Intraprostatic Fiducial Markers Research Articles

Long-Term Outcomes of a Prospective Study on Highly Hypofractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer for 3 Weeks

Reports of radiation therapy for prostate cancer using dose fractions between moderate hypofractionation and ultrahypofractionation are limited. This pilot study involved the application of highly hypofractionated intensity modulated radiation therapy (IMRT) in 15 fractions for 3 weeks and the number of fractions was intermediate between the 2 previously mentioned dose fractions. The long-term outcomes are reported. From April 2014 to September 2015, patients with low- to intermediate-risk prostate cancer received 54 Gy in 15 fractions (3.6 Gy per fraction) for 3 weeks using IMRT without intraprostatic fiducial markers or a rectal hydrogel spacer. Neoadjuvant hormone therapy (HT) was administered for 4 to 8 months. Adjuvant HT was not administered to any patients. Rates of biochemical relapse-free survival, clinical relapse-free survival, overall survival, and the cumulative incidence of late grade ≥2 toxicities were analyzed. Twenty-five patients were enrolled in this prospective study; 24 of them were treated with highly hypofractionated IMRT (17% had low-risk and 83% had intermediate-risk disease). The median neoadjuvant HT duration was 5.3 months. The median follow-up period was 77 months (range, 57-87 months). Biochemical relapse-free survival, clinical relapse-free survival, and overall survival rates were 91.7%, 95.8%, and 95.8% at 5 years, and 87.5%, 86.3%, and 95.8% at 7 years, respectively. Neither grade ≥2 late gastrointestinal toxicity nor grade ≥3 late genitourinary toxicity was observed. The cumulative incidence rates of grade 2 genitourinary toxicity were 8.5% and 18.3% at 5 and 7 years, respectively. Highly hypofractionated IMRT delivering 54 Gy in 15 fractions for 3 weeks for prostate cancer without intraprostatic fiducial markers facilitated favorable oncological outcomes without severe complications. This treatment approach may be a possible alternative to moderate hypofractionation, but further validation is needed.

Intra-prostatic gold fiducial marker insertion for image-guided radiotherapy (IGRT): five-year experience on 795 patients

IntroductionProstate cancer is the second most commonly diagnosed cancer in males. The use of intra-prostatic fiducial markers (FM) for image-guided radiotherapy (IGRT) has become widespread due to their accuracy, relatively safe use, low cost, and reproducibility. FM provides a tool to monitor prostate position and volume changes. Many studies reported low to moderate rates of complications following FM implantation. In the current study, we present our five years’ experience regarding the insertion technique, technical success, and rates of complication and migration of intraprostatic insertion of FM gold marker.MethodsFrom January 2018 to January 2023, 795 patients with prostate cancer candidate for IGRT (with or without a history of radical prostatectomy) enrolled in this study. We used three fiducial markers (3*0.6 mm) inserted through an 18-gauge Chiba needle under transrectal ultrasonography (TRUS) guidance. The patients were observed for complications up to seven days after the procedure. Besides, the rate of marker migration was recorded.ResultsAll procedures were completed successfully, and all patients tolerated the procedure well with minimal discomfort. The rate of sepsis after the procedure was 1%, and transient urinary obstruction was 1.6%. Only two patients experienced marker migration shortly after insertion, and no fiducial migration was reported throughout radiotherapy. No other major complication was recorded.DiscussionTRUS-guided intraprostatic FM implantation is technically feasible, safe, and well-tolerated in most patients. The FM migration can seldom occur, with negligible effects. This study can provide convincing evidence that TRUS-guided intra-prostatic FM insertion is an appropriate choice for IGRT.

Long-term outcomes of a pilot study on highly hypofractionated intensity-modulated radiation therapy over three weeks for localized prostate cancer.

