Hepatic Arterial Infusion Chemotherapy Followed by Lipiodol Infusion for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Single-Center Experience.

Background and Objectives: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) followed by lipiodol infusion in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Materials and Methods: Thirty-two patients with advanced HCC and PVTT who received HAIC with regimens of cisplatin, mitomycin-C, and 5-fluorouracil followed by lipiodol infusion were enrolled. The primary efficacy endpoint was tumor response rate. The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was used for assessment of treatment response. The secondary endpoints were overall survival (OS) and progression free survival (PFS). Prognostic factors for survival also were evaluated. Results: The median OS and PFS were 11.9 and 9.5 months, respectively. Seventeen patients (53.1%) achieved objective response, and 23 patients (71.9%) achieved disease control. The length of survival in the responder and disease control groups was longer than in the non-responder and progressive disease groups after two cycles of HAIC (responder vs. non-responder: 16.5 vs. 7.9 months, p = 0.001; disease control vs. progressive disease: 12.3 vs. 5.6 months, p < 0.001) and after completing HAIC (responder vs. non-responder: 15.7 vs. 6.9 months, p = 0.001; disease control vs. progressive disease: 13.6 vs. 6.9 months, p < 0.001). Better survival was associated with Child-Pugh A liver function (p = 0.013), with early response to two HAIC cycles (p = 0.009), and with response (p = 0.02) and disease control (p = 0.001) after completing HAIC treatment. Conclusion: HAIC followed by lipiodol infusion is a safe and feasible treatment for advanced HCC with PVTT. Patients with early response could continue HAIC treatment with expected prolonged survival.

Glutamine in Alleviation of Radiation-Induced Severe Oral Mucositis: A Meta-Analysis.

The aim of this meta-analysis was to assess the effectiveness of glutamine to treat severe mucositis induced by radiation therapy in patients with head and neck cancer. We undertook electronic searches of PubMed (1990 to January 2015), Embase (1990 to January 2015), and the Cochrane Library (2013, Issue 2) to identify relevant studies. We included randomized controlled trials of glutamine to alleviate oral mucositis (OM) in patients with head and neck cancer who received radiotherapy. Information regarding methods, patients, results, and risk of bias was independently extracted by two authors. Statistical analyses were conducted to calculate the odds ratio and 95% confidence intervals (95%CIs) using fixed-effect models. We identified five clinical studies that included 234 patients with head and neck cancer. All studies were assessed as being at low risk of bias in most items of six domains. In this meta-analysis, glutamine treatment showed a statistically significant benefit with respect to reducing the risk and severity of OM induced by radiotherapy compared to either placebo or no treatment (risk ratio 0.17, 95%CI 0.06-0.47). Overall, glutamine significantly reduces the risk and severity of OM during radiotherapy or chemotherapy. Further prospective and large trials are required to support the findings.

Hypothyroidism and hyperthyroidism related to gynecologic cancers: a nationwide population-based cohort study.

The purpose of this study was to assess the risks of hyperthyroidism and hypothyroidism related to gynecological cancers. Population-based retrospective cohort study. We conducted a cohort study using the Taiwan National Health Insurance Research Database to explore hyperthyroidism and hypothyroidism associated with site-specific gynecologic cancers in women from January 1, 2000 to December 31, 2018. The examined gynecologic cancers included endometrial (EC), uterine corpus cancer (UC), and ovarian cancer (OC). The incidence and hazard ratios were quantified using Cox proportional hazards models. The incidence of developing gynecological (Gyn) cancers in the hyperthyroid and hypothyroid women was 0.29 and 0.44 per 1000 person-years, which was 0.86 fold lower and 1.13 fold higher than that in the comparison cohort (p < 0.001). Compared with patients aged 20-40 years, patients in older age groups had a lower and higher risk of developing Gyn cancers (for hyperthyroid, 40-65 years: adjusted hazard ratio (aHR) = 0.82; > 65 years: aHR = 0.94; for hypothyroid, adjusted hazard ratio (aHR) = 1.26; > 65 years: aHR = 1.38). Compared with the non-hypothyroid women and non-hyperthyroid women beyond 6 years of follow-up, hypothyroid and hyperthyroid women showed decreased risk of Gyn cancers. Medication treatment for hyperthyroid and hypothyroid disease did not showed significant association in subgroup analyses (aHR = 0.99 and 0.80, respectively). Our results show that women with hyperthyroidism have a significantly reduced risk of gynecological cancers, whereas women with hypothyroidism have a slightly increased risk of gynecological cancers suggesting an association between thyroid function level and risk of gynecological cancers.

