Focal Salvage MR Imaging-Guided Cryoablation for Localized Prostate Cancer Recurrence after Radiotherapy: 12-Month Follow-up.

PURPOSE: To evaluate safety, quality of life (QoL), and local cancer control after focal salvage MR imaging-guided cryoablation in patients with local recurrence of prostate cancer (PCa) after radiotherapy. MATERIALS AND METHODS: A retrospective, single-center study was performed in 62 patients with radiorecurrent PCa who underwent MR imaging-guided cryoablation since May 2011 with a follow-up ≥12 months in December 2017. Rates and descriptions of adverse events were reported. Ablation complications were classified according to the Clavien and SIR systems. Validated questionnaires were used to observe functional outcomes and QoL before therapy and 6 and 12 months after therapy. Cancer control was defined as no biochemical failure according to Phoenix criteria and no other clinical evidence for local or metastatic disease. RESULTS: All procedures were technically feasible. The number of complications requiring major therapy (Clavien grade 3b/4 or SIR grade D/E/F) was low (2 [3.2%] and 1 [1.6%], respectively). After 12 months, the International Consultation of Incontinence Questionnaire-Short Form (P < .001) and 5-item International Index of Erectile Function (P = .001) scores became significantly worse, indicating increased symptoms of incontinence and diminished erectile function, without compromising QoL. Six patients developed metastases within 6 months. After 12 months, 36 patients (63%) were disease-free. CONCLUSIONS: Focal salvage MR imaging-guided cryoablation is safe and is associated with a high technical success rate, preservation of QoL, and local PCa control. This treatment can be a reasonable alternative to salvage radical prostatectomy in properly selected patients with low morbidity and preservation of QoL; however, longer follow-up is needed.

Does a decision aid for prostate cancer affect different aspects of decisional regret, assessed with new regret scales? A randomized, controlled trial.

OBJECTIVE: To develop and validate new regret scales and examine whether a decision aid affects different aspects of regret in the treatment choice for prostate cancer. METHODS: This was a multicentre trial (three sites) with imbalanced randomization (1 : 2). From 2008 to 2011, patients with localized prostate cancer were randomized 1 : 2 to usual care (N = 77) or usual care plus a decision aid presenting risks and benefits of different treatments (N = 163). The treatments were surgery and (external or interstitial) radiotherapy. Regret was assessed before, and 6 and 12 months after treatment, using the Decisional regret scale by Brehaut et al. (Medical Decision Making, 23, 2003, 281), and three new scales focusing on process, option and outcome regret. The relation between decision aid and regret was analysed by anova. RESULTS: The concurrent validity of the new regret scales was confirmed by correlations between regret and anxiety, depression, decision evaluation scales and health-related quality of life. With a decision aid, patient participation was increased (P = 0.002), but regret was not. If anything, in patients with serious morbidity the decision aid resulted in a trend to less option regret and less Brehaut regret (P = 0.075 and P = 0.061, with effect sizes of 0.35 and 0.38, respectively). Exploratory analyses suggest that high-risk patients benefitted most from the decision aid. CONCLUSION: The new regret scales may be of value in distinguishing separate aspects of regret. In general, regret was not affected by the decision aid. In patients with serious morbidity, a trend to lower option regret with a decision aid was observed.

Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): acute toxicity results from a randomised non-inferiority phase 3 trial.

