
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Liang Ouyang
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Ping Wang
- Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Wei Zhang
- Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, 410008, Changsha, China
| | - Meng Qiu
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Xianghui Fu
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Lunzhi Dai
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Gu He
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Hanshuo Yang
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Wei Cheng
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Li Yang
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Bo Liu
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Weimin Li
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Biao Dong
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Zongguang Zhou
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yuquan Wei
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China
| | - Yong Peng
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
| | - Heng Xu
- Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
- Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
| | - Jiankun Hu
- Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
| |
Collapse
|
|
33
|
Zhang S, Tong YX, Xu XS, Lin H, Chao TF. Prognostic significance of SATB1 in gastrointestinal cancer: a meta-analysis and literature review. Oncotarget 2018; 8:48410-48423. [PMID: 28430598 PMCID: PMC5564658 DOI: 10.18632/oncotarget.16867] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Accepted: 03/24/2017] [Indexed: 01/07/2023] Open
Abstract
Background The special AT-rich sequence-binding proteins 1 (SATB1) is a major regulator involved in cell differentiation. It has been shown that SATB1 acts as an oncogenic regulator. The clinical and prognostic significance of SATB1 in gastrointestinal cancer remains controversial. The purpose of this study is to conduct a systematic review and meta-analysis to elucidate the impact of SATB1 in gastrointestinal cancer. Results A total of 3174 gastrointestinal cancer patients from 15 studies were included. The correlation between SATB1 expression and OS or RFS was investigated in 12 and 5 studies respectively. The results of meta-analysis showed that SATB1 overexpression is inversely correlated with OS (combined HR: 1.79, p = 0.0003) and RFS (combined HR: 2.46, p < 0.0001). In subgroup analysis, SATB1 expression is significantly correlated with poor prognosis in gastrointestinal cancer in Asian population. SATB1 expression is associated with stage, invasion depth, lymph node metastasis and distant metastasis. Methodology Published studies with data on overall survival (OS) and/or relapse free survival (RFS) and SATB1 expression were searched from Cochrane Library, PubMed and Embase (up to Dec 30, 2016). The outcome measurement is hazard ratio (HR) for OS or RFS related with SATB1 expression. Two reviewers independently screened the literatures, extracted the data and performed meta-analysis using RevMan 5.3.0 software. The combined HRs were calculated by fixed- or random-effect models. Conclusions The results of this meta-analysis suggest that SATB1 overexpression is related to advanced stage, lymph node metastasis and distant metastasis. SATB1 overexpression is a marker indicating poor prognosis in gastrointestinal cancer.
Collapse
Affiliation(s)
- Sheng Zhang
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi Xin Tong
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Shang Xu
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hui Lin
- Tongji University, School of Medicine, Shanghai, China
| | - Teng Fei Chao
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
34
|
Sun F, Sun H, Mo X, Tang J, Liao Y, Wang S, Su Y, Ma H. Increased survival rates in gastric cancer, with a narrowing gender gap and widening socioeconomic status gap: A period analysis from 1984 to 2013. J Gastroenterol Hepatol 2018; 33:837-846. [PMID: 29052260 DOI: 10.1111/jgh.14024] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 08/14/2017] [Accepted: 10/10/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Gastric cancer (GC) has the fifth highest incidence rate of all cancers and has a poor prognosis. However, no recent large-scale and long-term studies have evaluated the incidence and survival rates of individuals with GC. METHODS In order to explore the change of GC incidence and survival rates by age, gender, race, and socioeconomic status (SES), incidence data and survival status of patients with GC between 1984 and 2013 were abstracted from the Surveillance, Epidemiology, and End Results database. Totally, 87 242 cases of GC were exported and were analyzed. RESULTS During these three decades, the incidence of GC was 7.4, 6.8, and 5.5 per 100 000 individuals in each decade. The 1-year relative survival rates (RSRs) improved from 42.4% to 44.3% to 49.0% (P < 0.0001), with a larger increase seen in the third decade. However, the long-term survival rates remained low (from 17.8% to 20.3% to 22.9% for the 5-year RSRs, P < 0.0001; from 14.1% to 16.4% to 18.6% for the 10-year RSRs, P < 0.0001). CONCLUSION Our analysis demonstrated the decreased incidence and increased survival rate of GC. In addition, lower SES was associated with lower survival rates. It is notable that others (primarily for Asians) had the highest incidence rate but had better outcomes than Whites and Blacks.
