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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.

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.

305 Background: The TRIP trial was a multicenter, phase 3 randomized investigation 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 radiotherapy (EBRT) for localized high-risk prostate cancer. Methods: The trial was done in 37 hospitals in Japan. Men between 40 to 79 years old with stage T2c-3a, or a prostate-specific antigen (PSA) >20 ng/ml or a Gleason score >7 received 6 months of ADT combined with I-125 brachytherapy at a prescription dose of 110 Gy, followed by EBRT of 45 Gy. Patients were randomly assigned either no further treatment (short arm) or 24 months of adjuvant ADT (long arm) after stratification. The primary endpoint was biochemical progression-free survival using the Phoenix definition of failure. Secondary endpoints included clinical progression, metastasis, salvage treatment, disease-specific survival, overall survival, and grade 3 or higher of adverse events. An intention-to-treat analysis was conducted with survival estimates determined using competing risk analyses. Results: Of 332 patients, 165 were randomized to the short and 167 to the long arm. The median follow-up periods were 9.43 and 9.24 years, respectively. 24 patients have died in each arm. The cumulative incidence for biochemical progression in the short vs. long arm were 10.4% (95% confidence interval [CI] 6.62-16.42) vs 9.5% (5.85-15.46) at 9 years, respectively (p=0.647). The cumulative incidences for clinical progression, distant metastases, salvage treatment, and disease-specific mortality events were not significantly different between the two arms. The overall survival rates of the short arm vs long arm were 87.2% (82.13-92.63%) and 85.9% (80.41-91.77%) at 9 years, respectively (p=0.914). Endocrine-related grade 3 morbidity for short arm vs long arm was 0.6% vs 1.8% (p=0.623), and radiation-related grade 3 morbidity was 1.2% vs 0.6% (p=0.622). Conclusions: In localized high-risk prostate cancer, TRIP did not demonstrate the superiority of 30 months vs. 6 months of ADT when combined with brachytherapy and EBRT. These data suggest that ultra-high radiation doses can be combined with a shorter course of ADT without compromising survival. Clinical trial information: UMIN000003992 .

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.

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

Treatment strategy for castration-resistant prostate cancer with neuroendocrine differentiation after radiation therapy has not been established.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 was0.2 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.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.

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.

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. 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. 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. 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.

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. 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). 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. 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. NCT00534196.

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.

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 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.

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.

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.

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.

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.

Purpose To broaden the current understanding of radiation exposure and risk and to provide concrete evidence of radiation safety related to 125I seed implantation. Methods and Materials Direct radiation exposure measurements were obtained from dosimeters provided to 25 patients who underwent 125I seed implantation, along with their family members. The estimated lifetime exposure dose and the precaution time for holding children near the patient's chest were calculated in two study periods. Results During the first and second study period, the mean estimated lifetime exposure doses were, respectively, 7.61 (range: 0.45, 20.21) mSv and 6.84 (range: 0.41, 19.20) mSv for patients, and 0.19 (range: 0.02, 0.54) mSv and 0.25 (range: 0.04, 1.00) mSv for family members. The mean ratios of first and second period measurements were 1.05 (range: 0.44, 3.18) for patients and 1.82 (range: 0.21, 7.04) for family members. The corresponding absolute differences between first and second period measurements were −0.77 (range: −11.40, 7.63) mSv and 0.06 (range: −0.26, 0.79) mSv, respectively. Assuming a dose limit of 1 mSv, the precaution times for holding a child every day of the first and second periods were 250.9 (range: 71.3, 849.4) min and 275.2 (range: 75.0, 883.4) min, respectively. Assuming a dose limit of 0.5 mSv, the corresponding precaution times were 179.0 (range: 35.6, 811.5) min and 178.9 (range: 37.5, 1131.8) min, respectively. Conclusions Our study demonstrated low radiation exposures to family members of patients undergoing 125I prostate implantation. It was clear that 125I seed implantation did not pose a threat to the safety of family members.