259 Background: A number of reports have been published on both moderately hypofractionated intensity-modulated radiation therapy (IMRT) for localized prostate cancers using 2.4 – 3.4 Gy per fraction over 4 – 6 weeks, and ultrahypofractionation over 1 – 2 weeks using 6 Gy or more per fraction. However, long-term outcomes have sparsely been reported using doses between these two fractionations (3.4 – 6.0 Gy per fraction) over 2 – 3 weeks (high hypofractionation). Therefore, we performed a pilot study of highly hypofractionated IMRT in 15 fractions using 3.6 Gy per fraction over 3 weeks for localized prostate cancer. We now report the long-term outcomes of the study. Methods: Twenty-five patients with low- to intermediate-risk prostate cancer were enrolled in this prospective study from April 2014 to September 2015. Fifty-four Gy in 15 fractions (3.6 Gy per fraction) was delivered over three weeks using IMRT with CBCT-based image guidance without intraprostatic fiducial markers. Based on an estimated alpha/beta ratio for prostate cancer of 1.5 Gy, the EQD2 was 78.7 Gy for the present dose fractionation. Neoadjuvant hormonal therapy (HT) was administered to intermediate-risk patients for 4 – 8 months, but was not mandatory in patients with low-risk disease. Adjuvant HT was not provided for any patient. Biochemical relapse-free survival (BRFS), clinical relapse-free survival (CRFS), overall survival (OS), and the cumulative incidence rate of late toxicities were analyzed using the Kaplan Meier method. Results: Twenty-four patients were treated with highly hypofractionated IMRT, except one case switched to conventionally fractionated IMRT because we could not meet the dose constraint of the small bowel in treatment planning. Among the 24 patients, 17 % had low-risk, and 83% had intermediate-risk disease. Neoadjuvant HT was administered to 23 patients, and the median duration of HT was 5.3 months. The median follow-up period was 77 months (range, 57–87 months). BRFS, CRFS, and OS were 91.7%, 95.8% and 95.8% at 5 years, and 87.5%, 86.3% and 95.8% at 7 years, respectively. No patient died of prostate cancer, but one patient died due to the other cancer. Neither grade ≥2 late gastrointestinal toxicity nor ≥3 late genitourinary toxicity was observed. Grade 2 late genitourinary toxicity did not occur during the first 4 years, but was developed in 5 patients after more than 4-year follow-up. The cumulative incidence rate was 12.9% and 22.8% at 5 and 7 years, respectively. Conclusions: Highly hypofractionated IMRT delivering 54 Gy in 15 fractions over 3 weeks for prostate cancer without intraprostatic fiducial markers demonstrates favorable oncological outcomes with no severe complications. This treatment approach could be a possible alternative of moderate hypofractionation, although further studies will be mandatory.

VMAT Focal Boost to MRI-Defined Intraprostatic Lesion in Localized Prostate Cancer: Results of a Phase II Trial

Advances in the identification of the dominant intraprostatic lesion (DIL) with multi-parametric magnetic resonance imaging (mpMRI) have enabled selective focal radiation dose intensification. The aim of this prospective phase II trial was to determine the PSA and mpMRI response, toxicity and quality of life (QOL) in men with localized prostate cancer (PCa) treated with image-guided focal boost to the DIL. We report early results on local and biological control and toxicity. The hypothesis is that differential boosting with focal dose escalation to an mpMRI defined DIL is associated with a higher clinical control without a significant increase in toxicity.From February 2017 to January 2020, 30 patients with intermediate and high risk PCa with a visible DIL identified on mpMRI were included in a prospective phase II trial. Matching point registration of planning TC and T2-weighted, diffusion-weighted and a gradient recalled echo (GRE) MRI images made in treatment position was used for prostate and DIL delineation. Treatment consisted on 35 daily fractions of 2.17 Gy with a concomitant focal boost to the intraprostatic nodule of 2.43 Gy using VMAT (volumetric modulated arc therapy) and IGRT (image guided radiation therapy) with daily CBCT (cone beam CT) and intraprostatic fiducial markers. Androgen derivation therapy (ADT) was allowed for unfavorable intermediate and high-risk tumors. Biochemical failure was analyzed using nadir+2 ng/ml criteria and local control using mpMRI evaluation at 6 and 9 months following RT. Acute and late toxicity were defined according to CTCAE v4.0 and RTOG/EORTC scales and QoL was assessed using IPSS, EPIC short-form and UCLA-PCI questionnaires.Dose intensification was feasible in the 30 patients. The median prostate dose was 77.6 Gy (IQR 77.3-78.1) and the median DIL RT dose was 85.2 Gy (IQR 85.0-85.4). With a median follow up of 33 moths (IQR 24.5 - 41.5), all 30 patients remain free of biochemical relapse. A mpMRI complete response was observed in 23 patients during the first post-treatment evaluation performed at 6 months. The remaining 7 patients achieved a complete response in the second mpMRI made at 9 months. Six out of 30 (20%) patients presented acute grade 2 urinary toxicity with no grade 3 acute complications. Acute rectal toxicity was only found in 2 (6.6%) patients (both grade 1). Only late grade 1 urinary (3 cases) and rectal (3 cases) complications were observed, with no grade 2 or more late toxicity.Although preliminary, the present results show that focal dose escalation RT using mpMRI guided VMAT technique is associated with an encouraging local and biochemical control and a safe toxicity profile. This trial was registered on ClinicalTrials.gov, NCT03030625.

