Bladder Radiotherapy Research Articles

The role of ultrasound-guided applicator placement in intracavitary brachytherapy for cervical cancer

Context: Intracavitary brachytherapy (ICBT) involves insertion of a tandem applicator through the cervical os into the uterine cavity. Proper placement is critical to the success of ICBT: inadequate applicator geometry is associated with significantly impaired local control and operative complications (uterine perforation). One technique for real-time verification of tandem position is intraoperative ultrasonography (USG). Aims: The aim of this study is to evaluate the role of intraoperative transabdominal ultrasound-guided tandem placement in brachytherapy for cervical cancer. Settings and Design: This was a retrospective interventional study. Subjects and Methods: This was a single institutional study conducted from October 2013 to September 2014. Seventy-seven patients (219 intracavitary applications) of locally advanced cervical cancer were treated with routine ultrasound-guided brachytherapy after pelvic external beam radiotherapy (EBRT). Results: In 62 of the study patients, the cervical os could be identified visually. In 13 patients, ultrasound guidance was necessary for accurate os identification and proper tandem placement due to cervical canal stenosis. In another 2, intraoperative ultrasound helped in identifying the patients suitable for interstitial brachytherapy rather than ICBT (as a result of cervical anatomy distortion). At 24 months, disease-free status was achieved by 68.85% of patients. Seven patients developed Grade 1 bladder Radiation Therapy Oncology Group toxicity, and one had Grade 2 toxicity. Ten patients had Grade 1, and three had Grade 2 Rectal toxicities. Conclusions: We encountered no case of tandem malplacement or uterine perforation in our study. The disease control and treatment toxicity were within acceptable limits. USG image-based tandem application provides an accurate, fast, easily available, and cost-effective method for proper brachytherapy applicator placement.

Toxicity and Survival Outcomes of a Randomized Phase 2 Trial of Hypofractionated Bladder Radiation Therapy in an Elderly Population With or Without Image Guided Adaptive Plan Selection (HYBRID - CRUK/12/055)

Toxicity and Survival Outcomes of a Randomized Phase 2 Trial of Hypofractionated Bladder Radiation Therapy in an Elderly Population With or Without Image Guided Adaptive Plan Selection (HYBRID - CRUK/12/055)

EP-1845: The impact of intra-fractional bladder filling on adaptive bladder radiotherapy

A retrospective audit on the “Plan of the day” (POD) selection and intra-fractional bladder fillings were carried out on twenty adaptive bladder radiotherapy patients at a single institution. Treatment time, differences in bladder volume and displacement of outer bladder wall expansion over the treatment fraction were analysed. Average treatment time was 8.9 minutes. The mean percentage difference in bladder volume pre and post treatment was 13.7%, resulting in expansion of the bladder predominately in the superior and anterior directions. This audit confirmed that the institution’s POD process sufficed without being significantly affected by the intra-fractional bladder filings.

PD12-11 DECREASED VASCULAR ENDOTHELIAL GROWTH FACTOR IN RADIATION CYSTITIS

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I1 Apr 2017PD12-11 DECREASED VASCULAR ENDOTHELIAL GROWTH FACTOR IN RADIATION CYSTITIS Bernadette Zwaans, Sarah Bartolone, Heinz Nicholai, Michael Chancellor, and Laura Lamb Bernadette ZwaansBernadette Zwaans More articles by this author , Sarah BartoloneSarah Bartolone More articles by this author , Heinz NicholaiHeinz Nicholai More articles by this author , Michael ChancellorMichael Chancellor More articles by this author , and Laura LambLaura Lamb More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.686AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radiation cystitis (RC) is a severely debilitating and inflammatory condition of the bladder resulting from radiation therapy to the pelvic area for which there is no curative therapy. 5-10% of cancer patients who have received pelvic radiation will develop RC, though little is known about the histological and molecular changes that drive the disease progression. A major histological hallmark of RC is vascular damage and hemorrhaging. Therefore, our study focuses on identifying early molecular changes that drive the vascular defect observed in RC using a mouse model of RC. In addition, we aim to identify potential urine biomarkers that could identify RC development prior to the appearance of symptoms. METHODS Female C57BL/6 mice received a single dose of 40 Gy radiation delivered specifically to the bladder using a Small Animal Radiation Research Platform, a technique that simulates radiation treatment in human patients. Bladder tissues were harvested at 2 and 12 weeks post irradiation and processed for histology or molecular analysis. In addition, changes in vascular endothelial growth factor (VEGF) and cytokine/chemokine expression were analyzed in human urine samples from cancer survivors that received pelvic radiation. RESULTS Bladder irradiation was well tolerated by mice. By 12 weeks, decreased bladder vascularization was detected in irradiated animals as was an increase in inflammatory cells clustered around blood vessels. This vascularization defect coincided with a loss of VEGF levels. Decreased VEGF expression was also identified in urine from symptomatic RC patients, in comparison to age-matched controls. CONCLUSIONS Radiation therapy for the treatment of pelvic tumors can cause severe damage to the bladder that can develop into radiation (hemorrhagic) cystitis. Blood loss through the urine is a major hallmark of RC and is caused by vascular defects that are currently not well understood. In this study irradiated mouse bladders developed reduced vascularization which coincided with a loss of VEGF expression. In addition, low levels of VEGF were also identified in the urine of symptomatic RC patients. Our findings suggest VEGF as a potential therapeutic target to treat the vascular defect in RC. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e269-e270 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Bernadette Zwaans More articles by this author Sarah Bartolone More articles by this author Heinz Nicholai More articles by this author Michael Chancellor More articles by this author Laura Lamb More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Assessment of Adaptive Margins Using a Single Planning Computed Tomography Scan for Bladder Radiotherapy

