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Purpose: The aim of this study was to investigate the influence of brachytherapy technique and applicator type on target dose, isodose surface volumes, and organ-at-risk (OAR) dose. Methods and Materials: Nine hundred two patients treated with tandem/ovoids (T&O) (n = 299) and tandem/ring (T&R) (n = 603) applicators from 16 EMBRACE centers were analyzed. Patients received external beam radiation therapy and magnetic resonance imaging guided brachytherapy with dose prescription according to departmental practice. Centers were divided into 4 groups, according to applicator/technique: Ovoids and ring centers treating mainly with the intracavitary (IC) technique and ovoids and ring centers treating routinely with the intracavitary/interstitial (IC/IS) technique. V85Gy EQD210, CTVHR D90% (EQD210), and bladder, rectum, sigmoid, and vaginal 5-mm lateral-point doses (EQD23) were evaluated among center groups. Differences between T&O and T&R were tested with multivariable analysis. Results: For similar point A doses, mean CTVHR D90% was 3.3 Gy higher and V85Gy was 23% lower for ring-IC compared with ovoids-IC centers (at median target volumes). Mean bladder/rectum doses (D2cm3 and ICRU-point) were 3.2 to 7.7 Gy smaller and vaginal 5-mm lateral-point was 19.6 Gy higher for ring-IC centers. Routine use of IC/IS technique resulted in increased target dose, whereas V85Gy was stable (T&R) or decreased (T&O); reduced bladder and rectum D2cm3 and bladder ICRU-point by 3.5 to 5.0 Gy for ovoids centers; and similar OAR doses for ring centers. CTVHR D90% was 2.8 Gy higher, bladder D2cm3 4.3 Gy lower, rectovaginal ICRU-point 4.8 Gy lower, and vagina 5-mm lateral-point 22.4 Gy higher for ring-IC/IS versus ovoids-IC/IS centers. The P values were

Background: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. Methods: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB–IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1–L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5–6 cycles, 1 day per cycle, plus 45–50 Gy external-beam radiotherapy delivered in 1·8–2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. Findings: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20–40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85–94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20–64), actuarial overall 5-year local control was 92% (95% CI 90–93). Actuarial cumulative 5-year incidence of grade 3–5 morbidity was 6·8% (95% CI 5·4–8·6) for genitourinary events, 8·5% (6·9–10·6) for gastrointestinal events, 5·7% (4·3–7·6) for vaginal events, and 3·2% (2·2–4·5) for fistulae. Interpretation: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. Funding: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems.

Purpose To describe the evolution of external beam radiation therapy (EBRT) from EMBRACE-I (general guidelines for EBRT) to the initial phase of the EMBRACE-II study (detailed protocol for EBRT). Methods and Materials EMBRACE-I enrolled 1416 locally advanced cervical cancer patients treated with chemoradiation including image-guided adaptive brachytherapy during 2008 to 2015. From March 2016 until March 2018, 153 patients were enrolled in the ongoing EMBRACE-II study, which involves a comprehensive detailed strategy and accreditation procedure for EBRT target contouring, treatment planning, and image guidance. EBRT planning target volumes (PTVs), treated volumes (V43 Gy), and conformity index (CI; V43 Gy/PTV) were evaluated in both studies and compared. Results For EMBRACE-I, conformal radiation therapy (60% of patients) or intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT; 40%) was applied with 45 to 50 Gy over 25 to 30 fractions to the elective clinical target volume (CTV). For pelvic CTVs (82%), median PTV and V43 Gy volumes were 1549 and 2390 mL, respectively, and CI was 1.54. For pelvic plus paraortic nodal (PAN) CTVs (15%), median PTV and V43 Gy volumes were 1921 and 2895 mL, and CI was 1.51. For pelvic CTVs treated with 45 to 46 Gy, the use of conformal radiation therapy was associated with a median V43 Gy volume that was 546 mL larger than with IMRT/VMAT. For pelvic CTVs treated with IMRT, the use of a dose prescription ≥48 Gy was associated with a median V43 Gy volumes that was 428 mL larger than with a dose prescription of 45 to 46 Gy. For EMBRACE-II, all patients were treated with: IMRT/VMAT, daily IGRT, 45 Gy over 25 fractions for the elective CTV, and simultaneously integrated boost for pathologic lymph nodes. For pelvic CTVs (61%), median PTV and V43 Gy volumes were 1388 and 1418 mL, and CI was 1.02. For pelvic plus PAN CTVs (32%), median PTV and V43 Gy volumes were 1720 and 1765 mL, and CI was 1.03. From EMBRACE-I to initial II, median V43 Gy was decreased by 972 mL (41%) and 1130 mL (39%), and median CI decreased from 1.54 to 1.02 and 1.51 to 1.03 for pelvic and pelvic plus PAN irradiation, respectively. Conclusions Application of IMRT/VMAT, IGRT, and a 45-Gy dose provides the potential of higher conformality inducing significant reduction of treated volume. Adherence to a detailed protocol including comprehensive accreditation, as in EMBRACE-II, reduces considerably V43 Gy and V50 Gy and improves conformality and interinstitutional consistency.