Feasibility of Same-Day Prostate Fiducial Markers, Perirectal Hydrogel Spacer Placement, and Computed Tomography and Magnetic Resonance Imaging Simulation for External Beam Radiation Therapy for Low-Risk and Intermediate-Risk Prostate Cancer

PurposeThe use of prostate fiducial markers and perirectal hydrogel spacers can reduce the acute and late toxic effects associated with prostate radiation therapy. These procedures are usually performed days to weeks before simulation during a separate clinic visit to ensure resolution of procedure-related inflammation. The purpose of this study was to assess whether same-day intraprostatic fiducial marker placement, perirectal hydrogel injection, and computed tomography (CT) and magnetic resonance imaging (MRI) simulation were feasible without adversely affecting hydrogel volume, perirectal spacing, or rectal dose. If feasible, performing these procedures on the same day as simulation would expedite the start of radiation therapy, improve patient convenience, and reduce costs. Methods and MaterialsTwenty-one patients with clinically localized prostate cancer who were enrolled on a prospective clinical trial (NCT01617161) underwent same-day marker placement, hydrogel injection, and CT and MRI simulation, then underwent T2 MRI verification scans 3 to 4 weeks later. The MRI scans were fused to the CT planning scans by clinical target volumes (CTVs) to generate comparison treatment plans (70 Gy in 28 fractions). Hydrogel volume and symmetry, perirectal spacing, CTV dose, and organ-at-risk dose were evaluated. ResultsVerification scans occurred a mean of 24.9 ± 4.6 days after simulation and 9.3 ± 4.9 days after treatment start. Prostate volume did not change between scans (median, 67.3 ± 22.1 cm3 vs 64.1 ± 21.8 cm3; P = .64). The median hydrogel change between simulation and verification was −1.8% ± 4.5% (P = .27). No significant differences in perirectal spacing (midgland: 1.33 ± 0.45 cm vs 1.3 ± 0.7 cm; 1 cm superior: 1.25 ± 0.95 cm vs 1.43 ± 0.91 cm; 1 cm inferior: 1.16 ± 0.28 cm vs 1.41 ± 0.49 cm) were identified. No significant differences in rectal V66 (median 2.3 ± 2.18% vs 2.3 ± 2.28%; P = .99), V35 (median 14.79 ± 7.61 vs 14.67 ± 8.4; P = .73), or D1cc (65.7 ± 9.2 Gy vs 68.2 ± 9.0 Gy; P = .80) were found. All plans met CTV and organ-at-risk constraints. ConclusionSame-day placement of intraprostatic fiducial markers, perirectal hydrogel, and simulation scans was feasible and did not significantly affect hydrogel volume, position, CTV coverage, or rectal dose.

Accuracy of an MR-only workflow for prostate radiotherapy using semi-automatically burned-in fiducial markers

BackgroundThe benefit of MR-only workflow compared to current CT-based workflow for prostate radiotherapy is reduction of systematic errors in the radiotherapy chain by 2–3 mm. Nowadays, MRI is used for target delineation while CT is needed for position verification. In MR-only workflows, MRI based synthetic CT (sCT) replaces CT. Intraprostatic fiducial markers (FMs) are used as a surrogate for the position of the prostate improving targeting. However, FMs are not visible on sCT. Therefore, a semi-automatic method for burning-in FMs on sCT was developed. Accuracy of MR-only workflow using semi-automatically burned-in FMs was assessed and compared to CT/MR workflow.MethodsThirty-one prostate cancer patients receiving radiotherapy, underwent an additional MR sequence (mDIXON) to create an sCT for MR-only workflow simulation. Three sources of accuracy in the CT/MR- and MR-only workflow were investigated. To compare image registrations for target delineation, the inter-observer error (IOE) of FM-based CT-to-MR image registrations and soft-tissue-based MR-to-MR image registrations were determined on twenty patients. Secondly, the inter-observer variation of the resulting FM positions was determined on twenty patients. Thirdly, on 26 patients CBCTs were retrospectively registered on sCT with burned-in FMs and compared to CT-CBCT registrations.ResultsImage registration for target delineation shows a three times smaller IOE for MR-only workflow compared to CT/MR workflow. All observers agreed in correctly identifying all FMs for 18 out of 20 patients (90%). The IOE in CC direction of the center of mass (COM) position of the markers was within the CT slice thickness (2.5 mm), the IOE in AP and RL direction were below 1.0 mm and 1.5 mm, respectively. Registrations for IGRT position verification in MR-only workflow compared to CT/MR workflow were equivalent in RL-, CC- and AP-direction, except for a significant difference for random error in rotation.ConclusionsMR-only workflow using sCT with burned-in FMs is an improvement compared to the current CT/MR workflow, with a three times smaller inter observer error in CT-MR registration and comparable CBCT registration results between CT and sCT reference scans.Trial registry Medical Research Involving Human Subjects Act (WMO) does apply to this study and was approved by the Medical Ethics review Committee of the Academic Medical Center. Registration number: NL65414.018.18. Date of registration: 21–08-2018.

