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Purpose: Intensity-modulated radiotherapy (IMRT) for cervical cancer yields favorable results in terms of oncological outcomes, acute toxicity, and late toxicity. Limited data are available on clinical results with volumetric modulated arc therapy (VMAT). This study's purpose is to compare outcome and toxicity with VMAT to conventional 3D conformal radiotherapy (3DCRT), giving special consideration to the influence of patient- and treatment-related parameters on side effects., Materials and Methods: Patients with cervical cancer stage I-IVA underwent radiotherapy alone or chemoradiotherapy using 3DCRT (n = 75) or VMAT (n = 30). Survival endpoints were overall survival, progression-free survival, and locoregional control. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Late Effects of Normal Tissues criteria were used for toxicity assessment. Toxicity and patient- and treatment-related parameters were included in a multivariable model., Results: There were no differences in survival rates between treatment groups. VMAT significantly reduced late small bowel toxicity (OR = 0.10, p = 0.03). Additionally, VMAT was associated with an increased risk of acute urinary toxicity (OR = 2.94, p = 0.01). A low body mass index (BMI; OR = 2.46, p = 0.03) and overall acute toxicity ≥grade 2 (OR = 4.17, p < 0.01) were associated with increased overall late toxicity., Conclusion: We demonstrated significant reduction of late small bowel toxicity with VMAT treatment, an improvement in long-term morbidity is conceivable. VMAT-treated patients experienced acute urinary toxicity more frequently. Further analysis of patient- and treatment-related parameters indicates that the close monitoring of patients with low BMI and of patients who experienced relevant acute toxicity during follow-up care could improve late toxicity profiles.

Purpose: To provide an analysis of dose distribution in sub-structures that could be responsible for urinary toxicity after Image-Guided Adaptive BrachyTherapy (IGABT) in Locally Advanced Cervical Cancer (LACC)., Methods: 105 LACC patients treated with radiochemotherapy and IGABT were selected. Sub-structures (bladder wall, trigone, bladder neck, urethra) were contoured on IGABT-planning MRIs. D 2cm3 and D 0.1cm3 , ICRU Bladder-Point (ICRU BP) and Posterior-Inferior Border of Symphysis points (PIBS, PIBS + 2 cm, PIBS - 2 cm) doses were extracted. Internal-Urethral-Ostium (IUO) and PIBS-Urethra (PIBS-U) points were defined as urethral dose surrogates. Finally, the Vaginal Reference Length (VRL) was extracted. Values were converted into total EBRT + BT equivalent dose in 2 Gy fractions using α/β = 3 and T 1/2  = 1.5 h., Results: Median D 2cm3 for bladder and trigone were 71.7[interquartile-range:66.5;74.1]Gy and 57.8[53.3;63.6]Gy, respectively, while median D 0.1cm3 were 82.2[77.6;89.1]Gy and 70.7[62.0;76.7]Gy, respectively. Median ICRU BP dose was 63.7[56.5;70.5]Gy and correlated with trigone D 2cm3 and D 0.1cm3 , while bladder and trigone D 2cm3 had poor correlation (R 2  = 0.492), as well as D 0.1cm3 (R 2  = 0.356). Bladder neck D 0.1cm3 was always lower than trigone D 0.1cm3 and higher than IUO. Correlation between PIBS + 2 cm and IUO was poor (R 2  = 0.273), while PIBS and PIBS-U were almost equal (R 2  = 0.990). VRL correlated with dose to bladder base., Conclusions: The study confirmed that ICRU BP and trigone doses correlate. Bladder D 2cm3 is not representative of trigone dose because hotspots are often placed in the bladder dome. VRL is a good indicator for bladder base sparing. In addition to D 2cm3 and D 0.1cm3 for whole bladder, ICRU BP, trigone D 2cm3 and D 0.1cm3 , IUO and PIBS are useful for lower urinary tract reporting., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: The present study aims to evaluate both early and late toxicity profiles of patients receiving immediate postoperative radiotherapy (RT; adjuvant RT or additive RT) compared to salvage RT., Methods: We evaluated 253 patients with prostate cancer treated with either immediate postoperative (adjuvant RT, n = 42; additive RT, n = 39) or salvage RT (n = 137). Thirty-five patients received salvage treatment but did not achieve a postoperative prostate specific antigen (PSA) level <0.1 ng/ml and thus were excluded from analysis., Results: A significantly higher rate of early grade 1/2 proctitis in the immediate postoperative RT group without additional pelvic RT was observed (p = 0.02). Patients in the immediate postoperative RT group without additional pelvic RT showed significantly more early urinary tract obstructions (p = 0.003). Toxicity rates of early (<3 months) and late (3-6 months) postoperative RT were similar (p > 0.05). Baseline recovery rate of erectile dysfunction was better in patients with immediate postoperative RT without additional pelvic RT (p = 0.02; hazard ratio (HR) = 2.22, 95%-confidence interval, 95%-CI: 1.12-4.37). Recovery rate of urinary incontinence showed no significant difference in all groups (p > 0.05)., Conclusion: Patients receiving immediate postoperative RT (adjuvant or additive RT) without additional pelvic RT experience early gastrointestinal (GI) side effect proctitis and, as well as early genitourinary (GU) toxicity urinary tract obstruction more frequently than patients treated with salvage RT. Therefore, complete recovery after surgery is essential. However, we suggest basing the treatment decision on the patient's postoperative clinical condition and evaluation of any adverse risk factors, since many studies demonstrate a clear benefit for immediate postoperative RT (adjuvant or additive RT) in terms of oncological outcome.

Purpose: To evaluate the incidence and predictors for late toxicity and tumor outcome after hypofractionated radiotherapy using three different image-guided radiotherapy (IGRT) systems (hypo-IGRT) compared with conventional fractionation without image guidance (non-IGRT)., Methods and Materials: We compared the late rectal and urinary toxicity and outcome in 179 prostate cancer patients treated with hypo-IGRT (70.2 Gy/26 fractions) and 174 non-IGRT patients (80 Gy/40 fractions). Multivariate analysis was performed to define predictors for late toxicity. 5- and 8-year recurrence-free survival (RFS) and overall survival (OS) were analyzed., Results: Mean follow-up was 81 months for hypo-IGRT and 90 months for non-IGRT group. Mainly mild late toxicity was observed: Hypo-IGRT group experienced 65 rectal (30.9% G1/G2; 6.3% G3/G4) and 105 urinary events (56% G1/G2; 4% G3/G4). 5- and 8-year RFS rates were 87.5% and 86.8% (hypo-IGRT) versus 80.4% and 66.8% (non-IGRT). 5- and 8-year OS rates were 91.3% and 82.7% in hypo-IGRT and 92.2% and 84% in non-IGRT group. Multivariate analysis showed that hypo-IGRT is a predictor for late genitourinary toxicity, whereas hypo-IGRT, acute urinary toxicity and androgen deprivation therapy are predictors for late rectal toxicity. Advanced T stage and higher Gleason score (GS) were correlated with worse RFS., Conclusions: A small increase in mild late toxicity, but not statistically significant increase in severe late toxicity in the hypo-IGRT group when compared with conventional non-IGRT group was observed. Our study confirmed that IGRT allows for safe moderate hypofractionation, offering a shorter overall treatment time, a good impact in terms of RFS and providing potentially more economic health care.

