Toru Nishiyama

Permanent prostate brachytherapy with or without supplemental external beam radiotherapy as practiced in Japan: Outcomes of 1300 patients

PURPOSE To report outcomes for men treated with iodine-125 ((125)I) prostate brachytherapy (BT) at a single institution in Japan. METHODS AND MATERIALS Between 2003 and 2009, 1313 patients (median age, 68 years) with clinically localized prostate cancer were treated with (125)I BT. Median prostate-specific antigen level was 7.6 ng/mL (range, 1.1-43.3). T-stage was T1c in 60%, T2 in 39%, and T3 in 1% of patients. The Gleason score was <7, 7, and >7 in 49%, 45%, and 6% of patients, respectively. Neoadjuvant androgen deprivation therapy was used in 40% of patients and combined external beam radiotherapy of 45 Gy in 48% of patients. Postimplant dosimetry was performed after 30 days after implantation, with total doses converted to the biologically effective dose. Survival functions were calculated by the Kaplan-Meier method and Cox hazard model. RESULTS Median followup was 67 months (range, 6-126). The 7-year biochemical freedom from failure for low-, intermediate-, and selected high-risk prostate cancers were 98%, 93%, and 81%, respectively (p < 0.001). Multivariate analysis identified the Gleason score, initial prostate-specific antigen level, positive biopsy rate, dose, and neoadjuvant androgen deprivation therapy as predictors for biochemical freedom from failure. The 7-year actuarial developing Grade 3+ genitourinary and gastrointestinal toxicity was 2% and 0.3%, respectively. Forty-four percent patients with normal baseline potency retained normal erectile function at 5 years. CONCLUSIONS (125)I prostate BT is a highly effective treatment option for low-, intermediate-, and selected high-risk prostate cancers. Side effects were tolerable. An adequate dose may be required to achieve successful biochemical control.

A Dose-response analysis of biochemical control outcomes after 125I monotherapy for patients with favorable-risk prostate cancer

PURPOSE To define the optimal dose for (125)I prostate implants by correlating postimplantation dosimetry findings with biochemical failure and toxicity. METHODS AND MATERIALS Between 2003 and 2009, 683 patients with prostate cancer were treated with (125)I prostate brachytherapy without supplemental external beam radiation therapy and were followed up for a median time of 80 months. Implant dose was defined as the D90 (the minimal dose received by 90% of the prostate) on postoperative day 1 and 1 month after implantation. Therefore, 2 dosimetric variables (day 1 D90 and day 30 D90) were analyzed for each patient. We investigated the dose effects on biochemical control and toxicity. RESULTS The 7-year biochemical failure-free survival (BFFS) rate for the group overall was 96.4% according to the Phoenix definition. A multivariate analysis found day 1 D90 and day 30 D90 to be the most significant factors affecting BFFS. The cutoff points for day 1 D90 and day 30 D90, calculated from ROC curves, were 163 Gy and 175 Gy, respectively. By use of univariate analysis, various dosimetric cutoff points for day 30 D90 were tested. We found that day 30 D90 cutoff points from 130 to 180 Gy appeared to be good for the entire cohort. Greater D90s were associated with an increase in late genitourinary or gastrointestinal toxicity ≥ grade 2, but the increase was not statistically significant. CONCLUSIONS Improvements in BFFS rates were seen with increasing D90 levels. Day 30 D90 doses of 130 to 180 Gy were found to serve as cutoff levels. For low-risk and low-tier intermediate-risk prostate cancer patients, high prostate D90s, even with doses exceeding 180 Gy, achieve better treatment results and are feasible.

Comparison of Preplanning and Intraoperative Planning for I-125 Prostate Brachytherapy

