GEC ESTRO Research Articles

Recommendations from GEC ESTRO Breast Cancer Working Group (I): Target definition and target delineation for accelerated or boost Partial Breast Irradiation using multicatheter interstitial brachytherapy after breast conserving closed cavity surgery

ObjectiveThe aim was to develop a delineation guideline for target definition for APBI or boost by consensus of the Breast Working Group of GEC-ESTRO. Proposed recommendationsAppropriate delineation of CTV (PTV) with low inter- and intra-observer variability in clinical practice is complex and needs various steps as: (1) Detailed knowledge of primary surgical procedure, of all details of pathology, as well as of preoperative imaging. (2) Definition of tumour localization before breast conserving surgery inside the breast and translation of this information in the postoperative CT imaging data set. (3) Calculation of the size of total safety margins. The size should be at least 2cm. (4) Definition of the target. (5) Delineation of the target according to defined rules. ConclusionProviding guidelines based on the consensus of a group of experts should make it possible to achieve a reproducible and consistent definition of CTV (PTV) for Accelerated Partial Breast Irradiation (APBI) or boost irradiation after breast conserving closed cavity surgery, and helps to define it after selected cases of oncoplastic surgery.

The Comparison Between Reporting Doses per GEC ESTRO and Estimation From Deformable Dose Accumulation

The GEC ESTRO guideline has been widely adopted in cervical cancer treatment that combines external beam radiation therapy (EBRT) and CT-guided HDR brachytherapy (BT). In this guideline the minimum dose to 90% (D90) High Risk Clinical Target Volume (HRCTV), to 2cc of bladder (BD(2cc)) or rectum (RD(2cc)) are used for plan evaluation. The total dose in EQD2 is obtained by direct summation of EQD2 dose from EBRT and BT. However, in fractionated BT the high dose region varies due to variation of tumor volume, insertion configuration, and bladder/rectum shape.

A Volumetric Analysis of GTVD and HR CTV as Defined by the GEC ESTRO Recommendations in FIGO Stage IIB Cervical Cancer Patients Treated With IGABT in a Prospective Multicentric Trial

A Volumetric Analysis of GTVD and HR CTV as Defined by the GEC ESTRO Recommendations in FIGO Stage IIB Cervical Cancer Patients Treated With IGABT in a Prospective Multicentric Trial

Utrecht Intertitial Applicator Shifts and Organ Movements in 3D CT-Based HDR Brachytherapy of Cervical Cancer

To investigate Utrecht intertitial applicator shifts, and its effects of organ movements on DVH parameters during 3D CT-based HDR brachytherapy of cervical cancer. 13 cervical cancer patients underwent brachytherapy after external beam radiation therapy for total dose to 45 Gy/25 fractions. The prescribed dose of HDR brachytherapy was 7 Gy×4 fractions. 6 patients received brachytherapy only for two fractions as their individual reasons. We got the permission of the patients for the investigation. The dose of brachytherapy were calculated and transformed to EQD2 values in Gyα/β, biologically weighted dose normalized to 2 Gy fractionation. The used α/β values for target volumes and OAR were 10 and 3 Gy, respectively. We adopted the Zephyr Patient Transport Sled included Lithotomy Stirrups. After the applicator implanted, CT imaging was achieved for oncologist contouring CTVhr, CTVir, and OAR, including bladder, rectum, sigmoid colon and small intestines, which were performed according to GYN GEC ESTRO recommendations. The treatment plan was optimized according to the CTVhr, and executed in the case of total dose of CTV-hr D90 controlled by 80 to 85 Gyα/β, and OAR dose constrained by 90 Gyα/β3 for bladder, 75 Gyα/β3 for others. After the treatment, CT imaging was repeated. Two CT imaging were matched by pelvic structures. In both imaging, we defined the tandem by the tip and the base as the marker point, and evaluated applicator shift, including X (left as negative and right as positive) , Y (head as negative and foot as positive) and Z (anterior as negative and posterior as positive). Based on the repeated CT imaging, oncologist contoured the target volume and OAR again. We combined the treatment plan with the repeated CT imaging and evaluated the total dose of the target and OAR. We evaluated the change range for the doses of CTV-hr D90, D2cc for OAR. The average applicator shift were 0.10 mm to -0.16mm for X, 1.49 mm to 2.14 mm for Y, and 2.3mm to 1.9 mm for Z. The change of average physical doses and EQD2 values in Gyα/β range for CTV-hr D90 decreased by 2.55% and 3.5%, bladder D2cc decreased by 5.94 % and 8.77%, rectum D2cc decreased by 2.94% and 4%, sigmoid colon D2cc decreased by 3.38% and 3.72%, and small intestines D2cc increased by 3.72% and 10.94%. Applicator shifts and organ movements induced the total dose inaccurately. Although we adopted the Zephyr Patient Transport Sled included Lithotomy Stirrups, which reduced the movement of patients, the doses of target volume and OAR were variated inevitably. Applicator shifts and organ movements during the process of treatment could not be ignored.

