UNIVERSITY OF WISCONSIN-LA CROSSE Graduate Studies A WRITTEN DIRECTIVE SURROGATE FOR PHYSICIAN REAL-TIME IGRT APPROVAL

Transcription

1 1 UNIVERSITY OF WISCONSIN-LA CROSSE Graduate Studies A WRITTEN DIRECTIVE SURROGATE FOR PHYSICIAN REAL-TIME IGRT APPROVAL A Research Project Report Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in Medical Dosimetry Antishea Connolly-Leven College of Science & Health Medical Dosimetry Program August 2011

2 2 A WRITTEN DIRECTIVE SURROGATE FOR PHYSICIAN REAL-TIME IGRT APPROVAL By Antishea Connolly-Leven We recommend acceptance of this project report in partial fulfillment of the candidate's requirements for the degree of Master of Science in Medical Dosimetry The candidate has met all of the project completion requirements. Nishele Lenards, M.S. Graduate Program Director August 15, 2011 Date

3 3 The Graduate School University of Wisconsin-La Crosse La Crosse, WI Author: Connolly-Leven, Antishea Title: A Written Directive Surrogate for Physician Real-Time IGRT Approval Graduate Degree/ Major: MS Medical Dosimetry Research Advisor: Nishele Lenards, M.S. Month/Year: August/ 2011 Number of Pages: 43 Style Manual Used: AMA, 10 th edition Abstract The objective of this study conducted at Anne Arundel Medical Center in Annapolis, MD, was to evaluate the feasibility of implementing a written directive surrogate in lieu of physician real-time image guided radiation therapy (IGRT) approval. A written directive surrogate could potentially minimize the interruptions of physicians from the clinic and allow for more efficient and timely treatment delivery, benefiting patients and staff. A retrospective review of IGRT prostate cancer patients localized with one of two IGRT modalities; the ACCULOC system and cone beam computed tomography (CBCT) was undertaken to evaluate a written directive tool developed; the IGRT Accuracy Threshold Form. The physician s directive for the radiation therapists was to achieve a < 3mm IGRT registration agreement. The IGRT Accuracy Threshold Form was used to detail the thresholds for shifts permitted to meet this tolerance before physician intervention was indicated. All IGRT cases studied were initially imaged, correlated and adjusted by the radiation therapist, with subsequent physician review. In an attempt to demonstrate the number of occasions that the physician s IGRT review differed significantly

4 4 from the radiation therapists, data was collected from the radiation treatment record of daily shifts and evaluated for how well the surrogate would produce similar results to the physicians. A literature review of IGRT clinical practices was conducted to support the development and implementation of the IGRT Accuracy Threshold Form. The study was successful in proving the hypothesis that a written directive could surrogate for real-time physician approval for a subset of the study population. Patients localized with the ACCULOC system met the criteria set 100% of the time, while patients localized with the CBCT had an 82.7% agreement. Implementation of the IGRT Accuracy Threshold Form was adopted for all ACCULOC localized patients. Further study of the remainder of the study population will continue. Keywords: ACCULOC, IGRT, Image-guided localization, CBCT

5 5 Table of Contents Abstract... 3 Chapter I: Introduction... 7 Statement of the Problem Purpose of the Study Assumptions and Limitations of the Study Definition of Terms Image-Guided Radiation Therapy (IGRT) Intensity Modulated Radiation Therapy (IMRT) Cone Beam Computed Tomography (CBCT) ACCULOC Chapter II: Literature Review Introduction: IGRT Considerations for Treating Prostate Cancer Historical Perspective Current Practice Modalities Stereoscopic/Orthogonal Kilovoltage (KV) Imaging Cone Beam Computed Tomography (CBCT) D Ultrasound Guided Prostate Localization (3D US) Implication for Smaller Planning Target Volumes (PTV) Treatment Delivery and Practice Guidelines Summary Conclusion Chapter III: Methodology... 27

6 6 Subject Selection and Description Instrumentation Data Collection Procedures Data Analysis Limitations Chapter IV: Results Patients Data Analysis Chapter V: Discussion Limitations Conclusions Recommendations References List of Tables List of Figures... 41

7 7 Chapter I: Introduction Image-guided radiation therapy (IGRT) is becoming widely accepted as the standard of care for the treatment of prostate cancer in radiation oncology. With the use of this treatment modality come many considerations. This paper s focus will be to address one specific aspect of introducing IGRT technology into the clinic, and that is: the logistical challenge of obtaining real-time physician approval for IGRT image acquisition. The challenge of physician availability to review and approve these cases has presented a unique opportunity to evaluate how a three physician, community-based cancer program approaches this task. Prostate cancer is the most common malignancy treated at Anne Arundel Medical Center in Annapolis, Maryland (AAMC). This fact is consistent with the American Cancer Society s statistics that report prostate cancer as the second most prevalent cancer among men after skin cancer. 1 Of the many treatment options available at AAMC for prostate cancer which include external beam radiation therapy (EBRT), interstitial brachytherapy prostate seed implants (PSI) and surgery, all employ some use of image guided technology for prostate localization. The prostate gland is a walnut sized organ that is situated between the bladder and the rectum in the pelvis. Due to its location adjacent to structures such as the bladder and rectum that are greatly influenced by filling and evacuation deformation, targeting this gland for treatment can present many challenges. IGRT technology has been a very important advancement in target localization for prostate treatment. A typical course of EBRT treatment of the prostate involves daily radiation therapy treatments, five days a week, over a period of several weeks depending on diagnosis and stage of disease. Patients are given daily appointment times with accommodations made for work and

