Pre-plan technique feasibility in multi-interstitial/endocavitary perineal gynecological brachytherapy

Purpose

The American Brachytherapy Society (ABS) together with the Groupe Européen de Curiethérapie and the Euro­pean Society for Radiotherapy and Oncology (GEC- ESTRO) have recommended magnetic resonance imaging (MRI) as the preferred image modality in image guided brachytherapy, specifically using the T2 acquisition sequence [1,2,3,4].
In locally advanced cervical carcinoma with moderate extension to the parametrium, combined endocavitary and interstitial applicators (Vienna [5] or Utrecht [6] applicators; Nucletron, Elekta AB, Stockholm, Sweden) are appropriate, although these have coverage limitations in patients with more advanced disease (distal parametrial affectation, medial or distal vaginal affectation, or extension to rectum or bowel), in which interstitial templates such as the Martinez universal perineal interstitial template (MUPIT) [7] (Nucletron, Elekta AB, Stockholm, Sweden) or the Syed template [8] (Best Medical International, Inc., Springfield, VA, USA) have been typically used. In an attempt to circumvent these difficulties, our department has developed a new gynecological applicator (Template Benidorm, TB) [9]. The device is a fully MRI-compatible applicator that engages titanium needles and an intrauterine tandem that allows the use of MRI-based dosimetry, thus providing the advantages of MRI volume definition. The use of MRI provide smaller and better defined target volumes, with statistically significant decrease of rectal toxicity, comparing with computed tomography (CT)-based treatments, as that is made using MUPIT template [10].
Pre-planning techniques are employed in external radiotherapy (EBRT), frequently in contrast with brachytherapy. Potential reasons of this, in addition to the lack of commercial applications in clinical routine, are the possible anatomic changes that are produced after the applicator insertion (uterus straighten).
To have a pre-plan is always desirable, because it is an important aid for achieving optimal implant geometry that is able to obtain the best dosimetry distribution and coverage of clinical target volume (CTV) in brachytherapy treatments. This is mainly in patients with cervix tumors with irregular volumes or poor responses to EBRT and chemotherapy. The advantages of use a pre-planning are evident, and any advance in this direction will have a significant benefit in clinical practice. This article pre­sents the implementation of a pre-planning technique using the TB in multi-interstitial perineal and endocavitary gynecological brachytherapy.

Material and methods

The template Benidorm (Lorca Marin, Murcia, Spain), Figure 1, born out of the idea to combine technical advan­tages of MUPIT, intrauterine probe, and imaging advantages of MRI-based brachytherapy, while preserving the stability, geometry, and robustness of the implant. The design allows covering any desired volume in gynecological cancer from distal vagina to uterus and distal parametrium, avoiding possible errors of free-hand needle placement. This device is constructed using a template, which is fixed to the peri­neum, allowing the employment of titanium needles and an intrauterine component to provide a central brachytherapy dose [9,10,11]. The template consists in two perineal plates with two central holes, allowing placement of a vaginal cylinder (available in different sizes) to accommodate different vaginal lengths. These cylinders can also change accommodate by engage different intrauterine tubes change at by of varying angles and lengths. Additionally, the plates are drilled with 12 rows of holes, with 1.1 cm apart, to introduce straight and angled titanium needles 1.9 mm in diameter and 200 mm length. The plates have three dimples where A-vitamin pellets are placed as a recognizable fiducial marker in MRI to be used in the reconstruction process. The number, location, and depth of the needles are decided by the physician, and they are customized for each patient.
The MRI scans of the patients were acquired with a 1.5 T MRI imager (Optima MRI 450w, software version DV24, GE Medical Systems Milwaukee, Wisconsin, USA). An eight-channel phased array receiver coil was employed, according to standard clinical MRI protocols. Following the GEC-ESTRO recommendations [1,2,3], the acquisition consists on axial T2 weighted fast recovery fast spin-echo (FRFSE) sequence, with a slice thickness reduced to 2 mm. This sequence is used for both delineating and reconstruction. Magnetic resonance imaging acquisition setting details were included in a previous publication from Richart et al. [11].
An applicator library has been specifically developed for this applicator, using free available software [12] (Figure 1). The anchor points are three inserted A-vitamin pellets. This library is feasible and very efficient; thus saving time, significantly reducing needle identification errors and avoiding uncertainty. It allows to solve all the steps involved in the treatment planning (contouring, reconstruction, and optimization) in just a MRI T2 sequence mainly in saving time.
The implemented pre-planning procedure is as follow: 1: Pre-brachytherapy MRI T2 acquisition is carried out with the template in place just with the vaginal cylinder (without uterine tube and needles) 3-5 days prior to brachytherapy implant. A vaginal obturator of a known length (40, 60, 100, or 130 mm according to the vaginal length) is introduced and the bladder is filled with 50 cc of saline solution. 2: On this image set, the CTV is drawn. Clinical and image gross target volume (GTV) at diagnosis and the GTV at the time of the brachytherapy were unified in a single CTV (including GTV, high-risk CTV [CTVHR] and intermediate-risk CTV [CTVIR]), based on GEC ESTRO recommendations [13,14,15]. The required needles and their depths are selected to encompass CTV (as conformal as possible). To facilitate this task, a Java based application linked to the treatment planning system (TPS) (Oncentra Prostate version 4.3, Elekta AB, Stockholm, Sweden) has been developed. From this procedure, each needle identification and its depth is obtained previously to the implant. 3: With this information, radiation oncologist proceeds with implantation and then, a post-implant MRI is performed, in which the contouring, needles plus tandem reconstruction, and optimization are stablished.