Improved survival of patients with cervical cancer treated with image-guided brachytherapy compared with conventional brachytherapy

ObjectiveSince the Group Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC–ESTRO) published recommendations for 3D MRI-based image-guided adaptive brachytherapy (IGBT) in the treatment of cervical cancer, many institutions have implemented this technique and favourable results were documented. We investigated if introduction of IGBT in our centre indeed improved treatment outcomes and reduced toxicity compared to conventional brachytherapy (CBT). MethodsA retrospective analysis was done of outcomes of patients with stage IB-IVA cervical cancer treated with primary radiation therapy with curative intent between 2000 and 2012. Outcome measures were overall and disease-free survival, pelvic control, distant metastasis and treatment related adverse events (AE). Results126 patients were analysed; 43 had been treated with CBT between 2000–2007, and 83 with IGBT between 2007–2012. External beam radiation (mean; 46.6Gy) was combined with concurrent weekly cisplatin (51.6%), or hyperthermia (24.6%); radiation alone was used in 23.8%. Median follow-up was 121.8months for CBT patients, vs. 42.3months for IGBT. Complete remission was achieved in 83.7% of patients in the CBT group and in 98.8% of IGBT patients (p<0.01). Overall survival at 3years was 51% and 86%, respectively (p=0.001). Pelvic recurrence was found in 32% vs. 7% (p<0.001). Most patients had low grade adverse events. High grade (3–4) AE occurred in 15.4% vs. 8.4% at 3years (p=0.06). ConclusionIntroduction of IGBT for cervical cancer has led to significantly increased 3-year locoregional control and survival rates, whilst reducing late morbidity.

Minimally Invasive Intraoperative Multicatheter Breast Implant for Perioperative High-Dose-Rate Brachytherapy in Early Breast Cancer Treated With Conservative Surgery

