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Background: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. Methods: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan–Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. Results: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01–14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39–10.89). Conclusions: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival. [ABSTRACT FROM AUTHOR]

High-grade liver laceration is a common injury with bleeding as the main cause of death. Timely resuscitation and hemostasis are keys to the successful management. The impact of in-hospital trauma system on the quality of resuscitation and management in patients with traumatic high-grade liver laceration, however, was rarely reported. We retrospectively reviewed the impact of team-based approach on the quality and outcomes of high-grade traumatic liver laceration in our hospital. Patients with traumatic liver laceration between 2002 and 2020 were enrolled in this retrospective study. Inverse probability of treatment weighting (IPTW)-adjusted analysis using the propensity score were performed. Outcomes before the trauma team establishment (PTTE) and after the trauma team establishment (TTE) were compared. A total of 270 patients with liver trauma were included. After IPTW adjustment, interval between emergency department arrival and managements was shortened in the TTE group with a median of 11 min (p < 0.001) and 28 min (p < 0.001) in blood test reports and duration to CT scan, respectively. Duration to hemostatic treatments in the TTE group was also shorter by a median of 94 min in patients receiving embolization (p = 0.012) and 50 min in those undergoing surgery (p = 0.021). The TTE group had longer ICU-free days to day 28 (0.0 vs. 19.0 days, p = 0.010). In our study, trauma team approach had a survival benefit for traumatic high-grade liver injury patients with 65% reduction of risk of death within 72 h (Odds ratio (OR) = 0.35, 95% CI = 0.14–0.86) and 55% reduction of risk of in-hospital mortality (OR = 0.45, 95% CI = 0.23–0.87). A team-based approach might contribute to the survival benefit in patients with traumatic high-grade liver laceration by facilitating patient transfer from outside the hospital, through the diagnostic examination, and to the definitive hemostatic procedures. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the efficacy and safety of induction chemotherapy (ICT), GOFL (gemcitabine, oxaliplatin plus fluorouracil (5-FU)/leucovorin) versus modified FOLFIRINOX (irinotecan, oxaliplatin plus 5-FU/leucovorin), followed by concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic adenocarcinoma (LAPC).Methods: Chemo-naive patients with measurable LAPC were eligible and randomly assigned to receive biweekly ICT with either mFOLFIRINOX or GOFL for 3 months. Patients without systemic progression would have 5-FU- or gemcitabine-based CCRT (5040 cGy/28 fractions) and were then subjected to surgery or continuation of chemotherapy until treatment failure. The primary endpoint was 9-month progression-free survival (PFS) rate.Results: Between July 2013 and January 2019, 55 patients were enrolled. After ICT, 21 (77.8%) of 27 patients who received mFOLFIRINOX and 17 (60.7%) of 28 patients who received GOFL completed CCRT. Of them, one and five had per-protocol R0/R1 resection. On intent-to-treat analysis, the 9-month PFS rate, median PFS and overall survival in mFOLFIRINOX and GOFL arms were 30.5% versus 35.9%, 6.6 (95% confidence interval: 5.9-12.5) versus 7.6 months (3.9-12.3) and 19.6 (13.4-22.9) versus 17.9 months (13.4-23.9), respectively. Grade 3-4 neutropenia and diarrhoea during induction mFOLFIRINOX and GOFL were 37.0% versus 21.4% and 14.8% versus 3.6%, respectively.Conclusion: Induction GOFL and mFOLFIRINOX followed by CCRT provided similar clinical outcomes in LAPC patients.Clinicaltrial: Gov Identifier: NCT01867892. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Due to differences in genetic background, it is unclear whether the genetic loci identified by the previous genome-wide association studies (GWAS) of pancreatic cancer also play significant roles in the development of pancreatic cancer among the Taiwanese population. Methods: This study aimed to validate the 25 pancreatic cancer GWAS-identified single nucleotide polymorphisms (SNPs) in a case-control study (278 cases and 658 controls) of pancreatic cancer conducted in Taiwan. Statistical analyses were conducted to determine the associations between the GWAS-identified SNPs and pancreatic cancer risk. Gene-environment interaction analysis was conducted to evaluate the interactions between SNPs and environmental factors on pancreatic cancer risk. Results: Among the 25 GWAS-identified SNPs, 7 (rs2816938 (~ 11 kb upstream of NR5A2), rs10094872 (~ 28 kb upstream of MYC), rs9581943 (200 bp upstream of PDX1) and 4 chromosome 13q22.1 SNPs: rs4885093, rs9573163, rs9543325, rs9573166) showed a statistically significant association with pancreatic cancer risk in the current study. Additional analyses showed two significant gene-environment interactions (between poor oral hygiene and NR5A2 rs2816938 and between obesity and PDX1 rs9581943) on the risk of pancreatic cancer. Conclusions: The current study confirmed the associations between 7 of the 25 GWAS-identified SNPs and pancreatic risk among the Taiwanese population. Furthermore, pancreatic cancer was jointly influenced by lifestyle and medical factors, genetic polymorphisms, and gene-environment interaction. Additional GWAS is needed to determine the genetic polymorphisms that are more relevant to the pancreatic cancer cases occurring in Taiwan. [ABSTRACT FROM AUTHOR]

