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Background: Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. Methods: A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016–2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019–2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. Results: The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4–8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3–63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P

Pancreatic cancer is a highly aggressive malignancy with a poor prognosis. Over the past decade, significant therapeutic advancements have improved the survival rates of patients with pancreatic cancer. One of the primary factors contributing to these positive outcomes is the evolution of chemotherapy, from monotherapy to doublet or triplet regimens, and the integration of multimodal approaches. Additionally, targeted agents tailored to patients with specific genetic alterations and the development of cell therapies show promise in benefiting certain subpopulations. This article focuses on examining pivotal studies that explore the role of chemotherapy in neoadjuvant, adjuvant, maintenance, and salvage settings; highlights interesting findings related to cell therapy; and provides an overview of ongoing trials concerning metastatic settings. This review primarily aimed to offer recommendations based on therapeutic evidence, recent advancements in new treatment combinations, and the most innovative approaches. A unique aspect of this review is the inclusion of published papers on clinical trials and real-world data in Taiwan, thus adding a valuable perspective to the overall analysis.

Abstract Background Gastrectomy remains the curative option in gastric cancer. However, the growing concern that preoperative waiting jeopardizes survival has not been fully addressed. The present population‐based cohort study aimed to clarify the impact of preoperative waiting time (PreWT). Methods We included patients with clinical Stage II–III gastric cancer who received curative surgery from 2008 to 2017 of Taiwan Cancer Registry. PreWT was defined as the time from endoscopic diagnosis to surgery. The prognostic impact on overall survival (OS) was evaluated with Cox and restricted cubic spline regressions. Results A total of 3059 patients with a median age of 68 years were evaluated. The median PreWT was 16 days (interquartile range, 11–24 days), and patients with a shorter PreWT were younger, had a more advanced disease and received adjuvant therapies. Despite a shorter OS occurring with prolonged PreWT (median OS by PreWT [days]: 7–13, 2.7 years; 14–20, 3.1 years; 21–27, 3.0 years; 28–34, 4.7 years; 35–31, 3.7 years; 42–48, 3.4 years; 49–118, 2.8 years; p = 0.029), the differences were not significant after adjustment. The Cox and restricted cubic spline regressions showed that prolonged PreWT was not a significant prognostic factor for OS (p = 0.719). Conclusions The population‐based study suggests that a PreWT of 49–118 days does not independently correlate with a poor prognosis in Stage II–III gastric cancer. The study provides rationale for a window period for preoperative therapies and patient optimization.

Background: The combination of bevacizumab and atezolizumab has been established as a standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). We examined the treatment outcomes of patients in Taiwan who received the combination in 2 pivotal clinical trials. Methods: All patients who resided in Taiwan, were enrolled in the IMbrave150 and GO30140 studies, and received bevacizumab and atezolizumab as the first-line systemic therapy for unresectable HCC were included. We extracted and pooled anonymous raw data from the study records. Results: We enrolled 40 patients, with the median age of 62.5 years; 36 (90%) had Barcelona Clinic Liver Cancer stage C disease. The response rate was 37.5%, including 3 (7.5%) complete responses. The disease control rate was 85%. The median duration of response was 21.4 months (95% confidence interval [CI], 16.6–not estimable). The median progression-free survival (PFS) and overall survival (OS) were 8.6 (95% CI, 5.6–18.6) and 24.9 months (95% CI, 14.2–not estimable), respectively. The most common adverse events of all grades were proteinuria (50%) and hypertension (37.5%), the median onset of which were 157 and 127 days, respectively. Bevacizumab and atezolizumab treatment had to be interrupted in 20 (50%) and 13 (32.5%) patients, respectively. Among patients whose treatment duration was ≥6 months, 50% of them had to skip bevacizumab, but no signal of poorer PFS or OS was observed. Conclusion: In Taiwanese patients with advanced HCC, the efficacy and safety outcomes of bevacizumab and atezolizumab treatment were generally consistent with the global intent-to-treat populations.