Comparative efficacy and safety of multimodality treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus: patient-level network meta-analysis.

Background: Portal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global consensus or standard guidelines on the management of hepatocellular carcinoma (HCC) with PVTT. Increasing evidence suggests that more aggressive treatment modalities, including transarterial chemoembolization, radiotherapy, targeted therapy, and various combination therapies, may improve the prognosis and prolong the survival of advanced hepatocellular carcinoma (aHCC) patients with PVTT. We aim to comprehensively review and compare the efficacy and safety of these advanced options for aHCC with PVTT. Methods: A comprehensive literature search was conducted on PubMed and EMBASE for phase II or III randomized controlled trials (RCTs) investigating multimodality treatments for aHCC with PVTT. Kaplan-Meier curves for overall survival (OS) and progression-free survival were constructed to retrieve individual patient-level data to strengthen the comparison of the benefits of all multimodality treatments of interest. Each study was pooled in a fixed-effects network meta-analysis (NMA). We also conducted subgroup analyses using risk ratios extracted from each study, including viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion or portal vein tumor thrombosis, and extrahepatic spread. Multimodality treatments were ranked using SUCRA scores. Results: We identified 15 randomized controlled trials with 16 multimodality regimens that met the inclusion criteria. Among them, 5,236 patients with OS results and 5,160 patients with PFS results were included in the analysis. The hepatic arterial infusion chemotherapy of fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) showed OS and PFS benefits over all the other therapies. In terms of OS, HAIC-FO, nivolumab, and TACE+Len were superior to sorafenib, lenvatinib, and donatinib monotherapies, as well as HAIC-FO+Sor. In terms of PFS, TACE+Len showed better benefits than lenvatinib, donatinib, and tremelimumab+durvalumab. A low heterogeneity (I 2 < 50%) and consistency were observed. The SUCRA score for OS ranked HAIC-FO+sorafenib as the best treatment option among all multimodality treatments in hepatitis B, MVI, or PVTT with EHS and AFP 400 µg/L subgroups. Conclusion: HAIC-FO and HAIC-FO+sorafenib are statistically better options for unresectable hepatocellular carcinoma with PVTT among the multimodality treatments, and their effective and safe implementation may provide the best outcomes for HCC-PVTT patients.

Comparison of target agent treatment strategies for platinum-resistant recurrent ovarian cancer: A Bayesian network meta-analysis.

BACKGROUND: We aimed to compare 7 newer immunotherapies and targeted therapies for platinum-resistant relapsed ovarian cancer. METHODS: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library electronic databases for phase III trials involving platinum-resistant recurrent ovarian cancer (PRrOC) patients treated with immunotherapy or targeted therapy in combination with chemotherapy. The quality of the included trials was assessed using the GRADE method. The primary outcome of comparison was progression-free survival, and secondary outcomes included overall survival and safety. RESULTS: This analysis included 7 randomized phase III controlled trials, encompassing 2485 PRrOC patients. Combining bevacizumab plus chemotherapy and lurbinectedin demonstrated statistically significant differences in progression-free survival compared to all other regimens of interest. However, no statistically significant differences were observed in the overall survival. Nivolumab and mirvetuximab exhibited fewer serious adverse events than the other regimens of interest. CONCLUSIONS: Our findings indicate that bevacizumab combined with chemotherapy and lurbinectedin monotherapy has significant efficacy in patients with PRrOC. For patients with PRrOC who have exhausted treatment options, nivolumab and mirvetuximab may be considered as alternatives because of their better safety profiles.

Systematic review and quality assessment of cost-effectiveness analysis of pharmaceutical therapies for advanced colorectal cancer.