To assess the safety and feasibility of MIOMBI in breast conservative surgery of breast cancer. Multicatheter Interstitial Breast Brachytherapy (MIBB) is an effective and safe technique for Accelerated Partial Breast Irradiation (APBI) in properly selected breast cancer patients treated with conservative surgery. MIBB technique allows reach the highest dose conformity and sparing healthy tissue ability respect of different APBI methods (Balloon, 3DCRT and Intraoperative Radiotherapy). MIBB is usually performed as closed-cavity procedure. This condition allows proper selection patients for APBI according to definitive pathological features but has some disadvantages since implies a second operation room visit for patient, determine a indirect visualisation of tumor bed with the consequently risk to make a geographical error dimmed frequently by performing extensive implants. Minimally Invasive Intraoperative Multicatheter Breast Implant (MIOMBI) represents an alternative to classic MIBB procedure with potential logistics, clinical and cosmetics advantages. Patients with early breast cancer candidates for conservative surgery were eligible for MIOMBI technique with 6F flexible catheters. Perioperative high-dose-rate brachytherapy (PHDRBT) was delivered as APBI (3.4 Gy for 10 in five days) in patients who met low- and intermediate-risk criteria according to GEC ESTRO recommendations, (women older than 40 years, infiltrating ductal carcinoma less than 2 cm with extensive intraductal carcinoma less than 25%, pN0, free margins more than 2mm and intraductal carcinoma less than 3 cm.) Those patients who did not meet previous criteria receive PHDRBT as anticipatory boost (4 fractions of 3.4 Gy in two days BAT) followed by hypofractionated whole breast irradiation 39.9 Gy in 15 fractions. From April 2010 to July 2013 101 consecutive breast cancer patients have been treated with conservative surgery and MIOMBI. The median time for MIOMBI procedure was 25 minutes. The median of number of catheter employed was 9 (4-14). No intraoperative complications were observed. Major complications RTOG grade 3-4 (acute and late) was observed only in one patient (1%) who suffered bleeding complication after implant remove. Infection (mastitis or abscess) was observed in 3 patients (2%). Fat necrosis with no symptoms was observed in 2 patients. PHDRBT was delivered as APBI in 64 patients (60%) and as a boost in 34 (40%). The median of CTV-T (clips zone plus 2 cm) was 41 cc with a median D90 of 3.27 Gy (96%) and DHI in CTV-T of 0.71. The median V100 and V150 was 60cc and 13cc, respectively, with a median DHI of 0.76. Median D10 in high-risk skin zone was 1.91 Gy (56%). With a median followup of 22 months (2-34) no (local, elsewhere, regional or distant) failure was observed. Cosmetic outcomes were evaluated in 46 of 64 APBI treatments (71%) with excellent and good results in 61% and 37%, respectively, and fair in 2%. Minimally invasive intraoperative multicatheter breast implant (MIOMBI) for perioperative high-dose-rate brachytherapy (PHDRBT) avoids a second surgical procedure, allows direct visualisation of tumor bed reducing the implant extension and keeps all advantages (dosimetric and proper selection patients for APBI) of the classic MIBB technique.

MRI Based 3D Brachytherapy Planning of the Cervical Cancer – Our Experiences with the Use of the Uterovaginal Vienna Ring MR‑ CT Applicator

Uterovaginal brachytherapy planning is conventionally based on the use of two orthogonal Xray projections. Currently, there is a large development of 3D brachytherapy planning based on the fusion of CT and MRI, which takes into account the extent of the tumor and the location of organs at risk. In this work, we evaluated the dosimetric data and first clinical results in patients with inoperable cervical cancer using MRI/ CT compatible applicator enabling 3D planning. Between June 2012 and March 2013, we performed 52 uterovaginal applications in 13 patients with inoperable cervical cancer using Vienna Ring MR CT applicator. Planning was carried out by the fusion of MRI and CT. Target volumes and organs at risk delineation were carried out on the basis of GEC ESTRO and ABS recommendations as well as doses report-ing. Overall radiotherapy duration was 37- 52 days with median of 45 days. The median total dose delivered to the HR CTV was 88 Gy (70.7- 97.9) EQD2. The median single dose in brachytherapeutic applications was D90 = 6.45 Gy (3.2- 9.82). The median total doses delivered to the rectum, sigmoid colon and bladder were D2ccrectum = 64.2 Gy (54.3- 74.1), D2ccsigmoid = 68.6 Gy (57- 74.7) a D2ccbladder = 73.9 Gy (58.3- 92.6). In 11 patients (84.6%), complete locoregional remission was achieved, in the remaining two patients (15.4%), partial locoregional remission was achieved. Twelve patients (92.3%) had complete regression of the tumor in the cervix, one patient (7.7%) developed metastatic spread to the liver. Yet we did not observe manifestations of a higher degree of toxicity than the first grade, both GI and GU. Late GI toxicity was manifested in two patients (15.4%) and late GU toxicity was manifested in five patients (38.5%). 3D brachytherapy planning of inoperable cervical cancer using the fusion of MRI and CT conclusively raises the possibility of the dose escalation to the tumor and significantly spares the surrounding organs at risk. Subsequently, this way of planning leads to better local control of the disease and to lower radiation morbidity.

