Transrectal ultrasound for intraoperative interstitial needle guidance in cervical cancer brachytherapy.

OBJECTIVE: This study aimed to prospectively assess the visibility of interstitial needles on transrectal ultrasound (TRUS) in cervical cancer brachytherapy patients and evaluate its impact on implant and treatment plan quality. MATERIAL AND METHODS: TRUS was utilized during and after applicator insertion, with each needle's visibility documented through axial images at the high-risk clinical target volume's largest diameter. Needle visibility on TRUS was scored from 0 (no visibility) to 3 (excellent discrimination, margins distinct). Quantitative assessment involved measuring the distance between tandem and each needle on TRUS and comparing it to respective magnetic resonance imaging (MRI) measurements. Expected treatment plan quality based on TRUS images was rated from 1 (meeting all planning objectives) to 4 (violation of High-risk clinical target volume (CTVHR) and/or organ at risk (OAR) hard constraints) and compared to the final MRI-based plan. RESULTS: Analysis included 23 patients with local FIGO stage IB2-IVA, comprising 41 applications with a total of 230 needles. A high visibility rate of 99.1% (228/230 needles) was observed, with a mean visibility score of 2.5 ±â€¯0.7 for visible needles. The maximum and mean difference between MRI and TRUS measurements were 8 mm and -0.1 ±â€¯1.6 mm, respectively, with > 3 mm discrepancies in 3.5% of needles. Expected treatment plan quality after TRUS assessment exactly aligned with the final MRI plan in 28 out of 41 applications with only minor deviations in all other cases. CONCLUSION: Real-time TRUS-guided interstitial needle placement yielded high-quality implants, thanks to excellent needle visibility during insertion. This supports the potential of TRUS-guided brachytherapy as a promising modality for gynecological indications.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

Feasibility of transrectal ultrasonography for assessment of cervical cancer.

PURPOSE: To retrospectively compare the maximum target width and target thickness in patients with locally advanced cervical cancer between magnetic resonance imaging (MRI) and transrectal ultrasonography (TRUS) in the course of primary radiochemotherapy. PATIENTS AND METHODS: T2-weighted MRI and TRUS were performed on patients with locally advanced cervical cancer at the same timepoint-either at the time of diagnosis, or at the time of brachytherapy before or after insertion of the applicator. Patients treated from 2009 to 2011 were selected for this study based on the availability of MRI and TRUS at the defined time points. The target was defined as the complete macroscopic tumor mass and the remaining cervix and was measured on transversal planes. Descriptive statistics and a linear regression analysis were performed for the groups. RESULTS: Images from 17 patients were available for analysis. Mean maximum target width was 4.2 ± 0.83 cm and 4.2 ± 0.79 cm for MRI and TRUS, respectively. Mean maximum target thickness was 3.3 ± 1.03 cm and 3.1 ± 1.15 cm for MRI and TRUS, respectively. Linear regression analysis for target width and thickness between TRUS and MRI demonstrated a correlation with R(2) = 0.842 and R(2) = 0.943, respectively. CONCLUSION: The feasibility of TRUS for the assessment of local target extension could be demonstrated. Comparison of the target width and thickness showed a high correlation between TRUS and MRI, indicating the potential of TRUS for target definition in image-guided adaptive brachytherapy.

Comparison of seed brachytherapy or external beam radiotherapy (70 Gy or 74 Gy) in 919 low-risk prostate cancer patients.

