Published papers

Purpose: The present study was undertaken to determine the incidence and predictors of seed migration after transperineal interstitial prostate brachytherapy using I-125 free seeds. Methods and Materials: Between September 2004 and November 2007, 158 patients who underwent transperineal interstitial prostate brachytherapy as monotherapy for clinical T1/T2 carcinoma of the prostate gland were reviewed. Implants had been performed with standard techniques. All 158 patients underwent followup radiographs (orthogonal chest radiographs, a kidney-ureter-bladder radiograph, and a posteroanterior pelvic radiograph) to assess the presence of seed migration at 3 months after transperineal interstitial prostate brachytherapy. Patient characteristics and treatment status were recorded. Univariate and multivariate analyses were performed to identify predictors of seed migration. Results: Seed migration occurred in 35 of 158 patients (22.2%). Univariate analyses revealed that preoperative prostate volume estimated by transrectal ultrasound, the number of needles, the number of seeds implanted, and the presence or absence of pubic arch interference (PAI) were significantly associated with seed migration. These results indicated that larger prostate glands were more likely to have seed migration. However, the absolute difference in prostate size was not overly impressive (22.4 vs. 26.3 cm3). Multivariate analysis revealed that the number of seeds implanted and the presence or absence of PAI were significant predictors of seed migration. Conclusion: The number of seeds implanted and the presence or absence of PAI provide the most predictive information on seed migration.

Purpose: We previously reported that most of axillary regions could be irradiated by the modified tangential irradiation technique (MTIT). The purpose of this study was to determine whether the three-dimensional conformal radiotherapy (3D-CRT) with a field-in-field technique improves dosimetry for the breast and axillary nodes. Methods and Materials: Fifty patients with left-sided breast cancer were enrolled. With MTIT, we planned the radiation field to be wider in the cranial direction than the standard tangential fields to include the axillary regions. With 3D-CRT, a field-in-field technique was used to spare the heart and contralateral breast to the extent possible by applying the multileaf collimator manually. Dose-volume histograms were compared for the breast, axillary region, heart, lung, and other normal tissues. Results: There were no significant differences in the percent volume of the breast receiving >90% of the prescribed dose (V90) between MTIT and 3D-CRT. The mean V90 of the level I to III axillary regions were increased from 93.7%, 48.2%, and 41.3% with MTIT to 97.6%, 85.8%, and 82.8% with 3D-CRT. 3D-CRT significantly reduced the volume of the heart receiving >30 Gy (mean, 7.6 vs. 15.9 mL), the percent volume of the bilateral lung receiving >20 Gy (7.4% vs. 8.9%), and the volume of other normal tissues receiving >107% of the prescribed dose (0.1 vs. 2.9 mL). Conclusion: The use of 3D-CRT with a field-in-field technique improves axillary node coverage, while decreasing doses to the heart, lungs, and the other normal tissues, compared with MTIT.

INTRODUCTION: We investigated tolerable doses to organs at risk (OARs) in the mediastinum and pulmonary hilum following stereotactic body radiotherapy for centrally located lung tumors. METHODS: Between 2005 and 2012, 381 patients with lung tumors were treated with stereotactic body radiotherapy of 40 to 60 Gy in five fractions. From among these patients, we extracted those who received greater than 25 Gy irradiation to OARs and analyzed dosimetric factors in relation to grade 3 to 5 toxicities. RESULTS: In total, 398 OARs in 133 patients were analyzed, with a median follow-up of 33 (range, 3-87) months. The numbers receiving greater than 25 Gy irradiation to the aorta, vena cava, pulmonary artery, pulmonary vein, bronchus, trachea, heart, and esophagus were 72, 33, 73, 60, 55, 13, 69, and 23, respectively. The corresponding median Dmax 0.5 ml were 43.8, 32.0, 32.2, 29.1, 28.4, 28.7, 41.1, and 21.7 Gy. Of these patients, two developed grade 5 and one grade 3 hemoptysis, and two had grade 3 obstructive pneumonia. Two patients with grade 5 hemoptysis received high doses at the pulmonary artery and bronchus (59.2 and 54.4 Gy, and 61.3 and 59.6 Gy, respectively). No other grade 3 to 5 toxicities occurred. CONCLUSION: Therapeutic indications and dose-intensity should be carefully determined for patients with central tumors, especially when doses to the pulmonary artery and bronchus in the pulmonary hilum exceed 50 Gy. Tolerable doses for other OARs might, however, be higher than in this study, though longer follow-up is necessary to assess this possibility.

High-dose melphalan has been gaining recognition as a highly emetogenic agent used in hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to elucidate the efficacy of aprepitant in preventing high-dose melphalan-induced emesis. Sixty patients who received melphalan (70 mg/m2/day, 2 days) and fludarabine (125 mg/m2/day, 5 days) as conditioning for allogeneic HSCT for hematological malignancies, and who received ondansetron and methylprednisolone as an antiemetic prophylaxis, were eligible. Twenty of these 60 patients also received aprepitant for 5 days (aprepitant group); the remaining 40 patients served as a control. The rates of complete response (CR), defined as no emesis without rescue medications, and complete protection (CP), defined as no emesis with or without rescue medications, were assessed between the two groups. The observation period was 12 days from the first day of melphalan administration. The CR and CP rates were significantly higher in the aprepitant group than in the control group during the observation period (35 % versus 10 %, P < 0.05; 85 % versus 33 %, P < 0.001; respectively). These results suggest that aprepitant in combination with ondansetron and steroid effectively ameliorates nausea and vomiting caused by the high-dose melphalan-based conditioning for allogeneic HSCT.

