Mario Federico

Adaptive image guided brachytherapy for cervical cancer: A combined MRI-/CT-planning technique with MRI only at first fraction

Purpose To investigate and test the feasibility of adaptive 3D image based BT planning for cervix cancer patients in settings with limited access to MRI, using a combination of MRI for the first BT fraction and planning of subsequent fractions on CT. Material and methods For 20 patients treated with EBRT and HDR BT with tandem/ring applicators two sets of treatment plans were compared. Scenario one is based on the “gold standard” with individual MRI-based treatment plans (applicator reconstruction, target contouring and dose optimization) for two BT applications with two fractions each. Scenario two is based on one initial MRI acquisition with an applicator in place for the planning of the two fractions of the first BT application and reuse of the target contour delineated on MRI for subsequent planning of the second application on CT. Transfer of the target from MRI of the first application to the CT of the second one was accomplished by use of an automatic applicator-based image registration procedure. Individual dose optimization of the second BT application was based on the transferred MRI target volume and OAR structures delineated on CT. DVH parameters were calculated for transferred target structures (virtual dose from MRI/CT plan) and CT-based OAR. The quality of the MRI/CT combination method was investigated by evaluating the CT-based dose distributions on MRI-based target and OAR contours of the same application (real dose from MRI/CT plan). Results The mean difference between the MRI based target volumes (HR CTVMRI2) and the structures transferred from MRI to CT (HR CTVCT2) was −1.7 ± 6.6 cm3 (−2.9 ± 20.4%) with a median of −0.7 cm3. The mean difference between the virtual and the real total D90, based on the MRI/CT combination technique was −1.5 ± 4.3 Gy EQD2. This indicates a small systematic underestimation of the real D90. Conclusions A combination of MRI for first fraction and subsequent CT based planning is feasible and easy when automatic applicator-based image registration and target transfer are technically available. The results show striking similarity to fully MRI-based planning in cases of small tumours and intracavitary applications, both in terms of HR CTV coverage and respecting of OAR dose limits. For larger tumours and complex applications, as well as situations with unfavourable OAR topography, especially for the sigmoid, MRI based adaptive BT planning remains the superior method.

Uncertainty analysis for 3D image-based cervix cancer brachytherapy by repetitive MR imaging: assessment of DVH-variations between two HDR fractions within one applicator insertion and their clinical relevance.

PURPOSEnTo investigate dosimetric uncertainties of MRI-based cervix cancer brachytherapy, when applying two HDR fractions for each applicator insertion and their clinical relevance.nnnMETHODSn21 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 16-20 h 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 2 Gy-fractionation (EQD2), added up to a total dose, and compared to a calculated total dose if only 1 MRI-examination per insertion is available.nnnRESULTSnThe total D(90) for High risk (HR) CTV was 1.2±2.7 Gy(αβ10) (1±3%) (mean±1SD) lower by individual MRI-evaluation of each fraction compared to 1 MRI per insertion. The D(2cm(3)) increased by 0.7±4.7 Gy(αβ3) (1±6%) for bladder, 1.1±2.4 Gy(αβ3) (2±4%) for rectum and decreased by 0.8±3.4 Gy(αβ3) (1±5%) for sigmoid. For HR CTV the individual approach did not identify any case with a decrease of D(90) >5 Gy(αβ10). For the bladder 3 cases, for the rectum no case and for the sigmoid 1 case was identified with an increase of D(2cm(3)) >5 Gy(αβ3). For the bladder all dose variations of more than 5 Gy(αβ3) could have been avoided by ensuring a constant bladder filling. Individual MRI-evaluation did not determine any case where dose constraints were not fulfilled.nnnCONCLUSIONSnFor 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.

High-risk clinical target volume delineation in CT-guided cervical cancer brachytherapy: Impact of information from FIGO stage with or without systematic inclusion of 3D documentation of clinical gynecological examination

Abstract 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.

Residual tumour volumes and grey zones after external beam radiotherapy (with or without chemotherapy) in cervical cancer patients. A low-field MRI study.