We examined the factors associated with urinary toxicities because of brachytherapy with iodine-125 with or without supplemental external beam radiotherapy (EBRT) for prostate cancer.We investigated 1313 patients with localized prostate cancer treated with iodine-125 brachytherapy with or without supplemental EBRT between 2003 and 2009. The International Prostate Symptom Score (IPSS) and Common Terminology Criteria for Adverse Events data were prospectively determined. Patients, treatment, and implant factors were investigated for their association with urinary toxicity or symptoms.IPSS resolution was not associated with biologically effective dose (BED). Baseline IPSS, total needles, and the minimal dose received by 30% of the urethra had the greatest effect according to multivariate analysis (MVA). Urinary symptom flare was associated with baseline IPSS, age, BED, and EBRT on MVA. Urinary symptom flare and urinary Grade 2 or higher (G2+) toxicity occurred in 51%, 58%, and 67% (p = 0.025) and 16%, 22%, and 20% (p = 0.497) of the180, 180-220, and220 Gy BED groups, respectively. Urinary G2+ toxicity was associated with baseline IPSS, neoadjuvant androgen deprivation therapy (NADT), and seed density on MVA. When we divided patients into four groups according to prostate volume (30 cc or ≥30 cc) and NADT use, urinary G2+ toxicity was most commonly observed in those patients with larger prostates who received NADT, and least in the patients with smaller prostates and no NADT.NADT was associated with urinary G2+ toxicity. Higher dose and supplemental EBRT did not appear to increase moderate to severe urinary toxicities or time to IPSS resolution; however, it influenced urinary symptom flare.

Purpose: To evaluate the feasibility of a simple estimation for the endolymphatic volume ratio (endolymph volume/total lymph volume = %ELvolume) from an area ratio obtained from only one slice (%EL1slice) or from three slices (%EL3slices). The %ELvolume, calculated from a time-consuming measurement on all magnetic resonance (MR) slices, was compared to the %EL1slice and the %EL3slices. Methods: In 40 ears of 20 patients with a clinical suspicion of endolymphatic hydrops, MR imaging was performed 4 hours after intravenous administration of a single dose of gadolinium-based contrast material (IV-SD-GBCM). Using previously reported HYDROPS2-Mi2 MR imaging, the %ELvolume values in the cochlea and the vestibule were measured separately by two observers. The correlations between the %EL1slice or the %EL3slices and the %ELvolume values were evaluated. Results: A strong linear correlation was observed between the %ELvolume and the %EL3slices or the %EL1slice in the cochlea. The Pearson correlation coefficient (r) was 0.968 (3 slices) and 0.965 (1 slice) for observer A, and 0.968 (3 slices) and 0.964 (1 slice) for observer B (P < 0.001, for all). A strong linear correlation was also observed between the %ELvolume and the %EL3slices or the %EL1slice in the vestibule. The Pearson correlation coefficient (r) was 0.980 (3 slices) and 0.953 (1 slice) for observer A, and 0.979 (3 slices) and 0.952 (1 slice) for observer B (P < 0.001, for all). The high intra-class correlation coefficients (0.991–0.997) between the endolymph volume ratios by two observers were observed in both the cochlea and the vestibule for values of the %ELvolume, the %EL3slices and the %EL1slice. Conclusion: The %ELvolume might be easily estimated from the %EL3slices or the %EL1slice.

Purpose To compare late genitourinary (GU) and gastrointestinal (GI) toxicity following different prostate cancer treatment modalities. Materials and methods This study included 1084 consecutive prostate cancer patients treated with conventional radiotherapy, intensity-modulated radiotherapy (IMRT), permanent iodine-125 implantation (PI) alone, and PI combined with external beam radiotherapy (PI+EBRT). The effects of treatment- and patient-related factors on late grade⩾2 (G2+) GU/GI toxicity risk were assessed. Results The median follow-up was 43months (range, 12–97months). Compared to the PI+EBRT, there was significantly less G2+ GU toxicity in the conventional radiotherapy (hazard ratio [HR]=0.39; 95% CI, 0.20–0.77) and the IMRT (HR=0.45, 95% CI, 0.27–0.73). Compared to the PI+EBRT, there was significantly more G2+ GI toxicity in the IMRT (HR=2.38; 95% CI, 1.16–4.87). In PI-related groups, prostate equivalent dose in 2Gy fractions was a significant predictor of G2+ GU toxicity ( p =0.001), and the rectal volume receiving more than 100% of the prescribed dose was a significant predictor of G2+ GI toxicity ( p =0.001). Conclusion The differences in the late G2+ GU/GI risk cannot be explained by the differences in treatment modalities themselves, but by the total radiation dose to the GU/GI tract, which had a causal role in the development of late G2+ GU/GI toxicity across all treatment modality groups.

