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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Predictive factors of long-term rectal toxicity following permanent iodine-125 prostate brachytherapy with or without supplemental external beam radiation therapy in 2216 patients.

PURPOSE: We analyzed factors associated with rectal toxicity after iodine-125 prostate brachytherapy (BT) with or without external beam radiation therapy (EBRT). METHODS AND MATERIALS: In total, 2216 prostate cancer patients underwent iodine-125 BT with or without EBRT between 2003 and 2013. The median followup was 6.9 years. Cox proportional hazards modeling was used for univariate and multivariate analyses to assess clinical and dosimetric factors associated with rectal toxicity. Dosimetric parameters from 1 day after implantation (Day 1) and 1 month after implantation (Day 30) were included in the analyses. RESULTS: The 7-year cumulative incidence of Grade 2 or higher rectal toxicity was 5.7% in all patients. The multivariate analysis revealed that antiplatelet or anticoagulant therapy, neoadjuvant androgen deprivation therapy, treatment modality, Day 1 rectal volume receiving 100% of the prescribed dose (RV100), and the Day 30 minimal percent of the prescribed dose delivered to 30% of the rectum (RD30) were associated with rectal toxicity. Day 1 RV100 was a common predictor in both BT-alone and the BT + EBRT groups. The 5-year cumulative incidence of Grade 2 or higher rectal toxicity was 12.6%, 5.9%, and 1.7% for BT + 3-dimensional conformal radiation therapy, BT + intensity-modulated radiation therapy, and the BT-alone groups, respectively (p < 0.001). CONCLUSIONS: Rectal dosimetric parameters in BT were associated with late rectal toxicity. Although the risk of rectal toxicity was higher when EBRT was combined with BT, with proper and achievable rectal dose constraints intensity-modulated radiation therapy yielded less toxicity than 3-dimensional conformal radiation therapy.

Prostate-specific antigen nadir within 12 months as an early surrogate marker of biochemical failure and distant metastasis after low-dose-rate brachytherapy or external beam radiotherapy for localized prostate cancer.

Prostate-specific antigen nadir (nPSA) after radiotherapy for localized prostate cancer has been investigated as a predictor. However, nPSA usually requires several years, limiting its clinical utility. We investigated the significance of nPSA within 12 months (nPSA12) after low-dose-rate prostate brachytherapy (LDR-PB) or external beam radiotherapy (EBRT) on treatment outcomes. Between 2006 and 2014, 663 patients with prostate cancer were treated with LDR-PB or EBRT at two institutions. Four hundred and seventy-four men received LDR-PB and 189 men received EBRT, without androgen deprivation therapy. The Kaplan-Meier method was used for biochemical failure (BF)-free survival (BFFS) and distant metastasis (DM)-free survival (DMFS) analyses, and multivariable Cox regression analysis was performed. The median follow-up was 61.3 months. The median nPSA12 in the LDR-PB and EBRT cohorts was 0.7 and 1.0 ng/mL, respectively. The 7-year BFFS and DMFS rates in LDR-PB patients with nPSA12 ≤ 0.7 ng/mL were 99.1% and 99.5%, respectively; when nPSA12 was >0.7 ng/mL, they were 90.2% and 94.8%, respectively. In EBRT patients with nPSA12 ≤ 1.0 ng/mL, BFFS and DMFS rates were 85.4% and 98.5%, respectively; when nPSA12 was >1.0 ng/mL, they were 67.1% and 87.2%, respectively. nPSA12 was an independent predictor of BF and DM in both cohorts (LDR-PB, P = 0.004 and 0.020, respectively; EBRT, P = 0.005 and 0.041, respectively). The nPSA12 after LDR-PB or EBRT is significantly associated with treatment outcomes of prostate cancer. Higher nPSA12 may identify patients at high risk of relapse who might benefit from salvage treatment.

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.

Variability of treatment planning of seed implantation: A Japanese multicenter simulation study.