Assessment of Adaptive Margins Using a Single Planning Computed Tomography Scan for Bladder Radiotherapy

Results of a randomised phase II study of hypofractionated bladder radiotherapy (RT) with or without image guided adaptive planning (HYBRID - CRUK/12/055).

283 Background: Muscle invasive bladder cancer (MIBC) incidence increases with age, with many patients (pts) unfit for radical therapy. We aimed to demonstrate feasibility of delivery & acceptable rates of hypofractionated RT toxicity using image guided adaptive techniques for these pts in a multicentre trial. Methods: Pts with T2-T4aN0M0 MIBC had 36 Gray (Gy) in 6 fractions (fr) over 6 weeks & were randomised (1:1) to standard (SP) or adaptive planning (AP). For AP 3 RT plans (small, medium, large) were generated with preRT cone beam (CB) CT used to select best fitting ‘plan of the day’ at each fr. A QA programme aided standardised CBCT image interpretation. The SP group had RT with 1 plan. The aim was to exclude ≥30% grade ≥3 (≥G3) acute (to 3 months (m)) non-genitourinary (GU) toxicity for AP in pts with no MIBC death by 3m (p0=0.7 p1=0.9 α=0.05 β=0.2). Secondary endpoints included 36Gy/6fr acute toxicity in pts who had ≥1 RT fr & proportion of AP fr using small/large plan. Adverse events (AEs) were assessed (CTCAE v4) weekly on RT, 4 weeks & 3m post RT. Blind independent review assessed relatedness of non-GU AEs to RT. Results: Between Apr 2014 & Aug 2016 65 pts were randomised (SP (n=32) AP (n=33)) from 12 UK sites. Median age was 85yrs; 68% male; 92% transitional cell MIBC; 99% grade 3; 25% clinical stage T3 & 6% T4. 58 pts are evaluable to date, ≥G3 acute non-GU adverse reactions (AR) were reported in 2/30 (7%; 90% CI: 1%–20%) AP (G3 hyperkalemia & hyponatremia; G3 diarrhea & dehydration) & 3/28 (11%; 90% CI: 3% –25%) SP pts (G3 fatigue; G3 hyperkalemia, weight loss & anorexia; G3 diarrhoea). 24/65 (37%; 90% CI: 27%-48%) pts who had ≥1 RT fr had ≥G3 acute AEs including G4 hyponatremia (2 AP pts), G5 pneumonia (1 SP, 1 AP), G5 sepsis (1 AP) & G5 renal failure (1 SP) (all G4/5 unrelated to RT). 7/65 pts received <6 fr RT due to toxicity. In the 33 AP pts 40/182 fr (22%) used a small plan & 29/182 (16%) large (adaption rate=38%; 95% CI: 31%-45%). Conclusions: Though overall ≥G3 AE rate was significant, 36Gy/6fr with AP is feasible, met predefined toxicity criteria (<30% ≥G3 acute non-GU ARs) & with >25% fr adapted has potential for benefit. Comparative randomised studies are needed to quantify benefits of AP over SP. Clinical trial information: 18815596.

