Kazuhito Toya

Brachytherapy with permanent seed implantation

Permanent interstitial brachytherapy with iodine-125 (I-125) or palladium 103 (Pd-103) seeds is a common treatment option in the United States, and numerous articles on outcomes after long-term follow up have been published. With the treatments apparent high efficacy and low morbidity, permanent seed implantation has become the most frequently employed procedure for localized prostate cancer and has replaced radical prostatectomy. Even taking into account the good features of the treatment, the performance of permanent seed implantation in Japan had not been allowed because of the countrys strict laws on radiation safety. However, after a long period of discussion between Japanese medical associations and the government, permanent interstitial brachytherapy with I-125 was finally approved in Japan in July 2003. The guidelines for this treatment include several restrictions that should be followed by each institution that is to perform the treatment. Over 70 institutes around the country had started the treatment before the end of June 2007. With high expectations for this new radiation therapy, which may be effective, and less invasive than previous treatments and with a low incidence of treatment morbidity, brachytherapy for prostate cancer will become more common in Japan. For the purpose of improving the quality of seed implantation, which may lead to better clinical outcomes and radiation safety, medical conferences and technical training courses have been carried out regularly, and multi-institutional clinical studies have also been carried out countrywide.

The value of drip infusion cholangiography using multidetector-row helical CT in patients with choledocholithiasis

The purposes of this study were to investigate the feasibility of drip infusion cholangiography computed tomography (CTCh) for choledocholithiasis and to compare the detection of the stone on CTCh with that of MR cholangiopancreatography (MRCP). CTCh examinations were performed after infusion of intravenous biliary contrast material (iotroxic acid meglumine, 100 ml) for patients with suspected biliary diseases and were reconstructed to maximum intensity projection (MIP) and multiplanar reformation (MPR). Of 432 patients who underwent CTCh, we identified 15 who underwent surgery or cholangioscopic removal for choledocholithiasis and 32 patients who underwent cholecystectomy due to cholecystolithiasis. Their MRCP images were compared with the CTCh images. The sensitivity and specificity of CTCh for detecting choledochal stones were 87% and 96% whereas those of MRCP were 80% and 88%. The sensitivity and specificity of CTCh for detecting gallstones were 78% and 100% whereas those of MRCP were 94% and 88%. CTCh allowed high sensitivity and specificity for detecting choledochal stones but diminished the detection for cholecystolithiasis compared with MRCP.

Prostate-specific antigen ‘bounce’ after permanent 125I-implant brachytherapy in Japanese men: a multi-institutional pooled analysis

To examine the incidence, timing, and magnitude of the prostate‐specific antigen (PSA) level ‘bounce’ after permanent prostate brachytherapy (BT) and correlate the PSA bounce with clinical and dosimetric factors in Japanese patients with prostate cancer.

Acute urinary morbidity following I-125 prostate brachytherapy

BackgroundIn Japan, iodine-125 (I-125) prostate brachytherapy has been legally approved since July 2003, and this method is becoming more popular. The purpose of the present study was to assess acute urinary morbidity within the first 6 months after I-125 prostate brachytherapy.MethodsA group of 130 consecutive patients with loca-lized prostate cancer was treated with I-125 prostate brachytherapy between September 2003 and June 2004,either alone (monotherapy; 66 patients) or in combination with external-beam radiotherapy (combined therapy; 64 patients). Urinary morbidity was evaluated using the National Cancer Institute – Common Terminology Criteria for Adverse Events, version 3.0.ResultsDuring the follow-up, 111 patients (85.4%) developed some degree of urinary symptoms such as frequency, retention, dysuria, incontinence, or hematuria. Urinaryfrequency (73.1%) and retention (66.9%) were the most common, and showed no significant differences between the monotherapy group and combined therapy group (P = 0.352 and P = 0.630, respectively). Six patients (4.6%) required catheterization for urinary obstruction; the median timeto onset was 1.5 days (range, 1–192 days). Five of these6 patients received monotherapy and the other received combined therapy.ConclusionManifestations of acute urinary morbidity, especially frequency and retention, are relatively common but acceptable events after I-125 prostate brachytherapy.