Collapse
Affiliation(s)
- Fengze Sun
- Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Huanhuan Sun
- Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Xiangqiong Mo
- Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Jianjun Tang
- Department of Gastroenterology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi, China
| | - Yifeng Liao
- Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Shuncong Wang
- Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Yonghui Su
- Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| | - Haiqing Ma
- Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
| |
Collapse
|
|
35
|
Chen LT, Oh DY, Ryu MH, Yeh KH, Yeo W, Carlesi R, Cheng R, Kim J, Orlando M, Kang YK. Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review. Cancer Res Treat 2017; 49:851-868. [PMID: 28052652 PMCID: PMC5654167 DOI: 10.4143/crt.2016.176] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 12/20/2016] [Indexed: 02/08/2023] Open
Abstract
Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.
Collapse
Affiliation(s)
- Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes and National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Do-Youn Oh
- Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Min-Hee Ryu
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Winnie Yeo
- Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China
| | | | | | | | | | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
36
|
Examining the gastric cancer survival gap between Asians and whites in the United States. Gastric Cancer 2017; 20:573-582. [PMID: 27866287 DOI: 10.1007/s10120-016-0667-4] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Accepted: 11/08/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Globally, Asian countries bear a disproportionate gastric cancer burden. Asian Americans, the fastest growing minority population in the US, have higher gastric cancer survival than non-Hispanic whites (NHWs) despite higher incidence. Benefitting from uniform cancer registry standards within the US, we examine for the first time the heterogeneity in the Asian American population, which may elucidate the causes of these disparities. METHODS SEER gastric cancer data from 2000 to 2012 were used to calculate 5-year survival estimates for NHWs and the six largest Asian ethnicities. Multivariate analyses were performed to identify critical prognostic factors and survival disparities between Asian groups and NHWs. RESULTS We analyzed 33,313 NHW and 8473 Asian gastric cancer cases. All Asian groups had significantly higher 5-year survival than NHWs, at 29.8%. Among Asians, Koreans and Vietnamese had the highest and lowest survival, at 45.4% and 35.7%, respectively. The Korean survival advantage was largely attributable to relatively high proportions of localized stage and low proportions of cardia tumors. After adjusting for major prognostic factors, the survival disadvantage of NHWs, while attenuated, remained significant in comparison to all Asian groups (HR: 1.33, 95% CI: 1.24-1.43; reference: Korean). The survival disparities within the Asian groups vanished with adjustment. CONCLUSIONS This study characterizes distinctive gastric cancer survival patterns among the six major Asian groups and NHWs in the US. The favorable survival for Koreans is largely attributable to specific clinical factors, particularly stage at diagnosis. The causes of the survival disadvantage for NHWs remain elusive.
Collapse
|
|
37
|
Lee DH, Lee SY, Oh SC. Hedgehog signaling pathway as a potential target in the treatment of advanced gastric cancer. Tumour Biol 2017. [DOI: 10.1177/1010428317692266] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Affiliation(s)
- Dae-Hee Lee
- Division of Brain Korea 21 Program for Biomedicine Science, College of Medicine, Korea University, Seoul, Republic of Korea
- Division of Oncology and Hematology, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Suk-young Lee
- Division of Oncology and Hematology, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Sang Cheul Oh
- Division of Brain Korea 21 Program for Biomedicine Science, College of Medicine, Korea University, Seoul, Republic of Korea
- Division of Oncology and Hematology, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
| |
Collapse
|
|
38
|
Yang K, Hu JK. Gastric cancer treatment: similarity and difference between China and Korea. Transl Gastroenterol Hepatol 2017; 2:36. [PMID: 28529990 DOI: 10.21037/tgh.2017.04.02] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 03/28/2017] [Indexed: 02/05/2023] Open
Abstract
Chinese populations have many demographic similarities to Korean populations. However, the long-term survival rates of gastric cancer patients in China are still not satisfactory when compared with Korea, especially for the advanced cases. In this article, we discuss about the similarity and difference of gastric cancer treatment in terms of screening, surgical approach, stomach resection, digestive tract reconstruction, lymphadenectomy, harvested lymph nodes, operative morbidity and mortality, postoperative chemotherapy as well as follow-up between China and Korea. Given that a variety of factors ranging from tumor characteristics to different treatment strategies are seen between the two countries, the reasons accounting for the differences in survival should be focused and the corresponding strategy should be considered and finally promote to improve the prognosis of gastric cancer.