Introduction/Background Despite modern techniques in external beam radiotherapy (EBRT), intensity modulated radiation therapy (IMRT) and stereotactic radiotherapy (SRT), brachytherapy (BT) remains one of the most important modalities for the treatment of advanced gynaecological cancer. In some special cases commercially available applicators for MRI-guided intracavitary/interstitial (IC/IS) BT do not offer proper target coverage. With the help of additive technologies, 3D-printed applicators can be tailored to the patient‘s tumour and anatomy. Methodology In this report two cases of gynaecological cancer, one vaginal and one recurrent endometrial cancer are presented. The design of the applicator was based on MRI images of the patient with the standard Varian vaginal cylinder inserted. Parallel and oblique needles were virtually added to the planning system to get the best possible coverage of the tumour while respecting the dose constraints to the organs at risk (OARs). Individual applicators were made from biocompatible polyamide PA 12 with selective laser sintering (SLS) technology (figure 1). The next BT was performed with an individual applicator in situ. Rectal ultrasound was used for needle guidance. The dose-volume histogram (DVH) parameters for each patient were compared according to the planning aims. The planning aim for D90 high-risk clinical target volume (CTV-THR) was to reach physical dose > 20.5 Gy per one BT fraction delivered in 24 pulses of pulsed dose rate (PDR) BT. Results The DVH parameters for both cases per one BT fraction are presented in table 1. The procedure and the implantation of the needles was performed without complications in regional anaesthesia. The applicator was well tolerated, no adverse effect was reported during the treatment or removal of the applicator. Conclusion The advantages of using an individually-designed multi-channel vaginal applicator are: better target coverage in advanced tumours extended in the vagina can be used in a narrow vagina implantation guidance of several oblique and parallel needles can be performed with minimized trauma to the surrounding tissue allows for the treatment of several tumour locations in the same BT fraction Disclosures Helena Barbara Zobec Logar, Robert Hudej and Manja Kobav have nothing to disclose.

BackgroundStandard applicators for cervical cancer Brachytherapy (BT) do not always achieve acceptable balance between target volume and normal tissue irradiation. We aimed to develop an innovative method of Target-volume Density Mapping (TDM) for modelling of novel applicator prototypes with optimal coverage characteristics. Patients and methods. Development of Contour-Analysis Tool 2 (CAT-2) software for TDM generation was the core priority of our task group. Main requests regarding software functionalities were formulated and guided the coding process. Software validation and accuracy check was performed using phantom objects. Concepts and terms for standardized workflow of TDM post-processing and applicator development were introduced.ResultsCAT-2 enables applicator-based co-registration of Digital Imaging and Communications in Medicine (DICOM) structures from a sample of cases, generating a TDM with pooled contours in applicator-eye-view. Each TDM voxel is assigned a value, corresponding to the number of target contours encompassing that voxel. Values are converted to grey levels and transformed to DICOM image, which is transported to the treatment planning system. Iso-density contours (IDC) are generated as lines, connecting voxels with same grey levels. Residual Volume at Risk (RVR) is created for each IDC as potential volume that could contain organs at risk. Finally, standard and prototype applicators are applied on the TDM and virtual dose planning is performed. Dose volume histogram (DVH) parameters are recorded for individual IDC and RVR delineations and characteristic curves generated. Optimal applicator configuration is determined in an iterative manner based on comparison of characteristic curves, virtual implant complexities and isodose distributions.ConclusionsUsing the TDM approach, virtual applicator prototypes capable of conformal coverage of any target volume, can be modelled. Further systematic assessment, including studies on clinical feasibility, safety and effectiveness are needed before routine use of novel prototypes can be considered.