Hyperbaric oxygen treatment reverses radiation induced pro-fibrotic and oxidative stress responses in a rat model

PurposeRadiotherapy is effective in the treatment of tumors in the pelvic area but is associated with side effects such as cystitis and proctitis. Hyperbaric Oxygen Therapy (HBOT) has emerged as a treatment modality for radiation-induced side effects. In a rat model for radiation cystitis, we studied the effects of HBOT on oxidative stress and pro-fibrotic factors. Materials and methodsSedated Sprague-Dawley rats underwent bladder irradiation of 20Gy with and without 20 sessions of HBOT during a fortnight. Control animals were treated with and without HBOT. All four groups of animals were euthanized 28 days later. Histopathological examinations, immunohistochemistry and quantitative polymerase chain reaction (qPCR) were used to analyze changes in oxidative stress (8-OHdG), anti-oxidative responses (SOD-1, SOD2, HO-1 and NRFα) and a panel of Th1-type and Th2-type cytokines (IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-α, TGF-β, IFN-γ) in the urinary bladder. ResultsBladder irradiation increased the expression of 8-OHdG, SOD2, HO-1, NRFα, IL-10, TNF-α and tended to increase TGF-β. These changes were completely reversed by HBOT while HBOT in control animals had no effects on the studied markers for oxidative stress, anti-oxidative responses and Th1-type and Th2-type cytokines. ConclusionsRadiation induced a significant elevation of oxidative stress, antioxidants and pro-fibrotic factors in our animal model for radiation cystitis that were completely reversed and normalized by HBOT. Our findings indicate that HBOT may prevent radiation-induced changes by affecting oxidative stress and inflammatory cascades induced by radiation. SummaryRadiotherapy may cause the development of chronic inflammation and fibrosis, significantly impairing organ function. We hypothesized that bladder irradiation induces an oxidative stress reaction, thereby triggering the redox system and thus initiating an inflammatory and pro-fibrotic response. We aimed to assess whether these changes would be reversed by hyperbaric oxygen using an animal model for radiation cystitis. Our study show that hyperbaric oxygen therapy may reverse oxidative stress and pro-inflammatory factors induced by radiation.

Comparison between standard and reduced volume radiotherapy in bladder preservation trimodality protocol for muscle-invasive bladder cancer patients.

AimOur aim is to compare the toxicity, pelvic nodal relapse, and overall survival of whole bladder irradiation only to the standard technique of whole pelvis irradiation followed by bladder boost in patients with muscle-invasive bladder carcinoma undergoing bladder preservation protocol.Material and methodA total of 60 patients with transitional cell carcinoma, stage T2-3, N0, M0 bladder cancer were subjected to maximal transurethral resection bladder tumour (TURB). Then, the patients were randomised into two groups: group I (30 patients) to receive whole pelvis radiotherapy 44 Gy followed by 20 Gy bladder boost. While group II (30 patients) were randomised to receive whole bladder radiotherapy alone for a total dose of 64 Gy. In both groups, concomitant cisplatin and paclitaxel were given weekly throughout the whole course of radiotherapy where conventional 2 Gy/fraction were used. Additionally, four cycles of adjuvant cisplatin and paclitaxel were given after the end of the chemoradiotherapy induction course.ResultsThe first assessment after the induction chemoradiotherapy showed that complete response was achieved in 73.3% of patients in group I and 76.7% of the patients in group II. After a median follow-up of 2 years, regional relapse occurred in 7.1% of patients in group I and 10.3% in group II. (p = 1). Distant metastases were detected in 17.9% of patient in group I and 13.8% in group II (p = 0.73). The 2-year disease-free survival was 60% in group I and 63.3% in group II (p = 0.79). The whole 2-year overall survival was 75% in group I and 79.3% in group II (p = 0.689). Radiation gastrointestinal (GI) acute toxicity was higher in group I than in group II (p = 0.001), while late GI radiation toxicity was comparable in both groups.ConclusionTreating the bladder only, without elective pelvic nodal irradiation, did not compromise pelvic control rate, but significantly decreased the acute radiation toxicity.