Background: The close anatomical relationship of the urogenital system is a significant, and sometimes limiting, factor in oncogynecology. Reducing adverse effects (treatment-associated toxicity) is an integral part of cancer treatment. Radical surgery, as well as oncological therapy, which represent milestones in the treatment of such malignancies, may require tailoring the extension of the intervention in order to preserve other non-gynecological structures. Despite the progress in minimally invasive surgery, and evolution of radiotherapy and systemic therapy, treatment-related complications remain; indeed, their increasing prevalence in women raises questions about quality of life., Aim: Here, we highlight the modalities used to treat gynecological cancer and discuss the most common urological adverse effects related to these interventions. Knowledge of side effects, as well as methods of prevention, is fundamental if we are to preserve quality of life., Conclusion: reatment of gynecological cancer is based on cooperation between members of the multidisciplinary team. From this point-of-view, combination of two radical modalities (mainly surgery and radiotherapy) remains problematic. However, the patients prognosis, and plans for other possible oncological therapies, play an essential role in management of urological adverse effects related to cancer treatment. Key words: gynecologic neoplasms - complication - urinary tract - quality of life This work was supported by project PROGES Q40. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 27. 9. 2018 Accepted: 21. 10. 2018.

Background and Purpose: The EMBRACE study is a prospective multi-institutional study on MRI guided adaptive brachytherapy (IGABT) in locally advanced cervix cancer (LACC). This analysis describes early to late urinary morbidity assessed by physicians and patients (PRO)., Material and Methods: A total of 1176 patients were analysed. Median follow up (FU) was 27 (1-83) months. Morbidity (CTCAE v.3) and PRO (EORTC QLQ-C30&CX24) was prospectively assessed at baseline (BL), and during FU., Results: The most frequent symptoms were frequency/urgency, incontinence, and cystitis with grade 2-4 prevalence rates of 4.3%, 5.0% and 1.7% and grade 1-4 prevalence rates of 24.5%, 16.1% and 5.8% at 3-years. The most frequent PRO endpoints were "urinary frequency" and "leaking of urine". Prevalence of "Quite a bit" or "very much" bother fluctuated from 14.0% to 21.5% for "frequency", while "leaking of urine" increased from 4.6% at BL to 9.3% at 3-years. Actuarial 3-year incidence of grade 3-4 urinary morbidity was 5.3% with most events being urinary frequency, incontinence and ureteral strictures. Grade 3-4 fistula, bleeding, spasm and cystitis were all <1.0% at 3/5-years. No grade 5 toxicity occurred., Conclusion: Urinary grade 3-4 morbidity with IGABT was limited. Urinary morbidity grade 2-4 comprises mainly frequency/urgency, incontinence and cystitis and has considerable prevalence in PRO. Various urinary morbidity endpoints have different patterns of manifestation and time course., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Hypofractionated radiation therapy (HFRT) for localized prostate cancer is safe and effective. The question that remains is which hypofractionation schedule to implement. We compared 2 different HFRT regimens in the present study., Methods and Materials: From June 2013 to July 2016, 160 patients with prostate cancer were randomly assigned (1:1), within this single-center phase III trial, to 56 Gy (16 fractions of 3.5 Gy; arm A) or 67 Gy (25 fractions of 2.68 Gy; arm B). Randomization was performed using computer-generated permuted blocks, stratified by previous transurethral resection of the prostate and the presence of a dominant intraprostatic lesion. Treatment allocation was not masked, and the clinicians were not blinded. The primary endpoint was acute gastrointestinal (GI) toxicity, assessed using the Common Terminology Criteria for Adverse Events, version 4.0, and Radiation Therapy Oncology Group toxicity scale. An interim analysis of acute toxicity was planned at 160 patients to prove the safety of both treatment regimens. If ≥22 of 72 patients had grade ≥2 GI toxicity, the study arm would be rejected. The study is registered at ClinicalTrials.gov (NCT01921803)., Results: In arm A, 20 patients (26%) and 1 patient (1%) developed acute grade 2 and grade 3 GI toxicity. In arm B, 16 patients (20%) reported acute grade 2 GI toxicity. In arm A, 42 (55%) and 5 (6%) patients developed acute grade 2 and grade 3 urinary toxicity. In arm B, 40 (49%) and 7 (9%) patients reported acute grade 2 and grade 3 urinary toxicity. Toxicity peaked during radiation therapy and resolved in the months after radiation therapy., Conclusions: With acute grade ≥2 GI toxicity reported in 21 of 77 patients in arm A and 16 of 82 patients in arm B, both treatment arms can be considered safe., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/aim: We experienced an unexpected high incidence of gastrointestinal (GI) toxicity in patients undergoing image-guided intensity-modulated radiotherapy (IG-IMRT) using helical tomotherapy in our initial 2.2 Gy/fraction schedule for prostate cancer; hence, a dose-reduction trial from 2.2 Gy to 2 Gy/fraction was conducted using modified planning target volume (PTV) contouring., Patients and Methods: We compared 130 patients treated using 2.2 Gy/fraction (Group A) and 144 treated using the 2 Gy/fraction (Group B) with modified PTV (excluding rectal volume) with a median follow-up period of 62 months. Prescribed dose was 72.6-74.8 Gy in 33-34 fractions (Group A) and 72-74 Gy in 36-37 fractions (Group B)., Results: Patients in Group B had a reduced rectal and bladder V10-V70 and were irradiated at the maximal dose. Their cumulative incidence of grade ≤2 GI toxicity at 5 years improved from 10.1% [95% confidence interval (CI), 4.9-15.3%] to 1.4% (0-3.3%). Grade 2≤ urinary toxicity also decreased from 5.5% (1.5-9.4%) in Group A to 1.4% (0-3.3%, p=0.0167) in Group B. The biochemical failure-free 5-year survival rate was 89.1% (95%CI=83.6-95.4%) and 87.5% (82.0-92.9%, p=0.75) in groups A and B, respectively., Conclusion: The reduced dose fraction schedule decreased the incidence of late GI toxicity without compromising prostate-specific antigen control. Careful target volume definition and fraction size are important even for IG-IMRT., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Purpose: Evaluate changes in bowel, urinary and sexual patient-reported quality of life following treatment with moderately hypofractionated radiotherapy (<5Gray/fraction) or stereotactic body radiation therapy (SBRT;5-10Gray/fraction) for prostate cancer., Materials and Methods: In a pooled multi-institutional analysis of men treated with moderate hypofractionation or SBRT, we compared minimally detectable difference in bowel, urinary and sexual quality of life at 1 and 2years using chi-squared analysis and logistic regression., Results: 378 men received moderate hypofractionation compared to 534 men who received SBRT. After 1year, patients receiving moderate hypofractionation were more likely to experience worsening in bowel symptoms (39.5%) compared to SBRT (32.5%; p=.06), with a larger difference at 2years (37.4% versus 25.3%, p=.002). Similarly, patients receiving moderate fractionation had worsening urinary symptom score compared to patients who underwent SBRT at 1 and 2years (34.7% versus 23.1%, p<.001; and 32.8% versus 14.0%, p<.001). There was no difference in sexual symptom score at 1 or 2years. After adjusting for age and cancer characteristics, patients receiving SBRT were less likely to experience worsening urinary symptom scores at 2years (odds ratio: 0.24[95%CI: 0.07-0.79])., Conclusions: Patients who received SBRT or moderate hypofractionation have similar patient-reported change in bowel and sexual symptoms, although there was worse change in urinary symptoms for patients receiving moderate hypofractionation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Most predictive models are not sufficiently validated for prospective use. We performed independent external validation of published predictive models for urinary dysfunctions following radiotherapy of the prostate., Materials/methods: Multivariable models developed to predict atomised and generalised urinary symptoms, both acute and late, were considered for validation using a dataset representing 754 participants from the TROG 03.04-RADAR trial. Endpoints and features were harmonised to match the predictive models. The overall performance, calibration and discrimination were assessed., Results: 14 models from four publications were validated. The discrimination of the predictive models in an independent external validation cohort, measured using the area under the receiver operating characteristic (ROC) curve, ranged from 0.473 to 0.695, generally lower than in internal validation. 4 models had ROC >0.6. Shrinkage was required for all predictive models' coefficients ranging from -0.309 (prediction probability was inverse to observed proportion) to 0.823. Predictive models which include baseline symptoms as a feature produced the highest discrimination. Two models produced a predicted probability of 0 and 1 for all patients., Conclusions: Predictive models vary in performance and transferability illustrating the need for improvements in model development and reporting. Several models showed reasonable potential but efforts should be increased to improve performance. Baseline symptoms should always be considered as potential features for predictive models., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The use of intensity-modulated radiotherapy (IMRT) to treat cervix carcinoma has increased, however prospective randomized trials are still lacking., Aim: To compare the dosimetric parameters and associated acute toxicity in patients with cervix carcinoma treated with three-dimensional (3D) conformal radiotherapy and IMRT., Patients and Methods: Forty patients were randomized in two arms each consisting of 20 patients. Patients in both arms received concurrent chemoradiation (cisplatin 40mg/m(2) weekly; 50Gy/25 fractions). Patients were treated with 3D conformal radiotherapy in one arm and with IMRT in another arm. After external beam radiotherapy, all patients received brachytherapy (21Gy/3 fractions at weekly interval). For dosimetric comparison, both kinds of the plans were done for all the patients. All patients were assessed throughout and until 90 days after completion of treatment for acute gastrointestinal, genitourinary and hematologic toxicities., Results: Both plans achieved adequate planning target volume coverage, while mean conformity index was found significantly better in IMRT plans (P-value=0.001). D35 (dose to 35% volume) and D50 for bladder was reduced by 14.62 and 32.57% and for rectum by 23.82 and 43.68% in IMRT. For IMRT, V45 (volume receiving 45Gy) of bowel were found significantly lesser (P-value=0.0001), non-tumour integral dose was found significantly higher (P-value=0.0240) and V20 of bone marrow was found significantly reduced (P-value=0.019) in comparison to that in 3D conformal radiotherapy. Significant reduction of grade 2 or more (20 vs 45%; P-value=0.058) and grade≥3 (5 vs 15%, P-value=0.004) acute genitourinary toxicity and grade 2 or more (20 vs 45%, P-value=0.003) and grade 3 or more (5 vs. 20%, P-value=0.004) acute gastrointestinal toxicity while no significant difference for grade 2 and 3 or more haematological toxicity was noted in patients treated with IMRT compared to 3D conformal radiotherapy., Conclusion: IMRT provide a good alternative for treatment of cervix carcinoma with lower acute gastrointestinal and acute genitourinary toxicity with similar target coverage compared to 3D conformal radiotherapy., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Aim: To retrospectively investigate the risk factors and time to occurrence of genitourinary (GU) toxicity after radiotherapy for localized prostate cancer., Patients and Methods: The study included 320 patients. The radiotherapy planning target volume encompassed the prostate with a 1-cm margin in the transverse plane and a 1-cm margin (Group A) or a 1.5-cm margin (Group B) in the longitudinal plane. Incidence rates, risk factors and time to occurrence of GU toxicity were evaluated., Results: After a median follow-up of 38.2 months, the rate of late grade 2-3 GU toxicity was 5.9% and the median interval was 18.3 months. The wider longitudinal margin was the single significant independent factor. The 2-year cumulative incidence rates of late grade ≥2 GU toxicity were 2.8% and 7.5% in Group A and B patients., Conclusion: A wider radiotherapy margin increased the risk of GU toxicity and led to earlier occurrence., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Introduction: The current experimental study aimed at evaluating the temperature raise of the irrigation fluid caused by the use of the thulium (Tm:YAG) and holmium laser (Ho:YAG) in the upper urinary tract (UT) of pigs., Materials and Methods: An experimental setting was designed for the investigation of differences in the temperature of the irrigation fluid in the renal pelvis of a porcine model under different flow rates and laser power settings. The experimental configuration included a single-use flexible ureteroscope, a Tm:YAG and a Ho:YAG laser system. A thermocouple was inserted through a 6F ureteral catheter that was placed parallel to the FlexVue in the renal pelvis. An additional thermocouple was placed next to the renal pelvis after open preparation of the kidney. Irrigation was achieved with either the irrigation bags placed 1 m above the level of the pig or with the use of an irrigation pump (30 and 60 compressions per minute)., Results: Tm:YAG (10, 20, 30, 40 W): The higher flow provided by the pump system minimized the increase of temperature within the renal pelvis regardless of the laser power. The external temperature increase was lower in comparison to the increase inside the renal pelvis. The internal temperature could increase up to 10.5°C from a baseline value of 23°C. Ho:YAG (10, 20 W): There was no temperature change or an increase of only 2.1°C under the different power and irrigation flow rate settings. There were no differences in the temperature between the inside and outside of the renal pelvis., Conclusion: The use of Tm:YAG in continuous mode with power settings up to 40 W and flow rates similar to those used in the clinical practice seemed to result in temperature increases in the irrigation fluid, which do not represent a risk for the renal tissue during the UT endoscopic surgery.

