eISSN: 2081-2841
ISSN: 1689-832X
Journal of Contemporary Brachytherapy
Current Issue Archive Supplements Articles in Press Journal Information Aims and Scope Editorial Office Editorial Board Register as Author Register as Reviewer Instructions for Authors Abstracting and indexing Subscription Advertising Information Links
SCImago Journal & Country Rank

3/2022
vol. 14
 
Share:
Share:
more
 
 
Original paper

Magnetic resonance imaging in cervical cancer interventional radiotherapy (brachytherapy): a pictorial essay focused on radiologist management

Luca Russo
1
,
Valentina Lancellotta
2
,
Maura Miccò
1
,
Bruno Fionda
2
,
Giacomo Avesani
1
,
Angeles Rovirosa
3, 4
,
Piotr Wojcieszek
5
,
Giovanni Scambia
6, 7
,
Riccardo Manfredi
1, 8
,
Luca Tagliaferri
2
,
Benedetta Gui
1

1.
Area Diagnostica per Immagini, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
2.
Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
3.
Fonaments Clinics Department, Faculty of Medicine, University of Barcelona, Barcelona, Spain
4.
Department of Radiation Oncology, Hospital Clinic i Universitari, Barcelona, Spain
5.
Brachytherapy Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
6.
UOC Ginecologia Oncologica, Dipartimento per la Salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
7.
Istituto di Ginecologia e Ostetricia, Università Cattolica del Sacro Cuore, Rome, Italy
8.
Dipartimento Universitario di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy
J Contemp Brachytherapy 2022; 14, 3: 287–298
Online publish date: 2022/06/30
Article file
- Magnetic resonance.pdf  [0.75 MB]
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
 

Purpose


Cervical cancer accounted for approximately 570,000 in 2018, becoming the fourth most frequent cancer in women [1]. Treatment depends on FIGO stage at diagnosis [2], performance status, and patients’ compliance.
Locally advanced cervical cancer (LACC), including stage IB3-IVA, is usually treated with platinum-based chemotherapy in association with external beam radiotherapy (EBRT), followed by brachytherapy (BT), often also called ‘interventional radiotherapy’ (IRT) [3, 4]. Magnetic resonance imaging (MRI) is the modality of choice in cervical cancer for both staging and response evaluation after concurrent chemoradiation therapy (CCRT) [2, 5].
Interventional radiotherapy in cervical cancer had advanced in the last ten years, using three-dimensional (3D) imaging and technological innovations [6-8]. Among imaging modalities, MRI is considered the most accurate imaging modality, compared with pathologic specimen, in the evaluation of the cervix tumor volume [9-12]. Several studies have proven that patient outcome improves using MRI in cervical cancer treatment [13-20]. MRI-guided IRT has been first proposed in 1992 [21], and since then has become the method of choice for planning IRT [22].
Image-guided IRT (IG-IRT) utilization is recently increasing; most of the centers use MRI-based planning at the first fraction, while few centers utilize MRI-based planning for each fraction [23]. It is due to the number of MRI scanner, increased effort demands, and a longer scan time.
The aim of this paper was to describe the MRI radiological workflow currently ongoing at our Institution. Furthermore, we provided a detailed MRI and IRT workflow, and a step-by-step approach in order to help, especially radiologists, in implementation of effective MRI-based IRT into general clinical practice.

Material and methods

Treatment procedure


Between July 2020 and April 2021, 65 consecutive patients with LACC underwent MRI-based IRT, following Gynecological Groupe Européen de Curietherapie-European Society for Radiotherapy and Oncology working group contouring and planning guidelines (Recommendations I and II by working group) [9, 24]. MR-safe applicators were used for all patients. Oncentra (Oncentra®Brachy treatment planning; Elekta, Sweden) system was applied to plan all treatments. Treatment was delivered using Elekta Flexitron afterloading machines with iridium-192 (192Ir) source.
Based on our protocol, interventional radiotherapy boost to high-risk clinical target volume (HR-CTV) and intermediate-risk CTV (IR-CTV) is performed after 45 Gy delivered with EBRT to low-risk CTV, IR-CTV, and HR-CTV, following GEC-ESTRO guidelines. The total IRT dose is 28 Gy to achieve a dose between 85 Gy to 95 Gy EQD2 (α/β = 10Gy) to D90 HR-CTV, and 14 Gy to IR-CTV in four high-dose-rate (HDR) fractions in order to achieve a D90 > 60 Gy EQD2 (α/β = 10Gy) [9].
The treatment was arranged following an internal protocol: 1) baseline MRI (staging MRI), 2) EBRT, 3) post-EBRT pelvic MRI (post-EBRT MRI: day 1), 4) first applicator insertion (day 1), 5) pelvic MRI with applicators (post-applicator insertion MRI: day 1), 6) first and second fractions treatment planning, delivery, and applicator removal (day 1 and day 2), 7) second applicator insertion, third and fourth fractions treatment planning, delivery and applicator removal (day 10 and day 11). Time associated with delivery of first fraction was recorded. Details regarding the first insertion are presented in Figure 1. Computed tomography (CT) was performed for every IRT fraction to elaborate treatment planning for each treatment (1st, 2nd, 3rd, and 4th fractions). Planning CT images were acquired with 0.625 mm slice thickness and transmitted to treatment planning system (Oncentra).