PURPOSE: The aim of this analysis was to compare the biochemical no evidence of disease (bNED) rates in low-risk prostate cancer patients treated at two centers of excellence using different approaches: seed brachytherapy (BT) and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A total of 919 low-risk prostate cancer patients, treated from 1998-2008, were identified in the two databases. In Utrecht, 667 patients received I-125 BT applying a dose of 144 Gy. In Vienna, 252 patients were treated with EBRT, applying a local dose of 70 Gy in 82 patients and 74 Gy in 170 patients. bNED rates (Phoenix definition) were assessed. RESULTS: The median follow-up was 46 months (range 1-148 months). The 5-year actuarial bNED rates were 94% for BT patients and 88% for EBRT patients (p = 0.002)-84% for patients receiving 70 Gy and 91% for patients receiving 74 Gy, respectively. In the univariate analysis, patients receiving 70 Gy showed significantly worse outcome compared to BT (p = 0.001) and a difference close to significance compared to 74 Gy (p = 0.06). In the multivariate analysis including tumor stage, Gleason score, initial PSA, hormonal therapy, and dose, patients receiving 70 Gy EBRT showed significantly worse bNED rates compared to BT patients. CONCLUSION: Low-risk prostate cancer patients receiving 74 Gy by EBRT show comparable biochemical control rates to patients receiving seed brachytherapy, whereas patients receiving 70 Gy show significantly worse outcome.

Comparison of PDR brachytherapy and external beam radiation therapy in the case of breast cancer.

Pulsed dose rate brachytherapy (PDR) was compared to external beam radiation therapy (EBRT) in the case of breast cancer. The benefits were figured out by evaluation of dosimetric parameters and calculating the normal tissue complication probability (NTCP). PDR plans were set up for five randomly chosen left-sided breast cancer patients delivering a total dose of 50.4 Gy to the target (dose rate 0.8 Gy h(-1)). For EBRT five left-sided breast cancer patients were planned using 3D-conformal tangential photon beams with a prescribed total dose of 50 Gy (2 Gy/fraction) to the total breast volume. For plan ranking and NTCP calculation the physical dose was first converted into the biologically effective dose (BED) and then into the normalized total dose (NTD) using the linear quadratic model with an alpha/beta ratio of 3 Gy. In PDR the relative effectiveness (RE) was calculated for each dose bin of the differential dose volume histogram to get the BED. NTCPs were calculated for the ipsilateral lung and the heart as contoured on CT slices based on the Lyman model and the Kutcher reduction scheme. Dosimetric parameters as V(th) (percentage of the total volume exceeding a threshold dose) and Jackson's f(dam) (fraction of the organ damaged) were also used to figure out the benefits. The comparison of calculated NTCPs in PDR and EBRT showed no difference between these two modalities. All values were below 0.01%. f(dam) derived from EBRT was always higher (mean value 8.95% versus 1.21% for the lung). The mean V(10) and V(20) of the lung related to BED were 6.32% and 1.72% for PDR versus 11.72% and 9.59% for EBRT. When using dosimetric parameters as V(th) and f(dam), PDR was mostly superior to EBRT in respect of sparing normal tissues. NTCP calculation as a single method of modality ranking showed a lack of information, especially when normal tissue was exposed to low radiation doses.

Image-guided adaptive brachytherapy for cervix carcinoma.

Sectional imaging has played an important role in the management of cervical cancer, in particular for staging, and is now considered for image-guided treatment planning, in particular for brachytherapy. Image-based three-dimensional brachytherapy is a relatively new approach that is increasingly replacing the traditional two-dimensional X-ray-based method. This overview focuses on the potential and some practicalities of this approach. The pros and cons of computed tomography- and magnetic resonance imaging-based brachytherapy are considered and an overview of the current state of research is given. The first encouraging clinical results are presented and future perspectives are discussed.

3D conformal HDR-brachy- and external beam therapy plus simultaneous cisplatin for high-risk cervical cancer: clinical experience with 3 year follow-up.