SP-0024: GEC-ESTRO guidelines for target definition in breast brachytherapy

GEC ESTRO first published guidelines for HDR prostate brachytherapy in 2005. Since then there has been a considerable expansion in knowledge and use of the technique as a result of which an update has now been produced by the UROGEC group of GEC ESTRO, published in Radiotherapy and Oncology. These are evidence-based consensus guidelines from the group resulting from rigorous appraisal of the literature and discussions between experienced practitioners in this area. Recommendations for patient selection, treatment facility, implant technique, dose prescription and dosimetry reporting are given. The indications for HDRBT in dose escalation schedules with external beam are wide ranging with all patients having localized disease eligible for this technique.Exclusion criteria are few encompassing patients medically unfit for the procedure and those with significant urinary outflow symptoms. It is recognised that both single step ultrasound based and two step CT or MR-based technique scan be used. There remain areas of uncertainty in prostate HDR brachytherapy reflected in the guidelines. These include the optimal dose prescription, organ at risk constraints, PTV definition, evaluation of implant quality and the role of HDR monotherapy and salvage in prostate cancer. The use of these guidelines will ensure that HDR brachytherapy in prostate cancer can be practiced effectively and safely. The main indication at present is dose escalation with external beam but in the future HDR monotherapy, focal therapy and treatment of recurrence will be important areas of development.

Papillon contact radiotherapy: past, present and future

Professor Arthur Sun Myint* speaks to Natasha Galukande, Commissioning Editor: Arthur Sun Myint graduated from the Institute of Medicine, Mingaladon, Burma in 1972 and came to the UK in 1977. He was appointed as a Clinical Scientist for the Medical Research Council Neutron trial project in 1983 and chaired the colorectal subgroup for neutron trials until 1995. He is now the Lead Clinician in papillon radiotherapy at the Clatterbridge Cancer Centre (Merseyside, UK) where he has worked as a consultant for nearly 25 years. His main research interest is in the treatment of rectal cancers and he introduced contact radiotherapy (Papillon) into the UK and started treating patients at The Clatterbridge Cancer Centre in 1993. So far, he has treated over 700 patients using the Papillon technique, which is the world’s largest cohort of patients. He is a founder member of the International Contact Radiotherapy Society (ICONE) and he was appointed specialist advisor for NICE for rectal brachytherapy and helped to write the guidelines published in December 2006. He also serves as an advisor to NCRI rectal and anal subgroups, has published over 50 peer-reviewed publications and is the author of four text book chapters. He has served on the council of the Association of Coloproctology and the council of the Royal College of Radiologists. He was appointed to chair the GEC–ESTRO brachytherapy group for rectal and anal cancers in 2011. He is the contact radiotherapy course director at the Clatterbridge Cancer Centre and he has organized the next course on 9–10 October 2014. He was awarded a Honorary Professor in Gastroenterology by the University of Liverpool in December 2012.

SP-0625: ICRU GEC ESTRO report on image guide adaptive brachytherapy in cancer of the cervix (IGABT)

SP-0625: ICRU GEC ESTRO report on image guide adaptive brachytherapy in cancer of the cervix (IGABT)

Accelerated partial breast irradiation with intraoperative electrons: Using GEC–ESTRO recommendations as guidance for patient selection

PurposeTo evaluate outcomes among early-stage breast cancer patients after conservative surgery and full-dose intraoperative radiotherapy electrons (ELIOT) by applying the Groupe Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology (GEC–ESTRO) recommendations for partial breast irradiation (APBI). Materials and MethodsOne-thousand eight-hundred and twenty-two patients were stratified into the three GEC–ESTRO categories of “good candidates”, “possible candidates” and “contraindication” in order to assess outcomes. ResultsAll the 1822 cases except 7 could be classified according to GEC–ESTRO groups: 573 patients met the criteria to be included in the “good candidates” group, 468 patients in the “possible candidates” group and 767 patients in the “contraindication” group. Median and mean follow-up length was 3.5years (range 0–10.5years) and 3.8years (SD 2.2), respectively.The 5-year rate of in-breast tumor reappearances for “good candidates”, “possible candidates” and “contraindication” groups were 1.9%, 7.4% and 7.7%, respectively (p 0.001). While the regional node relapse showed no difference, the rate of distant metastases was significantly different in the “contraindication” group compared to the other two categories, having a significant impact on survival. ConclusionsAmong the ELIOT population, the GEC–ESTRO recommendations enabled the selection of the good candidates with a low rate of local recurrence, but failed to differentiate the “possible candidates” and the “contraindication” groups.

