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.

Erectile function status is highly associated with prostate-specific antigen bounce in localized prostate cancer patients treated with permanent prostate brachytherapy.

OBJECTIVES: To examine the relationship between erectile function status and prostate-specific antigen bounce after prostate brachytherapy for localized prostate cancer. METHODS: We identified 154 patients who were followed up for at least 24 months after brachytherapy. Erectile function status was assessed prospectively before brachytherapy (baseline), and 3, 6, 12, 18, 24 and 36 months postoperatively using the International Index of Erectile Function-15 questionnaire. Prostate-specific antigen bounce was defined as an increase of at least 0.4 ng/mL from a previous prostate-specific antigen level with a subsequent decline equal to, or less than, the initial nadir without treatment. A logistic regression analysis was used to identify a significant set of independent predictors of prostate-specific antigen bounce after brachytherapy. RESULTS: Prostate-specific antigen bounce was observed in 38 (24.7%) men. The prostate-specific antigen bounce group had a higher erectile function domain score, higher orgasmic function domain score, and higher total International Index of Erectile Function-15 score before (at baseline) and after brachytherapy (3, 6, 12, 18, 24 and 36 months after brachytherapy) than their counterparts (P < 0.05). Of the 77 patients who completed the International Index of Erectile Function-15 questionnaire 18 months after brachytherapy (the median time of prostate-specific antigen bounce), sexual desire and intercourse satisfaction domain scores, and total International Index of Erectile Function scores 18 months after brachytherapy correlated with the occurrence of prostate-specific antigen bounce. A multivariate analysis identified the intercourse satisfaction domain score 18 months after brachytherapy as an independent indicator for the occurrence of prostate-specific antigen bounce (P = 0.008). CONCLUSIONS: International Index of Erectile Function-15 score seems to be correlated with the prostate-specific antigen bounce in prostate cancer patients undergoing brachytherapy, and an occurrence of prostate-specific antigen bounce seems to be more likely in those who are more sexually active.

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.

Five-year potency preservation after iodine-125 prostate brachytherapy.

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 (125)I 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.

A rare instance of latent systematic error in volumetric-modulated arc therapy with field-extended multi-isocentre irradiation leading to a serious dose-delivery accident.

Volumetric-modulated arc therapy (VMAT) with field-extended multi-isocentre irradiation (VMAT-FEMII) is an effective irradiation technique, particularly for large planning target volumes in the craniocaudal direction. A variety of treatment planning techniques have been reported to reduce the dosimetric impact. However, there is no guarantee that unexpected latent systematic errors would not occur. Herein, we report the experience with a rare case that could have led to a serious VMAT-FEMII-related accident. A patient with uterine cervical carcinoma was scheduled for VMAT-FEMII to the whole pelvis and the para-aortic lymph node region. A combination of the two sets of field groups with different isocentres was planned: one to cover the para-aortic lymph nodes and the other to cover the whole pelvis. Measurements based on the pretreatment dose delivery quality assurance (QA) revealed an unexpected overdose of >20% in the field overlap region. This overdose phenomenon is not reflected in the calculated dose distribution in the radiotherapy treatment planning system. Therefore, the plan was altered; a homogeneous dose distribution inside the dose junction was achieved. Several analyses were performed to elucidate the overdosing phenomenon. However, no conclusive answer was found to why non-reflection at the calculated dose distribution was found. The limitations to VMAT-FEMII are primarily related to systematic errors in the positional setup from patient-derived and/or mechanical sources. However, this report highlights a rare case of overdosing caused by inverse optimization and dose calculation. We recommend checking the aperture status of the jaw and multi-leaf collimator at each control point of the treatment plan and using a high-resolution image measurement system on a VMAT-FEMII QA to confirm the dose junction status.

Trimodality Therapy With Iodine-125 Brachytherapy, External Beam Radiation Therapy, and Short- or Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer: Results of a Multicenter, Randomized Phase 3 Trial (TRIP/TRIGU0907).

