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1.  Accelerated partial breast irradiation using external beam radiotherapy—A feasibility study based on dosimetric analysis 
To investigate the feasibility of using External Beam radiotherapy for accelerated partial breast irradiation by a comparative tumour and normal tissue dose volume analysis with that of high dose rate interstitial brachytherapy.
Accelerated Partial Breast Irradiation (APBI) is more clinically appealing because of the reduced treatment course duration and the irradiated area. Brachytherapy application is more dependent on the clinician's expertise when it is practised free hand without image guidance and a template. It happens to be an invasive procedure with the use of local anaesthesia which adds patient discomfort apart from its cost compared to External Beam Radiotherapy. But APBI with brachytherapy is more commonly practised procedure compared to EBRT owing to its previous reults. Hence in this research study, we intend to explore the use of EBRT with the radiobiological corrections for APBI in the place of brachytherapy. It is done as a dosimetric comparison of Brachytherapy treatment plans with that of EBRT plans.
Materials and methods
The computed tomography images of 15 patients undergoing ISBT planning were simulated with conformal photon fields. Various dose volume parameters of each structure were obtained from the DVH generated in the brachytherapy and the simulated external beam planning which can correlate well with the late toxicity. The plan quality indices such as conformity index and homogeneity index for the target volume were computed from the dosimetric factors. The statistical p values for CI, HI and normal tissue dosimetric parameters were calculated and the confidence levels achievable were analysed. The dose prescribed in brachytherapy was 3400cGy in ten fractions. The equivalent prescription dose for the external beam radiotherapy planning was 3000cGy in five fractions applied with radiobiological correction.
All the fifteen patients were with complete lung data and six were with left sided tumours having complete cardiac data. The lung dosimetry data and the cardiac dosimetry data of the patients were studied. Lower percentages of lung and cardiac V20 and V5 volumes were obtained with conformal planning. The conformity of radiation dose to the tumour volume was akin to the interstitial brachytherapy planning. Moreover the external beam planning resulted in more homogenous dose distribution. For the sampled population, the statistical analysis showed a confidence level of 95% for using EBRT as an alternate to multi catheter ISBT.
The EBRT planning for Accelerated Partial Breast Irradiation was found to be technically feasible in the institution where the interstitial brachytherapy happens to be the only available technique as evident from the dose volume parameters and the statistical analysis.
PMCID: PMC3863155  PMID: 24377024
APBI; Dose conformity; Dose homogeneity; Multicatheter ISBT
2.  System for Prostate Brachytherapy and Biopsy in a Standard 1.5 T MRI Scanner 
A technique for transperineal high-dose-rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI-guided transperineal prostate biopsies were obtained followed by placement of 14–15 hollow transperineal catheters for HDR brachytherapy. Mean needle-placement accuracy was 2.1 mm, 95% of needle-placement errors were less than 4.0 mm, and the maximum needle-placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized.
PMCID: PMC2396258  PMID: 15334592
MRI; brachytherapy; prostate; prostatic neoplasms; biopsy; interventional MRI
3.  “MRI Stealth” robot for prostate interventions 
The paper reports an important achievement in MRI instrumentation, a pneumatic, fully actuated robot located within the scanner alongside the patient and operating under remote control based on the images. Previous MRI robots commonly used piezoelectric actuation limiting their compatibility. Pneumatics is an ideal choice for MRI compatibility because it is decoupled from electromagnetism, but pneumatic actuators were hardly controllable. This achievement was possible due to a recent technology breakthrough, the invention of a new type of pneumatic motor, PneuStep (1), designed for the robot reported here with uncompromised MRI compatibility, high-precision, and medical safety. MrBot is one of the “MRI stealth” robots today (the second is described in this issue by Zangos et al.). Both of these systems are also multi-imager compatible, being able to operate with the imager of choice or cross-imaging modalities. For MRI compatibility the robot is exclusively constructed of nonmagnetic and dielectric materials such as plastics, ceramics, crystals, rubbers and is electricity free. Light-based encoding is used for feedback, so that all electric components are distally located outside the imager’s room. MRI robots are modern, digital medical instruments in line with advanced imaging equipment and methods. These allow for accessing patients within closed bore scanners and performing interventions under direct (in scanner) imaging feedback. MRI robots could allow e.g. to biopsy small lesions imaged with cutting edge cancer imaging methods, or precisely deploy localized therapy at cancer foci. Our robot is the first to show the feasibility of fully automated in-scanner interventions. It is customized for the prostate and operates transperineally for needle interventions. It can accommodate various needle drivers for different percutaneous procedures such as biopsy, thermal ablations, or brachytherapy. The first needle driver is customized for fully automated low-dose radiation seed brachytherapy. This paper gives an introduction to the challenges of MRI robot compatibility and presents the solutions adopted in making the MrBot. Its multi-imager compatibility and other preclinical tests are included. The robot shows the technical feasibility of MRI-guided prostate interventions, yet its clinical utility is still to be determined.
