Original article Strahlenther Onkol 2014 · 190:41–47 DOI 10.1007/s00066-013-0463-6 Received: 3 June 2013 Accepted: 11 September 2013 Published online: 17 November 2013 © Springer-Verlag Berlin Heidelberg 2013

R. Mazeron1 · J. Gilmore1, 2 · J. Champoudry3 · I. Dumas3 · J. Helou1 · P. Maroun1 · F. Martinetti3 · A. Gerbaulet1 · C. Haie-Meder1 1 Department of Radiation Oncology, Gustave Roussy, Villejuif Cedex 2 Department of Radiotherapy, Cork University Hospital, Wilton, Cork 3 Department of Medical Physics, Gustave Roussy, Villejuif

Volumetric evaluation of an alternative bladder point in brachytherapy for locally advanced cervical cancer

Management of locally advanced cervical cancer is based on a combination of external beam radiotherapy followed by utero-vaginal brachytherapy. For many years, dosimetry of brachytherapy has been based on the acquisition of orthogo­ nal rays and the prescription was based on geometrically constructed points (points A) or on isodose envelope selected according to clinical examination. Organs at risk (OAR) could not be identified directly on x-rays. Dose was, therefore, calculated with respect to the applicator and the bladder balloon, which was visible after injection of 7 cm3 of contrast. In 1985, the International Commission on Radiation Units and Measurements (ICRU report 38) recommended that dose points to both bladder and rectum should be reported. From the beginning, the bladder ICRU point was not considered as the maximum dose delivered to the bladder. It was designed to allow dose comparisons between different teams. The ability to integrate modern imaging techniques such as magnetic resonance image (MRI) or computed tomography (CT), or even ultrasonography in brachytherapy planning allowed delineation of target volumes and organs at risk [1]. Nowadays, the evaluation of the dose to OAR volume is based on dose–volume histograms. In 2005, GEC-ESTRO (“Groupe Européen de Curiethérapie”, European Society for Therapeutic Radiology and Oncology) issued two volumes of rec-

ommendations to define two clinical targets volumes, and to report maximal dose delivered to organs at risk in 2 cm3 [2, 3]. A decade ago, Briot et al. [4] led a dosimetric study on 15 patients and suggested that a point located 1.5 cm above the ICRU point, in a line parallel to the uterine tandem, is more representative of the dose actually received by the bladder (D3%). This point, called ALG (for Alain Gerbaulet), was then systematically constructed and used in the 2D as well in the 3D dosimetry performed at our institute. The purpose of this study was to investigate the performance of this point compared to the ICRU point, using D2cm3 as a reference in a large cohort of patients treated

for locally advanced cancer of the cervix with pulsed dose rate brachytherapy. The ICRU point of the rectum, being deemed more reliable than that of the bladder, was also reported and compared to D2cm3, to allow comparisons of correlations.

Material and methods As part of a retrospective study, the dosimetric data of 162 patients with locally advanced cervical cancers defined as FIGO stage 1B1 with positive pelvic ± paraaortic nodes (N+), 1B2-IVA, were reviewed. The treatment modalities were detailed elsewhere [5]. Briefly, all patients were treated with pelvic external beam radiother-

Fig. 1 8 Relationship between the localization of the ALG and ICRU points. a Sagittal view, b frontal view Strahlentherapie und Onkologie 1 · 2014 

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ALG (Gy)

Fig. 2 8 Orthogonal radiographs from a patient included in the study. a Sagittal view, b frontal view. The ALG point is located 1.5 cm above the ICRU point, following a line parallel to the tandem. In this case, the uterus is retroverted and deviated on the right side of the pelvis. The ALG point is therefore located, above, behind, and to the right of the ICRU bladder point. For this patient, the D2cm3 was 73.6 Gy, whereas the dose evaluated at points ALG and ICRU were 57.1 and 56.3 Gy, respectively. The balloon is indicated by yellow dashes. Tandem in red, vaginal sources in white dashes

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apy (EBRT) or extended field radiotherapy, depending on the staging, and the vast majority of them received concomitant chemotherapy consisting of weekly injections of cisplatinum, except in case of refusal or contraindication. Treatment was followed by MRI- or CT-guided utero-vaginal brachytherapy. Implantations were performed under general anesthesia. A personalized vaginal mould was used in nearly all patients, and the technique was intracavitary for all patients except two for whom additional needles were added in the paravagina for stage ­IIIA tumors. All patients were treated with pulsed dose rate with an empty bladder to ensure the re-

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Fig. 3 9 Comparison of bladder dose calculated at ALG point and D2cm3. conf. Int. confidence interval, obs observed

producibility of the repletion of the bladder between pulses, both at the time of the acquisition of images and during treatment. The pulses were repeated on an hourly basis 24 h/day for the duration of treatment.

