Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Prostatic Neoplasms

Adenocarcinoma

Carcinoma, Renal Cell

Congenital Abnormalities

Von Hippel-Lindau Disease

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Syndrome

Neurocutaneous Syndromes

Angiomatosis

Vascular Diseases

Ciliopathies

Abnormalities, Multiple

Genetic Diseases, Inborn

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

This study will consist of comparison of tracked imaging with near-simultaneous actual imaging .

Utilizing electromagnetic tracking technology as a fusion and navigation tool for minimally invasive interventional procedures.

EM Tracking

Bradford J Wood, M.D.

This study will evaluate the accuracy and effectiveness of an experimental tracking device for locating abnormalities during invasive procedures, such as biopsy or ablation, that cannot easily be visualized by usual imaging techniques, such as computed tomography (CT) scans or ultrasound. Some lesions, such as certain liver or kidney tumors, small endocrine abnormalities, and others, may be hard to find or only visible for a few seconds. The new method uses a needle with a miniature tracking device buried inside the metal that tells where the tip of the needle is located, somewhat like a mini GPS, or global positioning system. It uses a very weak magnet to localize the device like a miniature satellite system. This study will explore whether this system can be used in the future to more accurately place the needle in or near the desired location or abnormality.

Patients 18 years of age and older who have a lesion that needs to be biopsied or an ablation procedure that requires CT guidance may be eligible for this study. Candidates are screened with a medical history and review of medical records, including imaging studies.

Participants undergo the biopsy or ablation procedure as they normally would, with the following exceptions: some stickers are placed on the skin before the procedure and a very weak magnet is placed nearby. The needles used are similar to the ones that would normally be used except that they contain a metal coil or spring buried deep within the needle metal. The procedure involves the following steps:

1. Small 1-cm plastic donuts are place on the skin with tape.
2. A planning CT scan is done.
3. The CT scan is sent to the computer and matched to the patient's body location with the help of a very weak magnet.
4. The needle used for the procedure is placed towards the target tissue or abnormality and the "smart needle" location lights up on the old CT scan.
5. A repeat CT is done as it normally is to look for the location of the needle.
6. After the procedure the CT scans are examined to determine how well the new tool located the needle in the old scan.

Background:

The effectiveness of targeting lesions or a specific area for surgery, angiography, CT-guided, or ultrasound-guided biopsy, or ablation, currently may be limited by the visibility of a target during the procedure. Accurate therapeutic intervention may depend upon accurate device placement, which may be very difficult in certain settings, such as when a liver tumor only is visible for a brief moment in time during the transient arterial phase of a contrast injection, soon disappearing on dynamic imaging. Surgery, angiography, image guided therapies and diagnostic procedures could be vastly improved by enabling the use of pre-procedural imaging during the procedure \[such as location of difficult to visualize or transiently visible targets\].Tracking devices allow the use of preoperative imaging during the procedure. Having this information available could vastly improve targeting accuracy of surgery, angiography, CT-guided, or ultrasound-guided biopsy or ablation.

A method of improving targeting could potentially benefit patients in the future by reducing total radiation exposure during CT scan or fluoroscopic monitoring of a biopsy, or decreasing certain surgical risks, although these are not specific subjects of this study. Various methods of device tracking have been used in the past throughout the 20th and 21st century in neurosurgery with the use of stereotactic frames for a similar purpose, to register pre-operative imaging to the patient during invasive procedures to guide treatment.

Objectives:

To define the clinical utility of electromagnetic tracking during interventional procedures in specific patient populations.

Eligibility:

1. All patients must have a CT, MR, or PET scan available in digital format.
2. Age greater than 18 years.
3. Patients must be actively enrolled on an NIH protocol and be scheduled for surgery, angiography, or CT- or ultrasound-guided biopsy.

Design:

This is an exploratory interventional study examining the use of a guidance system for navigating and monitoring devices like biopsy and ablation needles, ultrasound transducers, needle guides, guidewires, scalpels, and cauterization devices (herein referred to as device(s) ) for localization in relation to pre-operative images. There are 9 cohorts included in this protocol: The Open / Laparoscopic surgery and Angiography surgery cohorts are no longer open for accrual.

