Key points

Introduction

Brachytherapy is a radiotherapy (RT) modality in which the radiation is delivered by positioning radioactive sources directly inside the tumor. Brachytherapy for the treatment of gynecologic malignancies was first proposed in the early 1900s, with an intracavitary radium applicator documented in 1905. More than 100 years later, brachytherapy remains the standard of care for a broad range of gynecologic malignancies. The use of brachytherapy to deliver a boost dose to the remaining tumor following external beam RT for the treatment of cervical cancer is the standard of care worldwide because it results in a significantly higher rate of survival than external beam RT alone. During the past decade, a decline in brachytherapy utilization in favor of external beam techniques has been associated with a decrease in the survival rate. In cervical cancer brachytherapy, typically, an applicator composed of a uterine tandem is inserted into the uterine canal and a vaginal component comprising either a ring-shaped applicator (ring) or 2 colpostats (ovoids) is positioned at the top of the vagina against the cervix. Historically, a standard desired-dose distribution, described as pear-shaped ( Fig. 1 ), has been used and the dose prescribed to the position referred to as point A. However, this method does not take into account patient-specific information on tumor size and largely disregards information on organs at risk (bladder, rectum, sigmoid, bowel). This practice is still widespread in places without MR–guidance capability, although less by choice than by necessity. Whereas ultrasound can assist in the correct identification of the uterine canal during tandem insertion and plain radiographs help identify the applicator in relation to landmarks to delineate points representing the bladder and the rectum, neither of these imaging modalities renders the residual tumor visible. Even on computed tomography (CT) scans that enable 3-dimensional (3D) planning and accurate definition of organs at risk, cervical tumors are difficult to distinguish from surrounding scar tissue resulting from the external beam treatment that precedes brachytherapy. The advent of remote afterloading systems allows the robotic deployment of a high-dose-rate or a pulsed-dose-rate source into the inside of the applicator, with the source resting for varying times at points along the applicator, creating a customized dose distribution. Nevertheless, the technical capability of delivering very precise customized dose distributions has limited value without accurate delineation of the gross tumor volume (GTV) and the surrounding areas likely containing microscopic disease (clinical target volume [CTV]).

( A ) Standard pear-shape distribution. ( B ) Sculpted pear.

The utility of MR imaging for cervical cancer delineation to assist with brachytherapy planning was first recognized in the early 1990s. With increased availability of MR scanners for use with RT, a growing interest in MR–guided insertions and planning resulted in a period of intense exploration of MR–guided cervical-cancer brachytherapy both in Europe, with publications as early as 1992, and in the United States, with the first prospective trial starting in 2004. The variability in MR scanner characteristics; MR sequences; applicator material and configuration; tumor-contouring methodologies; and dose prescription, planning, and reporting require careful interpretation of the data from many clinics. A task force was set up by the Group Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) to promote and standardize the use of MR imaging for cervical cancer brachytherapy. This effort culminated in a series of guidelines in Europe and in the United States (through the American Brachytherapy Society). The combination of tumor visibility on MR images and flexibility in dose planning shifted dose distributions from a standard pear-shape configuration to a sculpted-pear configuration (see Fig. 1 ). Clinical and physics investigations have since shown that customized planning provides better dosimetry, which translates into superior clinical outcomes. An international research effort to collect and analyze treatment data for cervical-cancer brachytherapy delivered according to the GEC-ESTRO guidelines is underway with the EMBRACE research trial ( www.embracestudy.dk ).

Technological advances and economic factors have increased the availability of MR scanners for brachytherapy procedures, especially high-field-strength scanners. Although the number of centers performing MR–guided insertions continues to grow, MR imaging planning based on a post facto scan (ie, a scan acquired after the insertion is completed and after patient transfer from the operating room) is already performed in a wide variety of centers. Guidelines on which MR imaging sequences should be used have been published and validated ; however, the fast pace of technological change may result in a separation between current imaging practices and available guidelines. For instance, 3 T MR is becoming more available and its use is expected to improve image quality and available resolution. Concerns regarding the applicability of existing contouring guidelines, image deformation, heating of the brachytherapy equipment, and image artifacts have been raised by some investigators. Experience in some major centers, notably in the Advanced Multimodality Image Guided Operating (AMIGO) suite at the Brigham and Women’s Hospital in Boston, has proven the feasibility of 3 T MR-based brachytherapy.

This article focuses on the state of the art and recent innovations in the use of MR guidance for gynecologic brachytherapy. The analysis is subdivided by thematic areas. First, the intraoperative role of MR imaging in the practice of gynecologic brachytherapy, allowing for the interactive adjustment of applicator positioning, is discussed. Second, the practical aspects of MR–guided gynecologic brachytherapy, with the presentation of recent innovations in the field, are discussed. Finally, some radiation therapy physics considerations regarding treatment planning and quality assurance are introduced.