PMCID: PMC3106223  PMID: 17763098
MRI Robot; image-guided intervention (IGI); MRI compatible; multi-imager compatible; pneumatic motor
4.  A Fully Actuated Robotic Assistant for MRI-Guided Prostate Biopsy and Brachytherapy 
Intra-operative medical imaging enables incorporation of human experience and intelligence in a controlled, closed-loop fashion. Magnetic resonance imaging (MRI) is an ideal modality for surgical guidance of diagnostic and therapeutic procedures, with its ability to perform high resolution, real-time, high soft tissue contrast imaging without ionizing radiation. However, for most current image-guided approaches only static pre-operative images are accessible for guidance, which are unable to provide updated information during a surgical procedure. The high magnetic field, electrical interference, and limited access of closed-bore MRI render great challenges to developing robotic systems that can perform inside a diagnostic high-field MRI while obtaining interactively updated MR images. To overcome these limitations, we are developing a piezoelectrically actuated robotic assistant for actuated percutaneous prostate interventions under real-time MRI guidance. Utilizing a modular design, the system enables coherent and straight forward workflow for various percutaneous interventions, including prostate biopsy sampling and brachytherapy seed placement, using various needle driver configurations. The unified workflow compromises: 1) system hardware and software initialization, 2) fiducial frame registration, 3) target selection and motion planning, 4) moving to the target and performing the intervention (e.g. taking a biopsy sample) under live imaging, and 5) visualization and verification. Phantom experiments of prostate biopsy and brachytherapy were executed under MRI-guidance to evaluate the feasibility of the workflow. The robot successfully performed fully actuated biopsy sampling and delivery of simulated brachytherapy seeds under live MR imaging, as well as precise delivery of a prostate brachytherapy seed distribution with an RMS accuracy of 0.98mm.
PMCID: PMC4112766  PMID: 25076821
Magnetic resonance imaging; image-guided intervention; MRI-compatible robot; prostate biopsy; prostate brachytherapy; piezoelectric actuation; automated needle insertion
5.  Catheter-based ultrasound hyperthermia with HDR brachytherapy for treatment of locally advanced cancer of the prostate and cervix 
A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2–4 cm length × 180 deg and 3–4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2–3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions. (NIHR01CA122276).
PMCID: PMC4112774  PMID: 25076820
Ultrasound; Hyperthermia; Thermal Therapy; Interstitial; Endocavity
6.  Low-dose-rate or high-dose-rate brachytherapy in treatment of prostate cancer – between options 
Permanent low-dose-rate (LDR-BT) and temporary high-dose-rate (HDR-BT) brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never to be conducted comparing these two forms of brachytherapy, a comparative analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. The aim of this paper is to look for possible similarities and differences between both brachytherapy modalities. Indications and contraindications for monotherapy and for brachytherapy as a boost to external beam radiation therapy (EBRT) are presented. It is suggested that each of these techniques has attributes that advocates for one or the other. First, they represent the extreme ends of the spectrum with respect to dose rate and fractionation, and therefore have inherently different radiobiological properties. Low-dose-rate brachytherapy has the great advantage of being practically a one-time procedure, and enjoys a long-term follow-up database supporting its excellent outcomes and low morbidity. Low-dose-rate brachytherapy has been a gold standard for prostate brachytherapy in low risk patients since many years. On the other hand, HDR is a fairly invasive procedure requiring several sessions associated with a brief hospital stay. Although lacking in significant long-term data, it possesses the technical advantage of control over its postimplant dosimetry (by modulating the source dwell time and position), which is absent in LDR brachytherapy. This important difference in dosimetric control allows HDR doses to be escalated safely, a flexibility that does not exist for LDR brachytherapy.
Radiobiological models support the current clinical evidence for equivalent outcomes in localized prostate cancer with either LDR or HDR brachytherapy, using current dose regimens. At present, all available clinical data regarding these two techniques suggests that they are equally effective, stage for stage, in providing high tumor control rates.
PMCID: PMC3635047  PMID: 23634153
brachytherapy; HDR; LDR; prostate cancer; seeds
7.  EM-Navigated Catheter Placement for Gynecologic Brachytherapy: An Accuracy Study 
Gynecologic malignancies, including cervical, endometrial, ovarian, vaginal and vulvar cancers, cause significant mortality in women worldwide. The standard care for many primary and recurrent gynecologic cancers consists of chemoradiation followed by brachytherapy. In high dose rate (HDR) brachytherapy, intracavitary applicators and/or interstitial needles are placed directly inside the cancerous tissue so as to provide catheters to deliver high doses of radiation. Although technology for the navigation of catheters and needles is well developed for procedures such as prostate biopsy, brain biopsy, and cardiac ablation, it is notably lacking for gynecologic HDR brachytherapy. Using a benchtop study that closely mimics the clinical interstitial gynecologic brachytherapy procedure, we developed a method for evaluating the accuracy of image-guided catheter placement. Future bedside translation of this technology offers the potential benefit of maximizing tumor coverage during catheter placement while avoiding damage to the adjacent organs, for example bladder, rectum and bowel. In the study, two independent experiments were performed on a phantom model to evaluate the targeting accuracy of an electromagnetic (EM) tracking system. The procedure was carried out using a laptop computer (2.1GHz Intel Core i7 computer, 8GB RAM, Windows 7 64-bit), an EM Aurora tracking system with a 1.3mm diameter 6 DOF sensor, and 6F (2 mm) brachytherapy catheters inserted through a Syed-Neblett applicator. The 3D Slicer and PLUS open source software were used to develop the system. The mean of the targeting error was less than 2.9mm, which is comparable to the targeting errors in commercial clinical navigation systems.
PMCID: PMC4112824  PMID: 25076828
gynecologic brachytherapy; electromagnetic tracking; catheter placement; image-guided therapy; radiation therapy
8.  Impact of intraoperative MRI/TRUS fusion on dosimetric parameters in cT3a prostate cancer patients treated with high-dose-rate real-time brachytherapy 
The purpose of this study was to evaluate the impact of intraoperative MRI/TRUS fusion procedure in cT3a prostate cancer patients treated with high-dose-rate (HDR) real-time brachytherapy.
