Robert Hudej

Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group: considerations and pitfalls in commissioning and applicator reconstruction in 3D image-based treatment planning of cervix cancer brachytherapy.

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 (< or =5 mm) is recommended or alternatively 3D MR sequences with isotropic voxel sizes. Preferably, contouring and reconstruction should be performed in the same image series in order to avoid fusion uncertainties. Clear and correct strategies for the applicator reconstruction will ensure that reconstruction uncertainties have limited impact on the delivered dose. Under well-controlled circumstances the reconstruction uncertainties are in general smaller than other brachytherapy uncertainties such as contouring and organ movement.

Uncertainties of target volume delineation in MRI guided adaptive brachytherapy of cervix cancer: a multi-institutional study.

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) (p<0.05). CONCLUSIONS 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.

Comparison of 3D MRI with high sampling efficiency and 2D multiplanar MRI for contouring in cervix cancer brachytherapy

Comparison of 3D MRI with high sampling efficiency and 2D multiplanar MRI for contouring in cervix cancer brachytherapy Background. 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. Patients 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 inter-observer 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 inter-approach 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. Conclusions. 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.

Distance Deviation Measure of Contouring Variability

Abstract Background. Several methods that are currently used for contouring analysis have problems providing reliable and/ or meaningful results. In this paper a solution to these problems is proposed in a form of a novel measure, which was developed based on requirements defined for contouring studies. Materials and methods. The proposed distance deviation measure can be understood as an extension of the closest point measures in such a way that it does not measure only distances between points on contours but rather analyse deviation of distances to both/all contours from each image point/voxel. The obtained result is information rich, reliable and provided in a form of an image, enabling detailed topographic analysis. In addition to image representation, results can be further processed into angular representation for compact topographic analysis or into overall scalar estimates for quick assessment of contour disagreement. Results. Distance deviation method is demonstrated on a multi observer contouring example with complex contour shapes, i.e., with pronounced extremes and void interior. 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 to interpret. It can be used in various situations, regarding the presence of reference contour or multiple test contours.

MRI-assisted cervix cancer brachytherapy pre-planning, based on application in paracervical anaesthesia: final report.

Abstract 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.

Multicentre evaluation of a novel vaginal dose reporting method in 153 cervical cancer patients

BACKGROUND AND PURPOSE Recently, 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 METHODS In a subset of patients from the EMBRACE study, vaginal doses were evaluated. Doses at the applicator surface left/right and anterior/posterior and at 5mm depth were measured. In addition, the dose at the Posterior-Inferior Border of Symphysis (PIBS) vaginal dose point and PIBS±2cm, corresponding to the mid and lower vagina, was measured. RESULTS 153 patients from seven institutions were included. Large dose variations expressed in EQD2 with α/β=3Gy 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 5mm 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±2cm was 41 (3-81)Gy, 54 (32-109)Gy and 5 (1-51)Gy, respectively. At PIBS+2cm (mid vagina) dose variation was coming from BT. The variation at PIBS-2cm (lower vagina) was mainly dependent on EBRT field border location. CONCLUSIONS This 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.

Definitive radiotherapy for uterine cervix cancer: long term results for patients treated in the period from 1998 till 2002 at the Institute of Oncology Ljubljana

Abstract 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.

Virtual modelling of novel applicator prototypes for cervical cancer brachytherapy

Abstract Background Standard 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. Results CAT-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. Conclusions Using 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.

Isodose surface volumes in cervix cancer brachytherapy: Change of practice from standard (Point A) to individualized image guided adaptive (EMBRACE I) brachytherapy

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 (<25 cm3), intermediate (25-35 cm3) and large (>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.

54 oral: Frequency-Distribution Mapping of HR-CTV in Locally Advanced Cervix Cancer: A New Tool for Development of Novel Brachytherapy Techniques

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.