Are simple verbal instructions sufficient to ensure that bladder volume does not deteriorate prostate position reproducibility during spot scanning proton therapy?

Objectives:The purpose of this study is to investigate whether verbal instructions are sufficient for bladder volume (BV) control not to deteriorate prostate position reproducibility in image-guided spot scanning proton therapy (SSPT) for localized prostate cancer.Methods:A total of 268 treatment sessions in 12 consecutive prostate cancer patients who were treated with image-guided SSPT with fiducial markers were retrospectively analyzed. In addition to strict rectal volume control procedures, simple verbal instructions to void urine one hour before the treatment were used here. The BV was measured by a Bladder Scan just before the treatment, and the prostate motion was measured by intraprostatic fiducial markers and two sets of X-ray fluoroscopy images. The correlation between the BV change and prostate motion was assessed by linear mixed-effects models and systematic and random errors according to the reproducibility of the BV.Results:The mean absolute BV change during treatment was from −98.7 to 86.3 ml (median 7.1 ml). The mean absolute prostate motion of the patients in the left-right direction was −1.46 to 1.85 mm; in the cranial-caudal direction it was −6.10 to 3.65 mm, and in the anteroposterior direction −1.90 to 5.23 mm. There was no significant relationship between the BV change and prostate motion during SSPT. The early and late genitourinary and gastrointestinal toxicity was minimal with a minimum follow up of 4.57 years.Conclusions:Simple verbal instructions about urination was suggested to be sufficient to control the BV not to impact on the prostate motion and clinical outcomes in image-guided SSPT. Careful attention to BV change is still needed when the seminal vesicle is to be treated.Advances in knowledge:Our data demonstrated that there was no apparent relationship between BV changes and prostate position reproducibility and simple verbal instruction about urination could be sufficient for image-guided SSPT.

Ultrasound-guided transrectal implantation of fiducial markers for image-guided radiotherapy of prostate cancer without local anesthesia: Patient-reported gastrointestinal-genitourinary system complications and pain.

The present study evaluates procedure-associated pain and side effects in the gastrointestinal-genitourinary system in patients with early-stage prostate cancer who were treated with image-guided radiotherapy (IGRT), accompanied by an ultrasound-guided transrectal implantation of fiducial markers, without local anesthesia. A total of 46 patients who referred to our clinics between 2012 and 2017 with a diagnosis of early-stage prostate cancer were included in the study. Before undergoing radiotherapy, all patients were implanted with three intraprostatic fiducial markers through the ultrasound-guided transrectal approach without local anesthesia. The patients underwent radiotherapy after the clinical target volumes were established, in accordance with the respective risk groups, and localization of the markers was confirmed before each therapy session. The levels of procedure-associated pain and side effects were graded immediately after the procedure through the use of a patient-based scoring system. The faces pain scale - revised version was used for the measurement of the severity of procedure-associated pain. Of the total study sample, the facial expressions of 38 patients (35%) corresponded to level 0 in the study, seven (15%) to level 2, and a single patient (2%) to level 4. None of the facial expressions of the patients corresponded to levels 6, 8, or 10. The evaluation of procedure-related genitourinary and gastrointestinal system side effects indicated that nine patients (20%) experienced side effects, while no side effects were reported in 37 patients (80%). The reported side effects included rectal bleeding in two patients (4%), dysuria in three patients (6%), hematuria in five patients (11%), and frequent urination in five patients (11%). None of the patients experienced fever or hematospermia. All side effects were reported by the respondents as "a little," while only one patient answered positively to the question on the frequency of urination. Among the patients who answered "yes" and "a little" to the questions evaluating genitourinary and gastrointestinal system side effects, the severity of these events was reported as Grade 1, corresponding to mild adverse, in only 9 (20%) patients. None of the patients experienced a Grade 2 or higher severe adverse event. In the comparison of the severity of pain of the patients during the fiducial marker procedure without local anesthesia with the severity of pain during the biopsy, 24 patients (80%) reported "lower" levels of pain, while five patients (20%) reported "equal" levels of pain. None of the patients stated that they had experienced "more" pain. IGRT accompanied by an ultrasound-guided implantation of fiducial markers without local anesthesia can be considered a safe method, given the associated acceptable levels of pain, low side effect profiles, and high prostate-specific antigen control rates.

Deformable MR-CBCT prostate registration using biomechanically constrained deep learning networks.