Abstract Background Cancer patients may develop prognostic awareness (PA) heterogeneously, but predictors of PA‐transition patterns have never been studied. We aimed to identify transition patterns of PA and their associated factors during cancer patients’ last 6 months. Methods For this secondary‐analysis study, PA was assessed among 334 cancer patients when they were first diagnosed as terminally ill and monthly till they died. PA was categorized into four states: (a) unknown and not wanting to know; (b) unknown but wanting to know; (c) inaccurate awareness; and (d) accurate awareness. The first and last PA states estimated by hidden Markov modeling were examined to identify their change patterns. Factors associated with distinct PA‐transition patterns were determined by multinomial logistic regressions focused on modifiable time‐varying variables assessed in the wave before the last PA assessment to ensure a clear time sequence for associating with PA‐transition patterns. Results Four PA‐transition patterns were identified: maintaining accurate PA (56.3%), gaining accurate PA (20.4%), heterogeneous PA (7.8%), and still avoiding PA (15.6%). Reported physician‐prognostic disclosure increased the likelihood of belonging to the maintaining‐accurate‐PA group than to other groups. Greater symptom distress predisposed patients to be in the still‐avoiding‐PA than the heterogeneous PA group. Patients with higher functional dependence and more anxiety/depressive symptoms were more and less likely to be in the heterogeneous PA group and in the still‐avoiding‐PA group, respectively, than in the maintaining‐ and gaining‐accurate PA groups. Conclusions Cancer patients heterogeneously experienced PA‐transition patterns over their last 6 months. Physicians’ prognostic disclosure, and patients’ symptom distress, functional dependence, and anxiety/depressive symptoms, all modifiable by high‐quality end‐of‐life care, were associated with distinct PA‐transition patterns.

Abstract 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.

BackgroundPatients with colorectal cancer (CRC) are more likely to develop cardiovascular disease (CVD) than those without cancer. Little is known regarding their CV risk after operative chemotherapy. We aimed to compare the risk of CV disease among different fluoropyrimidine derivatives.MethodsWe assembled a nationwide cohort of patients with newly diagnosed CRC between 2004 and 2015 who received fluoropyrimidine-based adjuvant chemotherapy for resected CRC by linking the Taiwan Cancer Registry (TCR), National Health Insurance Research Database (NHIRD), and Taiwan Death Registry (TDR). All eligible patients were followed from CRC diagnosis (index date) until a CV event, death, loss to follow-up, or December 31st 2018, whichever came first. CV outcomes included acute myocardial infarction (AMI), life-threatening arrhythmia (LTA), congestive heart failure (CHF), and ischemic stroke (IS). We used stabilized inverse probability of treatment weighting using propensity score (SIPTW) to balance all covariates among the three chemotherapy groups: tegafur-uracil (UFT), non-UFT, and mixed. In addition, survival analysis was conducted to examine the association between study outcomes and chemotherapy groups.ResultsFrom 2004 to 2015, 10,615 (32.8%) patients received UFT alone, 14,511 (44.8%) patients received non-UFT, and 7,224 (22.3%) patients received mixed chemotherapy. After SIPTW, the UFT group had significantly lower all-cause mortality and cancer-related death rates than the other two chemotherapy groups. However, the UFT group had significantly higher rates of cancer death, ischemic stroke, and heart failure than those of the other two chemotherapy groups. The UFT group also had a significantly higher AMI rate than the mixed group. There was no significant difference in LTA among the three groups. Similar findings were observed in the subgroup analysis (stage II and age

IntroductionThis multicenter, real-world cohort study aimed to evaluate the effectiveness of early cumulative dose administration and dosing pattern of liposomal irinotecan plus fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (mPDAC).Material and MethodsThe electronic medical records of mPDAC patients treated with nal-IRI+5-FU/LV in nine participating centers were manually reviewed. To accommodate to the NAPOLI-1 study population, only patients with an Eastern Cooperative Oncology Group Performance Score of 0–1 were included. The survival impact of the relative 6-week cumulative dose and dosing pattern (standard vs. reduced starting dose, with and without further dose modification) were investigated.ResultsOf the 473 included patients, their median overall survival (mOS) was 6.8 [95% CI, 6.2–7.7] months. The mOS of patients who received a relative 6-week cumulative dose of >80%, 60%–80%, and

