Current status and issues with the dosimetric assay of iodine-125 seed sources at medical facilities in Japan: a questionnaire-based survey†.

In conducting dosimetric assays of seed sources containing iodine-125 (125I), several major guidelines require the medical physicist to verify the source strength before patient treatment. Japanese guidelines do not mandate dosimetric assays at medical facilities, but since 2017, three incidents have occurred in Japan wherein seeds with incorrect strengths were delivered to medical facilities. Therefore, this study aimed to survey the current situation and any barriers to conducting the dosimetric assay of iodine-125 seeds at medical facilities in Japan. We conducted a questionnaire-based survey from December 2020 to April 2021, to examine whether seed assay and verification of the number of seeds delivered were being performed. We found that only 9 facilities (16%) performed seed assay and 28 (52%) verified the number of seeds. None of the facilities used an assay method that ensured traceability. The reasons for not performing an assay were divided into two categories: lack of resources and legal issues. Lack of resources included lack of instruments, lack of knowledge of assay methods, shorthand, or all of the above, whereas legal issues included the inability to resterilize iodine-125 seeds distributed in Japan and/or purchase seeds dedicated to the assay. Dosimetric assays, including simple methods, are effective in detecting calibration date errors and non-radioactive seeds. The study findings suggest that familiarization of medical personnel with these assay methods and investigation of the associated costs of labor and equipment should be recommended, as these measures will lead to medical reimbursement for quality assurance.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using multicatheter interstitial brachytherapy: clinical results with a median follow-up of 60 months.

BACKGROUND: We carried out the first multi-institutional prospective study on accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy in a shorter period for early breast cancer in Japan. METHODS: Patient eligibility criteria included positive hormone receptors, tumors ≤ 3 cm and TNM stage pN0M0. After breast-conserving surgery (Japanese cylindrical resection) and histological confirmation of negative surgical margins and the absence of lymph node metastasis, applicator implantation was performed either postoperatively or intraoperatively. High-dose-rate brachytherapy of 36 Gy in 6 fractions was delivered. RESULTS: Forty-six patients from six institutions received this treatment regimen, and the median follow-up time was 60 months (range 57-67 months). The median resected breast tissue volume was 81 cm3 (range 28-260 cm3). No Grade 4 late sequela, local recurrence nor death due to breast cancer were observed. Grade 2-3 sequelae such as rib fracture (2%), soft tissue necrosis (9%), fibrosis (20%), and breast pain (9%) were observed. The resected breast tissue volumes of the patients who had Grade ≥ 2 fibrosis and Grade < 2 fibrosis were 105.9 ± 32.3 cm3 and 76.3 ± 45.6 cm3, respectively, p = 0.02. The overall cosmetic outcome score of Excellent/Good was 74% at 60 months after APBI. Grade ≥ 1 fibrosis was observed in 44% and 92% of patients who scored Excellent/Good and Fair/Poor, respectively, p = 0.004. CONCLUSIONS: This study showed excellent local control and survival results with minimal late sequelae.

Successful treatment of tumor stage mycosis fungoides with total skin helical tomotherapy.

Total skin electron beam therapy (TSEBT) is a treatment option for mycosis fungoides (MF). In Japan, it has been rarely performed because of the time required for each treatment, physical burden on patients, and difficulties in providing uniform dosimetry. In recent years, helical tomotherapy, an intensity-modulated radiation therapy that applies helical computed tomography technology, has been used to treat cancer. Total skin helical tomotherapy (TSHT) has been suggested as a promising alternative to TSEBT for patients with MF, but there are few reports from Japan. We used TSHT to treat a 28-year-old Japanese woman with tumor stage MF. She achieved complete remission with TSHT (12 Gy in six fractions over 6 days) and remained in remission for 32 months without additional treatment. Treatment-related grade 4 myelosuppression was observed, but resolved with blood transfusions and subcutaneous injection of granulocyte colony stimulating factor. Other adverse events were tolerable. Although careful attention should be paid to myelosuppression, TSHT might be a useful treatment option for MF.

Radiation protection in radiological imaging: a survey of imaging modalities used in Japanese institutions for verifying applicator placements in high-dose-rate brachytherapy.

