Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III.

Long term-side effects from cancer therapies are a growing health care concern as life expectancy among cancer survivors increases. Damage to the bladder is common in patients treated with radiation therapy for pelvic cancers and can result in radiation (hemorrhagic) cystitis (RC). The disease progression of RC consists of an acute and chronic phase, separated by a symptom-free period. Gaining insight in tissue changes associated with these phases is necessary to develop appropriate interventions. Using a mouse preclinical model, we have previously shown that fibrosis and vascular damage are the predominant pathological features of chronic RC. The goal of this study was to determine the pathological changes during acute RC. We identified that radiation treatment results in a temporary increase in micturition frequency and decrease in void volume 4-8 weeks after irradiation. Histologically, the micturition defect is associated with thinning of the urothelium, loss of urothelial cell-cell adhesion and tight junction proteins and decrease in uroplakin III expression. By 12 weeks, the urothelium had regenerated and micturition patterns were similar to littermate controls. No inflammation or fibrosis were detected in bladder tissues after irradiation. We conclude that functional bladder defects during acute RC are driven primarily by a urothelial defect.

Diurnal rhythms of urine volume and electrolyte excretion in healthy young men under differing intensities of daytime light exposure.

In humans, most renal functions, including urine volume and electrolyte excretions, have a circadian rhythm. Light is a strong circadian entrainment factor and daytime-light exposure is known to affect the circadian rhythm of rectal temperature (RT). The effects of daytime-light exposure on the diurnal rhythm of urinary excretion have yet to be clarified. The aim of this study was to clarify whether and how daytime exposure to bright-light affects urinary excretions. Twenty-one healthy men (21-27 years old) participated in a 4-day study involving daytime (08:00-18:00 h) exposure to two light conditions, Dim (< 50 lx) and Bright (~ 2500 lx), in a random order. During the experiment, RT was measured continuously. Urine samples were collected every 3 ~ 4 h. Compared to the Dim condition, under the Bright condition, the RT nadir time was 45 min earlier (p = 0.017) and sodium (Na), chloride (Cl), and uric acid (UA) excretion and urine volumes were greater (all p < 0.001), from 11:00 h to 13:00 h without a difference in total daily urine volume. The present results suggest that daytime bright light exposure can induce a phase shift advance in urine volume and urinary Na, Cl, and UA excretion rhythms.

A prospective analysis of health-related quality of life in intermediate and high-risk prostate cancer patients managed with intensity modulated radiation therapy, with vs. without hormonal therapy.

INTRODUCTION: Combined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT). METHODS: Patients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RT + HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time. RESULTS: Of 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RT + HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RT + HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RT + HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores. CONCLUSION: Combined RT + HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT.

Management of Lower Urinary Tract Symptoms After Pelvic Radiation in Females.

PURPOSE OF REVIEW: To present the available literature pertaining to the management of lower urinary tract symptoms (LUTS) after pelvic radiation (RT) in female patients treated for pelvic malignancy. RECENT FINDINGS: Recent publications have focused on isolating de novo RT-induced LUTS in women from other contributors to urinary symptoms such as pelvic surgery and chemotherapy. There is a paucity of literature on the treatment of RT-related changes to urinary function. The treatment of pelvic malignancies in women alters voiding function. RT contributes to the deterioration of voiding function. More study is needed to evaluate the efficacy of available therapies.

Quality of life up to 10 years after external beam radiotherapy and/or brachytherapy for prostate cancer.