BackgroundRipretinib was recently approved for the fourth-line targeted therapy for advanced gastrointestinal stromal tumor (GIST) refractory to imatinib, sunitinib, and regorafenib based on the pivotal INVICTUS phase III study. The INVICTUS study demonstrated significantly improved median progression-free survival (PFS) of 6.3 months and an overall survival (OS) insignificant benefit of ripretinib of 15.1 months as compared with placebo in 85 patients with advanced metastatic GIST. However, treatment outcome for the Chinese population, including in Taiwan and Hong Kong, was lacking.Material and MethodA compassionate study regarding ripretinib use for patients with advanced/metastatic GIST was conducted from March 2020 to March 2021 to assess the treatment efficacy and safety in Taiwan and Hong Kong patients.ResultTwenty evaluable patients (16 men and 4 women) with heavily pretreated metastatic GIST receiving ripretinib from March 2020 to March 2021 were enrolled to evaluate the treatment outcome. The response and clinical benefit rates to ripretinib were 25% (5/20) and 60% (12/20), respectively. The median PFS and OS in this compassionate cohort receiving ripretinib were 6.1 months and not reachable, respectively. Albumin less than 3.5 and disease progression after ripretinib use were the two independent unfavorable factors for PFS. There were 14 out of 20 (70%) experiencing any grade adverse event (AE). Loss of hair is the most common grade I to II AE with an incidence of 55%. Grade III AEs included diarrhea, skin rash, and anemia with one patient (5%) for each AE.ConclusionsLate-line ripretinib use in pretreated Taiwan and Hong Kong patients with advanced GIST showed efficacy consistent with the INVICTUS study. Albumin less than 3.5 and disease progression after ripretinib use were the two independent unfavorable factors for PFS. Ripretinib is generally tolerable, with loss of hair being the most common AE.

Immune checkpoint inhibitors (ICIs) are a novel treatment option for cancer therapy, which help direct the immune system to recognize and target cancer cells. ICIs have been shown to provide significant mortality benefits for cancer patients, but they are also associated with immune-mediated toxicity. Unlike most immune-related adverse events, which are a common occurrence, reversible and can be treated effectively with glucocorticoid therapy, ICI-associated cardiotoxicities are uncommon, with serious complications and a relatively high mortality even when treated with glucocorticoids. ICI-associated cardiotoxicity can manifest in various ways, including myocarditis, arrhythmias and conduction disease, pericardial disease, myocardial infarction, non-inflammatory cardiomyocyte dysfunction, and even Takotsubo-like cardiomyopathy. The present review summarizes the current understanding of ICI-associated cardiotoxicities, examining the epidemiology and timing of onset, as well as their clinical presentation, diagnostic modalities, pathophysiology, clinical management and outcomes. Although the literature describing ICI-associated cardiotoxicity remains limited to case reports, case series and early clinical trials, strategies for the surveillance, diagnosis and management of this potentially fatal cardiovascular complication of cancer therapy have been proposed.

Abstract Background Chemotherapy with gemcitabine and cisplatin has been the standard of care in first-line chemotherapy for advanced biliary tract cancer (BTC) since the trial ABC-02 was published in 2010. We aimed to investigate the prognostic and predictive factors of this regimen in a cohort of Taiwanese patients with advanced BTC. Methods A total of 118 patients with histologically confirmed BTC treated at Chang Gung Memorial Hospital at Linkou from 2012 to 2017 were retrospectively reviewed. Results The median progression-free survival (PFS) and overall survival (OS) were 3.6 months and 8.4 months, respectively. In the multivariate analysis, neutrophil to lymphocyte ratio (NLR) > 7.45, biliary drainage requiring both percutaneous transhepatic cholangiography drainage (PTCD) and internal stenting, and tumor responses with progressive diseases and not assessed were independent poor prognostic factors for PFS. Male sex, NLR > 7.45, alkaline phosphatase> 94 U/L, biliary drainage requiring both PTCD and internal stenting, and tumor responses with stable disease, progressive diseases and not assessed were independent poor prognostic factors for OS. Monocyte to lymphocyte ratio (MLR) ≤ 0.28 was the only significant predictive factor for the tumor response. Patients with complete response/partial response had significantly lower MLR than patients with other tumor responses. Conclusion We identified three important prognostic factors, namely tumor response, NLR, and biliary drainage requiring both PTCD and internal stenting for both PFS and OS. MLR was the only significant predictive factor for the tumor response. These findings could provide physicians with more information to justify the clinical outcomes in patients with advanced BTC in real-world practice.

