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To investigate the incidence of gastrointestinal stromal tumors (GISTs) in Taiwan and the impact of imatinib on the overall survival (OS) of GIST patients. Methods: GISTs were identified from the Taiwan Cancer Registry (TCR) from 1998 to 2008. The age-adjusted incidence rates and the observed OS rates were calculated.
Chiang et al BMC Cancer 2014, 14:102 http://www.biomedcentral.com/1471-2407/14/102 RESEARCH ARTICLE Open Access The epidemiology of gastrointestinal stromal tumors in Taiwan, 1998–2008: a nation-wide cancer registry-based study Nai-Jung Chiang1,2, Li-Tzong Chen1,2,3,4*, Chia-Rung Tsai1 and Jeffrey S Chang1* Abstract Background: To investigate the incidence of gastrointestinal stromal tumors (GISTs) in Taiwan and the impact of imatinib on the overall survival (OS) of GIST patients Methods: GISTs were identified from the Taiwan Cancer Registry (TCR) from 1998 to 2008 The age-adjusted incidence rates and the observed OS rates were calculated Cox proportional hazards models were applied to examine the mortality risk in three time periods (1998–2001, 2002–2004, 2005–2008) according to the application and availability of imatinib Results: From 1998 to 2008, 2,986 GISTs were diagnosed in Taiwan The incidence increased from 1.13 per 100,000 in 1998 to 1.97 per 100,000 in 2008 The most common sites were stomach (47-59%), small intestine (31-38%), and colon/rectum (6-9%) The 5-year observed OS was 66.5% (60.3% for men, 74.2% for women, P < 0001) GISTs in the stomach had a better 5-year observed OS (69.4%) than those in the small intestine (65.1%) (P < 0001) The outcome of GIST improved significantly after the more widespread use of imatinib; the 5-year observed OS increased from 58.9% during 1998–2001 to 70.2% during 2005–2008 (P < 0001) Younger age, female sex, stomach location, and later diagnostic years were independent predictors of a better survival Conclusions: The incidence of GIST has been increasing in Taiwan, partially due to the advancement of diagnostic technology/method and the increased awareness by physicians The outcome of GIST has improved significantly with the availability and the wider use of imatinib Keywords: Gastrointestinal stromal tumors, Incidence, Imatinib, Survival Background Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal system, characterized by an unique histological morphology and the expression of the KIT protein [1] Previously, the majority of GISTs were diagnosed as smooth muscle tumors (e.g leiomyoma and leiomyosarcoma) or as tumors of the nerve sheath origin (e.g schwannoma and malignant nerve sheath tumors) [2,3] Because GISTs were previously difficult to define due to the lack of specific markers, few epidemiologic studies were * Correspondence: leochen@nhri.org.tw; jeffreychang@nhri.org.tw National Institute of Cancer Research, National Health Research Institutes, F, No 367, Sheng Li Road, Tainan 70456, Taiwan Division of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 70456, TaiwanFull list of author information is available at the end of the article published with no nation-wide cancer registry-based study of GISTs from Asia [4,5] The advancement of immunohistochemistry, molecular technology and the identification of KIT oncogene mutation in more than 80% of GISTs have accelerated our understanding of GISTs [6-8] In Taiwan, the diagnosis of GISTs by CD117 or KIT staining was established and widely adopted since 2002 Prior to 2002, the diagnosis of GISTs was based on histology and other immunohistochemical markers (CD34, vimentin, keratin, smooth muscle actin (SMA), and S100) [4,9] Using the Taiwan Cancer Registry (TCR) data from 1998 to 2008, our analysis elucidated the incidence and the distribution of GISTs before and after the implementation of CD117 or KIT staining for the definitive diagnosis of GISTs and compared them to those in the Western countries © 2014 Chiang et al.; licensee BioMed Central Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited Chiang et al BMC Cancer 2014, 14:102 http://www.biomedcentral.com/1471-2407/14/102 Complete surgical resection remains the only curative treatment of primary localized GISTs The 5-yr survival rate after complete surgical resection was 50% before the era of molecular targeted therapy [10,11] The approval of imatinib mesylate (Gleevec®, Novartis Pharma, Basel, Switzerland), an oral inhibitor of KIT and platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), to treat metastatic GIST by the USA FDA in 2002 has markedly changed