BACKGROUND AND PURPOSE: To assess feasibility, safety and effectiveness of CT-based 3D conformal external beam radiotherapy (EBRT) plus concurrent cisplatin and MRI-based 3D conformal HDR-brachytherapy (HDR-BT) in the treatment of advanced cervical cancer. PATIENTS AND METHODS: A total of 48 patients with advanced cervical cancer, treated with CT-based EBRT plus simultaneous cisplatin chemotherapy (40mg/m(2) of body surface per week for 5 weeks) and MRI-based HDR-BT, were included for analysis. RESULTS: All patients completed radiotherapy as planned and 90% received at least four cycles chemotherapy. Frequencies of CTC grade 3 anaemia, grade 3-4 leucopenia and grade 3 thrombocytopenia were 4, 23 and 10%, respectively. Two patients developed deep vein thrombosis and one non-fatal pulmonary embolism. Grade 4 genitourinary late side effects (bladder) occurred in 2 patients. No grade 3-4 gastrointestinal side effects were observed. Complete response (CR) was obtained in 45 patients (94%). After a median follow-up of 33 months, 27 patients were disease free. Actuarial overall survival at 3 years was 61%, progression free survival 51% and continuous complete remission for true pelvis 85%. CONCLUSIONS: MRI-based 3D HDR-BT and 3D EBRT plus cisplatin appears to be safe and effective, although acute haematological toxicity is increased. Gastrointestinal morbidity is minimal when prospectively applying 3D dose volume constraints and MRI-based 3D dose volume adaptation.

A multicenter study to quantify systematic variations and associated uncertainties in source positioning with commonly used HDR afterloaders and ring applicators for the treatment of cervical carcinomas.

PURPOSE: The reconstruction of radiation source position in the treatment planning system is a key part of the applicator reconstruction process in high dose rate (HDR) brachytherapy treatment of cervical carcinomas. The steep dose gradients, of as much as 12%/mm, associated with typical cervix treatments emphasize the importance of accurate and precise determination of source positions. However, a variety of methodologies with a range in associated measurement uncertainties, of up to ±2.5 mm, are currently employed by various centers to do this. In addition, a recent pilot study by Awunor et al. ["Direct reconstruction and associated uncertainties of (192)Ir source dwell positions in ring applicators using gafchromic film in the treatment planning of HDR brachytherapy cervix patients," Phys. Med. Biol. 58, 3207-3225 (2013)] reported source positional differences of up to 2.6 mm between ring sets of the same type and geometry. This suggests a need for a comprehensive study to assess and quantify systematic source position variations between commonly used ring applicators and HDR afterloaders across multiple centers. METHODS: Eighty-six rings from 20 European brachytherapy centers were audited in the form of a postal audit with each center collecting the data independently. The data were collected by setting up the rings using a bespoke jig and irradiating gafchromic films at predetermined dwell positions using four afterloader types, MicroSelectron, Flexitron, GammaMed, and MultiSource, from three manufacturers, Nucletron, Varian, and Eckert & Ziegler BEBIG. Five different ring types in six sizes (Ø25-Ø35 mm) and two angles (45° and 60°) were used. Coordinates of irradiated positions relative to the ring center were determined and collated, and source position differences quantified by ring type, size, and angle. RESULTS: The mean expanded measurement uncertainty (k = 2) along the direction of source travel was ±1.4 mm. The standard deviation associated with the source position reproducibility was within ±1.0 mm for all afterloaders. Maximum source positional variations of 2.1 and 3.9, 1.8 and 5.4, and 2.3 and 3.4 mm were observed at standard treatment positions for the Ø26, Ø30, and Ø32 mm sized 45° and 60° rings, respectively. Mean positional differences between a majority of the rings were within ±1.0 mm. Mean positional differences between a majority of the intracenter ring sets were within the expanded measurement uncertainty. When comparing the 45°-60° source paths, mean differences of 1.6, 0.9, and 0.9 mm were observed across the Ø26, Ø30 (MicroSelectron), and Ø32 mm (GammaMed) rings, respectively. When comparing to manufacturer source path models, maximum offsets of 1.9 and 2.1, 2.6 and 2.3, and 0.8 and 1.6 mm were observed for the Ø26, Ø30 (MicroSelectron), and Ø30 mm (Flexitron) sized 45° and 60° rings, respectively. When comparing the audit to ring commissioning data of participating centers, mean differences of up to 2.4 mm were observed. CONCLUSIONS: A majority of the audited rings showed a good degree of manufacturer consistency; however, substantial positional variation observed between some rings emphasizes the importance of commissioning each ring before clinical use. Differences observed between audit and commissioning data also indicate some variation in source treatment positions across centers.