Purpose: To expand the radiation dose rate measurement data set by measuring radiation under various prostate 125I brachytherapy situations. Methods and Materials: Measurements were obtained from 63 consecutive unselected patients at Tokyo Medical Center, Japan. Differences in factors during measurements, such as body postures, distances from the skin surface, and measurement directions were considered. Furthermore, shielding effects of lead-lined underwear, consisting mainly of 0.1-mm thickness of lead, were also assessed. Results: Radiation exposure varies according to the patient's body posture, with results differing as much as approximately 40.0% in measured radiation dose rates at 30. cm from the anterior skin surface. Weight, body mass index, and tissue thickness showed good correlations with measured radiation dose rates. The magnitude of radiation exposure attenuation by shielding was approximately 95.8%, similar to the attenuation ratio based on tissue measurements made in the lateral direction. The respective mean times required to reach 1. mSv were 1.2, 7.6, and 65.4 days in the standing position and 0.6, 4.6, and 40.4 days in the supine position at the site of contact, and at 30 and 100. cm from the anterior skin surface. Conclusions: This study obtained supplemental information pertaining to radiological protection and confirmed that shielding can be an effective tool for reducing exposures.

Purpose To define the optimal dose for 125I 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 125I 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.

Background: We aimed to evaluate long-term erectile function following prostate brachytherapy, based on patient characteristics and treatment factors.Methods: Between 2003 and 2006, 665 men with localized prostate cancer were treated with 125I permanent seed implantation. None was given adjuvant hormone therapy. Erectile function was assessed before treatment, and at 6 months, 1, 2, 3, 4 and 5 years after implantation using the Mount Sinai Erectile Function Score (MSEFS) of 0–3 (0 = no erections, 1 = erections insufficient for intercourse, 2 = suboptimal erections but sufficient for intercourse, 3 = normal erectile function). Potency was defined as score 2 or 3, and 382 men were potent before treatment. Univariate and multivariate analyses were performed on the data from these 382 patients to identify variables associated with potency preservation.Results: In patients who were potent before treatment, the actuarial potency preservation rate fell to 46.2 % at 6 months after brachytherapy, and then slowly recovered reaching 52.0 % at 5 years after brachytherapy. In multivariate logistic regression analysis, patient age (p = 0.04) and pre-treatment MSEFS (p < 0.001) were predictors of 5-year potency preservation. Neoadjuvant hormone therapy affected potency preservation only at 6 months after brachytherapy.Conclusions: Patient age at implantation and pre-treatment erectile function are predictive factors for the development of erectile dysfunction following prostate brachytherapy.

The efficacy of conventional radiation therapy for gastric cancer is controversial. In this study, we evaluated the in vitro and in vivo effects of continuous low-dose-rate irradiation by I-125 seeds on different histological types of gastric cancer cell lines. Three human gastric cancer cell lines (MKN74, MKN45, and NUGC4) were treated with or without continuous low-dose irradiation by I-125 seeds in vitro and in vivo. Cell viability, apoptosis, caspase-3 assay, and cell-cycle distribution were examined in vitro. Body weight and tumor volumes of BALB/c nude mice bearing MKN74, MKN45, and NUGC4 gastric cancer xenografts were measured, and in vivo cell proliferation and apoptosis assays were performed by Ki67 and TUNEL staining, respectively. Continuous low-dose-rate irradiation by I-125 seeds reduced cell viability and induced cell apoptosis through the activation of caspase-3, and led to the accumulation of cells in the G2/M phase in vitro. It also suppressed the growth of gastric cancer xenografts in nude mice, while inhibiting cell proliferation and inducing apoptosis as demonstrated by Ki67 and TUNEL staining. Therefore, our data suggest that continuous low-dose-rate irradiation by I-125 seeds could be a promising new option for gastric cancer treatment, regardless of histological origin.

Background: To report the outcomes of patients treated with combined iodine-125 (I-125) brachytherapy and external beam radiotherapy (EBRT) for high-risk prostate cancer.Methods: Between 2003 and 2009, I-125 permanent prostate brachytherapy plus EBRT was performed for 206 patients with high-risk prostate cancer. High-risk patients had prostate-specific antigen ≥ 20 ng/mL, and/or Gleason score ≥ 8, and/or Stage ≥ T3. One hundred and one patients (49.0%) received neoadjuvant androgen deprivation therapy (ADT) but none were given adjuvant ADT. Biochemical failure-free survival (BFFS) was determined using the Phoenix definition.Results: The 5-year actuarial BFFS rate was 84.8%. The 5-year cause-specific survival and overall survival rates were 98.7% and 97.6%, respectively. There were 8 deaths (3.9%), of which 2 were due to prostate cancer. On multivariate analysis, positive biopsy core rates and the number of high-risk factors were independent predictors of BFFS. The 5-year BFFS rates for patients in the positive biopsy core rate <50% and ≥50% groups were 89.3% and 78.2%, respectively (p = 0.03). The 5-year BFFS rate for patients with the any single high-risk factor was 86.1%, compared with 73.6% for those with any 2 or all 3 high-risk factors (p = 0.03). Neoadjuvant ADT did not impact the 5-year BFFS.Conclusions: At a median follow-up of 60 months, high-risk prostate cancer patients undergoing combined I-125 brachytherapy and EBRT without adjuvant ADT have a high probability of achieving 5-year BFFS.