Radiotherapeutic dose escalation to dominant intraprostatic lesions (DIL) in prostate cancer could potentially improve tumor control. The purpose of this study was to develop a method to accurately register multiparametric magnetic resonance imaging (MRI) with CBCT images for improved DIL delineation, treatment planning, and dose monitoring in prostate radiotherapy. We proposed a novel registration framework which considers biomechanical constraint when deforming the MR to CBCT. The registration framework consists of two segmentation convolutional neural networks (CNN) for MR and CBCT prostate segmentation, and a three-dimensional (3D) point cloud (PC) matching network. Image intensity-based rigid registration was first performed to initialize the alignment between MR and CBCT prostate. The aligned prostates were then meshed into tetrahedron elements to generate volumetric PC representation of the prostate shapes. The 3D PC matching network was developed to predict a PC motion vector field which can deform the MRI prostate PC to match the CBCT prostate PC. To regularize the network's motion prediction with biomechanical constraints, finite element (FE) modeling-generated motion fields were used to train the network. MRI and CBCT images of 50 patients with intraprostatic fiducial markers were used in this study. Registration results were evaluated using three metrics including dice similarity coefficient (DSC), mean surface distance (MSD), and target registration error (TRE). In addition to spatial registration accuracy, Jacobian determinant and strain tensors were calculated to assess the physical fidelity of the deformation field. The mean and standard deviation of our method were 0.93±0.01, 1.66±0.10mm, and 2.68±1.91mm for DSC, MSD, and TRE, respectively. The mean TRE of the proposed method was reduced by 29.1%, 14.3%, and 11.6% as compared to image intensity-based rigid registration, coherent point drifting (CPD) nonrigid surface registration, and modality-independent neighborhood descriptor (MIND) registration, respectively. We developed a new framework to accurately register the prostate on MRI to CBCT images for external beam radiotherapy. The proposed method could be used to aid DIL delineation on CBCT, treatment planning, dose escalation to DIL, and dose monitoring.

Interfraction prostate displacement during image-guided radiotherapy using intraprostatic fiducial markers and a cone-beam computed tomography system: A volumetric off-line analysis in relation to the variations of rectal and bladder volumes.

Prostate motion during the radiotherapy course is an important issue. This study investigated the inter-fraction prostate motion in controlled rectal filling condition. 10 prostate cancer patients underwent image-guided radiotherapy (IGRT) using a cone-beam computed tomography (CBCT) system, after the insertion of fiducial markers (FMs). The planning CT was the reference CT (CTref) used to estimate the reference intermarker distances, and CBCTs were used for off-line comparison with CTref. We evaluated the influence of rectal and bladder volume on prostate shifts. We calculated the required planning target volume (PTV) margins in this patient population. 120 CBCTs were analyzed. Mean prostate displacements (± SD) along the 3 axes (x, y, z) averaged over the 10 patients, were: 0.90 ± 0.84 mm in x, 0.00 ± 2.07 mm in y, -0.80 ± 1.28 mm in z. There is a statistically significant anti-correlation between prostate displacements and: bladder volume variations (P < 0.001) in the y-axis, and rectal volume variations (P < 0.05) in the z-axis. PTV margins obtained for the directions x, y and z are respectively 2.5, 5.6 and 3.9 mm. IGRT in reproducible empty rectum condition allow a high reduction of daily treatment uncertainties.

208. Investigation on target motion with intraprostatic fiducial markers and daily CBCT in radical radiotherapy for prostate cancer

Purpose Nowadays there is a great interest on the improvement of the patient setup variability and target motion in radical radiotherapy for prostate cancer thanks to the fiducial markers inside the target [1] . The prostate lies in proximity to hollow organs (bladder and rectum) which are at risk of toxicity and may be displaced due to filling of these organs. To assess the utility of this method, we evaluated setup and target motion errors with daily fiducial-based CBCT in prostate image-guided radiotherapy; the radio-opaque seeds makes possible to monitor the previous discussed soft tissue structures. Methods Ten patients with prostate adenocarcinoma at intermediate-risk underwent radical radiotherapy with RapidArc technique and daily CBCT. They were previously subjected to intra-prostatic radio-opaque fiducial markers implantation. PTV included prostate and seminal vesicles. Patients were aligned to the treatment isocenter by laser. During treatment, daily CBCT were acquired and a matching according to fiducials was performed. After that, coach shifts required for isocenter correction were carried out. We measured lateral-lateral (LL), anterior-posterior (AP) and cranial-caudal (CC) shift adjustments. Results Mean and Standard Deviation of shifts in longitudinal, vertical and lateral directions signed in daily CBCT-matching according to fiducial markers for each patient were estimated as reported in Fig. 1. As a preliminary result, lateral shift mean is higher than the other two, whereas longitudinal and vertical shifts are affected by higher standard deviation. It could be due to the inter-fraction morphologic variations of patients. Conclusions The correct reproducibility of prostate treatment is affected by setup error and organ motion. Daily IGRT with fiducial-based CBCT ensures accuracy of the treatment since it is able to track the target position, mainly in the modern radiotherapy techniques with dose escalation to the target. Download : Download high-res image (215KB) Download : Download full-size image

A pilot study of highly hypofractionated intensity-modulated radiation therapy over 3 weeks for localized prostate cancer.