Dose-volume histograms based on serial intravascular ultrasound: a calculation model for radioactive stents.

BACKGROUND AND PURPOSE: Radioactive stents are under investigation for reduction of coronary restenosis. However, the actual dose delivered to specific parts of the coronary artery wall based on the individual vessel anatomy has not been determined so far. Dose-volume histograms (DVHs) permit an estimation of the actual dose absorbed by the target volume. We present a method to calculate DVHs based on intravascular ultrasound (IVUS) measurements to determine the dose distribution within the vessel wall. MATERIALS AND METHODS: Ten patients were studied by intravascular ultrasound after radioactive stenting (BX Stent, P-32, 15-mm length) to obtain tomographic cross-sections of the treated segments. We developed a computer algorithm using the actual dose distribution of the stent to calculate differential and cumulative DVHs. The minimal target dose, the mean target dose, the minimal doses delivered to 10 and 90% of the adventitia (DV10, DV90), and the percentage of volume receiving a reference dose at 0.5 mm from the stent surface cumulated over 28 days were derived from the DVH plots. Results were expressed as mean+/-SD. RESULTS: The mean activity of the stents was 438+/-140 kBq at implantation. The mean reference dose was 111+/-35 Gy, whereas the calculated mean target dose within the adventitia along the stent was 68+/-20 Gy. On average, DV90 and DV10 were 33+/-9 Gy and 117+/-41 Gy, respectively. Expanding the target volume to include 2.5-mm-long segments at the proximal and distal ends of the stent, the calculated mean target dose decreased to 55+/-17 Gy, and DV 90 and DV 10 were 6.4+/-2.4 Gy and 107+/-36 Gy, respectively. CONCLUSIONS: The assessment of DVHs seems in principle to be a valuable tool for both prospective and retrospective analysis of dose-distribution of radioactive stents. It may provide the basis to adapt treatment planning in coronary brachytherapy to the common standards of radiotherapy.

Prescribing, recording, and reporting in endovascular brachytherapy. Quality assurance, equipment, personnel and education.

Endovascular brachytherapy is a new, rapidly growing field of interest in radiotherapy for the prevention of neointimal hyperplasia after angioplasty in both coronary and peripheral arteries. Many physics aspects of these treatments have already been addressed in the report of the American Association of Physicists in Medicine task group on 'Intravascular brachytherapy', but up to now there are no generally accepted recommendations for recording and reporting radiation doses and volumes. The terminology to be used by all individuals involved in such treatments (radiation oncologists, physicists, and interventionalists) is not clearly defined. The Endovascular Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology Working Group in this document presents recommendations for a common language for general use in endovascular brachytherapy. This proposal addresses general terms and concepts for target and dose specification as well as detailed recommendations for dose prescription, recording and reporting in endovascular brachytherapy for both peripheral and coronary arteries. Additionally, quality assurance and radiation safety aspects are briefly addressed, as are aspects related to equipment, personnel, and training and education related to endovascular brachytherapy.

TU-E-213CD-01: Image Guided Adaptive Brachytherapy for Cervical Cancer.