PURPOSE: The aim of this study was to evaluate quality-of-life changes up to 10 years following three different radiotherapy concepts. METHODS AND MATERIALS: In the years 2000-2003, 295 patients were treated with external beam radiotherapy (EBRT; n = 135; 70.2 Gy in 1.8 Gy fractions), low-dose-rate brachytherapy (LDR-BT with I-125; n = 94; 145 Gy), and high-dose-rate brachytherapy (HDR-BT with Ir-192; n = 66; 18 Gy in two fractions using 4-6 needles) as a boost to EBRT (50.4 Gy in 1.8 Gy fractions). Quality of life was assessed using the Expanded Prostate Cancer Index Composite at median time of 2, 6, and 10 years after treatment. RESULTS: The urinary function score 2 years after EBRT (mean 93 points) was significantly higher in comparison to HDR-BT + EBRT (80 points, higher doses to the urethra relevant) and LDR-BT (88 points). After 10 years, only HDR-BT + EBRT (75 points) remained worse (LDR-BT 92 points; EBRT 91 points). Urinary incontinence score decreased from 83 to 76 points in the HDR-BT + EBRT group. No significant differences or changes resulted in the bowel domain. The mean sexual function score (i.e., sexuality score) was significantly higher after LDR-BT versus HDR-BT + EBRT and EBRT (30 vs. 19 and 24 points after 2 years and 25 vs. 13 and 15 points after 10 years, respectively)-a lower patient age and a lower percentage with hormonal treatment need to be considered. CONCLUSION: Apart from decreasing sexual function for all patients, decreasing urinary scores were found in the HDR-BT + EBRT group predominantly as a result of increasing incontinence. This study demonstrates the need for optimum BT treatment planning.

Comparison of chronological changes in urinary function in patients who underwent low-dose-rate brachytherapy for prostate cancer-A randomized controlled trial of alpha-1 adrenoceptor antagonist alone versus combination with cyclooxygenase-2 inhibitor.

PURPOSE: To evaluate the add-on efficacy of a cyclooxygenase (COX)-2 inhibitor on the chronological changes in urinary function in patients who underwent low-dose-rate prostate brachytherapy. METHODS AND MATERIALS: A total of 310 patients with prostate cancer who underwent low-dose-rate-brachytherapy were enrolled. Patients were randomized and allocated to the monotherapy group (tamsulosin alone: 0.2 mg/d) and the combination group (tamsulosin 0.2 mg/d plus celecoxib: 200 mg/d). We compared the chronological change in the international prostate symptom score (IPSS), the overactive bladder symptom score (OABSS), uroflowmetric parameters, and the frequency volume chart. RESULTS: There was not a significant difference between the two groups in the chronological changes in IPSS and OABSS for 12 months after implantation. Regarding the frequency volume chart assessment, the mean daytime urinary frequency in the combination group at 3 and 6 months after implantation was significantly lower than that in the monotherapy group. Regarding IPSS recovery at 3 months after implantation, higher baseline IPSS and nonuse of external beam radiation therapy were independent factors, while smaller prostate volume and higher baseline IPSS were independent factors of IPSS recovery at 12 months after implantation based on multivariate analyses. CONCLUSIONS: There was not an additional effect of a COX-2 inhibitor to the action of an alpha-1 adrenoceptor antagonist on concerning the chronological changes in IPSS and OABSS. The use of a COX-2 inhibitor reduced the daytime urinary frequency and postvoid residual after seed implantation.

Patient-reported quality of life during definitive and postprostatectomy image-guided radiation therapy for prostate cancer.

PURPOSE: The importance of patient-reported outcomes is well-recognized. Long-term patient-reported symptoms have been described for individuals who completed radiation therapy (RT) for prostate cancer. However, the trajectory of symptom development during the course of treatment has not been well-described in patients receiving modern, image-guided RT. METHODS AND MATERIALS: Quality-of-life data were prospectively collected for 111 prostate cancer patients undergoing RT using the validated Prostate Cancer Symptom Indices, which assessed 5 urinary obstructive/irritative and 6 bowel symptoms. Patients who received definitive RT (N = 73) and postprostatectomy RT (N = 38) were analyzed separately. The frequency and severity of symptoms over multiple time points are reported. RESULTS: An increasing number of patients had clinically meaningful urinary and bowel symptoms over the course of RT. A greater proportion of patients undergoing definitive RT reported clinically meaningful urinary symptoms at the end of RT compared with baseline in terms of flow (33% vs 19%) and frequency (39% vs 18%). Individuals receiving postprostatectomy radiation also reported an increase in symptoms including frequency (29% vs 3%) and nocturia (50% vs 21%). Clinically meaningful bowel symptoms were less commonly reported. Patients receiving definitive RT reported an increase in diarrhea (9% vs 4%) and urgency (12% vs 6%) at the completion of RT compared with baseline. Both bowel and urinary symptoms approached their baseline levels by the time of first follow-up after treatment completion. The majority of patients who had clinically meaningful urinary or bowel symptoms during RT did not have them at 2 years or beyond, and development of new symptoms in the long term was uncommon. CONCLUSIONS: There is a modest increase in urinary and bowel symptoms over the course of treatment for individuals receiving definitive and postprostatectomy image-guided RT. These data can help inform both providers and patients regarding the trajectory of symptoms and allow for reasonable expectations regarding toxicity under treatment.

