Longitudinal evaluation of adverse events due to steroid use in primary immune thrombocytopenia: A population-based study.

This study aimed to investigate the association between the steroid use patterns and the risk of AEs in patients with primary immune thrombocytopenia (ITP). A total of 2691 newly diagnosed adults with ITP between 2011 and 2018 were identified from the National Health Insurance Research Database in Taiwan, and the date of first steroid use was defined as the index date. Post-index steroid use was calculated on a 90-day basis as a time-dependent variable and categorized by the average prednisolone-equivalent daily dose (<10 mg vs. ≥10 mg) and intensity (medication possession ratio <80% vs. ≥80%). Patients were followed up for 1 year from the index date for acute AE events, while chronic AEs were assessed until death, or end of 2019. Compared to patients with low-dose+low-intensity steroid use, those with high-dose+high-intensity steroid use were associated with a higher risk of acute AE (adjusted incident rate ratio [aIRR]: 1.57, 95% confidence interval [CI]: 1.38-1.78, p < 0.01) and chronic AE (aIRR: 1.26, 95% CI: 1.08-1.47, p < 0.01). Metabolic/endocrine and ophthalmologic disorders demonstrated the strongest correlation with a high dose and intensity. The joint effect of steroid dose and intensity was observed in patients with ITP, and the findings suggest that steroids should be used carefully.

Risk and impact of tuberculosis in patients with chronic myeloid leukemia: a nationwide population-based study in Taiwan.

The relationship between chronic myeloid leukemia (CML) and tuberculosis (TB) has not been determined. We conducted a national survey including 1,082 CML patients identified from the Taiwan National Health Insurance database covering a period between 1998 and 2011; the matched non-exposed cohort included 10,820 subjects without CML that were matched for age, sex and comorbidities. The impact of TB was measured by the overall mortality, and the risk factors were identified by a multivariate Cox proportional hazards model. We found the risk of TB was higher in the CML cohort, with an adjusted hazard ratio (aHR) of 3.76 (p = 0.001) for both pulmonary (aHR 3.23, p < 0.001) and extrapulmonary (aHR 9.77, p = 0.001) TB. Specific risk factors were: aged ≥ 60 (aHR 3.24, p = 0.022), being male (aHR 13.49, p = 0.012), receiving stem cell transplantation (aHR 10.50, p = 0.001) and interferon-α therapy (aHR 3.34, p = 0.011). CML patients with TB had a higher mortality rate than those without (aHR 2.04, p = 0.043). We conclude that the incidence of TB is significantly higher in CML patients of male sex, aged ≥ 60, having received either stem cell transplantation or interferon-α treatment. Careful screening strategies for TB should be considered for CML patients with high risk of the infection.

Anxiety and depressive disorders among patients with esophageal cancer in Taiwan: a nationwide population-based study.

BACKGROUND: The comorbidity of depression with anxiety disorders is associated with poorer treatment outcomes, worse quality of life, poorer adherence to treatment, and greater suicide risk in cancer patients. OBJECTIVE: To assess the risk of comorbid anxiety and depressive disorders after the diagnosis of esophageal cancer compared with a matched cohort by using the Taiwan National Health Insurance Research Database (NHIRD). METHODS: We conducted a retrospective study of 28,454 patients (14,227 patients with esophageal cancer and 14,227 matched patients) who were selected from the NHIRD. Patients were observed for a maximum of 12 years to determine the incidence of new-onset anxiety and depressive disorders for which antidepressants had been prescribed. A Cox regression analysis was performed to identify the risk factors associated with anxiety and depressive disorders in esophageal cancer patients. RESULTS: The cumulative incidence of anxiety and depressive disorders in the esophageal cancer patients was significantly higher than that in the matched cohort (P < .001). The adjusted hazard ratio (HR) was 2.24 (95 % confidence interval, CI = 1.95-2.56, P < .001) in the esophageal cancer cohort compared with the matched cohort. Independent risk factors for developing anxiety and depressive disorders among the patients with esophageal cancer included cirrhosis, cerebrovascular disease, and surgical treatment. CONCLUSION: Esophageal cancer may be a prominent risk factor for anxiety and depressive disorders. Based on our data, we suggest that attention should be focused on esophageal cancer patients with comorbid cirrhosis and cerebrovascular disease and those who have received surgical interventions.

