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Linac Based Imaging

James Gordon, Ph.D.Henry Ford Health System

Disclosures

• I participate in research funded by Varian Medical Systems and Philips Medical Systems

Outline of Presentation

• Learning Objectives• Benefits of IGRT• Achievable setup uncertainties, guidelines• Desirable Properties of Imaging Systems• Additional considerations• Conclusions

Learning Objectives

• Discuss achievable uncertainties & margins

• Discuss guidelines for use of IGRT

• Identify desirable characteristics of linac-based IGRT

Benefits of IGRT• Bujold et al [1] summarize the benefits of IGRT:

– IGRT can detect gross uncertainties and outlier patients, who fall outside predicted population-based margins

– IGRT reduces systematic and random errors, allowing margin reduction and potentially reduced toxicity

– By increasing treatment accuracy, IGRT enables new types of treatments (e.g., frameless SRS, SBRT)

– IGRT is a process control framework, use of which allows tightened control limits and a quantitative basis for setting margins

IGRT as Process Control Framework

Reproduced from Bujold et al [1]

IGRT can be considered as a process control tool, that ensures that your clinic’s treatments are an ‘in-control’ process. For an in-control process:

1. Errors and uncertainties are eliminated

2. All aspects of the treatment process are thoroughly documented

3. Errors and uncertainties are minimized through a combination of online and offline correction strategies

4. Errors and uncertainties are minimized through online correction strategies only

5. Errors and uncertainties are measured and minimized through offline and / or online correction strategies

10

IGRT can be considered as a process control tool, that ensures that your clinic’s treatments are an ‘in-control’ process. For an in-control process:

56%11%30%1%2% 1. Errors and uncertainties are eliminated





Correct answer: 5

1. Errors and uncertainties are eliminated





Ref: Bujold, Alexis, Tim Craig, David Jaffray, and Laura A Dawson. “Image-Guided Radiotherapy: Has It Influenced Patient Outcomes?” Seminars in Radiation Oncology 22, no. 1 (January 2012): 50–61

IGRT Caveats• IGRT is justified when patient benefits outweigh the

disadvantages

• Extra radiation dose should be considered, and minimized through appropriate imaging parameters (ALARA)

• Other disadvantages need to be weighed, e.g., risk of pneumothorax as a result of inserting markers

IGRT can be used:

1. always

2. when benefits outweigh risks and it can reasonably be judged to reduce net systematic and / or random treatment uncertainties

3. on a case-by-case basis, when judged to be useful

4. when significant motion or uncertainties are present

5. when its benefit outweighs risks to the patient, and it can be performed without extending treatment times excessively

10

IGRT can be used:

24%1%2%70%3% 1. always





Correct answer: 2

1. always





Ref: Bujold, Alexis, Tim Craig, David Jaffray, and Laura A Dawson. “Image-Guided Radiotherapy: Has It Influenced Patient Outcomes?” Seminars in Radiation Oncology 22, no. 1 (January 2012): 50–61

IGRT ApproachesMany options: [2]

• kV CBCT• orthogonal kV, MV (with 2D/2D or 2D/3D fusion)• implanted fiducials (active or passive)• optical surface matching• MV CBCT• ultrasound• digital tomosynthesis• CT on rails• ...

Factors Affecting Accuracy• Linac / imaging system isocenter alignment

– achievable accuracy < 1mm, < 1° [3]

• Inherent limitations of technique – e.g., 4D fusion cannot correct for pitch and roll

• Intra- and inter-observer variability of fusions– influenced by treatment site, image quality, artifacts, training

• Use of surrogate for localization– sensitive to changes in relative positions of target and surrogate

• Rigid body fusion may be accurate only at one location– rigid fusions cannot compensate for changes in relative positions of multiple targets,

or targets and normal tissues

• Relative motion of tissues and MLC– interplay effects

• Respiratory motion

Linac / Imaging System Isocenter Alignment

From Kim et al [3]:“Clinical Commissioning and Use of the Novalis Tx Linear Accelerator for SRS and SBRT”

Demonstrates isocenter accuracy < 1mm, < 1°

Outline of Presentation

• Learning Objectives• Benefits of IGRT• Achievable setup uncertainties, guidelines• Desirable Properties of Imaging Systems• Additional considerations• Conclusions

IGRT for Cranial SRS• Boda-Heggemann’s review article [4] concludes:

– skull bony anatomy is a good surrogate for the target, verification imaging after setup correction is recommended

– residual errors in image-guided stereotactic radiation therapy are small

– residual rotational errors are negligible for small spherical targets, but relevant for large complex targets, or simultaneous irradiation of multiple targets [5,6]

– intra-fractional motion in mask or bite-block systems is larger than for frame-based treatments, but still within acceptable limits of 1-2mm [7]

• Use of VMAT for single-isocenter, multi-target treatments is relatively new

– quantitative experience with residual uncertainties is needed for margin determination

IGRT for Lung SBRT• Challenges:

– Up to 3 cm tumor excursion during breathing [8]

– Inter-fraction anatomical changes (atelectasis, pleural effusion, etc) [9]

– Inter- and intra-fraction baseline shifts of up to ~ 5 mm [10]

– Breathing motion reproducibility [8]

• Motivation:– Improved control with dose escalation [11]

– Reduced toxicity with smaller margins [12,13]

IGRT for Lung SBRT• IGRT options: [8]

– ITV– gating– breath hold– tracking

• Registration to: [14]

– Bony anatomy– Tumor alone– Tumor plus lymph nodes– Implanted markers

IGRT for Lung SBRT ─ Guidelines• Per TG-76, TG-101, evaluate each patient (4DCT) for motion

management options– determine motion management approach– quantify residual motion– design treatment margins– quantify & account for any phase shift between tumor & respiratory signal

• Daily IGRT should be used to reduce residual uncertainties, correct for baseline shifts.