Background: The discovery of effective therapeutic options for treating metastatic poorly differentiated neuroendocrine carcinoma (NEC) after prior platinum‐based chemotherapy remains elusive. This study analyzed the efficacy of TLC388 (Lipotecan) Hydrochloride, a novel camptothecin analog, for pretreated patients with metastatic NEC. Methods: This single‐arm, two‐stage, phase II clinical trial was conducted at four community and academic centers in Taiwan. Patients aged 20 years or older with confirmed metastatic NEC and who had received prior systemic therapy with etoposide plus cisplatin were enrolled between July 2015 and May 2018. Patients received 40 mg/m2 of TLC388 intravenously on days 1, 8, and 15 of a 28‐day cycle until disease progression or unacceptable toxic effects. Gene mutations were analyzed by next‐generation sequencing. Results: Twenty‐three patients with a median age of 61 (range, 44–73) years, 18 of whom were men (78%), were enrolled. Patients received a median of 2 (range, 0–6) treatment cycles. Among 20 evaluable patients, 3 patients exhibited stable disease and no patient experienced a complete or partial remission, resulting in a disease control rate of 15%. Median progression‐free survival was 1.8 (95% confidence interval [CI], 0.4–15) months, and the median overall survival was 4.3 (95% CI, 1.7–15) months. The most common treatment‐related hematologic adverse events at grade 3 or higher were leukopenia (22.7%), anemia (31.8%), and thrombocytopenia (18.2%). The most frequent mutated genes in 35 patients with NEC were ARSA, DPYD, HEXB, BRCA1, HPD, MYBPC3, BBS2, IL7R, HSD17B4, and PRODH. Conclusion: TLC388 demonstrates limited antitumor activity in metastatic NEC. ClinicalTrials.govidentifier: NCT02457273. Implications for Practice: Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive. Currently, effective therapeutic options for treating metastatic poorly differentiated NECs beyond platinum‐based chemotherapy remain elusive. In this single‐arm, multicenter, phase II study, 23 patients with NEC were enrolled and received TLC388 (Lipotecan) Hydrochloride, which is a novel camptothecin analog. The results demonstrated the disease control rate of 15%, the median progression‐free survival of 1.8 (95% confidence interval [CI], 0.4–15) months, and the median overall survival of 4.3 (95% CI, 1.7–15) months. Most importantly, several novel genetic mutations and pathways were identified. These results offer the opportunity to develop future treatment strategies in this rare cancer. This article reports on the efficacy and safety of TLC388 in a second‐line setting for patients with poorly differentiated neuroendocrine carcinomas. [ABSTRACT FROM AUTHOR]

Background: Trauma is one of the leading causes of death in Taiwan, and its medical expenditure escalated drastically. This study aimed to explore the effectiveness of trauma team, which was established in September 2010, on medical resource utilization and quality of care among major trauma patients.Methods: This was a retrospective study, using trauma registry data bank and inpatient medical service charge databases. Study subjects were major trauma patients admitted to a medical center in Tainan during 2009 and 2013, and was divided into case group (from January, 2011 to August, 2013) and comparison group (from January, 2009 to August, 2010).Results: Significant reductions in several items of medical resource utilization were identified after the establishment of trauma team. In the sub-group of patients who survived to discharge, examination, radiology and operation charges declined significantly. The radiation and examination charges reduced significantly in the subcategories of ISS = 16 ~ 24 and ISS > 24 respectively. However, no significant effectiveness on quality of care was identified.Conclusions: The establishment of trauma team is effective in containing medical resource utilization. In order to verify the effectiveness on quality of care, extended time frame and extra study subjects are needed. [ABSTRACT FROM AUTHOR]