OBJECTIVE To compare two widely used permanent prostate brachytherapy techniques, preplanning and intraoperative planning, based on postimplant dosimetry, toxicity and biochemical outcomes. METHODS Between 2003 and 2006, 665 men with localized prostate cancer were treated with permanent interstitial implantation. The first 227 consecutive men were treated with the preplanning technique, followed by 438 men treated with the intraoperative technique. Late toxicity was scored by the Common Terminology Criteria for Adverse Events v.4.0. Biochemical failure was defined as a prostate-specific antigen increase of more than 2 ng/ml above the nadir value excluding a benign bounce. Univariate and multivariate analyses were performed to identify the variables associated with biochemical failure-free survival. RESULTS Postimplant target coverage was similar in the two groups, with a small difference in risk organ doses. Mean V100 was 96.3 vs. 96.7% (P = 0.205), D90 was 119.6 vs. 119.4% (P = 0.884), urethral D10 was 157.5 vs. 146.1% (P = 0.010), rectal V100 was 0.57 vs. 0.43 cc (P = 0.002) in the preplanning and intraoperative planning groups, respectively. Acute and late Grade 3 genitourinary and gastrointestinal toxicities were <1% for both methods. The 5-year biochemical failure-free survival rate was 95.4% for the preplanning and 94.0% for the intraoperative planning group (P = 0.776). Multivariate analysis revealed Gleason score, biopsy positive rate and V100 to be predictors of biochemical failure-free survival, while the planning technique was not significant. CONCLUSION This large-scale analysis of high-quality implants revealed similar postimplant dosimetry, toxicity profiles and biochemical failure-free survival for the preplanning and intraoperative planning methods.

Establishment of orthotopic mouse superficial bladder tumor model for studies on intravesical treatments

Various animal models of bladder tumor have been developed for the preclinical evaluation of therapeutic modalities for the treatment of bladder cancers. The ideal model for the investigation of therapeutic effects of proposed novel intravesical treatments requires the mass of the implanted tumor to be confined to the urothelium of the bladder at least for the initial phase. However, previously reported bladder tumor models are not suitable for the evaluation of intravesical therapies for the treatment of superficial bladder cancer, since the muscle invasive tumors have developed from the beginnings of the experiments. These models are too aggressive to study local treatment effects. In the current study, we demonstrated that careful instillation of MBT-2 mouse bladder cancer cells into the bladder of a syngenic C3H/HeJ mouse could establish a superficial bladder tumor with an incidence of 100%. The procedure and technique for handling animals are simple for standard animal investigators. Maintenance of the in vitro conditions of MBT-2 cells without contamination of Mycoplasma and careful selection of the substrain of C3H mouse seem to be essential for stable tumor establishment. This bladder tumor model appeared to be easy to reproduce among several investigators in different institutions. The orthotopic bladder tumor model, which was confined to urothelium, lets us evaluate various intravesical treatment strategies.

Outcomes following iodine-125 prostate brachytherapy with or without neoadjuvant androgen deprivation

PURPOSE To report the biochemical failure-free survival (BFFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with iodine-125 (I-125) brachytherapy for clinically localized prostate cancer. METHODS AND MATERIALS Between 2003 and 2009, I-125 permanent prostate brachytherapy without supplemental external-beam radiotherapy was performed for 663 patients with low-risk and low-tier intermediate-risk (defined as organ-confined disease, PSA <10ng/mL, and Gleason score 3+4 with biopsy positive core rate <33%) prostate cancer. Early in the study period, the preplanning method was used in the first 104 patients, and later the real-time planning method was used. Biochemical failure was determined using the American Society for Therapeutic Radiology Oncology (ASTRO) and Phoenix definitions. RESULTS The 7-year BFFS rates for the ASTRO and Phoenix definitions were 96.1% and 95.9%, respectively. The corresponding BFFS rates by risk group were 97.6% and 96.7% for low-risk, and 91.8% and 93.6% for low-tier intermediate-risk disease (p=0.007 and 0.08, respectively). The median times to biochemical failure in those who failed were 29.5 and 43.9months according to the ASTRO and Phoenix definitions, respectively. The 7-year CSS and OS were 99.1% and 96.4%. There was no significant difference in CSS or OS between the low-risk and low-tier intermediate-risk groups. In multivariate Cox regression analysis, risk group and prostate D90 were independent predictors of BFFS for the ASTRO definition, while only the prostate D90 was significant for the Phoenix definition. CONCLUSION I-125 prostate brachytherapy results in excellent 7-year BFFS, CSS, and OS for low-risk and low-tier intermediate-risk prostate cancer.