The purpose of this pilot study was to evaluate the feasibility of highly hypofractionated intensity-modulated radiation therapy (IMRT) in 15 fractions over 3 weeks for treating localized prostate cancer based on prostate position-based image-guided radiation therapy. Twenty-five patients with National Comprehensive Cancer Network (NCCN) very low- to unfavorable intermediate-risk prostate cancer were enrolled in this study from April 2014 to September 2015 to receive highly hypofractionated IMRT (without intraprostatic fiducial markers) delivering 54 Gy in 15 fractions over 3 weeks. Patients with intermediate-risk disease underwent neoadjuvant androgen suppression for 4–8 months. Twenty-four patients were treated with highly hypofractionated IMRT, and one was treated with conventionally fractionated IMRT because the dose constraint of the small bowel seemed difficult to achieve during the simulation. Seventeen percent had very low- or low-risk, 42% had favorable intermediate-risk, and 42% had unfavorable intermediate-risk disease according to NCCN guidelines. The median follow-up period was 31 months (range, 24–42 months). No Grade ≥3 acute toxicity was observed, and the incidence rates of Grade 2 acute genitourinary and gastrointestinal toxicities were 21% and 4%, respectively. No Grade ≥2 late toxicity was observed. Biochemical relapse was observed in one patient at 15 months, and the biochemical relapse-free survival rate was 95.8% at 2 years. A prostate-specific antigen bounce of ≥0.4 ng/ml was observed in 11 patients (46%). The highly hypofractionated IMRT regimen is feasible in patients with localized prostate cancer and is more convenient than conventionally fractionated schedules for patients and health-care providers.

In Vivo Validation of Elekta's Clarity Autoscan for Ultrasound-based Intrafraction Motion Estimation of the Prostate During Radiation Therapy

PurposeOur purpose was to perform an in vivo validation of ultrasound imaging for intrafraction motion estimation using the Elekta Clarity Autoscan system during prostate radiation therapy. The study was conducted as part of the Clarity-Pro trial (NCT02388308).Methods and MaterialsInitial locations of intraprostatic fiducial markers were identified from cone beam computed tomography scans. Marker positions were translated according to Clarity intrafraction 3-dimensional prostate motion estimates. The updated locations were projected onto the 2-dimensional electronic portal imager plane. These Clarity-based estimates were compared with the actual portal-imaged 2-dimensional marker positions. Images from 16 patients encompassing 80 fractions were analyzed. To investigate the influence of intraprostatic markers and image quality on ultrasound motion estimation, 3 observers rated image quality, and the marker visibility on ultrasound images was assessed.ResultsThe median difference between Clarity-defined intrafraction marker locations and portal-imaged marker locations was 0.6 mm (with 95% limit of agreement at 2.5 mm). Markers were identified on ultrasound in only 3 of a possible 240 instances. No linear relationship between image quality and Clarity motion estimation confidence was identified. The difference between Clarity-based motion estimates and electronic portal–imaged marker location was also independent of image quality. Clarity estimation confidence was degraded in a single fraction owing to poor probe placement.ConclusionsThe accuracy of Clarity intrafraction prostate motion estimation is comparable with that of other motion-monitoring systems in radiation therapy. The effect of fiducial markers in the study was deemed negligible as they were rarely visible on ultrasound images compared with intrinsic anatomic features. Clarity motion estimation confidence was robust to variations in image quality and the number of ultrasound-imaged anatomic features; however, it was degraded as a result of poor probe placement.

Pilot study of moderately-hypofractionated intensity-modulated radiation therapy over 3 weeks for localized prostate cancer.