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 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.

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.

We estimated variations in rectal volumes and dosimetry values including NTCP with interfractional motion during prostate IG-IMRT. Rectal volumes, DVH parameters, and NTCPs of 20 patients were analyzed. For this patient population, the median (range) volume on the initial plan for the rectum was 45.6 cc (31.3–82.0), showing on-treatment spread around the initial prediction based on the initial plan. DVH parameters of on-treatment CBCT analyses showed systematic regularity shift from the prediction based on the initial plan. Using the Lyman-Kutcher-Burman model, NTCPs of predicted late rectal bleeding toxicity of rectal grade ≥ 2 (RTOG) and the QUANTEC update rectal toxicity for the prediction based on the initial plan were 0.09% (0.02–0.24) and 0.02% (0.00–0.07), respectively, with NTCPs from on-treatment CBCT analyses being 0.35% (0.01–6.16) and 0.12% (0.00–4.11), respectively. Using the relative seriality model, for grade ≥ 2 bleeding rectal toxicity, NTCP of the prediction based on the initial plan was 0.64% (0.15–1.22) versus 1.48% (0.18–7.66) for on-treatment CBCT analysis. Interfraction variations in rectal volumes occur in all patients due to physiological changes. Thus, rectal assessment during 2D-based IG-IMRT using NTCP models has the potential to provide useful and practical dosimetric verification.

We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy.We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning in the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses.The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion.Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion.

To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after (125)I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter.To account for differences among radiation treatment modalities and fractionation schedules, rectal dose-volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUDsum) was determined by a summation of the brachytherapy and external-beam radiation therapy components.Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUDsum increased: 2.0% (2 of 102 patients) for70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUDsum (P=.000) as risk factors for grade 2+ rectal bleeding.Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.

Stereotactic body radiotherapy (SBRT) is the standard care for medically inoperable early non-small-cell lung cancer (NSCLC). However, it can be difficult to differentiate local recurrence from non-recurrence radiation-induced lung opacity. We retrospectively assessed (18)F-FDG PET/CT to detect local recurrence after SBRT for NSCLC.Between 2005 and 2011, 273 NSCLCs in 257 patients were treated with SBRT. Prescribed doses were 50Gy and 40Gy per 5 fractions for peripheral and central lesions, respectively. Tri-monthly follow-up CT scans were acquired. (18)F-FDG PET/CT scans were scheduled for screening at one year after SBRT or when recurrence was highly suspected. The dual-time-point maximum standardized uptake values (SUVmaxs) and their retention indexes (RIs) were obtained.A total of 214 (18)F-FDG PET/CT scans were obtained for 164 localized NSCLC tumors in 154 patients. The median follow-up period was 24.9 months (range: 6.3-72.1). Among these, 21 scans of 17 tumors were diagnosed as local recurrence. The median SUVmaxs on early and late images of recurrence and their RI were 5.0 (range: 3.2-10.7), 6.3 (range: 4.2-13.4), and 0.20 (range; 0-0.41), respectively. These were significantly higher than the respective values of non-recurrence images of 1.8 (range: 0.5-4.6), 1.7 (range: 0.5-6.1), and 0.00 (range: -0.37-0.41) (all p0.05). For SUVmaxs on early and late images, optimal thresholds were identified as 3.2 and 4.2. Using each threshold, the sensitivity and specificity were 100% and 96-98%, respectively. CT findings were classified into ground-glass opacity (N=9), scar or fibrotic change (N=96), consolidation with air-bronchogram (N=34), consolidation only (N=22), and nodule (N=17); the respective numbers of recurrence were 0, 0, 1, 3, and 17.SUVmaxs of (18)F-FDG PET/CT could detect local recurrence after SBRT for localized NSCLC. In contrast, CT scan results had a limited ability to diagnose local recurrence.