1. Prostate biopsy
2. Percutaneous biopsy for diagnostic correlation
3. percutaneous ablation for needle placement compilations
4. Open/Laparoscopic surgery
5. Angiography
6. Auto registration for biopsy
7. Auto registration for ablation
8. PET registration
9. prostate biopsy on which to determine the predictive value and relative strength of each MRI sequence in predicting cancer at a specific prostate core location.

The total accrual ceiling for this protocol is 3894 subjects.

All cohorts open for accrual are using exploratory interventions to define the specific patient population where fusion used during interventional procedures may have clinical value, and to characterize that clinical value in a specific patient population, such as but not limited to patients with specific regions of the prostate targeted, specific prostate volumes, prior negative prostate biopsies, or PSA values within a specific range.

Use of Tracking Devices to Locate Abnormalities During Invasive Procedures

Electromagnetic Tracking of Devices During Interventional Procedures

.It is not yet known if there will be a plan to make IPD available

"TRE" Target Registration Error (distance between "virtual" needle position (tracking data) and the actual needle position ("CT" Computed Tomography confirmation scan))

Primary effectiveness (success of ablation in local tumor control or success of biopsy in diagnostic biopsy sample). Successful ablation equals complete tumor ablation with a 5mm-1cm margin of normal tissue (if possible; quantified by the lack of enhancement of intravenous contrast material at 3 month follow up CT)

National Institutes of Health Clinical Center (CC)

Abdominal Neoplasms

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Patients are 18 years old or older. Patients are scheduled for tumor surgery in the abdominal/pelvic area and navigation surgery with a scheduled Cone Beam CT-scan in the operating room. Patients provide written 'informed consent'. The to be administered intervention is a percutaneous tracked ultrasound measurement of the patient's pelvic bone on the operating room after anesthesia.

Participation in the study will not involve additional visits to the hospital or additional CT scans for the included patients. For this experiment, 2D ultrasound images are obtained using an ultrasound transducer linked to the electromagnetic navigation system, which is already in place for the navigation at the operating room. After anesthesia and in parallel to the final preparations of the patient, two percutaneous ultrasound measurements of the pelvic bone are performed and recorded. The first measurements are performed in Trendelenburg patient position and the second measurements in supine patient position. When preparations are finished, normal workflow is continued, including the standard Cone Beam CT acquisition required for the navigation and sterile draping of the patient.

The acquired ultrasound scans will be analyzed post-operatively and offline. This measurement has no impact on the (navigated) surgical procedure itself.

Tracked ultrasound measurement

Theo Ruers, prof. dr.

The goal of this observational pilot study is to evaluate the feasibility and accuracy of tracked ultrasound registration on patients undergoing abdominal cancer navigation surgery. The main research question is: Could tracked ultrasound be applied as an alternative to standard CBCT scanning in surgical navigation? Participants will undergo tracked ultrasound measurements of the pelvic bone on the operating room after patient anesthesia and before surgical incision.

Image-guided navigation surgery allows for full utilization of pre-operative imaging during surgery and has the potential of reducing both irradical resections and morbidity. Currently, registration is done by Cone-Beam CT (CBCT) scanning on the operating room (OR) prior to navigation surgery. However, standard CBCT scanning has several limitations, mainly limited availability on the hybrid OR and radiation exposure. Furthermore, standard CBCT scanning can only be performed in horizontal patient position, while the patient position mostly differs during surgery, such as the Trendelenburg position. The use of tracked ultrasound instead of standard CBCT could overcome these limitations, which might lead to an increased navigation accuracy and improved surgical outcomes. Therefore, the goal of this research is to evaluate the feasibility and accuracy of tracked ultrasound registration on patients undergoing abdominal cancer navigation surgery. The main research question is: Could tracked ultrasound be applied as an alternative to standard CBCT scanning in surgical navigation?

Tracked Ultrasound for Patient Registration in Surgical Navigation During Abdominal Cancer Surgery

To evaluate the accuracy of tracked ultrasound registration on patients undergoing abdominal cancer navigation surgery. This will be assessed using the target registration error in mm, where a lower error means a better outcome.