BACKGROUND: In 2007, we began the randomised phase 3 multicentre HYPRO trial to investigate the effect of hypofractionated radiotherapy compared with conventionally fractionated radiotherapy on relapse-free survival in patients with prostate cancer. Here, we examine whether patients experience differences in acute gastrointestinal and genitourinary adverse effects. METHODS: In this randomised non-inferiority phase 3 trial, done in seven radiotherapy centres in the Netherlands, we enrolled intermediate-risk or high-risk patients aged between 44 and 85 years with histologically confirmed stage T1b-T4 NX-0MX-0 prostate cancer, a PSA concentration of 60 ng/mL or lower, and WHO performance status of 0-2. A web-based application was used to randomly assign (1:1) patients to receive either standard fractionation with 39 fractions of 2 Gy in 8 weeks (five fractions per week) or hypofractionation with 19 fractions of 3·4 Gy in 6·5 weeks (three fractions per week). Randomisation was done with minimisation procedure, stratified by treatment centre and risk group. The primary endpoint is 5-year relapse-free survival. Here we report data for the acute toxicity outcomes: the cumulative incidence of grade 2 or worse acute and late genitourinary and gastrointestinal toxicity. Non-inferiority of hypofractionation was tested separately for genitourinary and gastrointestinal acute toxic effects, with a null hypothesis that cumulative incidences of each type of adverse event were not more than 8% higher in the hypofractionation group than in the standard fractionation group. We scored acute genitourinary and gastrointestinal toxic effects according to RTOG-EORTC criteria from both case report forms and patients' self-assessment questionnaires, at baseline, twice during radiotherapy, and 3 months after completion of radiotherapy. Analyses were done in the intention-to-treat population. Patient recruitment has been completed. This study is registered with www.controlled-trials.com, number ISRCTN85138529. FINDINGS: Between March 19, 2007, and Dec 3, 2010, 820 patients were randomly assigned to treatment with standard fractionation (n=410) or hypofractionation (n=410). 3 months after radiotherapy, 73 (22%) patients in the standard fractionation group and 75 (23%) patients in the hypofractionation group reported grade 2 or worse genitourinary toxicity; grade 2 or worse gastrointestinal toxicity was noted in 43 (13%) patients in the standard fractionation group and in 42 (13%) in the hypofractionation group. Grade 4 acute genitourinary toxicity was reported for two patients, one (<1%) in each group. No grade 4 acute gastrointestinal toxicities were observed. We noted no significant difference in cumulative incidence by 120 days after radiotherapy of grade 2 or worse acute genitourinary toxicity (57·8% [95% CI 52·9-62·7] in the standard fractionation group vs 60·5% (55·8-65·3) in the hypofractionation group; difference 2·7%, 90% CI -2·99 to 8·48; odds ratio [OR] 1·12, 95% CI 0·84-1·49; p=0·43). The cumulative incidence of grade 2 or worse acute gastrointestinal toxicity by 120 days after radiotherapy was higher in patients given hypofractionation (31·2% [95% CI 26·6-35·8] in the standard fractionation group vs 42·0% [37·2-46·9] in the hypofractionation group; difference 10·8%, 90% CI 5·25-16·43; OR 1·6; p=0·0015; non-inferiority not confirmed). INTERPRETATION: Hypofractionated radiotherapy was not non-inferior to standard fractionated radiotherapy in terms of acute genitourinary and gastrointestinal toxicity for men with intermediate-risk and high-risk prostate cancer. In fact, the cumulative incidence of grade 2 or worse acute gastrointestinal toxicity was significantly higher in patients given hypofractionation than in those given standard fractionated radiotherapy. Patients remain in follow-up for efficacy endpoints. FUNDING: The Dutch Cancer Society.

Chronic radiation proctitis: tricks to prevent and treat.

OBJECTIVE: The purpose of this study was to give an overview of the measures used to prevent chronic radiation proctitis (CRP) and to provide an algorithm for the treatment of CRP. METHODS: Medical literature databases including PubMed and Medline were screened and critically analyzed for relevance in the scope of our purpose. RESULTS: CRP is a relatively frequent late side effect (5-20%) and mainly dependent on the dose and volume of irradiated rectum. Radiation treatment (RT) techniques to prevent CRP are constantly improving thanks to image-guided RT and intensity-modulated RT. Also, newer techniques like protons and new devices such as rectum spacers and balloons have been developed to spare rectal structures. Biopsies do not contribute to diagnosing CRP and should be avoided because of the risk of severe rectal wall damage, such as necrosis and fistulas. There is no consensus on the optimal treatment of CRP. A variety of possibilities is available and includes topical and oral agents, hyperbaric oxygen therapy, and endoscopic interventions. CONCLUSIONS: CRP has a natural history of improving over time, even without treatment. This is important to take into account when considering these treatments: first be conservative (topical and oral agents) and be aware that invasive treatments can be very toxic.