8 8 personal preferences. These accommodations are not usually in consideration of the physician s availability for IGRT imaging review as the logistics of this scheduling approach would be almost impossible when the physicians other clinic responsibilities are factored in. What has resulted in the clinic is a situation where physicians are constantly interrupted throughout the day to review IGRT imaging real-time at the onset of each IGRT treatment. With three linear accelerators and the center treating on average patients a day, of which approximately twenty percent are IGRT patients, the interruptions to the physicians are very difficult to manage while trying to maintain the timeliness of treatment delivery and other appointments within the clinic. Often time the wait for a physician to become available to review IGRT imaging adversely impacts the treatment machine s ability to stay on schedule. Prolonged waiting for image review also has the real potential for compromising the accuracy of the treatment itself due to patients becoming restless while waiting. The two IGRT modalities used for the delivery of EBRT at AAMC are the ACCULOC -EPID (electronic portal imaging device) system with the ISOLOC software by Civco Medical Solutions and the cone beam computed tomography (CBCT) on-board imager on the Varian Novalis Tx linear accelerator. The ACCULOC was designed precisely for the purpose of achieving high precision localization and has been in clinical use for well over a decade. Thousands of patients have received better localization with ACCULOC and the ISOLOC software. 2 The ACCULOC system is based on localizing gold marker seeds interstitially placed in the prostate gland by an urologist. In the case of CBCT used for IGRT, the prostate is localized based on a CBCT acquired daily pretreatment that is fused with and compared to the planning computerized tomography (CT) acquired at the time of simulation. Both of these

9 9 modalities for IGRT are used to compare and correct for any daily set-up variations from planned isocentric targeting. The current procedure at AAMC is for the radiation therapists to set-up the patients based on instructions generated from treatment planning and then acquire the appropriate imaging for comparison to planned target isocenter (ISO). Once the images are acquired and fused with original planning study, the interpreted corrections are made to align the prostate gland to the planned isocenter. The physician is paged to evaluate the therapists adjustments and make additional changes if desired. All of the shifts are recorded in the patient s treatment chart for documentation. The therapists initial shifts pre-physician review as well as any further adjustment made by the physician is recorded. A retrospective study of these two IGRT modalities used at AAMC will highlight the challenge of physician availability for real-time IGRT imaging review and the clinical and practical reasons why this review and approval process need not solely rest with the physician. This paper will present a literature review in support of developing a model for shared responsibility between the treating therapist and the physician in the IGRT image review process. Prostate localization variability will be studied in the target population of men receiving EBRT for prostate cancer at AAMC. Guidelines for evaluating prostate imaging will be developed and implemented as a physician directive for therapists to follow in localizing IGRT prostate patients for treatment without relying solely on physician resources for real-time review. The retrospective study of AAMC intact prostate patients treated with IGRT should reveal consistent and predictable variability of patient shifts required for each modality. If the variability is within acceptable limits as demonstrated in the literature, then a written directive with pre-determined tolerances should be a viable tool for guiding the radiation therapist to

10 10 achieve the physician directed adjustments. The fact that these first line adjustments have historically been made by radiation therapists at AAMC and then subsequently reviewed by the physician real-time, should build a solid case for the implementation of a written directive surrogate. This directive instrument would give pre-treatment review and approval responsibilities to the treating therapist. The documented shifts in the patients charts will provide all the data needed to evaluate this hypothesis. Particular focus will be on the surrogate instrument, the IGRT Accuracy Threshold Form, developed to guide therapist in the image acquisition, fusion and correction process of IGRT treatments. Statement of the Problem This study will evaluate image-guided radiation therapy real-time physician approval versus directive guided real-time radiation therapist approvals. Physicians are constantly being interrupted from their clinic responsibilities for real-time imaging review of prostate IGRT studies. Implementing a mechanism for a physician directive could minimize these interruptions and allow for more efficient and timely treatment delivery, benefiting patients and staff. A retrospective review of IGRT prostate patients treated at AAMC, from fall 2010 through the spring of 2011, will demonstrate the number of occasions that physician s IGRT review differed significantly from the radiation therapists initial assessment. A literature review of IGRT clinical practice will support the development and implementation of a physician directive tool that can be used to address the problem of physicians being interrupted from the clinic for realtime IGRT review and approval.

11 11 Purpose of the Study The goal of this study is to retrospectively review the IGRT corrections performed on intact prostate patients to support the position that radiation therapists given a set of guidelines or criteria, posses the necessary training and competence to correctly evaluate the shifts needed to target the prostate for treatment delivery with the two IGRT modalities being used at AAMC. As prostate cancer cases make up the majority of the clinics caseload the physician resources needed for real-time review of IGRT imaging studies for each prostate patient being treated presents a scheduling dilemma and has the potential for compromising the patient s treatment by extended wait times between imaging and treatment delivery when physician availability to review imaging is delayed. Patients are given pre-treatment instructions for daily bladder preparation in an attempt to reduce deviations in the setup from bladder filling deformation. These instructions are the same as were given for the original planning CT. When delays are introduced as a result of waiting for a physician for real-time approval, the patient can become uncomfortable due to their full bladder or may adjust their position on the table while waiting. The challenge of delivering accurate, targeted treatment is aided by being able to localize the prostate with imaging, make the necessary adjustments and deliver the treatment in the most expeditious manner. This approach will help to ensure that the effort expended to localize the patient has not been in vain. With the evidence based development and implementation of a physician directive tool, the process of setting up patients, imaging, correlation and making necessary adjustments has the potential for being a much more seamless and expeditious endeavor. The benefit to the patient is that the treatment time is shorter and the localization is potentially more accurate. In regards to flow of the clinic, the treatment machine is able to better manage their schedules and the

12 12 physician(s) are not constantly being interrupted from their clinic responsibilities to check IGRT images. Ultimately, all imaging will need physicians approval daily; however, this can be done at the physicians convenience or at the end of the day prior to the patient s next treatment. Assumptions and Limitations of the Study There have been many studies that have focused on various aspects of IGRT for prostate cancer. Most of these studies have been rooted in clinical outcomes, technical aspects of IGRT technology, quality assurance, IGRT tolerances, reducing target margins for IGRT treatments and patient set-up reproducibility. A limitation of this study is that there is no specific literature that addresses the actual roles or responsibility of the evaluator of IGRT imaging. While the American College of Radiologists (ACR), in conjunction with the American Society of Therapeutic Radiation Oncology, has established practice guidelines for IGRT, they do not specifically designate the role of daily real-time image review to a physician. The radiation oncologist is ultimately responsible for the approval of the IGRT treatment delivery; however, the recommendation is that Each facility should develop its own clinical guidelines for the initial and ongoing implementation and documentation of IGRT throughout a course of radiation treatment. 3 An assumption of this study is that all documentation for patient shifts will be complete for their course of treatment. The data could be very difficult to quantify as there are two different modalities that may have unique degrees of accuracy and predictability of variability in patient localization which may prove challenging to correlate. Definition of Terms Image-Guided Radiation Therapy (IGRT) - A procedure that uses a computer to create a picture of a tumor to help guide the radiation beam during radiation therapy. The pictures are