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 ¼ 0.205), D90 was 119.6 vs. 119.4% (P ¼ 0.884), urethral D10 was 157.5 vs. 146.1% (P ¼ 0.010), rectal V100 was 0.57 vs. 0.43 cc (P ¼ 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 ¼ 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.

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.

Purpose To evaluate the effectiveness of the single-energy metal artifact reduction (SEMAR) technique for improving the accuracy of I-125 seed identification in postimplant computed tomography (CT) after prostate brachytherapy. Methods and Materials Postimplant CT images of 40 patients treated with I-125 prostate brachytherapy were acquired. For all patients, 2 data sets were reconstructed, 1 with SEMAR algorithms (SEMAR image), and the other without SEMAR algorithms (non-SEMAR image). Seed locations are automatically detected by the automatic seed finder tool, and their locations were compared between the SEMAR and non-SEMAR images. Dosimetric parameters using seed locations as detected were compared. Results The true-positive fraction of properly detected seeds on the SEMAR image as determined from a reference seed distribution defined by one investigator was significantly higher than the true-positive fraction on the non-SEMAR image (p = 0.011). The variabilities in D90 (p = 0.001), V100 (p = 0.007), and V150 (p = 0.007) were significantly reduced for seed location on the SEMAR image as compared with non-SEMAR image. Conclusions Prostate postimplant CT with SEMAR improved the accuracy of seed localization and postimplant dosimetric parameters.

Purpose To investigate threshold dose (TD) of focal liver reaction (FLR) following stereotactic body radiotherapy (SBRT) for patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Materials and methods In consecutive 50 patients receiving SBRT for small HCC, 38 patients receiving SBRT and follow up >6months, FLR on follow-up CT had been previously studied. Patients with good concordance between FLR and highly irradiated area were eligible. Dose volume histogram (DVH) was used to identify TDs for FLR. Clinical factors were analyzed for correlation with TDs. Results Of 24 eligible patients, 23 had Child–Pugh score A and 1 scored B. Presence of FLR peaked at a median of 6 (range; 3–12) months. The median and 95% confidential intervals of TDs of pre-contrast and portal-venous phase CT were 32.4Gy (30.3–35.4) and 34.4Gy (31.9–36.0), respectively. Each median coefficient representing the concordance was 74.9% (range; 55.8–98.0%) and 80.5% (range; 70.8–92.4%), respectively. No clinical factors significantly correlated with the TDs. Conclusion We proposed 30Gy/5 fractions as TD of FLRs following SBRT for patients with HCC and liver cirrhosis. This TD will enable us to predict injured liver volume and to avoid complication beforehand from toxicity. Further pathological and clinical studies, in addition to more practical and precise data of DVH, are needed to clarify the significance of FLRs.

We investigated the usefulness of the fusion image created by transrectal ultrasonography (TRUS) and large-bore computed tomography (CT) for predicting pubic arch interference (PAI) during prostate seed brachytherapy. The TRUS volume study was performed in 21 patients, followed by large-bore computed tomography of patients in the lithotomy position. Then, we created TRUS-CT fusion images using a radiation planning treatment system. TRUS images in which the prostate outline was the largest were overlaid on CT images with the narrowest pubic arch. PAI was estimated in the right and left arch separately and classified to three grades: no PAI, PAI positive within 5 mm and PAI of >5 mm. If the estimated PAI was more than 5 mm on at least one side of the arch, we judged there to be a significant PAI. Brachytherapy was performed in 18 patients who were evaluated as not having significant PAI on TRUS. Intra-operative PAI was observed in one case, which was also detected with a fusion image. On the other hand, intra-operative PAI was not observed in one case that had been evaluated as having significant PAI with a fusion image. In the remaining three patients, TRUS suggested the presence of significant PAI, which was also confirmed by a fusion image. Intra-operative PAI could be predicted by TRUS-CT fusion imaging, even when it was undetectable by TRUS. Although improvement of the reproducibility of the patients’ position to avoid false-positive cases is warranted, TRUS-CT fusion imaging has the possibility that the uncertainty of TRUS can be supplemented.

