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Radiotherapy plays an important part in the management of breast cancer. Especially after breast-conserving surgery, external whole breast irradiation, occasionally with an additional local boost, is an integral part of breast conservation. Besides external radiation techniques, brachytherapy (BT) has long been among the treatment options, especially with regard to local boost application. With the emerging implementation of accelerated partial breast irradiation (APBI), BT in general and interstitial multi-catheter BT in particular, are gaining an increasing role in the management of a selected group of early breast cancer patients. APBI is an approach to reduce the irradiated area to the former tumor bed rather than treating the whole breast tissue in patients with a low baseline local recurrence risk. After a variety of phase I-III clinical studies, it is clearly evident that APBI will play a role in the treatment of this selected patient group. In this review, we focus on the clinical development and different available techniques of breast BT and provide a preview of prospects for its use. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the dosimetric results and first clinical experiences with a new designed balloon applicator with adjustable catheters for endoluminal brachytherapy for patients with locally advanced rectal cancer not undergoing surgery. Material and methods: The applicator consists of an inflatable rectal balloon with six attached Foley catheters used as guidance for the inserted brachytherapy plastic needles. The construction of the applicator and the dosimetric profile in terms of representative dose points in 0, 2, 5, 10 mm ipsilaterally and in 0 mm contralaterally are described. The first clinical outcomes in three patients are reported. Results: For all three patients, a reproducible dose gradient was achieved. The surface dose on the target side was 204 ± 19% of the normalized dose in 5 mm (100%) tissue depth, and 143 ± 8% in 2 mm and 64 ± 3% in 10 mm tissue depth, while the surface dose on the contra-lateral side was 20 ± 8%. After radiochemotherapy with 50 Gy external beam radiotherapy and concomitant administration of capecitabine, a HDR brachytherapy boost in 2-3 fractions of 7-10 Gy each was delivered. All patients achieved a clinical complete response 3 month after the treatment, and no major toxicity was observed. Conclusion: The use of the applicator was clinically feasible, and resulted in a stable and reproducible dose distribution. First clinical results are promising. [ABSTRACT FROM AUTHOR]

Purpose: The path of subsequent dwell positions of an afterloader source being moved through a ring applicator for cervix cancer brachytherapy deviates from an ideal circle and the position of marker wires. This can lead to deviations of several millimetres between real and assumed dwell positions for treatment planning with simplified source path models. The aim of this study was to test video- and autoradiography-based methods for source path determination, and to study the influence of dwell position accuracy on dose-volume histogram (DVH)-parameters. Material and methods: Videos of the exact motion of the source wire through three different (r = 26, 30, 34 mm) computed tomography/magnetic resonance (CT/MR) compatible plastic ring applicators were recorded. Observed dwell positions covering the whole length of each applicators channel were used to adjust the circular source path model. The agreement of the true source positions derived from video analysis with those of the corrected circular source path was verified using autoradiography. The impact of an accurate source path definition on dose planning was analysed by simulating clinically relevant uncertainties in 10 clinical treatment plans. Results: Depending on the ring size, source path diameters had to be increased by 0.5-1.0 mm in order to achieve acceptable maximum differences between observed and corrected dwell positions (1.3-2.0 mm). Autoradiography analysis showed a positional accuracy within ± 3 mm (extended standard deviation k = 2). For shifts of ± 2.5 mm for even all dwell positions, the systematic and random variation of the D2cm³ for bladder, rectum, and sigmoid was within 3%, while the impact on DVH uncertainties was much smaller for clinical target volume (CTV)HR and gross tumour volume (GTV). Conclusions: It is strongly advised to verify the real source path for ring applicators during acceptance testing in order to assure accurate source path definition and dose planning. Autoradiography can be used for source path veri- fication with acceptable accuracy for treatment planning and dose reporting. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the impact of magnetic resonance imaging (MRI)-morphologic differences in parametrial infiltration on tumour response during primary radiochemotherapy in cervical cancer. Material and methods. Eighty-five consecutive cervical cancer patients with FIGO stages IIB (n = 59) and IIIB (n = 26), treated by external beam radiotherapy (± chemotherapy) and image-guided adaptive brachytherapy, underwent T2-weighted MRI at the time of diagnosis and at the time of brachytherapy. MRI patterns of parametrial tumour infiltration at the time of diagnosis were assessed with regard to predominant morphology and maximum extent of parametrial tumour infiltration and were stratified into five tumour groups (TG): 1) expansive with spiculae; 2) expansive with spiculae and infiltrating parts; 3) infiltrative into the inner third of the parametrial space (PM); 4) infiltrative into the middle third of the PM; and 5) infiltrative into the outer third of the PM. MRI at the time of brachytherapy was used for identifying presence (residual vs. no residual disease) and signal intensity (high vs. intermediate) of residual disease within the PM. Left and right PM of each patient were evaluated separately at both time points. The impact of the TG on tumour remission status within the PM was analysed using χ2-test and logistic regression analysis. Results. In total, 170 PM were analysed. The TG 1, 2, 3, 4, 5 were present in 12%, 11%, 35%, 25% and 12% of the cases, respectively. Five percent of the PM were tumour-free. Residual tumour in the PM was identified in 19%, 68%, 88%, 90% and 85% of the PM for the TG 1, 2, 3, 4, and 5, respectively. The TG 3-5 had significantly higher rates of residual tumour in the PM in comparison to TG 1 + 2 (88% vs. 43%, p < 0.01). Conclusion. MRI-morphologic features of PM infiltration appear to allow for prediction of tumour response during external beam radiotherapy and chemotherapy. A predominantly infiltrative tumour spread at the time of diagnosis resulted in a significantly higher rate of residual tumour in the PM at the time of brachytherapy in comparison to a predominantly expansive tumour spread. [ABSTRACT FROM AUTHOR]