PURPOSE: This multicenter study was conducted to evaluate the current variability of treatment planning of seed implantation in Japanese centers and the feasibility of two virtual trials. METHODS AND MATERIALS: Two types of contour data were sent to 12 radiation oncologists with a request letter that asked them to make treatment plans on the data in the same manner as in their own practice. Five of the 12 radiation oncologists were asked to participate in the two virtual trials in which the D90 (dose to the hottest 90% of prostate volume) was 1) required to be set at just 180 Gy and 2) increased as much as possible without violating other limitations. RESULTS: A relatively high dose with a small deviation was irradiated to the prostate in Japanese centers (mean D90 = 188 Gy; SD = 10 Gy). In the virtual trials, all five physicians could achieve 180 Gy for the D90 with a very small deviation, although the urethral dose showed relatively large deviations. Dose escalation without increase of urethral dose or V150 was difficult, although the rectum could be spared by most of the physicians. CONCLUSION: Our study showed a relatively high dose with a small deviation was prescribed to the prostate in Japanese centers. Consolidated protocols such as D90 = 180 Gy could be available for future trials. Meanwhile, our study suggested that some cautions might be needed for urethral dose and the V150, even when a relatively low D90 was requested.

Quantitative analysis of genitourinary toxicity after iodine-125 brachytherapy for localized prostate cancer: Followup of the International Prostate Symptom Score and Overactive Bladder Symptom Score.

PURPOSE: To analyze genitourinary toxicity by followup of the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) after prostate brachytherapy. METHODS AND MATERIALS: Six hundred eighty patients were treated with iodine-125 brachytherapy for localized prostate cancer. IPSS, OABSS, and two categories of IPSS questions (storage symptom score [IPSS-S] and voiding symptom score [IPSS-V]) were evaluated. RESULTS: The median followup was 54 months (range, 24-108). All scales showed rapid increases followed by gradual decreases. The median times to IPSS peak and resolution were 1 and 6 months, respectively. The resolution rates of IPSS, IPSS-S, IPSS-V, and OABSS at the last followup were 84.2%, 86.3%, 89.5%, and 83.0%, respectively. The difference between IPSS baseline and peak was greater for larger preimplant prostate volumes (≥25 mL, p = 0.004). The time to resolution was longer for higher biologic effective dose (BED) (≥210 Gy, p = 0.019 [IPSS]), in those with larger prostate volumes (≥25 mL, p = 0.025 [OABSS]), in younger patients (younger than 70 years, p = 0.043 [IPSS-S]), and in those with androgen deprivation therapy (ADT) use (p = 0.049 [IPSS-V]). Urge incontinence, included in the OABSS, was observed more commonly in older patients (75 years and older, p = 0.018), with ADT use (p < 0.001), and for higher BED (≥210 Gy, p = 0.006). CONCLUSIONS: The IPSS and OABSS showed similar patterns of change. Urinary symptoms improved more rapidly in those with high baseline IPSS levels. The OABSS was useful for following urinary symptoms after prostate brachytherapy. Age, ADT use, preimplant prostate volume, and BED were significantly associated with urinary outcomes.

CSF Pulsation Artifacts on ADC Maps Obtained with Readout-segmented EPI.

PURPOSE: Diffusion-weighted imaging (DWI) using readout-segmented EPI (rs-EPI) can minimize distortion and blurring artifacts; however, we sometimes encounter cerebrospinal fluid (CSF) pulsation artifacts on apparent diffusion coefficient (ADC) maps, especially when the number of readout segments (NRS) is increased. The purpose of this study was to evaluate the effect of the NRS on the CSF pulsation artifacts in the ADC maps of healthy volunteers. METHODS: In 10 healthy volunteers, we obtained DWI from rs-EPI with a b-value of 0 and 1000 s/mm2. The NRS was set to 5, 7, or 9. An ADC map was generated from the trace image and the b = 0 image. Each scan was performed twice. A circular region of interest (ROI) was drawn in the pons and bilateral thalami. The standard deviation (SD) of the ROI was measured to assess the artifacts. Bilateral SD values were averaged for the ROIs in the thalami. The SD values from two successive scans of each NRS were averaged for the pons and thalami, respectively. For the qualitative analysis, the CSF pulsation artifacts on each ADC map were graded by two observers independently as 0, no artifact; 1, mild artifact; 2, moderate artifact; or 3, severe artifact. RESULTS: In the quantitative analysis, the SD values tend to increase with the increasing of NRS in both thalami and pons; however, the difference in the SD values from each NRS did not reach a statistically significant level. In the qualitative analysis, there was a statistically significant difference in the scores between 5 and 9 segments and between 7 and 9 segments with both the observers, respectively (P < 0.05). CONCLUSION: The CSF pulsation artifacts on ADC maps obtained with rs-EPI are affected by the NRS.

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.