Introduction

Brachytherapy is a radiotherapy (RT) modality in which the radiation is delivered by positioning radioactive sources directly inside the tumor. Brachytherapy for the treatment of gynecologic malignancies was first proposed in the early 1900s, with an intracavitary radium applicator documented in 1905. More than 100 years later, brachytherapy remains the standard of care for a broad range of gynecologic malignancies. The use of brachytherapy to deliver a boost dose to the remaining tumor following external beam RT for the treatment of cervical cancer is the standard of care worldwide because it results in a significantly higher rate of survival than external beam RT alone. During the past decade, a decline in brachytherapy utilization in favor of external beam techniques has been associated with a decrease in the survival rate. In cervical cancer brachytherapy, typically, an applicator composed of a uterine tandem is inserted into the uterine canal and a vaginal component comprising either a ring-shaped applicator (ring) or 2 colpostats (ovoids) is positioned at the top of the vagina against the cervix. Historically, a standard desired-dose distribution, described as pear-shaped ( Fig. 1 ), has been used and the dose prescribed to the position referred to as point A. However, this method does not take into account patient-specific information on tumor size and largely disregards information on organs at risk (bladder, rectum, sigmoid, bowel). This practice is still widespread in places without MR–guidance capability, although less by choice than by necessity. Whereas ultrasound can assist in the correct identification of the uterine canal during tandem insertion and plain radiographs help identify the applicator in relation to landmarks to delineate points representing the bladder and the rectum, neither of these imaging modalities renders the residual tumor visible. Even on computed tomography (CT) scans that enable 3-dimensional (3D) planning and accurate definition of organs at risk, cervical tumors are difficult to distinguish from surrounding scar tissue resulting from the external beam treatment that precedes brachytherapy. The advent of remote afterloading systems allows the robotic deployment of a high-dose-rate or a pulsed-dose-rate source into the inside of the applicator, with the source resting for varying times at points along the applicator, creating a customized dose distribution. Nevertheless, the technical capability of delivering very precise customized dose distributions has limited value without accurate delineation of the gross tumor volume (GTV) and the surrounding areas likely containing microscopic disease (clinical target volume [CTV]).

( A ) Standard pear-shape distribution. ( B ) Sculpted pear.

The utility of MR imaging for cervical cancer delineation to assist with brachytherapy planning was first recognized in the early 1990s. With increased availability of MR scanners for use with RT, a growing interest in MR–guided insertions and planning resulted in a period of intense exploration of MR–guided cervical-cancer brachytherapy both in Europe, with publications as early as 1992, and in the United States, with the first prospective trial starting in 2004. The variability in MR scanner characteristics; MR sequences; applicator material and configuration; tumor-contouring methodologies; and dose prescription, planning, and reporting require careful interpretation of the data from many clinics. A task force was set up by the Group Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) to promote and standardize the use of MR imaging for cervical cancer brachytherapy. This effort culminated in a series of guidelines in Europe and in the United States (through the American Brachytherapy Society). The combination of tumor visibility on MR images and flexibility in dose planning shifted dose distributions from a standard pear-shape configuration to a sculpted-pear configuration (see Fig. 1 ). Clinical and physics investigations have since shown that customized planning provides better dosimetry, which translates into superior clinical outcomes. An international research effort to collect and analyze treatment data for cervical-cancer brachytherapy delivered according to the GEC-ESTRO guidelines is underway with the EMBRACE research trial ( www.embracestudy.dk ).

Technological advances and economic factors have increased the availability of MR scanners for brachytherapy procedures, especially high-field-strength scanners. Although the number of centers performing MR–guided insertions continues to grow, MR imaging planning based on a post facto scan (ie, a scan acquired after the insertion is completed and after patient transfer from the operating room) is already performed in a wide variety of centers. Guidelines on which MR imaging sequences should be used have been published and validated ; however, the fast pace of technological change may result in a separation between current imaging practices and available guidelines. For instance, 3 T MR is becoming more available and its use is expected to improve image quality and available resolution. Concerns regarding the applicability of existing contouring guidelines, image deformation, heating of the brachytherapy equipment, and image artifacts have been raised by some investigators. Experience in some major centers, notably in the Advanced Multimodality Image Guided Operating (AMIGO) suite at the Brigham and Women’s Hospital in Boston, has proven the feasibility of 3 T MR-based brachytherapy.

This article focuses on the state of the art and recent innovations in the use of MR guidance for gynecologic brachytherapy. The analysis is subdivided by thematic areas. First, the intraoperative role of MR imaging in the practice of gynecologic brachytherapy, allowing for the interactive adjustment of applicator positioning, is discussed. Second, the practical aspects of MR–guided gynecologic brachytherapy, with the presentation of recent innovations in the field, are discussed. Finally, some radiation therapy physics considerations regarding treatment planning and quality assurance are introduced.