BackgroundGrey zones, which are defined as tissue with intermediate signal intensity in the area of primary hyperintense tumour extension, can be seen during radiationxa0with or without chemotherapy on the T2-weighted MRI in patients with cervical cancer. The purpose of this study was to systematically measure the tumour volume at the time of diagnosis and the residual tumour volume at the time of brachytherapy without and with consideration of the grey zones and to estimate tumour regression during external beam radiotherapy (EBRT).Material and methodsT2-weighted MRI datasets of 175xa0patients with locally advanced cervical cancer (FIGO stage IB–IVA), who underwent combined external beam radiotherapy and brachytherapyxa0with or without concomitant chemotherapy were available for this study. The gross tumour volume at the time of diagnosis (GTVinit) and at the time of first brachytherapy without (GTVres) and with (GTVres+u2009GZ) consideration of grey zones were measured for each patient. A descriptive statistical analysis was performed and tumour regression rates without (R) and with consideration of grey zones (RGZ) were calculated. Further, the role of prognostic factors on GTVinit, GTVres, GTVres+u2009GZ and tumour regression rates was investigated.ResultsThe median GTVinit, GTVres, GTVres+u2009GZ in all patients were 44.4xa0cm3, 8.2xa0cm3, 20.3xa0cm3, respectively. The median R was 78.5% and the median RGZ was 50.1%. The histology and FIGO staging showed a significant impact on GTVinit, GTVres and GTVres+u2009GZ.ConclusionGrey zones represent a substantial proportion of the residual tumour volume at the time of brachytherapy. Differentiation of high signal intensity mass and surrounding intermediate signal intensity grey zones may be reasonable.ZusammenfassungHintergrundSogenannte Grauzonen können im Verlauf der Radiochemotherapie auf der T2-gewichteten MRT bei Patientinnen mit Zervixkarzinomen als Areal mit intermediärer Signalintensität im Gebiet des initialen hyperintensen Tumors beobachtet werden. Das Ziel dieser Studie war es, das Tumorvolumen zum Zeitpunkt der Diagnose und zum Zeitpunkt der Brachytherapie mit und ohne Berücksichtigung der Grauzonen zu erfassen und die daraus resultierende Tumorregression während der externen Strahlentherapie (EBRT) zu berechnen.Material und MethodeT2-gewichtete MRT-Datensätze von 175xa0Patientinnen mit lokal fortgeschrittenem Zervixkarzinom (FIGO-Stadien IB–IVA), die mittels kombinierter EBRT und Brachytherapie mit und ohne konkomittante Chemotherapie behandelt worden waren, waren für diese Studie verfügbar. Für jede Patientin wurden das „Gross Tumor Volume“ (GTV) zum Zeitpunkt der Diagnose (GTVinit) sowie zum Zeitpunkt der Brachytherapie mit (GTVres+u2009GZ) und ohne Berücksichtigung der Grauzonen (GTVres) erfasst. Eine deskriptive statistische Analyse wurde durchgeführt und die Tumorregression mit (R) und ohne Berücksichtigung der Grauzonen (RGZ) berechnet. Desweiteren wurden der Einfluss prognostischer Faktoren auf GTVinit, GTVres, GTVres+u2009GZ und Tumorregressionsraten untersucht.ErgebnisseDas mediane GTVinit, GTVres und GTVres+u2009GZ aller Patientinnen betrug jeweils 44,4xa0cm3, 8,2xa0cm3 und 20,3xa0cm3. Die mediane R lag bei 78,5% und die mediane RGZ bei 50,1%. Die Histologie und das FIGO-Stadium hatten einen signifikanten Einfluss auf GTVinit, GTVres und GTVres+u2009GZ.SchlussfolgerungGrauzonen scheinen als Folge der Tumorregression zu entstehen und haben einen wesentlichen Anteil am Tumorvolumen zum Zeitpunkt der Brachytherapie. Eine MR-tomographische Unterscheidung des Resttumors zum Zeitpunkt der Brachytherapie in hohe und intermediäre Signalintensität erscheint sinnvoll.

