The incidence of neuroendocrine tumors (NETs) has been increasing in recent decades. Previously, we reported the incidence and survival of NETs in Taiwan by analyzing the 1996–2008 data from the Taiwan Cancer Registry. Here we performed an updated analysis on the incidence and survival of NETs in Taiwan from 1996 to 2015. The incidence of NETs was 0.244 per 100,000 in 1996 and increased to 3.162 per 100,000 in 2015. The most common site of NETs was rectum (29.65%), followed by lung/bronchus (17.22%), and pancreas (10.71%). The 5- and 10-year overall survival rates of all NETs were 54.6% and 45.3%, respectively. Female and younger NETs patients had a better survival. The survival of all NETs diagnosed between 2010 and 2015 was better than those diagnosed between 2004 and 2009. Among the common sites of NETs, an improved survival of pancreatic NETs diagnosed between 2010 and 2015 compared to those diagnosed between 2004 and 2009 was observed. Overall, the incidence of NETs in Taiwan has continued to increase. The survival of pancreatic NET has shown a recent improvement. The development of novel therapeutic agents has the potential to improve the prognosis of NETs of other sites in the near future.

Studies have indicated a significant rise in the incidence of pancreatic adenocarcinoma. However, the epidemiology of other rare histologic subtypes of pancreatic cancer is not well understood. This study analyzed the incidence and survival of pancreatic cancer in Taiwan by histologic subtype, sex, age group, and year of diagnosis. The incidence trends of pancreatic cancer in Taiwan from 2002 to 2013 were calculated using data from the Taiwan Cancer Registry. The survival of pancreatic cancer patients was assessed using the life‐table method and Cox proportional hazards analysis. The incidence of pancreatic cancer increased from 4.62 per 100,000 in 2002 to 6.04 per 100,000 in 2013 in Taiwan. The most common histologic subtype of pancreatic cancer was adenocarcinoma followed by carcinoma and neuroendocrine tumors (NETs). Adenocarcinoma and NETs showed a rapid increase in incidence, while the incidences of other subtypes did not change significantly. Patients with adenocarcinoma showed a poor survival with a 5‐year survival of 5.2%. Patients with endocrinomas, NETs, and lymphoma displayed a better survival than those with adenocarcinoma, with a 5‐year survival ranging from 41.8% to 59.1%. The survival of adenocarcinoma, lymphoma, and NETs improved after the introduction of novel therapies. Understanding the risk factors and identifying the biomarkers for the early diagnosis of pancreatic cancer are important to prevent the development and improve the survival of pancreatic cancer.

Lung cancer is the third most common cancer in the world and has the highest cancer mortality rate. A worldwide increasing trend of lung adenocarcinoma has been noted. In addition, the identification of epidermal growth factor receptor (EGFR) mutations and the introduction of EGFR inhibitors to successfully treat EGFR mutated non–small cell lung cancers are breakthroughs for lung cancer treatment. The current study evaluated the incidence and survival of lung cancer using data collected by the Taiwan Cancer Registry between 1996 and 2008. The results showed that the most common histologic subtype of lung cancer was adenocarcinoma, followed by squamous cell carcinoma, small cell carcinoma, large cell carcinoma, neuroendocrine tumors, lymphoma, and sarcoma. Overall, the incidence of lung cancer in Taiwan increased significantly from 1996 to 2008. An increased incidence was observed for adenocarcinoma, particularly for women, with an annual percentage change of 5.9, whereas the incidence of squamous cell carcinoma decreased. Among the subtypes of lung cancer, the most rapid increase occurred in neuroendocrine tumors with an annual percentage change of 15.5. From 1996–1999 to 2005–2008, the 1-year survival of adenocarcinoma increased by 10% for men, whereas the 1-, 3-, and 5-year survivals of adenocarcinoma for women increased by 18%, 11%, and 5%, respectively. Overall, the incidence of lung cancer has been increasing in Taiwan, although the trends were variable by subtype. The introduction of targeted therapies was associated with a significantly improved survival for lung adenocarcinoma in Taiwan; however, more studies are needed to explain the rising incidence of lung adenocarcinoma. In addition, it is important to investigate the molecular pathogenesis of the various subtypes of lung cancer to develop novel therapeutic agents.