PURPOSE: This phase 3 randomized investigation was designed to determine whether 30 months of androgen deprivation therapy (ADT) was superior to 6 months of ADT when combined with brachytherapy and external beam radiation therapy (EBRT) for localized high-risk prostate cancer. METHODS AND MATERIALS: This study was conducted at 37 hospitals on men aged 40 to 79 years, with stage T2c-3a, prostate-specific antigen >20 ng/mL, or Gleason score >7, who received 6 months of ADT combined with iodine-125 brachytherapy followed by EBRT. After stratification, patients were randomly assigned to either no further treatment (short arm) or 24 months of adjuvant ADT (long arm). According to the Phoenix definition of failure, the primary endpoint was the cumulative incidence of biochemical progression. Secondary endpoints included clinical progression, metastasis, salvage treatment, disease-specific mortality, overall survival, and grade 3+ adverse events. An intention-to-treat analysis was conducted using survival estimates determined using competing risk analyses. RESULTS: Of 332 patients, 165 and 167 were randomly assigned to the short and long arms, respectively. The median follow-up period was 9.2 years. The cumulative incidence of biochemical progression at 7 years was 9.0% (95% CI, 5.5-14.5) and 8.0% (4.7-13.5) in the short and long arms, respectively (P = .65). The outcomes of secondary endpoints did not differ significantly between the arms. Incidence rates of endocrine- and radiation-related grade 3+ adverse events for the short versus long arms were 0.6 versus 1.8% (P = .62) and 1.2 versus 0.6% (P = .62), respectively. CONCLUSIONS: Both treatment arms showed similar efficacy among selected populations with high-risk features. The toxicity of the trimodal therapy was acceptable. The present investigation, designed as a superiority trial, failed to demonstrate that 30-month ADT yielded better biochemical control than 6-month ADT when combined with brachytherapy and EBRT. Therefore, a noninferiority study is warranted to obtain further evidence supporting these preliminary results.

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.

Magnetic resonance imaging of endolymphatic hydrops: a comparison of methods with and without gadolinium-based contrast agent administration.

In the evaluation of endolymphatic hydrops (EH) using magnetic resonance (MR) imaging, hybrid of reversed image of positive endolymph signal and native image of perilymph signal multiplied with heavily T2-weighted MR cisternography (HYDROPS-Mi2) imaging with the intravenous administration of a gadolinium-based contrast agent (IV-GBCA) has been utilized. Recently, MR cisternography (MRC) without GBCA has been proposed as a potential alternative method. However, the feasibility of EH evaluation by MRC without GBCA has not been established. The present study aimed to compare HYDROPS-Mi2 imaging with IV-GBCA to MRC without IV-GBCA for the evaluation of EH. In 40 ears of 20 patients with clinically suspected EH, MRC at pre-IV-GBCA and HYDROPS-Mi2 images from 4 h post-IV-GBCA were analyzed. The saccular height on the MRC (SH-MRC) was measured. The percentage of the volume of the endolymphatic space within the whole lymphatic space of the vestibule on the HYDROPS-Mi2 image (%ELvolume-HYD) was measured. The correlation between the SH-MRC and %ELvolume-HYD was calculated. The receiver operating characteristic (ROC) of the SH-MRC and %ELvolume-HYD for the clinical diagnosis of EH was evaluated. The Spearman's rank correlation coefficient between the SH-MRC and %ELvolume-HYD was 0.102. The areas under the ROC curve were 0.570 for the SH-MRC, and 0.926 for the %ELvolume-HYD. In conclusion, there was no significant correlation between the MRC without IV-GBCA and the HYDOROPS-Mi2 with IV-GBCA in the evaluation of EH.

Evaluation of dose perturbations around iodine-125 seed sources in supplemental external beam prostate radiotherapy.

We investigated dose perturbations caused by 125I seeds in patients undergoing supplemental external beam radiotherapy (EBRT) for prostate cancer. We examined two types of nonradioactive seed models: model 6711 and model STM1251. All experiments were performed using a water-equivalent phantom. Radiochromic film was used to measure the dose distributions adjacent to the seeds upstream and downstream of the external beam source. Single and clusters of multiple seeds were placed in slots in a solid water (SW) slab to measure dose perturbations with separate versus dense seed placement at beam energies of 6 or 10 MV. Monte Carlo simulations (MCSs) were also performed to include the theoretical basis against film dosimetry. Distinct patterns of dose enhancement (buildup [BU]) were upstream, and dose reduction (builddown [BD]) were downstream of the radiation source. Model 6711 with lower photon beam energies produced larger dose perturbations of BU and BD than the model STM1251. The results showed the same tendency with different seed placements and beam energies. However, these differences were not observed in the rotational irradiation measurement, which replicated a clinical plan. Dose perturbations around seeds result in dose enhancement and dose reduction with varying impact depending on the photon beam energy and seed type. This has the potential to cancel out these perturbations using multiple beam direction fields.