the outcomes and treatment options for GISTs [12] In Taiwan, imatinib was approved for reimbursement by the National Health Insurance Administration since 2004 Our analysis assessed the survival of GISTs by three time periods: 1) 1998–2001, before the approval imatinib to treat GISTs; 2) 2002–2004, after the approval of imatinib to treat GISTs and before the coverage of imatinib by the National Health Insurance of Taiwan; and 3) 2005–2008, after the coverage of imatinib by the National Health Insurance of Taiwan Methods Data sources The GIST cases diagnosed from January 1, 1998 to December 31, 2008 were identified from the TCR established in 1979 to track the cancer incidence and mortality in Taiwan [13] Hospitals with more than 50 beds in Taiwan are mandated to report confirmed cases of malignancy to the TCR, which captures 97% of the cancer cases in Taiwan [13] The quality of a cancer registry is measured by the percentage of death certificate only cases (DCO%) and the percentage of morphologically verified cases (MV%), with a DCO% of and a MV% of 100 representing a perfect data quality [14] The quality of the TCR is comparable to the other well-established cancer registries in the world [15,16] with a DCO% of 1.2% and a MV% of 89% [13] Study population Before 2002, the diagnosis of GISTs by CD117 or c-KIT staining was unavailable; therefore, for cases diagnosed from January 1, 1998 to December 31, 2001, the morphology (M) codes of the International Classification of Disease for Oncology, Field Trial Edition (ICD-O-FT) were used to identify GIST cases with the algorithm established by Tran et al [17], which included stromal sarcoma (8930), leiomyosarcoma (8890), epithelioid leiomyosarcoma (8891), cellular leiomyosarcoma (8892), bizarre leiomyosarcoma (8893), myxoid leiomyosarcoma (8896), smooth muscle cell tumor (8897), sarcoma not otherwise specified (8800), spindle cell sarcoma (8801), giant cell sarcoma (8802), small cell sarcoma (8803), epithelioid sarcoma (8804), mesenchymoma (8990), fibrosarcoma (8810), fibromyxosarcoma (8811), ganglioneuroma (9490), ganglioneuromatosis (9491), neurobalstoma (9500), neuroepithelioma (9503), ganglioglioma (9505), neurofibroma Page of (9504), schwannoma (9650), paragangmaluganglioma (8680), glomus tumor (8711), angiosarcoma (9120), and hemangiopericytoma (9150) The origin of tumors was limited to the following primary sites: esophagus, stomach, small intestine, colon and rectum In addition, only those with confirmed malignant behavior by histological criteria (ICD-O-FT fifth digit of /3) were included GISTs diagnosed after January 1, 2002 were identified by the International classification of Diseases for Oncology, Third Edition (ICD-O-3) with the M code for gastrointestinal stromal sarcoma (8936) Only cases with confirmed malignant neoplasm (ICD-O-3 fifth digit of /3) were included Statistical analysis The crude annual incidence was calculated by dividing the number of annual incident GIST cases by the annual population reported by the Directorate-General of Budget, Accounting, and Statistics of Taiwan (http://www.dgbas gov.tw) The crude incidence rates were calculated for all GISTs combined, by sex, and by primary sites All incidence rates (per 100,000) were age-adjusted to the 2000 U.S standard population to generate the age-standardized incidence rates The observed overall survival (OS) rates were calculated for all patients and by sex, primary sites, and diagnostic periods Patients were followed from the date of diagnosis to death recorded in the national death database or to the end of follow-up on December 31, 2010 Cox proportional hazards models were performed to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of mortality associated with tumor site, sex, age, and the year of diagnosis Stage at diagnosis (localized or metastatic), tumor size, and mitotic index were excluded from the analysis because of incomplete or lack of information This study was approved by the Institutional Review Board of the National Health Research Institutes Results Characteristics of GIST patients During 1998–2008, 2,986 newly diagnosed GIST cases were recorded by the TCR The age of GIST patients ranged from 18 to 96 years old The median age was around 62–64 years old and almost 75% of cases were diagnosed at ≧50 years of age (Table 1) For both sexes, the most common primary sites of GISTs were stomach (47-59%), followed by small intestine (31-38%), and colon/rectum (6-9%) A higher percentage of GIST originated from the small intestine was observed among those aged