Calculation of Equivalent Dose to Target Volume and Critical Organs for Combination of IMRT and MRI Guided High-dose-rate Brachytherapy Using Deformable Image Registration in Cervical Cancer

To quantify the dose on MRI guided HDR brachytherapy from intensity modulated radiation therapy (IMRT) using deformable image registration method. Six cervical cancer patients who were treated with IMRT and 3D Intracavitary MRI guided HDR brachytherapy were retrospectively analyzed to evaluate the dose from IMRT on the MRI based brachytherapy plan. All patients had external beam radiation therapy (EBRT) of 45 Gy with 1.8 Gy per fraction with IMRT followed by 3D MRI guided HDR brachytherapy with Ring and Tandem applicator. Three of them had pelvic and paraortic nodes treated with 55 Gy in 25 fractions as SIB (simultaneous integrated boost). Prescription dose for brachytherapy was 5.5-6.0 Gy per fraction to HRCTV (high risk clinical target volume) with total 5 fractions. Total doses for HR CTV D90 and dose to 2cc of bladder, rectum and sigmoid (organs at risk-OARs) from EBRT and brachytherapy were summated and normalized to a biologically equivalent 2 Gy fraction size (EQD2). As per GEC ESTRO guidelines it is assumed that target volume (HRCTV) and critical organs get 45 Gy in 25 fractions with EBRT and thus, EQD2 contribution from EBRT to HRCTV and OARs are 44.3 Gy and 43.2 Gy, respectively for all 6 patients. Each brachytherapy fraction dose is then converted to EQD2 and added to that EBRT EQD2 for total dose. For this study we fused the MRI for each HDR fraction with external beam planning CT using deformable image registration method (Velocity v2.7). MRI image for each fraction from brachytherapy was used as a reference image and planning CT image was deformed to match to each MRI fraction based on intact uterus as well as bony anatomy. The dose contribution was calculated for HRCTV and critical organs including rectum, bladder and sigmoid. The mean EQD2 ±SD contribution from EBRT for HR CTV D90 was 46.2±0.7 Gy. Mean EQD2 to 2cc of bladder, rectum and sigmoid was 46.2±1.3 Gy, 46.3 ±1.0 Gy, 48.4±2.6 Gy, respectively. The difference in EQD2 based on uniform dose to target volume and critical organs and from deformable registration was statistically significant (p < 0.0001). The true dose to HRCTV and OARs were higher in comparison to calculation based on assumption of uniform dose distribution from EBRT. For composite dose calculation of EBRT and brachytherapy, EBRT contribution has been assumed to be uniform for all patients. However, true dose to HRCTV and OARs appears to be different and higher than calculated dose based on uniform dose distribution. Deformable registration method helps to quantify and individualize dose contribution from EBRT and future outcome analysis of image based brachytherapy should take this factor into account.

Impact of 3D image-based PDR brachytherapy on outcome of patients treated for cervix carcinoma in France: Results of the French STIC prospective study

