Search

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]

Abstract: Background and purpose: To analyse dose–response relationships for local control of cervical cancer after MR image-guided brachytherapy (IGBT) based on dose–volume histogram parameters. Methods and materials: The analysis includes 141 patients with cervix cancer (stages IB–IVA) treated with 45–50.4Gy EBRT±cisplatin plus 4×7Gy IGBT. Gross tumour volume (GTV), high risk clinical target volume (HR CTV) and intermediate risk CTV (IR CTV) were delineated and DVH parameters (D90, D100) were assessed. Doses were converted to the equivalent dose in 2Gy (EQD2) using linear-quadratic model (α/β =10Gy). Groups of patients were formed according to tumour size at diagnosis (GTVD) of 2–5cm (group 1) or >5cm (2), with subgroups of the latter for HR CTV size at first IGBT 2–5cm (2a) or >5cm (2b). Dose–response dependence for local recurrence was evaluated by logit analysis. Results: Eighteen local recurrences in the true pelvis were observed. Dose–response analyses revealed a significant effect of HR CTV D100 (p =0.02) and D90 (p =0.005). The ED50-values for tumour control were 33±15Gy (D100) and 45±19Gy (D90). ED90-values were 67Gy (95% confidence interval [50;104]) and 86Gy [77;113], respectively. Conclusions: A significant dependence of local control on D100 and D90 for HR CTV was found. Tumour control rates of >90% can be expected at doses >67Gy and 86Gy, respectively. [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]

Abstract: Background: To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT)±chemotherapy (ChT). Methods: Treatment schedule was EBRT with 45–50.4Gy±concomitant cisplatin chemotherapy plus 4×7Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90>85Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75Gy for rectum and sigmoid and 90Gy for bladder. Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. Findings: One hundred and fifty-six consecutive patients (median age 58years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42months for all patients. Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93±13Gy, D2cc 86±17Gy for bladder, 65±9Gy for rectum and 64±9Gy for sigmoid. Complete remission was achieved in 151/156 patients (97%). Overall local control at 3years was 95%; 98% for tumours 2–5cm, and 92% for tumours >5cm (p =0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3years was overall 74%, 83% for tumours 2–5cm, 70% for tumours >5cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3years was in total 68%, 72% for tumours 2–5cm, 65% for tumours >5cm, 74% for IB, 78% for IIB, 45% for IIIB. In regard to late morbidity in total 188 grade 1+2 and 11 grade 3+4 late events were observed in 143 patients. G1+2/G3+4 events for bladder were n =32/3, for rectum n =14/5, for bowel (including sigmoid) n =3/0, for vagina n =128/2, respectively. Interpretation: 3D conformal radiotherapy±chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings. [Copyright &y& Elsevier]

Purpose: To investigate dosimetric uncertainties of MRI-based cervix cancer brachytherapy, when applying two HDR fractions for each applicator insertion and their clinical relevance. Methods: 21 patients with 84 MRI-examinations and fractions were investigated. After insertion of the MRI compatible tandem-ring applicator, an MRI-set was recorded and the treatment plan optimised for the first fraction. Prior to the second fraction 16–20h later a second MRI-set was recorded, and the dose distribution from the plan of the previous day superimposed and analysed. The same procedure was repeated for fractions 3 and 4. Dose from EBRT and brachytherapy was normalised to 2Gy-fractionation (EQD2), added up to a total dose, and compared to a calculated total dose if only 1 MRI-examination per insertion is available. Results: The total D90 for High risk (HR) CTV was 1.2±2.7Gyαβ10 (1±3%) (mean±1SD) lower by individual MRI-evaluation of each fraction compared to 1 MRI per insertion. The increased by 0.7±4.7Gyαβ3 (1±6%) for bladder, 1.1±2.4Gyαβ3 (2±4%) for rectum and decreased by 0.8±3.4Gyαβ3 (1±5%) for sigmoid. For HR CTV the individual approach did not identify any case with a decrease of D90 >5Gyαβ10. For the bladder 3 cases, for the rectum no case and for the sigmoid 1 case was identified with an increase of >5Gyαβ3. For the bladder all dose variations of more than 5Gyαβ3 could have been avoided by ensuring a constant bladder filling. Individual MRI-evaluation did not determine any case where dose constraints were not fulfilled. Conclusions: For the treatment schedule as applied in this study, geometric differences between applicator, target and OAR result in overall dosimetric changes, which seem to be of minor relevance in regard to clinical dose volume constraints applied at present. [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]