Hiroshi Okusa

Single Infusion of Zoledronic Acid to Prevent Androgen Deprivation Therapy-induced Bone Loss in Men With Hormone-naive Prostate Carcinoma

Androgen‐deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone‐naive prostate carcinoma.

Genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with Hypofractionated External beam radiotherapy for localized prostate cancer: an analysis to determine the correlation between dose-volume histogram parameters in HDR brachytherapy and severity of toxicity.

PURPOSE To evaluate the severity of genitourinary (GU) toxicity in high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiotherapy (EBRT) for prostate cancer and to explore factors that might affect the severity of GU toxicity. METHODS AND MATERIALS A total of 100 Japanese men with prostate cancer underwent (192)Ir HDR brachytherapy combined with hypofractionated EBRT. Mean (SD) dose to 90% of the planning target volume was 6.3 (0.7) Gy per fraction of HDR. After 5 fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administrated. The urethral volume receiving 1-15 Gy per fraction in HDR brachytherapy (V1-V15) and the dose to at least 5-100% of urethral volume in HDR brachytherapy (D5-D100) were compared between patients with Grade 3 toxicity and those with Grade 0-2 toxicity. Prostate volume, patient age, and International Prostate Symptom Score were also compared between the two groups. RESULTS Of the 100 patients, 6 displayed Grade 3 acute GU toxicity, and 12 displayed Grade 3 late GU toxicity. Regarding acute GU toxicity, values of V1, V2, V3, and V4 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0-2 toxicity. Regarding late GU toxicity, values of D70, D80, V12, and V13 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0-2 toxicity. CONCLUSIONS The severity of GU toxicity in HDR brachytherapy combined with hypofractionated EBRT for prostate cancer was relatively high. The volume of prostatic urethra was associated with grade of acute GU toxicity, and urethral dose was associated with grade of late GU toxicity.

Profilin 1 overexpression in renal cell carcinoma

Objectives:  To gain information about overexpressed antigens in renal cell carcinoma (RCC) by using a chemical proteomics approach.

Four-year experience of interstitial permanent brachytherapy for Japanese men with localized prostate cancer.

OBJECTIVE To report 4 year results obtained with our initial 100 patients with localized prostate cancer treated by interstitial permanent brachytherapy. METHODS One-hundred Japanese men with clinically localized prostate cancer underwent interstitial permanent prostate brachytherapy using (125)I seeds. Median follow-up was 36 months (range, 30-42 months). Median initial prostate-specific antigen (PSA) level was 6.7 ng/ml (range, 1.5-25.2 ng/ml). Of these 100 patients, 31 received neoadjuvant hormone therapy for several months. Treatment morbidities were assessed using Radiation Therapy Oncology Group (RTOG) scale and National Cancer Institute Common Toxicity Criteria. RESULTS A mean of 95 seeds (range, 48-123 seeds) were successfully implanted in patients with prostate cancer. Mean prostate volume receiving at least 100% dose (V100) and dose to 90% of prostate volume (D90) for the 100 patients were 96.6% and 166.1 Gy, respectively. Urinary morbidity was common, but was usually not severe. Only four patients needed catheterization for urinary retention (Grade 3) during follow-up. Most patients displayed no rectal morbidity after implantation, with only 3% of patients showing RTOG Grade 2 rectal morbidity and no patients showing morbidity of Grade 3 or more. Three patients experienced biochemical failure according to Phoenix consensus definition during follow-up. One patient displayed clinical failure with lymph node recurrence. CONCLUSIONS These results indicate that interstitial permanent brachytherapy is safe and effective for Japanese patients with localized prostate cancer. The import of matured techniques developed in Western countries might allow bypass of the trial-and-error process in Japanese institutions.

SINGLE INFUSION OF ZOLEDRONIC ACID TO PREVENT ANDROGEN- DEPRIVATION THERAPY-INDUCED BONE LOSS IN MEN WITH HORMONE-NAÏVE PROSTATE CANCER

BACKGROUND: Androgen-deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone-naive prostate carcinoma. METHODS: Forty men received either a single infusion of zoledronic acid (4 mg intravenously on Day 1) or no infusion during ADT. BMD of the proximal femur and posteroanterior lumbar spine was measured by dual-energy x-ray absorptiometry and urinary N-telopeptide (u-NTx) at 6 and 12 months. RESULTS: At baseline, the overall BMDs demonstrated no significant difference in lumbar spine and hip regions. At 6months, mean (� standard error) BMD of the posteroanterior lumbar spine decreased 4.6% � 1.0% in control patients and increased 5.1% � 1.2% in patients receiving zoledronic acid, a significant difference (P ¼ .0002). At 12 months, the change in BMD between the 2 groups was statistically significantly different at the lumbar region (P ¼ .0004), indicating that zoledronate preserved BMD. For u-NTx, bone turnover was statistically significantly decreased in the zoledronate group compared with controls at 6 months (P < .0001), but returned to pretreatment levels at 12 months in the zoledronate group. CONCLUSIONS: Bone loss begins at 6 months with ADT. A single infusion of zoledronic acid in patients receiving ADT reduces bone mineral loss and maintains BMD at least at 12 months during ADT. Further study is needed to determine the best dosing schedule to prevent ADT-induced bone loss in men with hormone-naive prostate carcinoma. Cancer 2009;115:3468–74. V C 2009 American Cancer Society.

Changes in prostate-specific antigen and hormone levels following withdrawal of prolonged androgen ablation for prostate cancer

We conducted a study in order to characterize changes after withdrawal of androgen ablation (AA) for prostate cancer. AA was withdrawn in 38 Japanese patients with prostate cancer who had undergone this therapy for various periods. Patients were stratified into those who had undergone AA for less than 24 months (Group 1, n=12) and those with longer periods of AA (Group 2, n=26). Serial changes in hormones and prostate-specific antigen (PSA) were prospectively monitored following cessation of AA. The median durations of AA in the two groups were 8.5 and 54.5 months, respectively. Levels of total testosterone (T), luteinizing hormone and PSA increased significantly with time. At the end of 2 y, 30/38 patients (78.9%) had T levels above 50 ng/dl and 19/38 (50%) had levels above 320 ng/dl. Patients in Group 2 required significantly longer duration for T recovery. Complete T recovery is not always accompanied by rising PSA. Recovery of T levels is often slow following cessation of prolonged AA. Expression of PSA after AA is often variable and unpredictable. Thus, interpretation of outcomes in clinical trials incorporating AA needs caution and careful consideration.

SOM for classifying data sets with missing values: application to clinical data of bladder cancer patients

In this paper we investigate applying SOM (Self-Organizing Maps) for classification and rule extraction in data sets with missing values, in particular from real clinical data of bladder cancer patients. For this experiment, we used real data of bladder cancer patients provided by Kitasato University Hospital. When using input data with missing values for SOM, the missing value is either interpolated in the preprocessing stage, or the missing value is replaced with a specific value or property that marks it as a missing value. In either case, there is a possibility some rules can be extracted from data with missing values. On the other hand, these data can have a negative influence for the classification for data sets for which missing values should be neglected. In this research we propose a method where SOM is trained using an input vector in which the properties for the missing values are excluded. The influence of information on the missing values can be reduced by using the proposed method. Through computer simulation, we showed that the proposed method gave good results in classification and rule extraction from clinical data of bladder cancer patients.