Workflow planning


Our Institution’s MRI room is located close to the interventional oncology center (operative room and HDR-IRT bunker), taking 3-5 minutes to transfer patients between the two areas.

MRI protocol (for staging and evaluation post-EBRT, before and after applicator positioning)


Staging MRI and post-EBRT MRI were performed for all patients with a 1.5 T MR scanner (Echospeed Horizon and Infinity, General Electric Healthcare, GE), using a standard 8-channel phased-array body coil. MRI sequences included conventional MRI and diffusion-weighted imaging (DWI) sequences. Intra-muscular butylscopolamine (1 mg of buscopan, Schering) was administered to reduce bowel peristalsis. Conventional sequences included axial T2- and T1-weighted fast spin echo (FSE) sequence, high resolution FSE T2-weighted images in different imaging planes (sagittal/oblique axial and oblique coronal, respectively, perpendicular and parallel to the long axis of cervix). DWI sequence was performed on the same orientation of axial oblique FSE T2-WI, using single-shot diffusion-weighted echo-planar sequence, including two b-values (degree of diffusion weighting applied: 0 and 1,000 s/mm2). Axial T2-WI single-shot fast spin echo (SSFSE) and balanced steady-state gradient echo sequence (FIESTA, GE brand) were acquired up to the renal hila, to assess eventual lumbo-aortic lymphadenopathy and/or hydronephrosis. Detailed acquisition protocol is reported in Table 1.
After applicator insertion, patients were re-scanned with 1.5 T MRI. Post-applicator positioning MRI was performed with fast imaging protocol, including only high resolution FSE T2-WI in three planes (axial, sagittal, and coronal) according to tandem applicator axis (Table 2). The aim of this scan was to assess correct positioning of the tandem and its’ position relatively to the cervix and/or the residual tumor, to accurately plan IRT treatment.

Applicator insertion


The positioning of the applicator was performed under general anesthesia. A Foley catheter was positioned into the bladder. After dilatation of the cervical canal, the applicator was placed using a transrectal US-guided procedure to ensure the correct position and reduce the risk of uterus perforation. The IRT applicator would serve as a canal for transportation of radioactive source.
The applicator must be MR-safe. Different applicator models are commercially available. It can be made of stainless steel, titanium, or plastic, and is composed of two main parts, including central tandem with ovoids or central tandem with ring. The central tandem is located inside the uterus canal, functioning as a stabilizer and means of passage of the radioactive source to the cervix and the uterus. The ovoids or ring are attached to the lower part of the tandem, and are usually allocated in the vaginal fornices leaning on the cervix. In case of parametrial involvement, interstitial IRT is recommended. Then, rectal probe is placed in the rectum to confirm the correct positioning of the implant.

Treatment planning


Organs at risk (OARs), IR-CTV, and HR-CTV were delineated as follows: Organs at risk: Delineation of the rectum, bladder, sigmoid, and small bowel following their other contour.
Target volume delineation: IR-CTV carrying a significant microscopic tumor load, encompassed HR-CTV with a safety margin of 5-15 mm (with the exclusion of OARs). Amount of safety margin was chosen according to the tumor size and location, potential tumor spread, tumor regression, and treatment strategy.
HR-CTV included cervix + visible/palpable disease and gross tumor volume (GTV) – T2 bright areas [9]. Dose reporting was based on the total (EBRT + IRT) biologically equivalent dose in 2 Gy fractions (EQD2). Planning purposes were to deliver a minimum of 60 Gy to 90% isodose volume (D90), including IR-CTV, at least 85 Gy to D90 of HR-CTV, and more than 90 Gy to D98 of GTV preserving the established D2cc (the minimum doses calculated at the most irradiated 2cc volume) at OARs.