Introduction: The current experimental study aimed into evaluating the temperature raise of the irrigation fluid caused by the use of the Thulium:Yttrium aluminum garnet (Tm:YAG) laser. The study setting was designed to replicate conditions of upper urinary tract (UT) surgery., Materials and Methods: An experimental setting was designed for the investigation of differences in the temperature of the irrigation fluid in different flow rates, laser power settings, and laser activation times and modes. The experimental configuration included a burette equipped with a micrometric stopcock, a thermocouple, and a modified 40-mL vessel. A Tm:YAG and Holmium:Yttrium aluminum garnet (Ho:YAG) laser devices were used., Results: The Tm:YAG in the continuous mode and in power settings of 5, 10, and 20 W showed similar temperature changes during the 10-minute observation period. The temperatures of the Tm:YAG in the pulsed mode tended to range within similar levels (46.8°C-61°C) with the continuous mode (47.8°C-68°C) when power settings up to 20 W were considered. When the higher power settings (50 and 100 W) were investigated, the temperatures reached were significantly higher in both pulsed and continuous modes. The Ho:YAG showed similar temperatures in comparison to the Tm:YAG in all the flow rates and power settings. The temperatures ranged between 45.6°C and 68.7°C., Conclusion: The Tm:YAG in the pulsed and continuous mode with power settings up to 20 W seemed to have potential for UT use. By combining a power setting at the above limit and a low flow rate (as low as 2 mL/minute), it is possible to use the Tm:YAG with safety in terms of temperature.

Unlabelled: We treated a cohort of 116 patients with prostate cancer with three-dimensional conformal hypofractionated radiotherapy to a total dose of 52.8 Gy in 16 fractions (3.3 Gy per fraction). The correlation between acute and late gastrointestinal (GI) and genitourinary (GU) toxicity and dose-volume parameters was analysed. Comparison of observed incidence of toxicity and normal tissue complication probability calculated from dose-volume histograms (DVH) of all patients using radiobiological Lyman-Kutcher-Burman model was performed. The results of our study suggest that acute gastrointestinal toxicity ≥ grade 2 (G2) is the significant predictor of late toxicity ≥ G2 (p=0.006). Observed incidence of acute and late GI toxicities ≥ G2 was 9.7% and 11.5%, respectively. NTCPs of acute and late GI complications ≥ G2 were 11.3% and 2.5%. Observed incidence of late GU toxicity ≥ G2 was 14.2%, NTCP was 0.8%. Comparison of calculated probability of acute GI toxicity ≥ G2 and observed incidence indicates that parameters of radiobiological models are set appropriately. Comparison of observed incidence of late GI and GU complications ≥ G2 and calculated NTCPs shows the need of refinement of LKB model parameters for acute and late GI and GU complications ≥ G2., Keywords: prostate cancer, radiotherapy, acute and late toxicity, radiobiological modeling.

