Beam Radiotherapy For Prostate Cancer Research Articles

Transurethral Resection Versus Intermittent Catheterization in Patients with Retention after Combined Brachytherapy/External Beam Radiotherapy for Prostate Cancer: Intermittent Catheterization

Transurethral Resection Versus Intermittent Catheterization in Patients with Retention after Combined Brachytherapy/External Beam Radiotherapy for Prostate Cancer: Intermittent Catheterization

Transurethral Resection Versus Intermittent Catheterization in Patients with Retention after Combined Brachytherapy/External Beam Radiotherapy for Prostate Cancer: Transurethral Resection

Transurethral Resection Versus Intermittent Catheterization in Patients with Retention after Combined Brachytherapy/External Beam Radiotherapy for Prostate Cancer: Transurethral Resection

Late gastrointestinal and urogenital side-effects after radiotherapy – Incidence and prevalence. Subgroup-analysis within the prospective Austrian–German phase II multicenter trial for localized prostate cancer

PurposeIn general late side-effects after prostate cancer radiotherapy are presented by the use of actuarial incidence rates. The aim of this analysis was to describe additional relevant aspects of late side effects after prostate cancer radiotherapy. Materials and methodsAll 178 primary prostate-cancer patients were treated within the Austrian–German multicenter trial by three-dimensional radiotherapy up to a local dose of 70Gy (low/intermediate-risk) or 74Gy (high-risk), respectively. Late gastrointestinal/urogenital (GI/GU) side-effects were prospectively assessed by the use of EORTC/RTOG score. Maximum side-effects, actuarial incidence rate and prevalence rates, initial appearance and duration of ⩾grade 2 toxicity were evaluated. ResultsMedian follow-up was 74months. Late GI/GU side-effects ⩾grade 2 were detected in 15% (27/178) and 22% (40/178). The corresponding 5-year actuarial incidence rates for GI/GU side-effects were 19% and 23%, whereas the prevalence was 1–2% and 2–7% after 5years, respectively. Late side effects ⩾grade 2 appeared within 5years after radiotherapy in all patients with GI side-effects (27/27) and in 85% (34/40) of the patients with GU side-effects, respectively and lasted for less than 3years in 90% (GI) and 98% (GU). ConclusionsThis study demonstrates that the majority of late GI and GU side effects after primary external beam radiotherapy for prostate cancer are transient. Using only actuarial incidence rates for reporting side effects may lead to misinterpretation or overestimation. The combination of incidence and prevalence rates provides a more comprehensive view on the complex issue of late side effects.

Commentary on “Health-related quality of life after single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiotherapy for prostate cancer.” Morton GC, Loblaw DA, Chung H, Tsang G, Sankreacha R, Deabreu A, Zhang L, Mamedov A, Cheung P, Batchelar D, Danjoux C, Szumacher E, Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, ON, Canada: Int J Radiat Oncol Biol

Commentary on “Health-related quality of life after single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiotherapy for prostate cancer.” Morton GC, Loblaw DA, Chung H, Tsang G, Sankreacha R, Deabreu A, Zhang L, Mamedov A, Cheung P, Batchelar D, Danjoux C, Szumacher E, Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, ON, Canada: Int J Radiat Oncol Biol

Posttreatment Prostate Specific Antigen Nadir Predicts Prostate Cancer Specific and All Cause Mortality

We investigated whether the prostate specific antigen nadir predicts prostate cancer specific and all cause mortality in men treated in a randomized trial of radiation with or without 6 months of androgen deprivation therapy. The study included 204 men with cT1b-T2bN0M0 prostate adenocarcinoma and at least 1 unfavorable factor, including prostate specific antigen less than 10 to 40 ng/ml, Gleason 7 or greater, or T3 on magnetic resonance imaging. We performed Fine and Gray regression, and Cox multivariable analysis to determine whether an increasing prostate specific antigen nadir was associated with prostate cancer specific and all cause mortality, adjusting for treatment, age, Adult Comorbidity Evaluation 27 score and cancer prognostic factors. At a 6.9-year median followup median prostate specific antigen nadir was 0.7 ng/ml for radiation alone and 0.1 ng/ml for radiation plus androgen deprivation therapy. The prostate specific antigen nadir (adjusted HR 1.18/ng/ml increase, 95% CI 1.07-1.31, p=0.001) and Gleason 8 or greater (adjusted HR 8.05, 95% CI 1.01-64.05, p=0.049) significantly predicted increased prostate cancer specific mortality. Moderate/severe comorbidity carried a decreased risk (adjusted HR 0.13, 95% CI 0.02-0.96, p=0.045). Higher prostate specific antigen nadir (adjusted HR 1.10/ng/ml increase, 95% CI 1.04-1.17), older age (adjusted HR 1.10/year, 95% CI 1.04-1.15) and interaction between comorbidity score and randomization arm (each p<0.001) increased the all cause mortality risk. Men who achieved a prostate specific antigen nadir of the median value or less had lower estimated prostate cancer specific and all cause mortality at 7 years (3.7% vs 18.3%, p=0.0005 and 31.5% vs 55.0%, p=0.002). Posttreatment prostate specific antigen nadir is significantly associated with the risk of prostate cancer specific and all cause mortality after radiation with or without androgen deprivation therapy. A suboptimal prostate specific antigen nadir may identify candidates for earlier intervention to prolong survival.

