Isao Yokota

Feasibility and accuracy of computational robot-assisted partial nephrectomy planning by virtual partial nephrectomy analysis

To evaluate the feasibility and accuracy of virtual partial nephrectomy analysis, including a color‐coded three‐dimensional virtual surgical planning and a quantitative functional analysis, in predicting the surgical outcomes of robot‐assisted partial nephrectomy.

Prospective Study on the Incidence of Bone Metastasis (BM) and Skeletal-Related Events (SREs) in Patients (pts) with Stage IIIB and IV Lung Cancer—CSP-HOR 13

Background: Bone metastasis (BM) is a frequent complication in patients with advanced lung cancer and it causes skeletal-related events (SREs). Our study aim is to prospectively investigate the incidence of BM, incidence and types of SRE, and predictive factors of BM and SREs. Methods: Newly diagnosed, advanced non–small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC) patients were enrolled into the study. Patients were followed up every 4 weeks to monitor the development of SREs. Treatment for lung cancer was performed at the discretion of the investigator. Results: Two hundred seventy-four patients were enrolled in this study between April 2007 and December 2009 from 12 institutions. Patients included 77 cases of SCLC and 197 of NSCLC (stage IIIB/IV = 73/124). Median follow-up time was 13.8 months. The incidence of BM at initial diagnosis was 48% in stage IV NSCLC and 40% in extensive stage (ED)-SCLC. Forty-five percent of patients who developed BM had SREs consisting of pathologic fracture (4.7%), radiation to bone (15.3%), spinal cord compression (1.1%), and hypercalcemia (2.2%). Multivariate analysis revealed that factors predicting BM are stage IV, performance status 1 or greater and higher bone alkaline phosphatase in NSCLC patients, higher lactate dehydrogenase, and lower parathyroid hormone–related peptide in SCLC patients. Factors predicting SREs were stage IV, age 64 or younger, and lower albumin in NSCLC patients. Multivariate analysis of SRE was not performed for SCLC because of the small number of events. Conclusion: Predictive factors should be taken into consideration in future randomized studies evaluating BM and SREs.

Feasibility of multiparametric prostate magnetic resonance imaging in the detection of cancer distribution: histopathological correlation with prostatectomy specimens

Purpose To prevent overtreatment, it is very important to diagnose the precise distribution and characteristics of all cancer lesions, including small daughter tumors. The purpose of this study was to evaluate the efficacy of T2-weighted magnetic resonance imaging (T2W), diffusion-weighted magnetic resonance imaging (DWI), magnetic resonance spectroscopy (1H-MRS), and prostate biopsy (PBx) in the detection of intraprostatic cancer distribution. Methods All patients underwent T2W, DWI, 1H-MRS, and PBx followed by radical prostatectomy (RP). Individual prostates were divided into 12 segmental regions, each of which was examined for the presence or absence of malignancy on the basis of T2W, DWI, 1H-MRS, and PBx, respectively. These results were compared with the histopathological findings for RP specimens. Results We included 54 consecutive patients with biopsy-proven prostate cancer (mean age, 62.7 years; median prostate-specific antigen level, 5.7 ng/mL) in this study. We could detect cancer in 247 of 540 evaluable lesions. The area under the receiver operator characteristic curve analysis yielded a higher value for DWI (0.68) than for T2W (0.65), 1H-MRS (0.54), or PBx (0.56). In 180 cancerous regions of RP specimens with false-negative PBx results, T2W+DWI had the highest positive rate (53.3%) compared with that of each sequence alone, including T2W (45.6%), DWI (41.1%), and 1H-MRS (30.0%). Conclusions Multiparametric magnetic resonance imaging (T2W, 1H-MRS, DWI) enables the detection of prostate cancer distribution with reasonable sensitivity and specificity. T2W+DWI was particularly effective in detecting cancer distribution with false-negative PBx results.

