Quality of life and cost-utility of surgical treatment for patients with spinal metastases: prospective cohort study.

PURPOSE: Palliative surgery for patients with spinal metastasis provides good clinical outcomes. However, there have been few studies on quality of life (QOL) and cost-utility of this surgery. We aimed to elucidate QOL and cost-utility of surgical treatment for spinal metastasis. METHODS: We prospectively analyzed 47 patients with spinal metastasis from 2010 to 2014 who had a surgical indication. Thirty-one patients who desired surgery underwent spinal surgery (surgery group). Sixteen patients who did not want to undergo spinal surgery (non-surgery group). The EuroQol 5D (EQ-5D) and relevant costs were measured at one, three, six, and 12 months after study enrollment. Health state values were obtained by Japanese EQ-5D scoring and quality-adjusted life years (QALY) gained were calculated for each group. Cost-utility was expressed as the incremental cost-utility ratio (ICUR). RESULTS: Health state values improved from 0.036 at study enrollment to 0.448 at 12 months in the surgery group, but deteriorated from 0.056 to 0.019 in the non-surgery group, with a significant difference between groups (P < 0.05). The mean QALY gained at 12 months were 0.433 in the surgery group and 0.024 in the non-surgery group. The mean total cost per patient in the surgery group was $25,770 compared with $8615 in the non-surgery group. The ICUR using oneyear follow-up data was $42,003/QALY gained. CONCLUSIONS: Surgical treatment for spinal metastases is associated with significant improvement in health state value. In orthopaedic surgery, an ICUR less than $50,000/QALY gained is considered acceptable cost-effectiveness. Our results indicate that surgical treatment could be cost-effective.

Barriers and challenges to global clinical cancer research.

BACKGROUND: There are concerns about growing barriers to cancer research. We explored the characteristics of and barriers to global clinical cancer research. METHODS: The American Society of Clinical Oncology International Affairs Committee invited 300 selected oncologists with research experience from 25 countries to complete a Web-based survey. Fisher's exact test was used to compare answers between participants from high-income countries (HICs) and low- and middle-income countries (LMICs). Barriers to clinical cancer research were ranked from 1 (most important) to 8 (least important). Mann-Whitney's nonparametric test was used to compare the ranks describing the importance of investigated obstacles. RESULTS: Eighty oncologists responded, 41 from HICs and 39 from LMICs. Most responders were medical oncologists (62%) at academic hospitals (90%). Researchers from HICs were more involved with academic and industry-driven research than were researchers from LMICs. Significantly higher proportions of those who considered their ability to conduct academic research and industry-driven research over the past 5 years more difficult were from HICs (73% vs. 27% and 70% vs. 30%, respectively). Concerning academic clinical cancer research, a lack of funding was ranked the most important (score: 3.16) barrier, without significant differences observed between HICs and LMICs. Lack of time or competing priorities and procedures from competent authorities were the second most important barriers to conducting academic clinical research in HICs and LMICs, respectively. CONCLUSION: Lack of funding, lack of time and competing priorities, and procedures from competent authorities might be the main global barriers to academic clinical cancer research.

[Proposal of a novel dosing schedule of docetaxel by using alpha1-acid glycoprotein as an index].

This study was aimed to propose a novel dosing schedule of docetaxel based on alpha(1)-acid glycoprotein (AGP)as an index. For this purpose, we performed Monte Carlo simulation using a population pharmacokinetic/pharmacodynamic (PPK/PPD) model, which we previously developed to estimate the ANC Nadir distribution after docetaxel administration. AGP values, which were incorporated in PPK/PPD, were sampled from normal distributions (S.D. 44, range from 19 to 259), as various mean levels of 125, 150, 175 and 200 (mg/dl). Monte Carlo simulation was conducted using docetaxel doses of 40, 50 and 60 (mg/m(2)) for each AGP distribution. Simulation was performed 200 times, and distributions of ANC Nadir median were obtained from simulations. We accepted a dose when 20 percentile of the distribution of ANC Nadir median was greater than 500 (counts/microl), in order to avoid the grade 4 neutropenia. From the results of simulations, 40, 50, 60 and 60 doses (mg/m(2)) were recommended for 125, 150, 175, and 200 AGP mean (mg/dl) respectively. Secondly, to evaluate this dosing schedule, we adopted these recommended doses to 16 patients whose ANC Nadir observed is lesser than 500, and simulated the ANC Nadir. The number of patients whose simulated time below ANC=500 was higher than 6 days decreased from 8 to 2, implying that this dosing schedule might be effective to avoid neutropenia induced by docetaxel. In conclusion, we proposed a novel dosing schedule of docetaxel using AGP as an index, which might be effective to avoid neutropenia induced by docetaxel.

Clinical trial simulations for dosage optimization of docetaxel in patients with liver dysfunction, based on a log-binominal regression for febrile neutropenia.

This study was aimed to perform clinical trial simulations to evaluate the dose reduction strategy of docetaxel for Japanese patients with liver dysfunction, which we previously proposed. For this purpose, a log-binominal regression (LBR) was performed for febrile neutropenia (FN) induced by docetaxel in these patients. A LBR analysis was conducted using clinical data from cancer patients treated with docetaxel and incorporated in the subsequent trial simulation. Virtual patients with liver dysfunction were randomly assigned to receive the Japanese standard dose (60 mg/m(2)) or reduced dose (40 or 50 mg/m(2)) of docetaxel. The primary endpoint was overall survival of the reduced dose to the standard dose. The secondary endpoint was the number of patients who experienced FN in response to the two treatment regimens. From the LBR analysis, the performance status and the area under the plasma concentration-time curve (AUC) were selected as covariates associated significantly (p<0.05) with FN occurrence. From the results of the present trial simulation, the median proportion of patients who experienced FN was decreased by about 20% in the reduced dose arm. Non-inferiority criteria, the reduced dose group to the standard dose group were met in 85.5% of the simulated clinical trials with a decrease in the FN frequency. In conclusion, clinical trial simulation models for the efficacy (survival) and toxicity (FN) was first performed in Japanese patients, and the feasibility of docetaxel therapy for liver-dysfunction patients under the dose reduction strategy was supported.