Focus on MRI role

Staging MRI and post-EBRT MRI: Staging and treatment response evaluation


MRI has shown high accuracy in cervical cancer evaluation, mainly for tumor size, assessment of deep stromal invasion, and parametrial invasion (specificity 97%, negative predictive value [NPV] 100%) [25, 26]. In addition, internal os involvement can be assessed on
MRI with high sensitivity (90%) and specificity (98%).
At our Institution, response evaluation criteria in solid tumors (RECIST) version 1.1 are used to evaluate response to CCRT [27]. In case of complete response (CR) or partial response (PR)/stable disease (SD), patients are suitable for IRT. The standard method to assess the response to EBRT is to evaluate tumor size modification on post-EBRT MRI. Tumor size reduction is indicative of a good prognosis in LACC [28]. Full-thickness T2-WI low signal intensity is an indicator of reconstitution of cervical stroma integrity, configuring complete response to EBRT (NPV = 97%) [29]. However, hyperintense signal can be still visible on T2-WI, representing EBRT-induced inflammation, oedema, and necrosis [30]. DWI can improve detection of residual tumor, presenting as a focal hyperintense area on T2-WI and DWI, with corresponding hypointensity on the apparent diffusion coefficient (ADC) map [31, 32]. MRI evaluation of tumor response after therapy requires a comparative evaluation with staging MRI, in order to better interpret the imaging findings.
ADC can be helpful in differentiating residual tumor from post-radiotherapy fibrosis. Modifications of ADC value during and after EBRT have been associated with response to treatment and survival [33]. However, ADC value use is limited because of variable cut-offs reported in literature [34].
Concerning dynamic contrast enhancement (DCE) MRI, there is no consensus regarding its role for tumor response evaluation after EBRT treatment [34]. Some studies found that time-signal intensity evaluations are associated with treatment response [35, 36]. In our department, gadolinium-based contrast agent is not administered neither at staging MRI nor at post-EBRT MRI.
At our Institution, a standardized pro-forma reporting is used (Figure 2) for both staging MRI and post-EBRT MRI for correct staging of the tumor and evaluation of the response after EBRT, according to RECIST version 1.1. Moreover, every parameter and important sites of tumor extension are reported and compared between staging MRI and post-EBRT MRI.
Mandatory findings include tumor diameter, cervical stroma invasion, parametrial invasion, vaginal invasion, uterus corpus/fundus invasion, hydronephrosis, relationship with adjacent organs (bladder/rectum), and lymph nodes.
The type of applicator is evaluated on case-by-case basis, and if post-EBRT MRI shows evidence of progressive disease or vesicouterine or rectouterine/rectovaginal fistula, a deep discussion is done in order to define the best personalized approach (Figure 3). On T2-WI, fistulas are seen as high signal intensity breach of the wall between cervix/vagina and the rectum or bladder. Sagittal plane is the most appropriate one for the detection of fistulas. These findings must be promptly reported and considered for next treatments planning.
CCRT can be a cause of ancillary findings, especially inflammatory ones regarding the rectum, sigmoid, and bladder. Radiologists must be aware of these because patients are often asymptomatic. Free fluid in the pouch of Douglas is a common collateral finding. Proctitis or colitis can be detected as mucosal thickening of the rectum or sigmoid colon.

Evaluation after applicator positioning


Post-applicator MRI serves to evaluate applicator positioning and provide support to IRT planning, in terms of tumor position and extension related to the applicator (Figure 4). Radiologists dealing with MRI-guided IRT are required to know specific parts of the applicator (ring, ovoids, tandem, etc.) and how to use the device. Surgical packing can be detected in vaginal cavity around the applicator, as low-signal intensity material, and should not be mistaken as hemorrhage or residual tumor. At our Institution, it is possible to perform endocavitary and interstitial IRT procedure. If residual tumor is detected, its’ relationship with the tandem/any vaginal applicator should be described. A structured report is currently in use at our Institution for post-applicator positioning MRI (Figure 5). This report includes useful findings for interventional radiation oncologists during IRT treatment planning. Firstly, type and position of the applicator considering location of tandem and ovoids or ring are described (Figures 6, 7). Secondly, relationships between the tandem and eventual residual tumor are defined (Figures 8, 9). In details, cranio-caudal extension of residual tumor and its’ location and maximum thickness are reported using a clockwise system (Figures 10, 11).
After EBRT, cervical and uterine tissues change after radiation, and for this reason, a uterine perforation can occur. US-guided insertion and post-applicator MRI enable accurate detection of this complication [37, 38].
On MRI images, the adjacent OARs are identified [9, 10]. At our Institution, GTV, HR-CTV, IR-CTV, and OARs are segmented by radiation oncologist, who, whenever necessary, reviews images with the radiologist [9, 10]. After plan optimization approving, procedures are applied: • radiation oncologist approval, • calculation check by physicist, • review by therapists. Then, the treatment is delivered.