Aims: To report disease outcomes and late urinary toxicity profile. To assess the impact of changing technique and evolving quality assurance on genitourinary toxicity rates., Methods and Materials: One hundred eighty patients were treated with external beam radiation therapy and high-dose-rate brachytherapy (HDRB) for localized intermediate- and high-risk prostate cancer, between December 2002 and February 2012. The HDRB technique evolved over the period of this study, from 19.5 Gy/3 (n = 68), to 17 Gy/2 (n = 40), 18 Gy/2 (n = 39), and most recently 19 Gy/2 (n = 33). In the two fraction cohort, 68 patients underwent additional correction for catheter displacement before each fraction., Results: With a median followup of 5.2 years, 5-year freedom from failure was 93.7% for intermediate, and 76.0% for high risk patients. The 3- and 6-year cumulative stricture incidence for all patients was 7.8% and 15.3%, respectively. There was no statistically significant difference in stricture rate for the four dose levels used nor between the three fractions and the two fraction technique overall. The 19 Gy/2 fractionation group had the lowest 3-year stricture rate (3.0%). The addition of correction for intrafraction catheter displacement did not result in a statistically significant difference in stricture rates, although the severity of strictures has been reduced., Conclusions: Our biochemical control is consistent with other similar series. We found no increase in late urinary toxicity with a two fraction, two implant HDRB technique compared with three fractions. The HDRB dose did not correlate with stricture rates in our series. Correction of intra-fraction catheter displacement did not lead to a statistically significant reduction in stricture rates, although may have mitigated the effects of dose escalation., (Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation., Methods and Materials: Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months., Results: Spacer application was rated as "easy" or "very easy" 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption., Conclusions: Spacer application was well tolerated. Increased perirectal space reduced rectal irradiation, reduced rectal toxicity severity, and decreased rates of patients experiencing declines in bowel quality of life. The spacer appears to be an effective tool, potentially enabling advanced prostate RT protocols., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim is to estimate the possibility the new annual dose limit for eye lens to be exceeded and to study the impact of protective shield. Radiation exposure to medical personnel was evaluated with EDD-30 dosemeter in positions of operating surgeon, assisting doctor and nurse. At the operator's typical position for diagnosis and treatment of the urinary tract, the lens dose rates were 0.9 mSv h(-1) and 0.06 mSv h(-1) without and with lead shield. At the operator's position typical for percutaneous intervention dose rates were 1.9 and 0.02 mSv h(-1), respectively. At typical workload, the annual eye lens dose to the main operator without protective screen was estimated to be 29 mSv. With lead screen, operator lens dose can be reduced by a factor of 15-95 according to the procedure. Installation and use of lead screen and use of lead glasses were recommended to the endourology medical team., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We evaluated the predictive factors of acute urinary morbidity (AUM) after prostate brachytherapy. From November 2005 to January 2007, 62 patients with localized prostate cancer were treated using brachytherapy. The (125)Iodine ((125)I) seed-delivering method was a modified peripheral pattern. The prescribed dose was 144 Gy. Urinary morbidity was scored at 3 months after implantation. The clinical and treatment parameters were analysed for correlation with AUM. In particular, in this study, Du90 (the minimal dose received by 90% of the urethra), Dup90 (the minimal dose received by 90% of the proximal half of the urethra on the bladder side) and Dud90 (the minimal dose received by 90% of the distal half of the urethra on the penile side) were analysed. We found that 43 patients (69.4%) experienced acute urinary symptoms at 3 months after implantation. Of them, 40 patients had Grade 1 AUM, one patient had Grade 2 pain, and two patients had Grade 2 urinary frequency. None of the patients had ≥Grade 3. Univariate and multivariate analysis revealed that Du90 and Dup90 were significantly correlated with AUM. In this study, Du90 and Dup90 were the most significant predictors of AUM after prostate brachytherapy., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: To analyze late urinary toxicity after prostate cancer radiotherapy (RT): symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms., Methods: Nine hundred and sixty-five patients underwent RT in seventeen French centers for localized prostate cancer. Median total dose was 70 Gy (range, 65-80 Gy), using different fractionations (2 or 2.5 Gy/day) and techniques. Late urinary toxicity and the corresponding symptoms (urinary frequency, incontinence, dysuria/decreased stream, and hematuria) were prospectively assessed in half of the patients using the LENT-SOMA classification. Univariate and multivariate Cox regression models addressed patient or treatment-related predictors of late urinary toxicity (≥grade 2). Nomograms were built up, and their performance was assessed., Results: The median follow-up was 61 months. The 5-year (≥grade 2) global urinary toxicity, urinary frequency, hematuria, dysuria, and urinary incontinence rates were 15, 10, 5, 3 and 1 %, respectively. The 5-year (≥grade 3) urinary toxicity rate was 3 %. The following parameters significantly increased the 5-year risk of global urinary toxicity (≥grade 2): anticoagulant treatment (RR = 2.35), total dose (RR = 1.09), and age (RR = 1.06). Urinary frequency was increased by the total dose (RR = 1.07) and diabetes (RR = 4). Hematuria was increased by anticoagulant treatment (RR = 2.9). Dysuria was increased by the total dose (RR = 1.1). Corresponding nomograms and their calibration plots were generated. Nomogram performance should be validated with external data., Conclusions: The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.

Efforts have been made to minimize the damage to adjacent normal tissues during radiotherapy, primarily by shifting from the use of conventional radiotherapy to more advanced techniques. Reviewing the overall pattern on combined anatomic and functional imaging can enhance diagnostic accuracy. Several radiotracers can be used; [(18)F]fluorodeoxyglucose is the most common. Familiarity with the type and timing of previous radiation therapy, the spectrum of imaging findings after radiation injury, and the appropriate use of the different radiotracers can be crucial. This article summarizes postradiation histologic findings and multimodality imaging findings, with emphasis on PET/computed tomography., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims and Background: To evaluate the clinical outcome of a cohort of localized prostate cancer patients treated with 125I permanent brachytherapy at the University of Turin., Methods and Study Design: A retrospective analysis was carried out on 167 consecutive patients with early stage prostate adenocarcinoma who underwent 125I brachytherapy between January 2003 and December 2010. A minimum follow-up of ≥ 12 months was mandatory for inclusion. Biochemical disease-free survival (defined on the basis of the ASTRO definition and the ASTRO-Phoenix definition) was chosen as the primary end point. Secondary end points were gastrointestinal and genitourinary toxicity (acute and late, defined according to the RTOG scale)., Results: With a median follow-up of 42 months (range, 13.5-90.7), biochemical disease-free survival at 3 and 5 years was respectively 91.1% and 85.7%, according to the ASTRO definition and 94.5% and 85.1% according to ASTRO-Phoenix definition (for statistical purposes, only the ASTRO definition was used). Hormone treatment and nadir PSA (cutoff of 0.35 ng/ml) were the only factors affecting biochemical disease-free survival both on univariate (P = 0.02 and P = 0.001, respectively) and multivariate analysis (HR 0.024; P = 0.021 and HR 21.6; P = 0.006, respectively). Only 3.6% of patients experienced ≥ grade 3 acute urinary toxicity and 5% ≥ grade 3 late urinary toxicity. Prior transurethral prostate resection was the only independent predictor of grade 3 late urinary toxicity on multivariate analysis (HR 0.13; P = 0.009)., Conclusions: This mono-institutional series confirmed that brachytherapy is an effective and safe treatment modality for localized prostate cancer, with acceptable short- and long-term morbidity rates.