Urodynamic assessment of short-term effects of pelvic radiotherapy on bladder function in patients with gynecologic cancers.

OBJECTIVES: To determine the short-term effects of adjuvant or primary curative radiotherapy (RT) on the urinary system in women with gynecologic cancer. MATERIAL AND METHODS: This is a prospective, concurrent cohort study including 55 patients with gynecologic cancer who were divided into three groups. Group 1 included 10 patients who were administered adjuvant RT following a radical hysterectomy (RH); Group 2 included 36 patients who were administered adjuvant RT following a type 1 hysterectomy and Group 3 included 9 patients who were administered primary curative RT. Urogynecologic assessments were carried out on patients before and six months after the treatment. RESULTS: Compared to pretreatment, no significant differences were observed in any of the three groups after treatment in terms of incontinence, first urge to urinate, normal urge to urinate, severe urge to urinate and changes in residual urine volumes. There was a significant decrease in maximal vesical pressure after treatment in Group 1 and Group 3. The maxi-mum detrusor pressure decreased significantly in Group 1. The post-treatment decline in bladder capacity in Group 1 and Group 2 was also significant. CONCLUSIONS: RH and pelvic RT cause lower urinary system dysfunction. Especially patients who receive primary curative RT and patients who are administered RT after RH, where more pelvic denervation occurs, are at higher risk due to high doses of RT.

Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10.

PURPOSE: Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS: Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS: Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION: Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.

Estimated dose rates to members of the public from external exposure to patients with 131I thyroid treatment.

PURPOSE: Estimated dose rates that may result from exposure to patients who had been administered iodine-131 ((131)I) as part of medical therapy were calculated. These effective dose rate estimates were compared with simplified assumptions under United States Nuclear Regulatory Commission Regulatory Guide 8.39, which does not consider body tissue attenuation nor time-dependent redistribution and excretion of the administered (131)I. METHODS: Dose rates were estimated for members of the public potentially exposed to external irradiation from patients recently treated with (131)I. Tissue attenuation and iodine biokinetics were considered in the patient in a larger comprehensive effort to improve external dose rate estimates. The external dose rate estimates are based on Monte Carlo simulations using the Phantom with Movable Arms and Legs (PIMAL), previously developed by Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission. PIMAL was employed to model the relative positions of the (131)I patient and members of the public in three exposure scenarios: (1) traveling on a bus in a total of six seated or standing permutations, (2) two nursing home cases where a caregiver is seated at 30 cm from the patient's bedside and a nursing home resident seated 250 cm away from the patient in an adjacent bed, and (3) two hotel cases where the patient and a guest are in adjacent rooms with beds on opposite sides of the common wall, with the patient and guest both in bed and either seated back-to-back or lying head to head. The biokinetic model predictions of the retention and distribution of (131)I in the patient assumed a single voiding of urinary bladder contents that occurred during the trip at 2, 4, or 8 h after (131)I administration for the public transportation cases, continuous first-order voiding for the nursing home cases, and regular periodic voiding at 4, 8, or 12 h after administration for the hotel room cases. Organ specific activities of (131)I in the thyroid, bladder, and combined remaining tissues were calculated as a function of time after administration. Exposures to members of the public were considered for (131)I patients with normal thyroid uptake (peak thyroid uptake of ∼27% of administered (131)I), differentiated thyroid cancer (DTC, 5% uptake), and hyperthyroidism (80% uptake). RESULTS: The scenario with the patient seated behind the member of the public yielded the highest dose rate estimate of seated public transportation exposure cases. The dose rate to the adjacent room guest was highest for the exposure scenario in which the hotel guest and patient are seated by a factor of ∼4 for the normal and differentiated thyroid cancer uptake cases and by a factor of ∼3 for the hyperthyroid case. CONCLUSIONS: It was determined that for all modeled cases, the DTC case yielded the lowest external dose rates, whereas the hyperthyroid case yielded the highest dose rates. In estimating external dose to members of the public from patients with (131)I therapy, consideration must be given to (patient- and case-specific) administered (131)I activities and duration of exposure for a more complete estimate. The method implemented here included a detailed calculation model, which provides a means to determine dose rate estimates for a range of scenarios. The method was demonstrated for variations of three scenarios, showing how dose rates are expected to vary with uptake, voiding pattern, and patient location.