Intraoperative use of MR imaging for gynecologic cancer

The availability of MR imaging at the time of applicator insertion increases the likelihood of proper source placement inside the tumor. Optimization during planning is a poor substitute for less than ideal applicator positioning due to the potential for overdosing normal tissue proximal to the applicator when a curative dose needs to be projected into areas distant from the sources. Real-time image guidance during insertion of a brachytherapy applicator has historically been performed with ultrasound. Real-time ultrasound guidance is used as an instantaneous feedback for the attending physician. This form of continuous visualization is optimal for intraoperative procedures because it allows immediate corrections when departures from the ideal insertion path are noticed. A combination of real-time guidance, as is provided by ultrasound, and the superior imaging capabilities of MR would be ideal. Unfortunately, an MR-compatible ultrasound is not readily available. Real-time MR guidance has proven elusive in clinical practice. One example was the MR–guided interstitial therapy (MRT) experience at Brigham and Women’s Hospital. An open 0.5 T MR scanner, installed in 1994, was used between 2002 and 2006 for MR-guided gynecologic brachytherapy interventions. The MRT was a modified design to allow intervention in an open low-field scanner. Closed-bore MR scanners have the disadvantages of constraining access to the patient and causing logistical difficulty in obtaining real-time visualization. An alternative form of iterative MR guidance is delayed-feedback guidance in which a preliminary insertion is performed in the MR room, a scan is then obtained, and adjustments are performed. The process is repeated until the applicator position is considered satisfactory ( Fig. 2 ). This delayed feedback workflow requires optimization of MR sequences to provide time-effective information during and at the end of the insertion.

Delayed-feedback workflow.

In addition to MR imaging safety concerns typical of all MR imaging use, specific safety procedures need to be established in regard to ferromagnetic characteristics of brachytherapy applicators and equipment, and attention paid to training of personnel for the joint application of MR-specific safety rules and brachytherapy quality-assurance practices. A team that includes radiation oncologists, radiologists, radiation therapy and MR imaging physicists, radiation therapists, MR imaging technologists, and nurses is advisable. Once a process map of the procedure is established, optimization of the process, safety analysis, and dry-runs should be performed. This section discusses areas directly related to the use of MR imaging as the gynecologic insertion is occurring (see later discussion of MR-based planning that can also be performed with an MR image acquired post facto). The topics covered in this section are (1) how to best use potentially limited MR imaging access by prioritizing the insertions for which MR imaging is most useful, (2) brachytherapy-specific considerations relating to MR imaging safety and treatment quality, (3) practical considerations for set-up and sequence selection, and (4) maximizing visibility of tumor and of the brachytherapy applicator.

Prioritizing MR guidance in environments with limited MR imaging access

The utility of MR guidance varies from patient to patient. In departments in which MR access is limited and needs to be negotiated with other interventional and diagnostic services, it is important to identify cases that would benefit most from MR imaging use. An intracavitary applicator can be positioned effectively without MR guidance. Nevertheless, with such an approach there is no or limited visibility of the residual tumor to be treated, which then must be approximated by clinical examination at the time of applicator insertion. Lack of direct tumor visibility introduces uncertainty in the targeting of the radiation. Therefore, acquisition of an MR scan following at least the first applicator insertion is advised. If the use of MR imaging is not possible for subsequent insertions, use of CT, clinical examination, and radiographs combined with information from the first insertion MR imaging can be considered. If MR is not used during applicator insertion, the transfer of the patient to an MR scanner would probably substantially increase procedure time and use of clinic resources, potentially resulting in longer anesthesia time. Moreover, repeated transfer of a patient with applicator in situ increases the possibility of dislocation of the applicator from the inserted position.

Applicator selection is usually based on clinical examination at the time of the insertion, and on MR scans typically acquired before external beam RT. Because tumor response during external beam RT can vary considerably among patients, applicator selection can be suboptimal without the availability of an MR scan at the time of brachytherapy. This is of particular importance for patients with large residual tumors or asymmetric tumors. In these cases, a standard intracavitary applicator may not be sufficient to achieve good source distribution geometry due to the great distance between the uterine canal and the border of the tumor ( Fig. 3 ). The addition of needles has been shown to allow increased dose to the tumor while maintaining low toxicities for the organs at risk. Clear visibility of the tumor at the time of insertion is essential to the proper positioning of the needles inside tissue. MR–guided insertions provide maximum advantage for cases with large and/or asymmetric residual tumors, and for cases with tumors extending into the vagina with a significant paravaginal component.

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