PurposeIn 2005 a French multicentric non randomized prospective study was initiated to compare two groups of patients treated for cervix carcinoma according to brachytherapy (BT) method: 2D vs 3D dosimetry. The BT dosimetric planning method was chosen for each patient in each center according to the availability of the technique. This study describes the results for 705 out of 801 patients available for analysis. Patients and methodsFor the 2D arm, dosimetry was planned on orthogonal X-Rays using low dose rate (LDR) or pulsed dose rate (PDR) BT. For the 3D arm, dosimetry was planned on 3D imaging (mainly CT) and performed with PDR BT. Each center could follow the dosimetric method they were used to, according to the chosen radioelement and applicator. Manual or graphical optimization was allowed.Three treatment regimens were defined: Group 1: BT followed by surgery; 165 patients (2D arm: 76; 3D arm: 89); Group 2: EBRT (+chemotherapy), BT, then surgery; 305 patients (2D arm: 142; 3D arm: 163); Group 3: EBRT (+chemotherapy), then BT; 235 patients, (2D arm: 118; 3D arm: 117).The DVH parameters for CTVs (High Risk CTV and Intermediate Risk CTV) and organs at risk (OARs) were computed as recommended by GYN GEC ESTRO guidelines. Total doses were converted to equivalent doses in 2Gy fractions (EQD2). Side effects were prospectively assessed using the CTCAEv3.0. ResultsThe 2D and 3D arms were well balanced with regard to age, FIGO stage, histology, EBRT dose and chemotherapy. For each treatment regimen, BT doses and volumes were comparable between the 2D and 3D arms in terms of dose to point A, isodose 60Gy volume, dose to ICRU rectal points, and TRAK.Dosimetric data in the 3D arm showed that the dose delivered to 90% of the High Risk CTV (HR CTV D90) was respectively, 81.2Gyα/β10, 63.2Gyα/β10 and 73.1Gyα/β10 for groups 1, 2 and 3. The Intermediate Risk (IR) CTV D90 was respectively, 58.5Gyα/β10, 57.3Gyα/β10 and 61.7Gyα/β10 for groups 1, 2 and 3. For the OARs, doses delivered to D2cc ranged 60–70Gyα/β3 for the bladder, 33–61Gyα/β3 for the rectum, and 44–58Gyα/β3 for the sigmoid according to the regimen.At 24months, local relapse-free survival was 91.9% and 100% in group 1, 84.7% and 93% in group 2, 73.9% and 78.5% in group 3; grade 3–4 toxicity rate was 14.6% and 8.9% in group 1, 12.5% and 8.8% in group 2, and 22.7% and 2.6% in group 3 for 2D and 3D arm. ConclusionThis multicentric study has shown that 3D BT is feasible and safe in routine practice. It has improved local control with half the toxicity observed with 2D dosimetry. The combined treatment with radiotherapy and surgery was more toxic than definitive radiotherapy. For patients with advanced tumors, it is necessary to improve coverage of target volumes without raising toxicity.

Dosimetric Changes during Daily MR-Guided Pulse-Dose-Rate Brachytherapy for Cervix Cancer

Dosimetric Changes during Daily MR-Guided Pulse-Dose-Rate Brachytherapy for Cervix Cancer

Image and laparoscopic guided interstitial brachytherapy for locally advanced primary or recurrent gynaecological cancer using the adaptive GEC ESTRO target concept

PurposeTo retrospectively assess treatment outcome of image and laparoscopic guided interstitial pulsed dose rate brachytherapy (PDR-BT) for locally advanced gynaecological cancer using the adaptive GEC ESTRO target concept. Materials and methodsBetween June 2005 and December 2010, 28 consecutive patients were treated for locally advanced primary vaginal (nine), recurrent endometrial (12) or recurrent cervical cancer (seven) with combined external beam radiotherapy (EBRT) and interstitial PDR-BT. Treatment was initiated with whole pelvic EBRT to a median dose of 45Gy followed by PDR-BT using the Martinez Universal Perineal Interstitial Template (MUPIT). All implants were virtually preplanned using MRI of the pelvis with a dummy MUPIT in situ. The GEC ESTRO high risk clinical target volume (HR CTV), intermediate risk clinical target volume (IR CTV) and the organs at risk (OAR) were contoured and a preplan for implantation was generated (BrachyVision, Varian). The subsequent implantation was performed under laparoscopic visualisation. Final contouring and treatment planning were done using a post-implant CT. Planning aim of PDR-BT was to deliver 30Gy in 50 hourly pulses to HR CTV. Manual dose optimisation was performed with the aim of reaching a D90>80Gy in the HR CTV calculated as the total biologically equivalent to 2Gy fractions of EBRT and BT (EQD2). Dose to the OAR were evaluated using dose volume constraints for D2cc of 90Gy for bladder and 70Gy for rectum and sigmoid. ResultsFor HR CTV the median volume was 26cm3 (7–91cm3). Coverage of the HR CTV was 97% (90–100%) and D90 was 82Gy (77–88Gy). The D2cc for bladder, rectum, and sigmoid were 65Gy (47–81Gy), 61Gy (50–77Gy), and 52Gy (44–68Gy), respectively. Median follow up was 18months (6–61 months). The actuarial 2years local control rate was 92% (SE 5), while disease-free survival and overall survival were 59% (SE 11) and 74%, respectively (SE 10). No complications to the laparoscopic guided implantation were encountered. Late grade 2 (CTC v 3.0) complications were recorded in nine (32%) patients. One patient had a grade 3 vaginal complication. No grade 4–5 complications have been recorded so far. ConclusionImage and laparoscopic guided interstitial PDR-BT using the GEC ESTRO target concept is applicable for locally advanced primary vaginal or recurrent endometrial and cervical cancer resulting in an excellent local control rate and limited morbidity.