Purpose. The aim of the study was to improve computed tomography (CT)-based high-risk clinical target volume (HR CTV) delineation protocols for cervix cancer patients, in settings without any access to magnetic resonance imaging (MRI) at the time of brachytherapy. Therefore the value of a systematic integration of comprehensive three-dimensional (3D) documentation of repetitive gynecological examination for CT-based HR CTV delineation protocols, in addition to information from FIGO staging, was investigated. In addition to a comparison between reference MRI contours and two different CT-based contouring methods (using complementary information from FIGO staging with or without additional 3D clinical drawings), the use of standardized uterine heights was also investigated. Material and methods. Thirty-five cervix cancer patients with CT- and MR-images and 3D clinical drawings at time of diagnosis and brachytherapy were included. HR CTVstage was based on CT information and FIGO stage. HR CTVstage + 3Dclin was contoured on CT using FIGO stage and 3D clinical drawing. Standardized HR CTV heights were: 1/1, 2/3 and 1/2 of uterine height. MRI-based HR CTV was delineated independently. Resulting widths, thicknesses, heights, and volumes of HR CTVstage, HR CTVstage + 3Dclin and MRI-based HR CTV contours were compared. Results. The overall normalized volume ratios (mean± SD of CT/MRIref volume) of HR CTVstage and HR stage + 3Dclin were 2.6 (± 0.6) and 2.1 (± 0.4) for 1/1 and 2.3 (± 0.5) and 1.8 (± 0.4), for 2/3, and 1.9 (± 0.5) and 1.5 (± 0.3), for 1/2 of uterine height. The mean normalized widths were 1.5 ± 0.2 and 1.2 ± 0.2 for HR CTVstage and HR CTVstage + 3Dclin, respectively (p < 0.05). The mean normalized heights for HR CTVstage and HR CTVstage + 3Dclin were both 1.7 ± 0.4 for 1/1 (p < 0.05.), 1.3 ± 0.3 for 2/3 (p < 0.05) and 1.1 ± 0.3 for 1/2 of uterine height. Conclusion. CT-based HR CTV contouring based on FIGO stage alone leads to large overestimation of width and volume. Target delineation accuracy can systematically improve through incorporation of additional information from comprehensive 3D documentation of repetitive gynecological examination in the contouring protocol, and thus help to improve the accuracy of dose optimization in settings with limited access to imaging facilities at the time of brachytherapy. If CT information is only available, minimum 2/3 of uterine height may be a good surrogate for the height of HR CTV. [ABSTRACT FROM AUTHOR]

Abstract: The study aimed to determine whether post-radiation vaginal side effects in cervical cancer patients can be correlated with DVH parameter D2cc. The result was negative in that no correlation could be demonstrated between D2cc and the presence and grade of side effects in this patients’ subset treated with high brachytherapy doses. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To introduce and test a direct reconstruction concept for intracavitary tandem ring applicators in MR image-based brachytherapy treatment planning. Materials and methods: Optical measurements of transparent ring-phantoms provided the geometric relation between source path and the Vienna ring applicator as visible on MRI. For the manual direct reconstruction method (PLATO), the geometry plotted on a transparency was placed on the screen and rotated to fit with visible ring holes. With the software-integrated reconstruction method (OncentraGYN), the applicator geometry was directly used when placing the visible parts of the applicator in the 3D dataset. Clinical feasibility was tested in 10 clinical insertions. Reconstruction and dose calculation were performed independently on two treatment planning systems (PLATO and OncentraGYN) using MRI alone. DVH parameters for targets and organs at risk were analysed and compared to the clinically used radiograph/MRI registration-based method. Results: The direct reconstruction concept for both methods was feasible and reduced treatment planning time. Evaluated DVH parameters for plans using direct reconstruction methods differed from clinically used plans (traditional reconstruction) in mean differences ⩽0.2Gy for plans with 7Gy prescribed dose. Conclusion: If the relation between applicator shape visible on MRI and the source path is defined once, the reconstruction process can be performed by directly placing the applicator in the MRI dataset. [Copyright &y& Elsevier]

Abstract: Purpose: To investigate dose–volume histogram (DVH) parameters for organs at risk (OARs) in sectional three-dimensional image-based accelerated partial breast irradiation. Methods and Materials: Skin, lung, and ribs were defined as OARs and the heart was discussed. Two different skin-contouring methods were tested on phantom before applying to the patient cohort. First, an inside skin wall contour was delineated with three different wall thicknesses to demonstrate the influence of contouring on DVH parameter. Second a structure was defined, delineated outside of the phantom surface, such that a three-dimensional skin volume was extended like a virtual bolus contour. Point dose values and DVH parameters were reported for 25 patient cases. Results: The DVH parameters D 0.1 cc =65±21, D 1 cc =45±8, and D 10 cc =30±4cGy/pulse for the outside skin structure around the breast corresponded to skin surface areas of 1±1, 6±3, and 6±11cm2. Lung volume receiving 20Gyαβ3 was 8.3±11cm3. D 0.1 cc and D 2 cc in the most exposed rib were 0.7±0.3 and 0.4±0.2Gy/pulse, respectively. Conclusion: In accelerated partial breast irradiation treatment planning, dose to OAR can be reported in a more sophisticated way with DVH parameters than using points only. The suggested method of skin delineation using the defined outside structure allows calculating reliable and reproducible DVH parameters. [Copyright &y& Elsevier]