Purpose To assess the most suitable value of a relative prescribed dose in clinical treatment plans of stereotactic body radiotherapy (SBRT) using dynamic conformal multiple arc therapy to treat lung tumors. Methods and Materials We retrospectively generated alternative SBRT plans for typical examples of 8 patients who had been treated with SBRT for a lung tumor with a prescribed dose of 50 Gy in 5 fractions. The prescribed dose had been defined as 80% of the maximal dose in the planning target volume (PTV) ("the 80% isodose plan"). Alternative 20%-90% isodose plans at 10% intervals were generated (64 plans; 8 plans for each of the 8 patients), and factors related to leaf margins, target volume, normal lung volume, and monitor units were compared using dose-volume histogram analysis. Results We could generate all the 64 plans. Compared with the 80% isodose plan, the V20 and mean lung dose (MLD) were both lower in the 60% plan; the V20 was approximately 19% lower (4.72% vs 3.84%) and the MLD was 13% lower (4.0 Gy vs 3.5 Gy). Mean PTV and ITV doses were higher in the lower percentage isodose plans. Compared with the 80% isodose plan, in the 60% isodose plan the mean PTV was 19% higher (56.1 Gy vs 66.8 Gy) and the mean ITV was 30% higher (59.6 Gy vs 77.4 Gy). The mean total monitor units increased more steeply than did the mean homogeneity index. The mean conformity index values in the 60% and 70% isodose plans were less than 1.15. Conclusions The 60% isodose plan was considered the best plan in this analysis because of the lower comparative dosimetric factors in normal lung tissue (including V20 and MLD) and the higher comparative mean PTV and internal target volume doses achieved, along with good conformity index values. In clinical use, accurate estimation and commissioning should be performed for the dose distribution prior to selecting a plan. Further investigation is warranted to determine whether the calculated dosimetric advantages result in improved outcomes.

Esophageal cancer/Pleural effusion/Pericardial effusion/Radiotherapy/Chemoradiotherapy. Purpose: We investigated the incidences of pericardial and pleural effusions after definitive radiotherapy with or without concurrent chemotherapy were analyzed retrospectively. Methods: One hundred and forty-seven patients with esophageal cancer received definitive radiotherapy or concurrent chemoradiotherapy (CCR). Follow-up chest Computed Tomography scans were reviewed to detect pericardial and pleural effusions. Adverse events were graded according to the Radiation Therapy Oncology Group Common Toxicity Criteria. Results: The median follow-up was 34 (range, 6 to 84) months. Numbers of eligible pat ients evaluated for pericardial and pleural effusions were 107 and 101, respectively. Pericardial effusions exceeding grade 1 and grade 2 toxicities were obs erved in 46 (43%) and 15 (14%) patients, respectively. The corresponding numbers for pleural effusions were 44 (44%) and 18 (18%). Onset of effusion ranged from 1 to 65 months after treatment. Multivariate analysis identified radiation field width of the mediastinum exceeding 8 cm as a significant risk factor for both pericardial and pleural effusions. Age and field length exceeding 20 cm were identified as independent risk factors for pleural effusion. Conclusions: Pericardial and pleural effusions after radiotherapy or CCR are occasionally recognized as adverse events in patients with esophageal cancer. The mediastinal radiation field width can be a simple indicator for predicting those adverse events.