Mevalonate pathway blockage enhances the efficacy of mTOR inhibitors with the activation of retinoblastoma protein in renal cell carcinoma

Renal cell carcinoma (RCC) is the most common malignancy of kidney and remains largely intractable once it recurs after resection. mTOR inhibitors have been one of the mainstays used against recurrent RCC; however, there has been a major problem of the resistance to mTOR inhibitors, and thus new combination treatments with mTOR inhibitors are required. We here retrospectively showed that regular use of antilipidemic drug statins could provide a longer progression free survival (PFS) in RCC patients prescribed with an mTOR inhibitor everolimus than without statins (median PFS, 7.5 months vs. 3.2 months, respectively; hazard ratio, 0.52; 95% CI, 0.22-1.11). In order to give a rationale for this finding, we used RCC cell lines and showed the combinatorial effects of an mTOR inhibitor with statins induced a robust activation of retinoblastoma protein, whose mechanisms were involved in statins-mediated hindrance of KRAS or Rac1 protein prenylation. Finally, statins treatment also enhanced the efficacy of an mTOR inhibitor in RCC xenograft models. Thus, we provide molecular and (pre)clinical data showing that statins use could be a drug repositioning for RCC patients to enhance the efficacy of mTOR inhibitors.

The correlation between the change of distal motor latency of the median nerve and the abundant A-waves in Guillain-Barré syndrome.

A-waves are intermediate components that are observed between the compound muscle action potential (CMAP) and the F-waves. We recently suggested that abundant A-waves in Guillain-Barre syndrome (GBS) can be a novel marker of demyelination because they were strongly correlated with the acute inflammatory demyelinating polyneuropathy (AIDP) subtype and the absence of anti-glycolipid antibodies.1 Hiraga et al 2 reported that patients with AIDP without anti-ganglioside antibodies showed progressive prolongation of the distal motor latency (DML) of the median nerve, whereas the DML of patients with AIDP with anti-ganglioside antibodies may initially be prolonged but rapidly return to normal, suggesting an essentially axonal pathology. These results imply the possibility that the time course of DML of the median nerve (median DML) can be used as another marker of demyelination. In this report, we reanalysed the data collected in our previous study1 and compared the A-waves with other parameters, using the time course of the median DML as a gold standard. The data of 30 patients with GBS (21 men and 9 women, 43.7±19.5 years old) were reanalysed. The abundant A-waves were defined as three or more identifiable peaks between the CMAP and F-waves, observed in the median or ulnar nerves at least once during weeks 3–6 from onset.1 Clinical features of patients with abundant A-waves were compared with those without. Patients were classified into two groups using three different criteria, which were already determined in the preceding study.1 The first criterion was the abundant A-waves, which were positive in 9 and negative in 21patients. The second was Hos criteria,3 applied …

Abstract P2-13-04: Superior efficacy of anastrozole to tamoxifen as adjuvant therapy for postmenopausal patients with hormone-responsive breast cancer. Efficacy results of long-term follow-up data from N-SAS BC 03 trial