Introduction. Image guided adaptive brachytherapy (IGABT) for cervical cancer, using mainly MRI, is an evolving method, increasingly replacing the 2D approach based on conventional radiography. During the complex 4D chain of this procedure image-assistance is provided for disease assessment, provisional treatment planning (“pre-planning”), applicator placement and reconstruction, as well as for contouring, definitive treatment planning and quality control of dose delivery. With IGABT changes of topography adjacent to the applicator, caused by tumour regression, oedema, organ changes and dilation are identified. Thus, the CTV for IGABT is primarily based on the tumour volume at the time of BT and takes into account both time and spatial domains. IGABT requires systematic concepts for target, OAR, biological modelling, DVH analysis, and dose-volume-adaptation. Methods and Results. This report focuses on the advantages and uncertainties, dose-effect relations and clinical results of the IGABT procedure addressing the current status and future perspectives. Uncertainties during the 4D chain of IGABT are mainly related to target contouring, applicator reconstruction, as well as to inter-fraction, intra-fraction and inter-application variability, as caused by tumour response and organ changes. Different from EBRT where set-up uncertainties are compensated by adding a margin to the CTV, no margins to the lateral and anterior-posterior directions can be used for IGABT. Discussion. By 3D treatment planning for IGABT significant improvement of the DVH parameters is achieved compared to 2D library plans. In small tumours the benefit is primarily obtained by a decrease of dose to nearby OAR while in large tumours the use of supplementary interstitial techniques and optimization may double the target volume that can be treated at a therapeutic dose level. The clinical impact of IGABT could recently be demonstrated by the establishment of some correlations between target- and organ-related DVH parameters versus disease control and side effects, which need further clarification. Overall, a very high local control rate can be achieved with minor treatment related morbidity. This favourable therapeutic ratio seems to be now reproducible under different conditions at various treatment centres. These results have to be validated within the upcoming multi-centre prospective IntErnational study on MRI-guided brachytherapy in locally advanced cervical cancer (EMBRACE). [ABSTRACT FROM AUTHOR]

The global cervical cancer burden is disproportionately high in low- and middle-income countries (LMICs), and outcomes can be governed by the accessibility of appropriate screening and treatment. High-dose-rate (HDR) brachytherapy plays a central role in cervical cancer treatment, improving local control and overall survival. The American Brachytherapy Society (ABS) and Indian Brachytherapy Society (IBS) collaborated to provide this succinct consensus statement guiding the establishment of brachytherapy programs for gynecological malignancies in resource-limited settings. ABS and IBS members with expertise in brachytherapy formulated this consensus statement based on their collective clinical experience in LMICs with varying levels of resources. The ABS and IBS strongly encourage the establishment of HDR brachytherapy programs for the treatment of gynecological malignancies. With the consideration of resource variability in LMICs, we present 15 minimum component requirements for the establishment of such programs. Guidance on these components, including discussion of what is considered to be essential and what is considered to be optimal, is provided. This ABS/IBS consensus statement can guide the successful and safe establishment of HDR brachytherapy programs for gynecological malignancies in LMICs with varying levels of resources. [ABSTRACT FROM AUTHOR]

The sigmoid is an important organ at risk for gynecological brachytherapy (BT). However, the reliability of localization of high-dose regions during multi-fractionated treatment is limited. This work reports the methodological development of sigmoid points to summate multi-fractionated doses. Ten paired MRI data sets of ring-based intracavitary brachytherapy were obtained. Simulating a virtual endoscope, a reference line was created along the central axis of the anorectosigmoid for each implant. A trendline was generated, and linear dose was determined. Three-dimensional (3D) coordinates of high-dose regions were identified, and overlap was determined. In the next step, 3D coordinates of high-dose sigmoid points were localized in reference to cervical os and re-verified for location in reference to sigmoid lumen and corroboration with 2cc doses. With minor modifications, sigmoid points were proposed. In 6 of 10 patients, high-dose regions co-localized in subsequent fractions of BT. Three high-dose regions were identified along the sigmoid length and proposed as sigmoid points in reference to cervical os. (S1'= 0.5 cm right, 1.5 cm posterior, and 2.4 cm cranial; S2' = 0.3 cm anterior and 4.5 cm cranial; S3' = 2.7 cm left, 3 cm anterior, and 3.6 cm cranial to the cervical os). S1' and S2' were located in the sigmoid in 70% and 60% of data sets. The mean difference between D2cc and S1'/S2' was 0.30 Gy and 1.06 Gy respectively. S3' had limited corroboration to sigmoid lumen or 2 cc doses. The points S1' and S2' were further modified (minor) for applicability and proposed as sigmoid points 1 and 2 (SP1 0.5 right,1.5 posterior and 2.5 cm cranial to cervical os and SP2 (0.5 cm anterior and 4.5 cm cranial to cervical os)). SP1 and SP 2 are proposed as a surrogate for 2 cc sigmoid doses and may provide a method of reliable inter-fraction dose summation. This pilot work requires further validation. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To compare different dose–volume histogram (DVH) parameter concepts used for rectum and urethra. Methods and Materials: Thirty-eight postplan CT scans were used to contour the rectum with only one outer contour and as a wall structure. DVH analysis included dose to absolute and relative volumes of both contour types, from RD0.1cc to RD10cc and from RDmax to RD30, respectively. Volume parameters are reported (RV50–RV300) in cubic centimeters and percentages. The analysis of urethral dose parameters was based on 55 CTs with a urethral catheter. Relative (UD100 to UDmax) and absolute volume parameters (UD0.5cc to UD0.1cc, UV100, UV150) were evaluated, and also correlated to prostate parameters. The analysis was repeated for 10 MRI-based interstitial high-dose rate cases. Results: The correlation between organ and wall results was high for RD1, RD2cc, and RD0.1cc, with differences of <5%. DVH parameters reporting dose to a relative volume (e.g., RD10) or a relative volume related to a certain dose (e.g., RV100 [%]) are sensitive to the number of contoured slices. Dmax has a high uncertainty due to the sampling algorithm. RV100 (145Gy) of 1.5cc is similar to an RD2cc of 130Gy. The urethral UD10 and UD0.1cc correlate with a mean difference of 1%. The ratios of UD5/UD30, UD10/UD30, and UD5/UD10 were 1.12, 1.09, and 1.03, respectively. The correlation between D90 and D10 for prostate to urethra UD10 was poor. Conclusions: Only absolute volume parameters are stable in relation to different contouring concepts. When delineating the outer rectum contour, only RD2cc and RD0.1cc can be used. RV100 in cc correlates to RD2cc. Reporting UD5, UD10, and UD30 together is redundant. Additional information is given when reporting UV100 or UV150. [Copyright &y& Elsevier]

