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Open access

Barbara Segedin, Jasenka Gugic and Primoz Petric

Background. Accurate applicator placement is a precondition for the success of gynaecological brachytherapy (BT). Unrecognized uterine perforation can lead to bleeding, infection, high doses to pelvic organs and underdosage of the target volume, resulting in acute morbidity, long-term complications and reduced chance of cure. We aimed to assess the incidence and clinical characteristics of our cases with uterine perforation, review their management and impact on the treatment course.

Patients and methods. In all patients, treated with utero-vaginal image guided BT for gynaecological cancer between January 2006 and December 2011, the CT/MR images with the applicator in place were reviewed. The incidence of uterine perforations was recorded. Clinical factors that may have predisposed to increased risk of perforation were recorded. Management of perforations and their impact on treatment course was assessed.

Results. 219 patients (428 applications) were suitable for analysis. Uterine perforation was found in 13 (3.0%) applications in 10 (4.6%) patients. The most frequent perforation site was posterior uterine wall (n = 9), followed by anterior wall (n = 2) and fundus (n = 2). All cases were managed conservatively, without complications. Prophylactic antibiotics were administered in 8 cases. In 4 patients, abdominal and/or transrectal ultrasound (US) guidance was used on subsequent applications for applicator insertion; adequate applicator placement was achieved and treatment completed as planned in all cases.

Conclusions. 3D imaging for BT planning enables accurate identification of uterine perforations. The incidence of perforations at our department is one of the lowest reported in the literature. US guidance of applicator insertion is useful and feasible, allowing to complete the planned treatment even in challenging cases.

Open access

Peter Rogel, Robert Hudej and Primoz Petric

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.

Open access

Irena Oblak, Primoz Petric, Franc Anderluh, Vaneja Velenik and Peter Fras

Long term outcome after combined modality treatment for anal cancer

Background. The aim of the retrospective study was to evaluate the effectiveness and toxicity of radiochemotherapy in patients with squamous cell carcinoma of the anal canal treated at a single institution.

Patients and methods. Between 1/2003 and 9/2010, 84 patients were treated with radical radiochemotherapy at the Institute of Oncology Ljubljana, Slovenia. The treatment consisted of 3-dimensional conformal external beam radiotherapy with concurrent chemotherapy (5-fluorouracil and mytomycin C), followed by brachytherapy or external beam boost. The toxicity of therapy and its effectiveness were assessed.

Results. The treatment was completed according to the protocol in 79.8% of patients. The median follow-up time of 55 survivors was 53 months (range: 16-105 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS), overall survival (OS) and colostomy-free survival (CFS) rates were 71%, 68%, 81%, 67% and 85%, respectively. No treatment-related mortality was observed. The most frequent acute side-effect of the treatment was radiodermatitis (grade 3-4 in 58.2% of patients). LENT-SOMA grade 3-4 late radiation side effects were observed in 15 (18%) patients. In patients with brachytherapy boost a trend of less late side effects was observed compared to patients with external beam boost (P=0.066). On multivariate analysis, complete clinical disease response was identified as an independent prognostic factor for LRC, DFS and DSS, the salvage surgery for LRC and DFS, whereas Hb below 120 g/l retained its independent prognostic value for OS.

Conclusions. Radiochemotherapy provides an excellent disease control and the survival with preserving anal sphincter function in majority of patients. Surgical salvage with abdominoperineal resection for persistent or recurrent disease has curative potential.

Open access

Barbara Segedin and Primoz Petric

Abstract

Background

Modern radiotherapy techniques enable delivery of high doses to the target volume without escalating dose to organs at risk, offering the possibility of better local control while preserving good quality of life. Uncertainties in target volume delineation have been demonstrated for most tumour sites, and various studies indicate that inconsistencies in target volume delineation may be larger than errors in all other steps of the treatment planning and delivery process. The aim of this paper is to summarize the degree of delineation uncertainties for different tumour sites reported in the literature and review the effect of strategies to minimize them.

Conclusions

Our review confirmed that interobserver variability in target volume contouring represents the largest uncertainty in the process for most tumour sites, potentially resulting in a systematic error in dose delivery, which could influence local control in individual patients. For most tumour sites the optimal combination of imaging modalities for target delineation still needs to be determined. Strict use of delineation guidelines and protocols is advisable both in every day clinical practice and in clinical studies to diminish interobserver variability. Continuing medical education of radiation oncologists cannot be overemphasized, intensive formal training on interpretation of sectional imaging should be included in the program for radiation oncology residents.

Open access

Primoz Petric, Robert Hudej, Noora Al-Hammadi and Barbara Segedin

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.

Open access

Primoz Petric, Robert Hudej, Peter Rogelj, Mateja Blas, Barbara Segedin, Helena Logar and Johannes Dimopoulos

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.

Open access

Helena Barbara Zobec Logar, Barbara Segedin, Robert Hudej and Primoz Petric

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.