Material and methods
Prostate gland, dominant intraprostatic lesions (DILs), and extracapsular extension (ECE) were delineated in the pre-brachytherapy magnetic resonance images (MRI) of 9 consecutive patients. The pre-implant P-CTVUS (prostate clinical target volume) was defined as the prostate seen in the transrectal ultrasound (TRUS) images. The CTVMR includedthe prostate with the ECE image (ECE-CTV) as defined on the MRI. Two virtual treatment plans were performed based on the MRI/TRUS fusion images, the first one prescribing 100% of the dose to the P-PTVUS, and the second prescribing to the PTVMR. The implant parameters and dose-volume histogram (DVH) related parameters of the prostate, OARs, and ECE were compared between both plans.
Mean radial distance of ECE was 3.6 mm (SD: 1.1). No significant differences were found between prostate V100, V150, V200, and OARs DVH-related parameters between the plans. Mean values of ECE V100, V150, and V200 were 85.9% (SD: 15.1), 18.2% (SD: 17.3), and 5.85% (SD: 7) when the doses were prescribed to the PTVUS, whereas ECE V100, V150, and V200 were 99.3% (SD: 1.2), 45.8% (SD: 22.4), and 19.6% (SD: 12.6) when doses were prescribed to PTVMR (p = 0.028, p = 0.002 and p = 0.004, respectively).
TRUS/MRI fusion provides important information for prostate brachytherapy, allowing for better coverage and higher doses to extracapsular disease in patients with clinical stage T3a.
PMCID: PMC4105645  PMID: 25097555
extracapsular extension; high-dose-rate brachytherapy; MRI/TRUS fusion; prostate cancer
9.  Real-Time MRI-Guided Cryoablation of Small Renal Tumors at 1.5 T 
Investigative radiology  2013;48(6):437-444.
Real-time magnetic resonance imaging (MRI)-guided cryoablation has been investigated in open MRI systems with low magnetic fields (0.2–0.5 T). More advanced imaging techniques and faster imaging rates are possible at higher magnetic fields which often require a closed-bore magnet design. However, there is very little experience with real-time interventions in closed-bore 1.5 T MRI units. Herein, we report our initial experience with real-time MRI-guided cryoablation of small renal tumors using a prototype balanced steady-state free precession (bSSFP) imaging sequence in a closed-bore 1.5-T MRI system.
Materials and Methods
From August 2008 to April 2012, 18 patients underwent MRI-guided cryoablation of small renal tumors. A 1.5-T cylindrical MRI scanner with a 125 cm × 70 cm bore and a prototype bSSFP sequence (BEAT IRTTT) were used to guide the placement of 17-gauge cryoprobes in real time. Ice ball formation was monitored every 3 minutes in one or more imaging planes. Each ablation consisted of 2 freeze-thaw cycles. Contrast-enhanced MRI was performed after the second active thaw period. Follow-up consisted of clinical evaluation and renal protocol computed tomography (CT) or MRI performed at 1, 6, 12, 18, and 24 months and annually thereafter.
During the study period, we successfully ablated 18 tumors in 18 patients in 18 sessions. The mean tumor size was 2.2 cm (median, 2 cm; range: 1.2–4.4 cm). The number of cryoprobes used per patient was determined based on tumor size. The mean number of cryoprobes used per patient was 3 (median, 3 cryoprobes; range, 2–4 cryoprobes). Fifty-six cryoprobes, 9 biopsy needles, and 2 hydrodissection needles were successfully placed under real time MRI guidance using BEAT IRTTT sequence. Hydrodissection under MRI guidance was successfully performed in 4 patients. In each patient, contrast-enhanced MRI performed after the second active thaw period revealed a sharply defined avascular zone surrounding the targeted tumor, which confirmed complete ablation of the tumor with adequate margins. Although contrast media slowly accumulated in the targeted tumor in 9 patients immediately after the procedure, follow-up imaging studies performed at a mean of 16.7 months revealed no contrast enhancement within the ablation zone in these patients. Disease-specific, metastasis-free, and local recurrence–free survival rates were all 100%.
Real-time placement and manipulation of cryoprobes during MRI-guided cryoablation of small renal tumors in a closed-bore, high–magnetic field scanner is feasible. Technical and clinical success rates are similar to those of patients who undergo CT-guided radiofrequency ablation or cryoablation of small renal tumors. Our findings suggest that MRI-guided ablation has several advantages over CT-guided ablation, including real-time guidance for probe placement, multiplanar imaging, exquisite soft tissue contrast, and lack of ionizing radiation.
PMCID: PMC3899798  PMID: 23511191
Renal cell carcinoma; renal tumor; cryoablation; interventional MRI
10.  In vivo assessment of catheter positioning accuracy and prolonged irradiation time on liver tolerance dose after single-fraction 192Ir high-dose-rate brachytherapy 
To assess brachytherapy catheter positioning accuracy and to evaluate the effects of prolonged irradiation time on the tolerance dose of normal liver parenchyma following single-fraction irradiation with 192 Ir.
