To investigate the behaviour of the implantable cardioverter defibrillator (ICD) function during actual radiotherapy sessions.
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.
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.
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.
To investigate the effect of endorectal balloons (ERBs) on intrafraction and interfraction prostate motion during radiotherapy.
Thirty patients were treated with intensity-modulated radiotherapy, to ...a total dose of 80 Gy in 40 fractions. In 15 patients, a daily-inserted air-filled ERB was applied. Prostate motion was tracked, in real-time, using an electromagnetic tracking system. Interfraction displacements, measured before each treatment, were quantified by calculating the systematic and random deviations of the center of mass of the implanted transponders. Intrafraction motion was analyzed in timeframes of 150 s, and displacements >1 mm, >3 mm, >5 mm, and >7 mm were determined in the anteroposterior, left-right, and superoinferior direction, and for the three-dimensional (3D) vector. Manual table corrections, made during treatment sessions, were retrospectively undone.
A total of 576 and 567 tracks have been analyzed in the no-ERB group and ERB group, respectively. Interfraction variation was not significantly different between both groups. After 600 s, 95% and 98% of the treatments were completed in the respective groups. Significantly fewer table corrections were performed during treatment fractions with ERB: 88 vs. 207 (p = 0.02). Intrafraction motion was significantly reduced with ERB. During the first 150 s, only negligible deviations were observed, but after 150 s, intrafraction deviations increased with time. This resulted in cumulative percentages of 3D-vector deviations >1 mm, >3 mm, >5 mm, and >7 mm that were 57.7%, 7.0%, 0.7%, and 0.3% in the ERB-group vs. 70.2%, 18.1%, 4.6%, and 1.4% in the no-ERB group after 600 s. The largest reductions in the ERB group were observed in the AP direction. These data suggest that a 5 mm CTV-to-PTV margin is sufficient to correct for intrafraction prostate movements when using an ERB.
ERB significantly reduces intrafraction prostate motion, but not interfraction variation, and may in particular be beneficial for treatment sessions longer than 150 s.
•SBRT represents a valid treatment option for men with low/intermediate risk PCa.•Adding a focal boost to the intraprostatic tumor may improve disease control.•A focal boost might have favourable ...toxicity compared to whole-gland dose-escalation.•Currently, SBRT with a focal boost for PCa should be restricted to clinical trials.
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).
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.
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.
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,
< .001). At 5-year follow-up bDFS was 92% and 85%, respectively. We did not observe differences in prostate cancer-specific survival (
= .49) and overall survival (
= .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.
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.
To explore the influence of functional changes and dosimetric parameters on specific incontinence-related anorectal complaints after prostate external beam radiotherapy and to estimate dose-effect ...relations for the anal wall and rectal wall.
Sixty patients, irradiated for localized prostate cancer, underwent anorectal manometry and barostat measurements to evaluate anal pressures, rectal capacity, and rectal sensory functions. In addition, 30 untreated men were analyzed as a control group. In 36 irradiated patients, the anal wall and rectal wall were retrospectively delineated on planning computed tomography scans, and dosimetric parameters were retrieved from the treatment plans. Functional and dosimetric parameters were compared between patients with and without complaints, focusing on urgency, incontinence, and frequency.
After external beam radiotherapy, reduced anal pressures and tolerated rectal volumes were observed, irrespective of complaints. Patients with urgency and/or incontinence showed significantly lower anal resting pressures (mean 38 and 39 vs. 49 and 50 mm Hg) and lower tolerated rectal pressures (mean 28 and 28 vs. 33 and 34 mm Hg), compared to patients without these complaints. In patients with frequency, almost all rectal parameters were reduced. Several dosimetric parameters to the anal wall and rectal wall were predictive for urgency (e.g., anal D(mean)>38 Gy), whereas some anal wall parameters correlated to incontinence and no dose-effect relation for frequency was found.
Anorectal function deteriorates after external beam radiotherapy. Different incontinence-related complaints show specific anorectal dysfunctions, suggesting different anatomic and pathophysiologic substrates: urgency and incontinence seem to originate from both anal wall and rectal wall, whereas frequency seems associated with rectal wall dysfunction. Also, dose-effect relations differed between these complaints. This implies that anal wall and rectal wall should be considered separate organs in radiotherapy planning.
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.
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.
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.
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.
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.
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.
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.
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.
To delineate the individual pelvic floor muscles considered to be involved in anorectal toxicity and to investigate dose-effect relationships for fecal incontinence-related complaints after prostate ...radiotherapy (RT).
In 48 patients treated for localized prostate cancer, the internal anal sphincter (IAS) muscle, the external anal sphincter (EAS) muscle, the puborectalis muscle (PRM), and the levator ani muscles (LAM) in addition to the anal wall (Awall) and rectal wall (Rwall) were retrospectively delineated on planning computed tomography scans. Dose parameters were obtained and compared between patients with and without fecal urgency, incontinence, and frequency. Dose-effect curves were constructed. Finally, the effect of an endorectal balloon, which was applied in 28 patients, was investigated.
The total volume of the pelvic floor muscles together was about three times that of the Awall. The PRM was exposed to the highest RT dose, whereas the EAS received the lowest dose. Several anal and rectal dose parameters, as well as doses to all separate pelvic floor muscles, were associated with urgency, while incontinence was associated mainly with doses to the EAS and PRM. Based on the dose-effect curves, the following constraints regarding mean doses could be deduced to reduce the risk of urgency: ≤ 30 Gy to the IAS; ≤ 10 Gy to the EAS; ≤ 50 Gy to the PRM; and ≤ 40 Gy to the LAM. No dose-effect relationships for frequency were observed. Patients treated with an endorectal balloon reported significantly less urgency and incontinence, while their treatment plans showed significantly lower doses to the Awall, Rwall, and all pelvic floor muscles.
Incontinence-related complaints show specific dose-effect relationships to individual pelvic floor muscles. Dose constraints for each muscle can be identified for RT planning. When only the Awall is delineated, substantial components of the continence apparatus are excluded.
•Dose distributions for prostate SBRT were comparable between MRI-linac and conventional plans.
Recently, intermediate and high-risk prostate cancer patients have been treated in a multicenter phase ...II trial with extremely hypofractionated prostate radiotherapy (hypo-FLAME trial). The purpose of the current study was to investigate whether a 1.5 T magnetic resonance imaging guided linear accelerator (MRI-linac) could achieve complex dose distributions of a quality similar to conventional linac state-of-the-art prostate treatments.
The clinically delivered treatment plans of 20 hypo-FLAME patients (volumetric modulated arc therapy, 10 MV, 5 mm leaf width) were included. Prescribed dose to the prostate was 5 × 7 Gy, with a focal tumor boost up to 5 × 10 Gy. MRI-linac treatment plans (intensity modulated radiotherapy, 7 MV, 7 mm leaf width, fixed collimator angle and 1.5 T magnetic field) were calculated. Dose distributions were compared.
In both conventional and MRI-linac treatment plans, the V35Gy to the whole prostate was >99% in all patients. Mean dose to the gross tumor volume was 45 Gy for conventional and 44 Gy for MRI-linac plans, respectively. Organ at risk doses were met in the majority of plans, except for a rectal V35Gy constraint, which was exceeded in one patient, by 1 cc, for both modalities. The bladder V32Gy and V28Gy constraints were exceeded in two and one patient respectively, for both modalities.
Planning of stereotactic radiotherapy with focal ablative boosting in prostate cancer on a high field MRI-linac is feasible with the current MRI-linac properties, without deterioration of plan quality compared to conventional treatments.
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