Bladder radiotherapy treatment: A retrospective comparison of 3-dimensional conformal radiotherapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy plans

To examine tumor׳s and organ׳s response when different radiotherapy plan techniques are used. Ten patients with confirmed bladder tumors were first treated using 3-dimensional conformal radiotherapy (3DCRT) and subsequently the original plans were re-optimized using the intensity-modulated radiation treatment (IMRT) and volumetric-modulated arc therapy (VMAT)-techniques. Targets coverage in terms of conformity and homogeneity index, TCP, and organs׳ dose limits, including integral dose analysis were evaluated. In addition, MUs and treatment delivery times were compared. Better minimum target coverage (1.3%) was observed in VMAT plans when compared to 3DCRT and IMRT ones confirmed by a statistically significant conformity index (CI) results. Large differences were observed among techniques in integral dose results of the femoral heads. Even if no statistically significant differences were reported in rectum and tissue, a large amount of energy deposition was observed in 3DCRT plans. In any case, VMAT plans provided better organs and tissue sparing confirmed also by the normal tissue complication probability (NTCP) analysis as well as a better tumor control probability (TCP) result. Our analysis showed better overall results in planning using VMAT techniques. Furthermore, a total time reduction in treatment observed among techniques including gantry and collimator rotation could encourage using the more recent one, reducing target movements and patient discomfort.

Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells

Purpose: Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy mechanisms of the combined treatment.Materials and methods: The Adenovirus carrying E1A under control of UPII promoter and prostate stem cell antigen enhancer (PSCAE) were successfully constructed. The viability of bladder cancer cells BIU-87 and EJ was determined by MTT assay. The apoptotic assay was demonstrated by flow cytometry and TEM. Virus titer was determined by TCID50 assay, and proteins Mre11, Chk2-Thr68, and E1A were analyzed by Western blot method.Results: Oncolytic adenovirus combined with radiotherapy improved antitumor efficacy compared with the single treatment at a time and was X-ray dosage-dependent. When the adenovirus infection was scheduled at 24 h after irradiation, cancer cells had the lowest viability. Adenovirus and irradiation induced cell death through the caspase-3 related apoptotic pathway, and bladder cancer cells were arrested at the G1 (BIU-87) or S phase (EJ). Autophagic vacuoles were observed in bladder cancer cells treated with radiation and adenovirus. After irradiation, more virus particles were observed in the BIU-87 and EJ cells. However, by a TCID50 assay, there was no difference in virus titter between irradiated bladder cancer cells and unirradiated cells. The proteins Mre11, Chk2-Thr68 which involved in the DNA break repair pathway were decreased while γ-H2AX-Ser139 increased; at the same time, the E1A gene and the hexon proteins of oncolytic adenovirus were increased after irradiation.Conclusions: Our results proved synergistic antitumor effect of adenovirus Ad-PSCAE-UPII-E1A and radiation, which might be a potential therapeutic strategy for bladder cancer.

What is the outcome of paediatric gastrocystoplasty when the patients reach adulthood?

To document the long-term outcomes of paediatric augmentation gastrocystoplasty (AGC) in terms of preservation of renal function and maintenance of dryness, and to analyse the rate of complications. The medical records of children who had undergone AGC between 1992 and 2000 (minimum time interval of 15 years) were reviewed retrospectively. The following data were collected: age at surgery, the cause of bladder dysfunction, functioning of the AGC, any complications, and the long-term outcome of the patients. All of the patients were re-contacted by telephone. A total of 11 AGCs were carried out between 1992 and 2000, at a median (range) age of 11 (6.5-14) years. The diagnosis of patients undergoing AGC included myelomeningocele (four), bladder exstrophy (four), posterior urethral valves (one), irradiated bladder (one), and Prune Belly syndrome (one). The median [interquartile range (IQR)] follow-up was 17 (15-19.5) years. Renal function was preserved or improved in seven of the 11 patients and nine patients were dry after AGC. Seven of the 11 patients reported symptoms linked to haematuria-dysuria syndrome, which was resistant to treatment in one case and requiring excision of the gastric patch. Three of the 11 patients developed a tumour on the gastric graft after a median (range) delay of 20 (11-22) years after the initial procedure. All had gastric adenocarcinoma of which two were metastatic at the time of diagnosis requiring pelvectomy with pelvic lymph node dissection and adjuvant chemotherapy. Seven of the 11 patients underwent excision of the gastric patch after a median (IQR) time of 11 (8.5-20.5) years. Our long-term data confirmed that most patients undergoing AGC had preservation of their renal function and were continent. However, long-term, AGC was associated with a significant risk of malignant transformation and a high rate of surgical re-intervention involving removal of the gastric patch. These results question the use of this technique for bladder augmentation, irrespective of the indication. We highlight the importance of strict endoscopic follow-up of all patients already having undergone an AGC and the need to inform and educated patients about tumour-related symptoms.