Abstract: Background and purpose: To investigate the inter-observer variation of target contouring when using the GYN GEC-ESTRO recommendations for MR image-guided brachytherapy (IGBT) for cervical cancer. Materials and methods: Nineteen cervical cancer patients, treated by radiotherapy at the Institut Gustave Roussy (IGR) in France (n =9) or at the Medical University of Vienna (AKH) in Austria (n =10) were included in this study. IGBT was used for all patients. Two radiation oncologists, one from IGR and the other from AKH, outlined the target volumes on MRI at the time of brachytherapy according to the GYN GEC-ESTRO recommendations. The absolute, common and encompassing volumes and their conformity indices (CIs) were assessed for the GTV, HR CTV and IR CTV. D90 and D100 for each volume were assessed. Visual evaluation was made to assess the reasons for the most frequent inter-observer differences. Results: The mean volumes of GTV and HR CTV did not differ significantly between the observers, p >0.05. Significant differences were observed only for the mean volumes of the IR CTV of both centres, p <0.05. CIs ranged from 0.5 to 0.7. DVH-parameter analyses did not reveal any statistical differences, except for the D100 for the GTV at AKH, and the D90 for the IR CTV at IGR, p <0.05. Underlying reasons for inter-observer differences included image contrast adjustment and neglecting to consider anatomical borders. Conclusions: The results of this inter-observer study show that the application of the GYN GEC-ESTRO recommendations for IGBT contouring at two different institutions with two different traditions for applicators, CTV assessment, MR image acquisition and dose prescription is feasible, and it produces acceptable inter-observer variability. [Copyright &y& Elsevier]

Purpose: To compare magnetic resonance imaging (MRI) findings at different stages of cervix cancer treatment and to define the potential of MRI to delineate the gross tumor volume (GTV), clinical target volume (CTV), pathoanatomic structures, and organs at risk (OAR) in brachytherapy. Methods and Materials: Forty-nine patients underwent MRI at diagnosis and at brachytherapy. The ability to discriminate anatomic structures on MRI was assessed (quality factor: 0 = inability to discriminate; 1 = fair discrimination; 2 = good discrimination; 3 = excellent discrimination). The overall ability to visualize (percentage of patients with quality factors greater than 0) and the overall discrimination quality score (mean quality factors of all patients) were estimated for the applicator, GTV at diagnosis (GTVD), GTV at brachytherapy (GTVBT)/“gray zones,” cervix rim/uterine corpus, OAR, vaginal wall, and parametria. Results: The overall ability to visualize the applicator on MRI at brachytherapy was 100%; for the GTVBT/“gray zones,” cervix rim/uterine corpus, OAR, and vaginal wall, visualization was 98% (overall discrimination quality factors: 1.2, 2.9, 2.1, 1.9, 1.7, and 2.6). Three of 4 borders of parametrial space were defined in more than 98% (discrimination quality factors: 2.9, 2.1, and 1.2). Conclusion: Magnetic resonance imaging provides appropriate information for definition of the applicator, GTV, CTV, pathoanatomic structures, and OAR that enables precise delineation for cervix cancer brachytherapy. [Copyright &y& Elsevier]

Image-guided adaptive brachytherapy (IGABT) has been shown to improve local/regional control and survival for cervix cancer patients while reducing morbidity. However, the technique is complex involving several conceptual, methodological, and technical innovations compared to conventional brachytherapy. The delivery of high-quality IGABT which will translate into improved outcomes is therefore critically dependent on effective education and training of all health professionals involved in the brachytherapy treatment process. This paper reviews the (GEC)-ESTRO/EMBRACE initiatives for education and training to promote the dissemination and implementation of IGABT for cervix cancer worldwide. The new skills required in different health professionals for successful implementation of IGABT are described. The achievements and challenges of current educational strategies for disseminating IGABT are discussed. Innovations to improve the effectiveness of current and future educational strategies are explored. [ABSTRACT FROM AUTHOR]