Open access

Primoz Petric, Robert Hudej, Omar Hanuna, Primoz Marolt, Noora Mohammed A A Al-Hammadi, Mohamed P. Riyas and Barbara Segedin

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.

Open access

Noora Al-Hammadi, Palmira Caparrotti, Carole Naim, Jillian Hayes, Katherine Rebecca Benson, Ana Vasic, Hissa Al-Abdulla, Rabih Hammoud, Saju Divakar and Primoz Petric

Abstract

Background

During radiotherapy of left-sided breast cancer, parts of the heart are irradiated, which may lead to late toxicity. We report on the experience of single institution with cardiac-sparing radiotherapy using voluntary deep inspiration breath hold (V-DIBH) and compare its dosimetric outcome with free breathing (FB) technique.

Patients and methods

Left-sided breast cancer patients, treated at our department with postoperative radiotherapy of breast/chest wall +/– regional lymph nodes between May 2015 and January 2017, were considered for inclusion. FB-computed tomography (CT) was obtained and dose-planning performed. Cases with cardiac V25Gy ≥ 5% or risk factors for heart disease were coached for V-DIBH. Compliant patients were included. They underwent additional CT in V-DIBH for planning, followed by V-DIBH radiotherapy. Dose volume histogram parameters for heart, lung and optimized planning target volume (OPTV) were compared between FB and BH. Treatment setup shifts and systematic and random errors for V-DIBH technique were compared with FB historic control.

Results

Sixty-three patients were considered for V-DIBH. Nine (14.3%) were non-compliant at coaching, leaving 54 cases for analysis. When compared with FB, V-DIBH resulted in a significant reduction of mean cardiac dose from 6.1 +/– 2.5 to 3.2 +/– 1.4 Gy (p < 0.001), maximum cardiac dose from 51.1 +/– 1.4 to 48.5 +/– 6.8 Gy (p = 0.005) and cardiac V25Gy from 8.5 +/– 4.2 to 3.2 +/– 2.5% (p < 0.001). Heart volumes receiving low (10–20 Gy) and high (30–50 Gy) doses were also significantly reduced. Mean dose to the left anterior coronary artery was 23.0 (+/– 6.7) Gy and 14.8 (+/– 7.6) Gy on FB and V-DIBH, respectively (p < 0.001). Differences between FB- and V-DIBH-derived mean lung dose (11.3 +/– 3.2 vs. 10.6 +/– 2.6 Gy), lung V20Gy (20.5 +/– 7 vs. 19.5 +/– 5.1 Gy) and V95% for the OPTV (95.6 +/– 4.1 vs. 95.2 +/– 6.3%) were non-significant. V-DIBH-derived mean shifts for initial patient setup were ≤ 2.7 mm. Random and systematic errors were ≤ 2.1 mm. These results did not differ significantly from historic FB controls.

Conclusions

When compared with FB, V-DIBH demonstrated high setup accuracy and enabled significant reduction of cardiac doses without compromising the target volume coverage. Differences in lung doses were non-significant.

Open access

Noora Al-Hammadi, Palmira Caparrotti, Saju Divakar, Mohamed Riyas, Suparna Halsnad Chandramouli, Rabih Hammoud, Jillian Hayes, Maeve Mc Garry, Satheesh Prasad Paloor and Primoz Petric

Abstract

Background

Omitting the placement of clips inside tumour bed during breast cancer surgery poses a challenge for delineation of lumpectomy cavity clinical target volume (CTVLC). We aimed to quantify inter-observer variation and accuracy for CT- and MRI-based segmentation of CTVLC in patients without clips.

Patients and methods

CT- and MRI-simulator images of 12 breast cancer patients, treated by breast conserving surgery and radiotherapy, were included in this study. Five radiation oncologists recorded the cavity visualization score (CVS) and delineated CTVLC on both modalities. Expert-consensus (EC) contours were delineated by a senior radiation oncologist, respecting opinions of all observers. Inter-observer volumetric variation and generalized conformity index (CIgen) were calculated. Deviations from EC contour were quantified by the accuracy index (AI) and inter-delineation distances (IDD).

Results

Mean CVS was 3.88 +/− 0.99 and 3.05 +/− 1.07 for MRI and CT, respectively (p = 0.001). Mean volumes of CTVLC were similar: 154 +/− 26 cm3 on CT and 152 +/− 19 cm3 on MRI. Mean CIgen and AI were superior for MRI when compared with CT (CIgen: 0.74 +/− 0.07 vs. 0.67 +/− 0.12, p = 0.007; AI: 0.81 +/− 0.04 vs. 0.76 +/− 0.07; p = 0.004). CIgen and AI increased with increasing CVS. Mean IDD was 3 mm +/− 1.5 mm and 3.6 mm +/− 2.3 mm for MRI and CT, respectively (p = 0.017).

Conclusions

When compared with CT, MRI improved visualization of post-lumpectomy changes, reduced interobserver variation and improved the accuracy of CTVLC contouring in patients without clips in the tumour bed. Further studies with bigger sample sizes are needed to confirm our findings.