PURPOSE: To investigate the isodose surface volumes (ISVs) for 85, 75 and 60 Gy EQD2 for locally advanced cervix cancer patients.MATERIALS AND METHODS: 1201 patients accrued in the EMBRACE I study were analysed. External beam radiotherapy (EBRT) with concomitant chemotherapy was followed by MR based image-guided adaptive brachytherapy (MR-IGABT). ISVs were calculated using a predictive model based on Total Reference Air Kerma and compared to Point A-standard loading systems. Influence of fractionation schemes and dose rates was evaluated through comparison of ISVs for α/β 10 Gy and 3 Gy.RESULTS: Median V85 Gy, V75 Gy and V60 Gy EQD210 were 72 cm3, 100 cm3 and 233 cm3, respectively. Median V85 Gy EQD210 was 23% smaller than in standard 85 Gy prescription to Point A. For small (35 cm3) CTVHR volumes, the V85 Gy was 57 cm3, 70 cm3 and 89 cm3, respectively. In 38% of EMBRACE patients the V85 Gy was similar to standard plans with 75-85 Gy to Point A. 41% of patients had V85 Gy smaller than standard plans receiving 75 Gy at Point A, while 21% of patients had V85 Gy larger than standard plans receiving 85 Gy at Point A.CONCLUSIONS: MR-IGABT and individualized dose prescription during EMBRACE I resulted in improved target dose coverage and decreased ISVs compared to standard plans used with classical Point A based brachytherapy. The ISVs depended strongly on CTVHR volume which demonstrates that dose adaptation was performed per individual tumour size and response during EBRT.

Background. Optimal applicator insertion is a precondition for the success of cervix cancer brachytherapy (BT). We aimed to assess feasibility and efficacy of MRI-assisted pre-planning, based on applicator insertion in para-cervical anaesthesia (PCA). Patients and methods. Five days prior to BT, the pre-planning procedure was performed in 18 cervix cancer patients: tandem-ring applicator was inserted under PCA, pelvic MRI obtained and applicator removed. Procedure tolerability was assessed. High risk clinical target volume (HR CTV) and organs at risk were delineated on the pre-planning MRI, virtual needles placed at optimal positions, and dose planning performed. At BT, insertion was carried out in subarachnoidal anaesthesia according to pre-planned geometry. Pre-planned and actual treatment parameters were compared. Results. Pre-planning procedure was well tolerated. Median difference between the pre-planned and actual needle insertion depth and position were 2 (0―10) mm and 4 (0―30) degrees, respectively. The differences between the pre-planned and actual geometric and dosimetric parameters were statistically non-significant. All actual needles were positioned inside the HR CTV and outside the organs at risk (OAR). Conclusions. Our pre-planning approach is well tolerated and effective. Pre-planned geometry and dose distribution can be reproduced at BT.

BACKGROUND AND AIM: We aimed to quantify target volume delineation uncertainties in cervix cancer image guided adaptive brachytherapy (IGABT).MATERIALS AND METHODS: Ten radiation oncologists delineated gross tumour volume (GTV), high- and intermediate-risk clinical target volume (HR CTV, IR CTV) in six patients. Their contours were compared with two reference delineations (STAPLE-Simultaneous Truth and Performance Level Estimation and EC- expert consensus) by calculating volumetric and planar conformity index (VCI and PCI) and inter-delineation distances (IDD).RESULTS: VCISTAPLE and VCIEC were 0.76 and 0.72 for HR CTV, 0.77 and 0.68 for IR CTV and 0.59 and 0.58 for GTV. Variation was most prominent caudally and cranially in all target volumes and posterolaterally in IR CTV. IDDSTAPLE and IDDEC for HR CTV (3.6±3.5 and 3.8±3.4 mm) were significantly lower than for GTV (4.8±4.2 and 4.2±3.5 mm) and IR CTV (4.7±5.2 and 5.2±5.6 mm) (pCONCLUSIONS: Due to lower delineation uncertainties when compared to GTV and IR CTV, HR CTV may be considered most robust volume for dose prescription and optimization in cervix cancer IGABT. Adequate imaging, training and use of contouring recommendations are main strategies to minimize delineation uncertainties.