Registry of Genetic Alterations of Taiwan Non-Small Cell Lung Cancer by Comprehensive Next-Generation Sequencing: A Real-World Cohort Study-Taiwan Cooperative Oncology Group T1521.

PURPOSE: Tissue-based next-generation sequencing (NGS) analysis is highly recommended for patients with advanced/metastatic non-small cell lung cancer (NSCLC). We investigated a specific patient population with NSCLC that required tissue-based NGS analysis. MATERIALS AND METHODS: We enrolled 500 patients with advanced/metastatic (1) epidermal growth factor receptor (EGFR) mutations or anaplastic large-cell lymphoma kinase (ALK) rearrangement-positive NSCLC who had failed at minimum one line of tyrosine kinase inhibitor (TKI) therapy, (2) EGFR-/ALK-negative nonsquamous, and (3) non- or light-smoker patients with squamous NSCLC who were treatment-naïve or had failed at maximum two lines of systemic treatment. These patients were divided into five cohorts. Comprehensive tissue-based NGS testing (ACTOnco+) was conducted. RESULTS: Cohort 1: EGFR TKI-pretreated EGFR-mutated population (50.0%, n = 250), cohort 2: ALK inhibitor-pretreated ALK-positive population (1.6%, n = 8), cohort 3: treatment-naïve EGFR-/ALK-negative population (28.2%, n = 141), cohort 4: pretreated EGFR-/ALK-negative population (16.8%, n = 84), and cohort 5: squamous cell carcinoma (3.4%, n = 17). In cohort 1, 11.2% (28/250) of the patients had MET amplification, 32.4% (81/250) had been treated with osimertinib, and EGFR C797S was detected in 6.2% (5/81) of these patients. In cohort 2, resistance ALK mutation was detected in 37.5% (3/8) of the patients. In cohorts 3 and 4, targetable genetic alterations, including EGFR mutation (13.3%), ERBB2 mutation (9.3%), MET exon 14 skipping (5.3%), KRAS G12C mutation (4.4%), ROS1 fusion (2.7%), RET fusion (1.8%), and BRAF V600E mutation (1.3%), were detected. In cohort 5, MET exon 14 skipping was detected in 29.4% (5/17) of the patients. CONCLUSION: This multicenter registration study investigated tissue-based NGS for a specific patient population with NSCLC in Taiwan.

Stromal-derived factor-1 gene variations in pediatric patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) of childhood is an autoimmune disease characterized by abnormally increased destruction of platelets and decreased megakaryopoiesis. Stromal-derived factor-1 (SDF-1) plays a role in megakaryopoiesis and may be involved in the pathogenesis of ITP. Five single nucleotide polymorphisms (SNPs) of the SDF-1 gene, including rs1801157, rs2839693, rs2297630, rs1065297, and rs266085, were assessed in 100 children with ITP and 126 healthy controls. The genotypes were analyzed by tetra ARMS polymerase chain reaction and confirmed by direct sequencing. Compared with controls, the rs2839693 A/A and rs266085 C/T genotypes were decreased in ITP patients (P = 0.004 and 0.007, respectively). The odds ratios of the latter genotypes were 0.48, 95% CI 0.28-0.82. Further analysis of the relationship between SDF-1 polymorphisms and clinical features showed that rs2297630 A/G was associated with protection from chronicity (P = 0.002; OR, 0.07; 95% CI, 0.01-0.61) and steroid dependence (P = 0.007; OR, 0.10; 95% CI, 0.01-0.84) in ITP patients. However, rs266085 genotype C/C was associated with risk of steroid dependence (P = 0.012, OR 3.87, 95% CI 1.27-11.77). The findings of this study suggest that SDF-1 gene variations may be associated with the occurrence and prognosis of childhood ITP.