8 Background: The purpose of this trial was to prospectively evaluate the short-term outcomes of moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) for localized prostate cancer. Methods: In November 2013, we started a pilot study of MH-IMRT for prostate cancer. Eligible patients were 50 to 80 years old and had D’Amico’s low- or intermediate-risk disease. Fifty-four Gy in 15 fractions (3.6 Gy per fraction), in which the equivalent total dose in 2-Gy fractions to prostate cancer was estimated about 78 Gy, were delivered over 3 weeks using image-guided IMRT based on daily cone beam CT without intraprostatic fiducial markers. Neoadjuvant androgen deprivation therapy was given 4 to 8 months before the start of IMRT. The primary endpoint was incidence rates of acute toxicities, and the secondary endpoints were incidence rates of late toxicities at 2 years and biochemical relapse free survival (BRFS) at 2 years. Acute toxicities were evaluated based on the Common Terminology Criteria for Adverse Events version 4.0 criteria. Late toxicities were evaluated based on RTOG/EORTC Late Radiation Morbidity Scoring Schema. Biochemical relapse was defined according to the Phoenix definition (absolute nadir + 2 ng/ml). The planned sample size was 25 patients. Results: Twenty-five patients were enrolled in this trial. Twenty-four patients were treated with MH-IMRT, and 1 patient was treated with conventionally fractionated IMRT because his small intestine was close to the target. The median age in the cohort was 71 years old, and median follow-up period was 31 months (range 24-42). Four patients (17%) had low- and 20 (83%) had intermediate-risk disease. No grade ≥3 acute toxicity was observed and the incidence rates of grade 2 acute genitourinary and gastrointestinal toxicities were 21% and 4%, respectively. So far no grade ≥2 late toxicity has been observed and the 2-year BRFS is 95.8%. Transient PSA elevation over 0.4 ng/ml was observed in 11 patients (46%) and in 5 patients (21%) PSA rose ≥1.0 ng/ml above nadir. Conclusions: Sort-term outcome of MH-IMRT delivering 54 Gy in 15 fractions over 3 weeks for prostate cancer was comparable to that of conventionally fractionated IMRT. Clinical trial information: UMIN000012057.

Image-Guided Radiotherapy Dose Escalation in Intermediate and High Risk Cancer Prostate Patients and Its Effect on Treatment Toxicity

Purpose: To study the effect of escalating radiation dose; in intermediate and high risk prostate cancer patients; via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.

Fiduciels intraprostatiques dans le cadre de la radiothérapie stéréotaxique du cancer de la prostate

PurposeImage-guided radiotherapy for prostate cancer is widely used in radiotherapy departments. Intraprostatic gold fiducial markers are used to visualize prostate position and motion before and during treatment. The aim of this report is to describe our experience of implanting intraprostatic fiducial markers under local anesthesia before hypofractionated stereotactic radiotherapy for prostate cancer and to assess its tolerance and reproducibility. Patients and methodsOver a 6 and a half year period, 226 patients with prostate cancer received a stereotactic radiotherapy using the CyberKnife® system (Accuray) in our institution. Eighteen patients were treated for recurrence after prostatectomy; these patients were excluded from the study. Among the 208 remaining patients, 94 patients (45.2%) received stereotactic radiotherapy as a boost after external beam radiotherapy (three fractions of 6Gy); 36 patients (17.3%) were had a re-irradiation (six fractions of 6Gy) and 78 patients (37.5%) had a exclusive stereotactic radiotherapy (68 patients received five fractions of 7.25Gy and 11 patients five fractions of 6.25Gy). Four markers were implanted in all patients using transrectal ultrasound; the procedure was performed under local anesthesia, using transperineal access. The four fiducial markers were implanted in two strands with two fiducial each one, 1cm apart. In order to follow the recommendations of the image-guided radiotherapy system, the two strands of the two markers were located on the same plane in the middle of the prostate, at least 2cm apart from the midline. After insertion, correct positioning of fiducials markers was verified by X-ray. Dosimetry scanning was performed after the implantation procedure; prostate position tracking was possible before and during treatment through the kilovoltage incorporated system of the robotic accelerator. Clinical data, X-ray verification and dosimetry scanner have been retrospectively reviewed for all patients. ResultsThe tolerance to procedure was excellent; only four patients (1.8%) described pain related to implant. No urinary side effects were reported. Median time from fiducial implantation to dosimetry scanner was 16 days (4–113 days). Four fiducials were found within the prostate at dosimetry scanner in 181 patients and three in 27 remaining patients. All intraprostatic fiducials were used to track the prostate gland before and during treatment. ConclusionsIntraprostatic fiducial markers implantation is a safe and reproducible procedure that allows us to have reliable prostate information before and during stereotactic radiotherapy.

Improved Late Rectal and Urinary Toxicity With High-Dose Intensity Modulated Radiation Therapy Using Intraprostate Fiducial Markers for Localized Prostate Cancer