Materials and methods
Fifty patients with 76 malignant liver tumors treated by computed tomography (CT)-guided high-dose-rate brachytherapy (HDR-BT) were included in the study. The prescribed radiation dose was delivered by 1 - 11 catheters with exposure times in the range of 844 - 4432 seconds. Magnetic resonance imaging (MRI) datasets for assessing irradiation effects on normal liver tissue, edema, and hepatocyte dysfunction, obtained 6 and 12 weeks after HDR-BT, were merged with 3D dosimetry data. The isodose of the treatment plan covering the same volume as the irradiation effect was taken as a surrogate for the liver tissue tolerance dose. Catheter positioning accuracy was assessed by calculating the shift between the 3D center coordinates of the irradiation effect volume and the tolerance dose volume for 38 irradiation effects in 30 patients induced by catheters implanted in nearly parallel arrangement. Effects of prolonged irradiation were assessed in areas where the irradiation effect volume and tolerance dose volume did not overlap (mismatch areas) by using a catheter contribution index. This index was calculated for 48 irradiation effects induced by at least two catheters in 44 patients.
Positioning accuracy of the brachytherapy catheters was 5-6 mm. The orthogonal and axial shifts between the center coordinates of the irradiation effect volume and the tolerance dose volume in relation to the direction vector of catheter implantation were highly correlated and in first approximation identically in the T1-w and T2-w MRI sequences (p = 0.003 and p < 0.001, respectively), as were the shifts between 6 and 12 weeks examinations (p = 0.001 and p = 0.004, respectively). There was a significant shift of the irradiation effect towards the catheter entry site compared with the planned dose distribution (p < 0.005). Prolonged treatment time increases the normal tissue tolerance dose. Here, the catheter contribution indices indicated a lower tolerance dose of the liver parenchyma in areas with prolonged irradiation (p < 0.005).
Positioning accuracy of brachytherapy catheters is sufficient for clinical practice. Reduced tolerance dose in areas exposed to prolonged irradiation is contradictory to results published in the current literature. Effects of prolonged dose administration on the liver tolerance dose for treatment times of up to 60 minutes per HDR-BT session are not pronounced compared to effects of positioning accuracy of the brachytherapy catheters and are therefore of minor importance in treatment planning.
PMCID: PMC3179944  PMID: 21892943
11.  Initial clinical experience with real-time transrectal ultrasonography-magnetic resonance imaging fusion-guided prostate biopsy 
BJU international  2007;101(7):841-845.
To evaluate the feasibility and utility of registration and fusion of real-time transrectal ultrasonography (TRUS) and previously acquired magnetic resonance imaging (MRI) to guide prostate biopsies.
Two National Cancer Institute trials allowed MRI-guided (with or with no US fusion) prostate biopsies during placement of fiducial markers. Fiducial markers were used to guide patient set-up for daily external beam radiation therapy. The eligible patients had biopsy-confirmed prostate cancer that was visible on MRI. A high-field (3T) MRI was performed with an endorectal coil in place. After moving to an US suite, the patient then underwent TRUS to visualize the prostate. The US transducer was equipped with a commercial needle guide and custom modified with two embedded miniature orthogonal five-degrees of freedom sensors to enable spatial tracking and registration with MR images in six degrees of freedom. The MRI sequence of choice was registered manually to the US using custom software for real-time navigation and feedback. The interface displayed the actual and projected needle pathways superimposed upon the real-time US blended with the prior MR images, with position data updating in real time at 10 frames per second. The registered MRI information blended to the real-time US was available to the physician who performed targeted biopsies of highly suspicious areas.
Five patients underwent limited focal biopsy and fiducial marker placement with real-time TRUS-MRI fusion. The Gleason scores at the time of enrolment on study were 8, 7, 9, 9, and 6. Of the 11 targeted biopsies, eight showed prostate cancer. Positive biopsies were found in all patients. The entire TRUS procedure, with fusion, took ≈10 min.
The fusion of real-time TRUS and prior MR images of the prostate is feasible and enables MRI-guided interventions (like prostate biopsy) outside of the MRI suite. The technique allows for navigation within dynamic contrast-enhanced maps, or T2-weighted or MR spectroscopy images. This technique is a rapid way to facilitate MRI-guided prostate therapies such as external beam radiation therapy, brachytherapy, cryoablation, high-intensity focused ultrasound ablation, or direct injection of agents, without the cost, throughput, or equipment compatibility issues that might arise with MRI-guided interventions inside the MRI suite.
PMCID: PMC2621260  PMID: 18070196
magnetic resonance; ultrasound; prostate cancer; imaging; transrectal
12.  Dosimetric analysis and comparison of IMRT and HDR brachytherapy in treatment of localized prostate cancer 
Radical radiotherapy is one of the options for the management of prostate cancer. In external beam therapy, 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) are the options for delivery of increased radiation dose, as vital organs are very close to the prostate and a higher dose to these structures leads to an increased toxicity. In brachytherapy, low dose rate brachytherapy with permanent implant of radioactive seeds and high dose rate brachytherapy (HDR) with remote after loaders are available. A dosimetric analysis has been made on IMRT and HDR brachytherapy plans. Ten cases from each IMRT and HDR brachytherapy have been taken for the study. The analysis includes comparison of conformity and homogeneity indices, D100, D95, D90, D80, D50, D10 and D5 of the target. For the organs at risk (OAR), namely rectum and bladder, V100, V90 and V50 are compared. In HDR brachytherapy, the doses to 1 cc and 0.1 cc of urethra have also been studied. Since a very high dose surrounds the source, the 300% dose volumes in the target and within the catheters are also studied in two plans, to estimate the actual volume of target receiving dose over 300%. This study shows that the prescribed dose covers 93 and 92% of the target volume in IMRT and HDR brachytherapy respectively. HDR brachytherapy delivers a much lesser dose to OAR, compared to the IMRT. For rectum, the V50 in IMRT is 34.0cc whilst it is 7.5cc in HDR brachytherapy. With the graphic optimization tool in HDR brachytherapy planning, the dose to urethra could be kept within 120% of the target dose. Hence it is concluded that HDR brachytherapy may be the choice of treatment for cancer of prostate in the early stage.