What is the influence of patient position alteration on the surgical navigation accuracy for standard Cone Beam CT and tracked ultrasound registration methods? This will be assessed using the target registration discrepancy in mm.

The time duration of ultrasound measurements will be recorded and compared with the conventional Cone Beam CT method. A faster ultrasound measurement time means a better outcome.

The Netherlands Cancer Institute

Infections

Blood and Lymph Conditions

Immune System Diseases

Empyema

Communicable Diseases

Granuloma

Lymphoproliferative Disorders

Lymphatic Diseases

Suppuration

Inflammation

Procedure performed with Xperguide cone-beam Computed Tomography (CT) navigation

Procedure performed with Conventional Computed Tomography (CT) image guidance

Cone-beam computed tomography (CT)

Conventional Computed Tomography (CT)

Bradford Wood, M.D.

Background:

- Procedures that use medical tools in or near a possible abnormality in the body often use computed tomography (CT) scans to locate the abnormality and guide the path that a needle will take to collect a sample of tissue. Xperguide and electromagnetic (EM) tracking are two new procedures being studied to help guide the needle. Xperguide is software that uses CT images to help the doctor choose the needle path. EM tracking uses special medical tools with miniature coils that act like a Global Positioning Satellite (GPS) device to show the location of the needle in the body. Xperguide and EM tracking have been used in humans and have good results, but they have not been compared with each other and regular CT to determine whether they are better than the standard approach.

Objectives:

- To compare the results of Xperguide, electromagnetic tracking, and regular computed tomography during a guided percutaneous procedure.

Eligibility:

- Individuals at least 18 years of age who are required to have a CT-guided percutaneous procedure.

Design:

* Participants will be screened with a physical examination and medical history, and the results of any previous imaging studies will be examined before study enrollment.
* After a pilot phase, the study will involve two phases to compare the results of the different procedures. The first phase will involve comparing Xperguide to CT, and the second will involve comparing Xperguide to EM tracking.
* Phase 1 participants will be assigned to one of two procedure groups: Group 1 will have Xperguide, and Group 2 will have regular CT. Participants who are scheduled to have repeated procedures (like a biopsy before and after chemotherapy) will be randomized for the first procedure and the second procedure will be done using the other method.
* Phase 2 participants will be assigned to one of two procedure groups: Group 1 will have Xperguide, and Group 2 will have EM tracking. Participants who are scheduled to have repeated procedures (like a biopsy before and after chemotherapy) will be randomized for the first procedure and the second procedure will be done using the other method.
* Standard post-procedure followup care will be given after the study procedure is completed.

PR(SqrRoot) CIS

This is a phase II prospective randomized trial comparing a novel navigation method, Xperguide to conventional CT and electromagnetic tracking (EM) during percutaneous image guided procedures. Xperguide is a navigation tool that utilizes a cone beam CT (CBCT) obtained in the angiography suite overlaid on fluoroscopy for needle guidance during image guided procedures. The needle entry point and path are planned on the CBCT and the determined path is overlaid on fluoroscopy image for real time guidance.

SPECIFIC AIMS/OBJECTIVES

1. The primary aims are:

   a. Pilot trial:

   i. To familiarize operators with outcome measures allowing for fair comparison in the subsequent study

   b. Main trial will have 2 phases with similar outcomes criteria and aims (below):

   i. comparing Xperguide to conventional imaging (superiority design):

ii. comparing Xperguide to EM tracking (equivalence design):

1. To compare the accuracy of final device tip position and path (vector)
2. To compare the number of repositioning maneuvers
3. To compare the radiation dose
4. To compare rates of definitive pathological diagnosis and response rate per EASL criteria for ablations