Salvage focal brachytherapy in castration-resistant prostate cancer with neuroendocrine differentiation after radiation therapy.

Introduction: Treatment strategy for castration-resistant prostate cancer with neuroendocrine differentiation after radiation therapy has not been established. Case presentation: We described a case of castration-resistant prostate cancer with neuroendocrine differentiation after initial external beam radiotherapy followed by salvage androgen deprivation therapy. Magnetic resonance imaging detected recurrence of a suspicious lesion in the left lobe of the prostate, although the prostate-specific antigen level was <0.2 ng/mL. Transperineal prostate saturation needle biopsy detected adenocarcinoma with neuroendocrine differentiation. The patient underwent salvage focal brachytherapy and had a prostate-specific antigen progression-free survival of 20 months with no obvious adverse events. No recurrence has been detected on magnetic resonance imaging for 18 months. Conclusion: Salvage focal brachytherapy for prostate cancer after external beam radiotherapy can be one of the treatment strategies for local recurrence of castration-resistant prostate cancer with neuroendocrine differentiation.

Distribution of Gadolinium-based Contrast Agent after Leaking into the Cerebrospinal Fluid: Comparison between the Cerebral Cisterns and the Lateral Ventricles.

PURPOSE: Leakage of a small amount of intravenously administered gadolinium-based contrast agents (GBCAs) into the cerebrospinal fluid (CSF) space has been reported, even in healthy subjects without blood-brain barrier disruption. Several candidates including the choroid plexus and cortical veins have been proposed as the source of the leakage. The purpose of this study was to evaluate the distribution of intravenously administered GBCA leakage into the CSF by comparing the contrast enhancement of the cerebral cisterns to the lateral ventricles (LVs). METHODS: In 26 patients with a suspicion of endolymphatic hydrops (21-80 years old), a three-dimensional real inversion recovery (3D-real IR) image was obtained at pre-, and at 5 min, and 4 h post-intravenous administration of a single dose of GBCA (IV-SD-GBCA). In the 3D-real IR image, the signal intensities (SIs) in the anterior horn of the LV (LVante), the trigone of the LV (LVtri), the Sylvian fissure (SyF), the ambient cistern (Amb), the prepontine cistern (PPC), the cerebellopontine angle cistern (CPA), and the vitreous (Vit) were measured. The differences in the SI at pre-, and at 5 min and 4 h post-IV-SD-GBCA were evaluated for each region. The change in the SI pre- to post-IV-SD-GBCA (SIchange) were calculated for each region. The differences in the SIchange in each region were evaluated at 5 min and 4 h post-IV-SD-GBCA. A Steel-Dwass's test was applied to correct for multiple comparisons. RESULTS: The SIs of all regions at 4 h post-IV-SD-GBCA were significantly higher compared with pre-IV-SD-GBCA (P < 0.05). The SIchange in the SyF, Amb, PPC, and the CPA were significantly higher compared with those of the LVante, LVtri, and the Vit at 4 h post-IV-SD-GBCA (P < 0.05). CONCLUSION: The contrast enhancement in the cerebral cisterns was greater than that in the LVs.

Age-related changes in the distribution of intravenously administered gadolinium-based contrast agents leaked into the cerebrospinal fluid in patients with suspected endolymphatic hydrops.