Image-guidance plays an important role in modern radiation therapy, predominantly in external beam planning and delivery. In contrast, brachytherapy is still largely based on systems originally developed in the early 20th century. In recent years, with the advent of high/pulsed dose rate (HDR/PDR) afterloading technology, advanced treatment planning systems and CT and MRI compatible applicators, image-guided adaptive brachytherapy treatments are now achievable. With image guidance, the target can be delineated more precisely, resulting in delivering more controlled doses of radiation to the target while sparing surrounding healthy tissue. GEC-ESTRO guidelines are crucial for implementing robust and standardized image guided adaptive brachytherapy (IGABT). They rely on MRI-guided planning for cervical cancer. MRI can be performed for each brachytherapy (BT) fraction to adaptively plan and deliver the desired radiation dose with less toxicity to surrounding tissues. MR imaging has its advantages, but also challenges and limitations (image artifacts and distortion related to magnetic nonlinearity, MR sequence selection, accuracy of 3D applicator reconstruction) that need addressed. Moreover, MRI technology is not readily available in most Radiation Oncology departments, making its implementation hard. In such settings, CT or US-based planning can be used despite lacking the desired soft tissue resolution to accurately depict the target. Hybrid approaches have been proposed, where a first BT fraction is planed based on MRI, and subsequent fractions are performed with CT-guidance. Moreover, new intracavitary/interstitial applicators are becoming available and data from centers using existent applicators is maturing. Regardless of the type of adaptive image guided and applicators used, there are still ongoing debates regarding the prescription, the relevance of point A dose, treatment planning in general, and the use of inverse planning in particular, role of model-based dose calculation algorithms, adaptive strategies, intrafraction variability, in-vivo dosimetry, dose summation with external beam treatments, to mention just some of the challenges raised by implementing this treatment technique. This symposium is proposing to address all of these issues and update the community at large on the status of image guided adaptive brachytherapy for cervical cancer. LEARNING OBJECTIVES: 1. To discuss the physics perspective of role of IGABT in management of cervical cancer. 2. To compare IGABT approaches: MRI, CT, US, and Hybrid 3. To present the advantages, challenges, and limitations of MRI for IGABT. 4. To discuss hot topics in IGABT including planning strategies, role of model-based dose calculation algorithms, new applicators, dose specification.

Quantification of dose perturbation by plaque in vascular brachytherapy.

BACKGROUND: Dose prescription and reporting in vascular brachytherapy (VBT) is based on the assumption that the vessel wall is water equivalent, which does not consider a possible dose perturbation by plaque. As the extent of this perturbation is unknown, we aimed to quantify dose attenuation by atherosclerotic plaque for beta- and gamma-radiation. MATERIAL AND METHODS: The dose delivered from Strontium-90/Yttrium-90 ((90)Sr/Y) and Iridium-192 ((192)Ir) sources with and without human peripheral arteries ((90)Sr/Y: n = 38, (192)Ir: n = 7) surrounding the respective delivery catheter was determined with radiochromic films. Plaque and vessel wall thickness were measured using light microscopy. From the ratio-attenuated doseunattenuated dose (dose perturbation factor: DPF) we determined averaged attenuation coefficients for atherosclerotic plaque (micro(P)) and the residual part of the vessel wall (micro(W)) by regression analysis based on the function DPF = exp(-micro(P) * plaque thickness -micro(W) * residual wall thickness). RESULTS: Attenuation in case of (192)Ir was less than the measurement uncertainties. For beta-radiation correlation was found by discrimination between calcified and noncalcified plaque. Classifying noncalcified plaque as normal arterial tissue, the regression coefficient was r = 0.845 at micro(P)= 0.5356 mm(-1) and micro(W) = 0.0663 mm(-1). CONCLUSIONS: Vascular brachytherapy with beta radiation in calcified arteries results in significant dose attenuation within the vessel wall, which can be calculated on knowing the vascular morphometry. Thus, plaque thickness should be taken into account in treatment planning and retrospective analyses.

Percutaneous interventions in radiation-associated coronary in-stent restenosis.

This study was performed to evaluate the outcome of percutaneous revascularization in "edge restenoses" developing after radioactive stent implantation in de novo and in-stent lesions. Twenty-one consecutive patients undergoing target lesion revascularization (TLR) at any follow-up after phosphorus-32 radioactive stent implantation were included in this study. We assessed the incidence of death, myocardial infarction, repeated TLR and recurrent angina over the following 18 months. After 6 months, TLR rate was 28.6%, and no stent thromboses, deaths or Q-wave myocardial infarctions occurred. Among the patients with TLR there were significantly more subjects who had received a radioactive stent in a previous in-stent restenosis (66.7% vs. 0% in patients without second restenosis; P <0.001), or who had received two radioactive stents (83.3% vs. 33.3%; P = 0.038). After 18 months, TLR rate was 33.3%, and two patients (9.5%) had died. Restenosis after intravascular radiotherapy can be safely treated by percutaneous interventional techniques, yielding an acceptable clinical result within 18 months.