To analyze local control of oligometastatic lung tumors (OLTs) compared with that of primary lung cancer after stereotactic body radiotherapy (SBRT).Retrospective record review of patients with OLTs who received SBRT with 50Gy in 5 fractions. Local control rates (LCRs), toxicities, and factors of prognostic significance were assessed.Twenty-one colorectal OLTs, 23 OLTs from other origins, and 188 primary lung cancers were included. Multivariate analysis revealed only tumor origin was prognostically significant (p0.05). The 1-year/2-year LCRs in colorectal OLTs and OLTs from other origins were 80%/72% and 94%/94%, respectively. The LCR in colorectal OLTs was significantly worse than that in OLTs from the other origins and primary lung cancers with pathological and clinical diagnosis (p0.05, p0.0001 and p0.005). Among 44 OLT patients, Grades 2 and 3 radiation pneumonitis were identified in 2 and 1 patients, respectively. No other toxicities of more than Grade 3 occurred.SBRT for OLTs is tolerable. The LCR for OLTs from origins other than colorectal cancer is excellent. However, LCR for colorectal OLTs is worse than that from other origins. Therefore dose escalation should be considered to achieve good local control for colorectal OLTs.

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

The prevention of contrast-induced acute kidney injury (AKI) after coronary computed tomography angiography (CCTA) is important because patients referred for CCTA often need further contrast exposure such as an invasive coronary angiography. We aimed to examine the effects of oral volume intake on renal function in patients with preserved renal function referred for CCTA.We enrolled 180 patients who were referred for CCTA. The serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) levels were measured before, 24h, and a mean of 4.8 days after CCTA. The amount of unrestricted oral fluid intake for 24h was checked. The patients were divided into two groups: 106 subjects with a rise in SCr after CCTA (group A); and 74 without (group B).Significant correlations were observed between the amount of oral fluid intake and the percentage changes in SCr (%SCr) (r=-0.66, p0.0001) as well as the absolute changes in eGFR (ΔeGFR) (r=0.65, p0.0001). The percentage of patients showing hemoglobin-A1c (HbA1c)≥6.5% was greater in group A than in group B (29% vs. 18%, p0.001). Patients with HbA1c≥6.5% showed higher %SCr and lower ΔeGFR compared to those without it. Multiple regression analysis revealed that the amount of oral fluid intake was the only independent predictor for a rise in SCr (β=-0.731, p0.0001).Oral volume intake after CCTA is a very simple but important prophylactic procedure for contrast-induced AKI especially in diabetic patients.

This study aimed to assess the imaging appearances of focal liver reactions following stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) and to examine relationships between imaging appearance and baseline liver function. We retrospectively studied 50 lesions in 47 patients treated with SBRT (30- 40 Gy in 5 fractions) for HCC, who were followed up for more than 6 months. After SBRT, all patients underwent regular follow-ups with blood tests and dynamic CT scans. At a median follow-up of 18.1 months (range 6.2-43.7 months), all lesions but one were controlled. 3 density patterns describing focal normal liver reactions around HCC tumours were identified in pre-contrast, arterial and portal-venous phase scans: iso/iso/ iso in 4 patients (Type A), low/iso/iso in 8 patients (Type B) and low/iso (or high)/high in 38 patients (Type C). Imaging changes in the normal liver surrounding the treated HCC began at a median of 3 months after SBRT, peaked at a median of 6 months and disappeared 9 months later. Liver function, as assessed by the Child-Pugh classification, was the only factor that differed significantly between reactions to treatment showing ''non-enhanced'' (Type A and B) and ''enhanced'' (Type C) appearances in CT. Hence, liver tissue with preserved function is more likely to be well enhanced in the delayed phase of a dynamic contrast-enhanced CT scan. The CT appearances of normal liver seen in reaction to the treatment of an HCC by SBRT were therefore related to background liver function and should not be misread as recurrence of HCC.