METHODS/METHODOLOGY

For non-vascular image guided interventions, patients undergoing biopsies and ablations procedures requiring CT guidance are eligible for inclusion and randomization. An initial pilot study will be done in which each operator will perform at least 5 cases using Xperguide completing the case report forms. This will ensure experience with outcome measures and fair comparison in the subsequent study. Once one of the operators reaches the minimal required cases, the main trial will begin for that operator. However every other operator must each complete the minimal number of cases with the case report forms to enroll patients in the main trial. Initially, we will compare Xperguide with conventional CT with several cohorts of patients mainly: lung biopsies, and ablations, kidney biopsies/ablations and other abdominal biopsies/ ablations. In ablations of large lesions, Xperguide composite ablation software can provide input on the expected ablation zones. Each probe will be positioned in the same manner as any biopsy needle following steps described in section 4. If this specific composite ablation module of the

software is not commercially released and FDA cleared at the time of the study, then this software will only be used on protocol to help the physician determine ideal needle positioning for complete ablation. Once consent is obtained the participant is randomized to either conventional imaging or Xperguide. In addition, if it is known that the patient is participating in a trial which requires a repeat (paired, pre and post treatment) procedure of the same site, then the randomization will determine which modality is used for guidance at the first visit and the other modality will automatically be used for the second procedure. In these cases, if the patient gives consent they will be randomized to one of two categories:

1. Xperguide for the initial procedure and conventional CT for the 2nd procedure
2. Conventional CT for the initial procedure and Xperguide for the 2nd procedure

Then in the second phase of the trial, Xperguide will be compared to EM tracking for biopsies and ablations requiring CT guidance, in an equivalence study. Once consent is obtained, the participant will be randomized into EM tracking or Xperguide. The patients would be divided into different cohorts depending on the anatomic site of the interventions i.e. lung, kidney, liver and other abdomen. If the patients are participating in a trial requiring paired procedures (i.e. pre and post treatment), the randomization will determine which modality is used for the initial procedure and the other modality will be used for the second procedure. In summary there will be two potential categories:

1. EM tracking for the initial procedure and Xperguide for the 2nd procedure
2. Xperguide for the initial procedure and EM tracking for the 2nd procedure

If a patient has a lesion that is only visible on PET-CT/MR, or demonstrates heterogenous PET-CT/MR uptake, there will be a separate cohort of PET-CT/MR guided biopsies and ablations using Xperguide vs EM tracking. There is also the need for a cohort for ablations with complimentary use of ultrasound at the discretion of the operator in order to conform to our standard of care at the NIH.

ELIGIBILITY

Subjects are eligible if:

1. they are over 18 years of age
2. they are scheduled for image guided procedure
3. the lesion is not superficial (deeper than 3cm)

Subjects are excluded if:

1. they have an altered mental status that precludes understanding or consenting for the procedure
2. they are unable to hold reasonably still on a procedure table for the length of the procedure
3. they are unable to hold their breath if the procedure will be performed with conscious sedation and without general anesthesia
4. their gross body weight is over 375 pounds which the upper limit of the CT and

angiography tables

REQUIRED SAMPLE SIZE

A pilot study will be performed to ensure operator experience with Xperguide and EM tracking, for fair comparison. In the pilot study each operator must perform 5 cases with Xperguide completing the case report forms. There are 5 potential operators therefore a maximum of 25 patients (if all 5 operators participate to the fullest).

The first phase of the main trial comparing Xperguide with conventional CT was powered (for sample size) with a standard superiority design aimed to statistically establish that Xperguide is better than conventional CT (defined as requiring fewer needle repositioning efforts). These calculations yield a total sample size of 60 patients with 20 patients per anatomical site.

For the second phase of the trial comparing Xperguide to EM tracking, a two sided equivalence design (based on accuracy and number of needle repositioning) was used for sample size considerations, and yielded 192 patients. Therefore 16 patients per modality per anatomical site will be randomized with two additional cohorts for PET-CT/MR procedures and composite ablations.

Number of Participants: 277

Recruitment Time Frame: 4 years

Number of sites: 1

Type of Study: prospective randomized clinical trial after an initial pilot period

Comparing Xperguide vs. Conventional Methods During Percutaneous Image Guided Procedures

Prospective Randomized Trial Comparing Navigation With Xperguide vs. Conventional Methods During Percutaneous Image Guided Procedures

To compare the accuracy of the biopsy needle between the software guidance and conventional CT. The accuracy of the needle position was calculated in millimeters by using the difference between the x,y,z coordinates of the tip of the actual needle before specimen collection. Actual and planned needle paths were compared using coordinates and measured in millimeters.

