Conventional 3D conformal radiotherapy and volumetric modulated arc therapy for cervical cancer: Comparison of clinical results with special consideration of the influence of patient- and treatment-related parameters.

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.

Assessment of dose to functional sub-structures in the lower urinary tract in locally advanced cervical cancer radiotherapy.

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. D2cm3 and D0.1cm3, 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/ß = 3 and T1/2 = 1.5 h. RESULTS: Median D2cm3 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 D0.1cm3 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 D2cm3 and D0.1cm3, while bladder and trigone D2cm3 had poor correlation (R2 = 0.492), as well as D0.1cm3 (R2 = 0.356). Bladder neck D0.1cm3 was always lower than trigone D0.1cm3 and higher than IUO. Correlation between PIBS + 2 cm and IUO was poor (R2 = 0.273), while PIBS and PIBS-U were almost equal (R2 = 0.990). VRL correlated with dose to bladder base. CONCLUSIONS: The study confirmed that ICRU BP and trigone doses correlate. Bladder D2cm3 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 D2cm3 and D0.1cm3 for whole bladder, ICRU BP, trigone D2cm3 and D0.1cm3, IUO and PIBS are useful for lower urinary tract reporting.

Early and late toxicity profiles of patients receiving immediate postoperative radiotherapy versus salvage radiotherapy for prostate cancer after prostatectomy.

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.

Late toxicity of image-guided hypofractionated radiotherapy for prostate: non-randomized comparison with conventional fractionation.

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.

Physician assessed and patient reported urinary morbidity after radio-chemotherapy and image guided adaptive brachytherapy for locally advanced cervical cancer.

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.

4 Weeks Versus 5 Weeks of Hypofractionated High-dose Radiation Therapy as Primary Therapy for Prostate Cancer: Interim Safety Analysis of a Randomized Phase 3 Trial.

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.

Urinary Tract and Gynecologic Malignancies.

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.

Long-term Outcomes of a Dose-reduction Trial to Decrease Late Gastrointestinal Toxicity in Patients with Prostate Cancer Receiving Soft Tissue-matched Image-guided Intensity-modulated Radiotherapy.

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.

Patient-reported quality of life after stereotactic body radiation therapy versus moderate hypofractionation for clinically localized prostate cancer.

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.

Comparison of dosimetric parameters and acute toxicity of intensity-modulated and three-dimensional radiotherapy in patients with cervix carcinoma: A randomized prospective study.

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.

Independent external validation of predictive models for urinary dysfunction following external beam radiotherapy of the prostate: Issues in model development and reporting.

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.

Risk Factors and Time to Occurrence of Genitourinary Toxicity After External Beam Radiotherapy for Prostate Cancer.

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.

Thulium Laser in the Upper Urinary Tract: Does the Heat Generation in the Irrigation Fluid Pose a Risk? Evidence from an In Vivo Experimental Study.

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.

Does the Heat Generation by the Thulium:Yttrium Aluminum Garnet Laser in the Irrigation Fluid Allow Its Use on the Upper Urinary Tract? An Experimental Study.

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.

Prediction of toxicities of prostate cancer radiotherapy.

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.

[Treatment of long-term radiation injuries in the urinary tract]. / Therapie von Strahlenspätschäden am Harntrakt.

BACKGROUND: Radiotherapy plays a substantial role in the treatment of malignancies. The side effects and long-term sequelae of radiotherapy are manifold and depend on the single doses and the total dosage, the time interval between two doses, the size of the irradiated tissue area and the radiation sensitivity of individual tissues. The urological complications following radiotherapy include inflammatory alterations of the bladder (radiation-induced hemorrhagic cystitis), fibrosis with subsequent radiogenic shrunken bladder, stenosis of the ureter and formation of secondary retroperitoneal fibrosis. In addition, the formation of necrosis can result in rectourethral, uterovaginal and vesicovaginal fistulas up to formation of a cloaca. THERAPY: The main problem following radiotherapy is microangiopathy in the irradiated area. The therapy of radiation injuries in the urogenital tract depends on the extent and localization of the radiation damage. In particularly severe cases extremely complex reconstructive techniques are necessary for restoration of functionality of the urinary tract and preservation of renal function. CONCLUSION: Radiation injuries can remain asymptomatic for a long time so that a closely controlled urological surveillance is indispensable. The correct selection of the intestinal segments for surgical removal of radiation injuries in the urogenital tract is of pivotal importance.

Hydrogel Spacer Prospective Multicenter Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated Radiation Therapy.

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.

High-dose-rate brachytherapy boost for prostate cancer: Outcomes and genitourinary toxicity.

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.

Risk of radiation exposure to medical staff involved in interventional endourology.

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.

Acute urinary morbidity after a permanent 125I implantation for localized prostate cancer.

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.