Background: Aromatase inhibitors have been shown to be superior to tamoxifen as adjuvant therapy in postmenopausal patients with hormone-responsive breast cancer. Here we report the efficacy results of long-term follow-up data from N-SAS BC 03 trial (UMIN CTRID: C000000056), in which anastrozole was compared to tamoxifen in hormone-responsive postmenopausal early breast cancer patients who had taken tamoxifen for 1—4 years out of a total of 5 years of treatment as adjuvant therapy. Patients and methods: Out of a total of 706 recruited patients, 696 patients (tamoxifen group, n=345; anastrozole group, n=351) were used as the full analysis set for the present study. The log-rank test was used to compare the two groups in terms of disease-free survival (DFS) and relapse-free survival (RFS), Kaplan-Meier estimates were calculated. The treatment effects were estimated by Cox9s proportional hazard model and were expressed as hazard ratios, with associated 95% confidence intervals (CIs). Results: After a median follow-up of 76.1 months, (range: 1.3–110 months), the unadjusted hazard ratio was 0.87 (95%Cl 0.60–1.26; log-rank p = 0.457) for DFS and 0.77 (95%Cl 0.49–1.22; log-rank p = 0.266) for RFS, both in favor of anastrozole. The estimated hazard ratio (95%CIs) for DFS and for RFS until each time point (right censored data) was as follows: until 30 months: 0.54 (0.30–0.98) and 0.48 (0.23–0.98), until 42 months; 0.65 (0.40–1.06) and 0.53 (0.29–0.97), until 54 months: 0.77 (0.50–1.19) and 0.63 (0.37–1.06), until 66 months: 0.82 (0.55–1.24) and 0.72 (0.44–1.17), until 78 months: 0.83 (0.57–1.23) and 0.73 (0.46–1.17), respectively. The hazard ratios (95%CIs) for DFS and for RFS until 36 months were 0.72 (95%Cl 0.43–1.22) and 0.58 (95%Cl 0.30–1.12), and those after 36 months were 1.06 (95%Cl 0.62–1.81) and 0.98 (95%Cl 0.51–1.88), respectively. Conclusion: Superior efficacy of anastrozole to tamoxifen in the Japanese population was suggested over a long-term follow-up period. It was the greatest early after switching from tamoxifen and then decreased thereafter. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-04.

Abstract P2-13-07: Long-term follow-up data of the side effect profile of anastrozole compared with tamoxifen in Japanese women: findings from N-SAS BC03 trial.

Background: Aromatase inhibitors (AIs) are standard treatment in the adjuvant setting such as initial, switch and extended treatment in postmenopausal hormone-sensitive breast cancer patients overseas. Non-steroidal AIs have usually been used as adjuvant treatment in Japanese practice. We already reported the efficacy and short term adverse events by switching therapy from tamoxifen (TAM) to anastrozole (ANA) in Japan (Breast Cancer Res Treat. 2010;121:379–87). However, the usage of adjuvant hormone therapy currently shows a trend to continue for a long time. Furthermore, long-term follow-up data is very important for the safe use of AIs. Off course, there are many data on safety profiles in Western countries. However, there are limited data in the Asian population. Methods: We investigated the planned analyses by using the data of a randomized adjuvant study of tamoxifen alone versus sequential tamoxifen and anastrozole in hormone-responsive postmenopausal breast cancer patients (N-SAS BC 03 trial. UMIN CTRID: C000000056). We examined the chronological changes from baseline to 36 months after randomization between the TAM arm (351 cases) and the ANA arm (345 cases) according to the case report forms (CRFs). We prospectively collected the data and compared data on hot flushes, nausea & vomiting, anorexia, fatigue, mood distress, headaches, arthralgia, leukocytopenia, liver transaminase changes, thromboembolism, vaginal bleeding, vaginal discharge, cardio-vascular events, second primary cancer and contra-lateral breast cancer between the two arms every 3 months from baseline to 12 months, and every 6 months up to 36 months after randomization. The data were expressed as the difference in the incidence over the time course and were analyzed using chi-square tests and logistic regressions with the baseline value as a covariate via generalized estimating equation using robust standard errors. Results: The incidence of arthralgia are significantly better in the TAM arm than the ANA arm (p = 0.00002). However, there are no differences concerning all events excluding arthralgia between the two arms. Ten and twelve cases of second primary cancer occurred in the TAM and ANA arms, respectively (p = 0.6). Six and three cases of contralateral breast cancer occurred in the TAM and ANA arms, respectively (p = 0.3). According to analyses of the chronological changes, significant changes were observed in hot flushes (p = 0.001) and vaginal discharge (P Conclusion: Safety profiles of ANA were confirmed by long-term follow-up data of a clinical trial in Japanese women. Adjuvant switch ANA therapy is also one of the standard hormone treatments for hormone-sensitive postmenopausal Japanese women. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-07.