13 13 made using CT, ultrasound, X-ray, or other imaging techniques. IGRT makes radiation therapy more accurate and causes less damage to healthy tissue. 4 Intensity Modulated Radiation Therapy (IMRT) - A type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. 4 Cone Beam Computed Tomography (CBCT) - A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. 4 In the case of a CBCT, specialized computed tomography capabilities are an integral part of the linear accelerator, which allows for the acquisition of a CT scan while the patient is in the treatment position. ACCULOC - ACCULOC is a system that includes both hardware and ISOLOC software to provide high-precision localization based on three tiny implanted gold markers or bony anatomy for an internal reference system. 2 ISOLOC - A software user interface that provides magnified images allowing precise identification of gold markers and outputs exact, objective couch locations, removing the possibility of both interpretation and couch translation error. 2

14 14 Chapter II: Literature Review Introduction: IGRT Considerations for Treating Prostate Cancer The use of image guidance in the delivery of radiation therapy for prostate cancer has been used for over two decades. 10 The necessity for image-guided localization of the prostate is primarily due to the mobility of the prostate gland due to bladder and/or rectal filing deformation. Organ motion is the major problem to be addressed when using IGRT. 5 This retrospective study of patients with prostate cancer treated with IGRT at AAMC will require extensive literature review to frame the challenges of this procedure and provide historical as well as current perspectives on the evolution of image-guided therapy in this setting. Various treatment modalities used for IGRT will be presented in the literature and discussed as they pertain to organ motion, localization, and degree of accuracy or limitations in the treatment delivery of the target population being studied. Although this study s aim is to present a solution to the logistical conflict of physician resources needed to maintain primary real-time review and approval of IGRT treatments, many other facets will be presented from the published literature. Among some of the other topics to be researched are: the importance of competence and accuracy in evaluating IGRT imaging, the implications for smaller planning target volumes as a result of IGRT and the impact IGRT has had on physicians ability to escalate treatment doses. IGRT, when used with IMRT planning is of great benefit to patients and has not only enabled dose escalation and smaller target margins, but has allowed for more conformal planning to target volumes, better tissue sparing and more accurate delivery of treatment. 6 Treatment delivery considerations such as patient set-up, pre-treatment preparation, IGRT image acquisition and the timeliness of treatment delivery after localization are also areas

15 15 worth exploring. As this paper looks to formalize an institutional policy and procedure for IGRT treatment delivery at AAMC, a review of the established practice guidelines available from professional governing bodies and organizations will be of particular focus in this study. Historical Perspective The use of medical imaging in the delivery of cancer therapy has been a key component of radiation therapy as a treatment modality almost from its inception. Visualization of anatomy in three dimensional spatial relationship has been the single most important advancement in medical imaging. 8 The use of imaging in the delivery of radiation therapy has aided in overcoming many of the technical causes of radiation treatment failures such as: proper target delineation, patient set-up variations, and physiological variations as seen with rectal and bladder filling variability. All of these imaging challenges are of particular concern in this study s target population of patients with prostate cancer. For the purpose of this study, the historical perspective presented will be limited to the evolution of the two imaging modalities used at AAMC for IGRT treatment of the study group, which are CBCT and stereoscopic or orthogonal kilovoltage (kv) imaging technology. Cone beam computed tomography is essentially the same technology found in conventional computed tomography (CT) units, which became commercially available in the 1970 s. 8 The ability to condense this technology and incorporate it into linear accelerators has allowed for optimal target localization without having to move the patient from one piece of equipment to another. The first generation of CT units consisted of an x-ray tube opposing a single detector that rotated about the patient exposing and electronically capturing transmission information that could be reconstructed into an axial representation of anatomical information. This technology used the linear attenuation coefficient equation to formulate density values of

16 16 each pixel of measured information. 8 This pixel information was then assigned a value in Hounsfield units, which is a unit of electron density. Each type of tissue that the x-ray beam traversed has its own unique Hounsfield unit based on its respective electron density and atomic number. 8 As this technology evolved the number of detectors increased, the speed of the rotations of the x-ray source increased and the volume of tissue that could be scanned in a single revolution became greater. Some of the most important contributions of this technology to the field of radiation therapy were not only the ability to more accurately delineate target and critical structures in three dimensions (3D), but the quantitative value of more accurate dose calculations given the ability to relate the difference in tissue density to radiation attenuation in treatment planning. It has been demonstrated in early studies that, tumor coverage without CT was clearly inadequate in 20% of the patients, marginal in another 27%, and adequate in 53% of the studied population. 8 The importance of CT capabilities in targeting radiation treatments is well documented. The technological advances that now allow practitioners the ability to couple that imaging technology with the actual treatment delivery, affording almost simultaneous localization of the target volume and patient repositioning if indicated, is the benefit this technological evolution has provided. 3 CT imaging technology is not only the first step in the planning process of patients receiving radiation therapy but it also now bookends the entire treatment delivery process. CBCT used in daily treatment delivery is correlated to the original planning CT via a fusion or image registration process that allows for evaluation of the beams planned versus actual target location. Variations in planned versus actual alignment are generated based on a coordinates system relative to the isocenter location and adjustments can be made accordingly.

17 17 This process is near real-time in that it can be done very easily at the onset of each treatment or if necessary can be re-evaluated during the course of the treatment delivery. Long before the use of CT technology in radiation therapy there was simple orthogonal localization of target volumes. Orthogonal imaging is the use of two images taken at a fixed coordinate of 90-degrees apart. This basic imaging provided the basis for early two-dimensional planning, as it provided translation information in the x (right to left), y (superior to inferior), and z (anterior to posterior) planes. What 2D imaging lacked in regards to 3D information, was the rotational component of the target s spatial location. The conventional orthogonal imaging used in radiation therapy was generated using the treatment unit energy source to produce the image. In the days of using Cobalt-60 as a radiation source in treatment units, the image quality was quite poor due to scatter radiation and penumbra effects. As Megavoltage (MV) linear accelerators became more commonly used, the image quality improved some but not as well as that of diagnostic kv imaging that is now available in modern linear accelerators. The availability of diagnostic quality imaging capabilities in linear accelerators has developed into an IGRT modality that has demonstrated great usefulness and accuracy in localizing target volumes. In the late 1980 s, early 1990 s as IMRT and frameless stereotactic radiosurgery were being used more routinely the need for higher precision localization was sought. The scientific community was sparked to find solutions. Jones, a physicist at Virginia Mason Medical Center in Seattle, Washington, embarked on a quest to find a better solution. 10 Jones along with a group from the University of California, San Francisco (UCSF) developed an electronic portal imaging device (EPID) as a surrogate for film. 10 This technology made it possible to take the imaging process from a 15 minute to a 2 minute set-up time procedure. 10 The work done by Jones and