Collapse
Affiliation(s)
- Kun Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.,Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.,Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| |
Collapse
|
|
39
|
Spiegel D, Palta M, Uronis H. Role of Chemotherapy and Radiation Therapy in the Management of Gastric Adenocarcinoma. Surg Clin North Am 2017; 97:421-435. [PMID: 28325195 DOI: 10.1016/j.suc.2016.11.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Gastric adenocarcinoma is the fifth most common cancer worldwide and is often diagnosed at a late stage with nearly 50% of patients having locally advanced, unresectable, or metastatic disease at the time of presentation. Efforts to improve outcomes in patients with resected and unresectable gastric cancer with various chemotherapy and radiation regimens are ongoing. Appropriate evaluation and management is often not straightforward and requires the input of a multidisciplinary team. There is no consensus as to the best approach for treatment of gastric cancer; however, the available data and our institutional approach to the management of gastric cancer are discussed.
Collapse
Affiliation(s)
- Daphna Spiegel
- Department of Radiation Oncology, Duke University, DUMC Box 3085, Durham, NC 27710, USA
| | - Manisha Palta
- Department of Radiation Oncology, Duke University, DUMC Box 3085, Durham, NC 27710, USA
| | - Hope Uronis
- Division of Medical Oncology, Duke University, DUMC Box 2823, Durham, NC 27710, USA.
| |
Collapse
|
|
40
|
Schumacher SE, Shim BY, Corso G, Ryu MH, Kang YK, Roviello F, Saksena G, Peng S, Shivdasani RA, Bass AJ, Beroukhim R. Somatic copy number alterations in gastric adenocarcinomas among Asian and Western patients. PLoS One 2017; 12:e0176045. [PMID: 28426752 PMCID: PMC5398631 DOI: 10.1371/journal.pone.0176045] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Accepted: 04/04/2017] [Indexed: 12/20/2022] Open
Abstract
Gastric cancer, a leading worldwide cause of cancer mortality, shows high geographic and ethnic variation in incidence rates, which are highest in East Asia. The anatomic locations and clinical behavior also differ by geography, leading to the controversial idea that Eastern and Western forms of the disease are distinct. In view of these differences, we investigated whether gastric cancers from Eastern and Western patients show distinct genomic profiles. We used high-density profiling of somatic copy-number aberrations to analyze the largest collection to date of gastric adenocarcinomas and utilized genotyping data to rigorously annotate ethnic status. The size of this collection allowed us to accurately identify regions of significant copy-number alteration and separately to evaluate tumors arising in Eastern and Western patients. Among molecular subtypes classified by The Cancer Genome Atlas, the frequency of gastric cancers showing chromosomal instability was modestly higher in Western patients. After accounting for this difference, however, gastric cancers arising in Easterners and Westerners have highly similar somatic copy-number patterns. Only one genomic event, focal deletion of the phosphatase gene PTPRD, was significantly enriched in Western cases, though also detected in Eastern cases. Thus, despite the different risk factors and clinical features, gastric cancer appears to be a fundamentally similar disease in both populations and the divergent clinical outcomes cannot be ascribed to different underlying structural somatic genetic aberrations.