Results and discussion

The developed Java application presents a friendly user interface, as is showed in Figure 2. The user can select the needles efficiently (both straight and divergent) to be included together with the free length, and then their depth. This information is incorporated automatically into the applicator library. The pre-brachytherapy MRI is performed in T2 mode, which is recommended for contouring. Once the specific virtual number of needles and depths have been selected, a virtual plan is made in Oncentra TPS and optimizing according to the required dosimetry and CTV coverage, the needles “density” (distance within needles) and extension. Figure 3 shows a case of MRI virtual pre-plan and MRI planning for dosimetry. In the virtual plan, the template is reconstructed using the library according to Otal et al. [12]. A rendering view of a virtual plan example is shown in Figure 4, in which the A-vitamin pellets (A1-A3), the needles, and uterine tandem are illustrated.
The virtual pre-plan procedure has significant advantages: needle depth estimation, needle positions and number, the coverage of the CTV being optimized while minimizing doses in organ at risk. “A suboptimal implant can never be transformed into a satisfactory application by any form of treatment planning optimization” [16]. The corrections being by are limited in cases of a suboptimal dosimetry due to an uncovered treatment volume. Treatment planning, based exclusively on MRI is preferred to other traditionally employed image modalities, like CT or methods combining both MRI and CT. Uncertainties are reduced with exclusive MRI because of the inaccuracies derived from CT-MRI registration procedures [17]. There has been a consequent growing interest in developing fully MRI compatible devices that allow the real-time insertion and guidance of the brachytherapy applicators [18]. Another option is MRI pre-plan. The primary limitation of the pre-plan is the lack of an intrauterine/intracavitary component and the likelihood of divergence of the needles, particularly when rigid needles are not used. The position of the uterus varies in the majority of the patients, being straight after the insertion of the intrauterine tube. The pre-plan can be done with IC component under general [19] or paravaginal [20,21] anesthesia. In spite of a virtual pre-plan, these authors describe one sixth of all needles planned, and implanted as free needles due to the geometrical limitation of tandem/ring and needle applicator [19]. Perineal templates like TB avoids previous limitations due to the use of rigid needles, can add an intrauterine component and can cover all the directions of tumor extension.
This pre-planning procedure has been successfully applied in 10 consecutive patients. An excellent reproduction of the virtual pre-planning has been achieved. When hysterectomized patients are treated, there is only a small change from pre-plan to post-plan. From our experience, in patients without surgery, the needles changes are also small, both in number and position after the insertion (within 5 mm at the tip for a typical depth of 160 mm). The same experienced radiation oncologist (SR) has completed the contouring in both pre- brachytherapy MRI and post-implant MRI. In our opinion, this virtual pre-plan technique can be extended easily to others multi-interstitial applicators like MUPIT or Syed, with an optimized number of needles and appropriate depth. Pre-planning and library allows an easy implant and quick reconstruction that is safe and time saving.

Conclusions

A virtual pre-planning technique using multi-interstitial and endocavitary TB has been introduced for use in gynecological brachytherapy. With the data presented, this pre-planning MRI-based system has demonstrated reliability, efficiency, and usefulness in clinical practice by facilitating the work of specialists, and reducing uncertainties of the application.

Acknowledgments

The current study was supported in part by Spanish Government under Project No. FIS2013-42156.

Disclosure

Authors report no conflict of interest.

