Gastric cancer is not a top‐10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western ...countries add to the complexity of identifying standard‐of‐care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD‐L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein‐Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.
The aim of the study was to evaluate the short-term outcomes of KLASS-02-RCT, a multicenter randomized controlled trial comparing laparoscopic distal gastrectomy (LDG) with D2 lymphadenectomy with ...open distal gastrectomy (ODG).
Although several benefits of laparoscopic gastric cancer surgery have been reported, strong evidence is still limited, especially in locally advanced gastric cancer which requires extensive lymph node dissection.
Enrollment criteria included histologically confirmed cT2-4a and N0-1 gastric adenocarcinoma. Thirty-day morbidity, 90-day mortality, postoperative pain, and recovery were compared between LDG and ODG groups.
A total of 1050 patients were randomly assigned to LDG (n = 526) or ODG group (n = 524) between November 2011 and April 2015. After excluding patients who received bypass or no surgery, 1011 patients were analyzed as actual treatment group. Mean number of totally retrieved lymph nodes was similar in both groups (LDG = 46.6 vs ODG = 47.4, P = 0.451). Early morbidity rate was significantly lower after LDG (16.6%) than after ODG (24.1%; P = 0.003). Postoperative analgesics use and patients' reported pain score were significantly lower after LDG. First day of flatus was earlier after LDG (3.5 vs 3.7 d, P = 0.025) and postoperative hospital stay was shorter in LDG group (8.1 vs 9.3 d, P = 0.005). Ninety days' mortality rate was similar in both groups (LDG = 0.4% vs ODG = 0.6%, P = 0.682).
Laparoscopic distal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer shows benefits in terms of lower complication rate, faster recovery, and less pain compared with open surgery.
Characteristics of gastric cancer in Asia Rahman, Rubayat; Asombang, Akwi W; Ibdah, Jamal A
World journal of gastroenterology : WJG,
04/2014, Volume:
20, Issue:
16
Journal Article
Open access
Gastric cancer(GC)is the fourth most common cancer in the world with more than 70%of cases occur in the developing world.More than 50%of cases occur in Eastern Asia.GC is the second leading cause of ...cancer death in both sexes worldwide.In Asia,GC is the third most common cancer after breast and lung and is the second most common cause of cancer death after lung cancer.Although the incidence and mortality rates are slowly declining in many countries of Asia,GC still remains a significant public health problem.The incidence and mortality varies according to the geographic area in Asia.These variations are closely related to the prevalence of GC risk factors;especially Helicobacter pylori(H.pylori)and its molecular virulent characteristics.The gradual and consistent improvements in socioeconomic conditions in Asia have lowered the H.pylori seroprevalence rates leading to a reduction in the GC incidence.However,GC remains a significant public health and an economic burden in Asia.There has been no recent systemic review of GC incidence,mortality,and H.pylori molecular epidemiology in Asia.The aim of this report is to review the GC incidence,mortality,and linkage to H.pylori in Asia.
Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. Treatment of GC patients is ...currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future.
Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries,which show a higher mortality than other ...countries. The effectiveness of 3 new gastric cancer screening techniques,namely,upper gastrointestinal endoscopy,serological testing,and "screen and treat" method were extensively reviewed. Moreover,the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand,serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date,the effectiveness of new techniques for gastric cancer screening has remained limited. However,endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening.To effectively introduce new techniques for gastric cancer screening in a community,incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies.In addition to effectiveness evaluation,the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening.
Less than a century ago, gastric cancer was the most common cancer in the United States and perhaps throughout the world. Despite its worldwide decline in incidence over the past century, gastric ...cancer remains a major killer across the globe. This article reviews the epidemiology, screening, and prevention of gastric cancer. We first discuss the descriptive epidemiology of gastric cancer, including its incidence, survival, mortality, and trends over time. Next, we characterize the risk factors for gastric cancer, both environmental and genetic. Serologic markers and histological precursor lesions of gastric cancer and early detection of gastric cancer using these markers are reviewed. Finally, we discuss prevention strategies and provide suggestions for further research.
Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic ...factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.
Gastric cancer Van Cutsem, Eric, Prof; Sagaert, Xavier, MD; Topal, Baki, Prof ...
The Lancet (British edition),
11/2016, Volume:
388, Issue:
10060
Journal Article
Peer reviewed
Summary Gastric cancer is one of the leading causes of cancer-related death worldwide. Many patients have inoperable disease at diagnosis or have recurrent disease after resection with curative ...intent. Gastric cancer is separated anatomically into true gastric adenocarcinomas and gastro-oesophageal-junction adenocarcinomas, and histologically into diffuse and intestinal types. Gastric cancer should be treated by teams of experts from different disciplines. Surgery is the only curative treatment. For locally advanced disease, adjuvant or neoadjuvant therapy is usually implemented in combination with surgery. In metastatic disease, outcomes are poor, with median survival being around 1 year. Targeted therapies, such as trastuzumab, an antibody against HER2 (also known as ERBB2), and the VEGFR-2 antibody ramucirumab, have been introduced. In this Seminar, we present an update of the causes, classification, diagnosis, and treatment of gastric cancer.
Cancers of the stomach and esophagus are among the most challenging cancers of the GI tract to treat, associated with poor median survivals for metastatic disease and significant, sometimes ...prolonged, deteriorations in patient performance status as the diseases progress. However, in the past decade, we have begun to better understand disease biology and carcinogenesis, leading to the identification of subtypes of these diseases. There is also an increasing awareness of the global heterogeneity of disease and its impact on drug development. Our improved understanding of the molecular underpinnings of gastric and esophageal cancers has been accompanied with the development of novel therapeutic strategies. Recent actively investigated targets in this disease include human epidermal growth factor receptor 2, angiogenesis, MET, and immune checkpoint inhibition, with approvals of two new targeted agents, trastuzumab and ramucirumab. Improvements in our ability to deliver cytotoxic therapy, which is better tolerated and allows patients an opportunity to benefit from second- and more advanced lines of therapy, have also been observed. In this review, the current state-of-the-art management of advanced and metastatic gastric and esophageal adenocarcinomas, specifically highlighting the development of targeted therapies in these diseases, is described.
High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to ...investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.
We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1–d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.
In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group 14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24–0.96), P = 0.038, while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.
Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.
ClinicalTrials.gov NCT02915432.
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