Value of Magnetic Resonance Imaging Without or With Applicator in Place for Target Definition in Cervix Cancer Brachytherapy

PURPOSEnTo define, in the setting of cervical cancer, to what extent information from additional pretreatment magnetic resonance imaging (MRI) without the brachytherapy applicator improves conformity of CT-based high-risk clinical target volume (CTVHR) contours, compared with the MRI for various tumor stages (International Federation of Gynecology and Obstetrics [FIGO] stages I-IVA).nnnMETHODS AND MATERIALSnThe CTVHR was contoured in 39 patients with cervical cancer (FIGO stages I-IVA) (1) on CT images based on clinical information (CTVHR-CTClinical) alone; and (2) using an additional MRI before brachytherapy, without the applicator (CTVHR-CTpre-BT MRI). The CT contours were compared with reference contours on MRI with the applicator in place (CTVHR-MRIref). Width, height, thickness, volumes, and topography were analyzed.nnnRESULTSnThe CT-MRIref differences hardly varied in stage I tumors (n=8). In limited-volume stage IIB and IIIB tumors (n=19), CTVHR-CTpre-BT MRI-MRIref volume differences (2.6 cm(3) [IIB], 7.3 cm(3) [IIIB]) were superior to CTVHR-CTClinical-MRIref (11.8 cm(3) [IIB], 22.9 cm(3) [IIIB]), owing to significant improvement of height and width (P<.05). In advanced disease (n=12), improved agreement with MR volume, width, and height was achieved for CTVHR-CTpre-BT MRI. In 5 of 12 cases, MRIref contours were partly missed on CT.nnnCONCLUSIONSnPre-BT MRI helps to define CTVHR before BT implantation appropriately, if only CT images with the applicator in place are available for BT planning. Significant improvement is achievable in limited-volume stage IIB and IIIB tumors. In more advanced disease (extensive IIB to IVA), improvement of conformity is possible but may be associated with geographic misses. Limited impact on precision of CTVHR-CT is expected in stage IB tumors.

Quality assurance in MR image guided adaptive brachytherapy for cervical cancer: Final results of the EMBRACE study dummy run

PURPOSEnUpfront quality assurance (QA) is considered essential when starting a multicenter clinical trial in radiotherapy. Despite the long experience gained for external beam radiotherapy (EBRT) trials, there are only limited audit QA methods for brachytherapy (BT) and none include the specific aspects of image guided adaptive brachytherapy (IGABT).nnnMETHODS AND MATERIALSnEMBRACE is a prospective multicenter trial aiming to assess the impact of (MRI)-based IGABT in locally advanced cervical cancer. An EMBRACE dummy run was designed to identify sources and magnitude of uncertainties and errors considered important for the evaluation of clinical, and dosimetric parameters and their relation to outcome. Contouring, treatment planning and dose reporting was evaluated and scored with a categorical scale of 1-10. Active feedback to centers was provided to improve protocol compliance and reporting. A second dummy run was required in case of major deviations (score <7) for any item.nnnRESULTSnOverall 27/30 centers passed the dummy run. 16 centers had to repeat the dummy run in order to clarify major inconsistencies to the protocol. The most pronounced variations were related to contouring for both EBRT and BT. Centers with experience in IGABT (>30 cases) had better performance as compared to centers with limited experience.nnnCONCLUSIONnThe comprehensive dummy run designed for the EMBRACE trial has been a feasible tool for QA in IGABT of cervix cancer. It should be considered for future IGABT trials and could serve as the basis for continuous quality checks for brachytherapy centers.