Institutional imaging protocols for the verification of brachytherapy applicator placements were investigated in a survey study of domestic radiotherapy institutions. The survey form designed by a free on-line survey system was distributed via the mailing-list system of the Japanese Society for Radiation Oncology. Survey data of 75 institutions between August 2019 and October 2019 were collected. The imaging modalities used were dependent on resources available to the institutions. The displacement of a brachytherapy applicator results in significant dosimetric impact. It is essential to verify applicator placements using imaging modalities before treatment. Various imaging modalities used in institutions included a computed tomography (CT) scanner, an angiography X-ray system, a multi-purpose X-ray system and a radiotherapy simulator. The median total exposure time in overall treatment sessions was $\le$75 s for gynecological and prostate cancers. Some institutions used fluoroscopy to monitor the brachytherapy source movement. Institutional countermeasures for reducing unwanted imaging dose included minimizing the image area, changing the imaging orientation, reducing the imaging frequency and optimizing the imaging conditions. It is worth noting that half of the institutions did not confirm imaging dose regularly. This study reported on the usage of imaging modalities for brachytherapy in Japan. More caution should be applied with interstitial brachytherapy with many catheters that can lead to potentially substantial increments in imaging doses for monitoring the actual brachytherapy source using fluoroscopy. It is necessary to share imaging techniques, standardize imaging protocols and quality assurance/quality control among institutions, and imaging dose guidelines for optimization of imaging doses delivered in radiotherapy should be developed.

Patient-reported health-related quality of life up to three years after the treatment with permanent brachytherapy: Outcome of the large-scale, prospective longitudinal study in Japanese-Prostate Cancer Outcome Study by Permanent I-125 Seed Implantation (J-POPS).

PURPOSE: To evaluate long-term health-related quality of life (HRQOL) impact of I-125 permanent seed implantation (PI) in Japanese patients with localized prostate cancer. MATERIALS AND METHODS: This is a longitudinal, prospective study of 2353 patients who enrolled in the nationwide Japanese-Prostate Cancer Outcome Study by Permanent I-125 Seed Implantation (J-POPS) from July 2005 to June 2007. HRQOL was measured before and after treatment (3, 12, 24, and 36 months) using the Medical Outcomes Study 8-items Short-Form Health Survey (SF-8) and the Expanded Prostate Cancer Index Composite Japanese version questionnaire. RESULTS: Of the total of 1511 patients who returned anonymized HRQOL questionnaires to Translational Research Center for Medical Innovation, 1079 underwent PI alone (PI group) and 432 underwent combined PI and external beam radiation therapy (EBRT) treatment (EBRT combination therapy group). The mental component summary score of SF-8 was improved at 12, 24, and 36 months compared with the pretreatment level. Although the urinary summary score at 3 months in the PI group was significantly lower than that in the EBRT combination therapy group, which recovered thereafter and was comparable to the score of the EBRT combination therapy group. The bowel summary score in the PI group was significantly higher than that in the EBRT combination therapy group at 12, 24, and 36 months. CONCLUSION: This longitudinal, large-scale prospective study indicated that the general HRQOL for PI was almost maintained 3 years after treatment. These results provide important information for patients with localized prostate cancer, who may select to receive I-125 brachytherapy.

Biochemical outcomes and predictive factors by risk group after permanent iodine-125 seed implantation: Prospective cohort study in 2,316 patients.