Collapse
Affiliation(s)
- Steven E. Schumacher
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
- Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America
| | - Byoung Yong Shim
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
| | - Giovanni Corso
- Department of Human Pathology, University Hospital, Siena, Italy
| | - Min-Hee Ryu
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Yoon-Koo Kang
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Franco Roviello
- Department of Human Pathology, University Hospital, Siena, Italy
| | - Gordon Saksena
- Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America
| | - Shouyong Peng
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
| | - Ramesh A. Shivdasani
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
- Departments of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
- * E-mail: (RB); (AJB); (RAS)
| | - Adam J. Bass
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
- Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America
- Departments of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
- * E-mail: (RB); (AJB); (RAS)
| | - Rameen Beroukhim
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
- Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America
- Departments of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
- * E-mail: (RB); (AJB); (RAS)
| |
Collapse
|
|
41
|
Lowe KA, Danese MD, Gleeson ML, Langeberg WJ, Ke J, Kelsh MA. Racial and Ethnic Variability in the Prevalence and Incidence of Comorbidities Associated with Gastric Cancer in the United States. J Gastrointest Cancer 2017; 47:168-81. [PMID: 26961791 DOI: 10.1007/s12029-016-9809-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE Comorbidities are known to impact quality of life, treatment choices, and survival. Our objectives were to characterize comorbid conditions in a cohort of elderly gastric cancer patients and to determine if there is variability in the prevalence or incidence of the comorbid conditions across racial/ethnic groups. METHODS A total of 12,612 individuals, ≥66 years of age, diagnosed with gastric cancer between 2000 and 2007, and an equal number of gender- and region-matched cancer-free individuals, were identified using the National Cancer Institute's Surveillance, Epidemiology, and End Results registry linked to Medicare claims in the United States. The prevalence (%) in the year before diagnosis and the 12-month incidence rates after diagnosis were estimated for 32 chronic and ten acute comorbid conditions for the entire cohort and by race/ethnicity (Asian, Black, Hispanic, White, and other) and Asian subgroups (e.g., Chinese, Filipino, Japanese, Pacific Islander). RESULTS White and Black cases exhibited the highest prevalence of most comorbid conditions. Asian and Pacific Islander cases exhibited the lowest. There was substantial variability in the 12-month incidence of the comorbidities across the racial/ethnic groups. Electrolyte disorder was the most common incident condition among Whites and Blacks. With the exception of Whites, anemia was the most common incident condition in all racial and ethnic groups 180 days following chemotherapy. CONCLUSIONS There is variability in the prevalence and incidence in comorbidities across racial/ethnic groups.
Collapse
Affiliation(s)
| | | | | | | | - Juan Ke
- Amgen, Inc, Thousand Oaks, CA, USA
| | | |
Collapse
|
|
42
|
Russo A, Li P, Strong VE. Differences in the multimodal treatment of gastric cancer: East versus west. J Surg Oncol 2017; 115:603-614. [PMID: 28181265 DOI: 10.1002/jso.24517] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Revised: 11/27/2016] [Accepted: 11/27/2016] [Indexed: 02/06/2023]
Abstract
There has been a great deal of interest about varying treatment paradigms of gastric cancer in Eastern and Western countries. Differences in tumor biology, screening initiatives, surgical approach, extent of lymphadenectomy, and neoadjuvant versus adjuvant chemotherapy regimens have been studied and documented in the literature. The purpose of this review is to give an updated report on the current status and management differences in the treatment of gastric cancer between Eastern and Western countries.
Collapse
Affiliation(s)
- Ashley Russo
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ping Li
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.,Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Vivian E Strong
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| |
Collapse
|
|
43
|
Feingold PL, Kwong MLM, Davis JL, Rudloff U. Adjuvant intraperitoneal chemotherapy for the treatment of gastric cancer at risk for peritoneal carcinomatosis: A systematic review. J Surg Oncol 2016; 115:192-201. [PMID: 27878811 DOI: 10.1002/jso.24476] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 10/02/2016] [Indexed: 12/29/2022]
Abstract
The peritoneal surface is a frequent site of recurrence following surgery for gastric cancer. A systematic review and random effect analysis was undertaken to analyze current literature regarding the role of adjuvant intraperitoneal chemotherapy in gastric cancer. While pooled analysis supports the use of adjuvant IP chemotherapy in resectable gastric cancer, maximal benefit occured with intra-operative delivery, and possibly the use of MMC. J. Surg. Oncol. 2017;115:192-201. © 2016 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Paul L Feingold
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Mei Li M Kwong
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Jeremy L Davis
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Udo Rudloff
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| |
Collapse
|
|
44
|
Prognostic Importance of Cell Cycle Regulators Cyclin D1 ( CCND1) and Cyclin-Dependent Kinase Inhibitor 1B ( CDKN1B/p27) in Sporadic Gastric Cancers. Gastroenterol Res Pract 2016; 2016:9408190. [PMID: 27781065 PMCID: PMC5066010 DOI: 10.1155/2016/9408190] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 09/01/2016] [Indexed: 12/14/2022] Open
Abstract
Background. Gastric cancer is known for a notable variety in the course of the disease. Clinical factors, such as tumor stage, grade, and localization, are key in patient survival. It is expected that molecular factors such as somatic mutations and gene amplifications are also underlying tumor biological behavior and may serve as factors for prognosis estimation. Aim. The purpose of this study was to examine gene amplifications from a panel of genes to uncover potential prognostic marker candidates. Methods. A panel of gene amplifications including 71 genes was tested by multiplex ligation-dependent probe amplification (MLPA) technique in 76 gastric cancer samples from a Caucasian population. The correlation of gene amplification status with patient survival was determined by the Kaplan-Meier method. Results. The amplification of two cell cycle regulators, CCND1 and CDKN1B, was identified to have a negative prognostic role. The medial survival of patients with gastric cancer displaying amplification compared to patients without amplification was 192 versus 725 days for CCND1 (P = 0.0012) and 165 versus 611 days for CDKN1B (P = 0.0098). Conclusion. Gene amplifications of CCND1 and CDKN1B are potential candidates to serve as prognostic markers for the stratification of patients based on the estimate of survival in the management of gastric cancer patients.