18 18 UCSF was mainly focused on prostate cancer treatment and the use of fiducial seeds in the localization of the prostate gland. Jones team was among the pioneers of what we now call IGRT. This work by Jones was further developed to include special localization software and EPID images for target therapy of soft tissue structures and later became known as ACCULOC (accurate localization). By the year 2000 this system was commercially available as a highly accurate and very practical approach to IGRT. 10 This modern use of orthogonal imaging has developed into an imaging modality that uses a set of kv generated x-ray images captured by an EPID to visualize internally placed radiopaque or fiducial markers. These commercially available systems used a stereoscopic approach whereby two x-ray images are taken 90 degrees apart to render a 3D spatial representation of fiducial placement. Software is commercially available with these systems that calculate the vector displacement in 3D space of the actual target location in relationship to the expected location. 3 Some of these systems also have the ability to correct for rotational displacement of localized fiducials. In the case of this study group, the ACCULOC system was used as the stereoscopic kv imaging modality. Current Practice The use of IGRT in the treatment of prostate cancer has been studied by many researchers. 3,5-12 Examples of some of the more commonly used modalities are: ultrasound (US), CT scan, MV CT scan and kv imaging that are used to localize fiducial markers. A review of the literature available on this subject provides an overview of what is being studied and practiced currently in most radiation therapy centers. In a 2007 study by Gayou and Miften, three image guided modalities commonly used for prostate localization were studied to determine if they were equivalent in accuracy. This study

19 19 evaluated US-guided localization, MV CBCT and orthogonal MV imaging of seed markers (SM). The daily shifts were recorded, compiled and analyzed. This study data was comprised of over 1600 IGRT procedures. The conclusions drawn from the data were that CBCT and MV imaging of SM s were more accurate methods for prostate localization and would safely support minimizing target margins. 7,12 The US group showed greater variability in daily shifts. The findings appear to be well documented and the conclusions made were reasonable. Further research on the subject has looked at the use of CBCT and the implications for target volume margin reduction. Hammoud, Patel, Pradhan et al. conducted a study that was designed to dosimetrically evaluate the ability to reduce margins in the treatment of prostate cancer by utilizing daily cone-beam computed tomography. Five prostate patients receiving 140 CBCT s were studied. 6 Two separate intensity modulated radiation therapy (IMRT) plans were generated with two different PTV margins. One utilizing a 10 mm axial margin except for posteriorly using 6mm and the other version was planned with a 5mm axial margin except for posteriorly using 3mm. The daily CBCT s were performed and both plans were overlaid on the acquired scan to see which best resulted in adequate coverage and improved rectal/bladder sparing. The study concluded that the 10/6 mm margin scheme was a valid margin reduction technique in the absence of image guided radiation therapy capabilities. While there was only a 2% difference in prostate coverage between the two plans the seminal vesicle coverage was better with the 10/6 plan. 6 Rectum and bladder sparing were better with the 5/3 plan and the results suggest 3D image guided registration improves target localization and can be used to establish margin guidelines. 6 The primary goal in the delivery of radiation therapy is to treat the intended target with accuracy and with minimal collateral damage to normal tissue. IGRT uses imaging to guide the

20 20 focus of radiation to the intended target, which we aptly refer to as image-guided therapy (IGRT). The process of IGRT begins in the treatment planning phase. Usually the acquisition of a treatment planning CT at the time of simulation (CT SIM), with the patient immobilized in a reproducible treatment position is the first step. This initial CT is used not only for treatment planning and dose calculation but also to generate reference images. These reference images can be in the form of either a CT dataset to be used for CBCT correlation or the reconstructed pixel data that is used to generate a digitally reconstructed radiograph (DRR) for kv imaging correlation on the treatment unit. The IGRT principle is one that seeks to re-establish the exact localization of a target volume from a pre-determined, pre-approved treatment plan generated from the simulation CT. This process of pre-planning and delivery is standard procedure in the delivery of most external beam radiation therapy and is considered standard practice in radiation oncology today. Modalities Stereoscopic/Orthogonal Kilovoltage (KV) Imaging. The use of orthogonal imaging to localize the isocenter has been a technique used since the onset of isocentric radiation therapy. The ability to localize a target or point in tissue based on two dimensions gives a very good sense of spatial relationship in at least two dimensions of each projection taken. When two orthogonal images are used in concert a third dimension can be deduced if all other factors remain stationary or the same from one projection to another. The current use of stereoscopic imaging as a means of image guidance in the treatment of prostate cancer is not much more sophisticated than the principles used years ago. What technological advancement has afforded us with this technique is the ability to make this imaging capability available as an integral part of the linear

21 21 accelerator, or in some cases built into the treatment suite to afford imaging without compromising patient positioning. As an image guided modality, stereoscopic/orthogonal imaging is used in conjunction with fiducial markers. Typically three fiducial markers are placed in the prostate gland by the radiation oncologist or urologist prior to simulation via ultrasound guided needle placement. The stability of fiducial markers placed in the prostate gland has been well documented in the literature. 3 The stability allows for fiducial markers to act as a surrogate for the prostate. The daily acquired orthogonal images are compared to the treatment plan generated orthogonal pair. The fiducial markers are then manually identified on the acquired DRR. Using triangulation software, the location of isocenter in relationship to the fiducial markers can be determined. Any deviation between planned and actual may be corrected. Cone Beam Computed Tomography (CBCT). Most linear accelerators available for purchase today are now being offered with the option of onboard imaging capabilities. The use of a CT image to guide the localization of the prostate each day can offer great advantages to 3D treatment set-ups. Unlike fiducial marker localization, a CT scan provides information about the size, shape and daily changes in the prostate gland. 3 With the use of integrated CT capabilities on linear accelerators a CT scan is acquired daily through the region of interest, fused and correlated with the initial planning CT dataset. Special fusion and correlation software is used to aide in evaluating the position of the gland on a daily basis in relationship to the position of the gland at the time of initial planning. Any deviation in gland location to isocenter may be corrected for prior to treatment delivery. 3D Ultrasound Guided Prostate Localization (3D US). Ultrasound guidance has become a less popular image guided modality since many studies have reported on the