Objective: To analyze the frequency and structure of the urinary system malformations in children born to parents exposed to radiation., Material and Methods: The study included 1,139 children with various congenital malformations of the urinary system, which were examined and treated in the Department of Congenital and Hereditary Diseases from 2000 to 2011. The standard clinical, laboratory, instrumental and radiographic methods were applied to verify the diagnosis., Results and Conclusions: 1. The proportion of children with congenital malformations of the urinary system among all examined in the Department of Congenital and Hereditary Diseases in the 12 years was 68.24%. 2. The congenital malformations accounted for 31.16%, small anomalies for 68.31%, and their combinations for 4.57% among all malformations of the urinary system. 3. Such complications as a secondary pyelonephritis occurred in 4.39% of cases and developed mainly in children with obstructive uropathy., (Stepanova E. Y., Skvarskaja E. A., Usatenko Zh. V., Leonovych E. S., Abramova T. Ja., 2013.)

Background and Purpose: To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy., Materials and Methods: Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2)., Results: The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(β)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(β)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity., Conclusions: For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Videourodynamics is useful for evaluating and treating neurological disorders in children. Traditional urodynamic parameters can be obtained while simultaneous visualization of the urinary system can reveal anatomical anomalies. This additional information comes at the cost of radiation exposure to the child. We characterized radiation exposure from videourodynamics., Materials and Methods: We reviewed all recent videourodynamic studies and recorded patient demographics, urological diagnoses, physical attributes, total fluoroscopy time, total radiation exposure in mGy, bladder capacity and the number of filling cycles performed. Multivariate linear regression was used to identify patient factors that independently influenced total radiation exposure., Results: A total of 64 videourodynamic studies were performed in 34 female and 28 male patients with a mean age of 8.6 years (95% CI 7.2-10.0). The most common diagnosis was neurogenic bladder in 40 patients, although 49 had multiple diagnoses. Mean total fluoroscopy time was 1.8 minutes (95% CI 1.4-2.1) and mean total radiation exposure was 10 mGy (95% CI 7.5-13.3). On multivariate linear regression patient weight and bladder capacity were the only independent predictors of total radiation exposure., Conclusions: Videourodynamics entail significant radiation exposure. Patient weight and bladder capacity were independent predictors of total radiation exposure. Physician awareness of radiation exposure may result in the judicious use of fluoroscopy and aid in counseling parents on the risk of videourodynamics. Further research is needed to quantify organ specific doses of radiation due to medical imaging in children and the associated cancer risks., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To perform a methodological critique of the literature evaluating the relationship between external beam radiotherapy dose/volume parameters and chronic urinary dysfunction to determine why consistent associations between dose and dysfunction have not been found., Methods and Materials: The radiotherapy literature was reviewed using various electronic medical search engines with appropriate keywords and MeSH headings. Inclusion criteria comprised of; English language articles, published between 1999 and June 2009, incorporating megavoltage external beam photons in standard-sized daily fraction. A methodological critique was then performed, evaluating the factors affected in the quantification of radiotherapy dose and chronic urinary dysfunction., Results: Nine of 22 eligible studies successfully identified a clinically and statistically significant relationship between dose and dysfunction. Accurate estimations of external beam radiotherapy dose were compromised by the frequent use of dosimetric variables which are poor surrogates for the dose received by the lower urinary tract tissue and do not incorporate the effect of daily variations in isocentre and bladder position. The precise categorization of chronic urinary dysfunction was obscured by reliance on subjective and aggregated toxicity metrics which vary over time., Conclusions: A high-level evidence-base for the relationship between external beam radiotherapy dose and chronic urinary dysfunction does not currently exist. The quantification of the actual external beam dose delivered to the functionally important tissues using dose accumulation strategies and the use of objective measures of individual manifestations of urinary dysfunction will assist in the identification of robust relationships between dose and urinary dysfunction for application in widespread clinical practice., (Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.)

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to <10 cGy h(-1) and involve multiple patients to detect patient variability. Results may suggest a preference for high dose rate brachytherapy or LDR brachytherapy without permanent retention of the implant seeds (hence the dose rates in peripheral tissues and organs remain above IDRE thresholds).

Objective: To retrospectively evaluate the toxicity of low-dose-rate brachytherapy and to relate it to the dose-volume to organs at risk., Material and Methods: We study 160 patients with early prostate cancer, treated with (125)-I implants. Most of them were T1c (63.1%), T2a (35.6%) and Gleason < or =6 (96.2%). Median PSA was 7.2 ng/ml (2.3-13.5); 85.6% were lowrisk cases and 14.4% high-risk cases. Mean follow-up was 24 months (7-48)., Results: Acute urinary toxicity related to urological quality of life (UQL=CVU) was tolerable in 75% and unsatisfactory in 25%. Urinary retention was present in 6.9%. IPSS, V100 and D90 were related to the urinary toxicity grade. Rectal toxicity (RTOG) G2 was 0.6%. Sexual potency showed no changes with regard to the basal in 69%. Actuarial biochemical control was 89.8% at four years., Conclusions: Brachytherapy with (125)-I seeds yields acceptable toxicity and excellent biochemical control.

Objectives: To define the long-term morbidity in patients with prostate cancer who underwent iodine-125 brachytherapy., Methods: A total of 325 men with localized prostate cancer treated with iodine-125 brachytherapy had a median follow-up of 7 years (range 5 to 15). The American Urological Association symptom score, erectile function status, rectal bleeding incidence, and presence of urinary incontinence were collected prospectively before implantation and every 6 months thereafter. Comparisons were made between the pretreatment and treatment-related factors and their associations with quality-of-life changes. Associations were tested using the Student t, chi-square, and Wilcoxon signed rank tests., Results: The median prostate volume and maximal dose to 90% of the prostate was 36.6 cm3 and 167 Gy, respectively. Of the 325 men, 15.7% experienced prostate-specific antigen failure and 4% started androgen deprivation therapy. The mean total symptom and bother scores increased from baseline (P <0.001) to 6 months after implantation, steadily decreased, and were unchanged at the last follow-up visit (P = 0.6). There were no significant associations among patient age, race, hormonal therapy use, prostate size, radiation dose, and urinary morbidity. Incontinence occurred in 4 (1.2%) of the 325 patients at the last follow-up visit and was associated with transurethral resection of the prostate (odds ratio 8.8, 95% confidence interval 1.3 to 62, P = 0.008). Before implantation, 77.2% were able to have an erection adequate for intercourse and 50.6% were able to at the last follow-up visit. A significant correlation was found between potency preservation and age (P <0.001). Rectal bleeding occurred in 78 men (24%) 1 to 3 years after implantation. Nine patients (2.8%) complained of minor bleeding beyond 5 years, which was associated with greater radiation doses (P = 0.023)., Conclusions: The preservation of urinary, sexual, and rectal quality of life is excellent at long follow-up for patients implanted with iodine-125.