PMCID: PMC2884303  PMID: 20589121
Brachytherapy; conformity; intensity modulated radiotherapy; prostate
13.  MRS-guided HDR brachytherapy boost to the dominant intraprostatic lesion in high risk localised prostate cancer 
BMC Cancer  2010;10:472.
It is known that the vast majority of prostate cancers are multifocal. However radical radiotherapy historically treats the whole gland rather than individual cancer foci.
Magnetic resonance spectroscopy (MRS) can be used to non-invasively locate individual cancerous tumours in prostate. Thus an intentionally non-uniform dose distribution treating the dominant intraprostatic lesion to different dose levels than the remaining prostate can be delivered ensuring the maximum achievable tumour control probability.
The aim of this study is to evaluate, using radiobiological means, the feasibility of a MRS-guided high dose rate (HDR) brachytherapy boost to the dominant lesion.
Computed tomography and MR/MRS were performed for treatment planning of a high risk localised prostate cancer. Both were done without endorectal coil, which distorts shape of prostate during the exams.
Three treatment plans were compared:
- external beam radiation therapy (EBRT) only
- combination of EBRT and HDR brachytherapy
- combination of EBRT and HDR brachytherapy with a synchronous integrated boost to the dominant lesion
The criteria of plan comparison were: the minimum, maximum and average doses to the targets and organs at risk; dose volume histograms; biologically effective doses for organs at risk and tumour control probability for the target volumes consisting of the dominant lesion as detected by MR/MRS and the remaining prostate volume.
Inclusion of MRS information on the location of dominant lesion allows a safe increase of the dose to the dominant lesion while dose to the remaining target can be even substantially decreased keeping the same, high tumour control probability. At the same time an improved urethra sparing was achieved comparing to the treatment plan using a combination of EBRT and uniform HDR brachytherapy.
MRS-guided HDR brachytherapy boost to dominant lesion has the potential to spare the normal tissue, especially urethra, while keeping the tumour control probability high.
PMCID: PMC2941503  PMID: 20809986
14.  The American Brachytherapy Society Treatment Recommendations for Locally Advanced Carcinoma of the Cervix Part II: High Dose-Rate Brachytherapy 
Brachytherapy  2012;11(1):47-52.
This report presents the 2011 update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer.
Members of the American Brachytherapy Society (ABS) with expertise in cervical cancer brachytherapy formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder or interstitial applicators for locally advanced cervical cancer were revised based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy.
The Cervical Cancer Committee for Guideline Development affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion prior to treatment delivery. Applicator placement, dose specification and dose fractionation must be documented, quality assurance measures must be performed, and follow-up information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2 Gray (Gy) per fraction radiobiologic equivalence (EQD2) is 80–90 Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed.
These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011.
PMCID: PMC3489267  PMID: 22265437
15.  Dosimetric feasibility of stereotactic body radiation therapy as an alternative to brachytherapy for definitive treatment of medically inoperable early stage endometrial cancer 
This study was designed to evaluate the dosimetric feasibility of definitive stereotactic body radiation therapy (SBRT) for the treatment of medically inoperable early stage endometrial cancer.
CT simulation scans from 10 medically inoperable early stage endometrial cancer patients previously treated with high dose-rate (HDR) intracavitary brachytherapy were used to generate Helical Tomotherapy (HT) plans using the IMRT mode with clinical target volumes (CTVs) that included the uterus plus cervix. A prescription dose of 34 Gy in 4 fractions was used. The SBRT dosimetry was compared to the 10 prior intracavitary brachytherapy plans normalized to a standard dose. Organs at risk (OARs) evaluated were the bladder, rectum, sigmoid, femoral heads, and other bowel, including both large and small bowel. The simulation CT and daily image guidance for 4 patients treated with this technique were evaluated to assess for interfraction variation in the uterine position and effects on dosimetry.
Compared to intracavitary brachytherapy, HT SBRT produced significantly greater overall target coverage to the uterus, boost CTV, and PTV, with exception of the V150% of the uterus. HT SBRT significantly increased dose to the rectum, bowel, and femoral heads compared to intracavitary brachytherapy, though not outside of dose tolerance limits. Review of daily image guidance for patients treated with this technique demonstrated good reproducibility with a mean overlap index of 0.87 (range, 0.74 – 0.99).
Definitive SBRT for medically inoperable early stage endometrial cancer appears to be a feasible treatment option. Future studies are warranted to evaluate long-term clinical outcomes with this technique, compared to HDR intracavitary brachytherapy.
PMCID: PMC4118162  PMID: 25059785
SBRT; Medically inoperable; Endometrial cancer; Intracavitary brachytherapy
16.  A survey of quality control practices for high dose rate (HDR) and pulsed dose rate (PDR) brachytherapy in the United Kingdom 
A survey of quality control (QC) currently undertaken in UK radiotherapy centres for high dose rate (HDR) and pulsed dose rate (PDR) brachytherapy has been conducted. The purpose was to benchmark current accepted practice of tests, frequencies and tolerances to assure acceptable HDR/PDR equipment performance. It is 20 years since a similar survey was conducted in the UK and the current review is timed to coincide with a revision of the IPEM Report 81 guidelines for quality control in radiotherapy.