Patient-reported outcomes following stereotactic body radiation therapy for clinically localized prostate cancer.

BACKGROUND: Stereotactic body radiation therapy (SBRT) delivers high doses of radiation to the prostate while minimizing radiation to adjacent normal tissues. Large fraction sizes may increase the risk of functional decrements. Treatment-related bother may be more important to a patient than treatment-related dysfunction. This study reports on patient-reported outcomes following SBRT for clinically localized prostate cancer. METHODS: Between August 2007 and July 2011, 228 consecutive hormone-naïve patients with clinically localized prostate cancer were treated with 35-36.25 Gy SBRT delivered using the CyberKnife Radiosurgical System (Accuray) in 5 fractions. Quality of life was assessed using the American Urological Association Symptom Score (AUA) and the Expanded Prostate Cancer Index Composite (EPIC)-26. Urinary symptom flare was defined as an AUA score 15 or more with an increase of 5 or more points above baseline 6 months after treatment. RESULTS: 228 patients (88 low-, 126 intermediate- and 14 high-risk) at a median age of 69 (44-90) years received SBRT with a minimum follow-up of 24 months. EPIC urinary and bowel summary scores declined transiently at 1 month and experienced a second, more protracted decline between 9 months and 18 months before returning to near baseline 2 years post-SBRT. 14.5% of patients experienced late urinary symptom flare following treatment. Patients who experienced urinary symptom flare had poorer bowel quality of life following SBRT. EPIC scores for urinary bother declined transiently, first at 1 month and again at 12 months, before approaching pre-treatment scores by 2 years. Bowel bother showed a similar pattern, but the second decline was smaller and lasted 9 months to 18 months. EPIC sexual summary and bother scores progressively declined over the 2 years following SBRT without recovery. CONCLUSIONS: In the first 2 years, the impact of SBRT on urination and defecation was minimal. Transient late increases in urinary and bowel dysfunction and bother were observed. However, urinary and bowel function and bother recovered to near baseline by 2 years post-SBRT. Sexual dysfunction and bother steadily increased following treatment without recovery. SBRT for clinically localized prostate cancer was well tolerated with treatment-related dysfunction and bother comparable to conventionally fractionated radiation therapy or brachytherapy.

An MRI-based dose--reponse analysis of urinary sphincter dose and urinary morbidity after brachytherapy for prostate cancer in a phase II prospective trial.

PURPOSE: To compare dose-volume histogram variables for the internal and external urinary sphincters (IUS/EUS) with urinary quality of life after prostate brachytherapy. METHODS AND MATERIALS: Subjects were 42 consecutive men from a prospective study of brachytherapy as monotherapy with (125)I for intermediate-risk localized prostate cancer. No patient received hormonal therapy. Preplanning constraints included prostate V100 higher than 95%, V150 lower than 60%, and V200 lower than 20% and rectal R100 less than 1cm(3). Patients completed the Expanded Prostate Cancer Index Composite quality-of-life questionnaire before and at 1, 4, 8, and 12 months after implantation, and urinary domain scores were analyzed. All structures including the IUS and EUS were contoured on T2-weighted MRI at day 30, and doses received were calculated from identification of seeds on CT. Spearman's (nonparametric) rank correlation coefficient (ρ) was used for statistical analyses. RESULTS: Overall urinary morbidity was worst at 1 month after the implant. Urinary function declined when the IUS V285 was 0.4% (ρ=-0.32, p=0.04); bother worsened when the IUS V35 was 99% (ρ=-0.31, p=0.05) or the EUS V240 was 63% (ρ=-0.31, p=0.05); irritation increased when the IUS V35 was 95% (ρ=-0.37, p=0.02) and the EUS V265 was 24% (ρ=-0.32, p=0.04); and urgency worsened when the IUS V35 was 99.5% (ρ=-0.38, p=0.02). Incontinence did not correlate with EUS or IUS dose. CONCLUSIONS: Doses to the IUS and EUS on MRI/CT predicted worse urinary function, with greater bother, irritative symptoms, and urgency. Incorporating MRI-based dose-volume histogram analysis into the treatment planning process may reduce acute urinary morbidity after brachytherapy.