OBJECTIVE: To systematically review and assess the quality of cost-effectiveness analyses (CEAs) of pharmaceutical therapies for metastatic colorectal cancer (mCRC). DATA SOURCES: The MEDLINE, EMBASE, Cochrane, and EconLit databases were searched for the Medical Subject Headings or text key words quality-adjusted, QALY, life-year gained (LYG), and cost-effectiveness (January 1, 1999-December 31, 2009). STUDY SELECTION: Original CEAs of mCRC pharmacotherapy published in English were included. CEAs that measured health effects in units other than quality-adjusted life years or LYG and letters to the editor, case reports, posters, and editorials were excluded. DATA EXTRACTION: Each article was independently assessed by 2 trained reviewers according to a quality checklist created by the Panel on Cost-Effectiveness in Health and Medicine. RESULTS: Twenty-four CEA studies pertaining to pharmaceutical therapies for mCRC were identified. All studies showed a wide variation in methodologic approaches, which resulted in a different range of incremental cost-effectiveness ratios reported for each regimen. We found common methodologic flaws in a significant number of CEA studies, including lack of clear description for critique of data quality; lack of method for adjusting costs for inflation and methods for obtaining expert judgment; no results of model validation; wide differences in the types of perspective, time horizon, study design, cost categories, and effect outcomes; and no quality assessment of data (cost and effectiveness) for the interventions evaluation. CONCLUSIONS: This study has shown a wide variation in the methodology and quality of cost-effectiveness analysis for mCRC. Improving quality and harmonization of CEA for cancer treatment is needed. Further study is suggested to assess the quality of CEA methodology outside the mCRC disease state.

Multivitamin supplement use and risk of breast cancer: a meta-analysis.

BACKGROUND: The association between consumption of multivitamins and breast cancer is inconsistent in epidemiologic studies. OBJECTIVE: To perform a meta-analysis of cohort and case-control studies to evaluate multivitamin intake and its relationship with breast cancer risk. METHODS: The published literature was systematically searched and reviewed using MEDLINE (1950 through July 2010), EMBASE (1980 through July 2010), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010 issue 1). Studies that included specific risk estimates were pooled using a random-effects model. The bias and quality of these studies were assessed with REVMAN statistical software (version 5.0) and the GRADE method of the Cochrane Collaboration. RESULTS: Eight of 27 studies that included 355,080 subjects were available for analysis. The total duration of multivitamin use in these trials ranged from 3 to 10 years. The frequency of current use in these studies ranged from 2 to 6 times/week. In analyses by duration of use 10 years or longer or 3 years or longer and by frequency 7 or more times/week that were reported in these studies, multivitamin use was not significantly associated with the risk of breast cancer. Only 1 recent Swedish cohort study concluded that multivitamin use is associated with an increased risk of breast cancer. The results of a meta-analysis that pooled data from 5 cohort studies and 3 case-control studies indicated that the overall multivariable relative risk and odds ratio were 0.10 (95% CI 0.60 to 1.63; p = 0.98) and 1.00 (95% CI 0.51 to 1.00; p = 1.00), respectively. The association was not statistically significant. CONCLUSIONS: Multivitamin use is likely not associated with a significant increased or decreased risk of breast cancer, but these results highlight the need for more case-control studies or randomized controlled clinical trials to further examine this relationship.

Efficacy and safety of CDK4/6 and PI3K/AKT/mTOR inhibitors as second-line treatment in postmenopausal patients with hormone receptor-positive, HER-2-negative metastatic breast cancer: a network meta-analysis.