Collapse
|
|
45
|
Nakagawa M, Choi YY, An JY, Seo SH, Shin HB, Bang HJ, Li S, Kim HI, Cheong JH, Hyung WJ, Noh SH. When Eastern Surgeons Meet Western Patients: A Pilot Study of Gastrectomy with Lymphadenectomy in Caucasian Patients at a Single Korean Institute. Yonsei Med J 2016; 57:1294-7. [PMID: 27401666 PMCID: PMC4960401 DOI: 10.3349/ymj.2016.57.5.1294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 09/07/2015] [Accepted: 10/08/2015] [Indexed: 11/27/2022] Open
Abstract
East Asian surgeons generally report lower morbidity and mortality rates for gastrectomy with D2 lymphadenectomy than do surgeons in Western countries; however, the disparity remains unexplained. The aim of this article was to determine the feasibility and safety regarding cases in which East Asian surgeons perform such procedures in Caucasian patients (CPs). Twelve CPs underwent gastrectomy with lymphadenectomy for gastric cancer at Yonsei University Severance Hospital, Seoul, Korea between June 2011 and April 2014. Procedures performed included total gastrectomy (7 of 12, 58%), distal gastrectomy (4 of 12, 33%), and completion total gastrectomy (1 of 12, 8%). Nine patients (75%) underwent D2 lymphadenectomy, and D1+ lymphadenectomy was performed in three others (25%). In four patients (33%), combined resections were carried out. The median values of surgical parameters were as follows: operative time, 266.5 min (range, 120-586 min); estimated blood loss, 90 mL (range, 37-350 mL); retrieved lymph node count, 37.5 (range, 22-63); and postoperative hospital stay, 13.7 days (range, 5-63 days). No mortality was encountered, although two patients (17%) experienced complications (both Clavien-Dindo classification grade IIIa anastomotic leakages), which were successfully managed by conservative treatment. In the hands of East Asian surgeons, mortality and short-term morbidity appears to be acceptably low in CPs subjected to gastrectomy with lymphadenectomy for gastric cancer.
Collapse
Affiliation(s)
- Masatoshi Nakagawa
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Gastric Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yoon Young Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Yeong An
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hyuk Seo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Beak Shin
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Hui Jae Bang
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Shuangxi Li
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Gastrointestinal Surgery, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
| | - Hyung Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Ho Cheong
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Woo Jin Hyung
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hoon Noh
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Korea.
| |
Collapse
|
|
46
|
Polom K, Marrelli D, Pascale V, Roviello G, Voglino C, Rho H, Vindigni C, Marini M, Macchiarelli R, Roviello F. High-risk and low-risk gastric cancer areas in Italy and its association with microsatellite instability. J Cancer Res Clin Oncol 2016; 142:1817-1824. [PMID: 27206556 DOI: 10.1007/s00432-016-2181-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 05/10/2016] [Indexed: 02/08/2023]
Abstract
PURPOSE The different pathological characteristics and prognoses between gastric cancer patients coming from high-risk (group A) and low-risk (group B) areas of Italy were analyzed. We investigated a suspected difference in microsatellite instability (MSI) between these two groups. METHODS MSI analyses of 452 gastric cancer patients were performed using five quasimonomorphic mononucleotide repeats NR-21, NR-24, NR-27, BAT-25, and BAT-26. MSI analysis was done by PCR usage. An allelic profile of these five mononucleotides was detected on an automated DNA sequencer ABI PRISM 3100 Genetic Analyser. Data were analyzed according to high-risk and low-risk gastric cancer areas. RESULTS MSI was observed in 23.9 % of all gastric cancer patients studied. Patients from group A showed a higher rate of MSI (28.4 %) than from group B (13.5 %) (p < 0.001). We analyzed this association together with tumor location and Lauren classification: A nonsignificant differences were seen when analyzing cardia and non-cardia tumors (p = 0.854) but significant for Lauren histotype (p = 0.028). There was no statistical difference in survival between high-risk and low-risk areas (p = 0.437), with a nonsignificant trend for better survival in the high-risk group, especially when measured over a longer period of time. Analyzing MSI or MSS in these groups, the survival curves were almost the same. CONCLUSIONS A higher frequency of MSI in patients coming from high-risk areas may help explain geographical differences in gastric cancer. The trend of better survival in high-risk areas may be due to a higher rate of MSI gastric cancer patients.