Assessment of late urinary, bowel and sexual function after dose escalation from 70 to 76 Gy using image-guided radiotherapy in curative treatment of prostate cancer.

OBJECTIVE: The aim of this study was to evaluate the late urinary, bowel and sexual function among men with localized or locally advanced prostate cancer treated with curative radiotherapy after the introduction of image-guided radiotherapy to 76 Gy using the Swedish BeamCath® technique. MATERIAL AND METHODS: All patients treated with curative radiotherapy during 2003-2006 were invited to participate in this retrospective study. In total, 87% (158/181) participated in the study. The median observation time was 35 months. Comparisons were made between the standard 70 Gy (n = 73) and the 76 Gy (n = 85) treatment groups. Assessments of late urinary, bowel and sexual function were questionnaire based, and included function items in the Expanded Prostate Cancer Index Composite. RESULTS: Most late urinary and bowel symptoms were reported to occur seldom or never in the majority of men, while late sexual toxicity was reported in a large proportion (66%) of men. Seven men (4%) used diapers. Only 25% (n = 40) reported having an erection firm enough for intercourse. None of the reported urinary or sexual function symptoms differed between the treatment groups. Rectal urgency at least once daily was a more frequent symptom in the 70 Gy group than the 76 Gy group (28% vs 9%, p = 0.006). Painful bowel movements were a more common symptom in the 70 Gy group (11% vs 1%, p = 0.01). CONCLUSION: Dose escalation up to 76 Gy using the BeamCath technique was not associated with more late toxicities than the standard 70 Gy dose.

[Permanent implant brachytherapy for early, organ-confined prostate cancer]. / Permanens implantációs prosztata-brachyterápia korai, szervre lokalizált prosztatarák kezelésére.

PURPOSE: Implementation of permanent prostate implant (PPI) brachytherapy in Hungary and presentation of initial experience. PATIENTS AND METHODS: Between December 2008 and 2010, thirty-nine patients with low (n=26) and intermediate (n=13) risk prostate cancer were treated with PPI. Their mean age and initial PSA were 66 year (51-80 year) and 9 ng/ml (3,2-15 ng/ml). Iodine-125 loose seeds were implanted under spinal anaesthesia using the FIRST system (Nucletron, The Netherlands). Needles were inserted into the prostate through the perineum according to the preplan based on transrectal ultrasound images. The treatment plan was modified according to updated positions of the needles on live US images. The prescribed dose to the prostate was 145 Gy. Seed loading was performed under real-time US assistance. Implanted sources were checked by X-ray and CT images. Patients were discharged one day after the implantation. On follow-up visits PSA and toxicity were registered. RESULTS: The mean follow-up was 10 months (3-27 months), the median number of seeds was 53 (30-78), their mean activity was 0.48 mCi (0.41-0.52 mCi). The mean coverage of the prostate by the prescribed dose was 96% (92-98%). The mean percent dose of the prescribed dose that covered the 90% of the prostate (D90), 2 cm3 of the rectum (Dr2cm3) and 10% of the urethra (Du10) were 113% (104-121%), 85% (48-121%) and 124% (98-146%) respectively. Deviation from the requested dose-volume constraints never exceeded 3%. Acute >grade 2 proctitis, grade 2 and 3 cysto-prostatitis were observed in 0 (0%), 13 (33.3%) and 1 (2.6%) cases. Biochemical relapse occurred in one patient (2.6%). CONCLUSION: This is a report of the first application of PPI in Hungary. The observed rate of acute proctitis was negligible, the rate and severity of acute cysto-prostatitis was tolerable. With the use of intraoperative planning, dose distributions met the dose-volume constraints in most of the cases. The biochemical control is excellent but the follow-up time is still short.