BACKGROUND: We compared the efficacy and safety of combinations of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and PI3K/AKT/mTOR inhibitors as second-line treatment in postmenopausal women with HR+, HER2- metastatic breast cancer. METHODS: We searched the Medline, Embase, and Cochrane Library electronic databases for phase II/III randomized trials evaluating CDK4/6 and PI3K/AKT/mTOR inhibitors plus fulvestrant. We compared the results with a network meta-analysis. Study quality was assessed following the GRADE approach. Outcomes of interest were progression-free survival, overall response rate, overall survival and G3-4 adverse drug events (ADEs). RESULTS: Eight RCTs were identified in the network meta-analysis. PFS was significantly improved by treatment with abemaciclib plus fulvestrant and ribociclib plus fulvestrant compared to pictilisib plus fulvestrant. The ORR following treatment with abemaciclib plus fulvestrant, ribociclib plus fulvestrant, palbociclib plus fulvestrant, buparlisib plus fulvestrant, and alpelisib plus fulvestrant significantly differed from that observed following treatment with placebo plus fulvestrant. In terms of OS, compared with placebo plus fulvestrant, abemaciclib plus fulvestrant, ribociclib plus fulvestrant, and buparlisib plus fulvestrant had a significant difference. The risks of ADEs were similar among three CDK4/6 inhibitors. CONCLUSION: As second-line treatment, three CDK4/6 inhibitors showed superior clinical efficacy compared to other PI3K/AKT/mTOR inhibitors with comparable safety profiles.

Reliability of 95% confidence interval revealed by expected quality-of-life scores: an example of nasopharyngeal carcinoma patients after radiotherapy using EORTC QLQ-C 30.

BACKGROUND: Many researchers use observed questionnaire scores to evaluate score reliability and to make conclusions and inferences regarding quality-of-life outcomes. The amount of false alarms from medical diagnoses that would be avoided if observed scores were substituted with expected scores is interesting, and understanding these differences is important for the care of cancer patients. Using expected scores to estimate the reliability of 95% confidence intervals (CIs) is rarely reported in published papers. We investigated the reliability of patient responses to a quality-of-life questionnaire and made recommendations for future studies of the quality of life of patients. METHODS: A total of 115 patients completed the EORTC core questionnaire QLQ-C30 (version 3) after radiotherapy. The observed response scores, assumed to be one-dimensional, were summed and transformed into expected scores using the Rasch rating scale model with WINSTEPS software. A series of simulations was performed using a unified bootstrap procedure after manipulating scenarios with different questionnaire lengths and patient numbers to estimate the reliability at 95% confidence intervals. Skewness analyses of the 95% CIs were compared to detect different effects between groups according to the two data sets of observed and expected response scores. RESULTS: We found that (1) it is necessary to report CIs for reliability and skewness coefficients in papers; (2) data derived from expected response scores are preferable to making inferences; and (3) visual representations displaying the 95% CIs of skewness values applied to item-by-item analyses can provide a useful interpretation of quality-of-life outcomes. CONCLUSION: Reliability coefficients can be reported with 95% CIs by statistical software to evaluate the internal consistency of respondent scores on questionnaire items. The SPSS syntax procedures for estimating the reliability of the 95% CI, expected score generation and visual skewness analyses are demonstrated in this study. We recommend that effect sizes such as a 95% CI be reported along with p values reporting significant differences in quality-of-life studies.

Cost-effectiveness of trastuzumab as adjuvant therapy for early breast cancer: a systematic review.

OBJECTIVE: To identify published, original, cost-effectiveness analyses presenting cost/quality-adjusted life year (QALY) ratios for trastuzumab used as an adjuvant treatment for HER2-positive early breast cancer and to evaluate the quality of reporting the favorable cost-effectiveness ratios. DATA SOURCES: The terms trastuzumab adjuvant therapy, cost-effectiveness, quality-adjusted, QALY, and early breast cancer were searched in MEDLINE, PubMed, Embase, and CancerLit, as well as in Cochrane economic evaluation and reference lists from 1998 to June 2008. Only English-language publications were eligible. STUDY SELECTION AND DATA EXTRACTION: All published studies examining cost-effectiveness outcomes on the basis of modeling or clinical trials were included. Cost-effectiveness analysis that measured health effects in units other than QALY, life year gained, neoadjuvant data, reviews, and comments were excluded. Each study was assessed independently by 2 trained reviewers. DATA SYNTHESIS: Thirteen of the 239 articles identified met the inclusion criteria, with 23 cost-effectiveness ratios pertaining to treatment of early breast cancer. These ratios ranged from $5020/QALY to $134,610/QALY. Most studies reported favorable cost-effectiveness values (ie, below $50,000/QALY). About 84.6% were conducted using a Markov model based on data from clinical trials and 15.3% were analyzed by other economic or cost models; 84.6% reported sensitivity analysis, 11 studies (84.6%) clearly described a justification of selecting study design, and only 15.3% noted study limitations. All studies mentioned their perspective; 92.3% did not show the funding source. Methods of reporting costs, effectiveness, and time-horizons for disease states varied significantly. Nine (69.2%) studies used a discount rate of 3%, 3 studies used a discount rate of 5%, and 1 study used 3.5%. The mean quality of the studies was 4.43. CONCLUSIONS: Most studies presenting the frequently proposed threshold of QALY suggest that trastuzumab may be cost-effective for treatment of early breast cancer in a 1-year treatment regimen.