Apparent diffusion coefficients in GEC ESTRO target volumes for image guided adaptive brachytherapy of locally advanced cervical cancer

Background and purpose. T2 weighted MRI is recommended for image guided adaptive brachytherapy (IGABT) in cervical cancer. Diffusion weighted imaging (DWI) and the derived apparent diffusion coefficient (ADC) may add additional biological information on tumour cell density. The purpose of this study was to evaluate the distribution of the ADC within target volumes as recommended by GEC-ESTRO: Gross Tumour Volume at BT (GTVBT), High-Risk Clinical Tumour Volume (HR-CTV) and Intermediate-Risk Clinical Target Volume (IR-CTV) and to evaluate the change of diffusion between fractions of IGABT. Material and methods. Fifteen patients with locally advanced cervical cancer were examined by MRI before their first (BT1) and second (BT2) fraction of IGABT, resulting in a total of 30 MR examinations including both T2 weighted and DWI sequences. The Apparent Diffusion Coefficient (ADC) was calculated by use of three levels of b-values (0, 600, 1000 s/mm2). ADC maps were constructed and fused with the GEC ESTRO target contours. The mean ADC value within each target volume was calculated. Furthermore, volumes of low diffusion (ADClow) were defined based on an ADC threshold of 1.2 × 10−3 mm2/s, and overlap with target volumes was evaluated. Change of ADC level in target volumes and change of ADClow volume from BT1 to BT2 was also evaluated. Results. The mean ADC was significantly lower in GTVBT than in HR-CTV (p<0.001) which again was significantly lower than in IR-CTV (p<0.001). There was no significant change of the ADClow volume or ADC level within each target structure between BT1 and BT2 (p=0.242). All three GEC-ESTRO volumes contained volumes with low diffusion. The GTVBT contained 37.2% volume of low diffusion, HR-CTV 20.3% and IR-CTV 10.8%. Conclusion. With DWI we were able to find a significant difference in ADC-values for the three different GEC ESTRO targets. This supports the assumption that the target volumes used for dose prescription in IGABT contain tissues with different characteristics, with the tumour (GTVBT) being the volume with the lowest diffusion. No significant changes were found from BT1 to BT2 indicating that changes of ADC level and volumes are stable at the time of BT. Further studies are needed to evaluate the role of DWI in target contouring and dose prescription for IGABT.

Apport des techniques de curiethérapie optimisée grâce à l’imagerie tridimensionnelle dans la prise en charge des patientes atteintes d’un cancer du col utérin

Traditionally, prescription and treatment planning in intracavitary brachytherapy for cervix cancer have used either reference points (mainly points A and B) or reference isodoses (60 Gy according to ICRU recommendations) to report doses to the target volume. Doses to critical organs were reported at bladder and rectum ICRU points. This practice has been supported by a long-standing clinical experience that has yielded an acceptable therapeutic ratio. The recent development of imaging has contributed to the improvement in target and organs at risk knowledge. In 2005 and 2006, GEC–ESTRO recommendations publications on 3-D based image brachytherapy have defined the different volumes of interest. These recommendations have been validated with intercomparison delineation studies. With the concomitant development of remote after-loading projectors, provided with miniaturized sources, it is now possible to plan radiation doses by adjusting dwell positions and relative dwell time values. These procedures allow better coverage of the targets while sparing OAR. The recent literature data evidence a significant improvement in local control with no increase in complications. Further studies are needed to better define the dose recommended in both tumour and organs at risk. This is one of the goals of the European study on MRI-guided brachytherapy in locally advanced cervical cancer (EMBRACE) protocol.