Material and methods
All radiotherapy centres in the UK were invited by email to complete a comprehensive questionnaire on their current brachytherapy QC practice, including: equipment type, patient workload, source calibration method, level of image guidance for planning, prescribing practices, QC tests, method used, staff involved, test frequencies, and acceptable tolerance limits.
Survey data was acquired between June and August 2012. Of the 64 centres invited, 47 (73%) responded, with 31 centres having brachytherapy equipment (3 PDR) and fully completing the survey, 13 reporting no HDR/PDR brachytherapy, and 3 intending to commence HDR brachytherapy in the near future. All centres had comprehensive QC schedules in place and there was general agreement on key test frequencies and tolerances. Greatest discord was whether source strength for treatment planning should be derived from measurement, as at 58% of centres, or from the certified value, at 42%. IPEM Report 81 continues to be the most frequently cited source of QC guidance, followed by ESTRO Booklet No. 8.
A comprehensive survey of QC practices for HDR/PDR brachytherapy in UK has been conducted. This is a useful reference to which centres may benchmark their own practice. However, individuals should take a risk-assessment based approach, employing full knowledge of local equipment, clinical procedures and available test equipment in order to determine individual QC needs.
PMCID: PMC3561606  PMID: 23378853
high dose rate (HDR); brachytherapy; quality control (QC); quality assurance (QA); survey
17.  A Dosimetric Analysis of Radiation Therapy Oncology Group (RTOG) 0321: the Importance of Urethral Dose 
Practical radiation oncology  2013;4(1):27-34.
RTOG 0321 is the first multi-institutional cooperative group HDR prostate brachytherapy trial with complete digital brachytherapy dosimetry data. This is a descriptive report of the data and an analysis of toxicity.
Methods and Materials
Patients are treated with EBRT 45 Gy and one HDR implant with 19 Gy in 2 fractions. Implants are done with TRUS guidance, and CT-compatible non-metallic catheters. HDR planning is done on ≤ 3 mm-thick CT slices. The “mean DVH” of the PTV, implanted volume (IP), and organs at risk are calculated. This includes the mean and standard deviation of the volume at ten-percentage-point intervals from 10%–200% of the prescribed dose. The conformal index (COIN), homogeneity index (HI), catheters/implant, and patients/institution are calculated. Multivariate analysis and Hazard Ratios calculation of all the variables against reported Grade ≥ 2 (G2+) GU adverse events (CTCAEv3) are performed.
Dosimetry data is based on 122 eligible patients from 14 institutions. The mean of PTV, IP, catheters/implant, and patients/institution are: 54 cc, 63 cc, 19 and 9. The mean of %V100PTV, V80Bladder, V80Rectum, and V120Urethra were: 94%, 0.40cc, 0.15cc, and 0.25cc. There are too few G2+ GI AE for correlative analysis, thus the analysis has been performed on the more common G2+ GU AE. There are positive correlations noted between both acute and late G2+ GU AE and urethral dose at multiple levels. Positive correlations with late AE are seen with PTV and IP at high-dose levels. A negative correlation is seen between HI and acute AE. A higher patient accrual rate is associated with a lower rate of G2+ acute and late AE.
Higher urethral dose, larger high dose volumes and lower dose homogeneity are associated with greater toxicities. A mean DVH comparison at all dose levels should be used for quality control and future research comparison.
PMCID: PMC4000550  PMID: 24621420
Prostate cancer; High Dose Rate; Brachytherapy; RTOG; Multi-institutional clinical trial
18.  Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes 
Hepatic radiation toxicity restricts irradiation of liver malignancies. Better knowledge of hepatic tolerance dose is favourable to gain higher safety and to optimize radiation regimes in radiotherapy of the liver. In this study we sought to determine the hepatic tolerance dose to small volume single fraction high dose rate irradiation.
Materials and methods
23 liver metastases were treated by CT-guided interstitial brachytherapy. MRI was performed 3 days, 6, 12 and 24 weeks after therapy. MR-sequences were conducted with T1-w GRE enhanced by hepatocyte-targeted Gd-EOB-DTPA. All MRI data sets were merged with 3D-dosimetry data. The reviewer indicated the border of hypointensity on T1-w images (loss of hepatocyte function) or hyperintensity on T2-w images (edema). Based on the volume data, a dose-volume-histogram was calculated. We estimated the threshold dose for edema or function loss as the D90, i.e. the dose achieved in at least 90% of the pseudolesion volume.
At six weeks post brachytherapy, the hepatocyte function loss reached its maximum extending to the former 9.4Gy isosurface in median (i.e., ≥9.4Gy dose exposure led to hepatocyte dysfunction). After 12 and 24 weeks, the dysfunctional volume had decreased significantly to a median of 11.4Gy and 14Gy isosurface, respectively, as a result of repair mechanisms. Development of edema was maximal at six weeks post brachytherapy (9.2Gy isosurface in median), and regeneration led to a decrease of the isosurface to a median of 11.3Gy between 6 and 12 weeks. The dose exposure leading to hepatocyte dysfunction was not significantly different from the dose provoking edema.
Hepatic injury peaked 6 weeks after small volume irradiation. Ongoing repair was observed up to 6 months. Individual dose sensitivity may differ as demonstrated by a relatively high standard deviation of threshold values in our own as well as all other published data.