Background and Purpose: Studies of contouring variation face a difficulty of meaningful comparison of contours. Although several measures of contouring disagreement were proposed, each of them has certain limitations that prevent its widespread use. The purpose of this work was to develop a novel measure that can provide meaningful results for a wide range of contour analysis studies. Materials and Methods: The proposed novel measure of contouring variability, i.e., a distance deviation measure, is based on distances from certain points on the analyzed image to closest points on all analyzed contours. By performing such analysis for all image points/voxels a new image is obtained, providing information of local contour agreement, given in absolute distance units (millimeters). To present such information rich results, three presentation methods are proposed: image representation for detailed topographic analysis, angular representation for compact topographic analysis, and an overall scalar estimate for quick assessment of the level of contour disagreement. Results: Distance deviation method is demonstrated on a multi observer contouring example with complex contour shapes, i.e., with presence of holes or excrescences. The results are presented using the three proposed methods. Conclusions: The proposed method can detect and measure contour variation irrespective of contour complexity and number of contour segments, while the obtained results are easy interpret. It can be used in various situations, regarding the presence of reference contour or multiple test contours.

PurposeThis study analyzed functioning and symptom scores for longitudinal quality of life (QoL) from patients with locally advanced cervical cancer who underwent definitive chemoradiation therapy with image guided adaptive brachytherapy in the EMBRACE study.Methods and MaterialsIn total, 744 patients at a median follow-up of 21 months were included. QoL was prospectively assessed using European Organization for Research and Treatment of Cancer Quality of Life core module 30 (EORTC QLQ-C30) and EORTC cervical cancer module 24 (CX24) questionnaires at baseline, then every 3 months during the first year, every 6 months in the second and third years, and finally yearly thereafter in patients with no evidence of disease. Outcomes were evaluated over time and compared to those from an age-matched female reference population.ResultsGeneral QoL and emotional and social functioning were impaired at baseline but improved during the first 6 months after treatment, to reach a level comparable to that of the reference population, whereas cognitive functioning remained impaired. Both social and role functioning showed the lowest scores at baseline but which increased after treatment to reach a plateau at 6 months and then declined slightly at 3 and 4 years. The overall symptom experience was elevated at baseline and decreased to a level within the range of that of the reference population. Similarly, tumor-related symptoms (eg, pain, appetite loss, and constipation), which were present before treatment, decreased substantially at the first follow-up after treatment. Several treatment-related symptoms developed either immediately after and persisted over time (diarrhea, menopausal symptoms, peripheral neuropathy, and sexual functioning problems) or developed gradually after treatment (lymphedema and dyspnea).ConclusionsThis longitudinal prospective QoL analysis showed that patients' general QoL and functioning were impaired before treatment compared to those of reference data. Several tumor-related symptoms resolved after treatment, and functioning and general QoL returned to that of the level of the reference population, indicating a transient impact of diagnosis and treatment. However, several treatment-related symptoms and problems did develop and persist, either immediately or gradually after treatment.

Background and purposeRecently, a vaginal dose reporting method for combined EBRT and BT in cervical cancer patients was proposed. The current study was to evaluate vaginal doses with this method in a multicentre setting, wherein different applicators, dose rates and protocols were used.Material and methodsIn a subset of patients from the EMBRACE study, vaginal doses were evaluated. Doses at the applicator surface left/right and anterior/posterior and at 5 mm depth were measured. In addition, the dose at the Posterior–Inferior Border of Symphysis (PIBS) vaginal dose point and PIBS±2 cm, corresponding to the mid and lower vagina, was measured.Results153 patients from seven institutions were included. Large dose variations expressed in EQD2 with α/β = 3 Gy were seen between patients, in particular at the top left and right vaginal wall (median 195 (range 61–947) Gy/178 (61–980) Gy, respectively). At 5 mm depth, doses were 98 (55–212) Gy/91 (54–227) Gy left/right, and 71 (51–145) Gy/67 (49–189) Gy anterior/posterior, respectively. The dose at PIBS and PIBS±2 cm was 41 (3–81) Gy, 54 (32–109) Gy and 5 (1–51) Gy, respectively. At PIBS+2 cm (mid vagina) dose variation was coming from BT. The variation at PIBS−2 cm (lower vagina) was mainly dependent on EBRT field border location.ConclusionsThis novel method for reporting vaginal doses coming from EBRT and BT through well-defined dose points gives a robust representation of the dose along the vaginal axis. In addition, it allows comparison of vaginal dose between patients from different centres. The doses at the PIBS points represent the doses at the mid and lower parts of the vagina. Large variations in dose throughout the vagina were observed between patients and centres.