• In locally advanced cervical cancer (LACC) with residual tumor in distal parametrium or pelvic wall disease after concurrent radio-chemotherapy (CCRT) (category II). • Brachytherapy is technically challenging. • Our report highlights the clinical feasibility and outcome of patients treated at 2 Institutions. • BT was delivered using Vienna II BT Applicator (Vienna ring with add on cap) based IGABT. • This approach results in optimal outcome and acceptable grade 3 toxicities. Recent evidence from EMBRACE shows that around 16% patients with locally advanced cervical cancer (LACC) have residual tumor in distal parametrium (DP) and pelvic wall disease (LPW) after concurrent radio-chemotherapy (CCRT). Adequate target coverage with standard brachytherapy approaches represents a challenge. Therefore, we modified the Vienna I applicator with an add-on cap allowing for additional oblique needles into the DP/LPW (Vienna II). We report here the feasibility and clinical outcomes using Vienna II applicator in LACC patients treated in 2 institutions. 69 patients with residual disease in DP/LPW after CCRT were accrued. FIGO (2009) stage was 26% IIB, 52% III, 15% IVA, 7% IVB (para-aortic nodes). At diagnosis 91% had disease involving DP/LPW. After CCRT, patients underwent image guided adaptive brachytherapy (IGABT) using Vienna II applicator. IGABT details, acute complications, dose volume parameters and clinical outcome variables were compiled and analyzed. Residual DP/LPW disease at BT was found in 90% patients. Median total number of needles were 7 [3–15], oblique 4 [1–7]. Manageable intraoperative utero-vaginal complications occurred in 8 patients and manageable arterial bleeding in 6 patients during removal. Mean distance between tandem and outer contour of CTV HR was 38 mm and mean CTV HR (±SD) volume was 69 ± 32 cm3. The mean D 90 CTV HR was 86 ± 7 Gy (EQD2) and mean (±SD) D 2cm 3 (Gy, EQD2) 86 ± 12, 68 ± 7, 68 ± 9 for bladder, rectum and sigmoid respectively. Actuarial LC, PFS, OS at 3/5 years was 76/72%, 56/50%, 62/54% and G3-4 late toxicities (n = 23) were observed in 14 patients (20%). IGABT using Vienna II applicator allows for appropriate target coverage in tumors extending into DP/LPW at the time of BT. Clinical use is feasible and results in good local control, DFS and OS with moderate rate of acute and late ≥G3 toxicity. [ABSTRACT FROM AUTHOR]

Background and purpose Advancements in imaging and dose delivery enable boosting of the dominant intraprostatic lesions (DIL), while maintaining organs-at-risk (OAR) tolerances. This study aimed to assess the feasibility of DIL boosting for volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT) and high dose rate brachytherapy (HDR-BT). Material and methods DILs were defined on multiparametric magnetic resonance imaging and fused with planning CT for twelve patients. VMAT, IMPT and HDR-BT plans were created for each patient with an EQD2 α / β DIL aimed at 111.6 Gy, PTV initial D pres was 80.9 Gy (EBRT) with CTV D 90% = 81.9 Gy (HDR-BT). Hard dose constraints were applied for OARs. Results Higher boost doses were achieved with IMPT compared to VMAT, keeping major OAR doses at similar levels. Patient averaged EQD2 α / β D 50% to DIL were 110.7, 114.2 and 150.1 Gy(IsoE) for VMAT, IMPT and HDR-BT, respectively. Respective rectal wall D mean were 30.5 ± 5.0, 16.7 ± 3.6, 9.5 ± 2.5 Gy(IsoE) and bladder wall D mean were 21.0 ± 5.5, 15.6 ± 4.3 and 6.3 ± 2.2 Gy(IsoE). Conclusions DIL boosting was found to be feasible with all investigated techniques. Although OAR doses were higher than for standard treatment approach, the risk levels were reasonably low. HDR-BT was superior to VMAT and IMPT, both in terms of OAR sparing and DIL boosting. [ABSTRACT FROM AUTHOR]

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±3.4mm) were significantly lower than for GTV (4.8±4.2 and 4.2±3.5mm) and IR CTV (4.7±5.2 and 5.2±5.6mm) (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. [ABSTRACT FROM AUTHOR]

Abstract: Purpose and background: To study the dosimetric impact of interobserver delineation variability (IODV) in MRI-based cervical cancer brachytherapy. Materials and methods: MR images of six patients were distributed to 10 experienced observers worldwide. They were asked to delineate the target volumes and the organs at risk (OARs) for each patient. Two types of reference contours were created (Expert Consensus – EC and Simultaneous Truth and Performance Level Estimation – STAPLE). Optimised plans based on both EC- and STAPLE-contours were prepared. These plans were transferred to each of the observer contour sets and the resulting DVH parameters (D 90 and D 2cc) were calculated. For each patient the standard deviation (SD) for the 10 observers was calculated. Results: A mean relative SD of 8–10% was found for GTV and High Risk CTV (HR-CTV) D 90 analysing one single fraction. For rectum and bladder the mean relative SD for D 2cc was 5–8% while sigmoid was at 11%. For the whole treatment the IODV in HR-CTV caused an uncertainty of ±5Gyα/β=10 (1SD). The corresponding figure for OARs was ±2–3Gyα/β=3. The results were not sensitive as to which structure set was used for the optimisation. Conclusions: For the target volumes the dosimetric impact of IODV was smallest for the GTV and HR-CTV, while IODV had an even smaller impact on the bladder and rectum. [Copyright &y& Elsevier]