Downregulation of toll-like receptor 4 and IL-6 following irradiation of the rat urinary bladder.

The pathophysiology behind radiation cystitis is poorly understood. Here we investigated whether bladder irradiation affects the immune system of the rat urinary bladder. Female rats were sedated and exposed to one single radiation dose of 20Gy or only sedated (controls) and killed 16h to 14days later. Rats were placed in a metabolic cage at 16h, 3days, 7days and 14days following bladder irradiation. The urinary bladders were harvested and analysed with qPCR, immunohistochemistry and/or Western blot for the expression of interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, nitric oxide synthases (eNOS, iNOS and nNOS), tumour necrosis factor (TNF)-α and toll-like receptor 4 (TLR4). Urine was collected and analysed for IL-6 and nitrite (reflecting nitric oxide activity) with ELISA and the Griess reaction, respectively. Irradiation increased bladder frequency and decreased voiding volumes 14days following bladder irradiation. Bladder irradiation increased the expression of IL-10 and collagen in the bladder, while TLR4 and IL-6 expressions were decreased in the urothelium concomitantly with a decrease in mast cells in the submucosa and urine levels of IL-6 and nitrite. The present findings show that bladder irradiation leads to urodynamic changes in the bladder and may suppress important immunoregulatory pathways in the urinary bladder.

Assessment of Adaptive Margins Using a Single Planning Computed Tomography Scan for Bladder Radiotherapy

IntroductionA “plan of the day” (PoD) adaptive radiotherapy approach is presented for bladder cancer. The potential reduction in volumes of normal tissue and bowel bag receiving high-dose radiation is evaluated. Materials and MethodsPlanning computed tomography (pCT) and daily cone beam CT (CBCT) data sets were analyzed for eight previously treated bladder cancer patients. For each patient, a whole bladder clinical target volume (CTV) was delineated on a pCT. Then, the clinical target volume was expanded using five sets of anisotropic or isotropic margins to create five planning target volumes (PTVs). A library of five corresponding treatment PoDs was then created using volumetric modulated arc therapy. Offline PoD selection was performed by three independent radiation therapists (RTs) using daily CBCTs. Dosimetric results were compared between PoD treatments and two conventional treatments using isotropic 1.5- and 2.0-cm margins. ResultsThe smallest PTV using 1.0-cm isotropic margins was selected most frequently (70%). Three RTs demonstrated good agreement for daily PTV selections, choosing identical PoDs for 51% of all CBCTs. In addition, acceptable dosimetric coverage of the whole bladder was achieved for all PoD selections, similar to standard treatments. The average volume of bowel bag receiving 45 and 50 Gy and normal tissue receiving 95% prescription dose was significantly (P < .01) lower for PoD treatments compared with both conventional treatments. ConclusionsA PoD strategy using one pCT with isotropic and anisotropic margins can be used to treat bladder cancer and improve sparing of the bowel bag. Minimal dosimetric differences observed between three RTs suggests that PoD strategies are feasible for clinical implementation.

EP-1387: Outcomes after recurrent bladder cancer and (chemo)radiotherapy post TUR-B vs cystectomy

EP-1387: Outcomes after recurrent bladder cancer and (chemo)radiotherapy post TUR-B vs cystectomy

Quantification of Interobserver Variability in Image Registration Using Conebeam CT for Partial Bladder Radiotherapy

Quantification of Interobserver Variability in Image Registration Using Conebeam CT for Partial Bladder Radiotherapy

Evaluating the need for adaptive therapy when delivering conformal bladder radiotherapy

AbstractBackground and purposeThe purpose of this study was to audit positioning errors during bladder image-guided radiotherapy (IGRT) and quantify survival outcomes.Materials and methodsWe carried out a retrospective review of 141 patients treated between March 2007 and July 2010 with three-dimensional conformal radiotherapy. An offline imaging protocol using kV cone beam computed tomography (CBCT) was used. Positioning errors, clinical interventions and re-planning rates were quantified. Cancer outcomes and survival were collected by review of patient notes and a registry search.ResultsAmong all, 43% of the patients required no intervention. Isocentre corrections were used for systematic bony set-up error in 13% and to improve bladder coverage in 28%. Clinical interventions to improve bladder coverage were required in 16% of the patients and repeat computed tomography planning in a further 16%. Overall, 44% of the patients demonstrated some form of organ deformation that would have resulted in inadequate dose to the bladder or significant overdose to an organ at risk if not corrected for. Post-treatment check cystoscopy was undertaken in 107 patients (76%) with 72 noted to have a complete response. Overall survival was 47·8% at 3 years.ConclusionsOrgan deformation during radiotherapy for bladder cancer is a significant problem for over 40% of patients. Strategies to compensate are essential to ensure optimal plan delivery.