Aim Everolimus is an inhibitor of mTOR, approved for treatment of advanced pancreatic neuroendocrine tumors (NETs). The purpose of this observational study was to evaluate the efficacy and safety of everolimus in treatment of progressive, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Taiwan. Methods Fifty-three patients with progressive, advanced GEP-NETs who received everolimus treatment between January 2008 and August 2014 were selected. Patient characteristics, tumor features, safety profiles and treatment efficacy were retrospectively analyzed. Results Mean follow-up duration was 23.7 (1.2-70) months and 37 of 53 patients (69.8%) remained alive at the end of study. The one- and two-year overall survival rates were 90.5% and 75.4%, respectively. The median progression-free survival (PFS) was 18.9 (95% confidence interval; 10.9-26.8) months. Partial response was observed in 15 (28.3%) patients, 29 (54.7%) patients had stable disease and nine (17%) patients had progressive disease. Patients with World Health Organization (WHO) grade I NETs, nonfunctional tumors and liver metastasis burden <10% had significantly better PFS with everolimus treatment. Adverse events observed were stomatitis (35.8%), hyperglycemia (22.6%) and rash (18.8%). Seven (15.4%) patients experienced severe adverse events (grade 3 or more), including hyperglycemia (4.4%), anemia (4.4%), fatigue (2.2%) and elevated liver function (2.2%). One (2.2%) patient died from grade 5 interstitial pneumonitis. Conclusion Everolimus was an effective treatment for Taiwanese patients with progressive advanced GEP-NETs. Patients with nonfunctional NETs had a trend toward longer PFS, whereas patients with liver metastases burden <10% had a trend toward longer overall survival time receiving everolimus treatment. [ABSTRACT FROM AUTHOR]

Background/purpose: This study aims to examine the cost effectiveness of treating major cancers compared with other major illnesses in Taiwan.Methods: We collected data on 395,330 patients with cancer, 125,277 patients with end-stage renal disease, and 50,481 patients under prolonged mechanical ventilation during 1998-2007. They were followed for 10-13 years to estimate lifetime survival functions using a semiparametric method. EuroQol five-dimension was used to measure the quality of life for 6189 cancer patients and 1401 patients with other illnesses. The mean utility values and healthcare costs reimbursed by the National Health Insurance were multiplied with the corresponding survival probabilities to estimate quality-adjusted life expectancies and lifetime costs, respectively. Data of 22,344 cancer patients under hospice care (considered as a comparison group) were used to conduct a cost-effectiveness analysis. Sensitivity analysis was conducted by assuming patients without treatment survived for 2 years with a quality of life value of 0.5.Results: The costs of care for patients under prolonged mechanical ventilation and those with end-stage renal disease were US$41,780-53,708 per quality-adjusted life year (QALY) and US$18,222-18,465 per QALY, respectively, which are equivalent to 2.17-2.79 gross domestic product (GDP) per capita per QALY and 1.18-1.25 GDP per capita per QALY. The costs of care for the nine different cancers were less than 1 GDP per capita per QALY, with those of lung, esophagus, and liver cancers being the highest. Sensitivity analysis showed the same conclusion. Lifetime risks of six out of nine cancer sites show an increased trend.Conclusion: Cancer care in Taiwan seemed cost effective compared with that of other illnesses, but prevention is necessary to make the National Health Insurance more sustainable. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and Methods: Chemonaïve patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m2) infusion at a fixed dose rate (10 mg/m2/min), followed by 85 mg/m2 oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m2) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m2 gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity. Results: Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2–42.5%) and 70% (95% CI, 44.4–99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8–12.8) months and 14.5 (95% CI, 11.9–17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1–80.9%) and 20.6% (95% CI, 8.7–32.5%), respectively. Neutropenia was the most common Grade 3–4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18%). Conclusion: Three months of triplet ICT followed by gemcitabine-based CCRT is feasible, moderately active, and associated with encouraging survival in patients with LAPC. [Copyright &y& Elsevier]

Background: Cancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population., Methods: Exome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHR mut , including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy., Results: Overall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0-43.7), the median overall survival (OS) was not significantly different among patients with gHR mut , non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHR mut . Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7-33.7) versus 9.6 months (95% CI 5.9-17.6), P = 0.001. However, the median OS of patients without gHR mut was 14.5 months (95% CI 13.2-16.9) and 12.6 months (95% CI 10.8-14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis., Conclusions: Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHR mut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis., (© 2024. The Author(s).)