PMCID: PMC3090344  PMID: 21496320
19.  Efficacy and Safety of High-Dose-Rate Brachytherapy of Single Implant with Two Fractions Combined with External Beam Radiotherapy for Hormone-Naïve Localized Prostate Cancer 
Cancers  2011;3(3):3585-3600.
The purpose of this study was to evaluate the efficacy and safety of high-dose-rate (HDR) brachytherapy of a single implant with two fractions plus external beam radiotherapy (EBRT) for hormone-naïve prostate cancer in comparison with radical prostatectomy. Of 150 patients with localized prostate cancer (T1c–T2c), 59 underwent HDR brachytherapy plus EBRT, and 91 received radical prostatectomy. The median follow-up of patients was 62 months for HDR brachytherapy plus EBRT, and 64 months for radical prostatectomy. In patient backgrounds between the two cohorts, the frequency of T2b plus T2c was greater in HDR brachytherapy cohort than in prostatectomy cohort (27% versus 12%, p = 0.029). Patients in HDR brachytherapy cohort first underwent 3D conformal RT with four beams to the prostate to an isocentric dose of 50 Gy in 25 fractions and then, a total of 15–18 Gy in two fractions at least 5 hours apart. We prescribed 9 Gy/fraction for target (prostate gland plus 3 mm lateral outside margin and seminal vesicle) using CT image method for radiation planning. The total biochemical failure-free control rates (BF-FCR) at 3 and 5 years for the HDR brachytherapy cohort, and for the prostatectomy cohort were 92% and 85%, and 72% and 72%, respectively (significant difference, p = 0.0012). The 3-and 5-year BF-FCR in the HDR brachytherapy cohort and in the prostatectomy cohort by risk group was 100 and 100%, and 80 and 80%, respectively, for the low-risk group (p = 0.1418); 92 and 92%, 73 and 73%, respectively, for the intermediate-risk group (p = 0.0492); and 94 and 72%, 45 and 45%, respectively, for the high-risk group (p = 0.0073). After HDR brachytherapy plus EBRT, no patient experienced Grade 2 or greater genitourinay toxicity. The rate of late Grade 1 and 2 GI toxicity was 6% (n = 4). No patient experienced Grade 3 GI toxicity. HDR brachytherapy plus EBRT is useful for treating patients with hormone-naïve localized prostate cancer, and has low GU and GI toxicities.
PMCID: PMC3759211  PMID: 24212968
prostate cancer; high dose rate brachytherapy; external beam radiation therapy; radical prostatectomy
20.  The emerging role of high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer 
Journal of Radiation Research  2013;54(5):781-788.
High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new brachytherapy procedure for prostate cancer. In addition to the intrinsic advantages of brachytherapy, including radiation dose concentration to the tumor and rapid dose fall-off at the surrounding normal tissue, HDR brachytherapy can yield a more homogeneous and conformal dose distribution through image-based decisions for source dwell positions and by optimization of individual source dwell times. Indication can be extended even to T3a/b or a part of T4 tumors because the applicators can be positioned at the extracapsular lesion, into the seminal vesicles, and/or into the bladder, without any risk of source migration or dropping out. Unlike external beam radiotherapy, with HDR brachytherapy inter-/intra-fraction organ motion is not problematic. However, HDR monotherapy requires patients to stay in bed for 1–4 days during hospitalization, even though the actual overall treatment time is short. Recent findings that the α/β value for prostate cancer is less than that for the surrounding late-responding normal tissue has made hypofractionation attractive, and HDR monotherapy can maximize this advantage of hypofractionation. Research on HDR monotherapy is accelerating, with a growing number of publications reporting excellent preliminary clinical results due to the high ‘biologically effective dose (BED)’ of >200 Gy. Moreover, the findings obtained for HDR monotherapy as an early model of extreme hypofractionation tend to be applied to other radiotherapy techniques such as stereotactic radiotherapy. All these developments point to the emerging role of HDR brachytherapy as monotherapy for prostate cancer.
PMCID: PMC3766299  PMID: 23543798
prostate cancer; high-dose-rate (HDR); brachytherapy; monotherapy; hypofractionation
21.  Novel high dose rate lip brachytherapy technique to improve dose homogeneity and reduce toxicity by customized mold 
The purpose of this study is to describe a novel brachytherapy technique for lip Squamous Cell Carcinoma, utilizing a customized mold with embedded brachytherapy sleeves, which separates the lip from the mandible, and improves dose homogeneity.
Materials and methods
Seven patients with T2 lip cancer treated with a “sandwich” technique of High Dose Rate (HDR) brachytherapy to the lip, consisting of interstitial catheters and a customized mold with embedded catheters, were reviewed for dosimetry and outcome using 3D planning. Dosimetric comparison was made between the “sandwich” technique to “classic” – interstitial catheters only plan. We compared dose volume histograms for Clinical Tumor Volume (CTV), normal tissue “hot spots” and mandible dose. We are reporting according to the ICRU 58 and calculated the Conformal Index (COIN) to show the advantage of our technique.
The seven patients (ages 36–81 years, male) had median follow-up of 47 months. Four patients received Brachytherapy and External Beam Radiation Therapy, 3 patients received brachytherapy alone. All achieved local control, with excellent esthetic and functional results. All patients are disease free.
