The Epidemiology of Neuroendocrine Tumors in Taiwan: A Nation-Wide Cancer Registry-Based Study

<div><p>Background</p><p>The epidemiology of neuroendocrine tumors (NETs) is not well illustrated, particularly for Asian countries.</p><p>Methods</p><p>The age-standardized incidence rates and observed survival rates of NETs diagnosed in Taiwan from January 1, 1996 to December 31, 2008 were calculated using data of the Taiwan Cancer Registry (TCR) and compared to those of the Norwegian Registry of Cancer (NRC) and the US Surveillance, Epidemiology, and End Results (SEER) program.</p><p>Results</p><p>During the study period, a total of 2,187 NET cases were diagnosed in Taiwan, with 62% males and a mean age of 57.9 years-old. The age-standardized incidence rate of NETs increased from 0.30 per 100,000 in 1996 to 1.51 per 100,000 in 2008. The most common primary sites were rectum (25.4%), lung and bronchus (20%) and stomach (7.4%). The 5-year observed survival was 50.4% for all NETs (43.4% for men and 61.8% for women, <i>P</i><0.0001). The best 5-year observed survivals for NETs by sites were rectum (80.9%), appendix (75.7%), and breast (64.8%).</p><p>Conclusions</p><p>Compared to the data of Norway and the US, the age-standardized incidence rate of NETs in Taiwan is lower and the major primary sites are different, whereas the long-term outcome is similar. More studies on the pathogenesis of NETs are warranted to devise preventive strategies and improve treatment outcomes for NETs.</p></div

Survival analysis to assess the risk of death of patients with neuroendocrine tumors, Taiwan, 1996–2009.

a<p>Hazard ratio and 95% confidence interval were calculated using Cox proportional hazards model.</p>b<p>Hazard ratio and 95% confidence interval were calculated using Cox proportional hazards model, adjusted for all of the variables in the table.</p>c<p>Head and neck includes lip and oral cavity, pharynx, larynx, nasal cavity and paranasal sinuses, middle ear, and major salivary glands; Biliary includes gallbladder and extrahepatic bile duct; Others includes anus, bone, brain, cervix, intracranial gland, kidney, labia majora, mediastinum of the heart, peritoneum, pleura, retroperitoneum, skin, testis, thymus, thyroid, urinary bladder, uterus, vagina, and site undefined.</p><p>Abbreviations: CI, confidence interval; HR, hazard ratio.</p

Distribution of neuroendocrine tumors by sites, Taiwan, 1996–2008.

a.<p>Head and neck includes lip and oral cavity, pharynx, larynx, nasal cavity and paranasal sinuses, middle ear, and major salivary glands; Biliary includes gallbladder and extrahepatic bile duct; Others includes anus, bone, brain, cervix, intracranial gland, kidney, labia majora, mediastinum of the heart, peritoneum, pleura, retroperitoneum, skin, testis, thymus, thyroid, urinary bladder, uterus, vagina, and site undefined.</p

5-year observed survival probability of neuroendocrine tumors, Taiwan, 1996–2008.

a<p>The 5-year observed survival probabilities were calculated using the life-table method.</p>b<p><i>P</i>-values were calculated using the Kaplan-Meier method. <i>P</i> values were calculated only for the top eight most common sites.</p>c<p>Head and neck includes lip and oral cavity, pharynx, larynx, nasal cavity and paranasal sinuses, middle ear, and major salivary glands; Biliary includes gallbladder and extrahepatic bile duct; Others includes anus, bone, brain, cervix, intracranial gland, kidney, labia majora, mediastinum of the heart, peritoneum, pleura, retroperitoneum, skin, testis, thymus, thyroid, urinary bladder, uterus, vagina, and site undefined.</p>d<p>The 5-year observed survival probability for breast cancer includes male breast cancer cases.</p>e<p>The 5-year observed survival probability for esophageal cancer includes female esophageal cancer cases.</p

The comparison of male to female case number ratios by histologic subtypes in different primary sites, Taiwan.

<p>Abbreviations: AC = adenocarcinoma; NET = neuroendocrine tumor; SCC = squamous cell carcinoma. P-values were generated by chi-square tests to compare the distribution of sex between AC or SCC and NET.</p

Standardized incidence ratio (SIR) of second cancers following NETs, Taiwan, 1996-2008.

<p>Abbreviations: CI = confidence interval; N = number; SIR = standardized incidence ratio</p><p>^a SIR = observed N/expected N</p><p>^b Others: soft tissue (N=2), skin (N=1), peritoneum (N=1), thyroid (N=1), and ill-defined (N=2)</p

Age-standardized incidence rate (per 100,000) of neuroendocrine tumors, Taiwan, 1996–2008.

a<p>Incidence rates were age-standardized to the 2000 US standard population.</p

The age-standardized incidence rate of neuroendocrine tumors, Taiwan, 1996–2008.

<p>A) The age-standardized incidence rate overall and by sex; B) The age-standardized incidence rate by primary sites.</p

Risk of second cancer following NETs: univariable and multivariable Cox proportional hazards analysis, Taiwan, 1996-2008.

<p>Abbreviations: CI = confidence interval; HR = hazard ratio</p><p>^a Hazard ratio and 95% confidence interval were calculated using Cox proportional hazards model.</p><p>^b Hazard ratio and 95% confidence interval were calculated using Cox proportional hazards model, adjusted for all of the variables in the table.</p><p>^c Head and neck includes lip and oral cavity, pharynx, larynx, nasal cavity and paranasal sinuses, middle ear, and major salivary glands; Biliary includes gallbladder and extrahepatic bile duct; Others includes anus, bone, brain, cervix, intracranial gland, kidney, labia majora, mediastinum of the heart, peritoneum, pleura, retroperitoneum, skin, testis, thymus, thyroid, urinary bladder, uterus, vagina, and site undefined</p

Top five most common sites of neuroendocrine tumors in Taiwan, Norway, and USA^a.

a<p>References for data from Norway and US:</p>1<p>Hauso O, Gustafsson BI, Kidd M, Waldum HL, Drozdov I, et al. (2008) Neuroendocrine tumor epidemiology: contrasting Norway and.</p><p>North America. Cancer 113∶2655–2664.</p>2<p>Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, et al. (2008) One hundred years after “carcinoid”: epidemiology of and prognostic.</p><p>factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26∶3063–3072.</p><p>Abbreviations: NETs, neuroendocrine tumors.</p