Systematic review: anal and rectal changes after radiotherapy for prostate cancer.

PURPOSE: Pelvic radiotherapy may lead to changes of anorectal function resulting in incontinence-related complaints. The aim of this study was to systematically review objective findings of late anorectal physiology and mucosal appearance after irradiation for prostate cancer. METHODS: MEDLINE, EMBASE, and the Cochrane library were searched. Original articles in which anal function, rectal function, or rectal mucosa were examined ≥3 months after EBRT for prostate cancer were included. RESULTS: Twenty-one studies were included with low to moderate quality. Anal resting pressures significantly decreased in 6 of the 9 studies including 277 patients. Changes of squeeze pressure and rectoanal inhibitory reflex were less uniform. Rectal distensibility was significantly impaired after EBRT in 7 of 9 studies (277 patients). In 4 of 9 studies on anal and in 5 of 9 on rectal function, disturbances were associated with urgency, frequent bowel movements or fecal incontinence. Mucosal changes as assessed by the Vienna Rectoscopy Score revealed telangiectasias in 73 %, congestion in 33 %, and ulceration in 4 % of patients in 8 studies including 346 patients, but no strictures or necrosis. Three studies reported mucosal improvement during follow-up. Telangiectasias, particularly multiple, were associated with rectal bleeding. Not all bowel complaints (30 %) were related to radiotherapy. CONCLUSIONS: Low to moderate quality evidence indicates that EBRT reduces anal resting pressure, decreases rectal distensibility, and frequently induces telangiectasias of rectal mucosa. Objective changes may be associated with fecal incontinence, urgency, frequent bowel movements, and rectal bleeding, but these symptoms are not always related to radiation damage.

Choice between prostatectomy and radiotherapy when men are eligible for both: a randomized controlled trial of usual care vs decision aid.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Many patients are eligible for more than one treatment option for prostate cancer. In usual care, urologists have a large influence on the treatment choice. Decision aids, providing balanced information on the pros and cons of different treatment options, improve the match between patient preferences and treatment received. In men eligible for both surgery and external beam radiotherapy, treatment choice differed by hospital. Across the participating hospitals, the decision aid consistently led to fewer patients remaining undecided on their treatment preference and more patients choosing brachytherapy. OBJECTIVES: To examine the treatment choice for localized prostate cancer in selected men who were eligible for both prostatectomy and radiotherapy. To examine whether increased patient participation, using a decision aid, affected the treatment choice. PATIENTS AND METHODS: From 2008 to 2011, 240 patients with localized prostate cancer were enrolled from three separate hospitals. They were selected to be eligible for both prostatectomy and external beam radiotherapy. Brachytherapy was a third option for about half of the patients. In this randomized controlled trial, patients were randomized to a group which only discussed their treatment with their specialist (usual care group) and a group which received additional information from a decision aid presented by a researcher (decision aid group). The decision aid was based on a literature review. Predictors of treatment choice were examined. RESULTS: Treatment choice was affected by the decision aid (P = 0.03) and by the hospital of intake (P < 0.001). The decision aid led to more patients choosing brachytherapy (P = 0.02) and fewer patients remaining undecided (P < 0.05). Prostatectomy remained the most frequently preferred treatment. Age, tumour characteristics or pretreatment urinary, bowel or erectile functioning did not affect the choice in this selected group. Patients choosing brachytherapy assigned more weight to convenience of the procedure and to maintaining erectile function. CONCLUSIONS: Traditionally, patient characteristics differ between surgery and radiotherapy groups, but not in this selected group of patients. Men eligible for both prostatectomy and radiotherapy mostly preferred prostatectomy, and the treatment choice was influenced by the hospital they visited. Giving patients evidence-based information, by means of a decision aid, led to an increase in brachytherapy.