Conclusions


The workflow currently ongoing at our Institution was presented. 1.5 T MRI is performed before and after cervix applicator insertion, with unquestionable advantages. First, MRI is the imaging modality of choice for staging and treatment response assessment due to high accuracy in cervical cancer evaluation (tumor size, assessment of deep stromal invasion, and parametrial invasion). After concurrent EBRT, MRI with DWI provides accurate evaluation of treatment response. Furthermore, MRI scan after applicator insertion is essential for the evaluation of correct cervix applicator insertion, and provides accurate assistance for IRT treatment planning in order to achieve personalized approach.

Disclosure


The authors report no conflict of interest.
1. Bray F, Ferlay J, Soerjomataram I et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
2. Bhatla N, Aoki D, Sharma DN et al. Cancer of the cervix uteri. Int J Gynaecol Obstet 2018; 143 Suppl 2: 22-36.
3. Koh WJ, Abu-Rustum NR, Bean S et al. Cervical cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2019; 17: 64-84.
4. Campitelli M, Lazzari R, Piccolo F et al. Brachytherapy or external beam radiotherapy as a boost in locally advanced cervical cancer: a Gynaecology Study Group in the Italian Association of Radiation and Clinical Oncology (AIRO) review. Int J Gynecol Cancer 2021; 31: 1278-1286.
5. Fournier LS, Bats AS, Durdux C. Diffusion MRI: Technical principles and application to uterine cervical cancer. Cancer Radiother 2020; 24: 368-373.
6. Kim H, Beriwal S, Houser C et al. Dosimetric analysis of 3D image-guided HDR brachytherapy planning for the treatment of cervical cancer: is point A-based dose prescription still valid in image-guided brachytherapy? Med Dosim 2011; 36: 166-170.
7. Mayadev J, Viswanathan A, Liu Y et al. American Brachytherapy Task Group Report: a pooled analysis of clinical outcomes for high-dose-rate brachytherapy for cervical cancer. Brachytherapy 2017; 16: 22-43.
8. Soror T, Siebert FA, Lancellotta V et al. Quality assurance in modern gynecological HDR-brachytherapy (Interventional Radiotherapy): clinical considerations and comments. Cancers (Basel) 2021; 13: 912.
9. Haie-Meder C, Potter 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.
10. Harkenrider MM, Alite F, Silva SR et al. Image-based brachytherapy for the treatment of cervical cancer. Int J Radiat Oncol Biol Phys 2015; 92: 921-934.
11. Owrangi AM, Prisciandaro JI, Soliman A et al. Magnetic resonance imaging-guided brachytherapy for cervical cancer: initiating a program. J Contemp Brachytherapy 2015; 7: 417-422.
12. Tanderup K, Viswanathan AN, Kirisits C et al. Magnetic resonance image guided brachytherapy. Semin Radiat Oncol 2014; 24: 181-191.
13. Chargari C, Magne N, Dumas I et al. Physics contributions and clinical outcome with 3D-MRI-based pulsed-dose-rate intracavitary brachytherapy in cervical cancer patients. Int J Radiat Oncol Biol Phys 2009; 74: 133-139.
14. Dimopoulos JC, Potter R, Lang S et al. Dose-effect relationship for local control of cervical cancer by magnetic resonance image-guided brachytherapy. Radiother Oncol 2009; 93: 311-315.
15. Gill BS, Kim H, Houser CJ et al. MRI-guided high-dose-rate intracavitary brachytherapy for treatment of cervical cancer: the University of Pittsburgh experience. Int J Radiat Oncol Biol Phys 2015; 91: 540-547.
16. Mahantshetty U, Swamidas J, Khanna N et al. Reporting and validation of gynaecological Groupe Euopeen de Curietherapie European Society for Therapeutic Radiology and Oncology (ESTRO) brachytherapy recommendations for MR image-based dose volume parameters and clinical outcome with high dose-rate brachytherapy in cervical cancers: a single-institution initial experience. Int J Gynecol Cancer 2011; 21: 1110-1116.
17. Nomden CN, de Leeuw AA, Roesink JM et al. Clinical outcome and dosimetric parameters of chemo-radiation including MRI guided adaptive brachytherapy with tandem-ovoid applicators for cervical cancer patients: a single institution experience. Radiother Oncol 2013; 107: 69-74.
18. Potter R, Dimopoulos J, Georg P et al. Clinical impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer. Radiother Oncol 2007; 83: 148-155.
