45 or 50 Gy, Which is the Optimal Radiotherapy Pelvic Dose in Locally Advanced Cervical Cancer in the Perspective of Reaching Magnetic Resonance Image-guided Adaptive Brachytherapy Planning Aims?

In locally advanced cervical cancer, the dose delivered results from the sum of external beam radiotherapy and brachytherapy, and is limited by the surrounding organs at risk. The balance between both techniques influences the total dose delivered to the high-risk clinical target volume (HR-CTV). The aim of the present study was to compare the ability of reaching different planning aims after external beam radiotherapy pelvic doses of 45 Gy in 25 fractions or 50.4 Gy in 28 fractions, both considered as standard prescriptions. The optimised plans of 120 patients treated with pelvic chemoradiation followed by magnetic resonance image-guided intracavitary brachytherapy were reviewed. The doses per pulse were calculated, and the number of pulses required to reach the planning aims, or a limiting dose constraint to organs at risk, was calculated. All doses were converted to 2-Gy equivalents. Three scenarios were applied consisting of different sets of planning aims: 85 and 60 Gy for the HR-CTV and the intermediate-risk CTV (IR-CTV) D90 (minimal dose received by 90% of the volume) in scenario 1, 90 and 60 Gy, respectively, for scenarios 2 and 3. For organs at risk, dose constraints were 90, 75 and 75 Gy to the bladder, rectum and sigmoid D2cm(3), respectively, in scenarios 1 and 2, and 80, 65 and 70 Gy in scenario 3. A similar HR-CTV D90 could have been reached in scenarios 1 and 2 according to both pelvic doses. In scenario 3, a higher mean HR-CTV could have been reached in the 45 Gy arm (83.5 ± 8.0 versus 82.4 ± 8.0, P < 0.0001). The mean D2cm(3) of organs at risk was systematically and significantly increased after a delivery of 50.4 Gy to the pelvis, from 0.9 to 2.89 Gy. The proportions of plans reaching planning aims were 85.8, 72.5 and 42.5% after 45 Gy and 85.5, 67.5 and 33.3% after 50.4 Gy according to scenarios 1, 2 and 3, respectively. According to scenario 3, 50.4 Gy, the reachable HR-CTV D90 was higher in 30% of the cases, by 2 Gy in two cases. Those cases were unpredictable and due to unfavourable organs at risk topography and poor response to external beam radiotherapy. The delivery of 45 Gy in 25 fractions to the pelvis before brachytherapy warrants a higher probability to reach brachytherapy planning aims, in comparison with 50.4 Gy in 28 fractions.

Mazeron R ，Petit C ，Rivin E ，Limkin E ，Dumas I ，Maroun P ，Annede P ，Martinetti F ，Seisen T ，Lefkopoulos D ，Chargari C ，Haie-Meder C ... -  《-》

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 ... -  《-》

Proof of principle: Applicator-guided stereotactic IMRT boost in combination with 3D MRI-based brachytherapy in locally advanced cervical cancer.

To describe a new technique involving high-precision stereotactic intensity-modulated radiation therapy (IMRT) boost in combination with intracavitary-interstitial (IC-IS) brachytherapy (BT) in cervical tumors that cannot be sufficiently covered by IC-IS-BT due to extensive residual disease and/or difficult topography at the time of BT. Three patients with stage IIIB-IVA cervical cancer had significant residual disease at the time of BT. MRI-guided IC-IS-BT (pulsed-dose rate) was combined with a stereotactic IMRT boost guided according to the BT applicator in situ, using cone beam CT. The planning aim dose (total external beam radiotherapy and BT) for the high-risk clinical target volume (HR-CTV) was D90 >70-85 Gy, whereas constraints for organs at risk were D2cm3 <70 Gy for rectum, sigmoid, and bowel and <90 Gy for bladder in terms of equivalent total dose in 2 Gy fractions. An IMRT boost adapted to the BT dose distribution was optimized to target the regions poorly covered by BT. HR-CTV doses of D90 >81 Gy were obtained in the central HR-CTV and D90 >69 Gy in the distal regions of HR-CTV. Image-guided set up of the IMRT boost with the applicator in situ was feasible. The dose plans were robust to intra-fraction uncertainties of 3 mm. Local control with acceptable morbidity was obtained at a followup of 3, 2.5, and 1 year, respectively. The combination of MRI-guided BT with an applicator-guided stereotactic IMRT boost is feasible. This technique seems to be useful in the few cases where HR-CTV coverage cannot be obtained even with IS-IC-BT.

Assenholt MS ，Vestergaard A ，Kallehauge JF ，Mohamed S ，Nielsen SK ，Petersen JB ，Fokdal L ，Lindegaard JC ，Tanderup K ... -  《-》

Evaluation of offline adaptive planning techniques in image-guided brachytherapy of cervical cancer.

Modern three-dimensional image-guided intracavitary high dose rate (HDR) brachytherapy is often used in combination with external beam radiotherapy (EBRT) to manage cervical cancer. Intrafraction motion of critical organs relative to the HDR applicator in the time between the planning CT and treatment delivery can cause marked deviations between the planned and delivered doses. This study examines offline adaptive planning techniques that may reduce intrafraction uncertainties by shortening the time between the planning CT and treatment delivery. Eight patients who received EBRT followed by HDR boosts were retrospectively reviewed. A CT scan was obtained for each insertion. Four strategies were simulated: (A) plans based on the current treatment day CT; (B) plans based on the first fraction CT; (C) plans based on the CT from the immediately preceding fraction; (D) plans based on the closest anatomically matched previous CT, using all prior plans as a library. Strategies B, C, and D allow plans to be created prior to the treatment day insertion, and then rapidly compared with the new CT. Equivalent doses in 2 Gy for combined EBRT and HDR were compared with online adaptive plans (strategy A) at D90 and D98 for the high-risk CTV (HR-CTV), and D2 cc for the bladder, rectum, sigmoid, and bowel. Compared to strategy A, D90 deviations for the HR-CTV were -0.5 ± 2.8 Gy, -0.9 ± 1.0 Gy, and -0.7 ± 1.0 Gy for Strategies B, C, and D, respectively. D2 cc changes for rectum were 2.7 ± 5.6 Gy, 0.6 ± 1.7 Gy, and 1.1 ± 2.4 Gy for Strategies B, C, and D. With the exception of one patient using strategy B, no notable variations for bladder, sigmoid, and bowel were found. Offline adaptive planning techniques can shorten time between CT and treatment delivery from hours to minutes, with minimal loss of dosimetric accuracy, greatly reducing the chance of intrafraction motion.

Liu H ，Kinard J ，Maurer J ，Shang Q ，Vanderstraeten C ，Hayes L ，Sintay B ，Wiant D ... -  《Journal of Applied Clinical Medical Physics》