Background: Elderly patients with advanced pancreatic adenocarcinoma (APC) are conceived to be frailer and susceptible to treatment toxicity that has led to disparity in lower likelihood of receiving chemotherapy and survival. Optimal chemotherapy is an unmet medical need for elderly patients with APC., Patients and Methods: Patients with chemo-naive APC, age ≥70 years, and Eastern Cooperative Oncology Group (ECOG) performance score ≤2 were eligible. The treatment was consisted of biweekly gemcitabine 800 mg/m 2 , 10 mg/m 2 /min infusion on day 1 plus oral S-1 and leucovorin (40-60 and 30 mg, respectively) twice daily on days 1-7, the GSL regimen. The primary end-point was progression-free survival with an interested P 1 of 5.0 months., Results: Of the 49 enrolled patients, the median age was 76 years, ECOG performance score ≥1 in 59.2%, metastatic diseases in 65.3%, Vulnerable Elders Survey-13 score ≥3 in 71.4%, and Geriatric 8 score ≤14 in 93.9%. After a median 11 cycles of treatment, the overall response rate and disease control rate were 26.5% and 75.5%, respectively. The median progression-free and overall survivals were 6.6 months (95% confidence interval [CI], 5.4-9.2) and 12.5 months (95% CI, 8.9-14.7), respectively. The most common grade 3-4 treatment-related toxicities were anaemia (20.4%), neutropenia (18.4%), and mucositis (12.2%). Patients had improved emotional function and global health status scores during the GSL treatment., Conclusion: The study met its primary end-point, which supports further investigation on the merit of GSL in Asian elderly APC patients., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Chemotherapy is generally considered as the main treatment for metastatic gastric adenocarcinoma. The role of gastrectomy for metastatic gastric cancer without obvious symptoms is controversial. The objective of this study is to investigate survival outcomes of treatment modalities using a real-world data setting. A retrospective cohort study was designed using the Taiwan Cancer Registry database. We identified the treatment modalities and used Kaplan-Meier estimates and Cox regressions to compare patient survival outcomes. From 2008 to 2015, 5599 gastric adenocarcinoma patients were diagnosed with metastatic disease (M1). The median overall survival (OS) of patients with surgery plus chemotherapy had the longest survival of 14.2 months. The median OS of the patients who received chemotherapy alone or surgery alone was 7.0 and 3.9, respectively. Age at diagnosis, year of diagnosis, tumor grade, and treatment modalities are prognostic factors for survival. The hazard ratios for patients who received surgery plus chemotherapy, surgery alone, and supportive care were 0.47 (95% CI 0.44-0.51), 1.22 (95% CI 1.1-1.36), and 3.23 (95% CI 3.01-3.46), respectively, by multivariable Cox regression analysis when using chemotherapy alone as a referent. Chemotherapy plus surgery may have a survival benefit for some selected gastric adenocarcinoma patients with metastatic disease., (© 2021. The Author(s).)

Inconsistent results have been reported for the association between alcohol use and pancreatic cancer, particularly at low levels of alcohol consumption. Individuals genetically susceptible to the carcinogenic effect of alcohol might have higher pancreatic cancer risk after drinking alcohol. The current study investigated the association between alcohol use and pancreatic cancer with 419 pancreatic cancer cases and 963 controls recruited by a hospital-based case-control study in Taiwan. Gene-environment interaction between alcohol use and polymorphisms of two ethanol-metabolizing genes, ADH1B and ALDH2, on pancreatic risk was evaluated. Our results showed no significant association between alcohol drinking and an increased pancreatic cancer risk, even at high levels of alcohol consumption. Even among those genetically susceptible to the carcinogenic effect of alcohol (carriers of ADH1B*2/*2(fast activity) combined with ALDH2*1/*2(slow activity) or ALDH2*2/*2(almost non-functional)), no significant association between alcohol use and pancreatic cancer was observed. Overall, our results suggested that alcohol drinking is not a significant contributor to the occurrence of pancreatic cancer in Taiwan., (© 2021. The Author(s).)