Vacuum Erection Devices Revisited: Its Emerging Role in the Treatment of Erectile Dysfunction and Early Penile Rehabilitation Following Prostate Cancer Therapy

Vacuum erection devices (VEDs) are becoming first-line therapies for the treatment of erectile dysfunction and preservation (rehabilitation) of erectile function following treatment for prostate cancer. Currently, there is limited efficacy of the use of phosphodiesterase type 5 inhibitors in elderly patients, or patients with moderate to severe diabetes, hypertension, and coronary artery disease. The article aims to study the role of VED in patients following prostate cancer therapy. Alternative therapies such as VED have emerged as one of the primary options for patients refractory to oral therapy. VED has also been successfully used in combination treatment with oral therapy and penile injections. More recently, there has been interest in the use of VED in early intervention protocols to encourage corporeal rehabilitation and prevention of postradical prostatectomy veno-occlusive dysfunction. This is evident by the preservation of penile length and girth that is seen with early use of the VED following radical prostatectomy. There are ongoing studies to help preserve penile length and girth with early use of VED following prostate brachytherapy and external beam radiation for prostate cancer. Recently, there has also been interest in the use of VED to help maintain penile length following surgical correction of Peyronie's disease and to increase penile size prior to implantation of the penile prosthesis. VEDs can be one of the options for penile rehabilitation after prostate cancer therapy.

Dose reduction in LDR brachytherapy by implanted prostate gold fiducial markers

The dosimetric impact of gold fiducial markers (FM) implanted prior to external beam radiotherapy of prostate cancer on low dose rate (LDR) brachytherapy seed implants performed in the context of combined therapy was investigated. A virtual water phantom was designed containing a single FM. Single and multi source scenarios were investigated by performing Monte Carlo dose calculations, along with the influence of varying orientation and distance of the FM with respect to the sources. Three prostate cancer patients treated with LDR brachytherapy for a recurrence following external beam radiotherapy with implanted FM were studied as surrogate cases to combined therapy. FM and brachytherapy seeds were identified on post implant CT scans and Monte Carlo dose calculations were performed with and without FM. The dosimetric impact of the FM was evaluated by quantifying the amplitude of dose shadows and the volume of cold spots. D(90) was reported based on the post implant CT prostate contour. Large shadows are observed in the single source-FM scenarios. As expected from geometric considerations, the shadows are dependent on source-FM distance and orientation. Large dose reductions are observed at the distal side of FM, while at the proximal side a dose enhancement is observed. In multisource scenarios, the importance of shadows appears mitigated, although FM at the periphery of the seed distribution caused underdosage (<prescription dose). In clinical cases, the FM reduced the dose to some voxels by up to 50% and generated shadows with extents of the order of 4 mm. Within the prostate contour, cold spots (<95% prescription dose) of the order of 20 mm(3) were observed. D(90) proved insensitive to the presence of FM for the cases selected. There is a major local impact of FM present in LDR brachytherapy seed implant dose distributions. Therefore, reduced tumor control could be expected from FM implanted in tumors, although our results are too limited to draw conclusions regarding clinical significance.

Learning image context for segmentation of the prostate in CT-guided radiotherapy

Accurate segmentation of the prostate is the key to the success of external beam radiotherapy of prostate cancer. However, accurate segmentation of the prostate in computer tomography (CT) images remains challenging mainly due to three factors: (1) low image contrast between the prostate and its surrounding tissues, (2) unpredictable prostate motion across different treatment days and (3) large variations of intensities and shapes of the bladder and rectum around the prostate. In this paper, an online-learning and patient-specific classification method based on the location-adaptive image context is presented to deal with all these challenging issues and achieve the precise segmentation of the prostate in CT images. Specifically, two sets of location-adaptive classifiers are placed, respectively, along the two coordinate directions of the planning image space of a patient, and further trained with the planning image and also the previous-segmented treatment images of the same patient to jointly perform prostate segmentation for a new treatment image (of the same patient). In particular, each location-adaptive classifier, which itself consists of a set of sequential sub-classifiers, is recursively trained with both the static image appearance features and the iteratively updated image context features (extracted at different scales and orientations) for better identification of each prostate region. The proposed learning-based prostate segmentation method has been extensively evaluated on 161 images of 11 patients, each with more than nine daily treatment three-dimensional CT images. Our method achieves the mean Dice value 0.908 and the mean ± SD of average surface distance value 1.40 ± 0.57 mm. Its performance is also compared with three prostate segmentation methods, indicating the best segmentation accuracy by the proposed method among all methods under comparison.

Reducing the side effects of external beam radiotherapy in prostate cancer: role of imaging techniques

Imaging plays an important role in prostate radiotherapy. New imaging technologies have improved our ability to visualize tumors within the gland and allow accurate guidance of treatment delivery. Imaging is increasingly an integral part of ‘state of the art’ radiation planning and delivery, which gives the promise of increasing cancer control while reducing the side effects of treatment.

Urethra sparing – potential of combined Nickel–Titanium stent and intensity modulated radiation therapy in prostate cancer

Background and purposeTo investigate a novel method for sparing urethra in external beam radiotherapy of prostate cancer and to evaluate the efficacy of such a treatment in terms of tumour control using a mathematical model. Materials and methodsThis theoretical study includes 20 patients previously treated for prostate cancer using external beam radiotherapy. All patients had a Nickel–Titanium (Ni–Ti) stent inserted into the prostate part of urethra. The stent has been used during the treatment course as an internal marker for patient positioning prior to treatment. In this study the stent is used for delineating urethra while intensity modulated radiotherapy was used for lowering dose to urethra. Evaluation of the dose plans were performed using a tumour control probability model based on the concept of uniform equivalent dose. ResultsThe feasibility of the urethra dose reduction method is validated and a reduction of about 17% is shown to be possible. Calculations suggest a nearly preserved tumour control probability. ConclusionsA new concept for urethra dose reduction is presented. The method relies on the use of a Ni–Ti stent as a fiducial marker combined with intensity modulated radiotherapy. Theoretical calculations suggest preserved tumour control.

Single blind randomized Phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial

BackgroundThe treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer.Methods/DesignThe FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer) is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm) with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain accurate dose-effect information for both the macroscopic tumor and subclinical disease in prostate cancer. The rationale, study design and the first 50 patients included are described.Trial registrationThis study is registered at ClinicalTrials.gov: NCT01168479

Results of Patterns of Care Study of Patients Treated with External Beam Radiotherapy for Prostate Cancer in 2004

Results of Patterns of Care Study of Patients Treated with External Beam Radiotherapy for Prostate Cancer in 2004

Delivered Dose To Bladder Can Be Higher Than Planned Dose: Dependence On Planning Bladder Volume

For patients undergoing external beam radiation for prostate cancer, the planning bladder volume (PBV) can vary considerably among patients, resulting in poor correlation between planned dose and GU toxicity. The purpose of this study is to characterize the planning dose volume histograms (DVHs) as a function of bladder volume, to evaluate changes of daily bladder volume, and to quantify differences between planned and treatment DVHs of the bladder.

7027 POSTER Postoperative External Beam Radiotherapy in Prostate Cancer -Results of the Spanish Registry of Prostate Cancer

7027 POSTER Postoperative External Beam Radiotherapy in Prostate Cancer -Results of the Spanish Registry of Prostate Cancer

SU‐E‐T‐37: A New Metric to Predict Rectal Bleeding Based on Dose‐Surface Properties

Purpose: To test a new property that can be used as an effective prognostic indicator of rectal toxicity against rectal bleeding data in prostate cancer patients. Methods: The method is based on dose to surface and accounts for spatial relationship between rectal surface elements. A property that is a function of the dose at 2 points on the rectal surface weighted by a function dependent on the distance between the points is proposed as an alternative to DVH criteria for predicting rectal toxicity. The weighting function was described as a logistic function. The shortest distance between the points i and j on the rectal surface was approximated using the multistencil fast marching method (MFMM). This approach approximates a solution to the Eikonal equation which describes the propagation of an advancing wavefront from a source point, i. Then, the distance between any points, i and j, can easily be determined if the speed is constant. For each patient the maximum value of the property calculated for all surface elements is considered as a candidate for predicting rectal bleeding. The property was calculated for 170 patients who underwent external beam radiotherapy for prostate cancer and followed‐up for rectal bleeding. The prognostic value of the property was evaluated using log‐rank test for actuarial incidence of complications. A range of logistic function parameters was considered. Results: Eighty seven cases using various combinations of the constants that control the slope and inflection point of the logistic function have been processed. The maximum value of the metric spanned a range from 32.37 to 599.8 (Gy·cm)̂2. The analysis for the prognostic power of the property is in progress. Conclusions: The proposed rectal surface property incorporates dose as well as spatial relationship between rectal surface elements. It is easily calculated for an arbitrarily complex geometry.

SU‐E‐T‐270: A “Rolling Average” Adaptive Planning Technique to Compensate Target Volume Changes in Prostate Cancer Radiotherapy

Purpose: In external beam radiotherapy of prostate cancer, the inter‐fractional motion can have several forms: changes in position, shape and volume. The changes in position can be corrected by online image guidance, while the shape and volume changes are typically handled through the patient‐population based margins in treatment planning. In this study, we propose a rolling‐average (RA) adaptive replanning method to account for the volume variation of the target. The effectiveness of RA is evaluated by comparing with the standard online image guidance (IG) only strategy and a single replanning hybrid strategy. Methods: Twenty‐eight (28) patients with at least 16 helical CT scans each were included. Treatment of both low‐risk patient (LRP, CTV=prostate) and intermediate‐risk patient (IRP, CTV=prostate+seminal vesicles) were simulated. A new cumulative index of target volume, CITV, was proposed for the comparison of RA and other strategies. Two hypothetical scenarios: Type Ascending and Descending, simulated by sorting the CTV volumes of actual patient data, were also included in the investigation for a better evaluation of the techniques. Results: Modest target volume shrinkages were observed in our patient group. The CITV comparison demonstrates that the RA is superior to the online IG and hybrid techniques. For LRP, RA is beneficial if there is significant time trend in target volume. The optimal number of fractions necessary for the internal target volume construction is 2 for LRP and 3 for IRP. Conclusions: The RA is effective in compensating the target volume changes during the treatment course. However, the magnitude of improvement depends on how significantly and rapidly the changes in the patient population. The RA requires multiple replanning and is significantly more complex than the online only and hybrid strategies. Effectiveness and efficiency should be balanced in the implementation of RA.

Endorectal MRI after radiation therapy: Questioning the sextant analysis

To evaluate whether the information gained by three coregistration systems (sextant, hemi-prostate, and whole gland) differs significantly, suggesting that one approach should be routinely favored over the others. Despite its known limitations, sextant is the generally accepted standard for magnetic resonance imaging (MRI) and biopsy coregistration; nevertheless, depending on the magnitude of localization errors, other options may be adequate. Institutional Review Board approval was obtained and the study was Health Insurance Portability and Accountability Act (HIPAA)-compliant. We identified 70 patients who underwent 1.5 T endorectal MRI of the prostate between 1999 and 2008 after external beam radiotherapy for prostate cancer. A single reader reviewed all T2-weighted images for the presence or absence of tumor. The performance of each approach was quantified using receiver operating characteristic (ROC) curve analysis. Transrectal ultrasound-guided sextant biopsies were used as a standard of reference. The areas under the ROC curve indicating accuracy for each MRI approach were 0.63 (sextant), 0.68 (hemi-prostate), and 0.71 (whole gland). There was no statistically significant difference among these approaches. As expected, the point estimate was higher for the whole-gland approach, but not significantly. Reliable assessment of locally recurrent prostate cancer after external beam radiotherapy by endorectal MRI may be made using a sextant, hemi-prostate, or whole gland approach. The option for one or another approach should not be solely based on estimations of imaging accuracy, but on the purpose of the procedure.

Stability of serrated gold coil markers in prostate localization

We investigated the stability of serrated gold coils (Visicoil) implanted within the prostate glands of patients undergoing definitive external beam radiotherapy for prostate cancer. Radiopaque Visicoils of diameter 0.75 mm and median length 3 cm (range 2–4 cm) were implanted, one into each lobe of the prostate glands of 30 patients planned for external beam treatment. The coils were visualized on CT simulation and again after 25 fractions of treatment (5WK). Data from 30 patients were studied, of whom 19 also received androgen ablation therapy. The average change in the distance between the two coils over five weeks of treatment was 0.8 mm (± 0.6 mm), with a maximum of 2.5 mm in one patient. Average residual errors (standard deviations) for the positions of individual coil segments after five weeks of therapy were only 0.7 mm LAT, 0.6 mm AP, and 0.4 mm SI. The average change in distance between the coils over five weeks compared favorably with published data regarding marker seed stability. Overall, less than a 2 mm margin (i.e., 2 standard deviations) would adequately compensate for positioning uncertainty of the coils in more than 95% of cases.PACS number: 87.55.kh

Urethroplasty for Radiotherapy Induced Bulbomembranous Strictures: A Multi-Institutional Experience

Radiotherapy induced urethral strictures are often difficult to manage due to proximal location, compromised vascular supply and poor wound healing. To determine the success of urethroplasty for radiation induced strictures we performed a multi-institutional review of men who underwent urethroplasty for urethral obstruction. A total of 30 men (mean age 67 years) underwent urethroplasty at 3 separate institutions. Excision with primary anastomosis was used in 24 of 30 patients (80%), with 4 of 30 requiring a genital fasciocutaneous skin flap and 2 a buccal graft. Hospitalization was less than 23 hours for 70% of the patients. Recurrence was defined as cystoscopic identification of urethral narrowing to less than 16Fr in diameter. All strictures were located in the bulbomembranous region. Mean stricture length was 2.9 cm (range 1.5 to 7). External beam radiotherapy for prostate cancer was the etiology of stricture disease in 15 men (50%), with brachytherapy in 7 (24%) and a combination of the 2 modalities in 8 (26%). Successful urethral reconstruction was achieved in 22 men (73%) at a mean of 21 months. Mean time to stricture recurrence was 5.1 months (range 2 to 8). Two men required balloon dilation after stricture recurrence and none required urinary diversion. Incontinence was transient in 10% and persistent in 40%, with 13% requiring an artificial urinary sphincter. The rate of erectile dysfunction was unchanged following urethroplasty (47% preoperative, 50% postoperative). Urethroplasty for radiation induced strictures has an acceptable rate of success and can be performed without tissue transfer techniques in most cases. Almost half of men will experience some degree of incontinence as a result of surgery but erectile function appears to be preserved.

Three‐dimensional external beam radiotherapy for prostate cancer increases the risk of hip fracture

Hip fracture is associated with high morbidity and mortality. Pelvic external beam radiotherapy (EBRT) is known to increase the risk of hip fractures in women, but the effect in men is unknown. From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, 45,662 men who were aged ≥66 years and diagnosed with prostate cancer in 1992-2004 were identified. By using Kaplan-Meier methods and Cox proportional hazards models, the primary outcome of hip fracture risk was compared among men who received radical prostatectomy (RP), EBRT, EBRT plus androgen suppression therapy (AST), or AST alone. Age, osteoporosis, race, and other comorbidities were statistically controlled. A secondary outcome was distal forearm fracture as an indicator of the risk of fall-related fracture outside the radiation field. After covariates were statistically controlled, the findings showed that EBRT increased the risk of hip fractures by 76% (hazards ratio [HR], 1.76; 95% confidence interval [CI], 1.38-2.40) without increasing the risk of distal forearm fractures (HR, 0.80; 95% CI, 0.56-1.14). Combination therapy with EBRT plus AST increased the risk of hip fracture 145% relative to RP alone (HR, 2.45; 95% CI, 1.88-3.19) and by 40% relative to EBRT alone (HR, 1.40; 95% CI, 1.17-1.68). EBRT plus AST increased the risk of distal forearm fracture by 43% relative to RP alone (HR, 1.43; 95% CI, 0.97-2.10). The number needed to treat to result in 1 hip fracture during a 10-year period was 51 patients (95% CI, 31-103). In men with prostate cancer, pelvic 3-D conformal EBRT was associated with a 76% increased risk of hip fracture. This risk was slightly increased further by the addition of short-course AST to EBRT. This risk associated with EBRT must be site-specific as there was no increase in the risk of fall-related fractures in bones that were outside the radiation field.