Cross validation of the prostate cancer radiotherapy late toxicity (PCRT) questionnaire with the expanded prostate cancer index composite (EPIC) instrument.

INTRODUCTION: A 29-item prostate cancer radiotherapy (PCRT) questionnaire with genitourinary (GU), gastrointestinal (GI), and sexual (S) domains has been previously validated for the assessment of late toxicity health-related quality of life (HRQoL) effects. The study objective was to cross-validate the PCRT domains versus the expanded prostate cancer index composite (EPIC) questionnaire urinary (U), bowel (B), hormonal (H), and S subscales. METHODS AND MATERIALS: A single-institution cross-sectional PCRT patient cohort was surveyed. Descriptive and intra- and inter-class correlation coefficient statistics for the various EPIC and PCRT HRQoL domain scores were generated. Univariable and multivariable Cox and logistic regressions were performed depending on the HRQoL endpoint being assessed. RESULTS: A total of 189/276 patients (68%) completed questionnaires with EPIC and PCRT missing data rates of 9% and 4%, respectively. Mean age was 75.8 years (SD 5.5) and the mean time of questionnaire completion after radiotherapy was 852 days (range 212-1454 days). Mean EPIC urinary (85.1 SD 12.9), bowel (84.1 SD 15.8), sexual (21.8 SD 20.7), and hormonal (85.3 SD 13.7) as well as PCRT genitourinary (66.1 SD 15.3), gastrointestinal (83.6 SD 14.3), and sexual (39.4 SD 21.6) domain scores were calculated. Intraclass correlation coefficients comparing corresponding EPIC/PCRT domains ranged from 0.50-0.88. Interclass correlation coefficients for non-corresponding EPIC/PCRT domains ranged from 0.16-0.43 and 0.23-0.30, respectively. EPIC B/U, PCRT GI/GU and PCRT S required arcsin square root transformation and EPIC S/H domains required dichotomous transformations prior to univariable/multivariable analyses. Multivariable analysis demonstrated novel associations between predictive variables and HRQoL domains including between the PTV-bladder overlap volume and PCRT GU score. CONCLUSIONS: The PCRT is a compact, valid, and HRQoL instrument with very high questionnaire compliance rates and similar statistical properties to the EPIC instrument. However, dichotomization of the PRCT S data was not required which suggests some potential statistical advantage to the PCRT.

Prophylactic vesical instillations with 0.2% chondroitin sulfate may reduce symptoms of acute radiation cystitis in patients undergoing radiotherapy for gynecological malignancies.

INTRODUCTION AND HYPOTHESIS: We studied the feasibility and efficacy of intravesical instillations with 40 ml chondroitin sulfate 0.2% solution to prevent or reduce acute radiation cystitis in women undergoing pelvic radiotherapy. METHODS: In a comparative pilot study in 20 patients, half of the patients received instillations. Instillations' bother was measured with visual analog scores (VAS, 0-10); bladder pain, with VAS; micturition-related quality of life, with the urogenital distress inventory (UDI). RESULTS: One of the instilled patients discontinued the instillations. The first median "acceptability"-VAS was 0 (range, 0-3); the last median was 1 (range, 0-3). "Bladder pain"-VAS peaked halfway in the treatment among controls (median, 1; range, 0-5) and after treatment in the instilled patients (median, 1; range, 1-3). UDI scores showed over time median follow-up scores at or above median baseline scores in controls and at or below median baseline scores in instilled patients. CONCLUSION: Intravesical instillations with chondroitin sulfate 0.2% solution may decrease the bother related to bladder symptoms and are well tolerated.

Photoentrainment in blind and sighted rodent species: responses to photophase light with different wavelengths.