PURPOSE: The purpose of this retrospective study was to investigate the relationship between age and leakage of intravenously administered gadolinium-based contrast agents (GBCAs) into the cerebrospinal fluid (CSF) by volumetric segmentation of the whole-cranium CSF. MATERIALS AND METHODS: In 30 patients clinically diagnosed with suspected endolymphatic hydrops, the three-dimensional real inversion recovery (3D-real IR) images were obtained at pre- and 4 h post-intravenous administration of a single dose of GBCA. The volume of interest was set on the whole-cranium CSF in the 3D-real IR image. The signal intensity (SI)-increase of the ventricular CSF and the extra-ventricular CSF at 4 h post-administration of GBCA compared to pre-administration was measured. The relationship between the age of the patient and the SI-increase was evaluated. RESULTS: A correlation between age and the SI-increase was observed in the whole-cranium CSF. The correlation coefficient between age and the SI-increase in the ventricular CSF was higher than that in the extra-ventricular CSF. CONCLUSION: An age-related leakage of the intravenously administered GBCAs was found in the whole-brain CSF. The age-related change in the distribution of the GBCA leakage was more prominent in the ventricular CSF than in the extra-ventricular CSF.

Radiation dose rate variations in different measurement scenarios after prostate 125I brachytherapy.

PURPOSE: This study aimed to directly compare different measurement scenarios using a supplemental radiation exposure measurement data set. MATERIALS AND METHODS: Two sets of measurement scenarios comparing different body postures, such as standing and chair sitting positions, and different measurement directions, such as anterior and posterior directions, were assessed for radiation dose rate variations in this study at the Tokyo Medical Center, Japan. The estimated precaution time for holding children in the spoon position while sitting was also calculated. RESULTS: Different radiation dose rate measurement scenarios showed different variation tendencies. Radiation dose rate measurement showed higher mean values of measured radiation dose tendency in the standing position than in the sitting positions. The measurement from the anterior direction showed a slightly lower tendency than that from the posterior direction. Assuming a dose limit of 1 mSv, the precaution time calculated for children being held in the spoon position for a certain duration every day was 51.5 (range, 12.5-152.2) minutes. CONCLUSIONS: Our study presented a supplemental radiation exposure measurement data set and directly compared different measurement scenarios. Several trends in radiation exposure variations were found in the measurement scenarios at different body postures and different measurement directions. Our study data set could be a useful source of concrete information regarding radiation safety and contribute to the review and revision of public guidance in the future.

Quantification of Endolymphatic Space Volume after Intravenous Administration of a Single Dose of Gadolinium-based Contrast Agent: 3D-real Inversion Recovery versus HYDROPS-Mi2.

PURPOSE: Recently, the use of 3D real inversion recovery (3D-real IR) imaging has been proposed for the evaluation of endolymphatic hydrops (EH). This method shows similar contrast between the endolymphatic and perilymphatic spaces and surrounding bone compared with the hybrid of reversed image of positive endolymph signal and native image of perilymph signal multiplied with heavily T2-weighted MR cisternography (HYDROPS-Mi2) image. We measured the volume of the endolymphatic space using 3D-real IR and HYDROPS-Mi2 images, and compared the measurements obtained with both techniques. METHODS: HYDROPS-Mi2 and 3D-real IR images were obtained for 30 ears from 15 patients with clinical suspicion of EH; imaging was performed 4 h after intravenous administration of a single dose of gadolinium-based contrast agent. We measured the volume of the endolymphatic space in the cochlea and vestibule by manually drawing the regions of interest. The correlation between endolymphatic volume determined from HYDROPS-Mi2 images and 3D-real IR images was calculated. RESULTS: There was a strong positive linear correlation between the cochlear and vestibular endolymphatic volume determined from HYDROPS-Mi2 and 3D-real IR images. The Spearman's rank correlation coefficient (ρ) between the measurements obtained with both images was 0.805 (P < 0.001) for the cochlea and 0.826 (P < 0.001) for the vestibule. CONCLUSION: The endolymphatic volume measured using 3D-real IR images strongly correlated with that measured using HYDROPS-Mi2 images. Thus, 3D-real IR imaging might be a suitable method for the measurement of endolymphatic volume.

Comparison of prostate verification with implanted gold markers in tissue surrounding the prostate and pelvic bony anatomy for external beam radiation therapy following low-dose-rate brachytherapy: a prospective clinical trial.