The growth of 3,4,9,10-perylenetetracarboxylic dianhydride on Si(001) was examined in the light of varying flux of impinging molecules. Using atomic force microscopy and synchrotron radiation photoelectron spectroscopy Vollmer–Weber growth mode was observed on a wide range of growth rates. The island size initially decreases rapidly with growth rate, for the low growth rate reaches a minimum, and then gradually increases. Polarization dependent photoemission indicates that the orientation of the molecules within the islands remains flat on the substrate.

Current-voltage (I-V) characteristic measurements of Ag/3,4,9,10-Perylenetetracarboxylic Dianhydride/In/Si(001) heterostructures demonstrate that when the structure temperature approaches the In melting point the I-V characteristic changes from rectifying to Ohmic and the current amplitude increases by several orders of magnitude. The synchrotron radiation photoemission investigation of the 3,4,9,10-Perylenetetracarboxylic Dianhydride (PTCDA) layers of the same thickness grown on In in the same temperature range show strong In diffusion throughout the PTCDA layers as thick as 1 μm. The In 4 PTCDA coordination compound was not observed on the PTCDA surface and it appears to be limited to the region near the In/PTCDA interface [1].

Samples comprising 1-μm-thick layers of 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) sandwiched between top-most In contact and bottom-most Ag contact were synthesized on n-Si(100) substrates. Current–voltage (I–V) characteristics were measured on the structures with all the layers evaporated in sequence, and on the structures with air exposed PTCDA/In and Ag/PTCDA interfaces. The current transport in the structures fabricated without interruption of vacuum is controlled by the space charge and by the traps. Air exposure of the In/PTCDA interface introduces additional trap sites in the PTCDA layer, yielding the space-charge-limited current in the presence of traps, exponentially distributed in energy, and with a hopping transport mobility. Air exposure of the Ag/PTCDA interface introduces a discrete level of traps in addition to exponentially distributed traps.

Transient photocurrent measurements were employed to investigate the electronic charge transport in thin layers of 3,4,9,10-perylenetetracarboxylic dianhydride deposited by high-vacuum evaporation onto In-covered Si(001) substrates. Measurements performed at two different bias polarities indicate that both holes and electrons are transported in the direction perpendicular to the molecular layers. Charge transport is strongly dependent on the electric field.

Electronic transport measurements of Ag/3,4,9,10-perylenetetracarboxylic dianhydride In/Si(001) heterostructures demonstrate that when the structure temperature approaches the In melting point a current-voltage characteristic changes from rectifying to ohmic. The synchrotron radiation photoemission investigation of the 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) layers of the same thickness grown on In in the same temperature range show strong In diffusion throughout the PTCDA layers as thick as 1 μm. The formation of In-related coordination compound appears to be limited to the region near the In/PTCDA interface.

The penetration resistance of a prototypical model-membrane system (HS-(CH2)(11)-OH self-assembled monolayer (SAM) on Au(111)) to the tip of an atomic force microscope (AFM) is investigated in the presence of different solvents. The compressibility (i.e., height vs tip load) of the HS-(CH2)(11)-OH SAM is studied differentially, with respect to a reference structure. The reference consists of hydrophobic alkylthiol molecules (HS-(CH2)(17)-CH3) embedded as nanosized patches into the hydrophilic SAM by nanografting, an AFM-assisted nanolithography technique. We find that the penetration resistance of the hydrophilic SAM depends on the nature of the solvent and is much higher in the presence of water than in 2-butanol. In contrast, no solvent-dependent effect is observed in the case of hydrophobic SAMs. We argue that the mechanical resistance of the hydroxyl-terminated SAM is a consequence of the structural order of the solvent-SAM interface, as suggested by our molecular dynamics simulations. The simulations show that in the presence of 2-butanol the polar head groups of the HS-(CH2)(11)-OH SAM, which bind only weakly to the solvent molecules, try to bind to each other, disrupting the local order at the interface. On the contrary, in the presence of water the polar head groups bind preferentially to the solvent that, in turn, mediates the release of the surface strain, leading to a more ordered interface. We suggest that the mechanical stabilization effect induced by water may be responsible for the stability of even more complex, real membrane systems.