Impact of late anorectal dysfunction on quality of life after pelvic radiotherapy.

PURPOSE: Anorectal dysfunction is common after pelvic radiotherapy. This study aims to explore the relationship of subjective and objective anorectal function with quality of life (QoL) and their relative impact in patients irradiated for prostate cancer. METHODS: Patients underwent anal manometry, rectal barostat measurement, and completed validated questionnaires, at least 1 year after prostate radiotherapy (range 1-7 years). QoL was measured by the Fecal Incontinence Quality of Life scale (FIQL) and the Expanded Prostate Cancer Index Composite Bowel domain (EPICB)-bother subscale. Severity of symptoms was rated by the EPICB function subscale. RESULTS: Anorectal function was evaluated in 85 men. Sixty-three percent suffered from one or more anorectal symptoms. Correlations of individual symptoms ranged from r = 0.23 to r = 0.53 with FIQL domains and from r = 0.36 to r = 0.73 with EPICB bother scores. They were strongest for fecal incontinence and urgency. Correlations of anal sphincter pressures, rectal capacity, and sensory thresholds ranged from r = 0.00 to r = 0.42 with FIQL domains and from r = 0.15 to r = 0.31 with EPICB bother scores. Anal resting pressure correlated most strongly. Standardized regression coefficients for QoL outcomes were largest for incontinence, urgency, and anal resting pressure. Regression models with subjective parameters explained a larger amount (range 26-92 %) of variation in QoL outcome than objective parameters (range 10-22 %). CONCLUSIONS: Fecal incontinence and rectal urgency are the symptoms with the largest influence on QoL. Impaired anal resting pressure is the objective function parameter with the largest influence. Therefore, sparing the structures responsible for an adequate fecal continence is important in radiotherapy planning.

Predictive value of MRI in the localization, staging, volume estimation, assessment of aggressiveness, and guidance of radiotherapy and biopsies in prostate cancer.

Multiparametric magnetic resonance imaging (MRI) has the potential of being the ideal prostate cancer (PCa) assessment tool. Information gathered with multiparametric MRI can serve therapy choice, guidance of interventions, and treatments. The purpose of this review is to discuss the potential role of multiparametric MRI in focal therapy with respect to patient selection and directing (robot-guided) biopsies and intensity-modulated radiation therapy (IMRT). Multiparametric MRI is a versatile and promising technique. It appears to be the best available imaging technique at the moment in localizing, staging (primary as well as recurrent disease, and local as well as distant disease), determining aggressiveness, and volume of PCa. However, larger study populations in multicenter settings have to confirm these promising results. However, before such studies can be performed more research is needed in order to achieve standardized imaging protocols.

Ferumoxtran-10 MR lymphography for target definition and follow-up in a patient undergoing image-guided, dose-escalated radiotherapy of lymph nodes upon PSA relapse.

PURPOSE: Evaluation of the lymph node situation in patients with prostate cancer is essential for effective radiotherapy. Using magnet resonance imaging (MRI) of the lymph nodes with ferumoxtran-10 (MR lymphography), it is possible to detect lymph node metastasis. We present our initial experience with ferumoxtran-10 MR lymphography as the basis for image-guided, dose-escalated lymph node radiotherapy and for early follow-up after radiotherapy. PATIENTS AND METHODS: A patient with suspicion for lymph node metastasis after radical prostatectomy was examined with MR lymphography with the lymph node-specific contrast media ferumoxtran-10. Radiotherapy was performed as intensity-modulated radiotherapy with a total dose of 44 Gy to the whole lymphatic drainage, 60 Gy to the area of affected lymph nodes, 71 Gy to the prostate bed, and 75 Gy to the anastomosis region. 8 weeks after completion of radiotherapy, a follow-up MR lymphography with ferumoxtran-10 was performed. RESULTS: In the first MRI with ferumoxtran-10, 5 metastatic lymph nodes were found in the iliac region. The scan 8 weeks postradiotherapy no longer showed lymph nodes suspicious for metastases. PSA (prostate-specific antigen) decreased from 2.06 ng/ml pretherapeutically to 0.02 ng/ml at 2 weeks after treatment and was no longer detectable at 8 months after treatment. CONCLUSIONS: Lymph node staging with ferumoxtran-10 and subsequent dose escalation with intensity-modulated radiotherapy led to the elimination of positive lymph nodes and a decrease in the PSA value.