P38-associated pathway involvement in apoptosis induced by photodynamic therapy with Lonicera japonica in human lung squamous carcinoma CH27 cells.

Photodynamic therapy (PDT) is an effective therapy for local malignant tumors. Lonicera japonica was found to have the anti-tumor effect. The aim of this study is to explore the mechanisms of apoptosis induced by PDT in lung CH27 carcinoma cells with alcohol extract from Lonicera japonica as photosensitizer. Our study indicated that Lonicera japonica extracts exhibited significant photocytotoxicity in CH27 cells at a concentration range of 50-150 microg/ml, with 0.4-1.2J/cm2 light dose. PDT with Lonicera japonica extracts-induced cell death is a typical apoptosis that was accompanied by DNA condensation, externalization of phosphatidylserine and formation of apoptotic bodies. PDT with Lonicera japonica extracts was shown to be caspase-3-independent apoptosis via activation of AIF in this study. P38-associated pathway may be involved in apoptosis induced by PDT with Lonicera japonica extracts in CH27 cells. We also have demonstrated that PDT with Lonicera japonica extracts-induced CH27 cells apoptosis was probably related to its ability to change the protein expression and distribution of heat shock protein 27.

Efficacy and safety of a combination of HER2-targeted agents as first-line treatment for metastatic HER2-positive breast cancer: a network meta-analysis.

BACKGROUND: Using network meta-analysis, we assessed the efficacy and safety of a combination regimen of HER2-targeted agents as first-line treatment for metastatic HER2-positive breast cancer. METHODS: We searched the Medline, Embase, and Cochrane Library electronic databases (through December 2016) for phase II/III randomized controlled trials that compared regimens of one or two HER2-targeted agents combined with trastuzumab or chemotherapy. A network meta-analysis including direct and indirect analyses was conducted in WinBUGS using fixed and random effects. Study quality was assessed following the Grading of Recommendations, Assessment, Development and Evaluations method. The primary outcome was overall survival. RESULTS: The network meta-analysis incorporated nine HER2-targeted regimens with 9 direct comparisons and 28 indirect comparisons for the main outcomes (8 studies; n = 3976). Combining direct and indirect effects showed significant increased efficacy of trastuzumab and docetaxel plus pertuzumab (TDP) over other regimens as first-line treatment. With indirect comparison of overall safety, TDP, TDM-1, and TDM-1 plus pertuzumab demonstrated a lower risk of grade 3-4 adverse events compared to other regimens. CONCLUSIONS: TDPs are a preferred first-line treatment for HER2-positive metastatic breast cancer compared with other target agent regimens.

Cost-effectiveness of pertuzumab combined with trastuzumab and docetaxel as a first-line treatment for HER-2 positive metastatic breast cancer.

OBJECTIVE: To provide perspective for the National Health Insurance Bureau (NHIB), we determined the cost-effectiveness of pertuzumab combined with trastuzumab and docetaxel (TDP) versus trastuzumab and docetaxel (TD) as a first-line treatment for HER-2 positive metastatic breast cancer. METHODS: We used a Markov model to simulate cost-effectiveness, disease progression, and survival, based on clinical data and transition probabilities extracted from the CLEOPATRA study. Direct medical costs were acquired from the NHIB claims database.The utilities in health state were based on a recent cost-effectiveness study on trastuzumab and pertuzumab. Outcomes included quality-adjusted life-years (QALYs), costs in New Taiwan dollars (NT$), and the incremental cost-effectiveness ratio (ICER). We performed one-way deterministic and probabilistic sensitivity analyses to assess the impact of specific parameters on the model. RESULTS: Modeled median survival was 39.1 months for TD and 50.1 months for TDP. The ICER was NT$18,999,687 (US$593,741) per QALY gained. The sensitivity analyses indicated that TDP could be cost-effective under favorable assumptions; TDP had a 68% chance of being cost-effective, if TDP costs could be reduced with 10% in the stable disease state. CONCLUSION: Our model predicted that TDP would be cost-effective as a first-line treatment for HER-2 positive metastatic breast cancer, but only under favorable drug cost assumptions.

Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis.

Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor. The 12-LOX is found to be involved in the progression of human cancers and the inhibitor of 12-LOX offers a target for the prevention cancer. We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. Treatment of baicalein inhibited the growth of H460 cells in a dose-dependent manner. Following 24h exposure to 50muM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Furthermore, baicalein induced the most of H460 cell apoptosis after treatment for 48h. H460 cells formed vesicles and apoptotic body, and then floated after treatment with baicalein. Baicalein-induced H460 cell apoptosis was confirmed by DNA condensation and fragmentation. Baicalein-induced apoptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels. Pretreatment with a specific caspase-3 inhibitor, Ac-DEVD-CHO, partially reduced baicalein-induced cell death, indicating baicalein induces apoptosis is partially dependent on caspase-3 pathway in H460 cells. These data suggest that baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins.

Kaempferol induces apoptosis in human lung non-small carcinoma cells accompanied by an induction of antioxidant enzymes.

Kaempferol (3, 4',5,7-tetrahydroxyflavone) is one of the most commonly found dietary flavonols. The biological and pharmacological effects of kaempferol may depend upon its behavior as either an antioxidant or a prooxidant. However, the clear biological effects of prooxidant or antioxidant character of kaempferol has not been clarified yet. The overall objective of the present study is to explore the role of prooxidant or antioxidant in kaempferol-induced cell toxicity. In this paper, we have proved that antioxidant pathway may be involved in kaempferol induces H460 cell apoptosis. Kaempferol-induced H460 cell apoptosis is a typical apoptosis that was accompanied by a significant DNA condensation and increasing intracellular ATP levels. Kaempferol-induced apoptosis is related to its ability to change the expression of apoptotic markers, such as caspase-3 (caspase-dependent) and AIF (caspase-independent). The overexpression of antioxidant enzyme Mn SOD protein levels, which was promoted to a new type tumor suppressor gene in several human cancer cells recently, may be an important role in kaempferol-induced H460 cell apoptosis.

Interaction between traditional Chinese medicine and Western medicine in rats--In-Chen-How and acetaminophen.

The purpose of this study is to evaluate the interaction effects of In-Chen-How (Artemisia capillaries Thunb.) on the pharmacokinetics of acetaminophen and on liver microsomal cytochrome P450 enzyme activity in rats. The rats were divided into control group (n = 8) without In-Chen-How and the pretreated group (n = 8) administered with In-Chen-How (approximately 1.0 mL x kg(-1), according to weight) for 5 consecutive days. Rats in the control group received water simultaneously. Each rat was then given acetaminophen. The pharmacokinetic parameters of acetaminophen of the two groups were significantly different. In the In-Chen-How pretreated group, the maximum concentration of acetaminophen and the area under the plasma concentration-time curve were reduced about 58.4%, 56.7% and 55.4%. To further explain the results, liver microsomal suspensions were obtained from rats that were randomly divided into control and In-Chen-How pretreated group. The levels of CYP1A2 and CYP2E1 in hepatic microsomal protein from pretreated group were increased as compared to that from the control group. It indicated that In-Chen-How can stimulate the activity of CYP isozymes. The changes in the pharmacokinetics of acetaminophen resulting from the administration of In-Chen-How are related to an increase in metabolic activity of CYP1A2 and CYP2E1.

Cost-utility of stereotactic radiation therapy versus proton beam therapy for inoperable advanced hepatocellular carcinoma.