Background. The aim of this retrospective study was to analyse results of the two-dimensional (2D) uterine cervix cancer treatment at the Institute of Oncology Ljubljana from 1998 till 2002, before the three-dimensional (3D) approach was introduced in our clinical practice. Methods. Ninety-eight patients with the following FIGO stage distribution were analysed: 10% IB, 7% IIA, 37% IIB, 4% IIIA and 42% IIIB. The influence of age, haemoglobin level, histology, grade, stage, lymph node status, cumulative point A dose, and an overall treatment time on the survival and local control (LC) were evaluated. Acute and late side effects were assessed. Results. Five and 8-year overall survival (OS), disease specific survival (DSS) and LC rate were as follows: 47.2% and 43.0%, 54.7% and 53.4%, 74.9% and 72.5%, respectively. Point A dose and histology of the tumour influenced OS, positive lymph nodes DSS and point A dose LC rate. Probability of grade three and four late complications in the first five years was 7.1% for gastrointestinal tract and 3.3% for genitourinary system and vagina. Conclusions. Point A dose was independent predictor of OS and LC rate, lymph node status predicted DSS, while histology of the tumour influenced OS.

Introduction: MRI sequences with short scanning times may improve accessibility of image guided adaptive brachytherapy (IGABT) of cervix cancer. We assessed the value of 3D MRI for contouring by comparing it to 2D multi-planar MRI. Material and methods: In 14 patients, 2D and 3D pelvic MRI were obtained at IGABT. High risk clinical target volume (HR CTV) was delineated by 2 experienced radiation oncologists, using the conventional (2D MRI-based) and test (3D MRI-based) approach. The value of 3D MRI for contouring was evaluated by using the inter-approach and interobserver analysis of volumetric and topographic contouring uncertainties. To assess the magnitude of deviation from the conventional approach when using the test approach, the inter-approach analysis of contouring uncertainties was carried out for both observers. In addition, to assess reliability of 3D MRI for contouring, the impact of contouring approach on the magnitude of inter-observer delineation uncertainties was analysed. Results: No approach- or observer - specific differences in HR CTV sizes, volume overlap, or distances between contours were identified. When averaged over all delineated slices, the distances between contours in the interapproach analysis were 2.6 (Standard deviation (SD) 0.4) mm and 2.8 (0.7) mm for observers 1 and 2, respectively. The magnitude of topographic and volumetric inter-observer contouring uncertainties, as obtained on the conventional approach, was maintained on the test approach. This variation was comparable to the inter-approach uncertainties with distances between contours of 3.1 (SD 0.8) and 3.0 (SD 0.7) mm on conventional and test approach, respectively. Variation was most pronounced at caudal HR CTV levels in both approaches and observers. Conclusion: 3D MRI could potentially replace multiplanar 2D MRI in cervix cancer IGABT, shortening the overall MRI scanning time and facilitating the contouring process, thus making this treatment method more widely employed.

Compared to film radiography, the use of CT images for gynecologic radiotherapy represents a significant improvement, as it provides an accurate 3D representation of the patients' anatomy. In CT based brachytherapy treatment planning, it is important to use CT images with a slice thickness as small as 1 mm, to enable accurate applicator reconstruction. To avoid a deterioration of the images by streak artifacts, the use of plastic rather than metal applicators is recommended. Because of its superior soft tissue contrast, MRI is becoming the imaging modality of choice in gynecologic radiotherapy. A variety of contrast mechanisms can be applied, simply by changing the pulse sequences in a protocol. Several sequences applied for gynecologic malignancies are described. T2-weighted sequences are particularly important because tumors can be well distinguished from the surrounding tissue. A drawback of MRI is that it is prone to artifacts that distort the geometry, particularly close to the body surface, and near brachytherapy applicators. The heating that may occur in conductive circuits such as guidewires and catheters requires specific attention in brachytherapy applications. While the introduction of 3T MRI scanners may improve image quality even more, further work is required, in particular for brachytherapy, to mitigate these artifacts.