PURPOSE: To evaluate the biochemical freedom from failure (bFFF) by risk group and treatment modality and the predictive factors of bFFF by risk group in patients with prostate cancer undergoing permanent seed implantation (PI) with or without external beam radiation therapy (EBRT) in a nationwide prospective cohort study (Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 [I-125] Seed Implantation) in Japan during the first 2 years. METHODS AND MATERIALS: The analyses included 2,316 participants in 42 institutions; bFFF was evaluated using the Phoenix definition and calculated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify the factors associated with bFFF. RESULTS: Median followup period was 60.0 months. The 5-year bFFF rates in all patients, 1,028 low-risk patients, 1,114 intermediate-risk patients, and 133 high-risk patients were 93.6%, 94.9%, 92.7%, and 91.1%, respectively. The 5-year bFFF rates in the PI group and EBRT combination therapy group were 93.7% and 93.3%, respectively. In a multivariate analysis, younger age, higher Gleason score (GS), higher percent positive biopsies (%PB), and lower prostate V100 (p = 0.0012, 0.0030, 0.0026, and 0.0368) in all patients; younger age, higher pretreatment prostate-specific antigen, and lower prostate V100 (p = 0.0002, 0.0048, and 0.0012) in low-risk patients; higher GS, higher %PB, and no hormonal treatment (p = 0.0005, 0.0120, and 0.0022) in intermediate-risk patients; and higher GS and higher %PB (p = 0.0329 and 0.0120) in high-risk patients were significantly associated with bFFF. CONCLUSIONS: PI with or without EBRT resulted in excellent short-term biochemical outcomes in all risk groups, especially in high-risk patients. Age, pretreatment prostate-specific antigen, and prostate V100 in low-risk patients; GS, %PB, and hormonal treatment in intermediate-risk patients; and GS and %PB in high-risk patients were independently affected bFFF.

Genitourinary toxicity after permanent iodine-125 seed implantation: The nationwide Japanese prostate cancer outcome study of permanent iodine-125 seed implantation (J-POPS).

PURPOSE: The purpose of this study was to evaluate acute and late genitourinary (GU) toxicity and to elucidate factors associated with GU toxicity in patients with prostate cancer treated with permanent seed implantation (PI) enrolled in a nationwide prospective cohort study in Japan. METHODS AND MATERIALS: Of 2,354 patients enrolled in this study, GU toxicity was evaluated in 2,339 patients at 3, 12, 24, and 36 months after PI. To elucidate independent factors predictive of acute and late Common Terminology Criteria for Adverse Events Grade 2 or higher (Grade ≥2) GU toxicity, multivariate logistic regression analyses were carried out. Regarding acute urinary retention (AUR), the incidence rate and the recovery rate for AUR were estimated using the Kaplan-Meier curve. RESULTS: Approximately 53% of the patients treated with PI alone and 42% of those treated with combination therapy with PI therapy and external beam radiation therapy showed urinary frequency/urgency at 3 months. The multivariate analysis revealed that age, prostate volume, pretreatment international prostate symptom score, drinking status, and PI were independent predictors of acute GU toxicity Grade ≥2. Of all patients, 53 (2.3%) suffered from AUR, and 49 (92.5%) recovered from AUR with a median time of 4.3 months during the followup period. CONCLUSIONS: The results of GU toxicity in Japanese patients who underwent low-dose-rate brachytherapy were acceptable and comparable to those previously reported in U.S. PATIENTS: The patients treated with PI alone showed a significantly higher incidence rate of GU toxicity than did those undergoing combination therapy with PI and external beam radiation therapy in the acute phase.

Institutional patient accrual volume and the treatment quality of I­125 prostate seed implantation in a Japanese nationwide prospective cohort study.

PURPOSE: It is unclear whether experience at high-volume institute improves the treatment quality of prostate seed implantation. The aim of this study was to evaluate the effect of institutional experience on postimplant dosimetric parameters in a nationwide prospective cohort study. METHODS: From July 2005 to June 2007, 2354 patients were registered in the Japanese Prostate Cancer Outcome Study of Permanent I­125 Seed Implantation (J-POPS), and 1126 patients treated with seed implantation alone were evaluated. As a surrogate for institutional experience, we classified the J­POPS institutions as high-volume (patient accrual volume was ≥120 patients per institution) or low-volume institutions (patient accrual volume was <120 patients per institution). To compare treatment quality between institutions, we evaluated the postimplant dosimetric parameters including D90, V100/150 (prostatic dose parameters), UD5/90, U200 (urethral dose parameters), and rectum R100/150 (rectal dose parameters). RESULTS: In the 5 high-volume institutions (n = 601 patients), most of the patients were treated with >144 Gy of D90, whereas in the 20 low-volume institutions (n = 525) some of the patients were treated with <144 Gy. The V100 of most of the high-volume institution patients were >90%, whereas in the low-volume institutions a considerable percentage of patients showed lower V100. Although there was no correlation between D90 and rectal dose parameters, UD90 had a moderate positive correlation with D90 in both the high- and low-volume institutions. U200 varied more widely in the low-volume institutions. CONCLUSIONS: Our findings indicate that the institutional patient accrual volume is associated with the treatment quality of I­125 prostate seed implantation.