Serial changes of international prostate symptom score following I-125 prostate brachytherapy.

BackgroundThis study was conducted to assess serial changes in the International Prostate Symptom Score (IPSS) within the first 12 months after iodine-125 (I-125) prostate brachytherapy.MethodsBetween September 2003 and June 2004, a group of 103 patients with localized prostate cancer was treated with I-125 prostate brachytherapy, either alone (monotherapy; 60 patients) or in combination with external-beam radiotherapy (combined therapy; 43 patients). The IPSS was obtained at preimplant, and at 1, 6, and 12 months after treatment. The minimum IPSS follow-up for this study was 12 months. Dosimetry was based on computed tomography (CT) scan 1 month postimplant. Clinical, treatment-related, and dosimetric factors were assessed for correlations with the maximum IPSS increase (the peak IPSS minus the preimplant IPSS).ResultsThe median preimplant IPSS was 7.0, with a median peak of 16 at 1 month. The IPSS returned to baseline in 42 patients (40.8%) and it returned to within 3 points of the baseline in 64 (62.1%) at 1-year follow-up. On univariate and multivariate analyses, the maximum IPSS increase was best predicted by lower preimplant IPSS, in both the monotherapy and combined therapy groups.ConclusionIn our series, IPSS after prostate brachytherapy peaked at 1 month and gradually returned to approximately baseline at 12 months.

Dose Constraint for Minimizing Grade 2 Rectal Bleeding Following Brachytherapy Combined With External Beam Radiotherapy for Localized Prostate Cancer: Rectal Dose-Volume Histogram Analysis of 457 Patients

PURPOSE To determine the rectal tolerance to Grade 2 rectal bleeding after I-125 seed brachytherapy combined with external beam radiotherapy (EBRT), based on the rectal dose-volume histogram. METHODS AND MATERIALS A total of 458 consecutive patients with stages T1 to T3 prostate cancer received combined modality treatment consisting of I-125 seed implantation followed by EBRT to the prostate and seminal vesicles. The prescribed doses of brachytherapy and EBRT were 100 Gy and 45 Gy in 25 fractions, respectively. The rectal dosimetric factors were analyzed for rectal volumes receiving >100 Gy and >150 Gy (R100 and R150) during brachytherapy and for rectal volumes receiving >30 Gy to 40 Gy (V30-V40) during EBRT therapy in 373 patients for whom datasets were available. The patients were followed from 21 to 72 months (median, 45 months) after the I-125 seed implantation. RESULTS Forty-four patients (9.7%) developed Grade 2 rectal bleeding. On multivariate analysis, age (p = 0.014), R100 (p = 0.002), and V30 (p = 0.001) were identified as risk factors for Grade 2 rectal bleeding. The rectal bleeding rate increased as the R100 increased: 5.0% (2/40 patients) for 0 ml; 7.5% (20/267 patients) for >0 to 0.5 ml; 11.0% (11/100 patients) for >0.5 to 1 ml; 17.9% (5/28 patients) for >1 to 1.5 ml; and 27.3% (6/22 patients) for >1.5 ml (p = 0.014). Grade 2 rectal bleeding developed in 6.4% (12/188) of patients with a V30 ≤35% and in 14.1% (26/185) of patients with a V30 >35% (p = 0.02). When these dose-volume parameters were considered in combination, the Grade 2 rectal bleeding rate was 4.2% (5/120 patients) for a R100 ≤0.5 ml and a V30 ≤35%, whereas it was 22.4% (13/58 patients) for R100 of >0.5 ml and V30 of >35%. CONCLUSION The risk of rectal bleeding was found to be significantly volume-dependent in patients with prostate cancer who received combined modality treatment. Rectal dose-volume analysis is a practical method for predicting the risk of development of Grade 2 rectal bleeding.

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.

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.