Collapse
Affiliation(s)
- Karol Polom
- General Surgery and Surgical Oncology Department, University of Siena, viale Bracci 16, 53-100, Siena, Italy.
| | - Daniele Marrelli
- General Surgery and Surgical Oncology Department, University of Siena, viale Bracci 16, 53-100, Siena, Italy
| | - Valeria Pascale
- General Surgery and Surgical Oncology Department, University of Siena, viale Bracci 16, 53-100, Siena, Italy
| | - Giandomenico Roviello
- Section of Pharmacology and University Center DIFF-Drug Innovation Forward Future, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Costantino Voglino
- General Surgery and Surgical Oncology Department, University of Siena, viale Bracci 16, 53-100, Siena, Italy
| | - Henry Rho
- University of Medical Sciences, Poznan, Poland
| | - Carla Vindigni
- Department of Pathology, Azienda Ospedaliera Universitaria Senese, Siena, Italy
| | - Mario Marini
- Department of Medicine, Surgery and Neurosciences, Unit of Endoscopy and Gastroenterology, University of Siena, Siena, Italy
| | - Raffaele Macchiarelli
- Department of Medicine, Surgery and Neurosciences, Unit of Endoscopy and Gastroenterology, University of Siena, Siena, Italy
| | - Franco Roviello
- General Surgery and Surgical Oncology Department, University of Siena, viale Bracci 16, 53-100, Siena, Italy
| |
Collapse
|
|
47
|
Yang K, Choi YY, Zhang WH, Chen XZ, Song MK, Lee J, Zhang B, Chen ZX, Kim HI, Chen JP, Cheong JH, Zhou ZG, Hyung WJ, Hu JK, Noh SH. Strategies to improve treatment outcome in gastric cancer: a retrospective analysis of patients from two high-volume hospitals in Korea and China. Oncotarget 2016; 7:44660-44675. [PMID: 27191995 PMCID: PMC5190126 DOI: 10.18632/oncotarget.9378] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 04/23/2016] [Indexed: 02/05/2023] Open
Abstract
China has high incidence of gastric cancer (GC). However, the treatment outcomes of China were unsatisfactory compared to those of Korea. We performed this study to compare tumour characteristics, treatment parameters, and survival outcomes of GC patients between Korea and China based on the databases of two high-volume hospitals, with the aim of identifying indicators of GC prognosis. Data of patients undergoing gastrectomy for GC from 2006 to 2010 were analysed retrospectively. Subgroup survival analyses, stratified by clinicopathologic factors and multivariable analyses, were performed. The interactive roles of chemotherapy and D2 lymphadenectomy for overall survival were also investigated. Among 1365 Chinese and 4981 Korean patients, the proportion of early cancer detection in Chinese patients was much lower relative to that of Korean patients. There were no significant differences between countries in terms of surgical morbidity and mortality. The overall 5-year survival rates were 54.3% and 81.4%; when stratified by clinicopathologic factors, the survival were generally statistically higher in Korean patients. Gender, age, T stage, N stage, extent of lymphadenectomy, radicality of surgery, resection type, and chemotherapy were independently associated with survival in patients without metastasis. Survival rates for stage II and III GC differed significantly between the two countries, but this difference was eliminated among patients who underwent D2 lymphadenectomy or received chemotherapy. These treatments were given to patients with advanced-stage diagnoses (approximately 20% and 80% of patients, respectively). Treatment type was selected as independent prognostic factors in stage I-III and D2/D2+, with chemotherapy resulting in the best prognosis. Many differences in GC tumour characteristics exist between two countries. Early cancer detection and standardized treatment in Korea contribute to superior survival rates. Promotion of an early screening program, training and dissemination of standard D2 lymphadenectomy, and appropriate applications of chemotherapy would improve survival outcomes.