Abstract: The GYN GEC-ESTRO working group issued three parts of recommendations and highlighted the pivotal role of MRI for the successful implementation of 3D image-based cervical cancer brachytherapy (BT). The main advantage of MRI as an imaging modality is its superior soft tissue depiction quality. To exploit the full potential of MRI for the better ability of the radiation oncologist to make the appropriate choice for the BT application technique and to accurately define the target volumes and the organs at risk, certain MR imaging criteria have to be fulfilled. Technical requirements, patient preparation, as well as image acquisition protocols have to be tailored to the needs of 3D image-based BT. The present recommendation is focused on the general principles of MR imaging for 3D image-based BT. Methods and parameters have been developed and progressively validated from clinical experience from different institutions (IGR, Universities of Vienna, Leuven, Aarhus and Ljubljana) and successfully applied during expert meetings, contouring workshops, as well as within clinical and interobserver studies. It is useful to perform pelvic MRI scanning prior to radiotherapy (“Pre-RT-MRI examination”) and at the time of BT (“BT MRI examination”) with one MR imager. Both low and high-field imagers, as well as both open and close magnet configurations conform to the requirements of 3D image-based cervical cancer BT. Multiplanar (transversal, sagittal, coronal and oblique image orientation) T2-weighted images obtained with pelvic surface coils are considered as the golden standard for visualisation of the tumour and the critical organs. The use of complementary MRI sequences (e.g. contrast-enhanced T1-weighted or 3D isotropic MRI sequences) is optional. Patient preparation has to be adapted to the needs of BT intervention and MR imaging. It is recommended to visualise and interpret the MR images on dedicated DICOM-viewer workstations, which should also assist the contouring procedure. Choice of imaging parameters and BT equipment is made after taking into account aspects of interaction between imaging and applicator reconstruction, as well as those between imaging, geometry and dose calculation. In a prospective clinical context, to implement 3D image-based cervical cancer brachytherapy and to take advantage of its full potential, it is essential to successfully meet the MR imaging criteria described in the present recommendations of the GYN GEC-ESTRO working group. [Copyright &y& Elsevier]

Purpose: To establish dose-response relationships for late side effects of the rectum and bladder in cervix cancer patients after magnetic resonance image-guided adaptive brachytherapy (IGABT). Methods and Materials: A cohort of 141 patients was treated with 45 to 50.4 Gy with or without cisplatin plus 4 fractions of 7 Gy IGABT. Doses for the most exposed 2, 1, and 0.1-cm3 (D2cc, D1cc, D0.1cc) volumes of the rectum and bladder were converted into the equivalent dose in 2 Gy fractions (EQD2), using a linear quadratic model (α/β = 3 Gy). Late side effects were prospectively assessed (using late effects in normal tissues subjective, objective, management and analytic [LENT SOMA]) scales. Dose-response relationships were determined by logit analyses. Results: Eleven patients developed rectal side effects, and 23 patients had urinary side effects. A significant dose effect was found for all rectal dose-volume histogram (DVH) parameters for patients with side effect grades of 1 to 4 but was only significant for D2cc and D1cc for grades ≥2. The ED10 values for D2cc were 73 Gy for grades 1 to 4 and 78 Gy for grades 2 to 4 rectal morbidity. For bladder side effects, a significant dose effect was shown for all DVH parameters for complication grades ≥2; the respective ED10 was 101 Gy. Conclusions: Well-defined dose-response curves could be established for D2cc in the rectum and the urinary bladder. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: It has been shown that a cumulative dose of ⩾87Gy (EQD2) of external beam radiotherapy (EBRT) and image guided adaptive brachytherapy (IGABT) to the high risk clinical target volume (HR CTV) confer a local control rate >95% in locally advanced cervical cancer. This study examines the dose distribution within the HR CTV and intermediate (IR) CTV in patients with cervical cancer treated with definitive EBRT +/− concomitant chemotherapy and MRI-based IGABT between patients with local recurrence (LR) and patients in continuous complete local remission (CCLR). Material and methods: From 1998 to 2010, 265 patients were treated with definitive EBRT +/− concomitant chemotherapy and IGABT. Twenty-four LRs were documented. For the statistical analysis all patients with LR were matched to patients in CCLR from our database according to the following criteria: FIGO stage, histology, lymph node status, tumour size and chemotherapy. DVH parameters (D50, D90, D98, D100) were reported for HR CTV and IR CTV. In order to report the minimum dose in the region where the recurrence occurred, the HR CTV/IR CTV were divided into four quadrants on transversal planes. The minimum dose at the HR CTV/IR CTV contour was measured (within the corresponding quadrant closest to the LR) in the treatment planning system. A mean minimum point dose (MPD) was calculated by averaging these measurements on four consecutive slices at the level of the recurrence for each of the 4 brachytherapy fractions. EQD2 doses were calculated by summation of all BT and external beam therapy fractions. For each matched patient in the control group the measurements were performed on the same quadrant and at the same level. Results: Sufficient image data were available for 21 LRs. Eight central failures and 13 non-central failures were observed. The mean D90 and D100 for HR CTV were 77Gy and 61Gy for patients with LR and 95Gy and 71Gy for patients in CCLR, respectively (p <0.01). The MPD for HR CTV was 72Gy for patients in the LR arm and 99Gy for patients in the CCLR arm (p <0.01). In the LR arm seven patients had a D90 for HR CTV ⩾87Gy, however, in only three patients the MPD was ⩾87Gy. Conclusion: This study demonstrated significant differences in local outcome according to the delivered dose. In 85% of the LRs systematic low dose regions with less than 87Gy were found at HR CTV contour. Systematic low dose regions leading to local recurrence could be detected even if a D90 HR CTV ⩾87Gy was applied. In addition to DVH parameters, inspection of the spatial dose distribution remains a key point in dose prescription. [Copyright &y& Elsevier]