Abstract Background Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. Methods Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45– cells and cCSCs as CD133+EpCAM+Hoechst+CD45– cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. Results We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is currently the standard second-line treatment for patients with pancreatic ductal adenocarcinoma (PDAC) after previous failed gemcitabine-based therapy. This population-based study aimed to evaluate the efficacy and safety of nal-IRI + 5-FU/LV and the association of pre-emptive nal-IRI dosing with treatment outcomes in patients with PDAC. Methods: We retrospectively enrolled a total of 667 consecutive patients with PDAC who received nal-IRI plus 5-FU/LV treatment between August 2018 and November 2020 at 9 medical centers in Taiwan. Patients were allocated into groups according to pre-emptive nal-IRI dosing (⩾75%, 50–74%,

Background: We developed a hybrid platform using a negative combined with a positive selection strategy to capture circulating tumor cells (CTCs) and detect epidermal growth factor receptor (EGFR) mutations in patients with metastatic lung adenocarcinoma. Methods: Blood samples were collected from patients with pathology-proven treatment-naïve stage IV lung adenocarcinoma. Genomic DNA was extracted from CTCs collected for EGFR mutational tests. The second set of CTC-EGFR mutational tests were performed after three months of anti-cancer therapy. Results: A total of 80 samples collected from 28 patients enrolled between July 2016 and August 2018. Seventeen patients had EGFR mutations, including Exon 19 deletion (n = 11), L858R (n = 5), and de-novo T790 and L858R (n = 1). Concordance between tissue and CTCs before treatment was 88.2% in EGFR- mutant patients and 90.9% in non-mutant patients. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EGFR mutation tests for CTCs were 89.3%, 88.2%, 90.9%, 93.8%, and 83.3%, respectively. Conclusions: CTCs captured by a hybrid platform using a negative and positive selection strategy may serve as a suitable and reliable source of lung cancer tumor DNA for detecting EGFR mutations, including T790M.

Background: The real-world effectiveness of oxaliplatin in stage III colon cancer has not been determined in a large-scale population. We aimed to assess the real-world impact of adjuvant oxaliplatin treatment on the survival of these patients.Methods: Based on Taiwan cancer registry, we evaluated 17,801 patients with resected stage III colon cancer, including 14,168 patients receiving adjuvant chemotherapy and 3,633 not receiving adjuvant chemotherapy as the control group between 2004 and 2014. We used the controlled interrupted time-series analysis to assess the three-year disease-free survival and five-year overall survival rates before (2004–2008) and after (2009–2014) the addition of oxaliplatin.Results: The introduction of oxaliplatin was associated with no significant improvement in the slopes (per half-year) of the three-year disease-free survival rate (0.2%, 95% CI: −1.7∼2.2%) and five-year overall survival rate (0.6%, 95% CI: −1.8∼3%). The patients receiving oxaliplatin-based chemotherapy also showed no significant increase in the slopes (per half-year) of the three-year disease-free survival rate (0.6%, 95% CI: −1.4∼2.6%) and five-year overall survival rate (1%, 95% CI: −1.5∼3.5%). The nonsignificant results were consistent across subgroup analyses of age (6). However, oxaliplatin-based chemotherapy significantly increased the slope (per half-year) of the five-year OS (2%, 95% CI: 0.2∼3.8%) for patients in the high-risk group (T4 or N2). The present results were robust in several sensitivity analyses.Conclusion: Among real-world patients with stage III colon cancer, the introduction of oxaliplatin does not yield a significant improvement in survival. Future work should identify the subpopulation(s) of patients who benefit significantly from the addition of oxaliplatin.