References

1. Viswanathan A, Thomadsen B. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part I: general principles. Brachytherapy 2012; 11: 33-46.
2. Haie-Meder C, Pötter R, van Limbergen E, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005; 74: 235-245.
3. Pötter R, Haie-Meder C, van Limbergen E, et al. Recommendations from Gynaecological (GYN) GEC ESTRO Working Group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother Oncol 2006; 78: 67-77.
4. Dimopoulos J, Petrow P, Tanderup K, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (IV): Basis principles and parameters for MRI imaging within the frame of image based adaptive cervix cancer brachytherapy. Radiother Oncol 2012; 110: 113-122.
5. Kirisits C, Lang S, Dimopoulus J, et al. The Vienna applicator for combined intracavitary and interstitial brachytherapy of cervical cancer: design, application, treatment planning and dosimetric results. Int J Radiat Oncol Biol Phys 2006; 65: 624-630.
6. Nomden CN, de Leeuw AA, Moerland MA, et al. Clinical use of the Utrecht applicator for combined intracavitary/interstitial brachytherapy treatment in locally advanced cervical cancer. Int J Radiat Oncol Biol Phys 2012; 82: 1424-1430.
7. Martinez A, Cox RS, Edmundson GK. A multiple-site perineal applicator (MUPIT) for treatment of prostatic, anorectal and gynecologic malignancies. Int J Radiat Oncol Biol Phys 1984; 10: 297-305.
8. Syed A, Puthawala AA, Neblett D, et al. Transperineal interstitial intracavitary “Syed-Neblett” applicator in the treatment of carcinoma of the uterine cervix. Endocuriether Hypertherm 1986; 2: 1-13.
9. Rodríguez S, Richart J, Otal A, et al. A new template for MRI based intracavitary/interstitial gynecologic brachytherapy: design and clinical implementation. J Contemp Brachytherapy 2015; 7: 265-272.
10. Rodríguez S, Richart J, Otal A, et al. Development and clinical implementation of a new template for MRI-based intracavitary/interstitial gynecologic brachytherapy for locally advanced cervical cancer: from CT-based MUPIT to the MRI compatible Template Benidorm. Ten years of experience. J Contemp Brachytherapy 2016; 8: 404-414.
11. Richart J, Otal A, Rodriguez S, et al. A practical MRI-based reconstruction method for a new endocavitary and interstitial gynecological template. J Contemp Brachytherapy 2015; 5: 407-414.
12. Otal A, Richart J, Rodríguez S, et al. A method to incorporate the interstitial component into the TPS gynecologic rigid applicator library. Submitted to J Contemp Brachytherapy 2017; 9: 59-65.
13. Yoshida K, Yamazaki H, Takenaka T, et al. A dose-volume analysis of magnetic resonance image-aided high dose rate image-based interstitial brachytherapy for uterine cervical cancer. Int J Radiat Oncol Biol Phys 2010; 77: 765-772.
14. Viswanathan A, Dimopoulos J, Kirisits C, et al. Computed tomography versus magnetic resonance image-based contouring in cervical cancer brachytherapy: results of a prospective trial and preliminary guidelines for standardized contours. Int J Radiat Oncol Biol Phys 2007; 68: 491-498.
15. Viswanathan A, Erickson B, Rownd J. Image guided approaches to interstitial brachytherapy. In: Gynecologic radiation therapy: novel approaches to image-guidance and management. Viswanathan A, Kiristis C, Erickson B, Potter R (eds.). Springer, Berlin-Heidelberg 2011; p. 247-259.
16. Garbaulet A, Pötter R, Mazeron JJ, et al. The GEC ESTRO Handbook of Brachytherapy. ESTRO, Brussels 2002.
17. Hellebust TP, Kirisits C, Berger D, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group: Considerations and pitfalls in commissioning and applicator reconstruction in 3D image-based treatment planning of cervix cancer brachytherapy. Radiother Oncol 2010; 96: 153-160.
18. Viswanathan AN, Cormack R, Holloway CL, et al. Magnetic resonance-guided interstitial therapy for vaginal recurrence of endometrial cancer. Int J Radiat Oncol Biol Phys 2006; 66: 91-99.
19. Fokdal L, Tanderup K, Hokland SB, et al. Clinical feasibility of combined intracavitary/interstitial brachytherapy in locally advanced cervical cancer employing MRI with a tandem/ ring applicator in situ and virtual preplanning of the interstitial component. Radiother Oncol 2013; 107: 63-68.
20. Petric P, Hudej R, Music M. MRI assisted cervix cancer brachytherapy pre-planning, based on the insertion of the applicator in para-cervical anesthesia: preliminary results of a prospective study. J Contemp Brachytherapy 2009; 1: 163-169.
21. Petric P, Hudej R, Hanuna O, et al. MRI-assisted cervix cancer brachytherapy pre-planning, based on application in paracervical anesthesia: final report. Radiol Oncol 2014; 48: 293-300.