To investigate factors associated with Gradeor=3 radiation pneumonitis (RP) in patients with lung tumors treated with stereotactic body radiotherapy (SBRT).We retrospectively analyzed 128 patients with 133 lung tumors treated with SBRT. RP was graded according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate analyses were used to identify predictive factors for RP.The median follow-up period after SBRT was 12 months (range, 5-45 months). Incidences of Grades 0, 1, 2, and 3 RP were 27%, 52%, 16%, and 5%, respectively. No patients suffered Grade 4 or 5 RP. For all patients with Grade 2 or 3, symptoms occurred either simultaneously with or subsequent to graphical appearances. The latent period was the only significant factor associated with Gradeor=3 RP (p0.01). A latent period of 1 or 2 months indicated a 40% (6/15) risk for Grade 3. However, the risk for Grade 3 was 1.2% (1/82) 3 months after SBRT. No pretreatment clinical or dosimetric factors were significantly associated with Gradeor=3 RP. However, 4 of 7 patients with Grade 3 RP had severe pulmonary comorbidities.Only the latency period was a significant factor in the development of RP. No pretreatment clinical or dosimetric factors were significantly associated with Gradeor=3 RP. Patients, especially those with severe pulmonary comorbidities, should be carefully observed for the graphical appearance of RP within a few months during the follow-up period after SBRT.

Purpose To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel–based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m 2 ]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade ≥3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

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

Background: One of the most important factors in stereotactic radiosurgery (SRS) for intracranial arteriovenous malformation (AVM) is to determine accurate target delineation of the nidus. However, since intracranial AVMs are complicated in structure, it is often difficult to clearly determine the target delineation.Purpose: To investigate the usefulness of principal component analysis (PCA) on intra-arterial contrast enhanced dynamic CT (IADCT) images as a tool for delineating accurate target volumes for stereotactic radiosurgery of AVMs.Materials and Methods: IADCT and intravenous contrast-enhanced CT (IVCT) were used to examine 4 randomly selected cases of AVM. PCA images were generated from the IADCT data. The first component images were considered feeding artery predominant, the second component images were considered draining vein predominant, and the third component images were considered background. Target delineations were first carried out from IVCT, and then again while referring to the first and second components of the PCA images. Dose calculation simulations for radiosurgical treatment plans with IVCT and PCA images were performed. Dose volume histograms of the vein areas as well as the target volumes were compared.Results: In all cases, the calculated target volumes based on IVCT images were larger than those based on PCA images, and the irradiation doses for the vein areas were reduced.Conclusion: In this study, we simulated radiosurgical treatment planning for intracranial AVM based on PCA images. By using PCA images, the irradiation doses for the vein areas were substantially reduced.

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

Background: To investigate rectal morbidity after I-125 prostate brachytherapy and to analyze predictive factors of rectal morbidity. Methods: A group of 227 consecutive patients with localized prostate cancer were treated with I-125 prostate brachytherapy with or without external beam radiotherapy (EBRT) between September 2003 and January 2005. Rectal morbidity (diarrhea, bleeding and pain) was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Dosimetry was based on computerized tomography (CT) scan 1 month post-implant. The clinical, treatmentrelated and dosimetric factors were evaluated for the risk of grade 2 rectal morbidity. Rectal dosimetric factors included the rectal volume that received .100% and 150% of the prescribed dose, and the maximal rectal dose which was defined as the sum of the minimal dose received by 1% of the rectum volume and the prescribed dose of EBRT. Results: Grade 2 rectal bleeding occurred in 10 (4.4%): for nine patients within the first year and for one patient between the first and second year. Grade 2 diarrhea occurred in one patient (0.4%) within the first year. No patient reported grade 2 pain. In the univariate analysis with grade 2 rectal bleeding, there were significant correlations with number of seeds, supplemental EBRT, and all of the rectal dosimetric parameters. On subsequent multivariate analysis, the only significant factor was the maximal rectal dose (P , 0.001). Rectal dose . 160 Gy was correlated to grade 2 rectal morbidity. All the patients with rectal dose . 160 Gy received EBRT. Conclusions: Manifestations of rectal morbidity are acceptable events after I-125 prostate brachytherapy. Rectal dose‐volume histogram for the brachytherapy is a predictive method for assessing the risk of developing grade 2 rectal bleeding. Delivery of the rectal dose should not exceed 160 Gy in order to avoid rectal complications.