Abstract Background We previously developed a robust prognostic model (GS model) to predict the survival outcome of patients with advanced pancreatic cancer (APC) receiving palliative chemotherapy with gemcitabine plus S‐1 (GS). This study aimed to validate the application of the GS model in APC patients receiving chemotherapy other than the GS regimen. Patients and methods We retrospectively analyzed 727 APC patients who received first‐line palliative chemotherapy other than the GS regimen between 2010 and 2016 at four institutions in Taiwan. The patients were categorized into three prognostic groups based on the GS model for comparisons of survival outcome, best tumor response, and in‐group survival differences with monotherapy or combination therapy. Results The median survival times for the good, intermediate, and poor prognostic groups were 13.4, 8.4, and 4.6 months, respectively. The hazard ratios for the comparisons of intermediate and poor to good prognostic groups were 1.51 (95% confidence interval [CI]), 1.22‐1.88, P

Abstract Introduction Palliative chemotherapy is the standard treatment for patients with unresectable pancreatic cancer. Whether the early initiation of palliative chemotherapy is associated with a favorable survival outcome for these patients is not known. This study aimed to analyze the association of the time interval between cancer diagnosis and initiation of palliative chemotherapy with survival outcome in patients with pancreatic cancer. Method A total of 838 patients with unresectable pancreatic cancer who underwent palliative chemotherapy from 2010 to 2016 at 4 institutions in Taiwan were retrospectively enrolled. All patients were categorized according to time interval between cancer diagnosis and initiation of palliative chemotherapy for comparison of the survival outcome. Result The median time interval was 14 days (range, 0 to 163 days) in our patient cohort. Accordingly, 22%, 29%, and 49% of the patients underwent palliative chemotherapy within 1, 1 to 2, and >2 weeks after cancer diagnosis, respectively. The survival outcome had no statistical difference among these 3 patient groups. Subgroup analyses revealed that patients with the time interval ≤2 weeks exhibited poorer survival outcome than those with the time interval >2 weeks if they initially presented with jaundice (6.1 months vs 8.4 months, P = 0.029). In contrast, patients with the time interval ≤2 weeks revealed a better survival outcome than those with the time interval >2 weeks if they initially presented with pain (8.0 vs 6.3 months, P = 0.014). Conclusion In our study, time interval between cancer diagnosis and the initiation of palliative chemotherapy >2 weeks was not associated with a poorer survival outcome for patients with unresectable pancreatic cancer. Our result might help clinicians to clarify that early initiation of palliative chemotherapy might provide survival benefit for patients who present with tumor pain, but not for those who present with jaundice.

Abstract Objective Studies have rarely explored the efficacy of S‐1 in treating advanced pancreatic cancer outside Japan. This study compared the survival outcomes of patients with advanced pancreatic cancer treated with S‐1 with the survival outcomes of those without S‐1 treatment before and after S‐1 reimbursement was introduced in Taiwan in June of 2014. Method We retrospectively analyzed 838 patients with locally advanced or metastatic pancreatic cancer who underwent palliative chemotherapy from 2010 to 2016 at 4 institutes in Taiwan. For survival analysis, patients were categorized into two groups according to whether they received S‐1 treatment as palliative chemotherapy after diagnosis: (a) S‐1‐treated (n = 335) and (b) non‐S‐1‐treated (n = 503) groups. Results The median overall survival was longer in the S‐1‐treated group than in the non‐S‐1‐treated group (10.7 vs 6.0 mo, P

Summary: Background: Radical gastrectomy and extended lymph node (D2) dissection followed by adjuvant chemotherapy is the optimal treatment for patients with stage III gastric cancer in Asian population. The clinical factors associated with patient propensity to receive adjuvant chemotherapy and outcomes were analyzed. Methods: In total, 509 patients with stage III gastric cancer who had undergone D2 surgery between 2007 and 2017 at a single medical center in Taiwan were analyzed. The patients' preoperative clinical characteristics relevant to adjuvant chemotherapy adherence were analyzed using multivariate regression. Significant variables were analyzed using recursive partitioning analysis (RPA) for identifying specific patient groups with the lowest and highest probabilities of adjuvant chemotherapy adherence. Results: After surgery, 361 (70.9%) patients in the cohort had received adjuvant chemotherapy. All patients were categorized into five probability groups with adherence to adjuvant chemotherapy according to age, Eastern Cooperative Oncology Group (ECOG) performance status grade, and American Society of Anesthesiologists (ASA) class, which were discovered to be independent factors in the RPA-based probability prediction. In general, adjuvant chemotherapy improved survival across broad categories of stage III gastric cancer patients (overall survival hazard ratio: 0.53–0.75 and disease-free survival hazard ratio: 0.47–0.76). Conclusions: Our study identified that age, ECOG grade, and ASA class were independent clinical factors associated with patient propensity to receive adjuvant chemotherapy in stage III gastric cancer. Knowledge of the clinical factors of patients may help clinicians identify and encourage specific patients to receive the adjuvant chemotherapy. Keywords: Stage III gastric cancer, Adjuvant chemotherapy, Clinical factors, Survival outcome