22 22 comparatively greater uncertainty and margin for errors to CBCT or stereoscopic fiducial localization. 7 User variability and interpretation has been a shortcoming of this modality. The degree that a user depresses the ultrasound probe can have an adverse deformation affect on the prostate gland being localized. A study by Artignan et al. describes the displacement caused by the minimum amount of pressure required to acquire an adequate image of the prostate gland of 3.1mm. 7,13 Of the three major image guided modalities described in this paper, US has proven to be the least reliable. US results are comparable to not using any image guidance at all due to the susceptibility to subtle sources of error and inter-user variability as stated by Gayou and Miften. 7 When comparing the three modalities described based on level of accuracy, data from a comprehensive study looking at the comparison of the three modalities are presented to provide a sense of predictability of accuracy when choosing an image guidance modality for radiation therapy delivery. Gayou and Miften conducted a study comparing CBCT, US guidance and fiducial based prostate localization. 7 The study results found that US alignment had the greatest variability of the three. The mean shift error was greatest for the US at ( mm) compared to fiducial and CBCT which were ( mm and mm respectively). The results of this study are typical for placing US as the least reliable of the three modalities presented. Figure 1 demonstrates images of the three IGRT modalities described. Implication for Smaller Planning Target Volumes (PTV) The successful immobilization and localization of the target volume holds the potential for supporting smaller planning target volumes. Depending on the modality used for localization, the accuracy of targeted treatment can dictate margin size on the target volume. Many factors contribute to patient setup errors, such as interfractional target motion, target deformation from

23 23 rectal and bladder filling effects, as well as the accuracy of the localization method. It is well documented in the literature that image guidance improves accurate treatment delivery and allows for the use of reduced target volumes, which ultimately results in reduced normal tissue doses. In a study by Pawlowski, Eddy, Yang et al. which looked at whether image guidance in prostate cancer improved target dose delivery and organ at risk sparing, there was evidence to support this hypothesis. 14 The three goals of the study were to: evaluate conventional skin marks alignment and bony anatomy, determine whether image-guided localization utilizing implanted fiducial markers allowed for margin reduction and quantify if reducing margins would have an effect on organs at risk without compromising target coverage. For the first goal of this study the average shift of the studied cases was 6mm. The second goal was evaluated retrospectively by applying reduced margins to original treatment plan. The original PTV margins were reduced from PTV8/6 (prostate plus 8mm axially except for 6mm posteriorly) to PTV6/4 and PTV4/3. 14 With image-guidance, all of the margin reduction schemes allowed for adequate coverage to target volume. When compared to no image localization, just patient skin marks for setup, reducing margins from original PTV8/6 was not advised. The benefit of margin reduction to adjacent organs at risk provided more favorable outcomes to the rectum and bladder over IGRT alone without any margin reduction. In combination IGRT and target volume margin reduction produced better target coverage and fewer organs at risk toxicity. 6,14 Treatment Delivery and Practice Guidelines In most clinics, the radiation therapists are ultimately responsible for the safe and accurate delivery of the radiation therapy treatment plan, whether IGRT is used or not. In the case of IGRT at the study facility, AAMC, IGRT treatments have had an overwhelming impact on the physician s ability to manage the constant interruptions for real-time IGRT review and

24 24 approval. The model that has been used in this clinic is one that relied exclusively on physician real-time approval for all IGRT treatments prior to delivery. The radiation therapists role in the study facility is to acquire the IGRT image, correlate, make correction and then page an available physician for review and approval. It became apparent after some time that in most instances little or no changes were being made in the majority of cases reviewed, particularly with patients localized with the ACCULOC system. A retrospective study of the documented discrepancies and the usefulness of the IGRT Accuracy Threshold Form as a surrogate for physician real-time approval was undertaken. This data will be presented later in this paper. In the guidelines set forth by the ACR-ASTRO task group the recommendation states that each facility should develop quality assurance (QA) procedures to assure reproducibility and reliability of the IGRT process. 3 While IGRT images need to be reviewed and approved by the physician initially and ultimately, this approval is not required real-time prior to each subsequent treatment. Verification and/or accuracy requires that the practitioner or therapist be trained and have a competent working knowledge of the IGRT modality being used and possess the ability to interpret the IGRT images in relationship to those acquired at the time of treatment planning. The ACR-ASTRO practice guidelines suggests that each facility should develop its own guidelines for initial as well as ongoing implementation and documentation of IGRT practice throughout a patient s treatment course. 3 Clear instruction should be given when establishing thresholds for treatment parameters, that if exceeded will prompt physician involvement before treatment is delivered. The aim of this study will be to follow these recommendations in developing a written directive instrument to aid the radiation therapists in the delivery of IGRT.

25 25 Summary The literature presented covers many areas that were considered when weighing the role of a physician directive tool as a solution to the clinical demands of real-time physician approval prior to daily IGRT delivery. The first step in evaluating the feasibility or clinical implications of changing clinical practice was to take a retrospective look at the foundational work of the present clinical practices. It was important to gain a historical perspective of what constituted good clinical practice as well as look at how current practices have developed based on past achievements. As the effectiveness of radiation therapy is measured in large part due to the practitioner s ability to deliver targeted and accurate treatments with the least amount of collateral damage to healthy tissue, image guidance has become our greatest tool in this quest. The literature presented demonstrates the advancements made in imaging technology that have propelled us into an era of current practice where; being able to consistently and accurately deliver treatments to target volumes with the least amount of normal tissue damage is the new standard of care. The three most prevalent modalities used in image-guided radiation therapy have been described and presented in terms of their respective capabilities, limitations and strengths. The use of US guided localization was at the forefront of image-guided localization for prostate cancer for many years. While 3DUS is still very effective in prostate seed implants for organ localization, its usefulness in the arena of current IGRT modalities pales in comparison to onboard imaging modalities integrated into the newer generation of linear accelerators such as CBCT and/or stereoscopic imaging hardware and software capabilities. In the end, the ultimate goal of image-guidance is to better target the disease site and minimize normal tissue damage. The ability to decrease target volume margins and escalate dose