Comparing the accuracy of the path the biopsy needle took to get to the site

Comparing radiation doses to determine if there is a change in the dose between the two interventions

To compare the number of times the needle must be repositioned during the guidance of the needle to the biopsy.

Definitive pathologic diagnosis was defined as an adequate specimen as judged by the pathologist and a diagnosis confirmed by surgery or clinical follow-up.

Cone Beam CT

Conventional CT

Pilot participants were enrolled to familiarize operators with performing Xperguide procedures.

Pilot Arm

Procedures performed with Xperguide without randomization to familiarize operators.

PILOT

Total

Age, Categorical

Sex: Female, Male

Bradford Wood, MD

Participants enrolled in the PILOT Arm were not randomized to the Cone Beam CT or Conventional CT Arms and were not included in the analysis. PILOT Participants were enrolled to familiarize operators with performing Xperguide procedures.

Comparing the Accuracy of Final Device Tip Position

Convetional CT

Accuracy of Final Device Path (Vector)

Radiation Doses Between Xperguide and Conventional CT

Compare the Number of Repositioning Maneuvers

Rates of Definitive Pathologic Diagnosis

Overall Study

This is a single-center observational feasibility study to develop an automatic segmentation and registration algorithm based on ultrasound imaging of the pelvic arteries. The duration of this study will be approximately 1 year. Patients scheduled for a laparotomy at the NKI are eligible for inclusion. Patients are informed about the study before the planned surgery and, after being provided with the necessary information regarding participation in the study, will be asked for informed consent. The ultrasound acquisitions for this study will be performed intra-operatively with CE marked equipment for intra-operative ultrasound. There is no impact on the standard surgical procedure or decision making of the surgery. After surgery, no further participation or cooperation of the patient is required.

A patient-specific 3D model will be created using an available pre-operative CT scan. Anatomical target points are selected on this virtual model before the start of the surgery. Prior to surgery, a patient-reference electromagnetic (EM) sensor will be placed between the patient and the matrass on the operating table to account for patient movement during acquisition. Intra-operatively, an initial point registration of the 3D model with the electromagnetic tracking system (EMTS) will be performed based on ultrasound (US) imaging of the arterial bifurcations by the surgeon. Then, the surgeon will acquire multiple US sweeps of the pelvic arteries (abdominal aorta and left and right iliac arteries). For validation purposes, the pre-operatively defined anatomical target points will be visualized on US imaging and by pinpointing the EM tracked pointer. All tracking and US data will be recorded and stored for post-operative analysis.

Intra-operative ultrasound measurement

Marijn Hiep, MSc

Theo Ruers, Prof. Dr.

Wout Heerink, Dr.

Harald Groen, Dr.

In this study we aim to develop an automatic pelvic artery segmentation algorithm, which is required for future clinical implementation of US registration for surgical navigation. Various registration methods will be evaluated with the data of this study to obtain most optimal results. If automatic segmentation and registration is successful, the final accuracy of the developed US registration method for tumor tracking should be evaluated in future studies in patients eligible for surgical navigation. Eventually, we aim to replace the CBCT-scan with an automatic tracked US registration pipeline for a more efficient and accurate registration procedure, which could improve the applicability and accuracy of surgical navigation and patient outcomes.

Image-guided navigation surgery allows for full utilization of pre-operative imaging during surgery and has the potential of reducing both irradical resections and morbidity. To use navigation, a registration procedure is required to correlate pre-operative imaging with the patient's position on the operating room (OR). Currently, registration is done by Cone-Beam CT (CBCT) scanning on the OR prior to navigation surgery. However, the main limitation of the CBCT method is that it cannot compensate for per-operative changes such as bed rotation, retractor placement and tissue displacement due to the surgery. Alternatively, by using intra-operative tracked ultrasound and vessel-based patient registration, changing conditions during surgery can better be dealt with. This improved patient registration method could lead to an increased navigation accuracy and improved clinical usability and outcomes.

