Hung-Chih Hsu

Chemotherapy with gemcitabine plus cisplatin in patients with advanced biliary tract carcinoma at Chang Gung Memorial Hospital : a retrospective analysis

BACKGROUND A gemcitabine-cisplatin combination is a standard treatment option for patients with advanced biliary tract carcinoma (BTC). We assessed the efficacy and safety of this regimen at Chang Gung Memorial Hospital. METHODS Between April 2009 and December 2010, 30 chemotherapy-naïve patients (13 men and 17 women; median age: 61.5 years) with advanced BTC were retrospectively analyzed. Treatment consisted of gemcitabine (Gemmis(®); TTY, Taipei, Taiwan) 1000 mg/m(2), followed by cisplatin 30 mg/m(2) on days 1 and 8 every 3 weeks. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 2-3 cycles. The toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3. RESULTS At the end of July, 2011, 27 patients were evaluated using the RECIST criteria. According to the intent to treat analysis of response, 5 patients (16.7%) had a partial response, 10 patients (33.3%) had stable disease and 12 patients (40.0%) had progressive disease. The median time to progression (TTP) and median overall survival (OS) of the 30 patients were 4.8 months and 13.4 months, respectively. The patients with biliary obstruction requiring drainage before treatment had a significantly shorter OS than those without biliary obstruction (p = 0.02) even though the TTP showed no statistically significant difference (p = 0.69) between groups. The major grade III/IV adverse events in the 30 patients included infection (n = 8, 26.7%), anemia (n = 5, 16.7%), neutropenia (n = 4, 13.3%), and elevated alanine aminotransferase (n = 2, 6.7%). There were no treatment-related deaths. CONCLUSIONS Gemcitabine plus cisplatin is a feasible chemotherapy regimen with manageable toxicity in patients with advanced BTC. Maintaining good biliary drainage is essential for these patients.

The Association of Ursodeoxycholic Acid Use With Colorectal Cancer Risk: A Nationwide Cohort Study

AbstractData from preclinical studies suggest that ursodeoxycholic acid (UDCA) has a chemopreventive effect on colorectal cancer (CRC) development, but no large observational study has examined this possibility.The aim of this study was to investigate the association of UDCA use with CRC risk in a nationwide population-based cohort.This nationwide population-based cohort study used data from the Taiwan National Health Insurance Research Database for the period from 2000 through 2010. This study included data from 7119 Taiwanese adults who received ≥28 cumulative defined daily doses (cDDDs) of UDCA and 14,238 patients who did not receive UDCA (<28 cDDDs). UDCA nonusers were matched 1:2 for age, sex, enrollment date, and presence of chronic liver disease, viral hepatitis, cholelithiasis, and alcoholic liver disease. The 2 cohorts were followed until December 31, 2010 or occurrence of CRC. Cox proportional hazards regression with robust Sandwich variance estimator, which can cooperate with matching design, was used to examine the association between UDCA use and CRC risk.During 109,312 person-years of follow-up (median, 5 years), 121 patients had newly diagnosed CRC: 28 UDCA users (76.7 per 100,000 person-years) and 93 nonusers (127.7 per 100,000 person-years) (log-rank test, P = 0.0169). After multivariate adjustment for age, UDCA use was associated with a reduced risk of CRC (hazard ratio, 0.60; 95% confidence interval [CI], 0.39–0.92). The adjusted hazard ratios were 0.55 (95% CI, 0.35–0.89), 0.89 (95% CI, 0.36–2.20), and 0.63 (95% CI, 0.16–2.53) for patients with 28 to 180, 181 to 365, and >365 cDDDs, respectively, relative to nonusers.UDCA use was associated with reduced risk of CRC in a cohort mainly comprising patients with chronic liver diseases. However, further studies are needed to determine the optimal dosage of UDCA.