We aimed to investigate whether gold marker implantation in the tissue surrounding the prostate could accurately monitor setup errors during external beam radiation therapy (EBRT) following low-dose-rate (LDR) brachytherapy. Thirty-eight patients had confirmed intermediate- or high-risk prostate cancer and received EBRT following LDR brachytherapy. In >175 computed tomography imaging sessions, the average values of the weekly setup error during EBRT to the prostate centroid at the time of gold marker matching in the surrounding tissue of the prostate and pelvic bone matching were measured and then compared using the Wilcoxon signed-rank test. Gold marker matching in the surrounding tissue of the prostate estimated setup errors better than those estimated by bone matching (3D displacement = 2.7 ± 2.0 vs 3.8 ± 2.6 mm, P < 0.01). Overall, the standard deviation of systematic (Σ) and random (σ) setup error was lower with gold marker matching than with bone matching (3D displacement = 1.8 and 1.1 mm vs 2.1 and 1.6 mm, respectively). With gold marker matching, the setup error of the position of the prostate centroid was smaller, and the optimal setup margin was lower than that with bone matching (2Σ + 0.7σ and 2.5Σ + 0.7σ of 3D displacement = 4.3 and 5.2 mm vs 5.3 and 6.4 mm, respectively). This high-precision radiotherapy approach placing gold markers in the surrounding tissue of the prostate can allow more accurate setup during EBRT following LDR brachytherapy.

Signal Intensity of the Cerebrospinal Fluid after Intravenous Administration of Gadolinium-based Contrast Agents: Strong Contrast Enhancement around the Vein of Labbe.

PURPOSE: Since the first report on the deposition of gadolinium in the brain parenchyma after repeated intravenous administrations of gadolinium-based contrast agent GBCA (IV-GBCA), the mechanisms of penetration and retention are still remaining a hot topic of discussion and a target of investigation. We routinely obtain endolymphatic hydrops (EH) images at 4 h after IV administration of a single dose (SD) of GBCA (IV-SD-GBCA) using heavily T2-weighted three-dimensional fluid-attenuated inversion recovery imaging (hT2W-3D-FLAIR). Occasionally, we have encountered cases, which indicate high-signal intensity (SI) in the cerebrospinal fluid (CSF) surrounding the vein of Labbe. The purpose of the present study was to investigate the degree of contrast enhancement of the CSF surrounding the vein of Labbe on hT2W-3D-FLAIR after IV-SD-GBCA in comparison with other CSF spaces. MATERIALS AND METHODS: In 25 patients with a suspicion of EH, a magnetic resonance cisternography (MRC) and an hT2W-3D-FLAIR were obtained at 4 h after IV-SD-GBCA. The perivascular space (PVS) in the basal ganglia, CSF spaces in the ambient cistern (CSF-Amb), the CSF surrounding the superficial middle cerebral vein (CSF-SMCV), and the CSF surrounding the vein of Labbe (CSF-VL) were segmented on MRC. The PVS and CSF regions were co-registered onto the hT2W-3D-FLAIR and the SI of the PVS and CSF spaces were measured. The SI ratio (SIR) of the post-contrast hT2W-3D-FLAIR to the pre-contrast hT2W-3D-FLAIR was measured. Significant differences were evaluated using Steel-Dwass's test for multiple comparisons. RESULTS: The SIR of the CSF-VL was significantly higher than that of the PVS (P = 0.008), the CSF-Amb (P = 0.021), and the CSF-SMCV (P = 0.023). CONCLUSION: The strong contrast enhancement of CSF space around the vein of Labbe was confirmed on hT2W-3D-FLAIR at 4 h after IV-GBCA compared to the PVS and the other CSF spaces.

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.

Hypofractionated stereotactic radiotherapy with and without transarterial chemoembolization for small hepatocellular carcinoma not eligible for other ablation therapies: Preliminary results for efficacy and toxicity.