Image-guided brachytherapy in cervical cancer is increasingly replacing X-ray based dose planning. In image-guided brachytherapy the geometry of the applicator is extracted from the patient 3D images and introduced into the treatment planning system; a process referred to as applicator reconstruction. Due to the steep brachytherapy dose gradients, reconstruction errors can lead to major dose deviations in target and organs at risk. Appropriate applicator commissioning and reconstruction methods must be implemented in order to minimise uncertainties and to avoid accidental errors. Applicator commissioning verifies the location of source positions in relation to the applicator by using auto-radiography and imaging. Sectional imaging can be utilised in the process, with CT imaging being the optimal modality. The results from the commissioning process can be stored as library applicators. The importance of proper commissioning is underlined by the fact that errors in library files result in systematic errors for clinical treatment plans. While the source channel is well visualised in CT images, applicator reconstruction is more challenging when using MR images. Availability of commercial dummy sources for MRI is limited, and image artifacts may occur with titanium applicators. The choice of MR sequence is essential for optimal visualisation of the applicator. Para-transverse imaging (oriented according to the applicator) with small slice thickness (

Purpose To report on preliminary results of a prospective study on MRI-assisted cervix cancer brachytherapy pre-planning. Material and methods In six locally advanced cervix cancer patients, five days before the first brachytherapy fraction, tandem & ring applicator was inserted under para-cervical anaesthesia, MRI performed and applicator removed. Procedure-time and patient-tolerability were recorded. High risk CTV and organs at risk were delineated, virtual needles placed and dose planning performed. At brachytherapy, insertion was carried out under subarachnoidal anaesthesia, according to pre-planned geometry. Pre-planned and actual needle positions and DVH parameters were compared. Results The procedure was well tolerated and short. All inserted needles were inside high risk CTV and outside organs at risk. Differences in pre-planned and actual DVH parameters and implant geometry were small. Conclusions The procedure was well tolerated and feasible. Pre-planned geometry could be reproduced thoroughly at brachytherapy application.

Purpose To perform a qualitative and quantitative comparison of different treatment planning methods used in different centres for MRI-based brachytherapy (BT) of cervical cancer. Materials and methods Two representative patients with advanced cervical cancer (1 "limited volume case"; 1 "extensive volume case") were planned for brachytherapy (BT) with a tandem-ring applicator by six different centres. During a workshop all centres produced an institutional standard plan and an MRI-based adaptive treatment plan for each case. Optimisation was based on the fractionation schedule (HDR, PDR) and method according to the institutional protocol. Results The loading pattern, dwell times, shape of the point A isodose varied considerably between institutional standard plans, as did dose–volume parameters for high risk CTV (HR-CTV) and also for the D 2cc for OAR, violating the dose–volume constraints in many situations. During optimisation, the centres stayed as close as possible to the standard loading pattern and dwell times. The dose distributions and dose–volume parameters between the plans from the different centres became much more comparable after optimisation. The prescribed dose to the HR-CTV could be achieved in the limited volume case by all centres, in the extensive case only if additional needles were applied. Conclusion Treatment planning for gynaecologic brachytherapy based on different traditions shows less variation in regard to target coverage and OAR dose, when 3D image-based optimisation is performed with a uniform prescription protocol.

The purpose of the present study was to evaluate the introduction of 3D MRI-based treatment planning for uterine cervix cancer at the Institute of Oncology Ljubljana. The evaluation was based on standard versus optimized plan comparison. D90, V100 for high-risk clinical target volume and D2cc for bladder, rectum and sigmoid colon were compared. The results showed that by optimization it was possible to increase D90 and V100 for HR-CTV. At the same time, D2cc was reduced for all organs at risk except for rectum in large tumor group where D2cc was increased but still remained below the institutional dose restrictions. The study provided confirmation that 3D MRI-based treatment planning was indeed a considerable improvement of the planning process with respect to the standard planning.