19. Potter R, Georg P, Dimopoulos JC et al. Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer. Radiother Oncol 2011; 100: 116-123.
20. Sturdza A, Potter R, Fokdal LU et al. Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study. Radiother Oncol 2016; 120: 428-433.
21. Schoeppel SL, Ellis JH, LaVigne ML et al. Magnetic resonance imaging during intracavitary gynecologic brachytherapy. Int J Radiat Oncol Biol Phys 1992; 23: 169-174.
22. Beddy P, Rangarajan RD, Sala E. Role of MRI in intracavitary brachytherapy for cervical cancer: what the radiologist needs to know. AJR Am J Roentgenol 2011; 196: W341-347.
23. Grover S, Harkenrider MM, Cho LP et al. Image guided cervical brachytherapy: 2014 Survey of the American Brachytherapy Society. Int J Radiat Oncol Biol Phys 2016; 94: 598-604.
24. Potter 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.
25. Sahdev A, Sohaib SA, Wenaden AE et al. The performance of magnetic resonance imaging in early cervical carcinoma: a long-term experience. Int J Gynecol Cancer 2007; 17: 629-636.
26. Epstein E, Testa A, Gaurilcikas A et al. Early-stage cervical cancer: tumor delineation by magnetic resonance imaging and ultrasound – a European multicenter trial. Gynecol Oncol 2013; 128: 449-453.
27. Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-247.
28. Angeles MA, Baissas P, Leblanc E et al. Magnetic resonance imaging after external beam radiotherapy and concurrent chemotherapy for locally advanced cervical cancer helps to identify patients at risk of recurrence. Int J Gynecol Cancer 2019; 29: 480-486.
29. Sala E, Rockall AG, Freeman SJ et al. The added role of MR imaging in treatment stratification of patients with gynecologic malignancies: what the radiologist needs to know. Radiology 2013; 266: 717-740.
30. Vincens E, Balleyguier C, Rey A et al. Accuracy of magnetic resonance imaging in predicting residual disease in patients treated for stage IB2/II cervical carcinoma with chemoradiation therapy: correlation of radiologic findings with surgicopathologic results. Cancer 2008; 113: 2158-2165.
31. Gui B, Micco M, Valentini AL et al. Prospective multimodal imaging assessment of locally advanced cervical cancer patients administered by chemoradiation followed by radical surgery – the “PRICE” study 2: role of conventional and DW-MRI. Eur Radiol 2019; 29: 2045-2057.
32. Thomeer MG, Vandecaveye V, Braun L et al. Evaluation of T2-W MR imaging and diffusion-weighted imaging for the early post-treatment local response assessment of patients treated conservatively for cervical cancer: a multicentre study. Eur Radiol 2019; 29: 309-318.
33. Erbay G, Onal C, Karadeli E et al. Predicting tumor recurrence in patients with cervical carcinoma treated with definitive chemoradiotherapy: value of quantitative histogram analysis on diffusion-weighted MR images. Acta Radiol 2017; 58: 481-488.
34. Manganaro L, Lakhman Y, Bharwani N et al. Staging, recurrence and follow-up of uterine cervical cancer using MRI: Updated Guidelines of the European Society of Urogenital Radiology after revised FIGO staging 2018. Eur Radiol 2021; 31: 7802-7816.
35. Jalaguier-Coudray A, Villard-Mahjoub R, Delouche A et al. Value of dynamic contrast-enhanced and diffusion-weighted MR imaging in the detection of pathologic complete response in cervical cancer after neoadjuvant therapy: a retrospective observational study. Radiology 2017; 284: 432-442.
36. Mayr NA, Wang JZ, Zhang D et al. Longitudinal changes in tumor perfusion pattern during the radiation therapy course and its clinical impact in cervical cancer. Int J Radiat Oncol Biol Phys 2010; 77: 502-508.
37. Sullivan T, Yacoub JH, Harkenrider MM et al. Providing MR imaging for cervical cancer brachytherapy: lessons for radiologists. Radiographics 2018; 38: 932-944.
38. Viswanathan AN, Beriwal S, De Los Santos JF et al. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high-dose-rate brachytherapy. Brachytherapy 2012; 11: 47-52.
Copyright: © 2022 Termedia Sp. z o. o. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
 
Quick links
© 2022 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.