Magnetic resonance linear accelerator boost for para-urethral cancer: a new treatment paradigm replacement for brachytherapy

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Radiat Oncol J. 2025;43(2):104-108

Publication date (electronic) : 2025 June 4

doi : https://doi.org/10.3857/roj.2024.00584

Amir Owrangi^,1,2,*, David Chiu^2,*, Star Okolie², Kevin Albuquerque²

¹Department of Radiation Oncology, Baylor College of Medicine, Houston, TX, USA

²Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, USA

Correspondence: Amir Owrangi Department of Radiation Oncology, Baylor College of Medicine, 1919 Old Spanish Trl, Houston, TX 77054, USA Tel: +214-770-3366 E-mail: maowrangi@gmail.com, Amir.Owrangi@bcm.edu

*These authors contributed equally to this work.

Received 2024 August 31; Revised 2024 December 26; Accepted 2025 January 8.

Abstract

Introduction

The standard treatment protocol for individuals diagnosed with locally advanced gynecological cancer typically includes a combination of external beam radiation therapy (EBRT) and concurrent chemotherapy, followed by a brachytherapy (BT) boost [1]. However, para-urethral gynecological cancers (PUC), including those of the urethra, vagina, and bladder neck, pose a significant therapeutic challenge. In cases where the previously administered chemoradiotherapy followed by a BT boost is not an option, EBRT treatment approaches may be considered to avoid the need for extensive surgical resection, such as pelvic exenteration, mainly because surgical resection typically requires highly morbid exenteration. While the use of a sequential BT boost has demonstrated improved outcomes in patients with locally advanced or recurrent gynecological cancer [2-4], not all individuals are suitable candidates for this method due to factors such as tumor size or location, infiltration of the pelvic wall or adjacent organs such as bladder neck and urethra, bone infiltration, or the presence of multiple medical conditions that preclude them from undergoing anesthesia. Moreover, in some patients, poor anatomical accessibility of certain tumors for applicator placement prevents them from undergoing BT.

Moreover, in the curative treatment of cervical cancer, BT boost is relied upon primarily due to difficulty visualizing and protecting normal organs while delivering sufficiently high-dose external RT alone. Advances in imaging, including magnetic resonance imaging (MRI) visualization and adaptive re-planning, may overcome this limitation and reduce morbidity of organ preservation. Using MRI for initial and adaptive planning helps reduce target margins and generate a more accurate target dose distribution with a simultaneously integrated boost while sparing critical organs at risk such as urethra. Patients with gynecologic cancers who might find magnetic resonance–guided radiation therapy (MRgRT) beneficial include those with locoregional recurrences after surgery and those with oligometastatic conditions who are no longer responding to systemic therapy or are ineligible for systemic therapy due to comorbidities [5]. For the latter group, stereotactic body radiation therapy (SBRT) can be applied to both nodal and soft tissue metastases to achieve target tumor control with minimal morbidity. The use of SBRT for oligometastatic disease has been reported to enhance survival while preserving the quality of life [6].

While using MRgRT might be beneficial for patients with a variety of gynecological cancers, registration of images on the day of treatment with the images from the reference plan can be challenging. This may cause more pelvic structures’ contours to need to be updated. More contouring on the day of treatment will overall increase the time that the patient is in the magnetic resonance linear accelerator (MR-Linac). In this manuscript, we report on a novel approach of MR-Linac–based (with intravaginal cylinder spacer) adaptive radiation therapy boost (MR-CART).

Case Report

A pilot single-center retrospective study was conducted of five female patients with advanced PUC who received definitive /salvage radiation with MR-CART boost, following standard Linac-based chemoradiation to primary and regional lymphatics. All patients had undergone a hysterectomy and no patient had an intact uterus. A 3-dimensional-printed intravaginal cylinder, shown in Fig. 1, was used for every boost fraction, as previously described. The cylinder was developed as a vial to hold fluid with different outer diameters to fit the vaginal space snugly. The insertion depth was indexed on the surface of the device for better reproducibility between each fraction. The cylinder was inserted before each fraction and a MR survey was taken to ensure the insertion angle matched the planned geometry before acquiring adaptive planning images. MR-CART was delivered using MR-guided adapt-to-shape adaptive RT as needed to address tissue deformation and cylinder positioning changes in order to cover the primary target and small elective surrounding volume of bladder neck, urethra and/or vagina at physician discretion.

Fig. 1.

Illustration of a 3-dimensional printed intravaginal cylinder.