Dosimetry After implantation, patients were transferred to the radiology department for a pelvic MRI or to the radiotherapy department for a CT scan, if MRI was unavailable or refused by the patient. For MRI, a 1.5 T machine was used. Dummy sources were inserted into the 3 tubes of the ap-

plicator to accurately visualize the tip end position of the sources and facilitate the reconstruction of the applicator. Sequence fast spin echo T2-weighted axial, coronal, and sagittal images were acquired without contrast enhancement, with a thickness of 3 mm without gap and a matrix size of 256×224. The images were then transferred onto OncentraGyn® or Plato® platforms (Nucletron Medical Systems, an Elekta company, Stockholm, Sweden) for delineation of HR and intermediate-risk clinical target volume (IR CTV) and organs at risk (OAR; rectum, sigmoid, and bladder) and the bladder catheter balloon. In addition to 3D imaging, orthogonal radiographs were also taken to check the reconstruction of the catheters. Point A, ICRU rectum, and bladder points were reconstructed on the radiographs according to the ICRU recommendations, then digitized in Plato and reported on MRI or CT using a coordinate system. For the ALG point, the same process was applied, and localized 1.5 cm above the ICRU point of the bladder parallel to the tandem (frontal and sagittal, . Fig. 1 and . Fig. 2). Their visualization on 3D imaging ensured no reporting error. When MRI was not available or in case of refusal by the patient, a CT scan was used for planning purposes. In this situation, axial slices were acquired (2–3 mm thick) with intravenous iodine injection to enhance the cervix.

Abstract · Zusammenfassung In all cases, the bladder was empty during image acquisition, and during the treatment, the bladder catheter remained opened during the whole brachytherapy procedure. The active lengths were determined based on the delineation of target volumes and clinical examination. The optimization was performed manually with Plato, following the recommendations of the GEC-ESTRO. The planning aim was to deliver at least 60 Gy to the CTV-IR and a minimum of 85 Gy to the CTV-HR in 2 Gy equivalent (EqD2), adding brachytherapy and external beam radiotherapy doses. Applied dose constraints to OAR for dosimetry were 75 Gy to the 2 cm3 of the rectum, and 85 Gy to the 2 cm3 of the bladder (EqD2). By analogy with the rectum, we limited the dose at the sigmoid colon to 75 Gy. From our 2D experience, additional constraints were applied to limit late toxicities: V100% (15 Gy, absolute dose) limited to 250 cm3 and total reference air kerma (TRAK) ≤2 cGy/m2 when compatible with the probability of local control. At the end of the procedure the prescription was adapted to a maximum dose rate of less than 0.6 Gy per pulse to organs at risk. Consequently, prescriptions ranged from 50 cGy/h×30 pulses to 25 cGy/h×60 pulses. The treatment was continuous and began the day of the insertion.

Analysis Doses at ICRU points as well as to ALG and D2cm3 were prospectively evaluated. For this study, they were converted into dose equivalent in 2 Gy (EQD2) using an α/β ratio of 3 for the bladder and rectum, with a half time for repair of 1.5 h. The same model was applied to convert EBRT doses to EqD2. To evaluate the total dose delivered to OAR, doses delivered with external beam radiotherapy and brachytherapy were added. For this operation, it was considered that the studied points and 2 cm3 of the bladder or rectum studied had received 100% of the prescribed dose for external beam radiotherapy. Statistical analyses were performed using XLSTAT software for windows, version 2012. Correlation tests were performed by Pearson’s correlation analysis.

Strahlenther Onkol 2014 · 190:41–47  DOI 10.1007/s00066-013-0463-6 © Springer-Verlag Berlin Heidelberg 2013 R. Mazeron · J. Gilmore · J. Champoudry · I. Dumas · J. Helou · P. Maroun · F. Martinetti · A. Gerbaulet · C. Haie-Meder

Volumetric evaluation of an alternative bladder point in brachytherapy for locally advanced cervical cancer Abstract Purpose.  To evaluate an alternative dose point, so-called ALG (for Alain Gerbaulet), for the bladder in comparison to the International Commission on Radiation Units and Measurements (ICRU) point and D2cm3 (minimal dose to maximally exposed 2 cm3) in a large cohort of patients with locally advanced cervical cancer treated with external beam radiotherapy followed by image-guided pulsed dose rate brachytherapy. Methods and materials.  For each patient, the ALG point was constructed 1.5 cm above the ICRU bladder, parallel to the tandem (coronal and sagittal planes). The dosimetric data from 162 patients were reviewed. Results.  Average doses to ALG and bladder points were 19.40 Gy±7.93 and 17.14±8.70, respectively (p=0.01). The 2 cm3 bladder dose averaged 24.40±6.77 Gy. Ratios between D2cm3 and dose points were 1.37±0.46 and 1.68±0.74 (p