Off-line setup corrections only marginally reduce the number of on-line corrections for prostate radiotherapy using implanted gold markers.

PURPOSE: To evaluate the efficiency of combining on-line and off-line corrections for the positioning of patients receiving external beam radiotherapy for prostate cancer. MATERIALS AND METHODS: Daily portal images were acquired during the treatment of 102 patients to verify and correct the position of the prostatic gland using implanted gold markers. In addition to an existing off-line procedure, on-line corrections were applied in the anterior-posterior (AP) direction only, to limit the increase in daily workload. The possible increase in workload of the combined correction procedure for on-line corrections in either two or three directions was further investigated by simulating the required position corrections for 500 treatments. RESULTS: The combined correction procedure in AP-direction resulted in a systematic dispersion and random variation of 0.3mm (1 SD) and 1.0mm (1 SD), respectively. Application of off-line corrections during pre-treatment setup reduced the number of required on-line corrections from 22+/-4 (1 SD) to 17+/-4 (1 SD), at the cost of 1.4+/-1.0 (1 SD) off-line corrections. For on-line corrections in two or three directions, application of a combined on-line/off-line procedure did not noticeably reduce the number of setup corrections. CONCLUSIONS: The on-line procedure is feasible and significantly improves both systematic and random errors to below 1 mm with a limited impact on the workload and treatment time. The application of off-line setup corrections during pre-treatment patient positioning only marginally reduces the number of on-line setup corrections.

Offering a treatment choice in the irradiation of prostate cancer leads to better informed and more active patients, without harm to well-being.

PURPOSE: To examine, in prostate cancer patients, the effect of (1) being offered a choice between radiation doses in three-dimensional conformal radiotherapy, and of (2) accepting or declining the possibility to choose. METHODS AND MATERIALS: A total of 150 patients with localized prostate cancer (T1-3N0M0) were offered a choice with a decision aid between two radiation doses (70 and 74 Gy). A control group of 144 patients received a fixed radiation dose without being offered a choice. Data were collected at baseline (before choice), before treatment (after choice), and 2 weeks and 6 months after treatment completion. RESULTS: Compared with the control group, the involvement group, receiving the decision aid, showed increased participation in decision making (p < 0.001), increased knowledge (p < 0.001), and improved risk perception (p < 0.001); they were more satisfied with the quality of information (p = 0.002) and considered their treatment a more appropriate treatment (p = 0.01). No group differences were found in well-being (e.g., general health, European Organization for Research and Treatment of Cancer quality of life, anxiety). Within the involvement group, accepting or declining the option to choose did not affect well-being either. CONCLUSIONS: Offering a choice of radiation dose, with a decision aid, increased involvement in decision making and led to a better-informed patient. In contrast to earlier suggestions, a strong increase in involvement did not result in improved well-being; and in contrast to clinical concerns, well-being was not negatively affected either, not even in those patients who preferred to leave the decision to their physician. This study shows that older patients, such as prostate cancer patients, can be informed and involved in decision making.

A biodegradable rectal balloon implant to protect the rectum during prostate cancer radiotherapy for a patient with active Crohn's disease.