Our study examined the impact of daylight (photophase) wavelength on the photoentrainment sensitivity of two species with vastly different visual systems. Social voles (Microtus socialis) and 'blind' mole rats (Spalax ehrenbergi) were exposed to short-wavelength (479 nm) or long-wavelength (697 nm) light at an intensity of 293 µW cm(-2). Rhythms of urine production, urinary 6-sulfatoxymelatonin (6-SMT), urinary metabolites of adrenaline and cortisol, and oxygen consumption (VO(2)) were used as markers for the sensitivity of the photoentrainment system. Significant 24-h rhythms were detected in all variables for both species under short-wavelength light, whereas ultradian rhythms of 12- or 8-h were detected under long-wavelength light. Wavelength inversely affected 6-SMT levels in M. socialis (negative correlation) and S. ehrenbergi (positive correlation). Increased levels of stress hormone metabolites were detected in M. socialis under the long-wavelength light whereas, in S. ehrenbergi elevated levels were secreted under short-wavelength light. Long-wavelength light increased VO(2) in M. socialis and decreased it in S. ehrenbergi; short-wavelength light elicited the opposite effects. Our results indicate that photophase wavelength is an integral light property for modulating photoperiodic responses in mammals, including visually challenged species. Finally, the spectral-induced differential responses between the two species potentially represent adaptive physiological flexibility in species with contrasting visual and habitat challenges.

Photosensitivity to different light intensities in blind and sighted rodents.

Photoperiod is an important cue regulating biological rhythms in mammals, including 'blind' subterranean and sighted fossorial rodent species. These species may respond differentially to changes in light quality according to their retinal complexity. The effects of increasing light intensity on daily rhythms of urine excretion and urinary output of 6-sulfatoxymelatonin levels were compared in 'blind' mole rats Spalax ehrenbergi and sighted social voles, Microtus socialis. Our results show that the threshold irradiance required to entrain rhythms of voles is three magnitudes greater than that for mole rats. The results suggest that mole rats have an operational photoreceptive pathway with a lower threshold irradiance than voles. Such a low threshold reflects the remarkable capability of this 'blind' species to utilize light signals even under challenging light conditions.

cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer.

BACKGROUND: To evaluate the impact of external beam radiation therapy (XRT) on weekly ultrasound determined post-void residual (PVR) urine volumes in patients with prostate cancer. METHODS: 125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66) or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59). All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes. RESULTS: The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively). Patients with a larger baseline PVR (>40 cc) had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR (<40 cc) had no demonstrable change throughout treatment. CONCLUSION: Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes.

Conformal radiotherapy of clinically localized prostate cancer: analysis of rectal and urinary toxicity and correlation with dose-volume parameters.

AIMS AND BACKGROUND: Rectal and urinary toxicities are the principal limiting factors in delivering a high target dose to patients affected by prostate cancer. The verification of such toxicity is an important step before starting a dose-escalation program. The present observational study reports on the acute and late rectal and urinary toxicity in relation with dose-volume parameters in 104 patients with localized prostate cancer treated with 3-dimensional conformal radiation therapy. METHODS AND STUDY DESIGN: One hundred and four patients with stage T1b-T3b prostate cancer were treated with three-dimensional conformal radiation therapy to a total dose of 74 Gy, 2 Gy per fraction. Rigid dose constraints were applied for rectum and bladder. Acute and late rectal and urinary toxicities were analyzed also in relation to dose-volume histograms. Biochemical relapse-free survival was defined according to the American Society of Therapeutic Radiation Oncology (ASTRO) criteria and to the RTOG-ASTRO Phoenix Consensus Conference Recommendations using the Kaplan-Meier method. RESULTS: No grade 3 toxicity was observed. Acute and late grade 2 toxicity rates were 5.8% and 9.0% for rectum and 12.5% and 2.0% for bladder, respectively. Rectal V70 influenced the occurrence of late grade 2 toxicity. A relationship between acute and late urinary toxicity was also found. After a median follow-up of 30 months (range, 20-50), the actuarial overall and biochemical relapse-free survival rates were 84% and 77%, respectively, with a significant difference between low-intermediate and high-risk patients. CONCLUSIONS: Conformal radiotherapy to the dose of 74 Gy was administered with good compliance. The incidence of acute and late toxicity was relatively low in accord with our dose constraints. Rectal V70 proved to be a reliable prognosticator of late toxicity. Overall survival and biochemical relapse-free survival rates were more favorable for low and intermediate-risk and significantly less favorable for high-risk patients.