The main difference between CBCT and proposed ultrasound registration is that CBCT is based on bones, while the ultrasound is based on vessels. Bones can be very easily imaged on the CBCT and therefore used for bone-bone registration with pre-operative CT-scans. However, vessels are more difficult to acquire, especially with ultrasound, and an automatic registration process with pre-operative imaging is needed for efficient clinical usability. For this, the vessels need to be extracted from the tracked ultrasound images to create a 3D representation that can be registered. Therefore, an algorithm needs to be developed that can automatically segment the pelvic vessels from ultrasound images.

One group to evaluate the feasibility and accuracy of the proposed methods.

Vessel-based Ultrasound Registration

Intra-operative Pelvic Vessel Acquisition, Towards Ultrasound Registration for Surgical Navigation

An automatic segmentation algorithm for real-time intra-operative pelvic vessel segmentation from tracked US images will be developed. The accuracy of this network will be evaluated using the Dice similarity coefficient, ranging from 0 to 1 where a higher score means a better outcome.

To evaluate the accuracy of different patient registration methods of intra-operative US imaging with pre-operative CT imaging, such as 3D model or centerline registration.

Evaluation of the intraoperative usability of the tracked US device and visualization of pelvic vessels by the surgeons will be evaluated using the system usability scale (SUS). This scale ranges from 0-100 where a higher score means a better outcome.

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

During the fraction 1 insertion, the custom MRI-compatible vaginal cylinder will be placed in the patient, and will contain the 6 degree-of-freedom (DOF) sensor. The electromagnetic navigation system and computer will have been setup in the operating room (OR) prior to the procedure and will be used to actively insert up to 25 catheters into the target. The catheters will be inserted using a custom metallic stylet that has a custom 5-DOF sensor embedded in the tip for tracking its position in real-time. The physician may use ultrasound for assistance in target visualization as well. Catheter deflections will be detected and corrected for in real-time by the radiation oncologist as the catheter is inserted into the patient during the procedure, this will occur when the EM system is in use.

For the second group of patients in the trial the same protocol will be followed as in the first group, the only difference will be that the electromagnetic navigation is used during the second implantation procedure immediately preceding fraction 3 as opposed to fraction 1, the time at which it was used for the first group of patients.

Electromagnetic navigation is a form of surgical navigation that can be incorporated into the cervical interstitial brachytherapy workflow to improve the current standards of guidance.

Electromagnetic Navigation

Ananth Ravi, PhD

Phase I study evaluating the feasibility of using electromagnetic navigation (EMN) for the catheter implantation procedure required of cervical brachytherapy. The addition of EMN to the current HDR brachytherapy workflow has the potential to dramatically improve implant quality and efficiency for the gynecological interstitial brachytherapy program. Implant quality has been reported to be an important predictive factor for local control and late toxicity.

Cervical cancer poses a significant local and global health problem. In 2017 over 1,500 Canadian women were predicted to develop cervical cancer, and another 400 were approximated to die from the disease. Cervical cancer rates have steadily decreased in developed nations largely due to regular gynaecological screening and public human papillomavirus vaccination programs; however, the disease accounts for up to 12% of all female cancer diagnoses in developing nations, and poses a disproportionate burden on aboriginal women across Canada. Much work needs to be done to address disparities in care and treatment for cervical cancer, both in Canada and worldwide.

FIGO stage IA - IB1 is considered localized disease and treated primarily with surgery. In contrast to early stage disease, tumours that extend greater than 4 cm and beyond the cervix are considered locally advanced. The standard of care for locally advanced cervical cancer defined as FIGO stages IB2 - IVA is external beam radiation therapy with concurrent chemotherapy followed by brachytherapy.

Brachytherapy is a crucial component of therapeutic management that has been shown to be associated with improved local control. High dose rate brachytherapy involves the treatment of local bulky disease using a remotely loaded Iridium-192 source. Brachytherapy delivery exploits rapid dose fall off, allowing for the central pelvis to receive a very high dose while sparing the bladder, rectum, sigmoid and small bowel. This dose escalation is beyond what is conventionally achievable using external radiation therapy methods. More specifically, image guided adaptive brachytherapy employing intracavitary applicators allows for dose optimization and improves target dose coverage for limited size tumours.