MRgRT was performed with a 1.5 Tesla MR-Linac. All patients were evaluated for contraindications (such as claustrophobia, metallic implants, pacemakers, etc.). Before treatment, written informed consent was taken from all patients and before the scan, a hollow plastic vaginal cylinder filled with water as an MRI contrast was inserted. A computed tomography simulation scan with a slice thickness of 2 mm in the same position was obtained for electron density assignment. High-resolution MR scanning was acquired on axial view providing T2/T1-weighted images. The axial, sagittal, coronal view of the vaginal cylinder is shown in Fig. 2. Headrests, headphones, knee support, a soft bed, and flexible torso coils were used in the supine position for simulation and treatment Fig. 3. Patients were instructed to empty their bladder before simulation or treatment. Laxatives and a low enema were used for rectal preparation if needed. Gross tumor volume (GTV) is defined based on visible tumor on T2-weighted MR images. Clinical target volume (CTV) extended from GTV to cover potential microscopic spread, incorporating surrounding tissue (vagina, urethra, bladder neck). Planning target volume (PTV) generated by adding a margin around the CTV to account for positional uncertainties and patient movement, 5 mm based on institutional guidelines. Our protocol consisted of five fractions of 5 Gy, for a total prescribed dose of 25 Gy. Baseline treatment planning was performed using static field intensity-modulated radiation therapy by means of 14 beams. Our planning objectives were to cover at least 95% of the PTV with maximum hot spot dose of less than 107%. The following constraints were applied: (1) D_max ≤ 2,675 cGy for the bladder; (2) V_{18 Gy} ≤ 35%, V_{28 Gy} ≤ 10%, V_{32 Gy} ≤ 5%, and D_max ≤ 1,710 cGy for the rectum; (3) D_max ≤ 2,650 cGy for the urethra; (4) D_max < 1,935 cGy for sigmoid. An adaptive plan was created for each treatment session, resulting in a total of five adapt-to-shape plans per patient. The average total treatment time (from setup to treatment delivery) was approximately 50 minutes, including imaging and adaptive planning when needed.

Fig. 2.

Illustration of axial (A), coronal (B), and sagittal (C) view of the vaginal cylinder. All contouring was performed on magnetic resonance imaging.

Fig. 3.

(A) Intravaginal cylinder insertion. (B, C) Patient setup in magnetic resonance (MR) linear accelerator. SBRT, stereotactic body radiation therapy; VacBag, vacuum bag.

With MR-guided radiotherapy we were able to spare the urethra—from hotspots unlike BT—with the D_0.1cc below 80 Gy in a normalized total doses of 2 Gy per fraction. Also we were able to cover entire circumference of urethra if needed.

Local, regional, and distant failure and available toxicity data were recorded with a retrospective chart review. Patients were evaluated for treatment response and toxicities. Patients were examined weekly during the treatment and every 3 months thereafter by the treating physician; the results of these examinations are recorded in the hospital database. Toxicity was described using the Common Terminology Criteria for Adverse Events version 5.0.

The cohort consisted of five patients with a median age at diagnosis of 75 years and ages ranging from 70-81 years. Two patients had vaginal cancer invading the urethra (stage III), one patient had vaginal cancer invading the bladder (stage IVA), one patient had endometrial cancer (grade 1), and one patient had recurrent cervical cancer (stage IVA). As shown in Table 1, MRgRT which was administered in hypofractionated form in most cases with doses between 4.5 to 5 Gy per fraction, following standard fractionation pelvic chemoradiation. Patient tumor location, total target, and organ-at-risk doses areas shown in Table 1 in equivalent dose in 2 Gy fractions format.

Table 1.

Dosimetric characteristics of tumor and normal structures

MRgRT boost was delivered successfully to these patients with a median follow-up of 14.4 months (range, 1.1 to 17.6 months) with complete response on exam and imaging. Acute toxicities included dysuria reported by one patient at 5 weeks and vaginal pain reported by two patients within three months. Chronic toxicities (at least 3 months after treatment) included dysuria reported by one patient, vaginal pain reported by one patient, and urinary incontinence reported by two patients. Two patients also reported worsening of existing neuropathy. The online MR-Linac allowed very tight dose control of primary site while sparing normal unaffected tissues.

MRgRT was well tolerated by all patients. Overall survival was 100%. The rate of recurrence was 20%, and the rate of recurrence-free survival and the local control rate were 80%. Toxicities are shown in Table 2. None of the patients in this cohort had grade >3 late genitourinary toxicities.

Table 2.

Patient characteristics

Discussion

This study presented a novel approach to the treatment of PUC, including those of the urethra, vagina, and bladder neck, using MRgRT with a focus on utilizing vaginal cylinders as surrogates for image registration.

This study demonstrates the feasibility and efficacy of MRgRT in patients ineligible for BT boost, providing a valuable alternative treatment option. The vaginal cylinder facilitated accurate image registration on treatment days, potentially reducing the need for contour updates and shortening treatment time in the MR-Linac. This is crucial for MRgRT, where image guidance is essential for precise tumor targeting and minimizing dose to surrounding organs. It’s most important purpose however was to displace the rectum from the para-urethral tumor—thus ensuring a low rectal dose and, potentially reducing the risk of radiation-related toxicities. This is particularly important for SBRT, which delivers high radiation doses in fewer fractions.

To date, there are limited studies that have investigated the role of MRgRT in patients diagnosed with gynecological cancers. As not every patient is suitable for BT, some studies [7,8] investigated the feasibility of magnetic resonance–guided SBRT boost following chemoradiotherapy.

However, several limitations warrant consideration. The sample size of five patients is relatively small, limiting the generalizability of the findings. Additionally, the retrospective nature of the study and the lack of a control group preclude definitive conclusions regarding the efficacy of MRgRT compared to standard treatment modalities.

In conclusion, the study provides valuable insights into the use of MRgRT with vaginal cylinders for the treatment of PUC. This study shows that vaginal cylinder not only can be used as a surrogate for vaginal cancer image registration, it can also separate rectum from the treatment volume. This initial experience of MRgRT shows excellent short-term functional and tumor control results and could be a change in paradigm management for these patients. We hope to expand this cohort and continue follow-up for our patients. While preliminary findings are promising, further research is needed to validate these findings and establish MRgRT as a standard-of-care treatment modality for patients with locally advanced gynecological malignancies.

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