Targeted ultra-deep sequencing unveils a lack of driver-gene mutations linking non-hereditary gastrointestinal stromal tumors and highly prevalent second primary malignancies: random or nonrandom, that is the question

The association of non-hereditary (sporadic) gastrointestinal stromal tumors (GISTs) and second primary malignancies is known to be nonrandom, although the underlying molecular mechanisms remain unknown. In this study, 136 of 749 (18.1%) patients with sporadic GISTs were found to have additional associated cancers, with gastrointestinal and genitourinary/gynecologic/breast cancers being the most prevalent. Gene mutations in GISTs and their associated colorectal cancers (CRCs) (n=9) were analyzed using a panel of 409 cancer-related genes, while a separate group of 40 sporadic CRCs not associated with GISTs served as controls. All 9 of the GISTs had either KIT (8 of 9) or PDGFRA (1 of 9) mutations that were not present in their associated CRCs. Conversely, all but one of the 9 GIST-associated CRCs exhibited an APC mutation, a TP53 mutation or both, while none of their corresponding GISTs harbored either APC or TP53 mutations. The genetic profile of CRCs with and without associated GISTs did not differ. Although population-based studies and case series worldwide, including ours, have unanimously indicated that the GIST-CRC association is nonrandom, our targeted ultra-deep sequencing unveiled a lack of driver-gene mutations linking sporadic GISTs to highly prevalent second primaries. Further studies are needed to elucidate other genetic alterations that may be responsible for this puzzling contradiction.

A Simple Risk Model to Predict Survival in Patients With Carcinoma of Unknown Primary Origin.

AbstractCarcinoma of unknown primary origin (CUP) is characterized by diverse histological subtypes and clinical presentations, ranging from clinically indolent to frankly aggressive behaviors. This study aimed to identify prognostic factors of CUP and to develop a simple risk model to predict survival in a cohort of Asian patients.We retrospectively reviewed 190 patients diagnosed with CUP between 2007 and 2012 at a single medical center in Taiwan. The clinicopathological parameters and outcomes of our cohort were analyzed. A risk model was developed using multivariate logistic regression and a prognostic score was generated.The prognostic score was calculated based on 3 independent prognostic variables: the Eastern Cooperative Oncology Group (ECOG) scale (0 points if the score was 1, 2 points if it was 2–4), visceral organ involvement (0 points if no involvement, 1 point if involved), and the neutrophil-to-lymphocyte ratio (0 points if ⩽3, 1 point if >3). Patients were stratified into good (score 0), intermediate (score 1–2), and poor (score 3–4) prognostic groups based on the risk model. The median survival (95% confidence interval) was 1086 days (500–1617, n = 42), 305 days (237–372, n = 75), and 64 days (44–84, n = 73) for the good, intermediate, and poor prognostic groups, respectively. The c-statistics using the risk model and ECOG scale for the outcome of 1-year mortality were 0.80 and 0.70 (P = 0.038), respectively.In this study, we developed a simple risk model that accurately predicted survival in patients with CUP. This scoring system may be used to help patients and clinicians determine appropriate treatments.

Modified biweekly oxaliplatin and capecitabine for advanced gastric cancer: A retrospective analysis from a medical center

Background: We modified 3-week XELOX regimen with oxaliplatin to 85 mg/m 2 on Day 1 and capecitabine 1000 mg/m 2 BID for 10 days every 14 days to be more practical in clinical practice for advanced gastric cancer. The aim of this retrospective analysis is to evaluate the safety profile and efficacy of the modified oxaliplatin plus capecitabine (XELOX) regimen as the first-line treatment for patients with advanced gastric cancer in a medical center in Taiwan. Methods: From March 2009 to December 2010, among the 614 patients diagnosed with gastric cancer in a medical center, 49 patients with unresectable advanced or metastatic gastric adenocarcinoma were treated with oxaliplatin (85 mg/m 2 ) on Day 1 and capecitabine (1000 mg/m 2 BID) for 10 days every 2 weeks (mXELOX). CT scan was performed for tumor response evaluation. Clinical outcome and adverse events after mXELOX treatment were analyzed retrospectively. Results: A total of 354 mXELOX sessions (median: 6) were administered in 49 patients. The overall tumor response rate was 39.1% among 46 evaluated patients: three complete response (6.5%) and 15 partial response (32.6%). Seven patients had stable disease (15.2%) and 21 (45.7%) patients had progressive disease. The median progression-free survival and median overall survival were 4.37 months and 12.26 months, respectively. The most common grade III/IV hematologic toxicity was anemia (10.2%), and non-hematologic toxicity effects were numbness (8.2%), hand-foot syndrome (10.2%), diarrhea (6.1%), thrombocytopenia (6.1%), and abdominal pain (6.1%). Conclusion: This modified biweekly oxaliplatin and capecitabine combination chemotherapy is practical and effective for unresectable advanced or metastatic gastric cancer in our daily practice.