The cost-utility of proton beam therapy was compared to stereotactic body radiation therapy for inoperable advanced hepatocellular carcinoma. A Markov decision-analytic model was performed following time to progression and survival using phase II trial data. Patients transitioned between three health states. Clinical outcomes were estimated for quality of life using utility estimates in the published literature and measured as incremental cost-effectiveness ratios (ICERs) and net monetary benefits (NMBs). Real direct medical costs were extracted from the Bureau of National Health Insurance database. One-way and probabilistic sensitivity analyses assessed the impact of specific variables on the model. In the base-case scenario, the modeled median survival was 16 months for proton beam therapy and 10 months for SBRT. Proton beam therapy resulted in an additional 2.61 quality-adjusted life years (QALYs) at an incremental cost of NT$ 557,907 compared to SBRT. The ICER was NT$ 213,354 per QALY gained. The probabilistic sensitivity analysis predicted a 97 % chance of proton beam therapy being cost-effective at the willingness to pay NT$2,157,024 per QALY gained. Thus, proton beam therapy is a cost-effective therapy for inoperable advanced hepatocellular carcinoma at the willingness-to-pay threshold of Taiwan.

Late cardiac morbidity of adjuvant radiotherapy for early breast cancer - A population-based study.

PURPOSE: The purpose of this study was to assess the long-term cardiac morbidity and mortality after breast irradiation using contemporary irradiation techniques. METHODS: We used the Catastrophic Illness dataset from the National Health Insurance Research Database to explore the possible association between late cardiotoxicity and women with early breast cancer treated with breast conservation therapy from 2000 to 2010. The Cox proportional-hazards model was used to compare breast cancer patients who received adjuvant radiotherapy versus without adjuvant radiotherapy for the end points with the following primary diagnoses (International Classification of Diseases, 9th Revision codes): ischemic heart disease (410-414, 36.0, 36.1), valvular heart disease (394-397, 424, 35), congestive heart failure (428, 402.01, 402.11, 402.91), and conduction abnormalities (426, 37.7-37.8, 37.94-37.99). RESULTS: Three hundred and thirty patients received adjuvant radiotherapy and 4802 patients did not receive radiotherapy. Median follow-up was 3.5 years. There was no difference in overall morbidity and mortality from any cardiac cause (p=0.13) in breast cancer patients who received adjuvant radiotherapy versus without radiotherapy by using modern radiotherapy techniques. CONCLUSION: There were no significant differences in cardiac morbidity and mortality after radiotherapy for breast cancer with a 9-year follow-up period in our population.

Cost-effectiveness of Gemcitabine Plus Modern Radiotherapy in Locally Advanced Pancreatic Cancer.

PURPOSE: The purpose of this study was to evaluate the cost-effectiveness of gemcitabine plus modern radiotherapy versus gemcitabine alone in the treatment of locally advanced pancreatic cancer in Taiwan. METHODS: A Markov decision-analytic model was performed to compare the cost-effectiveness of 3 treatment regimens; gemcitabine alone (gem-alone), gemcitabine plus intensity-modulated radiotherapy (gem-IMRT), and gemcitabine plus stereotactic body radiotherapy (gem-SBRT). Patients transitioned between 5 health states: stable disease, local progression, distant metastasis, local and distant metastasis, and death. FINDINGS: The incremental cost-effectiveness ratio for gem-IMRT and gem-SBRT compared with gem-alone were NT$27,120,168 and NT$2,145,683 per quality-adjusted life-year gained, respectively. A willingness to pay threshold of 3 times the per capita gross domestic product was adopted according to the definition of the World Health Organization. The Taiwan per capita gross domestic product in 2015 was NT$673,920 (US$22,464; 1 NT$ = US$0.03333 in Taiwan); thus, a threshold was considered as NT$2,021,760 (US$67,392). The Monte-Carlo simulation found that the probability of cost-effectiveness at a willingness to pay threshold of NT$2,021,760 per quality-adjusted life-year was 0% chance for gem-IMRT and 50% for gem-SBRT. IMPLICATIONS: This study indicated that gem-IMRT or gem-SBRT in locally advanced pancreatic cancer is not cost-effective at a willingness to pay as defined by World Health Organization guideline in Taiwan.

Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. METHODS: A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. RESULTS: The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO's guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. CONCLUSION: This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan.