Pretrial Quality Assurance for Hypofractionated Salvage Radiation Therapy After Prostatectomy in the Multi-Institutional PERYTON-trial.

Purpose: The PERYTON trial is a multicenter randomized controlled trial that will investigate whether the treatment outcome of salvage external beam radiation therapy (sEBRT) will be improved with hypofractionated radiation therapy. A pretrial quality assurance (QA) program was undertaken to ensure protocol compliance within the PERYTON trial and to assess variation in sEBRT treatment protocols between the participating centers. Methods and Materials: Completion of the QA program was mandatory for each participating center (N = 8) to start patient inclusion. The pretrial QA program included (1) a questionnaire on the center-specific sEBRT protocol, (2) a delineation exercise of the clinical target volume (CTV) and organs at risk, and (3) a treatment planning exercise. All contours were analyzed using the pairwise dice similarity coefficient (DSC) and the 50th and 95th percentile Hausdorff distance (HD50 and HD95, respectively). The submitted treatment plans were reviewed for protocol compliance. Results: The results of the questionnaire showed that high-quality, state-of-the-art radiation therapy techniques were used in the participating centers and identified variations of the sEBRT protocols used concerning the position verification and preparation techniques. The submitted CTVs showed significant variation, with a range in volume of 29 cm3 to 167 cm3, a mean pairwise DSC of 0.52, and a mean HD50 and HD95 of 2.3 mm and 24.4 mm, respectively. Only in 1 center the treatment plan required adaptation before meeting all constraints of the PERYTON protocol. Conclusions: The pretrial QA of the PERYTON trial demonstrated that high-quality, but variable, radiation techniques were used in the 8 participating centers. The treatment planning exercise confirmed that the dose constraints of the PERYTON protocol were feasible for all participating centers. The observed variation in CTV delineation led to agreement on a new (image-based) delineation guideline to be used by all participating centers within the PERYTON trial.

Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Based Clinical Target Volume Delineation Guideline for Postprostatectomy Salvage Radiation Therapy: The PERYTON Guideline.

PURPOSE: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan is the standard imaging procedure for biochemical recurrent prostate cancer postprostatectomy because of its high detection rate at low serum prostate-specific antigen levels. However, existing guidelines for clinical target volume (CTV) in prostate bed salvage external beam radiation therapy (sEBRT) are primarily based on experience-based clinical consensus and have been validated using conventional imaging modalities. Therefore, this study aimed to optimize CTV definition in sEBRT by using PSMA PET/CT-detected local recurrences (LRs). METHODS AND MATERIALS: Patients with suspected LR on PSMA PET/CT postprostatectomy were retrospectively enrolled in 9 Dutch centers. Anonymized scans were centrally reviewed by an expert nuclear medicine physician. Each boundary of the CTV guideline from the Groupe Francophone de Radiothérapie en Urologie (GFRU) was evaluated and adapted to improve the accuracy and coverage of the area at risk of LR (CTV) on PSMA PET/CT. The proposed CTV adaptation was discussed with the radiation oncologists of the participating centers, and final consensus was reached. To assess reproducibility, the participating centers were asked to delineate 3 new cases according to the new PERYTON-CTV, and the submitted contours were evaluated using the Dice similarity coefficient (DSC). RESULTS: After central review, 93 LRs were identified on 83 PSMA PET/CTs. The proposed CTV definition improved the coverage of PSMA PET/CT-detected LRs from 67% to 96% compared with the GFRU-CTV, while reducing the GFRU-CTV by 25%. The new CTV was highly reproducible, with a mean DSC of 0.82 (range, 0.81-0.83). CONCLUSIONS: This study contributes to the optimization of CTV definition in postprostatectomy sEBRT by using the pattern of LR detected on PSMA PET/CT. The PERYTON-CTV is highly reproducible across the participating centers and ensures coverage of 96% LRs while reducing the GFRU-CTV by 25%.

Evaluation of two independent dose prediction methods to personalize the automated radiotherapy planning process for prostate cancer.

BACKGROUND AND PURPOSE: Currently, automatic approaches for radiotherapy planning are widely used, however creation of high quality treatment plans is still challenging. In this study, two independent dose prediction methods were used to personalize the initial settings for the automated planning template for optimizing prostate cancer treatment plans. This study evaluated the dose metrics of these plans comparing both methods with the current clinical automated prostate cancer treatment plans. MATERIAL AND METHODS: Datasets of 20 high-risk prostate cancer treatment plans were taken from our clinical database. The prescription dose for these plans was 70 Gy given in fractions of 2.5 Gy. Plans were replanned using the current clinical automated treatment and compared with two personalized automated planning methods. The feasibility dose volume histogram (FDVH) and modified filter back projection (mFBP) methods were used to calculate independent dose predictions. Parameters for the initial objective values of the planning template were extracted from these predictions and used to personalize the optimization of the automated planning process. RESULTS: The current automated replanned clinical plans and the automated plans optimized with the personalized template methods fulfilled the clinical dose criteria. For both methods a reduction in the average mean dose of the rectal wall was found, from 22.5 to 20.1 Gy for the FDVH and from 22.5 to 19.6 Gy for the mFBP method. CONCLUSIONS: With both dose-prediction methods the initial settings of the template could be personalized. Hereby, the average dose to the rectal wall was reduced compared to the standard template method.

Urethral and bladder dose-effect relations for late genitourinary toxicity following external beam radiotherapy for prostate cancer in the FLAME trial.

PURPOSE OR OBJECTIVES: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical disease-free survival increased, without significantly increasing toxicity. The aim of the present study was to investigate the association between radiation dose to the bladder and urethra and genitourinary (GU) toxicity grade ≥2 in the entire cohort. MATERIAL AND METHODS: The dose-effect relations of the urethra and bladder dose, separately, and GU toxicity grade ≥2 (CTCAE 3.0) up to five years after treatment were assessed. A mixed model analysis for repeated measurements was used, adjusting for age, diabetes mellitus, T-stage, baseline GU toxicity grade ≥1 and institute. Additionally, the association between the dose and separate GU toxicity subdomains were investigated. RESULTS: Dose-effect relations were observed for the dose (Gy) to the bladder D2 cm3 and urethra D0.1 cm3, with adjusted odds ratios of 1.14 (95% CI 1.12-1.16, p < 0.0001) and 1.12 (95% CI 1.11-1.14, p < 0.0001), respectively. Additionally, associations between the dose to the urethra and bladder and the subdomains urinary frequency, urinary retention and urinary incontinence were observed. CONCLUSION: Further increasing the dose to the bladder and urethra will result in a significant increase in GU toxicity following EBRT. Focal boost treatment plans should incorporate a urethral dose-constraint. Further treatment optimization to increase the focal boost dose without increasing the dose to the urethra and other organs at risk should be a focus for future research, as we have shown that a focal boost is beneficial in the treatment of prostate cancer.

Anorectal dose-effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial.

BACKGROUND AND PURPOSE: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2). MATERIAL AND METHODS: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm3 and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute. RESULTS: A dose-effect relation for D2cm3 and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p < 0.0001) and 1.20 (95% CI 1.14-1.25, p < 0.0001) for GI toxicity, respectively. CONCLUSION: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose-effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.

The ROCOCO performance scoring system translates dosimetric differences into clinically relevant endpoints: Comparing IMPT to VMAT in an example pilocytic astrocytoma dataset.

BACKGROUND AND PURPOSE: Proton therapy is expected to outperform photon-based treatment regarding organs at risk (OAR) sparing but to date there is no method to practically measure clinical benefit. Here, we introduce the novel ROCOCO Performance Scoring System (RPSS) translating dose differences into clinically relevant endpoints and apply this to a treatment plan comparison of volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in 20 pilocytic astrocytoma patients. MATERIAL AND METHODS: The RPSS was developed on the basis of expert-based weighting factors and toxicity scores per OAR. The imaging datasets of 20 pilocytic astrocytoma patients having undergone radiotherapy were included in this in silico dosimetric comparison trial as proof of principle. For each of these patients, treatment plans to a total dose of 54 Gy (RBE) were generated for VMAT and IMPT and these were compared regarding radiation dose to the clinical target volume (CTV) and OARs. The RPSS was calculated for each treatment plan comparing VMAT and IMPT. RESULTS: In 40 analysed treatment plans, the average and low dose volumes to various OARs were significantly reduced when using IMPT compared to VMAT (p < 0.05). Using the RPSS, a significant difference between both treatment modalities was found, with 85% of the patients having a lower RPSS in favour of the IMPT plan. CONCLUSION: There are dosimetric differences between IMPT and VMAT in pilocytic astrocytoma patients. In absence of clinically validated NTCP models we introduce the RPSS model in order to objectively compare treatment modalities by translating dosimetric differences in potential clinical differences.

MR-Guided Adaptive Radiotherapy for Bladder Cancer.

Radiotherapy has an important role in the curative and palliative treatment settings for bladder cancer. As a target for radiotherapy the bladder presents a number of technical challenges. These include poor tumor visualization and the variability in bladder size and position both between and during treatment delivery. Evidence favors the use of magnetic resonance imaging (MRI) as an important means of tumor visualization and local staging. The availability of hybrid systems incorporating both MRI scanning capabilities with the linear accelerator (MR-Linac) offers opportunity for in-room and real-time MRI scanning with ability of plan adaption at each fraction while the patient is on the treatment couch. This has a number of potential advantages for bladder cancer patients. In this article, we examine the technical challenges of bladder radiotherapy and explore how magnetic resonance (MR) guided radiotherapy (MRgRT) could be leveraged with the aim of improving bladder cancer patient outcomes. However, before routine clinical implementation robust evidence base to establish whether MRgRT translates into improved patient outcomes should be ascertained.

Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial.

PURPOSE: This study investigates whether focal boosting of the macroscopic visible tumor with external beam radiotherapy increases biochemical disease-free survival (bDFS) in patients with localized prostate cancer. PATIENTS AND METHODS: In the phase III, multicenter, randomized controlled Focal Lesion Ablative Microboost in Prostate Cancer trial, 571 patients with intermediate- and high-risk prostate cancer were enrolled between 2009 and 2015. Patients assigned to standard treatment received 77 Gy (fractions of 2.2 Gy) to the entire prostate. The focal boost arm received an additional simultaneous integrated focal boost up to 95 Gy (fractions up to 2.7 Gy) to the intraprostatic lesion visible on multiparametric magnetic resonance imaging. Organ at risk constraints were prioritized over the focal boost dose. The primary end point was 5-year bDFS. Secondary end points were disease-free survival (DFS), distant metastases-free survival, prostate cancer-specific survival, overall survival, toxicity, and health-related quality of life. RESULTS: Median follow-up was 72 months. Biochemical DFS was significantly higher in the focal boost compared with the standard arm (hazard ratio 0.45, 95% CI, 0.28 to 0.71, P < .001). At 5-year follow-up bDFS was 92% and 85%, respectively. We did not observe differences in prostate cancer-specific survival (P = .49) and overall survival (P = .50). The cumulative incidence of late genitourinary and GI toxicity grade ≥ 2 was 23% and 12% in the standard arm versus 28% and 13% in the focal boost arm, respectively. Both for late toxicity as health-related quality of life, differences were small and not statistically significant. CONCLUSION: The addition of a focal boost to the intraprostatic lesion improved bDFS for patients with localized intermediate- and high-risk prostate cancer without impacting toxicity and quality of life. The Focal Lesion Ablative Microboost in Prostate Cancer study shows that a high focal boost strategy to improve tumor control while respecting organ at risk dose constraints is effective and safe.

Knowledge-Based Assessment of Focal Dose Escalation Treatment Plans in Prostate Cancer.

PURPOSE: In a randomized focal dose escalation radiation therapy trial for prostate cancer (FLAME), up to 95 Gy was prescribed to the tumor in the dose-escalated arm, with 77 Gy to the entire prostate in both arms. As dose constraints to organs at risk had priority over dose escalation and suboptimal planning could occur, we investigated how well the dose to the tumor was boosted. We developed an anatomy-based prediction model to identify plans with suboptimal tumor dose and performed replanning to validate our model. METHODS AND MATERIALS: We derived dose-volume parameters from planned dose distributions of 539 FLAME trial patients in 4 institutions and compared them between both arms. In the dose-escalated arm, we determined overlap volume histograms and derived features representing patient anatomy. We predicted tumor D98% with a linear regression on anatomic features and performed replanning on 21 plans. RESULTS: In the dose-escalated arm, the median tumor D50% and D98% were 93.0 and 84.7 Gy, and 99% of the tumors had a dose escalation greater than 82.4 Gy (107% of 77 Gy). In both arms organs at risk constraints were met. Five out of 73 anatomic features were found to be predictive for tumor D98%. Median predicted tumor D98% was 4.4 Gy higher than planned D98%. Upon replanning, median tumor D98% increased by 3.0 Gy. A strong correlation between predicted increase in D98% and realized increase upon replanning was found (ρ = 0.86). CONCLUSIONS: Focal dose escalation in prostate cancer was feasible with a dose escalation to 99% of the tumors. Replanning resulted in an increased tumor dose that correlated well with the prediction model. The model was able to identify tumors on which a higher boost dose could be planned. The model has potential as a quality assessment tool in focal dose escalated treatment plans.

Quantitative MRI Changes During Weekly Ultra-Hypofractionated Prostate Cancer Radiotherapy With Integrated Boost.

Purpose: Quantitative MRI reflects tissue characteristics. As possible changes during radiotherapy may lead to treatment adaptation based on response, we here assessed if such changes during treatment can be detected. Methods and Materials: In the hypoFLAME trial patients received ultra-hypofractionated prostate radiotherapy with an integrated boost to the tumor in 5 weekly fractions. We analyzed T2 and ADC maps of 47 patients that were acquired in MRI exams prior to and during radiotherapy, and performed rigid registrations based on the prostate contour on anatomical T2-weighted images. We analyzed median T2 and ADC values in three regions of interest (ROIs): the central gland (CG), peripheral zone (PZ), and tumor. We analyzed T2 and ADC changes during treatment and compared patients with and without hormonal therapy. We tested changes during treatment for statistical significance with Wilcoxon signed rank tests. Using confidence intervals as recommended from test-retest measurements, we identified persistent T2 and ADC changes during treatment. Results: In the CG, median T2 and ADC values significantly decreased 12 and 8%, respectively, in patients that received hormonal therapy, while in the PZ these values decreased 17 and 18%. In the tumor no statistically significant change was observed. In patients that did not receive hormonal therapy, median ADC values in the tumor increased with 20%, while in the CG and PZ no changes were observed. Persistent T2 changes in the tumor were found in 2 out of 24 patients, while none of the 47 patients had persistent ADC changes. Conclusions: Weekly quantitative MRI could identify statistically significant ADC changes in the tumor in patients without hormonal therapy. On a patient level few persistent T2 changes in the tumor were observed. Long-term follow-up is required to relate the persistent T2 and ADC changes to outcome and evaluate the applicability of quantitative MRI for response based treatment adaptation.

Stereotactic body radiation therapy with optional focal lesion ablative microboost in prostate cancer: Topical review and multicenter consensus.

Stereotactic body radiotherapy (SBRT) for prostate cancer (PCa) is gaining interest by the recent publication of the first phase III trials on prostate SBRT and the promising results of many other phase II trials. Before long term results became available, the major concern for implementing SBRT in PCa in daily clinical practice was the potential risk of late genitourinary (GU) and gastrointestinal (GI) toxicity. A number of recently published trials, including late outcome and toxicity data, contributed to the growing evidence for implementation of SBRT for PCa in daily clinical practice. However, there exists substantial variability in delivering SBRT for PCa. The aim of this topical review is to present a number of prospective trials and retrospective analyses of SBRT in the treatment of PCa. We focus on the treatment strategies and techniques used in these trials. In addition, recent literature on a simultaneous integrated boost to the tumor lesion, which could create an additional value in the SBRT treatment of PCa, was described. Furthermore, we discuss the multicenter consensus of the FLAME consortium on SBRT for PCa with a focal boost to the macroscopic intraprostatic tumor nodule(s).

Intensity-modulated proton therapy decreases dose to organs at risk in low-grade glioma patients: results of a multicentric in silico ROCOCO trial.

BACKGROUND AND PURPOSE: Patients with low-grade glioma (LGG) have a prolonged survival expectancy due to better discriminative tumor classification and multimodal treatment. Consequently, long-term treatment toxicity gains importance. Contemporary radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO) and intensity-modulated proton therapy (IMPT) enable high-dose irradiation of the target but they differ regarding delivered dose to organs at risk (OARs). The aim of this comparative in silico study was to determine these dosimetric differences in delivered doses. MATERIAL AND METHODS: Imaging datasets of 25 LGG patients having undergone postoperative radiotherapy were included. For each of these patients, in silico treatment plans to a total dose of 50.4 Gy to the target volume were generated for the four treatment modalities investigated (i.e., IMRT, VMAT, TOMO, IMPT). Resulting treatment plans were analyzed regarding dose to target and surrounding OARs comparing IMRT, TOMO and IMPT to VMAT. RESULTS: In total, 100 treatment plans (four per patient) were analyzed. Compared to VMAT, the IMPT mean dose (Dmean) for nine out of 10 (90%) OARs was statistically significantly (p < .02) reduced, for TOMO this was true in 3/10 (30%) patients and for 1/10 (10%) patients for IMRT. IMPT was the prime modality reducing dose to the OARs followed by TOMO. DISCUSSION: The low dose volume to the majority of OARs was significantly reduced when using IMPT compared to VMAT. Whether this will lead to a significant reduction in neurocognitive decline and improved quality of life is to be determined in carefully designed future clinical trials.

Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial.

PURPOSE: To compare toxicity rates in patients with localized prostate cancer treated with standard fractionated external beam radiotherapy (EBRT) with or without an additional integrated boost to the macroscopically visible tumour. MATERIAL AND METHODS: FLAME is a phase 3 multicentre RCT (NCT01168479) of patients with pathologically confirmed localized intermediate or high-risk prostate cancer. The standard treatment arm (n = 287) received a dose to the entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n = 284) received 77 Gy in 35 fractions to the entire prostate, with an integrated boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within the prostate. Treatment related toxicity was measured using the CTCAE version 3.0. Grade 2 or worse GU or GI events up to two years were compared between groups by presenting proportions and by Generalized Estimating Equations (GEE) analyses for repeated measures. RESULTS: Ninety percent of the 571 men randomly assigned between September 2009 and January 2015 had high-risk disease (Ash 2000), of whom nearly 66% were prescribed hormonal therapy up to three years. Median follow-up was 55 months at the time of this analysis. Toxicity prevalence rates for both GI and GU increased until the end of treatment and regressed thereafter, with no obvious differences across treatment groups. Late cumulative GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group, respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses showed that both GU toxicity and GI toxicity (≥grade 2) up to two years after treatment were similar between arms (OR 1.02 95%CI 0.78-1.33p = 0.81 and (OR 1.19 95%CI 0.82-1.73p = 0.38), respectively. CONCLUSIONS: In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible.

Local Protocol Variations for Image Guided Radiation Therapy in the Multicenter Dutch Hypofractionation (HYPRO) Trial: Impact of Rectal Balloon and MRI Delineation on Anorectal Dose and Gastrointestinal Toxicity Levels.

PURPOSE: The phase 3 HYpofractionated irradiation for PROstate cancer (HYPRO) trial randomized patients with intermediate- to high-risk localized prostate cancer to conventionally fractionated (78 Gy in 39 fractions) or hypofractionated (64.6 Gy in 19 fractions) radiation therapy. Differences in techniques and treatment protocols were present between participating centers. This study aimed to compare dose parameters and patient-reported gastrointestinal symptoms between these centers. METHODS AND MATERIALS: From the trial population, we selected patients (N=572) from 4 treatment centers who received image guided (IG) intensity modulated radiation therapy (IMRT). Center A (n=242) applied planning target volume (PTV) margins of 5 to 6 mm and was considered the reference center. In center B (n=170, 7-mm margins), magnetic resonance imaging (MRI) was integrated in treatment planning. An endorectal balloon (ERB) was applied in center C (n=85, 7-mm margins). Center D (n=75) applied the largest PTV margins of 8 mm. The study protocol provided identical anorectal dose constraints, and local protocols were applied for further treatment optimization. Anorectal dose-surface histograms were compared by applying t tests. Rectal complaints during follow-up (6 months to 4 years) were compared in a generalized linear model, adjusting for age, follow-up, treatment arm, and hormone therapy. RESULTS: Favorable anorectal dose distributions were found for center B (MRI delineation) and center C (ERB application) as compared with centers A and D. These were associated with significantly lower incidences of patient-reported complaints of rectal incontinence, use of incontinence pads, and rectal discomfort in these centers. Furthermore, lower incidences of increased stool frequency (≥4 per day) and mucous loss were observed for center C. CONCLUSIONS: Despite comparable IG-IMRT techniques and predefined dose constraints, pronounced differences in dose distributions and toxicity rates were observed. MRI delineation and ERB application were associated with favorable rectal dose parameters and toxicity profiles, whereas a 2- to 3-mm difference in PTV margins did not translate into observed differences. We conclude that choices for treatment optimization of IG-IMRT are important and clinically relevant for patients since these affect symptoms experienced in daily life.

Adult prostatic sarcoma: A contemporary multicenter Rare Cancer Network study.

INTRODUCTION: Adult prostatic sarcoma (PS) is a rare disease. While surgery is considered the standard approach, the role of other therapies is not completely established. We report results of the largest multicentric contemporary cohort of PS patients. MATERIALS AND METHODS: This study included 61 adult PS patients treated in 16 American and European Institutions. Median age was 64.4 years (range: 22-87). Curative surgery was delivered in 48 patients (prostatectomy = 26, cystoprostatectomy = 22), usually with lymphadenectomy (n = 40). Curative radiotherapy (RT) was delivered in 32 patients, as radical (n = 5), neoadjuvant (n = 10), or postoperative treatment (n = 17). Eighteen patients received chemotherapy. None of the patients received hormonal therapy. RESULTS: Median follow-up was 72 months (95%CI: 55-not reached). Five-year local control (LC), overall survival (OS), cancer-specific survival, disease-free survival, and metastases-free rates were 47%, 53%, 56%, 35%, and 35%, respectively. Notably, curative RT (neoadjuvant, adjuvant, or definitive) was associated with improved 5-year LC (55% vs. 31%, P = 0.02) and OS (59% vs. 46%, P = 0.1). Surgically treated patients presenting with a cT3-4 tumor (n = 31), who received RT (n = 24), had a significantly improved 5-year LC (68% vs, 33%, P = 0.004) and OS (65% vs. 21%, P < 0.001) rates compared to patients not receiving RT. cT4 patients demonstrated a significantly lower 5-year OS (43% vs. 61%, P = 0.006) and LC (29% vs. 69%, P < 0.001) rates. Histologic subtype was not associated with LC and OS, but patients with prostatic stromal sarcoma, rhabdomyosarcoma, or sarcomatoid carcinoma had worse 5-year LC compared to other types (47% vs. 55%) and OS (49% vs. 58%). CONCLUSION: Adult PS has a poor prognosis. Locally advanced tumors have poor LC and OS rates. Curative RT should be considered part of the multidisciplinary approach to PS.

Lymphotropic nanoparticle-enhanced MRI in prostate cancer: value and therapeutic potential.

Nodal staging in prostate cancer is suboptimal both with respect to current imaging modalities and pelvic lymph node dissection, and thus other techniques are being explored. Lymphotropic nanoparticle-enhanced MRI, also called magnetic resonance lymphography (MRL), is a technique that has shown high sensitivity (65-92 %) and excellent specificity (93-98 %) in detecting prostate cancer lymph node metastases. This technique aids in the detection of metastases in non-enlarged small nodes. MRL has been useful in determining the location and pathways of spread in nodal chains. Knowledge of the location of lymph node involvement is important for decisions regarding appropriate therapeutic options, such as image-guided therapy.. A geographic miss in radiotherapy can be avoided with the use of MRL-guided focal therapy. This paper provides an overview of current literature, lessons learned, and new therapeutic options with nanoparticle-enhanced MRI.

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.

High incidence of implantable cardioverter defibrillator malfunctions during radiation therapy: neutrons as a probable cause of soft errors.

AIMS: To investigate the behaviour of the implantable cardioverter defibrillator (ICD) function during actual radiotherapy sessions. METHODS AND RESULTS: Fifteen patients with an ICD underwent 17 radiation treatments for cancer [cumulative dose to the tumour was between 16 Gray (Gy) and 70 Gy; photon beams with maximum energies between 6 megaelectronvolt (MeV) and 18 MeV were employed]. During every session, the ICD was programmed to a monitoring mode to prevent inappropriate therapy delivery. Afterwards, the ICDs were interrogated to ensure proper function. Calculated radiation dose at the ICD site was <1 Gy in all patients. In 5 out of 17 radiation treatments (29%) the ICDs showed 6 malfunctions (35%). We noticed four disturbances in the memory data or device resets during radiation treatment and one case of inappropriate ventricular fibrillation detection due to external noise. In one case a late device data error was observed. All malfunctions occurred at 10 and 18 MeV beam energies. CONCLUSION: Despite the fact that all recommended precautions were taken to minimize the damage to the ICDs during radiotherapy and the calculated dose to the ICDs was <1 Gy, in 29% of the treatments a malfunction occurred. We observed a possible correlation between the beam energy and the malfunctions. This correlation may be due to an interaction between neutrons produced in the head of the linear accelerator at beam energies ≥10 MeV, and boron-10 which is present in the integrated circuit.