Collapse
Affiliation(s)
- Kun Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Department of Surgery, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
- Robot and Minimal Invasive Surgery Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Yoon Young Choi
- Department of Surgery, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Wei-Han Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Mi Kyung Song
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jinae Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhi-Xin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hyoung-Il Kim
- Department of Surgery, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
- Robot and Minimal Invasive Surgery Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Jia-Ping Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jae-Ho Cheong
- Department of Surgery, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Zong-Guang Zhou
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Woo Jin Hyung
- Department of Surgery, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
- Robot and Minimal Invasive Surgery Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Sung Hoon Noh
- Department of Surgery, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
48
|
Lu M, Yang Z, Feng Q, Yu M, Zhang Y, Mao C, Shen L, Tang J. The characteristics and prognostic value of signet ring cell histology in gastric cancer: A retrospective cohort study of 2199 consecutive patients. Medicine (Baltimore) 2016; 95:e4052. [PMID: 27399088 PMCID: PMC5058817 DOI: 10.1097/md.0000000000004052] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Although signet ring cell cancer (SRCC) has long been regarded as an adverse prognostic factor of gastric cancer, the findings of existing studies on this issue are inconsistent. We conducted a retrospective cohort study of 2199 consecutive patients with gastric cancer treated in a tertiary cancer hospital in Beijing, China, 1994 to 2013. The characteristics of SRCC and non-SRCC were compared. The prognostic effects of SRCC and other important clinicopathological factors on overall survival were evaluated by both univariate and multivariate Cox regression analyses and expressed as hazard ratio (HR) with 95% confidence interval (CI). SRCC accounted for 16.1% of gastric cancer, increasing from 6% to 20% over the last 2 decades, and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. SRCC (HR: 1.387, 95% CI: 1.177-1.634), stage (HR: 1.752, 95% CI: 1.458-2.106), surgery (palliative resection: HR: 0.712, 95% CI: 0.590-0.859; curative resection: HR: 0.490, 95% CI: 0.380-0.633), performance status (HR: 1.849, 95% CI: 1.553-2.201), and age (HR: 1.070, 95% CI: 1.001-1.143) were independent prognostic factors for gastric cancer, whereas time period of diagnosis, sex, and tumor location were not statistically significantly associated with overall survival. Subgroup analyses showed that the prognostic value of SRCC did not vary much with age, sex, performance status, stage, and surgery and chemotherapy status. As compared with non-SRCC, SRCC accounted for increasingly more of gastric cancer and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. It was an independent prognostic factor associated with worse survival in gastric cancer.
Collapse
Affiliation(s)
- Ming Lu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zuyao Yang
- Division of Epidemiology, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Qi Feng
- Division of Epidemiology, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Mei Yu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yuelun Zhang
- Division of Epidemiology, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Chen Mao
- Division of Epidemiology, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China
- Correspondence: Lin Shen, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China (e-mail: )
| | - Jinling Tang
- Division of Epidemiology, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| |
Collapse
|
|
49
|
Duma N, Sanchez LJ, Castro YS, Jennis AA, McCain DA, Gutierrez ME, Bamboat ZM. Gastric adenocarcinoma: clinicopathologic differences among Hispanics and non-Hispanic whites. A single Institution's experience over 14 years. Ann Gastroenterol 2016; 29:325-31. [PMID: 27366033 PMCID: PMC4923818 DOI: 10.20524/aog.2016.0030] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Accepted: 03/21/2016] [Indexed: 12/13/2022] Open
Abstract
Background Gastriccancer is a leading cause of cancer death worldwide and has significant ethnic and socioeconomic differences in distribution. The aim of this study was to compare clinicopathologic characteristics and survival between Hispanics (H) and non-Hispanic whites (NHW) with gastric cancer. Methods We reviewed the records of all patients diagnosed with gastric cancer between 1999 and 2013 at our institution. A total of 638 patients were studied. Demographics, tumor characteristics and survival rate were analyzed. Kaplan-Meier was used for survival analysis. Results There were 101 H and 537 NHW. The median age at diagnosis was 63 years in H and 69 years in NHW. At diagnosis, 48 (48%) of H patients had stage IV disease compared with 195 (36%) of NHW (P<0.03). H were more likely to have distal cancers and poorly differentiated tumors compared to NHW (44% vs. 15%, P<0.0001; 70% vs. 50%, P<0.0002, respectively). There was a significant difference in median overall survival between the two groups, being 51 months for H (95% CI: 34.6-66.9) and 99 months for NHW (95% CI: 77.3-120.7) P<0.0001. In multivariate analysis, age (OR: 1.02, 95% CI: 1.02-1.03, P<0.0001), poor differentiation (OR: 1.21, 95% CI: 1.02-1.43, P<0.02), ethnicity (OR: 1.69, 95% CI: 1.07-2.55, P<0.02), and stage (OR: 1.95, 95% CI: 1.77-2.15, P<0.0001) were independent predictors of survival. Conclusions H patients were diagnosed with gastric cancer at a younger age, to present with advanced disease at diagnosis, and had shorter overall survival compared to NHW.