Summary: Background: Determining the survival outcome for gastric cancer patients with metastases to more than 15 regional lymph nodes is difficult. This study aims to develop a lymph node metastatic ratio (LNR)-based prognostic model to predict the survival outcome after D2 surgery in such patient groups. Methods: Our study retrospectively enrolled 139 gastric cancer patients with metastases to more than 15 regional lymph nodes who underwent D2 surgery between 2007 and 2014. Clinicopathologic variables to predict overall survival (OS) using multivariate Cox regression were selected to create a prognostic model. Results: The prognostic model for predicting OS was developed based on five independent factors, namely, T-classification (T2 or T3 vs. T4), LNR (

Background/purpose: To investigate the diagnostic accuracy of 68Ga-DOTATOC and 18F-FDG PET/CT to identify the primary foci in Taiwanese patients with clinically suspected neuroendocrine tumors (NET) and NET of unknown primary site. Methods: Patients with clinically suspected NET and NET of unknown primary site were eligible. All participants underwent a conventional workup (including CT, MR, endoscopic ultrasound), 68Ga-DOTATOC, and 18F-FDG PET/CT. The results of pathology and findings on clinical follow-up served as the gold standard. Results: Among the 36 patients included in the study, we were able to identify the primary tumor in 17 participants (47.2%). The overall sensitivity values of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 88%, 41%, and 53%, respectively, whereas the specificities were 100%, 100%, 68%, respectively. The areas under curve of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 0.941, 0.706, and 0.607, respectively. 68Ga-DOTATOC was more sensitive than 18F-FDG and more specific than conventional workup. Treatment changes as a result of 68Ga-DOTATOC PET/CT findings occurred in 12 (33.3%) of the 36 study participants. Conclusion: Our data confirm the usefulness of 68Ga-DOTATOC in the identification of NET. In addition, treatment modifications as a result of 68Ga-DOTATOC PET/CT findings were evident in approximately one third of NET patients. Keywords: 68Ga-DOTATOC, 18F-FDG, Neuroendocrine tumors, PET/CT

Oxaliplatin-based chemotherapy is an alternative systemic treatment for patients with metastatic hepatocellular carcinoma (HCC) who were refractory or intolerant to sorafenib. To date, there have been no biomarkers reported to monitor the therapeutic efficacy and to predict the outcomes of HCC patients receiving oxaliplatin-based chemotherapy. Methods: Eighty-one HCC patients with elevated baseline α-fetoprotein (AFP) levels and extrahepatic spreading who received oxaliplatin-based chemotherapy between 2012 and 2014 were retrospectively enrolled in this study. Two AFP tests were performed, at baseline and 2–4 weeks after the initiation of chemotherapy. The change in AFP levels was calculated for survival analysis. Results: In the AFP decline group (decreased compared to baseline), the median progression-free survival (PFS) and overall survival (OS) were 7.0 months and 12.3 months, respectively. In the AFP nondecline group, the median PFS and OS were 2.3 months and 3.0 months, respectively. The difference in OS between the two groups was significant (p