Case report of a dose-volume histogram analysis of rib fracture after accelerated partial breast irradiation: interim analysis of a Japanese prospective multi-institutional feasibility study.

We initiated the first multi-institutional prospective study of accelerated partial breast irradiation for early breast cancer in Japan. Our early clinical results showed that the treatment methods were technically reproducible between institutions and showed excellent disease control at a median follow-up of 26 months in our previous report. At present, total 46 patients from six institutions underwent the treatment regimen from October 2009 to December 2011, and the median follow-up time was 60 months (range, 57-67 months). In 46 patients, we experienced one patient who had rib fracture as a late complication. The dose-volume histogram (DVH) result of this patient was analyzed. The D0.01cc, D0.1cc, and D1cc values of the patient were 913, 817, and 664 cGy per fraction, respectively. These values were the highest values in 46 patients. The average D0.01cc, D0.1cc, and D1cc values of the other 45 patients were 546, 500, and 419, respectively, cGy per fraction. From this result, DVH values showing high-dose irradiated volume (D0.01cc, D0.1cc, and D1cc) seem to be a good predictive factor of rib fracture for accelerated partial breast irradiation. However, further investigation is necessary because of the small number of patients investigated.

National survey of intracavitary brachytherapy for intact uterine cervical cancer in Japan.

To review the current status of, and labor expended for (in terms of time required), intracavitary brachytherapy (ICBT) in definitive radiotherapy/chemoradiotherapy for cervical cancer patients, two national surveys were performed. The first survey was conducted between July and August 2016 and consisted of a questionnaire of 12 items regarding ICBT procedures for cervical cancer, which was sent to 173 centers installed with high-dose-rate remote after-loading brachytherapy systems. Between November and December 2016, another survey was performed in 79 centers to evaluate labor required for ICBT procedures in terms of time spent and number of staff involved. In the first survey, the response rate was 77% of the 173 centers. ICBT was performed for cervical cancer in 118 (89%) centers. Imaging modalities used after applicator insertion were X-ray alone in 46 (40%), computed tomography in 69 (60%) and magnetic resonance imaging in 5 (4%) centers. Three-dimensional (3D) planning was performed in 55 centers (48%). Fifty-five (70%) centers responded to the second survey regarding ICBT-mandated labor. The median cumulative duration of the entire ICBT procedure was 330 min (the sum of the times spent by each staff member) and was longer in the 3D image-guided brachytherapy (3D-IGBT) (405 min) than in the X-ray group (230 min). This trend was significant for the specific processes of image acquisition and treatment planning, especially for radiation oncologists. In definitive radiotherapy/chemoradiotherapy for cervical cancer patients, 3D-IGBT use has been gradually spreading in Japan. The present survey revealed that ICBT, especially 3D-IGBT, requires substantial labor and time from staff.

Nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS): first analysis on survival.

BACKGROUND: Investigating oncological outcomes in patients registered in the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS) in terms of biochemical relapse-free survival (bRFS) by the Phoenix and the newly developed J-POPS definitions, exploration of predictive factors for bRFS, and preliminary verification of pitfalls of prostate-specific antigen (PSA) failure definitions. METHODS: Between July 2005 and June 2007, 2316 clinically localized patients underwent permanent seed implantation. The primary endpoint was bRFS. One of the secondary endpoints was overall survival (OS). RESULTS: The median age was 69 and performance status was 0 in 99.1% of participants. The median biologically effective dose (BED) was about 180 Gy2. During a median follow-up of 60.0 months, 8.4 and 5.9% had PSA failure by the Phoenix and the J-POPS definitions, respectively. The 5-year bRFSs based on the Phoenix and the J-POPS definitions were 89.1 and 91.6%, respectively. The 5-year OS was 97.3%. According to multivariate analyses, only age affected bRFS based on the Phoenix definition, whereas the risk group and BED independently affected bRFS based on the J-POPS definition. A spontaneous PSA decrease was seen in 91.1% of participants after PSA failure based on the Phoenix definition alone, but in only 22.2% after PSA failure based on the J-POPS definition alone. CONCLUSION: The world's largest registration study, J-POPS, consisted of patients with longevity, and a highly quality-controlled BED resulted in excellent bRFS and OS. The high likelihood of PSA bounce by the Phoenix definition should be taken into account, especially in younger patients. CLINICAL TRIAL INFORMATION: NCT00534196.