26 26 to target volumes are paramount in the quest for better clinical outcomes. The degree of accuracy in treatment delivery becomes even more important as we look to treat smaller volumes to higher doses. Unlike standard fractionation to generous margins in a typical 3D plan, IGRT is usually coupled with IMRT to sculpt the dose to very discretely defined target volumes. This has resulted in closer, more frequent oversight by physicians of this process. At the study facility this closer oversight of the IGRT process equated to the paging of physicians throughout the day for daily real-time approval prior to each IGRT delivery. When seeking the literature to support the idea of a surrogate for this function, the ACR-ASTRO practice guidelines were a great resource in guiding this facility to a surrogate solution to physician real-time IGRT approval. 3 Conclusion As a result of assessing the need for a surrogate to real-time physician approval and supported by the literature on the key areas of consideration, a written directive was developed for use as a surrogate for real-time physician approval. Figure 2 represents the IGRT Accuracy Threshold Form that was implemented into the clinic as a means of guiding the radiation therapist in the acquisition, correlation, evaluation, and delivery of IGRT treatments. This form was completed at the onset of each patient s treatment and while the physicians were still called for all real-time pre-treatment review and approvals, the directive was a tool in place to communicate the physicians IGRT thresholds and imaging protocols. The purpose of this research to establish a surrogate solution to physician real-time approval could also result in the validation of this tool as a surrogate instrument.

27 27 Chapter III: Methodology This study was undertaken to explore an alternative solution to the logistical challenge of the physicians availability for real-time IGRT review and approval. As the target population of prostate patients makes up the majority of our centers case mix, the demand for physician resources for IGRT real-time approval has resulted in delays in treatment delivery for patients waiting for a physician to become available for image review. It also compromises the accuracy of corrective shifts as delays in review and approval process leaves more opportunity for the patient to move off of their localized position. 11 As the radiation therapists are essentially performing the image acquisition, correlation, initial shifts and are in most instances only waiting for a physician to review and approve what is already done, it seems highly probable that given a set of criteria or physician directives this review and preliminary approval process could be completed by the radiation therapists. In this chapter the sample population will be examined more closely. The reasons for selection and the description of study group will be explained. The instrumentation used will be defined and the procedure for data collection detailed. The data analysis section will describe the statistical tools used to analyze, quantify, and correlate the data in support of the hypothesis. Lastly, the limitations of the study will be revealed and discussed as it relates to or may impact the study outcomes. Subject Selection and Description The sample population for the retrospective study was male patients at AAMC from late fall of 2010 through spring of 2011 that were treated for prostate cancer with EBRT. For the purpose of this study only patients with intact prostates will be considered. All study subjects

28 28 were treated with IGRT in combination with an IMRT treatment plan. Only patients who received the full course of prescribed treatments with evidence of complete documentation of daily IGRT shifts were included in the study group. Instrumentation The instrumentation for this study will be a written log of daily shifts. The IGRT Accuracy Threshold Form, which was a written directive tool developed to instruct the radiation therapists in the IGRT acquisition, correlation and alignment process. The IGRT Accuracy Threshold Form was developed specifically for the IGRT modalities used at AAMC. The physicians provided a completed IGRT Accuracy Threshold Form detailing all of the criteria and thresholds to be adhered to during the IGRT process for each IGRT patient. These instruments have been in place at AAMC as a means of documentation and guidance of daily shifts made during the IGRT process and are in compliance with the ACR-ASTRO established IGRT guidelines. 3 In addition to this record of shifts, a treatment planning document is provided to the radiation therapists which gives the location of the implanted gold seed marker coordinates in relationship to the isocenter. This information is provided for all patients scheduled for ACCULOC localization and will also serve as an instrument to correlate shift data collected. For patients being treated with CBCT as an IGRT modality, a similar log is maintained in the patient s chart. The documentation of the physician changes made to the radiation therapists correlation and adjustments are also routinely documented. This will serve to demonstrate the incidence of deviation from shifts made by the radiation therapist.

29 29 Data Collection Procedures AAMC has a procedure in place whereby a log is kept as part of the patient s treatment record to document all daily IGRT shifts made. This log will be the primary source of data collection. These log sheets will be compiled for the patient population being studied. Only completed logs will be included in the data collected. Logs for both patients treated with the ACCULOC system as well as logs from patients being treated with CBCT have been maintained and are available as a data instrument. Data Analysis The study population was comprised of all prostate cancer patients completing a course of IGRT from January 1, 2011 through April 30, Twenty-three prostate patients were identified for the study group. The data collected were tallied, correlated and analyzed as follows: each patient s shift log of x, y, z coordinates was tabulated for evaluation. The average, minimum, maximum, and mean shift values were determined for each patient s course of treatment. The standard deviation values were also analyzed. This data was correlated and presented in line graphs to show tendencies and range of deviation from the sample population anticipated x, y and z values of 0, 0, 0 respectively. The physicians were asked to complete an IGRT Accuracy Threshold Form, a directive instrument, with criteria for shift(s) and threshold for physician intervention in the pretreatment IGRT process. The IGRT Accuracy Threshold Form is designed to allow the physician to set a shift threshold that the radiation therapists are permitted to make, before a physician is required to evaluate the study. For the ACCULOC system the agreement threshold is set at 3mm. This means that orthogonal imaging is performed, correlated and adjustments made; upon physician review if the agreement is within 3mm of desired alignment, no adjustment is required. If the

30 30 discrepancy is > 3mm the adjustment is made. Also, the IGRT Accuracy Threshold Form allows for a directive to be communicated in regards to what degree of a correction may be made before a physician must be called to review the IGRT imaging. At AAMC, the study facility, for intact prostate localization that value is 1 cm. If the initial filming requires greater than a 1cm shift to acquire proper localization the physician must be notified prior to treatment for imaging review. The established tolerance for IGRT agreement of < 3mm is based on two factors; one the PTV margin used institutionally on intact prostate cases which vary between the three Radiation Oncologists at the facility but is no less than 8mm in any dimension. Secondly, the scientific literature which details the variances in the IGRT modalities used in the study to be within an accuracy threshold of + 3.5mm on average is the basis for setting a 3mm agreement threshold. These physician directives served as the control values for evaluating the retrospective data collected and how well the radiation therapists shifts would have met the physician s criteria for approval if the IGRT Accuracy Threshold Form were to be adopted as a surrogate for a physician real-time approval. Limitations There are certainly limitations to this methodology that will prove challenging. One is the user proficiency for image correlation which is a variable based on radiation therapist rotation from one treatment machine to the next. Consistency in IGRT image evaluation cannot be controlled and could sway results. It is also assumed that the data collection instrument will be consistently completed with the necessary changes made by physicians notated. These two limitations of this study are procedural weaknesses that will be difficult to evaluate.