Intracavitary applicators have been shown to be adequate from covering symmetric small tumours less than 30 cc. However, for large or complex asymmetric tumours with/without vaginal involvement they are not sufficient to cover the target while respecting normal tissue tolerances. To compensate for these limitations, improvements in local control have been achieved using a combined interstitial and intracavitary technique for larger tumours. Combined intracavitary - interstitial applicators have been designed to target tumours that are not adequately covered by intracavitary applicators alone. The addition of the interstitial technique involves the insertion of catheters into the tumour enabling higher dose conformity and normal tissue sparing. This combined technique has been shown in large tumours with extensive parametrial involvement as well as in cases with unfavourable topography to be effective. Employing this combined technique, perineal-based interstitial image guided adaptive brachytherapy makes it possible to deliver higher doses to the high risk clinical target volume without increasing dose to the bladder, rectum or sigmoid.

The combined interstitial and intracavitary brachytherapy workflow for locally advanced cervical cancer at the Odette Cancer Centre typically consists of four treatment fractions. The workflow begins with a pre-brachytherapy assessment MRI that is taken before brachytherapy treatment to assist in preplanning of catheter depth and location. At the time of this MRI the patient will have a vaginal cylinder in place. 1-2 weeks after the MRI, the implant and treatment is performed. Prior to the implantation procedure, the patient is given light sedation and a spinal anesthetic, subsequently a vaginal cylinder (Best Medical Systems, Inc, Springfield VA) is inserted into the patient. A perineal template that contains a central opening is fit on the vaginal cylinder. The template is then advanced until it is appositional on the perineum of the patient. Plastic catheters (6F 24 cm) containing metal stylets are inserted through the template and along the grooves of the vaginal cylinder thereby penetrating the perineum and the vagina, respectively. The number, position and depth of the catheters that are used are based on the pre-brachytherapy assessment MRI. After the implantation procedure the template is sutured to the patient and the patient is transferred to an MRI suite where an image of her anatomy is acquired with the catheters and applicators in place. The patient is then sent for a CT scan that is to be used for treatment planning.

Treatment planning involves the registration of the CT and MR datasets. The MR images are used to identify the soft tissue organs at risk and the targets. The CT is used to identify the catheters implanted in the patient. Using the knowledge of where the applicator/catheters are with respect to the targets and organs at risk, a dose distribution is designed to target the cancer while sparing normal tissue. On the same day as the implantation, one treatment fraction is delivered and the patient is admitted overnight. The next day the patient may as a standard of care, depending on the clinical indication undergo one or two additional fractions, separated by at least 6 hours. A week later the same process for the first two fractions will be repeated for the remaining two fractions.

During the insertion of catheters, it has been recognized that they can converge or diverge as they pierce stiff tissues along the implantation path. Without proper image guidance, a template guided interstitial implant could result in an increase in risk of normal tissue complications. Real-time image guidance for catheter insertion is institution dependent, at the Odette Cancer Centre trans-abdominal ultrasound is used for placement of the tandem and more recently the trans-rectal ultrasound has been investigated for catheter placement. Other forms of real-time catheter guidance used at different centres include fluoroscopy, computed tomography (CT), and magnetic resonance imaging (MRI).

The quality of interstitial brachytherapy implants has been reported to be an important predictive factor for local control and late toxicity. The quality of the implant is dependent on the geometry of the catheters, and real time image guidance for interstitial cervical brachytherapy is markedly lacking.

At the Odette Cancer Centre, a four-patient study was conducted to characterize the amount of catheter deflection and angulation during gynaecological high-dose-rate interstitial brachytherapy. Results from this study demonstrated that the mean value of the maximum catheter deflection at the level of the GTV was 9.1 mm +/- 3.2 mm (range 3.0 - 18.4 mm) and can approach as much as 2 cm at the level of the GTV. Although the catheter deflection observed in this study did not result in any significant dosimetric impact the sample size was small and the authors of the study suggested that further investigation into real-time catheter guidance may be necessary into alleviating this deviation to prevent suboptimal plan quality.