BACKGROUND: Radiotherapy in patients with active inflammatory bowel disease (IBD) is usually considered an absolute exclusion criterion for prostate cancer radiotherapy treatment.There are no reports available on the use of a biodegradable rectal balloon implantation (RBI) in patients with active IBD for prostate cancer radiotherapy. CASE PRESENTATION: We report on a patient with high-risk prostate cancer with the comorbidity of an active IBD with pancolitis location. He was treated with neo-adjuvant hormonal therapy and high-dose external beam radiotherapy to the prostate and the seminal vesicles. Before radiotherapy treatment, a biodegradable RBI was implanted between the prostate and the anterior rectal wall to push the rectum outside of the high-dose area. This patient at high-risk for rectal toxicity was successfully irradiated to his prostate with only a grade I urinary toxicity, no acute rectal toxicity or toxicity flare of the IBD. CONCLUSIONS: This case describes the use of a RBI implantation in patients with active IBD for prostate cancer radiotherapy. The use of a biodegradable RBI proved to be a promised solution for such patients, and have to be further investigated.

Ultrasound-guided transrectal implantation of gold markers for prostate localization during external beam radiotherapy: complication rate and risk factors.

PURPOSE: To report the complication rate and risk factors of transrectally implanted gold markers, used for prostate position verification and correction procedures. METHODS AND MATERIALS: In 209 consecutive men with localized prostate cancer, four gold markers (1 x 7 mm) were inserted under ultrasound guidance in an outpatient setting, and the toxicity was analyzed. All patients received a questionnaire regarding complications after marker implantation. The complications and risk factors were further evaluated by reviewing the medical charts. RESULTS: Of the 209 men, 13 (6.2%) had a moderate complication, consisting of pain and fever that resolved after treatment with oral medication. In 1.9% of the men, minor voiding complaints were observed. Other minor transient complications, defined as hematuria lasting >3 days, hematospermia, and rectal bleeding, occurred in 3.8%, 18.5%, and 9.1% of the patients, respectively. These complications were seen more often in patients with advanced tumor stage, younger age, and shorter duration of hormonal therapy. CONCLUSION: Transrectal gold marker implantation for high-precision prostate radiotherapy is a safe and well-tolerated procedure.

Reduced late rectal mucosal changes after prostate three-dimensional conformal radiotherapy with endorectal balloon as observed in repeated endoscopy.

PURPOSE: The aim of this study was to investigate prospectively the rectal wall (Rwall) spatial dose distribution, toxicity, and mucosal changes after prostate cancer radiotherapy with or without an endorectal balloon (ERB). METHODS AND MATERIALS: A total of 24 patients with ERB and 24 without ERB (No-ERB) were treated with three-dimensional conformal radiotherapy (3D-CRT) to a dose of 67.5 Gy. The Rwall was divided into 16 mucosal areas and Rwall dose surface maps were constructed. After 3 months, 6 months, 1 year, and 2 years a rectosigmoidoscopy was performed, and each mucosal area was scored on telangiectasia, congestion, ulceration, stricture, and necrosis. Late rectal toxicity was correlated with the endoscopic findings. RESULTS: The ERB significantly reduced the Rwall volume exposed to doses >40 Gy. Late rectal toxicity (grade >or=1, including excess of bowel movements and slight rectal discharge) was reduced significantly in the ERB group. A total of 146 endoscopies and 2,336 mucosal areas were analyzed. Telangiectases were most frequently seen and appeared after 6 months. At 1 and 2 years, significantly less high-grade telangiectasia (T 2-3) was observed in the ERB group at the lateral and posterior part of the Rwall. In mucosal areas exposed to doses >40 Gy, less high-grade telangiectases (T 2-3) were seen in the ERB group compared with the No-ERB group. CONCLUSIONS: An ERB reduced the Rwall volume exposed to doses >40 Gy, resulting in reduction of late rectal mucosal changes and reduced late rectal toxicity. Although further analysis is needed, these data suggest an ERB-induced increased tolerance for late Rwall damage.

Prostate and lymph node proton magnetic resonance (MR) spectroscopic imaging with external array coils at 3 T to detect recurrent prostate cancer after radiation therapy.