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

Purpose: Reported local failure rates for FIGO stage II-IVA vaginal cancer usually range between 20% and 60%, even in recent series. In this study we investigate the clinical feasibility and report about the first treatment outcomes of MRI image guided brachytherapy (IGBT) in these pts using the same strategy as recently developed for cervix cancer. Materials: Forty pts with vaginal cancer were treated at our institution from 1999-2006. Thirteen pts met the inclusion criteria for this study and received IGBT based on a prospective protocol. FIGO stage distribution was: stage II=4, stage III=5, stage IV=4. Five pts had positive pelvic lymph nodes and in 7 pts tumour size was >5cm. All pts received EBRT (40-50Gy) and 11 pts concurrent chemotherapy (9 cisplatin and 2 MMC+5-FU). IGBT dose prescription was either 4x7 Gy (HDR) or 35-40 Gy (0.5-0.8Gy; PDR) to the HR CTV. In 10 cases a combined intravaginal/interstitial application technique was used. Based on the recent developments in the treatment of cervical cancer pts with IGBT (Gyn GEC ESTRO Recommendations), systematic concepts for HR CTV, OAR, biological modelling, DVH-analysis, dosevolumeadaptation (D90, D2cc), and dose escalation were integrated into the treatment (planning) of all pts. Reported doses were converted to the equivalent dose in 2Gy (EQD2) applying the LQ-model (α/β of 10 for tumour and 3 for OAR). Clinical results were calculated using the KaplanMeier method. Results: Spatial relations between vaginal cylinder +/needle applicators, HR CTV, and OAR were clearly visible on MRI in all cases. Mean total prescribed dose was 80Gy EQD2 (1SD±8Gy).Mean D90 for HR CTV was 86Gy EQD2 (1SD±13Gy). For OAR the following mean D2cc were documented: 80Gy (1SD±20Gy) for bladder, 76Gy (1SD ±16Gy) for urethra, 70Gy (1SD ±9Gy) for rectum and 60Gy (1SD±9Gy) for sigmoid colon. All pts achieved complete remission at 3 months. Median follow up was 43 months (range: 1987 months). Two pts developed fistula (1 vesico-vaginal, 1 recto-vaginal) due to tumour-necrosis and 1 with distal vaginal involvement complete vaginal obliteration. Three recurrences were documented: 1 local in a patient with FIGO stage III and 2 distant. All these pts had positive pelvic lymph nodes. Actuarial local control, OS and CSS rates at three years were 92%, 85% and 85%. For FIGO stages II, III, and IV they were 100%, 80% and 75%, respectively. Conclusions: IGBT for vaginal cancer seems to be feasible similar to the concepts as introduced for cervix cancer. Clinical and dosimetric results of this first experience with IGBT for locally advanced vaginal cancer are promising. Local control and survival in this small series seems to be significantly higher than in previous reports about conventional X-ray based brachytherapy, associated at the same time with acceptable morbidity. However, further prospective studies with more pts are needed to confirm these results.

A correlation of bladder and rectal point doses with 3-d volume-based treatment planning for intracavitary brachytherapy in the treatment of locally advanced cervical cancers

Purpose: The dose of radiation which can be delivered to a cervical cancer is limited by the tolerance of the organs at risk (OAR), i.e., the bladder and rectum. The ICRU 38 recommendations for 2-D image based planning for Intracavitary Brachytherapy (ICBT) dates back to the eighties and comes with its share of limitations. In this era of 3-D image based planning and dosimetry, its relevance is therefore arguable. Though, there are recommendations from bodies like the ABS (2004) and the GYN GEC ESTRO (2006) but there is still no consensus for the volume based dose constraints for the OARS.

Systematic comparison of two methods of bladder contouring in cervix cancer brachytherapy: “Direct” vs. “indirect”

Purpose: The importance of accurate contouring of organs at risk including the bladder is critical in the setting of radical pelvic radiotherapy, and in particular for brachytherapy due to high doses and steep dose gradients near organs at risk. While a dose response effect has been demonstrated for the rectum, similar demonstration for the bladder has remained elusive. One possible reason for this involves the accuracy of traditional bladder contouring. We compared two methods of contouring the bladder; traditional outer bladder drawings (GEC ESTRO recommendations), with a new method using inner bladder drawings.