We compared health-related quality-of-life (HRQL) after intensity-modulated radiotherapy (IMRT) with statuses obtained after old and new protocols of three-dimensional conformal radiation therapy (3DCRT) for localized prostate cancer. We measured the general and disease specific HRQL using the MOS 36-Item Health Survey (SF-36), and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI), respectively. IMRT resulted in similar profiles of general and disease-specific HRQL to two other methods within the first year after treatment. Moreover, IMRT gave rise to comparable urinary, intestinal and sexual side effects despite the high dose of radiation applied.

Objective: Radiation therapy (RT) is commonly used for the treatment of prostate cancer, either via brachytherapy or external beam, and is often accompanied by dose-related obstructive and irritative lower urinary tract symptoms (LUTS). This review will analyze the current state of knowledge of LUTS secondary to RT for prostate cancer and review treatment options for this complication., Methods: A review of the literature., Results: Radiation-induced effects in the lower urinary tract that result in LUTS include injury to peripheral neurons, interstitial fibrosis of the bladder, and loss of muscle fibers in the muscularis propria. LUTS are associated with a diminished quality of life and impaired sexual function. Numerous nonrandomized studies and one randomized study support the proposition that the occurrence of LUTS secondary to RT is effectively mitigated by alpha1-adrenoreceptor blockade., Conclusions: Basic and clinical science studies as well as clinical guidelines relevant for LUTS secondary to RT suggest that the routine use of alpha1-adrenoreceptor antagonists should be considered in patients treated with RT, either prophylactically or at the earliest sign of LUTS.

Purpose: We report on the long-term results and late toxicity outcomes of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer., Materials and Methods: Between 1996 and 2000 a total of 561 patients with clinically localized prostate cancer were treated with intensity modulated radiation therapy. All patients were treated to a dose of 81 Gy prescribed to the planning target volume. Prostate specific antigen relapse was defined according to the American Society for Therapeutic Radiology and Oncology consensus and Houston definitions (absolute nadir plus 2 ng/ml dated at the call). Median followup was 7 years (range 5 to 9)., Results: The 8-year actuarial PSA relapse-free survival rates for patients in favorable, intermediate and unfavorable risk groups according to the American Society for Therapeutic Radiology and Oncology definition were 85%, 76% and 72%, respectively (p <0.025). The 8-year actuarial prostate specific antigen relapse-free survival rates for patients in favorable, intermediate and unfavorable risk groups according to the Houston definition were 89%, 78% and 67%, respectively (p = 0.0004). The 8-year actuarial likelihood of grade 2 rectal bleeding was 1.6%. Three patients (0.1%) experienced grade 3 rectal toxicity requiring either 1 or more transfusions or a laser cauterization procedure. No grade 4 rectal complications have been observed. The 8-year likelihood of late grade 2 and 3 (urethral strictures) urinary toxicities were 9% and 3%, respectively. Among patients who were potent before intensity modulated radiation therapy, erectile dysfunction developed in 49%. The cause specific survival outcomes for favorable, intermediate and unfavorable risk cases were 100%, 96% and 84%, respectively., Conclusions: These long-term results confirm our previous observations regarding the safety of high dose intensity modulated radiation therapy for clinically localized prostate cancer. Despite the application of high radiation doses, the incidence of rectal bleeding at 8 years was less than 2%. Despite the increased conformality of the dose distribution associated with intensity modulated radiation therapy, excellent long-term tumor control outcomes were achieved.

Appreciation of the different methods of tissue handling is a prerequisite to obtaining accurate and biologically relevant tissue-based information. When a tissue sample is removed from its environment, biological changes are induced within its constituent cell population. It is inevitable that artefacts will be induced through obtaining and processing tissues, irrespective of whether the samples comprise a few cells derived by fine-needle aspiration or larger specimens obtained surgically. Depending upon the level of sophistication of the analytical methods subsequently employed, such changes might be irrelevant, or might result in acquisition of spurious data. While even brief ischemia alters expression of some genes, detectable by appropriate molecular techniques, the same changes might make no appreciable difference to tissue histomorphology. Furthermore, the phenotype of viable cells is known to change during tissue collection and handling. For example, transitional epithelial cells voided in urine are not phenotypically identical to those retained within the urothelium. Such phenotypic changes are temporary and might be of little consequence to subsequent analyses. Surprisingly, many cells in tissues preserved in an ischemic state can remain viable for several hours, and are believed to remain genotypically stable in the short term.

Background: In Japan, iodine-125 (I-125) prostate brachytherapy has been legally approved since July 2003, and this method is becoming more popular. The purpose of the present study was to assess acute urinary morbidity within the first 6 months after I-125 prostate brachytherapy., Methods: A group of 130 consecutive patients with localized prostate cancer was treated with I-125 prostate brachytherapy between September 2003 and June 2004,either alone (monotherapy; 66 patients) or in combination with external-beam radiotherapy (combined therapy; 64 patients). Urinary morbidity was evaluated using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0., Results: During the follow-up, 111 patients (85.4%) developed some degree of urinary symptoms such as frequency, retention, dysuria, incontinence, or hematuria. Urinary frequency (73.1%) and retention (66.9%) were the most common, and showed no significant differences between the monotherapy group and combined therapy group (P = 0.352 and P = 0.630, respectively). Six patients (4.6%) required catheterization for urinary obstruction; the median time to onset was 1.5 days (range, 1-192 days). Five of these 6 patients received monotherapy and the other received combined therapy., Conclusion: Manifestations of acute urinary morbidity, especially frequency and retention, are relatively common but acceptable events after I-125 prostate brachytherapy.

Background: Neural prostheses are a technology that uses electrical activation of the nervous system to restore function to individuals with neurological or sensory impairment., Introduction: This article provides an introduction to neural prostheses and lists the most successful neural prostheses (in terms of implanted devices)., Current Treatment: The article then focuses on neurogenic bladder dysfunction and describes two clinically available implantable neural prostheses for treatment of neurogenic bladder dysfunction. Special attention is given to the usage of these neural prostheses in children., Future Treatment: Finally, three new developments that may lead to a new generation of implantable neural prostheses for bladder control are described. They may improve the neural prostheses currently available and expand further the population of patients who can benefit from a neural prosthesis.

Much experimental evidence has been accumulated assessing the tolerance of various tissues to IORT, and much of the tolerance data have resulted from the use of canine models. Guidelines of IORT tissue tolerance established in experimental models have been used in the clinical application of IORT at numerous institutions. Although the radiotolerance of differing tissues can vary among species, sufficient clinical experience has accumulated to validate the canine tissue tolerance model as representative of human tissue responses to IORT. Cellular effects from radiation principally stem from direct damage to DNA, and thus proliferating tissues are among the most radiosensitive, with arrested or abnormal cell division. These tissues can manifest striking early toxicity, reflecting the rate of cell division that is affected by the radiation. Irradiation of nonproliferating or slowly proliferating tissues may show little or no early toxicity, but late effects can be manifested to considerable and varying degrees. In much of this late toxicity, pathologic changes develop from progressive ischemia, brought about by the gradual obliteration of small blood vessels. Irradiated endothelium often becomes replaced by a thickened fibrous layer, which, in small vessels, leads to occlusion and ischemic necrotic changes in the supplied tissue. In larger vessels, fibrosis can lead to wall weakening and aneurysmal dilatation, rupture, or thrombosis. The common denominator, then, of radiation damage to many tissues is related to vascular effects. Although the tolerance to IORT-induced toxicity can vary considerably among tissues, doses ranging to 25 Gy can generally be tolerated without significant toxicity. Vital areas where IORT dose must be carefully monitored include critical vasculature, gastrointestinal viscera, ureter, significant motor or sensory nerve trunks, and central nervous system structures. Higher doses can generally be delivered safely to anatomic areas at risk for tumor that are at a distance from sensitive organs or tissues. The general principle providing the rationale of IORT should always be practiced: maximize the radiation dose to the tumor and tumor-harboring tissues while minimizing dose exposure to surrounding normal tissues.