Residual tumour volumes and grey zones after external beam radiotherapy (with or without chemotherapy) in cervical cancer patients@@@Residuale Tumorvolumen und Grauzonen nach externer Strahlentherapie (mit und ohne Chemotherapie) bei Zervixkarzinompatientinnen: A low-field MRI study@@@Eine Niederfeld-MRT-Studie

BackgroundGrey zones, which are defined as tissue with intermediate signal intensity in the area of primary hyperintense tumour extension, can be seen during radiationxa0with or without chemotherapy on the T2-weighted MRI in patients with cervical cancer. The purpose of this study was to systematically measure the tumour volume at the time of diagnosis and the residual tumour volume at the time of brachytherapy without and with consideration of the grey zones and to estimate tumour regression during external beam radiotherapy (EBRT).Material and methodsT2-weighted MRI datasets of 175xa0patients with locally advanced cervical cancer (FIGO stage IB–IVA), who underwent combined external beam radiotherapy and brachytherapyxa0with or without concomitant chemotherapy were available for this study. The gross tumour volume at the time of diagnosis (GTVinit) and at the time of first brachytherapy without (GTVres) and with (GTVres+u2009GZ) consideration of grey zones were measured for each patient. A descriptive statistical analysis was performed and tumour regression rates without (R) and with consideration of grey zones (RGZ) were calculated. Further, the role of prognostic factors on GTVinit, GTVres, GTVres+u2009GZ and tumour regression rates was investigated.ResultsThe median GTVinit, GTVres, GTVres+u2009GZ in all patients were 44.4xa0cm3, 8.2xa0cm3, 20.3xa0cm3, respectively. The median R was 78.5% and the median RGZ was 50.1%. The histology and FIGO staging showed a significant impact on GTVinit, GTVres and GTVres+u2009GZ.ConclusionGrey zones represent a substantial proportion of the residual tumour volume at the time of brachytherapy. Differentiation of high signal intensity mass and surrounding intermediate signal intensity grey zones may be reasonable.ZusammenfassungHintergrundSogenannte Grauzonen können im Verlauf der Radiochemotherapie auf der T2-gewichteten MRT bei Patientinnen mit Zervixkarzinomen als Areal mit intermediärer Signalintensität im Gebiet des initialen hyperintensen Tumors beobachtet werden. Das Ziel dieser Studie war es, das Tumorvolumen zum Zeitpunkt der Diagnose und zum Zeitpunkt der Brachytherapie mit und ohne Berücksichtigung der Grauzonen zu erfassen und die daraus resultierende Tumorregression während der externen Strahlentherapie (EBRT) zu berechnen.Material und MethodeT2-gewichtete MRT-Datensätze von 175xa0Patientinnen mit lokal fortgeschrittenem Zervixkarzinom (FIGO-Stadien IB–IVA), die mittels kombinierter EBRT und Brachytherapie mit und ohne konkomittante Chemotherapie behandelt worden waren, waren für diese Studie verfügbar. Für jede Patientin wurden das „Gross Tumor Volume“ (GTV) zum Zeitpunkt der Diagnose (GTVinit) sowie zum Zeitpunkt der Brachytherapie mit (GTVres+u2009GZ) und ohne Berücksichtigung der Grauzonen (GTVres) erfasst. Eine deskriptive statistische Analyse wurde durchgeführt und die Tumorregression mit (R) und ohne Berücksichtigung der Grauzonen (RGZ) berechnet. Desweiteren wurden der Einfluss prognostischer Faktoren auf GTVinit, GTVres, GTVres+u2009GZ und Tumorregressionsraten untersucht.ErgebnisseDas mediane GTVinit, GTVres und GTVres+u2009GZ aller Patientinnen betrug jeweils 44,4xa0cm3, 8,2xa0cm3 und 20,3xa0cm3. Die mediane R lag bei 78,5% und die mediane RGZ bei 50,1%. Die Histologie und das FIGO-Stadium hatten einen signifikanten Einfluss auf GTVinit, GTVres und GTVres+u2009GZ.SchlussfolgerungGrauzonen scheinen als Folge der Tumorregression zu entstehen und haben einen wesentlichen Anteil am Tumorvolumen zum Zeitpunkt der Brachytherapie. Eine MR-tomographische Unterscheidung des Resttumors zum Zeitpunkt der Brachytherapie in hohe und intermediäre Signalintensität erscheint sinnvoll.