Most acute myeloid leukemia (AML) cells are argininosuccinate synthetase‐deficient. Pegylated arginine deiminase (ADI‐PEG20) monotherapy depletes circulating arginine, thereby selectively inducing tumor cell death. ADI‐PEG20 was shown to induce complete responses in ~10% of relapsed/refractory or poor‐risk AML patients. We conducted a phase I, dose‐escalation study combining ADI‐PEG20 and low‐dose cytarabine (LDC) in AML patients. Patients received 20 mg LDC subcutaneously twice daily for 10 days every 28 days and ADI‐PEG20 at 18 or 36 mg/m² (dose levels 1 and 2) intramuscularly weekly. An expansion cohort for the maximal tolerated dose of ADI‐PEG20 was planned to further estimate the toxicity and preliminary response of this regimen. The primary endpoints were safety and tolerability. The secondary endpoints were time on treatment, overall survival (OS), overall response rate (ORR), and biomarkers (pharmacodynamics and immunogenicity detection). Twenty‐three patients were included in the study, and seventeen patients were in the expansion cohort (dose level 2). No patients developed dose‐limiting toxicities. The most common grade III/IV toxicities were thrombocytopenia (61%), anemia (52%), and neutropenia (30%). One had an allergic reaction to ADI‐PEG20. The ORR in 18 evaluable patients was 44.4%, with a median OS of 8.0 (4.5‐not reached) months. In seven treatment‐naïve patients, the ORR was 71.4% and the complete remission rate was 57.1%. The ADI‐PEG20 and LDC combination was well‐tolerated and resulted in an encouraging ORR. Further combination studies are warranted. (This trial was registered in ClinicalTrials.gov as a Ph1 Study of ADI‐PEG20 Plus Low‐Dose Cytarabine in Older Patients With AML, NCT02875093).

Background: Helicobacter pylori eradication has been shown to decrease gastric adenocarcinoma risk. The epidemiology of gastric lymphoma, which is also associated with H. pylori, and other rare subtypes of gastric cancer is less clear. This study comprehensively evaluated the incidence trend and the survival of gastric cancer in Taiwan by histologic subtype. Methods: The incidence trends of gastric cancer in Taiwan from 1996 and 2013 were evaluated using data from the Taiwan Cancer Registry. The life-table method and the Cox proportional hazards analysis were used to evaluate the survival of gastric cancer. Results: The incidence of all gastric cancers in Taiwan decreased from 15.97 per 100,000 in 1996 to 11.57 per 100,000 in 2013. The most frequent histologic subtype of gastric cancer in Taiwan was adenocarcinoma, followed by lymphoma and sarcoma (mainly gastrointestinal stromal tumor). The best survival was in patients with sarcoma, followed by lymphoma, neuroendocrine tumor, and adenocarcinoma. Generally, women had a better survival than men. The incidence of adenocarcinoma significantly decreased from 13.56 per 100,000 in 1996 to 9.82 per 100,000 in 2013 (P < 0.0001). In contrast, the incidences of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma did not decrease. Conclusions: The incidence of adenocarcinoma and lymphoma, both of which are associated with H. pylori, showed diverging trends. The survival of gastric cancer differed by histologic subtype and sex. Impact: The disparity in the incidence trends between gastric lymphoma and adenocarcinoma, both associated with H. pylori, warranted the need to search for additional risk factors of gastric lymphoma.

Pancreatic neuroendocrine tumor (pNET) is a pancreatic neoplasm with neuroendocrine differentiation. pNET in early stage can be treated with surgical resection with long‐term survival, whereas the prognosis of pNET with locoregional or distant metastasis is relatively poor. Lymphangiogenesis is essential for tumor metastasis via the lymphatic system and may overhead distant metastasis. c‐Myc overexpression is involved in tumorigenesis. The role of c‐Myc in lymphangiogenesis is unclear. In this study, we evaluated the mechanism and effect of c‐Myc on lymphangiogenesis of pNET via interaction of lymphatic endothelial cells (LECs) and pNET cells. Lymph node metastasis was evaluated in pNET xenograft mice. Potential target agents to inhibit lymph node metastasis were evaluated in an animal model. We found that vascular endothelial growth factor C (VEGFC) expression and secretion was increased in pNET cell lines with c‐Myc overexpression. c‐Myc transcriptionally upregulates VEGFC expression and the secretion of pNET cells by directly binding to the E‐box of the VEGFC promoter and enhances VEGF receptor 3 phosphorylation and the tube formation of LECs. c‐Myc overexpression is associated with lymph node metastasis in pNET xenograft mice. Combinational treatment with an mTOR inhibitor and c‐Myc inhibitor or VEGFC‐neutralizing chimera protein reduced lymph node metastasis in the mice with c‐Myc overexpression. The mTOR inhibitor acts on lymphangiogenesis by reducing VEGFC expression in pNET cells and inhibiting the tube formation of LECs. In conclusion, mTOR and c‐Myc are important for lymphangiogenesis of pNET and are potential therapeutic targets for prevention and treatment of lymph node metastasis in pNET.