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

In 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. For 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. The 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 60 Gy 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, 81.2Gy(α/β10), 63.2Gy(α/β10) and 73.1Gy(α/β10) for groups 1, 2 and 3. The Intermediate Risk (IR) CTV D90 was respectively, 58.5Gy(α/β10), 57.3Gy(α/β10) and 61.7Gy(α/β10) for groups 1, 2 and 3. For the OARs, doses delivered to D2cc ranged 60-70Gy(α/β3) for the bladder, 33-61Gy(α/β3) for the rectum, and 44-58Gy(α/β3) for the sigmoid according to the regimen. At 24 months, 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. This 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.

Charra-Brunaud C ，Harter V ，Delannes M ，Haie-Meder C ，Quetin P ，Kerr C ，Castelain B ，Thomas L ，Peiffert D ... -  《-》

[Preliminary results of a French prospective-multicentric study of 3D pulsed dose-rate brachytherapy for cervix carcinoma].

Charra-Brunaud C ，Peiffert D 《Cancer Radiotherapie》

Long term experience with 3D image guided brachytherapy and clinical outcome in cervical cancer patients.

To report our 10years' experience and learning curve of the treatment of cervical cancer patients with chemo radiotherapy and MRI (or CT in 9 selected patients) guided brachytherapy using pulsed dose rate (PDR) brachytherapy (BT). Hundred and seventy consecutive patients with cervical cancer FIGO stage IB-IVB (without metastases beyond the para-aortic nodal region) were treated in our institute between 2002 and 2012. Patients received external beam radiotherapy (nodal boost to the lymph nodes positive at diagnosis)±chemotherapy followed by a pulsed or low dose rate brachytherapy boost. MRI (or CT) images were taken with the applicator in situ. The first 16 patients were treated according to X-ray-based plans, optimized on MRI. High-risk CTV, intermediate-risk CTV, bladder, rectum and sigmoid were retrospectively contoured according to the GEC-ESTRO recommendations. In all other patients, treatment plans were optimized after delineation of the target volumes and organs at risk at MRI (or CT). Doses were converted to the equivalent dose in 2Gy (EQD2) by applying the linear quadratic model. The median age of the patients was 55years (range 16-88). 41% had stage III or IV disease. Of the 170 patients, 91 patients had on imaging metastatic lymph nodes at diagnosis (62 patients pelvic lymph node involvement and 29 para-aortic). In 27 (16%) patients the intracavitary technique was combined with interstitial brachytherapy. The mean D90 and D100 for the high-risk CTV were 84.8±8.36Gy and 67.5±6.29Gy for the entire patient group. Mean D90 and D100 values for the IR CTV were 68.7±5.5Gy and 56.5±6.25Gy. There was an important learning curve between both patient groups, with an increase in mean D90 of 75.8Gy for the first 16 patients compared to 85.8Gy for the second group. At the same time, the mean dose to 2cm3 of bladder and sigmoid decreased from 86.1Gy to 82.7Gy and from 70Gy to 61.7Gy, respectively. At a median follow-up of 37months (range 2-136months), local control rate for all patients was 96%, the regional control (pelvic and para-aortic) rate 81% and crude disease free survival rate 55%. The overall survival at 5years is 65%. The higher dose to the target volume resulted in an increase in local control from 88% in the first 16 patients compared to 97% in the second patient group. Regarding late toxicity, 21 patients (12%) presented grade 3-4 late morbidity. Rectal, urinary, sigmoid and vaginal morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006). Although the majority of the patients presented with locally advanced carcinoma, excellent local and regional control rates were achieved. Rectal, urinary, sigmoid and vaginal grade 3-4 morbidity was 5%, 6%, 2% and 5%, respectively. A correlation between rectal D2cm3 >65Gy and grade >3 late morbidity was found (p=0.006).

Ribeiro I ，Janssen H ，De Brabandere M ，Nulens A ，De Bal D ，Vergote I ，Van Limbergen E ... -  《-》

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

To 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. Between 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 45 Gy 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 30 Gy in 50 hourly pulses to HR CTV. Manual dose optimisation was performed with the aim of reaching a D90>80 Gy in the HR CTV calculated as the total biologically equivalent to 2 Gy fractions of EBRT and BT (EQD2). Dose to the OAR were evaluated using dose volume constraints for D(2cc) of 90 Gy for bladder and 70 Gy for rectum and sigmoid. For HR CTV the median volume was 26 cm(3) (7-91 cm(3)). Coverage of the HR CTV was 97% (90-100%) and D90 was 82 Gy (77-88 Gy). The D(2cc) for bladder, rectum, and sigmoid were 65 Gy (47-81 Gy), 61 Gy (50-77 Gy), and 52 Gy (44-68 Gy), respectively. Median follow up was 18 months (6-61 months). The actuarial 2 years 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. Image 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.

Fokdal L ，Tanderup K ，Nielsen SK ，Christensen HK ，Røhl L ，Pedersen EM ，Schønemann NK ，Lindegaard JC ... -  《-》

Dynamics of High Risk Clinical Target Volume reduction during Brachytherapy and impact on its coverage in patients with inoperable cervical cancer.

Pobijakova M ，Scepanovic D ，Paluga M ，Fekete M ，Mardiak J ... -  《NEOPLASMA》