Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study.

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.

Safety and efficacy of nilotinib in routine clinical practice in patients with chronic myeloid leukemia in chronic or accelerated phase with resistance or intolerance to imatinib: results from the NOVEL study.

BACKGROUND: Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), is approved for the treatment of patients with chronic myeloid leukemia (CML) in many countries, including Taiwan. Though a number of controlled clinical trials have demonstrated the safety and efficacy of nilotinib, studies assessing the safety and efficacy of nilotinib in routine clinical practice are limited. METHODS: The current study was an open-label, single-arm study conducted across 12 centers in Taiwan in adult patients with CML in chronic or accelerated phase with confirmed Ph+ chromosome (or BCR-ABL) and resistant or intolerant to one or more previous TKIs. The primary objective was to collect the long-term safety data in patients treated with nilotinib 400 mg, twice daily for up to 2 years. RESULTS: The study enrolled 85 patients with CML, including 76 in the chronic phase (CML-CP) and 9 in the accelerated phase (CML-AP). Overall, 1166 adverse events (AEs) were reported in 80 patients (94.1%), of which 70 AEs (6%) in 28 patients (32.9%) were serious and 336 AEs (28.8%) reported in 60 patients (70.6%) were drug-related. Common drug-related AEs were thrombocytopenia (21.2%), increased alanine aminotransferase (21.2%) and pruritus (17.7%). Of the 85 patients, 19 switched from imatinib due to intolerance - AEs were resolved in 16 of these 19 patients (84.2%). By 24 months, the cumulative rates of complete cytogenetic response (CCyR), major molecular response (MMR), MR4.0 (BCR-ABL1IS ⩽0.01%) and MR4.5 (BCR-ABL1IS ⩽0.0032%) were 75.3, 56.8, 16.2 and 7.4%, respectively. Patients with CML-CP at baseline had higher overall survival (OS) and progression-free survival (PFS) than those with CML-AP. CONCLUSION: This is the first study that demonstrated that nilotinib is effective and well-tolerated in patients resistant or intolerant to imatinib in the real-world setting in Taiwan, reflecting effective management of CML by physicians under routine clinical practice in Taiwan.

[Effect of ditching for drain on control of Oncomelania hupensis snail in beaches of Dongting Lake].

OBJECTIVE: To evaluate the effect of ditching for drain on the control of the breed of Oncomelania hupensis snails in beaches of Dongting Lake. METHODS: From November, 2009 to November, 2012, an 0. hupensis snail infested beach of the Yueyang jail and an O. hupensis snail infested beach of Junshan District were selected as research fields in the eastern Dongting Lake area, and the former, as the intervention field, was performed with the ditching for drain by excavators and the latter, as the control field, was not. RESULTS: Before the project implemented, the average soil moisture contents on the beaches in dry seasons of the two fields were both about 35.56%. After the project implemented, in the intervention field, the average soil moisture content was 26.53% which was significantly lower than that (35.56%) in the control field (F = 6.53, P < 0.05). The underground water levels in different heights in the intervention field were lower than those in the control field (χ2 = 33.33, P < 0.05). Before the project implemented, the natural death rates of the snails were 0.98% and 0.89% in the two research fields respectively (P > 0.05), and after the project implemented (in 2012), no adult and young snails were found in the interventional field, but in the control field, the average densities of living snails and young snails were 29.37 snails/0.1 m2 and 213 ± 108.45 snails/0.1 m2 respectively. CONCLUSION: The intervention of ditching for drain can decrease the soil moisture contents quickly and change the ecological condition, therefore, can control the breed of O. hupensis snails in the beaches of Dongting Lake.

Emerging kinetics of BCR-ABL1 mutations and their effect on disease outcomes in chronic myeloid leukemia patients with imatinib failure.

Some chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitor (TKI) do not respond or relapse. BCR-ABL1 mutations are the principal cause of TKI resistance, but the kinetics of emerging mutations in CML patients treated with imatinib remain to be determined. To investigate the emergence dynamics of mutations and their effects on outcomes, we conducted a systematically longitudinal study of BCR-ABL1 mutation dynamics during TKI therapy. Seminested polymerase chain reaction followed by denaturing high-performance liquid chromatography with sequence confirmation were used to detect BCR-ABL1 mutations in 202 CML patients with imatinib resistance at different CML phases. We detected 68 mutations in 58 imatinib-failure patients. Mutations were present in 27.6% of patients who failed front-line imatinib therapy and in 68.1% with advanced disease. Mutations were not detected in patients before commencing imatinib treatment. Pyrosequencing was then used to quantitatively monitor the mutant levels sequentially and also traced back for their earlier appearance. The mutants differed in rapidity of emergence which appeared to arise in different time frame as well as in speed of rising mutant levels. In the 78 front-line imatinib-failure patients, mutation positive patients had significantly higher risk of disease progression or relapse and inferior progression-free survival compared to those without mutations (p=0.006). Our study demonstrates kinetics of different BCR-ABL1 mutant emergence and an association between BCR-ABL1 mutations and disease progression.

[Study on correlated factors and clinical features of fungal rhinosinusitis].

OBJECTIVE: To investigate the correlated factors and clinical features of fungal rhinosinusitis. METHODS: The clinical data of 110 patients with fungal rhinosinusitis treated by surgery and another group of 110 patients with chronic rhinosinusitis who were sampled randomly between January 1999 and June 2004 in our hospital were retrospectively compared. The correlated factors and the clinical features of fungal rhinosinusitis were investigated by using the multiple factor Logistic regression analysis and chi-square test. The pathological types of 110 fungal rhinosinusitis were classified by using Gomori methenamine silver staining which was special for fungi. RESULTS: The logistic regression predictive equation for fungal rhinosinusitis was : y = -8.713 + 0.496x1 + 4.575x2 + 1. 190x3 + 4.119x4 + 1.199x5 + 2. 698x6, P = exp (y)/[1 + exp(y)], in which the concomitant variables were course of the disease (x1), haem-nasal discharge (x2), headache (x3), calcified plaque in CT scan (x4), age (x5) and unilateral/bilateral sinus lesion (x6), respectively. The P value meant the probability of suffering fungal rhinosinusitis. Compared with chronic rhinosinusitis, the clinical features of fungal rhinosinusitis were female, over 40-year-old, course of disease < 3 years, headache, haem-nasal discharge, unilateral sinus lesion and calcified plaque in CT scan. Among the 110 patients with fungal rhinosinusitis, 34 cases were chronic invasive and 76 were non-invasive. CONCLUSIONS: The clinical features of fungal rhinosinusitis are significant for the diagnosis, and it can be predicted by using the suitable logistic predictable equation.