Background: Radiotherapy alone or in combination with radical hysterectomy remains a potentially curative treatment for cervical carcinoma. Late urological complications after curative radiotreatment are rare but often present difficult problems of management due to the progressive nature of radiogenic tissue damage. We reviewed all cases of radiogenic urologic complications after radiotherapy for cervical carcinoma treated at our institution over the past 10 years., Patients and Methods: In a retrospective analysis, out of all female patients treated for hydronephrosis (n = 543), 93 patients with hydronephrosis occurring after curative treatment for gynecological malignancies were identified. The most frequent cause was progressive disease (n = 55); 30 patients without recurrence had severe radiogenic urological complications (study population)., Results: Out of 30 patients with a mean age of 44.9 years at the time of treatment for cervical cancer, 6 had undergone primary radiotherapy and 24 had received adjuvant radiotreatment after radical hysterectomy. The observed late urological complications were: distal ureteral stenoses (bilateral in 4 cases, unilateral in 15 cases), distal ureteral necrosis (n = 1), bilateral ureteral reflux (n = 3), vesico-vaginal fistulae (n = 5), vesico-intestinal fistula (n = 1), severe fibrotic bladder shrinkage (n = 6) and urethral stenosis (n = 2). Marked signs of radiogenic cystitis were observed in almost all patients. The mean latency time between radiotherapy and manifestation of severe radiogenic urological sequelae was 19.4 years (range 0.5-41.5). Primary treatment of urological complications consisted in temporary urinary diversion by percutaneous nephrostomies or insertion of internal ureteral stents. Permanent treatment for radiogenic ureteral stenosis in all patients with sufficient general health consisted of surgical or endourological urinary diversion or reconstruction. However, the majority of patients were managed by permanent endourological measures. Lower tract fistulae were treated by distal ureteral occlusion and diversion., Conclusions: Although severe late urological sequelae of curative radiotherapy for cervical carcinoma are rare they represent major complications, result in considerable distress for the patient, and often present difficult therapeutic problems for the urologist. As these urological complications can have extremely long latency times, focussed follow-up for early detection may be advisable., (Copyright 2003 S. Karger GmbH, Freiburg)

The aim of this study was to evaluate self-assessed late side effects in patients with prostate cancer treated with frameless stereotactic dose-escalation radiotherapy using BeamCath, a new technique that has been developed for accurate positioning of the prostate at treatment set-up, and in which a specially designed urethral catheter containing high-density fiducial markers is used. The method was tested in the first 104 patients in a Scandinavian dose-escalation study with doses up to 76 Gy. Side effects were reported in a daily diary and evaluated at the start of treatment (baseline) and at 1-year follow-up. The patients were compared with those treated with conventional (n = 53) and conformal techniques (n = 175). Dose-escalation radiotherapy (76 Gy) decreased urinary frequency, urgency and starting problems at 1-year in comparison with baseline. The dose-escalation therapy did not induce any increase in gastrointestinal side effects in comparison with the effect of conformal therapy < or = 70 Gy at the 1-year follow-up, apart from a slight increase in rectal mucus in the 76 Gy group. All groups, except patients receiving the 74 Gy with smaller fields, reported a slight increase in gastrointestinal toxicity at 1-year compared with baseline. Dose-escalation radiotherapy of prostate cancer using the BeamCath technique did not induce any significant increase in late side effects in comparison with conformal technique.

Purpose: Prostate brachytherapy has been reported to have less morbidity for patients than radical prostatectomy or external beam irradiation. However, to date there have been no long-term data to support these claims. With radiation doses in excess of 140 Gy required to control the tumor, disabling chronic urinary symptoms and associated quality of life (QOL) changes might be expected to occur. This study prospectively assessed the long-term effects of (125)I prostate brachytherapy on urinary morbidity., Methods and Materials: A total of 248 patients with a median age of 67 years (range, 43-83 years) who presented with T1-T2 prostate cancer were treated with (125)I seed implantation and followed up for a minimum of 18 months after treatment (range, 18 to 108 months; median, 31 months). There were 177 T1b-T2a cases and 41 patients with prostate-specific antigen >10 ng/ml; 20.2% were treated with hormonal therapy. All patients prospectively reported their urinary symptoms and QOL assessment on American Urological Association symptom score records before treatment and at each follow-up visit. Urinary symptoms at last follow-up were compared with pretreatment scores. Radiation doses to the prostate (dose delivered to 90% of the gland; D(90)) and urethra (D(30)) were determined by CT-based dosimetry., Results: The median prostate D(90) was 165 Gy (range, 16.5-260 Gy), and the median urethra D(30) was 192 Gy (range, 23.5-306 Gy). Mean individual scores and QOL ranged from 0.31 to 1.65 before implantation and 0.39 to 1.73 afterward. There were no significant differences between pretreatment and last mean scores for any of the categories except for a small but significant increase in urgency (p=0.01) and weak stream (p=0.03). The cohort of patients who initially presented with marked urinary symptoms (initial score >or=3) had improvement in individual scores by 31.4% to 58.2%, total score by 31.1% (p=0.0005), and QOL by 40.6% (p<0.0001)., Conclusions: This study suggests that prostate brachytherapy is associated with minimal long-term urinary morbidity. The subgroup of patients who present with marked urinary symptoms before implantation has improvement in symptoms and QOL after implantation. These data substantiate the favorable long-term QOL outcomes associated with modern brachytherapy techniques.

Background: New data suggest that a higher radiation dose will improve outcome in treatment of localized prostate cancer. External beam radiotherapy (EBRT) may on the other hand induce disturbances in the patient's urinary and intestinal function. Since 1997, 195 patients have been treated with a stereotactic boost of 4-8 Gy added to conventional 70 Gy EBRT. Late side effects were prospectively evaluated 3 years after dose-escalated EBRT., Methods: Urinary and intestinal problems were prospectively evaluated with a validated self-assessment questionnaire, the Prostate Cancer Symptom Scale (PCSS). Two hundred and eighty-seven patients completed the questionnaire at the 1 year follow-up, and 153 at 3 years after treatment. Pre-treatment mean age was 66 years. One hundred and sixty-eight patients were treated with the conformal technique and 195 were treated with the dose-escalated stereotactic BeamCath technique. Mean total dose in the conformal group (< or =70 Gy) was 66 Gy (60.8-70.4 Gy). The dose-escalated group consists of three dose levels, 74 Gy (n = 68), 76 Gy (n = 74), and 78 Gy (n = 53)., Results: Analyzing the whole population 3 years after treatment, urgency and starting problems decreased in comparison to pre-treatment. A minor increase in urinary incontinence was reported 3 years after treatment in comparison to pre-treatment. No increases in other urinary symptoms were reported. Intestinal symptoms were slightly increased during the follow-up period in comparison to pre-treatment. Dose escalation with stereotactic EBRT (74-78 Gy) did not increase gastrointestinal or genitourinary late side effects at 1 year or 3 years in comparison to doses < or =70 Gy., Conclusions: The stereotactic BeamCath EBRT technique facilitates safe dose escalation of patients with prostate cancer., (Copyright 2002 Elsevier Science Ireland Ltd.)