31 31 Chapter IV: Results In an effort to evaluate a surrogate solution to the logistic problem of obtaining physician real-time approval of all IGRT imaging prior to daily treatment delivery, a retrospective study was conducted. The population studied evaluated all external beam intact prostate cancer patients treated with IGRT at AAMC, utilizing one of two modalities: CBCT or the ACCULOC system. The period studied extended from January 1, 2011 through April 30, Patients completing their course of treatments during this period were selected for a retrospective analysis of daily treatment shifts. In total, 23 patients were evaluated for a total of 985 treatments. The analysis of this data was to determine the incidence of physician review and approval of the radiation therapists IGRT shifts that resulted in the need for an additional correction. Patients The 23 patients identified were further broken out into two groups for analysis. The groups were: Group 1, which consisted of 9 patients implanted with fiducial gold seed markers localized with the ACCULOC system for intact prostate treatment and Group 2: 14 patients localized with CBCT for prostate treatments. The factors that influenced the choice of IGRT modality used for prostate cases were patient preference, ineligibility for surgically implanted fiducial placement due to other medical co-morbidities or the decision was left up to the discretion of the attending physician. All patients were given the same pre-treatment instructions for bladder prep, to try and make bladder filling as consistent as possible over the course of treatment. Bowel prep is not a part of the study facility treatment protocol for prostate cancer treatment and so no such prep was used. The IGRT Accuracy Threshold Form as shown in Figure 2 was completed for each patient and used by the radiation therapist as a written directive of IGRT guidelines for treatment. This

32 32 form was used to establish which imaging modality was to be used as well as the frequency, quality, and correction thresholds permitted before physician intervention should be sought. It also provided a means of instructing the radiation therapist as to which alternate modality to use in the event that the prescribed IGRT modality was unavailable or inoperable. In addition, any shifts made after initial imaging correlation by radiation therapist were recorded in the patient s treatment record. Data Collection A list of patients who completed their course of treatments from the time period studied of January 1, 2011 to April 30, 2011 was generated from the facility s billing database. The patients charts were pulled and copies were made of the shifts log, prescription, and the IGRT Accuracy Threshold Form. All selected charts were checked for completeness of documentation of coordinate shifts made for daily IGRT localization. Patients with shifts made after initial radiation therapist image acquisition, correlation and alignment were identified for further analysis. The information tallied were, number of patients per modality, the number of fractions per patient, and the average shift corrections per patient. Table 1 & 2 represent the tabular data generated from the data collected. Data Analysis The data collected was grouped as described above and further correlated based on minimum, maximum, mean, and standard deviation values for the average x, y, and z coordinate shifts for each patient. The percentage of agreement between the radiation therapists IGRT alignment and the radiation oncologist review and approval was determined by dividing the number of mutual agreement treatments by the total number of treatments per patient s course. A line graph representation of the average x, y and z shifts for patients in groups 2 is presented in

33 33 Figure 3. Group 1, which were prostate patients localized with the ACCULOC system all had no deviations from radiation therapists alignment. More specifically all 383 treatments that were localized by the radiation therapists and subsequently reviewed by the physician required either no further adjustment or fell within the accuracy threshold of < 3mm. There is no graph presented as all 9 patients treated to 383 treatments collectively were found to be acceptable to reviewing radiation oncologists for 100 percent of the treatments. In Figure 3 Group 2, it is noticeable that the greatest variability in patient alignment occurred in the anterior to posterior, or z, direction. This observation is most likely attributed to the effects of variability due to rectal and bladder filling as is well documented in the literature. 6,7,11 There appeared to be less variability in the x and y directions. The degree of error or change made from radiation therapists interpretation and physicians review was relatively small and fell well within the study facility PTV margins of no less than 7mm in any single dimension. The greatest variation for the CBCT cases was minimum/maximum values off of zero at 0.00/-0.76 cm. The mean x, y, z values for Group 2 were , 0.011, cm. The overall mean agreement amongst Group 2 was 82.7%. Further details of the statistical analysis are demonstrated in Table 2.

34 34 Chapter V: Discussion This study of the degree of discrepancy between radiation therapists IGRT alignment and physician s review provided the evidence needed to evaluate whether a written directive could be used as a surrogate for physician real-time approval. The development and implementation of a written directive in the form of the IGRT Accuracy Threshold Form presented in Figure 2, was ultimately the tool that allowed for validation of the ability of the radiation therapist to meet the physicians desired criteria for IGRT alignment. The retrospective evaluation of 985 IGRT treatments further supported the hypothesis that the majority of IGRT localization performed by the radiation therapists was not adjusted further upon physician review. This hypothesis was overwhelmingly proven in Group 1 patients that were localized based on implanted fiducial gold seed markers using the stereoscopic localization system, ACCULOC. As a result of the early results showing the relatively infrequent occurrence of the physician making a change from the radiation therapists alignment; adoption of the IGRT Accuracy Threshold Form as a surrogate for real-time physician approval was implemented before the study period was over for prostate patients treated with fiducial markers and utilizing the ACCULOC localization system. Limitations The anticipated limitations of this study were, finding the literature to support the use of a written directive surrogate for physician real-time approval, the assumption that the data collection instrument would be consistently completed for study subjects, concerns about the quantity and quality of the data and the variability in the accuracy of one IGRT modality over the other.