Aim To analyze agreement between target volumes, delineated by two observers on transverse (T) and paratransverse (perpendicular to the long cervical axis – PT) MR images for cervix cancer brachytherapy. Materials and methods In 13 patients, High Risk-CTV (HR-CTV) was outlined by two observers in T and PT MR image plane, respecting the GYN GEC-ESTRO recommendations for 3D-image based cervix cancer brachytherapy [1] . Contouring time was measured. HR-CTV sizes were compared, and conformity index (CI) was assessed. Interobserver variations in contour-extent along eight radial directions were compared between delineation planes. After applying a standard treatment plan, an intercomparison of DVH-parameters V100, D90, and D100 for the HR-CTV was carried out. Results Contouring time was slightly longer in T than PT orientation. Interplane CI did not differ significantly between observers (0.72 vs. 0.71), nor did the interobserver CI between planes (0.79 vs. 0.78). Variations in contour-extent between different radial directions and interplane deviations in DVH parameters were non-significant. Conclusion Contouring in PT, as compared to T plane, allows for a “circumferential view of the cervix” and facilitates comprehensive understanding of spatial relations between the applicator and patho-anatomical structures. It is marked by a lower contouring difficulty and leads to a comparable outcome in terms of DVH parameters. Interobserver inconsistencies can be minimized by systematic training and following the published recommendations.

The solid-state solar cells comprising dye-sensitized nanostructured SnO and vacuum-evaporated 3,4,9,10-perylene tetracarboxylic dianhydride (PTCDA) layers exhibit significant photoresponse. Despite of unfavorable electronic energy level alignment at the dye/PTCDA interface, photon-to-electron conversion efficiencies as high as 1% were observed.

Purpose: Reported local failure rates for FIGO stage II-IVA vaginal cancer usually range between 20% and 60%, even in recent series. In this study we investigate the clinical feasibility and report about the first treatment outcomes of MRI image guided brachytherapy (IGBT) in these pts using the same strategy as recently developed for cervix cancer. Materials: Forty pts with vaginal cancer were treated at our institution from 1999-2006. Thirteen pts met the inclusion criteria for this study and received IGBT based on a prospective protocol. FIGO stage distribution was: stage II=4, stage III=5, stage IV=4. Five pts had positive pelvic lymph nodes and in 7 pts tumour size was >5cm. All pts received EBRT (40-50Gy) and 11 pts concurrent chemotherapy (9 cisplatin and 2 MMC+5-FU). IGBT dose prescription was either 4x7 Gy (HDR) or 35-40 Gy (0.5-0.8Gy; PDR) to the HR CTV. In 10 cases a combined intravaginal/interstitial application technique was used. Based on the recent developments in the treatment of cervical cancer pts with IGBT (Gyn GEC ESTRO Recommendations), systematic concepts for HR CTV, OAR, biological modelling, DVH-analysis, dosevolumeadaptation (D90, D2cc), and dose escalation were integrated into the treatment (planning) of all pts. Reported doses were converted to the equivalent dose in 2Gy (EQD2) applying the LQ-model (α/β of 10 for tumour and 3 for OAR). Clinical results were calculated using the KaplanMeier method. Results: Spatial relations between vaginal cylinder +/needle applicators, HR CTV, and OAR were clearly visible on MRI in all cases. Mean total prescribed dose was 80Gy EQD2 (1SD±8Gy).Mean D90 for HR CTV was 86Gy EQD2 (1SD±13Gy). For OAR the following mean D2cc were documented: 80Gy (1SD±20Gy) for bladder, 76Gy (1SD ±16Gy) for urethra, 70Gy (1SD ±9Gy) for rectum and 60Gy (1SD±9Gy) for sigmoid colon. All pts achieved complete remission at 3 months. Median follow up was 43 months (range: 1987 months). Two pts developed fistula (1 vesico-vaginal, 1 recto-vaginal) due to tumour-necrosis and 1 with distal vaginal involvement complete vaginal obliteration. Three recurrences were documented: 1 local in a patient with FIGO stage III and 2 distant. All these pts had positive pelvic lymph nodes. Actuarial local control, OS and CSS rates at three years were 92%, 85% and 85%. For FIGO stages II, III, and IV they were 100%, 80% and 75%, respectively. Conclusions: IGBT for vaginal cancer seems to be feasible similar to the concepts as introduced for cervix cancer. Clinical and dosimetric results of this first experience with IGBT for locally advanced vaginal cancer are promising. Local control and survival in this small series seems to be significantly higher than in previous reports about conventional X-ray based brachytherapy, associated at the same time with acceptable morbidity. However, further prospective studies with more pts are needed to confirm these results.