The aim of this retrospective analysis was to evaluate bowel and urinary acute and late morbidity in patients with low to intermediate risk endometrial carcinoma, submitted to total abdominal hysterectomy and bilateral salpingo-oophorectomy, without lymphadenectomy, and postoperative high-dose-rate brachytherapy (HDR-B) as the sole treatment. From March 1996 to June 1998, 70 patients were treated on an outpatient basis, to a total dose of 30-50 Gy, given in two fractions per week. A total of 4-5 fractions of 6-10 GY was delivered. Three patients (4.2%) developed severe bowel complications, with one patient experiencing severe rectal bleeding. Local control was observed in 68 (97.1%) patients. Five-year actuarial disease and complication-free survival were 94.3% and 96.8%, respectively. In conclusion, it seems that a modest dose fraction schedule of HDR-B yields very high local control rates and low morbidity rates., (Copyright 2002 Wiley-Liss, Inc.)

Background: Good results have been obtained with radiation therapy for cervical cancer, but many patients suffer radiation-induced complications of adjacent organs. Some authors have reported that about 10% of patients treated with radiotherapy experience radiation-induced complications. We have previously reported that the incidence of spontaneous rupture of the urinary bladder is high in Japan but extremely low in the United States and Europe. In this study, we examined whether incidence or type of radiation-induced complications differs between Japan and the United States and Europe., Methods: A retrospective study was performed to determine the incidence among Japanese women of severe complications requiring surgical intervention following radiotherapy for cervical cancer. A total of 271 patients were treated at Kobe City General Hospital using external-beam therapy from December 1981 to March 1989. In 232 external-beam therapy was combined with high-dose-rate intracavitary brachytherapy with a remotely controlled afterloading system (RALS). The incidence and type of radiation-induced complications of the urinary tract, rectum, and intestine were determined following exclusion of 74 patients with evidence of disease recurrence or progression., Results: A total of 16 patients (8.1%) had urologic complications that required surgical intervention following irradiation, while a total of 26 patients (13.2%) had complications of the rectum or intestine that required surgical intervention following irradiation. Urologic complications occurred significantly later than those of the rectum and intestine (6.4 and 2.2 years, respectively) (P < 0.0001). The overall incidence of severe complications was comparatively higher than reported in the United States and Europe. The incidence of spontaneous rupture of the urinary bladder was particularly high (2.0%) in Japan., Conclusions: The incidence of severe complications following radiotherapy is comparatively higher in Japan than in the United States and Europe. In particular, spontaneous rupture of the urinary bladder is common in Japan. This might be due to the use of high-dose-rate brachytherapy. Since brachytherapy is currently being used for prostate cancer, urologists and radiologists must consider the possibility of a high incidence of such severe complications, especially when using high-dose-rate brachytherapy., (Copyright 2001 Academic Press.)

The concerted effort to minimize the radiation exposure to normal human tissues while delivering a high radiation dose to the tumor often results in complications. This limits the efficacy of radiation treatment. Analysis of radiation tolerance dose with organ weight in 15 human organs yields a correlation coefficient of 0.62, whereas the correlation of radiation tolerance dose with blood and water content yields correlation coefficients of 0.82 and 0.60, respectively. Results indicate that as the organ weight and/or blood and water content increases, radiation tolerance dose decreases.

The objective of this paper was to evaluate the acute urinary morbidity associated with I-125 interstitial implantation of the prostate gland. From 1991-1995, 117 patients underwent ultrasound (U/S)-guided implantation of the prostate gland. Median dose to 90% of the gland (d90) was 14.68 Gy (range = 1.65-21.75 Gy). The patients' urinary symptoms were recorded pre-implantation and at regular intervals after implantation using the International Prostate Symptom Score (IPSS), a self-assessment questionnaire in which patients scored 7 symptoms: incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Median follow-up was 12 months. The natural history of implant-related urinary symptoms was assessed in this manner. In addition, dosimetric factors including U/S prostate volume, total activity, activity per seed, dose volume histogram (DVH) values for dose to gland, and dose area histogram (DAH) values for dose to urethra and bladder were examined for correlation to the severity of each symptom as well as to total IPSS (sum of the individual symptom scores). Total IPSS peaked at 1 month post-implant and gradually returned to approximately baseline at 24 months. Total IPSS directly correlated with total activity and DVH for the prostate. Total IPSS, however, did not correlate with bladder or urethral DAH. With the exception of frequency, individual symptoms did not correlate with dose to gland, bladder, or urethra. Frequency scores did, however, correlate not only with dose to prostate gland but also dose to urethra. The acute urinary side effects of I-125 prostate implantation are transient and peak at 1 month post-implant. The severity of the urinary irritative symptoms developed are closely related to total dose to the gland. Urethral dose appears to affect frequency most significantly. Urinary symptoms, therefore, may be a limiting factor when considering dose escalation with I-125.

Background and Purpose: There is still a concern that the use of HDR brachytherapy might result in an increase of late tissue damage. This restrospective study evaluates the incidence and severity of late complications in patients with carcinoma of the cervix who underwent combined external beam radiation (EBR) and Ir-192 HDR brachytherapy and attempts to identify pretreatment and treatment parameters correlating with late complications., Material and Methods: Between 1985 and 1992, 161 patients with carcinoma of the cervix (FIGO stages IB-IVB) received EBR to the pelvis (ave, max. dose 48.8 Gy) followed by 1-6 Ir-192 HDR placements (median 2). Doses to point A ranged from 8.5 to 38.7 Gy (median 17 Gy). Parameters examined included age, diabetes, obesity, history of inflammatory bowel disease or diverticulitis, prior surgery, hemoglobin level, FIGO stage, EBR dose, technique and daily dose fraction, number of HDR treatments and total dose to point A, maximum doses to bladder and rectum delivered by brachytherapy and cumulative dose to point A. Median follow-up for all patients was 37 months. Complications were rated using an in-house scoring system and according to the French-Italian Glossary (FIG)., Results: Actuarial 5-year survival was 93%, 57%, 46%, and 0% for stages IB, II, IIIB, and IV, respectively. Of 161 patients, 11% developed moderate and 3.7% severe sequelae (FIG: 2.5%, 3.7%). Since some patients experienced more than one complication, the overall incidence was 13.6% and 4.9% (FIG: 3.1%, 4.9%) with respective 5-year actuarial rates of 14% and 5% for moderate, and 2% and 8% for severe bowel and genitourinary tract complications (FIG: 3.5%, 0, and 2%, 8%). All severe bowel complications occurred within 1.5 years whereas urinary tract sequelae continued to develop throughout the follow-up period. FIGO stage was associated with a significant increase in late sequelae (P = 0.015). Analysis of the remaining pretreatment and treatment parameters failed to reveal any statistically significant correlation with moderate or severe sequelae., Conclusion: In our series using HDR brachytherapy, complication and survival rates were comparable with other series employing either LDR or HDR procedures. Of all parameters analysed, stage of disease was the only parameter significantly correlated with complications in univariate and multivariate analysis.

Conventional 4-field box radiotherapy technique induces high morbidity for patients with localized prostatic cancer. Using a patient daily diary, the present study compared side-effects after conventional radiotherapy with conformal radiotherapy for prostate cancer. Fifty-eight patients treated with the conventional technique (with or without sucralfate) were compared with 72 patients treated with conformal technique. The patient groups were compared with an age-matched control population. Patients treated with conformal technique were also evaluated regarding acute and late urinary problems. Results showed that patients treated with conformal technique reported significantly fewer side-effects as compared with conventional technique. Patients treated with sucralfate also showed slightly decreased intestinal morbidity in comparison to non-sucralfate group. Acute and late morbidity evaluated by the patients was decreased after conformal radiotherapy as compared with the conventional technique. Sucralfate may be of value if conformal radiotherapy is used for dose escalation in prostatic cancer patients.