To evaluate the impact of intensity modulated radiation therapy (IMRT) with intraprostate fiducial markers on the incidence of late urinary and rectal toxicity compared to 3D conformal radiation therapy (3DCRT) for patients with prostate cancer (PC) treated in a dose-escalation protocol. The hypothesis is that IMRT with image guided radiation therapy (IGRT) allows increasing dose with less toxicity than 3DCRT. Between 1995 and 2015, 1022 consecutive patients with localized PC were treated with dose-escalation radiation therapy (RT) of which 733 patients were enrolled in this study. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up >23 months. The study included 438 patients treated with 3DCRT and 295 treated with IMRT using intraprostate gold fiducial markers IGRT. The median ICRU radiation dose was 79.8 Gy (range, 72.1-87.1), 78.7 Gy and 80.7 Gy for 3DCRT and IMRT/IGRT respectively (P<0.001). Acute and late toxicities were assessed using the EORTC/RTOG and CTCAEs v4.0 definition. A logistic regression analysis was performed to identify clinical and dosimetric prognostic factors affecting the risk of late urinary and rectal complications. Statistical analyses were carried out using statistical analysis software. The mean follow-up for the entire cohort was 75 months (range, 24-204 months). The incidence of late grade ≥ 2 urinary complications was 5.4% and 13.0% for IMRT/IGRT and 3DCRT respectively (P = 0.001) and the incidence for grade ≥ 2 rectal toxicity was 3.7% and 9.4% for IMRT/IGRT and 3DCRT respectively (P = 0.004). On multivariate analysis, the use of IMRT/IGRT (odds ratio [OR] = 0.374, P = 0.001) and the antecedent of prior transurethral resection of the prostate (OR = 2.452, P = 0.005), were the only independent factors correlated with late grade ≥2 urinary complications. Other factors like the presence of acute urinary symptoms during RT (OR = 1.780, P = 0.060) and the use of hormone therapy (OR = 0.596, P = 0.069) were of borderline statistical significance but with potential clinical relevance. The use of IMRT/IGRT (OR = 0.378, P = 0.014), the antecedent of colon diverticula (OR = 3.515, P<0.001) and the patient age (OR = 0.941, P = 0.040) were significantly correlated with late grade ≥ 2 rectal toxicity. High-dose IMRT/IGRT with intraprostatic fiducial markers is associated with a significantly lower rate of rectal and urinary side effects compared to 3DCRT in spite of higher radiation dose. Further follow up is needed to confirm the protective effect of hormone therapy on late urinary complications.

MRI to CT Prostate Registration for Improved Targeting in Cancer External Beam Radiotherapy.

External radiotherapy is a major clinical treatment for localized prostate cancer. Currently, computed tomography (CT) is used to delineate the prostate and to plan the radiotherapy treatment. However, CT images suffer from a poor soft-tissue contrast and do not allow an accurate organ delineation. On the contrary, magnetic resonance imaging (MRI) provides rich details and high soft-tissue contrast, allowing tumor detection. Thus, the intraindividual propagation of MRI delineations toward the planning CT may improve tumor targeting. In this paper, we introduce a new method to propagate MRI prostate delineations to the planning CT. In the first step, a random forest classification is performed to coarsely detect the prostate in the CT images, yielding a prostate probability membership for each voxel and a prostate hard segmentation. Then, the registration is performed using a new similarity metric which maximizes the probability and the collinearity between the normals of the manual registration (MR) existing contour and the contour resulting from the CT classification. The first study on synthetic data was performed to analyze the influence of the metric parameters with different levels of noise. Then, the method was also evaluated on real MR-CT data using manual alignments and intraprostatic fiducial markers and compared to a classically used mutual information (MI) approach. The proposed metric outperformed MI by 7% in terms of Dice score coefficient, by 3.14 mm the Hausdorff distance, and 2.13 mm the markers position errors. Finally, the impact of registration uncertainties on the treatment planning was evaluated, demonstrating the potential advantage of the proposed approach in a clinical setup to define a precise target.

EP-1505: Assessment of migration of intraprostatic fiducial markers during radiotherapy

EP-1505: Assessment of migration of intraprostatic fiducial markers during radiotherapy

Calcifications intraprostatiques : marqueurs fiduciels naturels dans la radiothérapie guidée par l’image du cancer de la prostate

PurposeTo establish whether intraprostatic calcifications can serve as natural fiducials for image-guided radiotherapy (IGRT), replacing the implantation of intraprostatic fiducial markers. Patients and methodsPatients with prostate cancer, having intraprostatic calcifications visible on CT scan were selected and underwent intensity-modulated radiotherapy/3D conformal radiotherapy with IGRT in the department of radiotherapy of Henri-Mondor Hospital. All cone-beam computed tomographies (CBCT) were repositioned on intraprostatic calcifications. For each acquired image, displacements of intraprostatic calcifications were calculated with reference to position on planning CT in three directions: lateral, longitudinal and vertical. ResultsBetween 2011 and 2013, nine patients had 183 CBCT. For each image, three displacements and space coordinates were calculated using a single reference (intraprostatic calcification). Mean lateral, longitudinal and vertical movements were 0.26±5.7mm, −1±4.6mm and 0.42±3.5mm, respectively. ConclusionStudies exploring prostatic movements with fiducial markers as reference and ours with natural fiducials yield similar results. Our data confirm previous studies that have suggested that intraprostatic calcifications can be used as natural fiducials with potential reduction of iatrogenic risks and costs associated with the implantation of fiducial markers.