Uncertainty of cosmetic evaluation after accelerated partial breast irradiation: interim analysis of a Japanese prospective multi-institutional feasibility study.

PURPOSE: We conducted a multi-institutional prospective study on accelerated partial breast irradiation (APBI) using interstitial brachytherapy. The clinical results over a minimum follow-up period of 30 months are presented here. MATERIALS AND METHODS: Forty-six patients with breast cancer were treated with breast-conserving surgery and postoperative APBI. After confirmation of negative surgical margins and negative lymph nodes, a high-dose-rate brachytherapy protocol of 36 Gy/6 fractions was carried out. All clinical data were prospectively collected using the Common Terminology Criteria for Adverse Events ver. 3.0. RESULTS: No recurrence was observed. Cumulative rates of grade 2 or higher late sequelae were 25% for fibrosis, 2% for fractures, 9% for pain, and 9% for soft tissue necrosis. Rates of excellent or good cosmetic results as assessed by the physician and patient were 93 and 89% at the 12-month follow-up and 76 and 74% at the 30-month follow-up, respectively. Large volumes of resected tissue in small breasts were associated with fibrosis of grade 2 or higher. CONCLUSION: APBI in Japanese women provides satisfactory clinical results except for cosmetic outcomes. There is some difficulty with the assessment of fibrosis and cosmetic outcomes, especially in patients with small breasts. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000001677.

Predictive factors of rectal toxicity after permanent iodine-125 seed implantation: Prospective cohort study in 2339 patients.

PURPOSE: To evaluate the incidence and the associated factors of rectal toxicity in patients with prostate cancer undergoing permanent seed implantation (PI) with or without external beam radiation therapy (EBRT) in a nationwide prospective cohort study in Japan (J-POPS) during the first 2 years. METHODS AND MATERIALS: A total of 2,339 subjects were available for the analyses. Rectal toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. RESULTS: The 3-year cumulative incidence for grade ≥2 rectal toxicity was 2.88%, 1.76%, and 6.53% in all subjects, PI group and EBRT combination therapy group, respectively. On multivariate analysis, among all subjects, grade ≥2 rectal toxicity was associated with rectal volumes receiving 100% of the prescribed dose (R100; p < 0.0001) and EBRT combination therapy (p = 0.0066). R100 in the PI group (p = 0.0254), and R100 (p = 0.0011) and interactive planning (p = 0.0267) in the EBRT combination therapy group were also associated with grade ≥2 toxicity. The 3-year cumulative incidence of grade ≥2 rectal toxicity was 3.80% and 1.37% for R100 ≥ 1 mL and R100 < 1 mL, respectively, in the PI group (p = 0.0068), and 14.09% and 5.52% for R100 ≥ 1 mL and R100 < 1 mL, respectively, in the EBRT combination therapy group (p = 0.0070). CONCLUSIONS: Rectal toxicity was relatively rare in this study compared with previous reports. For Japanese prostate cancer patients, R100 < 1 mL in both PI and EBRT combination therapy groups and interactive planning in EBRT combination therapy group may be effective in decreasing the incidence of rectal toxicity.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy: clinical results with a median follow-up of 26 months.