Abstract Background Gastric cancer is one of the leading causes of cancer-related deaths in both sexes worldwide, especially in Eastern Asia. This study aimed to estimate the economic burden of advanced gastric cancer (AGC) in Taiwan. Methods The costs of AGC in 2013 were estimated using resource use data from a chart review study (n = 122 with AGC) and national statistics. Annual per-patient costs, where patients’ follow-up periods were adjusted for, were estimated with 82 patients who had complete resource use data. The costs were composed of direct medical costs, direct non-medical costs (healthcare travel and caregiver costs), morbidity costs, and mortality costs. Relevant unit costs were retrieved mainly from literature and national statistics, and applied to the resource use data. A broad definition of morbidity and mortality costs was employed to value the productivity loss in patients with unpaid employment, economically inactive and unemployed as well as the life years after the age of retirement. Their narrow definitions were also used in sensitivity analyses, using age- and/or sex-specific employment rates. Forgone future earnings/productivity loss were discounted at 3%. Annual per-patient costs were projected to estimate the total costs of AGC at the national level with an estimated number of patients with AGC (N = 2611) in Taiwan in 2013. Results The mean age of the 82 patients was 59.3 (SD: 11.9) years, and 67.1% were male. Per-patient costs were US$26,431 for direct medical costs, US$4669 for direct non-medical costs, US$5758 for morbidity costs, and US$145,990 for mortality costs (per death). These per-patient costs were projected to incur total AGC costs of US$423 million at the national-level. Mortality costs accounted for 77.3% of the total costs, followed by direct medical costs (16.3%), morbidity costs (3.6%), and direct non-medical costs (2.9%). Conclusion AGC was found to exert a significant economic burden in Taiwan, incurring US$423 million in 2013. This represents about 0.08% of the Taiwanese economy. Mortality costs appeared to be the single greatest contributor to the burden, followed by direct medical costs. Early detection and providing effective treatments will help to reduce its burden on patients, caregivers and society as a whole. A poster of this study was presented at the 2016 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, CA, USA.

Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, tumor mutation burden (TMB), and microsatellite instability (MSI), for patients undergoing ICIs, as well as the possible predictive value for ICIs. We examined the association of CIN70 with TMB and MSI, as well as the impact of these biomarkers on the survival of 33 cancer cohorts from The Cancer Genome Atlas (TCGA) databank. The predictive value of the ICIs of CIN70 in previously published reports was also validated. Using the TCGA dataset, CIN70 scores were frequently (either positively or negatively) associated with TMB, but were only significantly associated with MSI status in three types of cancer. In addition, our current study showed that all TMB, MSI, and CIN70 had their own prognostic values for survival in patients with various cancers, and that they could be cancer type-specific. In two validation cohorts (melanoma by Hugo et al. and urothelial cancer by Snyder et al.), no significant difference of CIN70 scores was found between responders and non-responders (p-value = 0.226 and 0.108, respectively). In addition, no overall survival difference was noted between patients with a high CIN70 and those with a low CIN70 (p-value = 0.106 and 0.222, respectively). In conclusion, the current study, through a comprehensive bioinformatics analysis, demonstrated a correlation between CIN70 and TMB, but CIN70 is not the predictor for cancer patients undergoing ICIs. Future prospective studies are warranted to validate these findings.

Targeted anticancer therapies, unlike the traditional cytotoxic chemotherapies which lead to systemic toxicities, frequently cause cutaneous adverse events that are symptomatic and manifest in cosmetically sensitive areas. The most common dermatologic toxicities related to epidermal growth factor receptor (EGFR) inhibitors are papulopustular eruption, xerosis, pruritus and paronychia. Vascular endothelial growth factor receptor (VEGFR) inhibitors usually cause hand-foot skin reaction. Reports of dermatologic side effects such as abnormalities of hair growth and mucosal changes also increased. These events may contribute to poor adherence, dose interruption and discontinuation of the regimens. In addition, psychosocial discomfort causing reduction in the quality of life does occur. However, the presence and severity of cutaneous adverse events has shown to have positive correlation with treatment response. The management of these side effects can be categorized into prophylaxis and reactive treatment. Systemic antibiotics and topical corticosteroid could possibly prevent or alleviate symptoms caused by EGFR inhibitors. The prevention of sun exposure is recommended to all patients on targeted therapy, and emollients and lubricants can be used to relieve and improve the hand-foot skin reaction.