Electromagnetic tracking can minimize the uncertainties related to implant quality. The operation of an electromagnetic tracking device depends on a field generator producing a magnetic field that extends across the anatomy of interest. The tracked sensor in this system induces a distance-dependent voltage that is used to determine the spatial position of the sensor within the volume of interest. This technology is extensively used in clinical practice, examples include, surgical interventions, guidance of biopsies, and motion monitoring.

Electromagnetic navigation can be incorporated into the cervical interstitial brachytherapy workflow as a form of real-time catheter guidance. By incorporating this guidance into the current workflow it is possible that a higher degree of accuracy in catheter placement will be achieved when used in conjunction with image-guided brachytherapy. This study seeks to evaluate the efficacy of electromagnetic navigation on the perineal-based interstitial cervix image-guided brachytherapy workflow as part of a phase I clinical trial.

2 arms of patients will undergo standard routine brachytherapy treatment. A part of the treatment involves the placement of catheters. For both arms of the study the placement of these catheters will be assisted by an electromagnetic navigation system. The difference between the arms will be that the navigation system will be used at different times in the course of their brachytherapy treatment to eliminate bias. One group will undergo electromagnetic navigation assisted catheter placement during their first fraction of treatment while the second arm will undergo electromagnetic navigation assisted catheter placement during their third fraction of treatment.

ElectroMagnetic-guided Interstitial Catheter Navigation for Gynecological brachyTherapy

ElectroMagnetic-guided Interstitial Catheter Navigation for Gynecological brachyTherapy: A Phase I Trial

Results will be made available to relevant stakeholders within the Odette Cancer Centre as these results may assist in the translation of this trial into routine clinical practice.

The treatment plans generated during the course of treatment for participants will be evaluated. The evaluation of the treatment plans will use the dose received by specific target structures and the dose received by structures that are defined as organs at risk. The specific metric that will be used represents how much dose is received by a certain percentage of a volume. For example, the D98 GTV refers to how much dose is received by 98 percent of the gross tumour volume. The dose is a value that is measured in the unit, Gray. In addition to the dose constraint for the D98 GTV the other dose constraints that will be used for evaluation purposes are, D90 HR-CTV, D98 HR-CTV, D98 IR-CTV and OAR constraints. A significance level of 5% will be used to identify differences between the dose constraints for treatment plans that are generated when EMN is used and when EMN is not used.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Use of Tracking Devices to Locate Abnormalities During Invasive Procedures	NCT00102544	Adenocarcinoma Prostate Neopla... Prostate Cancer Renal Cell Carc... Von Hippel Lind...	EM Tracking	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Tracked Ultrasound for Patient Registration in Surgical Navigation During Abdominal Cancer Surgery	NCT05637359	Abdominal Cance...	Tracked ultraso...	18 Years -	The Netherlands Cancer Institute
Use of Tracking Devices to Locate Abnormalities During Invasive Procedures	NCT00102544	Adenocarcinoma Prostate Neopla... Prostate Cancer Renal Cell Carc... Von Hippel Lind...	EM Tracking	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Comparing Xperguide vs. Conventional Methods During Percutaneous Image Guided Procedures	NCT01287013	Infection Cancer Neoplasm Empyema Granuloma	Cone-beam compu... Conventional Co...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Vessel-based Ultrasound Registration	NCT05637346	Abdominal Cance...	Intra-operative...	18 Years -	The Netherlands Cancer Institute
Tracked Ultrasound for Patient Registration in Surgical Navigation During Abdominal Cancer Surgery	NCT05637359	Abdominal Cance...	Tracked ultraso...	18 Years -	The Netherlands Cancer Institute
Tracked Ultrasound for Patient Registration in Surgical Navigation During Abdominal Cancer Surgery	NCT05637359	Abdominal Cance...	Tracked ultraso...	18 Years -	The Netherlands Cancer Institute
ElectroMagnetic-guided Interstitial Catheter Navigation for Gynecological brachyTherapy	NCT03781271	Cervical Cancer	Electromagnetic...	-	Sunnybrook Health Sciences Centre
Vessel-based Ultrasound Registration	NCT05637346	Abdominal Cance...	Intra-operative...	18 Years -	The Netherlands Cancer Institute

Spots Global Cancer Trial Database for electromagnetic tracking