BACKGROUND: A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy was performed. The first clinical results were reported with a median follow-up of 26 months. PATIENTS AND METHODS: Forty-six female breast cancer patients with positive hormone receptors and tumors ≤3 cm, pN0M0, completed the protocol treatment. After breast-conserving surgery and histological confirmation of negative surgical margins and pN0, brachytherapy applicators were implanted either postoperatively (n = 45) or intraoperatively (n = 1). High-dose-rate brachytherapy of 36 Gy/6 fractions was delivered. All clinical data were prospectively collected using case report forms and the Common Terminology Criteria for Adverse Events ver.3.0. RESULTS: At the median follow-up of 26 months, no breast cancer recurrence of any type was observed. Sequelae ≥G2 were dermatitis (G2, 7 %), fibrosis (G2, 11 %; G3, 4 %), fracture (G2, 2 %), pain (G2, 7 %; G3, 2 %), and soft tissue necrosis (G2, 6 %). Cosmetic outcomes evaluated by excellent/good scores were 100 % at pre-therapy (n = 46), 94 % at 12 months (n = 46), and 81 % at 24 months (n = 36), respectively. CONCLUSIONS: Disease control and sequelae were satisfactory due to the strict eligibility and protocol-defined treatment parameters. The cosmetic outcomes were comparable to those of previous Japanese breast-conserving therapy series.

Seed migration after transperineal interstitial prostate brachytherapy by using loose seeds: Japanese prostate cancer outcome study of permanent iodine-125 seed implantation (J-POPS) multi-institutional cohort study.

BACKGROUND: The incidence and associated factors of loose seed migration were investigated in cohort 1 of the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS). METHODS: The study subjects were 2160 patients, consisting of 1641 patients who underwent permanent iodine-125 seed implantation (PI) and 519 patients who underwent PI combined with external beam radiation therapy (PI + EBRT). The presence or absence of seed migration to the chest and abdominal/pelvic region was determined. RESULTS: Seed migration was observed in 22.7 % of PI group patients and 18.1 % of PI + EBRT group patients (p = 0.0276). Migration to the lungs and abdominal/pelvic region was observed in 14.6 % and 11.1 % of the patients in the PI group, and 11.2 % and 8.5 % of the patients in the PI + EBRT group, respectively. In the PI group, the number of implanted seeds was associated with the seed migration incidence. Neither the PI nor the PI + EBRT group showed any difference in the volume of the prostate receiving 100 % of the prescribed dose (V100 [%]) or the minimal dose received by 90 % of the prostate volume (D90 [Gy]) between the patients with and without seed migration. CONCLUSIONS: This prospective cohort study investigating the largest number of past cases showed no difference in D90 (Gy) or V100 (%) between seed migration or the absence thereof in both the PI group and PI + EBRT group. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00534196.

Urinary and Rectal Toxicity Profiles After Permanent Iodine-125 Implant Brachytherapy in Japanese Men: Nationwide J-POPS Multi-institutional Prospective Cohort Study.

PURPOSE: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT). METHODS AND MATERIALS: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiation therapy. RESULTS: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment. CONCLUSIONS: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other studies.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy: treatment planning and quality assurance.

BACKGROUND: In Japan, breast-conserving surgery with closed cavity has generally been performed for breast cancer patients, and accelerated partial breast irradiation (APBI) is considered difficult because Asian females generally have smaller breast sizes than Western females. Therefore, common identification of target and treatment plan method in APBI is required. A prospective multicenter study was conducted in Japan to determine institutional compliance with APBI using high-dose-rate interstitial brachytherapy (ISBT) designed for Japanese female patients. METHODS: For this study, 46 patients were recruited at eight institutions from January 2009 to December 2011. The reproducibility of the ISBT-APBI plan was evaluated using three criteria: (1) minimum clinical target volume dose with a clip dose ≥ 6 Gy/fraction, (2) irradiated volume constraint of 40-150 cm(3), and (3) uniformity of dose distribution, expressed as the dose non-uniformity ratio (DNR, V150/V100) < 0.35. The ISBT-APBI plan for each patient was considered reproducible when all three criteria were met. When the number of non-reproducible patients was ≤ 4 at study completion, APBI at this institution was considered statistically reproducible. RESULTS: Half of the patients (52 %) had a small bra size (A/B cup). The mean values of the dose-constrained parameters were as follows: Vref, 117 cm(3) (range, 40-282), DNR, 0.30 (range, 0.22-0.51), and clip dose, 784 cGy (range, 469-3146). A total of 43/46 treatment plans were judged to be compliant and ISBT-APBI was concluded to be reproducible. CONCLUSIONS: This study showed that multi-institutional ISBT-APBI treatment plan was reproducible for small breast patient with closed cavity.