In a patient suspected of having recurrent prostate cancer after radiation therapy, we demonstrate the feasibility of noninvasive proton magnetic resonance spectroscopic (1H-MRS) imaging of the prostate and a lymph node at 3 T using a matrix of external surface coils. Written informed consent was obtained from the patient. With 1H-MRS imaging, high choline with low citrate signal was observed in the prostate, and in the lymph node a signal of choline-containing compounds was identified. The tissue level of the compounds in the enlarged lymph node was estimated to be 8.1 mmol/kg water. Subsequent histopathological analysis of systematic transrectal ultrasound-guided prostate biopsy and computed tomography-guided biopsy of the lymph node confirmed the presence of prostate cancer in both.

A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate.

In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 µg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo). Pathway analyses revealed that the intervention with selenium was associated with down-regulated expression of genes involved in cellular migration, invasion, remodeling and immune responses. Specifically, expression of well-established epithelial markers, such as E-cadherin and epithelial cell adhesion molecule EPCAM, was up-regulated, while the mesenchymal markers vimentin and fibronectin were down-regulated after intervention with selenium. This implies an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to EMT. In conclusion, our explorative data showed that selenium affected expression of genes implicated in EMT in the transition zone of the prostate.

Bladder filling variation during radiation treatment of prostate cancer: can the use of a bladder ultrasound scanner and biofeedback optimize bladder filling?

PURPOSE: To investigate the use of a bladder ultrasound scanner in achieving a better reproducible bladder filling during irradiation of pelvic tumors, specifically prostate cancer. METHODS AND MATERIALS: First, the accuracy of the bladder ultrasound scanner relative to computed tomography was validated in a group of 26 patients. Next, daily bladder volume variation was evaluated in a group of 18 patients. Another 16 patients participated in a biofeedback protocol, aiming at a more constant bladder volume. The last objective was to study correlations between prostate motion and bladder filling, by using electronic portal imaging device data on implanted gold markers. RESULTS: A strong correlation between bladder scanner volume and computed tomography volume (r = 0.95) was found. Daily bladder volume variation was very high (1 SD = 47.2%). Bladder filling and daily variation did not significantly differ between the control and the feedback group (47.2% and 40.1%, respectively). Furthermore, no linear correlations between bladder volume variation and prostate motion were found. CONCLUSIONS: This study shows large variations in daily bladder volume. The use of a biofeedback protocol yields little reduction in bladder volume variation. Even so, the bladder scanner is an easy to use and accurate tool to register these variations.

Systematic review of the effect of radiation dose on tumor control and morbidity in the treatment of prostate cancer by 3D-CRT.

PURPOSE: A higher radiation dose is believed to result in a larger probability of tumor control and a higher risk of side effects. To make an evidence-based choice of dose, the relation between dose and outcome needs to be known. This study focuses on the dose-response relation for prostate cancer. METHODS AND MATERIALS: A systematic review was carried out on the literature from 1990 to 2003. From the selected studies, the radiation dose, the associated 5-year survival, 5-year bNED (biochemical no evidence of disease), acute and late gastrointestinal (GI) and genitourinary (GU) morbidity Grade 2 or more, and sexual dysfunction were extracted. With logistic regression models, the relation between dose and outcome was described. RESULTS: Thirty-eight studies met our criteria, describing 87 subgroups and involving up to 3000 patients per outcome measure. Between the (equivalent) dose of 70 and 80 Gy, various models estimated an increase in 5-year survival (ranging from 10% to 11%), 5-year bNED for low-risk patients (5-7%), late GI complications (12-16%), late GU complications (8-10%), and erectile dysfunction (19-24%). Only for the overall 5-year bNED, results were inconclusive (range, 0-18%). CONCLUSIONS: The data suggest a relationship between dose and outcome measures, including survival. However, the strength of these conclusions is limited by the sometimes small number of studies, the incompleteness of the data, and above all, the correlational nature of the data. Unambiguous proof for the dose-response relationships can, therefore, only be obtained by conducting randomized trials.