Purpose: To evaluate the predictive value of dose–volume histogram (DVH) parameters for late side effects of the rectum, sigmoid colon, and bladder in image-guided brachytherapy for cervix cancer patients. Methods and Materials: A total of 141 patients received external-beam radiotherapy and image-guided brachytherapy with or without chemotherapy. The DVH parameters for the most exposed 2, 1, and 0.1 cm3 (D2cc, D1cc, and D0.1cc) of the rectum, sigmoid, and bladder, as well as International Commission on Radiation Units and Measurements point doses (DICRU) were computed. Total doses were converted to equivalent doses in 2 Gy by applying the linear-quadratic model (α/β = 3 Gy). Late side effects were prospectively assessed using the Late Effects in Normal Tissues–Subjective, Objective, Management and Analytic score. The following patient groups were defined: Group 1: no side effects (Grade 0); Group 2: side effects (Grade 1–4); Group 3: minor side effects (Grade 0–1); and Group 4: major side effects (Grade 2–4). Results: The median follow-up was 51 months. The overall 5-year actuarial side effect rates were 12% for rectum, 3% for sigmoid, and 23% for bladder. The mean total D2cc were 65 ± 12 Gy for rectum, 62 ± 12 Gy for sigmoid, and 95 ± 22 Gy for bladder. For rectum, statistically significant differences were observed between Groups 1 and 2 in all DVH parameters and DICRU. Between Groups 3 and 4, no difference was observed for D0.1cc. For sigmoid, significant differences were observed for D2cc and D1cc, but not for D0.1cc in all groups. For bladder, significant differences were observed for all DVH parameters only comparing Groups 3 and 4. No differences were observed for DICRU. Conclusions: The parameters D2cc and D1cc have a good predictive value for rectal toxicity. For sigmoid, no prediction could be postulated because of limited data. In bladder, DVH parameters were predictive only for major toxicity. [Copyright &y& Elsevier]

Purpose: To investigate the value of dose–volume histogram (DVH) parameters for predicting local control in magnetic resonance (MR) image-guided brachytherapy (IGBT) for patients with cervical cancer. Methods and Materials: Our study population consists of 141 patients with cervical cancer (Stages IB–IVA) treated with 45–50 Gy external beam radiotherapy plus four times 7 Gy IGBT with or without cisplatin. Gross tumor volume (GTV), high-risk clinical target volume (HRCTV), and intermediate-risk clinical target volume (IRCTV) were contoured, and DVH parameters (minimum dose delivered to 90% of the volume of interest [D90] and D100) were assessed. Doses were converted to the equivalent dose in 2 Gy (EQD2) by applying the linear quadratic model (α/β = 10 Gy). Groups were defined for patients with or without local recurrence (LR) in the true pelvis for tumor size at diagnosis (GTV at diagnosis [GTVD] of 2–5 cm (Group 1) or greater than 5 cm (Group 2) and for tumor size response at IGBT (HRCTV) of 2–5 cm (Group 2a) or greater than 5 cm (Group 2b). Results: Eighteen LRs were observed. The most important DVH parameters correlated with LR were the D90 and D100 for HRCTV. Mean D90 and D100 values for HRCTV were 86 ± 16 and 65 ± 10 Gy, respectively. The D90 for HRCTV greater than 87 Gy resulted in an LR incidence of 4% (3 of 68) compared with 20% (15 of 73) for D90 less than 87 Gy. The effect was most pronounced in the tumor group (Group 2b). Conclusions: We showed an increase in local control in IGBT in patients with cervical cancer with the dose delivered, which can be expressed by the D90 and D100 for HRCTV. Local control rates greater than 95% can be achieved if the D90 (EQD2) for HRCTV is 87 Gy or greater. [Copyright &y& Elsevier]

Abstract: Background: Recurrent disease (restenosis) after endovascular treatment of the superficial femoral artery (SFA) remains a major problem. We evaluated the efficacy of beta-endovascular brachytherapy using the CORONA centering catheter in patients with SFA restenosis in a single-arm Phase II trial. Methods and results: A total of 28 patients (mean age 70 years; 16 female, 12 male) with recurrent SFA stenosis were treated, and in-stent restenosis was present in 17 patients (61%). Brachytherapy was performed with strontium-90 beta source using a 7-French CO2-filled one-segment centering catheter. New stents had to be applied in two cases. Mean interventional length was 129 mm (range 20–240 mm). A dose of 14 Gy in vessel radius (postinterventional) plus 2 mm was applied in 24 patients and 18.4 Gy in four patients. Treatment time was 7 min 32 s per radiation segment. No major adverse events occurred. Patients were followed by ankle-brachial index and duplex sonography for a median of 42 months. Cumulative restenosis rates at 1, 2, and 3 years were 9%, 28%, and 40%, respectively. Target vessel revascularization was performed in seven cases (25%). Conclusions: In comparison to literature data, the treatment of SFA restenosis with beta brachytherapy may improve long-term patency. [Copyright &y& Elsevier]