Impact of image registration surrogates on the planning target volume geometry for bladder radiation therapy

PurposeThe use of Lipiodol and cone beam computed tomography (CT) has facilitated the generation of patient-specific planning target volumes (PTV) to reduce irradiation of normal tissue. However, injecting Lipiodol to demarcate the target volume is an invasive procedure. Center of bladder (COB) and bladder wall surface (BWS) encompassed by the clinical target volume (CTV) are proposed to be the alternative noninvasive surrogates. This study examines the impact of using these 3 surrogates for image registration on the resultant geometry of patient-specific PTVs. Methods and materialsTwenty bladder cancer patients who had Lipiodol injection before planning CT were included. Lipiodol, CTV, and bladder were delineated on the planning CT. In addition, CTVs were delineated on 5 cone beam CT scans from each patient. Cone beam CT scans were registered to planning CT using Lipiodol, COB, and BWS to generate Lipiodol-PTV, COB-PTV, and BWS-PTV. Using Lipiodol as the reference, the difference in the 2-dimensional/3-dimensional displacement values and the geometry of the resultant PTVs were quantified. ResultsA total of 1200 displacement values and 60 volumes were included for analysis. The overall median and standard deviation (SD) of the 3-dimensional displacement (mm) measured by Lipiodol, BWS, and COB are 25 (SD, 15), 24 (SD, 14), and 21 (SD, 15), respectively. Lipiodol-PTV has the smallest mean volume, followed by BWS-PTV and COB-PTV. BWS-PTV was more geometrically similar to Lipiodol-PTV when compared with COB-PTV. Six of 20 COB-PTVs who had CTV located at either the dome or the base of the bladder were larger than the corresponding Lipiodol-PTV by more than 20%. ConclusionLipiodol is the optimal image registration surrogate for partial bladder radiation therapy. However, for patients who are contraindicated for Lipiodol injection, BWS is the preferred noninvasive surrogate because the derived PTV has a smaller geometric variation from the Lipiodol-PTV when compared with COB, especially when the CTV was located at the dome or the base of the bladder.

Quantification of Interobserver Variability in Image Registration Using Cone-beam CT for Partial Bladder Radiation Therapy

Quantification of Interobserver Variability in Image Registration Using Cone-beam CT for Partial Bladder Radiation Therapy

PD-0461: Population-based vs patient-specific margins for intrafractional motion in adaptive bladder radiotherapy

PD-0461: Population-based vs patient-specific margins for intrafractional motion in adaptive bladder radiotherapy

Intravesical Liposomal Tacrolimus Protects against Radiation Cystitis Induced by 3-Beam Targeted Bladder Radiation

We primarily determined whether the small animal radiation research platform could create a rat radiation cystitis model via targeted bladder irradiation (phase I). The response to treating early phase radiation cystitis in rats with transurethral catheter instillation of liposomal tacrolimus was also examined (phase II). In phase I 16 adult female Sprague Dawley® rats were used. Metabolic urination patterns were analyzed before and after exposure to 20, 30 or 40 Gy radiation. In phase II irradiated rats were randomly assigned to receive a single instillation of saline or liposomal tacrolimus. The 40 Gy radiation dose induced statistically significant reductions in the intermicturition interval compared to the lower radiation doses. By approximately 20 minutes 40 Gy radiation caused a significant decrease in the mean intermicturition interval (p < 0.0001). Histological analysis revealed degenerative epithelial changes and urothelial swelling with evidence of pseudocarcinomatous epithelial hyperplasia. Therefore, 40 Gy were chosen for the phase II efficacy study. There was no measurable change in total voided urine volume after irradiation, or after liposomal tacrolimus or saline instillation. Liposomal tacrolimus significantly increased the post-irradiation intermicturition interval by approximately 30 minutes back to baseline (p < 0.001). The radiation cystitis rat model showed a dose dependent decrease in the intermicturition interval without inducing short-term skin or gastrointestinal damage. This study demonstrates that liposomal tacrolimus may be a promising new intravesical therapy for the rare, serious condition of radiation cystitis.