Results of central pathology review of prostatic biopsies in a contemporary series from a phase III, multicenter, randomized controlled trial (SHIP0804).

To investigate contemporary rates of variation in the biopsy Gleason grading in prostate cancer, between local and central pathologists, based on central review of the pathological slides from Seed and Hormone for Intermediate-risk Prostate Cancer (SHIP) 0804, a phase III, multicenter, randomized, controlled study. From April 2008 to May 2011, 18 Japanese institutions participated. All H&E slides were reviewed independently, without clinical information, and a tumor grade was assigned according to the modified Gleason grading system proposed by the International Society of Urological Pathology (ISUP). Prostate biopsy specimens of 642 cases were available for evaluation. An exact concordance rate of Gleason score (GS) between local and central pathologists was determined to be 65.3%; with the under-grading and over-grading of grades to be 14.6% and 20.1%, respectively. The central review resulted in numbers of tumor-bearing cores reassigned in 99 of 616 cases in which such information by the local pathologists was available (16.1%). Discordance in biopsy Gleason grading was still found in one third of the cases in the SHIP0804 study. This information is valuable in extrapolating the diagnostic error range in contemporary clinical studies conducted without central pathological review.

Nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS).

BACKGROUND: To evaluate the safety and efficacy of brachytherapy with permanent iodine-125 seed implantation (PI) for prostate cancer. The nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS) has continued since July 2005. This manuscript presents the rationale, J-POPS study design, and the characteristics of initial participants enrolled in this study from July 2005 to June 2007. METHODS: All participants were treated with PI in accordance with the American Brachytherapy Society recommendations. The primary outcome measure was biochemical progression-free survival. Progression-free survival, overall survival, cause-specific survival, longitudinal changes in health-related quality of life, disease-specific quality of life, the International Prostate Symptom Score, and the incidence of adverse events were also investigated as secondary outcome measurements. RESULTS: Overall, 6,927 patients were enrolled by the end of 2010, that is approximately 40 % of all cases treated around the country. During the first 2 years, 2,354 participants were enrolled and 2,339 were actually treated with PI. The age range of participants was 45 to 89 years (median 69 years) and their risk classifications were 1,037 (44.3 %) at low risk, 1,126 (48.1 %) at intermediate risk, and 134 (5.7 %) at high risk, in addition to 16 participants whose classification was unknown. Of all patients, 76.6 % were treated with PI without external beam radiation therapy and 49.3 % received neoadjuvant hormone therapy. CONCLUSIONS: The J-POPS, a nationwide prospective cohort study that enrolled approximately 40 % of all PI cases in Japan, will provide highly reliable evidence, including outcomes and quality of life, after long-term follow-up.

Postmortem radiation safety and issues pertaining to permanent prostate seed implantation in Japan.

PURPOSE: If a prostate cancer patient treated with (125)I brachytherapy dies within 12 months after the treatment, prostate removal before cremation is recommended to avoid problems related to radioactivity in the ashes, such as inhalation of airborne particulate matter by crematorium staff or nearby residents. To provide guidance for such cases, a manual prepared under the editorial supervision of several professional associations was issued in 2008 in Japan. Herein, we investigated the incidence and causes of death, and the actions taken subsequent to death, among prostate cancer patients who died within 12 months after (125)I brachytherapy over a 10-year period in Japan; and we compared the results before and after the manual was issued. METHODS AND MATERIALS: Data extracted from the Japan Radioisotope Association database for the period from September 2003 to the end of December 2013 were used. RESULTS: Of 27,976 patients who underwent (125)I brachytherapy during the specified period, 79 died within 12 months after implantation, including 3 who died in the 2011 earthquake and tsunami. The prostate and brachytherapy source were retrieved at autopsy from 69 of the 79 patients. Autopsy could not be performed on the other 10 patients, 2 of whom died in the earthquake. Autopsy and retrieval of the brachytherapy source were significantly more common after issuance of the manual than before (22/28 cases before; 47/49 cases after; p=0.021). CONCLUSION: In most cases of early death after (125)I brachytherapy in Japan, the brachytherapy source was retrieved.