Abstract: Purpose: Correlation of dosimetric parameters for MRI-based 3D treatment planning with rectoscopic findings and clinical rectal side effects. Methods and materials: Rectosigmoidoscopy and rectal morbidity assessment were performed on 35 cervical cancer patients treated with external beam radiotherapy (EBRT) and HDR-intracavitary brachytherapy (ICB). The total doses, normalised to 2Gy fractions (EQD2, α/β =3Gy), in 0.1, 1.0 and 2.0cm3 (D 0.1cc, D 1cc, D 2cc) of rectum were determined by summation of EBRT and ICB plans. Correlation analysis between clinical symptoms (LENT/SOMA) and rectoscopic changes (Vienna Rectoscopy Score, VRS) was performed. For dose–response analyses, the logit model was applied. Results: Mean follow-up was 18months. LENT/SOMA score was 1 in 4 patients, 2 in 8 patients, 4 in 1 patient. Telangiectasia was found in 26 patients (74%), five of them had ulceration corresponding to the 0.1cm3 volume (anterior wall). Mean values D 0.1cc, D 1cc, and D 2cc were 81±13, 70±9 and 66±8Gy, respectively. The ED50 values for VRS⩾3 and for LENT/SOMA⩾2 significantly increased with decreasing volumes. D 2cc was higher in patients with VRS⩾3 compared to VRS<3 (72±6 vs 62±7Gy; p <0.001) and in symptomatic vs asymptomatic patients (72±6 vs 63±8Gy; p <0.001). VRS correlated with the LENT/SOMA score. Conclusions: Rectosigmoidoscopy is sensitive in detecting mucosal changes, independent of clinical symptoms. The localization of these changes corresponds to the high dose volumes as defined by imaging. The development of mucosal and clinical changes in the rectum follows a clear dose–effect and volume–effect. DVH parameters could be established. [Copyright &y& Elsevier]

Purpose: To compare the contours and dose–volume histograms (DVH) of the tumor and organs at risk (OAR) with computed tomography (CT) vs. magnetic resonance imaging (MRI) in cervical cancer brachytherapy. Methods and Materials: Ten patients underwent both MRI and CT after applicator insertion. The dose received by at least 90% of the volume (D90), the minimal target dose (D100), the volume treated to the prescription dose or greater for tumor for the high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) and the dose to 0.1 cm3, 1 cm3, and 2 cm3 for the OARs were evaluated. A standardized approach to contouring on CT (CTStd) was developed, implemented (HR- and IR-CTVCTStd), and compared with the MRI contours. Results: Tumor height, thickness, and total volume measurements, as determined by either CT or CTStd were not significantly different compared with the MRI volumes. In contrast, the width measurements differed in HR-CTVCTStd (p = 0.05) and IR-CTVCTStd (p = 0.01). For the HR-CTVCTStd, this resulted in statistically significant differences in the volume treated to the prescription dose or greater (MRI, 96% vs. CTStd, 86%, p = 0.01), D100 (MRI, 5.4 vs. CTStd, 3.4, p <0.01), and D90 (MRI, 8.7 vs. CTStd, 6.7, p <0.01). Correspondingly, the IR-CTV DVH values on MRI vs. CTStd, differed in the D100 (MRI, 3.0 vs. CTStd, 2.2, p = 0.01) and D90 (MRI, 5.6 vs. CTStd, 4.6, p = 0.02). The MRI and CT DVH values of the dose to 0.1 cm3, 1 cm3, and 2 cm3 for the OARs were similar. Conclusion: Computed tomography-based or MRI-based scans at brachytherapy are adequate for OAR DVH analysis. However, CT tumor contours can significantly overestimate the tumor width, resulting in significant differences in the D90, D100, and volume treated to the prescription dose or greater for the HR-CTV compared with that using MRI. MRI remains the standard for CTV definition. [Copyright &y& Elsevier]

Purpose: To present a combined intracavitary and interstitial dedicated applicator and magnetic resonance imaging (MRI) treatment planning for cervical cancer brachytherapy. Methods and Materials: A modified ring applicator allows interstitial needles to be implanted in parallel to the intrauterine tandem. MRI treatment planning based on a standard loading pattern with stepwise dwell weight adaptation and needle loading is performed to achieve optimal dose coverage and sparing of organs at risk. Dose constraints are applied for dose–volume histogram parameters. Results: The use of additional interstitial needles provides prescription dose up to 15 mm lateral to point A. Twenty-two patients with high-risk clinical target volumes of mean 44 cm3 were treated with a mean prescribed total dose of 85 Gy (biologically equivalent to 2 Gy fractionation, α/β = 10 Gy) and 93% coverage (V100). The dose to organs at risk was within standard limits for intracavitary brachytherapy alone. Conclusions: A combined interstitial-intracavitary applicator results in reproducible implants for cervical cancer brachytherapy. MRI-based treatment planning based on a target concept, dose–volume constraints, and limitations for the relative dwell weight allows for an increase in target coverage, treated volume, and total dose without increasing the dose to critical structures. [Copyright &y& Elsevier]