IMRT boost dose planning on dominant intraprostatic lesions: gold marker-based three-dimensional fusion of CT with dynamic contrast-enhanced and 1H-spectroscopic MRI.

PURPOSE: To demonstrate the theoretical feasibility of integrating two functional prostate magnetic resonance imaging (MRI) techniques (dynamic contrast-enhanced MRI [DCE-MRI] and 1H-spectroscopic MRI [MRSI]) into inverse treatment planning for definition and potential irradiation of a dominant intraprostatic lesion (DIL) as a biologic target volume for high-dose intraprostatic boosting with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: In 5 patients, four gold markers were implanted. An endorectal balloon was inserted for both CT and MRI. A DIL volume was defined by DCE-MRI and MRSI using different prostate cancer-specific physiologic (DCE-MRI) and metabolic (MRSI) parameters. CT-MRI registration was performed automatically by matching three-dimensional gold marker surface models with the iterative closest point method. DIL-IMRT plans, consisting of whole prostate irradiation to 70 Gy and a DIL boost to 90 Gy, and standard IMRT plans, in which the whole prostate was irradiated to 78 Gy were generated. The tumor control probability and rectal wall normal tissue complication probability were calculated and compared between the two IMRT approaches. RESULTS: Combined DCE-MRI and MRSI yielded a clearly defined single DIL volume (range, 1.1-6.5 cm3) in all patients. In this small, selected patient population, no differences in tumor control probability were found. A decrease in the rectal wall normal tissue complication probability was observed in favor of the DIL-IMRT plan versus the plan with IMRT to 78 Gy. CONCLUSION: Combined DCE-MRI and MRSI functional image-guided high-dose intraprostatic DIL-IMRT planned as a boost to 90 Gy is theoretically feasible. The preliminary results have indicated that DIL-IMRT may improve the therapeutic ratio by decreasing the normal tissue complication probability with an unchanged tumor control probability. A larger patient population, with more variations in the number, size, and localization of the DIL, and a feasible mechanism for treatment implementation has to be studied to extend these preliminary tumor control and toxicity estimates.

Who will benefit most from hydrogel rectum spacer implantation in prostate cancer radiotherapy? A model-based approach for patient selection.

BACKGROUND AND PURPOSE: Previous studies confirmed that implantable rectum spacers (IRS) decreased acute gastro-intestinal (GI) toxicity in a significant percentage of prostate cancer patients undergoing intensity modulated radiation therapy (IMRT). We developed decision rules based on clinical risk factors (CRFs) to select those patients who are expected to benefit most from IRS implantation. MATERIALS AND METHODS: For 26 patients dose distributions with (IMRT+IRS) and without (IMRT-IRS) IRS were calculated. Validated nomograms based on CRFs and dosimetric criteria (anorectal V40Gy and V75Gy) were used to predict probabilities for grade 2-3 (G2-3) acute GI toxicity, G2-3 late rectal bleeding (LRB), G3 LRB, and G2-3 faecal incontinence (FI) for IMRT+IRS and IMRT-IRS. All permutations of CRFs were generated to identify most benefit scenarios (MBS) in which a predicted toxicity reduction of ⩾5% points in ⩾25% of the cohort was present due to IRS implantation. RESULTS: IMRT+IRS revealed a significant reduction in V40Gy (p=0.0357) and V75Gy (p<0.0001) relative to IMRT-IRS. For G2-3 acute GI toxicity and G2-3 LRB, the predicted toxicity rates decreased in 17/26 (65%) and 20/26 (77%) patients, and decision rules were derived for 22/32 (69%) and 12/64 (19%) MBS, respectively. From the decision rules, it follows that diabetes status has no impact on G2-3 acute toxicity, and in absence of pre-RT abdominal surgery, the implantation of an IRS is predicted to show no clinically relevant benefit for G2-3 LRB. CONCLUSIONS: Prostate cancer patients who are expected to benefit most from IRS implantation can be identified prior to IMRT based on their CRFs profile.