NOVEL-1st: an observational study to assess the safety and efficacy of nilotinib in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in Taiwan.

Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). However, the real-world evidence of nilotinib in newly diagnosed untreated Ph+ CML-CP is limited in Taiwan. The NOVEL-1st study was a non-interventional, multi-center study collecting long-term safety and effectiveness data in patients with newly diagnosed and untreated Ph+ CML-CP receiving nilotinib. We enrolled 129 patients from 11 hospitals. Overall, 1,466 adverse events (AEs) were reported; among these, 151 were serious and 524 were nilotinib-related. Common hematological AEs were thrombocytopenia (31.0%), anemia (20.9%), and leukopenia (14.0%); common nilotinib-related AEs were thrombocytopenia (29.5%), anemia (14.7%), and leukopenia (12.4%). Early molecular response, defined as BCR-ABL ≤ 10% at Month 3, was seen in 87.6% of patients. By 36 months, the cumulative rates of complete hematologic response, complete cytogenetic response, major molecular response, molecular response 4.0-log reduction, and molecular response 4.5-log reduction were 98.5, 92.5, 85.8, 65.0, and 45.0%, respectively. Nilotinib is effective and well-tolerated in patients with newly diagnosed Ph+ CML-CP in the real-world setting. Long-term holistic care and a highly tolerable AE profile may contribute to good treatment outcomes in Ph+ CML-CP under first-line treatment with nilotinib.

A Cross-sectional Study of Patients and Physicians on the Impact of Myeloproliferative Neoplasms on Patient Health: The Landmark Survey From Taiwan.

Patients with myeloproliferative neoplasm (MPN), including myelofibrosis, polycythemia vera, and essential thrombocythemia, experience a pronounced symptom burden. This study aimed to collect information from physicians and patients in Taiwan to explore their perceptions regarding MPN, treatment goals, and satisfaction with disease management. A cross-sectional, online survey was conducted among patients and physicians from September 2018 to November 2018 in Taiwan as a subset of the expansion of the Landmark survey. Overall, 50 patients with MPN and 30 physicians participated in this study. The symptom burden was low, with the mean number of symptoms experienced being 1.8. The most frequent symptom per physicians' perception was fatigue, whereas it is not the most common symptom from MPN patients' perspective. Blood count was the key indicator to determine treatment success from patients' view, whereas presence of a new symptom was the key indicator from physicians' perspective. Concordant with previous studies, our study revealed a lack of alignment between physician and patient perceptions relating to treatment goals and disease management. Nevertheless, the physical, emotional, work/activities and financial impacts on patients were minimal in Taiwan.

The efficacy and safety of everolimus for the treatment of progressive gastroenteropancreatic neuroendocrine tumors: A multi-institution observational study in Taiwan.

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.

Risk of cancer in patients with irritable bowel syndrome: a nationwide population-based study.

PURPOSE: The aim of our study was to evaluate the overall cancer risk among patients with the irritable bowel syndrome (IBS) by using a nationwide population-based data set. METHODS: We obtained data on newly diagnosed IBS patients (age ≥ 20 years) without antecedent cancer from the Taiwan National Health Insurance Research Database for the period between 2000 and 2010. Standardized incidence ratios (SIRs) were calculated for various types of cancer in the IBS patients. RESULTS: A total of 1,043 people among the 29,838 IBS patients had developed cancer, and the follow-up was 139,185 person-years (median, 4.56 years), leading to a significantly increased SIR (1.18; 95% confidence interval [CI]) = 1.11-1.26) among all cancer types. However, after excluding cancer that developed within the first year after IBS diagnosis, the increased SIR of overall cancer was nonsignificant. In particular, the IBS patients exhibited an increased risk of cancers of the colon and rectum (SIR = 1.51; 95% CI = 1.31-1.73), liver and biliary tract (SIR = 1.40; 95% CI = 1.21-1.62), pancreas (SIR = 1.56; 95% CI = 1.02-2.28), and kidney (SIR = 1.56; 95% CI = 1.10-2.15). CONCLUSIONS: An increased SIR in IBS patients was observed only within the first year of IBS diagnosis. The findings of this study might have resulted from detection bias, localized symptoms, or paraneoplastic syndromes associated with IBS-like symptoms. Additional prospective studies are necessary to confirm these findings.