Background/purpose: Grade C postoperative pancreatic fistula (POPF), as defined by International Study Group of Pancreatic Fistula (ISGPF), is the most life-threatening complication after pancreatoduodenectomy (PD). This study aims to evaluate risk factors for Grade C POPF after PD., Methods: This is a prospective, multicenter study based in Japan and Taiwan. Between December 2014 and May 2017, 3022 patients were enrolled in this study and 2762 patients were analyzed. We analyzed risk factors of Grade C POPF based on the updated 2016 ISGPF scheme (organ failure, reoperation, and/or death)., Results: Among 2762 patients, 46 patients (1.7%) developed Grade C POPF after PD. The mortality rate of the 46 patients with Grade C POPF was 37.0%. On the multivariate analysis, six independent risk factors for Grade C POPF were found; BMI ≥ 25.0 kg/m 2 , chronic steroid use, preoperative serum albumin <3.0 mg/dL, soft pancreas, operative time ≥480 minutes, and intraoperative transfusion. The c-statistic of our risk scoring model for Grade C POPF using these risk factors was 0.77. The score was significantly higher in Grade C POPF than in Grade B POPF (P < .001) or none/biochemical leak (P < .001)., Conclusions: This prospective study showed risk factors for Grade C POPF after PD., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Liposomal irinotecan plus 5-fluorouracil/leucovorin (nal-IRI + 5-FU/LV) has shown to provide survival benefits for patients with gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (PDAC) in NAPOLI-1 trial, in which Asian patients experienced more hematological toxicity and subsequent dose modification. A retrospective chart review to investigate the administration pattern, therapeutic efficacy and safety profile of nal-IRI + 5-FU/LV in 44 consecutive patients with gemcitabine-refractory advanced PDAC treated between December 2016 and December 2018 in National Cheng Kung University Hospital, Taiwan. Most of them had metastatic diseases (88.6%), one-line of prior treatment (72.7%), ECOG PS 0-1 (72.7%) and starting dose of nal-IRI at 60 mg/m 2 (≈52 mg/m 2 irinotecan free-base) in 65.9%. The overall response rate was 9.1%. The median OS was 6.6 months for the entire cohort, and 7.8 and 2.7 months for patients of ECOG PS 0-1 and>2, respectively. The median OS of ECOG PS 0-1 patients with nal-IRI starting doses at 80 mg/m 2 (≈70 mg/m 2 irinotecan free-base, n = 13) and 60 mg/m 2 (n = 19) were 7.5 and 8.4 months, respectively. Thirty-four percent of patients experienced manageable grade 3-4 hematological toxicity. Our results confirm the clinical benefit of nal-IRI + 5-FU/LV for patients of gemcitabine-refractory advanced PDAC with good performance status in a real-world setting.

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., (©2019 American Association for Cancer Research.)

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., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Periodontal disease (PD) is increasingly recognized as an emerging risk factor for various systemic diseases, including diabetes, cardiovascular diseases, and cancer. The current study examined the association between PD (periodontitis, gingivitis, and others) and pancreatic cancer., Methods: A total of 139,805 subjects with PD and 75,085 subjects without PD were identified from the National Health Insurance Research Database of Taiwan. Cox proportional hazards regression was performed to compare the incidence of pancreatic cancer between the 2 groups., Results: Periodontal disease was positively associated with pancreatic cancer risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.02-2.33). This positive association occurred predominantly among those aged 65 years or older (HR, 2.17; 95% CI, 1.03-4.57) and was not observed among those aged younger than 65 years (HR, 0.83; 95% CI, 0.52-1.34). Further analysis showed that PD is a risk factor for pancreatic cancer independent of diabetes, hyperlipidemia, allergies, viral hepatitis, peptic ulcer, pancreatitis, chronic obstructive pulmonary disease (as a proxy for cigarette smoking), and alcoholic-related conditions (as a proxy for alcohol drinking)., Conclusions: Our results indicated a significantly positive association between PD and risk of pancreatic cancer. The underlying biological mechanisms for the positive association between PD and pancreatic cancer require further investigation.

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.

Background: To evaluate the predictors for resectability and survival of patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based neoadjuvant therapy (GBNAT)., Methods: Between May 2003 and Dec 2009, 41 tissue-proved LAPC were treated with GBNAT. The location of pancreatic cancer in the head, body and tail was 17, 18 and 6 patients respectively. The treatment response was evaluated by RECIST criteria. Surgical exploration was based on the response and the clear plan between tumor and celiac artery/superior mesentery artery. Kaplan-Meier analysis and Cox Model were used to calculate the resectability and survival rates., Results: Finally, 25 patients received chemotherapy (CT) and 16 patients received concurrent chemoradiation therapy (CRT). The response rate was 51% (21 patients), 2 CR (1 in CT and 1 in CRT) and 19 PR (10 in CT and 9 in CRT). 20 patients (48.8%) were assessed as surgically resectable, in which 17 (41.5%) underwent successful resection with a 17.6% positive-margin rate and 3 failed explorations were pancreatic head cancer for dense adhesion. Two pancreatic neck cancer turned fibrosis only. Patients with surgical intervention had significant actuarial overall survival. Tumor location and post-GBNAT CA199 < 152 were predictors for resectability. Post-GBNAT CA-199 < 152 and post-GBNAT CA-125 < 32.8 were predictors for longer disease progression-free survival. Pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, and post-op CEA < 6 were predictors for longer overall survival., Conclusion: Tumor location and post-GBNAT CA199 < 152 are predictors for resectability while pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, post-GBNAT CA-199 < 152 and post-op CEA < 6 are survival predictors in LAPC patients with GBNAT.