Background: The time schedules for response evaluation of epidermal growth factor receptor-tyrosine kinase Inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients are still ill-defined. Methods: Stage IIIB/IV patients with histologically proven NSCLC were enrolled in this study if the tumor cells bore EGFR mutations other than T790M. Eligible patients were treated with either 250 mg of gefitinib or 150 mg of erlotinib once daily. The early response rate [computed tomography (CT) scan on Day 14], definitive response rate determined on Day 56, progression-free survival (PFS), overall survival (OS), and toxicity profile were assessed prospectively. Results: Thirty-nine patients were enrolled in this study. A total of 29 patients (29/39, 74.4%) achieved partial response (PR). Twenty-one patients (21/39, 53.8%) had early radiological response on Day 14. The early radiological response rate in patients with PR was 72.4% (21/29). Only eight patients without a PR on early CT still ended with PR. Among the 29 patients with PR, the PFS (8.1 months) and OS (18.3 months) of the 21 patients with early CT response were shorter than those of the 8 patients without early CT response (11.9 and 24.0 months for PFS and OS, respectively). But the survival differences were statistically non-significant. Conclusions: A very high percentage (72.4%, 21/29) of NSCLC patients with EGFR mutations with PR demonstrates early radiological response to EGFR-TKIs, which would advocate early radiological examination for EGFR-TKI therapy in NSCLC patients.

AIM: Sunitinib has shown benefit in patients with imatinib (IM)–resistant gastrointestinal stromal tumor (GIST). However, its advantages are somewhat diminished because of associated toxicities. Herein, we clarify the efficacy and safety of fractioned dose regimen of sunitinib by a pharmacokinetic and efficacy study. MATERIALS AND METHODS: Between 2001 and March 2013, a total of 214 patients with metastatic GIST was treated at Chang Gung Memorial Hospital. Among them, 55 (11.6%) patients who received sunitinib were investigated. One group of patients was administered with standard dose of once-daily sunitinib (standard dose group) and the other group was administered with standard total daily dose of sunitinib in fractioned doses (fractioned dose group). RESULTS: Thirty-two male and 23 female patients with a median age of 55 years received sunitinib. The median duration of sunitinib administration was 9.2 months. The clinical benefit was 65.2%. The mean peak blood level of sunitinib in patients with fractioned doses was significantly lower than that in those with once-daily dose (83.4 vs 50.1 ng/ml, P = .01). The rates of adverse effects of hand-foot syndrome, mucositis, and yellow skin were significantly decreased by fractioned doses of sunitinib. However, the progression-free and overall survival did not differ between patients with different treatment regimens. CONCLUSION: The fractioned dose regimen of sunitinib appears to be a safe and effective treatment for patients with IM-resistant/intolerant GISTs. Significantly decreased toxicity of this regimen could be explained by significantly lower peak sunitinib blood level. However, the treatment efficacy is not reduced by this regimen.

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.

Background: This prospective phase II clinical trial evaluated the efficacy and toxicity of cisplatin, oral tegafur-uracil, leucovorin, and mitomycin C in patients with recurrent or metastatic nasopharyngeal carcinoma. Methods: Patients with histologically proven non-keratinizing or undifferentiated nasopharyngeal carcinoma were prospectively enrolled from April 2002 to June 2005. Cisplatin 50 mg/m 2 on day 1, 22 and mitomycin C 6 mg/m 2 on day 1 were administered. Oral tegafur-uracil 300 mg/m 2 /day and oral leucovorin 60 mg/day were given on day 1-14 and day 22-35, respectively. Each cycle was repeated every 6 weeks. Primary and secondary endpoints are response rate and toxic profiles with survivals, respectively. Results: Twenty-two patients with the median age of 47 (35-69) years were enrolled in the study. Sixteen (72.7%) patients had undifferentiated nasopharyngeal carcinoma. The regimen was well-tolerated by all patients with the exception of one patient (4.6%) who experienced grade IV anorexia, and two patients (9.1%) who had grade IV vomiting. There was no treatment-related death. The overall response rate was 59.1%, including 3 (13.6%) complete remissions. The median duration of response was 15.9 months, the median time to tumor progression was 10.0 months, and the median overall survival was 16.0 months. Conclusion: This outpatient chemotherapy regimen is acceptably effective and toxic among patients with recurrent or metastatic nasopharyngeal carcinoma.