Development of second primary malignancy in patients with non-Hodgkin lymphoma: a nationwide population-based study.

BACKGROUND: With the improved survival of non-Hodgkin lymphoma (NHL) patients, development of second primary malignancy (SPM) has become an increasingly important issue in these long-term survivors. METHODS: We conducted a retrospective study to analyze NHL patients diagnosed between January 1997 and December 2010 in Taiwan. Standardized incidence ratios (SIRs) were applied to compare the risk of SPMs in NHL patients and the general population. Multivariate analysis was performed to determine the independent predictors of SPM. RESULT: NHL patients have a significantly greater risk of developing SPM [SIR 1.43; 95 % confidence interval (CI) 1.32-1.55; p < 0.001). A significantly high SIR was noted for leukemia, myeloma, and neoplasms of the bone and soft tissue, thyroid, central nervous system, skin, stomach, head and neck, liver and biliary tract, and the lungs and mediastinum. Multivariate analysis revealed that age ≥60 years [hazard ratios (HR) 2.04], being male (HR 1.22), comorbidities of chronic obstructive pulmonary disease (HR 1.34), liver cirrhosis (HR 1.50), hepatitis C infection (HR 1.94) and therapy containing radiotherapy (HR 1.38) were the significant predictors for SPM occurrence. The median follow-up time and survival time were 3.37 and 9.45 years, respectively. CONCLUSION: This Taiwanese population-based study provides updated data about the risk of SPM in NHL patients, demonstrating an approximately 1.5 time greater risk of SPM compared to the general population. A high risk of SPM for myeloma and hepatocellular carcinoma is unique to Asian patients.

Secondary primary malignancy risk among patients with esophageal cancer in Taiwan: a nationwide population-based study.

BACKGROUND: To evaluate the risk and sites of metachronous secondary primary malignancies (SPMs) among patients with esophageal cancer. METHODS: Newly diagnosed esophageal cancer patients between 1997 and 2011 were recruited. To avoid surveillance bias, SPMs that developed within one year were excluded. Standardized incidence ratios (SIRs) of metachronous SPMs in these patients were calculated by comparing to the cancer incidence in the general population. Risk factors for SPM development, included age, sex, comorbidities and cancer-related treatments, were estimated by Cox proportional hazards models. RESULTS: During the 15-year study period, 870 SPMs developed among 18,026 esophageal cancer patients, with a follow-up of 27,056 person-years. The SIR for all cancers was 3.53. The SIR of follow-up period ≥ 10 years was 3.56; 5-10 years, 3.14; and 1-5 years, 3.06. The cancer SIRs of head and neck (15.83), stomach (3.30), lung and mediastinum (2.10), kidney (2.24) and leukemia (2.72), were significantly increased. Multivariate analysis showed that age ≥ 60 years (hazard ratio [HR] 0.74), being male (HR 1.46) and liver cirrhosis (HR 1.46) were independent factors. According to the treatments, major surgery (HR 1.24) increased the risk, but chemotherapy was nearly significant. CONCLUSIONS: Patients with esophageal cancer were at increased risk of developing metachronous SPMs. The SIR remained high in follow-up > 10 years, so that close monitoring may be needed for early detection of SPM among these esophageal cancer patients.