35 35 While the literature review covered many areas of consideration such as a historical perspective of IGRT, current practice, comparison of IGRT modalities, clinical implications of implementing IGRT, treatment delivery and practice guidelines; ultimately the literature did support the feasibility of implementing a surrogate solution to AAMC s logistical challenges of physician s availability for timely real-time IGRT approval. The ACR-ASTRO task group recommendation that each facility should develop QA procedures for the assurance of reproducibility and reliability of the IGRT process 3 was the professional endorsement needed to support the undertaking of the study. The concern about completeness of the data collection instruments was unfounded. As the IGRT documentation policy in place at AAMC was developed in compliance with ACR accreditation guidelines for treatment documentation, the data collection was not at all compromised by incomplete shifts documentation. All treatment records reviewed had complete documentation of the data and information being studied. The quantity of data was challenging to tally but since the main focus of the study was to evaluate the discrepancy between the radiation therapists interpretation of required localization shifts versus the physicians, the volume of relevant data was considerably reduced. The concerns regarding the limitation of variability in accuracy between the IGRT modalities in use at AAMC were validated. As previously noted, the patients in Group 1 localized with the ACCULOC system yielded remarkable results. All 9 patients in Group 1 who completed 383 treatments during the study period, were localized and shifted by the treating radiation therapist without any further adjustment or changes by reviewing physician. There was also no noted physician intervention needed due to shift thresholds exceeding physician directive as detailed in IGRT Accuracy Threshold Form. As a result of such overwhelming positive

36 36 results, the decision was made three-quarters through the study period to adopt the IGRT Accuracy Threshold Form as a surrogate for physicians real-time approval. This change in process provided immediate relief to the logistical challenges this study hoped to address of freeing up the demand on the physicians availability for real-time approval. Conclusions The study was successful in proving the hypothesis that a written directive surrogate can be implemented as an alternative to real-time physician approval for IGRT cases. Based on early study findings the decision was made to adopt a written directive surrogate in lieu of physician real-time approval for all patients being localized with the ACCULOC system. The findings for Groups 2, the CBCT patients, were promising but it was decided that this subset of the study population should continue to be followed as the CBCT modality is still new to the study facility, having only been installed in September of As a result of this study, a second study is underway to evaluate CBCT cases for further evaluation of the reasons for discrepancy in shifts. This secondary study will evaluate patients anatomical variability as well as shift variation related to user or treating therapist. Ultimately, the problem that this research sought to remedy was successfully addressed for a subset of the study population, with high expectation that in the near future this written directive surrogate will be implemented as a class solution for all prostate IGRT patients treated at AAMC. The validation of the IGRT Accuracy Threshold Form as an effective tool for guiding IGRT treatments has contributed greatly to improved workflow and treatment of patients. Whether used as a surrogate to real-time physician approval or just as a written directive for delivery of physicians intended criteria, this tool has positively impacted the quality of care for our patients and work conditions for the staff involved in the IGRT process.

37 37 Recommendations The ability to use research to change or improve clinical practices or address concerns in the clinic is an opportunity that should not go untapped. Decisions that have the potential to affect clinical outcomes and/or the health of patients should never be made without proper research and consideration of associated factors. This study demonstrates how a scientific research process can be implemented even on a small scale, to address a very specific concern with outcomes that can make a positive contribution to any clinic. This study has provided the impetus for continued study of this center s prostate IGRT challenges. As a result of conducting this study and the experience gained, I would recommend that more clinicians make a commitment to this approach of conducting responsible research as a means of changing or addressing clinical practice issues

38 38 References 1. Prostate Cancer Overview. American Cancer Society Web site. December 13, Accessed Apr 10, ACCULOC-EPID. CIVCO Medical Solutions Web site. Accessed April 10, Potter L, Gaspar L, Kavanagh B, et al. American society for therapeutic radiology and oncology (ASTRO) and American college of radiology (ACR) practice guidelines for image guided radiation therapy (IGRT). International journal radiation oncology biological physics. 2010;12(2): Dictionary of Cancer Terms. National Cancer Institute Web site. Accessed April 22, Shirato H, Shimizu S, Kitamura K, et al. Organ motion in image-guided radiotherapy: lessons from real-time tumor-tracking radiotherapy. International journal of clinical oncology. 2007;12: Hammoud R, Patel S, Pradhan D, et al. Examining margin reduction and its impact on dose distribution for prostate cancer patients undergoing daily cone-beam computed tomography. International journal radiation oncology biological physics. 2008; 71(1): Gayou O, Miften M. Comparison of mega-voltage cone-beam computed tomography prostate localization with online ultrasound and fiducial markers methods. Medical physics. 2008;35(2): Chen GTY, Pelizzari CA. Imaging in radiotherapy. In Khan FM, Potish RA eds. Treatment Planning in Radiation Oncology. Baltimore, MD: Williams & Wilkins;1998: Johnston H, Hilts M, Beckham W, et al. 3D ultrasound for prostate localization in radiation therapy: a comparison with implanted fiducial markers. Medical physics. 2008;35(6): Etchells L, Ahlers K. IGRT: history in the making. Program; for radiation oncology professionals. Fall/winter Orange City, IA. Civco Medical Solutions. 11. Adamson J, Wu Q. Inferences about prostate intrafraction motion from pre- and posttreatment volumetric imaging. International journal radiation oncology biological physics. 2009;75(1),

39 Barney BM, Lee RJ, Handrahan D et al. Image-guided radiotherapy (IGRT) for prostate cancer comparing kv imaging of fiducial markers with cone beam computed tomography (CBCT). International journal radiation oncology biological physics. 2011;80(1), Artignan X, Smitsmans M, Lebesque JV et al. Online ultrasound image guidance for radiotherapy of prostate cancer: Impact of image acquisition on prostate displacement. International journal radiation oncology biological physics. 2004;59(2), Pawlowski JM, Yank ES, Malcolm AW et al. Reduction of dose delivered to organs at risk in prostate cancer patients via image-guided radiation therapy. International journal radiation oncology biological physics. 2010;76(3),

40 40 List of Tables Table 1. Group 1 - Prostate Patients Localized with ACCULOC Data Prostate Patients Localized with ACCULOC Patient # # of Treatments Agreement % X (cm) right/left Y (cm) sup/inf Z (cm) ant/post Total Table 2. Group 2 - Prostate Patients Localized with CBCT Data Prostate Patients Localized with CBCT Patient # # of Treatments Agreement % X (cm) right/left Y (cm) sup/inf Z (cm) ant/post Minimum Mean Maximum Std Deviation Total

41 41 List of Figures Figure 1. IGRT Modalities: a)3d US, b)cbct, c) and d) Orthogonal Films