Acute aortic dissection in a patient with metastatic renal cell carcinoma treated with axitinib

axitinib is a potent, selective, second-generation inhibitor of vascular endothelial growth factor receptor (VEgFr) 1, 2, and 3, and has been approved for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy. Compared with first-generation tyrosine kinase inhibitors (TKis), such as sorafenib, axitinib is a more specific VEgFr inhibitor. The toxicity profile of axitinib is tolerable. Common adverse events of axitinib include diarrhea, hypertension, and fatigue, and they have also been reported after using other TKis. Other adverse events, such as palmar-plantar erythrodysesthesia, cutaneous toxicity, and myelosuppression, are less commonly reported after using axitinib than after using other TKis [1]. a 51-year-old man with a renal tumor, but without any other comorbidities including hypertension, underwent left radical nephrectomy. Pathological examination revealed the tumor as a pT3aN0M0 clear cell renal cell carcinoma. six months after surgery, multiple lung metastases were detected via thoracic computed tomography (CT), after which sunitinib was administered as a four-weeks-on and two-weeks-off schedule. sunitinib was discontinued owing to grade 3 palmar-plantar erythrodysesthesia after two cycles of treatment, and the patient was switched to axitinib. Ten days after receiving axitinib, he presented to the urology outpatient department with sudden midsternal pain. He looked well, and his blood pressure was 127/66 mmHg. an electrocardiogram showed sT-segment elevation in all leads. Contrast-enhanced thoracoabdominal CT revealed acute aortic dissection (stanford type a) from the ascending aorta to the left external iliac artery (Figure 1). The patient underwent emergency reconstruction of the ascending aorta. acute aortic dissection is a life-threatening entity. The most common predisposing factor is hypertension, followed by atherosclerosis, history of cardiac surgery, Marfan syndrome, and iatrogenic causes [2]. Hypertension is a frequent adverse event with axitinib and other small-molecule TKis. Other cardiovascular toxicities including heart failure, left ventricular systolic dysfunction, and QT prolongation have also been reported. The mechanism of TKiassociated cardiotoxicity remains poorly understood. Possible mechanisms include the loss of vascular stability because of endothelial cell damage or decreased production of nitric oxide through inhibition of VEgF pathways [3]. To our knowledge, this is the first case of acute aortic dissection in a patient treated with axitinib. Only two cases of aortic dissection during treatment with small-molecule multitargeted TKis (1 with sorafenib [4] and 1 with sunitinib [5]) were

The Initial Case Report: Salvage Robotic Assisted Radical Prostatectomy After Heavy Ion Radiotherapy

Salvage radical prostatectomy is one of treatments after radiation therapy to patients with prostate cancer. To date, no case of the salvage robotic assisted radical prostatectomy (RARP) following heavy ion radiotherapy (HIRT) has been published. We report on a 70-year-old man with a history of HIRT for prostate cancer in 2011. For 3 years after. HIRT, his serum PSA levels were permissible range. However, his PSA levels were increased. We had diagnosis localized prostate cancer after HIRT. We had carried out salvage RARP. Until 10 months after salvage RARP, his PSA level was not detectable.

Schmorl Nodes Mimicking Osteolytic Bone Metastases.

Bone is the third most common site of metastasis from upper tract urothelial carcinoma after radical nephroureterectomy. Although bone biopsy is the gold standard for the diagnosis of bone metastases, they can usually be diagnosed on the basis of imaging tests. We describe a case of upper tract urothelial carcinoma after radical nephroureterectomy presenting with a Schmorl node in the third lumbar vertebra, mimicking lytic bone metastasis. Differentiation of bone metastases from Schmorl nodes is essential for the appropriate management of patients with malignancy.

Mapping Prostate Biopsy Results following Continuous PSA Rises in Patients Treated with Iodine-125 Prostate Brachytherapy

on normalized EPIC QOL scores were used to compare clinical and dynamic changes over time between the two treatment groups (p!0.05). Results: Eighty-four and 125 patients were treated on the SBRT and HDR boost studies, with a median followup of 51 and 61 months, respectively. There were no significant differences in any of the domains at baseline between the two treatment groups (pO0.05). There was a significant difference in MCIC between treatments in the urinary (17% vs 58%, p! 0.0001) and sexual domains (50% vs 71%, p50.007) (figure 1). Overall, no significant difference was noted in the bowel domain (32% vs 44%, p50.25). Of patients who reported no problem with their sexual function at baseline, 6% and 23% respectively considered it to be a moderate to big problem on followup (p50.007). On univariate and multivariate analysis, higher baseline scores (ie. better QOL) predicted for greater chance of MCIC in the sexual domain (p!0.0001). Conclusions: Long-term followup data suggests that a greater percentage of patients with localized prostate cancer treated with HDR-boost reported deterioration of QOL particularly in sexual domains in comparison with SBRT alone. The relative contribution of the brachytherapy and external beam components of treatment to this is unknown.