Collapse
Affiliation(s)
- Narjust Duma
- Department of Internal Medicine, Newark, Rutgers-New Jersey Medical School (Narjust Duma, Larysa J. Sanchez, Yulanka S. Castro), NJ, USA
| | - Larysa J Sanchez
- Department of Internal Medicine, Newark, Rutgers-New Jersey Medical School (Narjust Duma, Larysa J. Sanchez, Yulanka S. Castro), NJ, USA
| | - Yulanka S Castro
- Department of Internal Medicine, Newark, Rutgers-New Jersey Medical School (Narjust Duma, Larysa J. Sanchez, Yulanka S. Castro), NJ, USA
| | - Andrew A Jennis
- Department of Medical and Surgical Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack (Andrew A. Jennis, Donald A. McCain, Martin E. Gutierrez, Zubin M. Bamboat), NJ, USA
| | - Donald A McCain
- Department of Medical and Surgical Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack (Andrew A. Jennis, Donald A. McCain, Martin E. Gutierrez, Zubin M. Bamboat), NJ, USA
| | - Martin E Gutierrez
- Department of Medical and Surgical Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack (Andrew A. Jennis, Donald A. McCain, Martin E. Gutierrez, Zubin M. Bamboat), NJ, USA
| | - Zubin M Bamboat
- Department of Medical and Surgical Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack (Andrew A. Jennis, Donald A. McCain, Martin E. Gutierrez, Zubin M. Bamboat), NJ, USA
| |
Collapse
|
|
50
|
Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial. Br J Cancer 2016; 114:855-62. [PMID: 27031850 PMCID: PMC4984795 DOI: 10.1038/bjc.2016.30] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Revised: 12/29/2015] [Accepted: 01/20/2016] [Indexed: 01/01/2023] Open
Abstract
Background: In the phase III AVAGAST trial, the addition of bevacizumab to chemotherapy improved progression-free survival (PFS) but not overall survival (OS) in patients with advanced gastric cancer. We studied the role of Angiopoietin-2 (Ang-2), a key driver of tumour angiogenesis, metastasis and resistance to antiangiogenic treatment, as a biomarker. Methods: Previously untreated, advanced gastric cancer patients were randomly assigned to receive bevacizumab (n=387) or placebo (n=387) in combination with chemotherapy. Plasma collected at baseline and at progression was analysed by ELISA. The role of Ang-2 as a prognostic and a predictive biomarker of bevacizumab efficacy was studied using a Cox proportional hazards model. Logistic regression analysis was applied for correlations with metastasis. Results: Median baseline plasma Ang-2 levels were lower in Asian (2143 pg ml−1) vs non-Asian patients (3193 pg ml−1), P<0.0001. Baseline plasma Ang-2 was identified as an independent prognostic marker for OS but did not predict bevacizumab efficacy alone or in combination with baseline VEGF. Baseline plasma Ang-2 correlated with the frequency of liver metastasis (LM) at any time: Odds ratio per 1000 pg ml−1 increase: 1.19; 95% CI 1.10–1.29; P<0.0001 (non-Asians) and 1.37; 95% CI 1.13–1.64; P=0.0010 (Asians). Conclusions: Baseline plasma Ang-2 is a novel prognostic biomarker for OS in advanced gastric cancer strongly associated with LM. Differences in Ang-2 mediated vascular response may, in part, account for outcome differences between Asian and non-Asian patients; however, data have to be further validated. Ang-2 is a promising drug target in gastric cancer.
Collapse
|