The Customized Mold Sandwich technique (CMS) reduced the high dose region receiving 150% (V150) by an average of 20% (range 1–47%), The low dose region (les then 90% of the prescribed dose) improved by 73% in average by using the CMS technique. The COIN value for the CMS was in average 0.92 as opposed to 0.88 for the interstitial catheter only. All differences (excluding the low dose region) were statistically significant.
The CMS technique significantly reduces the high dose volume and increases treatment homogeneity. This may reduce the potential toxicity to the lip and adjacent mandible, and results in excellent tumor control, cosmetic and functionality.
PMCID: PMC4299482  PMID: 25533624
Brachytherapy; Lip; SCC; HDR; Customized mold technique
22.  Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer 
Radiotherapy and Oncology  2011;100(1):116-123.
To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT) ± chemotherapy (ChT).
Treatment schedule was EBRT with 45–50.4 Gy ± concomitant cisplatin chemotherapy plus 4 × 7 Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90 > 85 Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75 Gy for rectum and sigmoid and 90 Gy for bladder.
Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis.
One hundred and fifty-six consecutive patients (median age 58 years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5 cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42 months for all patients.
Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93 ± 13 Gy, D2cc 86 ± 17 Gy for bladder, 65 ± 9 Gy for rectum and 64 ± 9 Gy for sigmoid.
Complete remission was achieved in 151/156 patients (97%). Overall local control at 3 years was 95%; 98% for tumours 2–5 cm, and 92% for tumours >5 cm (p = 0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3 years was overall 74%, 83% for tumours 2–5 cm, 70% for tumours >5 cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3 years was in total 68%, 72% for tumours 2–5 cm, 65% for tumours >5 cm, 74% for IB, 78% for IIB, 45% for IIIB.
In regard to late morbidity in total 188 grade 1 + 2 and 11 grade 3 + 4 late events were observed in 143 patients. G1 + 2/G3 + 4 events for bladder were n = 32/3, for rectum n = 14/5, for bowel (including sigmoid) n = 3/0, for vagina n = 128/2, respectively.
3D conformal radiotherapy ± chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3 years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings.
PMCID: PMC3165100  PMID: 21821305
Cervical cancer; Image guided adaptive brachytherapy; Clinical outcome; GEC-ESTRO recommendations
23.  Current Status of Brachytherapy for Prostate Cancer 
Korean Journal of Urology  2012;53(11):743-749.
Brachytherapy was developed to treat prostate cancer 50 years ago. Current advanced techniques using transrectal ultrasonography were established 25 years ago. Transrectal ultrasound (TRUS) has enabled the prostate to be viewed with improved resolution with the use of modern ultrasound machines. Moreover, the development of software that can provide images captured in real time has improved treatment outcomes. Other new radiologic imaging technologies or a combination of magnetic resonance and TRUS could be applied to brachytherapy in the future. The therapeutic value of brachytherapy for early-stage prostate cancer is comparable to that of radical prostatectomy in long-term follow-up. Nevertheless, widespread application of brachytherapy cannot be achieved for several reasons. The treatment outcome of brachytherapy varies according to the skill of the operator and differences in patient selection. Currently, only three radioactive isotopes are available for use in low dose rate prostate brachytherapy: I-125, Pd-103, and Cs-131; therefore, more isotopes should be developed. High dose rate brachytherapy using Ir-192 combined with external beam radiation, which is needed to verify the long-term effects, has been widely applied in high-risk patient groups. Recently, tumor-selective therapy or focal therapy using brachytherapy, which is not possible by surgical extraction, has been developed to maintain the quality of life in selected cases. However, this new application for prostate cancer treatment should be performed cautiously because we do not know the oncological outcome, and it would be an interim treatment method. This technique might evolve into a hybrid of whole-gland treatment and focal therapy.
PMCID: PMC3502731  PMID: 23185664
Brachytherapy; Neoplasms; Prostate
24.  Catheter displacement prior to the delivery of high-dose-rate brachytherapy in the treatment of prostate cancer patients 
The purpose of this work was to report measured catheter displacement prior to the delivery of high-dose-rate brachytherapy (HDR) in the treatment of prostate cancer.
Material and methods
Data from 30 prostate cancer patients treated with HDR brachytherapy were analyzed retrospectively. Eighteen transperineal hollow catheters were inserted under transrectal ultrasound guidance. Gold marker seeds were also placed transperineally into the base and apex of the prostate gland. Five treatment fractions of 7.5 Gy each were administered over 3 days. The patient underwent CT scanning prior to each treatment fraction. Catheter displacement was measured from the pre-treatment CT dataset reconstructed at 1.25 mm slice thickness.
Most of catheters were displaced in the caudal direction. Variations of 18 catheters for each patient were small (standard deviations < 1 mm for all but one patient). Mean displacements relative to the apex marker were 6 ± 4 mm, 12 ± 6 mm, 12 ± 6 mm, 12 ± 6 mm, and 12 ± 6 mm from plan to 1st, 2nd, 3rd, 4th, and 5th fractions, respectively.
Our results indicate that catheter positions must be confirmed and if required, adjusted, prior to every treatment fraction for the precise treatment delivery of HDR brachytherapy, and to potentially reduce over-dosage to the bulbo-membranous urethra.
PMCID: PMC4105648  PMID: 25097556
brachytherapy; catheter displacement; high-dose-rate; prostate cancer
25.  High dose rate brachytherapy for oral cancer 
Journal of Radiation Research  2012;54(1):1-17.
Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.
PMCID: PMC3534285  PMID: 23179377
brachytherapy; oral cancer; high dose rate

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