AIM: To investigate the efficacy and toxicity of hypofractionated stereotactic radiotherapy for the treatment of patients presenting with hepatocellular carcinoma (HCC) in a single institutional setting. METHODS: Sixteen patients who presented with solitary HCC, including two patients with a tumor thrombus of the portal veins, were treated with stereotactic radiotherapy with or without transarterial chemoembolization. The criteria for stereotactic radiotherapy were existence of technical difficulties for other ablation therapies, inoperable disease or refusal to undergo surgery, tumor staged as Grade A or B according to the Child-Pugh classification, and solitary tumor distant from the gastrointestinal tract and kidney with a tumor volume <100 cm(3). In 14 of 16 patients, a total dose of 35- 50 Gy was delivered in 5-7 fractions over 5-9 days. RESULTS: At the end of a mean follow-up of 612 days (median 611 days; range 244-994 days), all patients were alive. Eight of 16 patients had complete responses and seven others were judged as stable with lipiodol accumulation. In one patient, local recurrence developed after 489 days. Intrahepatic recurrences developed outside the treated volume in six patients and no extrahepatic metastases developed during follow-up. No serious treatment-related toxic manifestations developed. CONCLUSIONS: Stereotactic radiotherapy for HCC with or without transarterial chemoembolization is feasible therapy and provides good local control with a short treatment period. Stereotactic radiotherapy may be of clinical benefit in patients who are inoperable or for whom there are difficulties in other ablation therapies.

Relationship between Contrast Enhancement of the Perivascular Space in the Basal Ganglia and Endolymphatic Volume Ratio.

PURPOSE: We routinely obtain the endolymphatic hydrops (EH) image using heavily T2-weighted three dimensional-fluid attenuated inversion recovery (hT2w-3D-FLAIR) imaging at 4 hours after intravenous administration of a single-dose of gadolinium-based contrast media (IV-SD-GBCM). While repeating the examination, we speculated that the contrast enhancement of the perivascular space (PVS) in the basal ganglia might be related to the degree of EH. Therefore, the purpose of this study was to investigate the relationship between the endolymphatic volume ratio (%ELvolume) and the signal intensity of the PVS (SI-PVS). MATERIALS AND METHODS: In 20 patients with a suspicion of EH, a heavily T2-weighted 3D-turbo spin echo sequence for MR cisternography (MRC) and an hT2w-3D-FLAIR as a positive perilymph image (PPI) were obtained at 4 hours after IV-SD-GBCM. The %ELvolume of the cochlea and the vestibule were measured on the previously reported HYDROPS2-Mi2 image. The PVS in the basal ganglia was segmented on MRC using a region-growing method. The PVS regions were copied and pasted onto the PPI, and the SI-PVS was measured. The larger value of the right and the left ears was employed as the %ELvolume, and the weighted average of both sides was employed as the SI-PVS. The correlation between the %ELvolume and the SI-PVS was evaluated. RESULT: There was a strong negative linear correlation between the %ELvolume of the cochlea and the SI-PVS (r = -0.743, P < 0.001); however, there was no significant correlation between the %ELvolume of the vestibule and the SI-PVS (r = -0.267, P = 0.256). CONCLUSION: There was a strong negative correlation between the cochlear %ELvolume and the SI-PVS. Contrast enhancement of PVS might be a biomarker of EH.

Plan reproducibility of intraoperatively custom-built linked seeds compared to loose seeds for prostate brachytherapy.

PURPOSE: Few studies have compared the implant quality of linked and loose seeds for prostate brachytherapy. This study aimed to evaluate and compare plan reproducibility of intraoperatively built custom linked seeds and loose seeds for prostate brachytherapy. MATERIAL AND METHODS: Between December 2010 and March 2014, 76 localized prostate cancer patients received Iodine-125 brachytherapy with external beam radiotherapy. Linked and loose seeds were implanted in 39 and 37 patients, respectively. The primary endpoint was the mean (± standard deviation) of the absolute change in the minimum dose received by 90% of the prostate volume between intraoperative and post-operative planning (ΔD90) to confirm plan reproducibility. Comparisons between the groups were evaluated using 2-sample t tests. RESULTS: The ΔD90 values were 6.95 ± 11.6% and -0.41 ± 8.5% for the loose and linked seed groups, respectively (p < 0.01). The linked seed group showed decreased post-operative D90 (118.8% vs. 127.2%), V150 (51.7% vs. 66.7%), and RV100 (0.44 ml vs. 0.61 ml) compared to the loose seed group (p < 0.01), whereas lung migration tended to be reduced (0% vs. 8%). CONCLUSIONS: The plan reproducibility of the linked seed group was better than that of the loose seed group. Moreover, the linked seed group showed less migration and lower rectal dose.