• Volumetric imaging gives better registration of deforming anatomy, identifies shifts in relative positions of target and critical structures.

AAPM TG-76 Report 91 Process• TG-76 Report 91 Summary and

Recommendations section summarizes key considerations under 5 headings:

– Clinical process recommendations

– Treatment planning recommendations

– Personnel recommendations

– Quality assurance recommendations

– Recommendations for further investigations

IGRT for Lung SBRT ─ Guidelines• Register 3D CBCT to average (not free-breathing) CT

(free-breathing CT risks capturing the tumor at one point on its trajectory)

• Registration to tumor (not bony anatomy) minimizes margins(but, e.g., could register first to bony anatomy, then adjust based on soft tissue match to ensure target is within PTV)

• Fluoroscopic imaging, 4D CBCT or triggered imaging can assess breathing motion & target coverage at treatment time

• Note: Daily IGRT minimizes dose deviations to targets, but significant dose deviations can still occur for normal tissues [12]

4D CBCT to Assess Treatment Motion Prior to Treatment

4D CT

4D CBCT to Assess Treatment Motion Prior to Treatment

4D CBCT

Relative Motion of Target and Critical Structure

Planning CT

patient re-positioned

CBCT Target Localized Heart Inside High Dose Region

CBCT Target Re-Localized Heart Outside High Dose Region

Slide courtesy of D. Jaffray

IGRT for Lung SBRT ─ Significant Normal Tissue Dose Deviations

Daily IGRT for lung treatments can:

%

%

%

%

%1. reduce target geometric misses

2. reduce treatment times

3. improve target coverage, though significant normal tissue dose deviations can still occur

4. improve target coverage and normal tissue sparing

5. compensate for relative motion of target and normal tissues

10

Daily IGRT for lung treatments can:

9%

23%

55%

0%

13% 1. reduce target geometric misses





Correct (best) answer: 3

Ref: Galerani, Ana Paula, Inga Grills, Geoffrey Hugo, Larry Kestin, Nasiruddin Mohammed, K Kenneth Chao, Andrew Suen, Alvaro Martinez, and Di Yan. Dosimetric Impact of Online Correction via Cone-Beam CT-Based Image Guidance for Stereotactic Lung Radiotherapy. International Journal of Radiation Oncology, Biology, Physics 78, no. 5 (December 1, 2010): 1571–78

1. reduce target geometric misses





Margins for Lung RTInstitution ITV CTV (mm) PTV (mm)

A GTV1 GTV2 … GTV10 ITV + 5CTV + 5 (IGRT)CTV + 10 (no IGRT)

B GTV from MIP ITVSBRT: ITV + 5 STD Fx: ITV + 10

C GTV1 GTV2 … GTV4

SBRT: ITVSTD Fx (no 4D): GTV + 10STD Fx (4D): ITV + 5

CTV + 6 (IGRT)CTV + 5 (no IGRT)CTV + 10 (no IGRT)

D GTV from MIP or expected percentiles (gating)

SBRT: ITVSTD Fx: ITV + 5

CTV + 5 (IGRT)CTV + 7 (no IGRT)

Adapted from “Lung Panel”, Kestin et al. ASTRO State of the Art Meeting, 2011Slide courtesy of I.Chetty

Gating, Breath-Hold & Tracking• Gating & Breath-hold:

– Gating & BH can extend treatment time by a factor of 2-5– This disadvantage is mitigated for high-dose rate FFF beams– However, dose deviations due to interplay effects may be

exacerbated for FFF beams [15,16]

• Tracking:– One disadvantage has been excessive dose associated with

fluoroscopic imaging– Active markers (i.e, EM transponders) may provide a solution

for a subset of patients

IGRT for Liver SBRT• Used to treat HCC, potentially oligometastases

• Same IGRT challenges and motivations as for lung SBRT

• Dawson [17] makes a number of recommendations:– Contrast with multi-phasic imaging required for tumor delineation

– Daily IGRT is required, implanted fiducials not required (but may be beneficial for some patients)

– Given poor soft tissue visualization, its desirable to use gated / multiple breath-hold CBCT with breath-hold patients, or 4D CBCT for non-breath-hold patients

– PRVs are needed if the potential exists for baseline shifts to move targets closer to critical structures, such as the cord

– See Dawson et al [17] and AAPM TG-76 [7] for residual uncertainty estimates

Desirable Properties of Imaging Systems

• Accurate setup / localization• Ability to verify clinical setup / localization accuracy

• Ability to setup / localize at non-zero couch angles

• Ability to monitor positional deviations during treatment

• Ability to interrupt treatment if deviation exceeds tolerance

• Ability to export motion data for offline analysis, for purposes of treatment verification, margin analysis and quality control


• Accurate setup / localization

• Ability to verify clinical setup / localization accuracy• Ability to setup / localize at non-zero couch angles




Verifying Clinical Accuracy• The ability to accurately ‘treat’ a phantom is a necessary, but not a

sufficient, condition for accurately treating a patient

• End-to-end phantom tests, demonstrating accuracy <~ 2mm, are not a substitute for measurements of clinical uncertainties

• How to measure clinical uncertainties?– Repeat / verification measurements of position corrections, utilizing the primary imaging

system, are a check on setup accuracy

– E.g., if you setup using CBCT, then immediately measure residual error using CBCT or orthogonal kV/MV pair, the residual error should be small

– Verification measurements using a secondary imaging system, having independent failure modes, provides better assurance

– E.g., perform initial setup with CBCT, then measure residual error using ExacTrac or other independent imaging system

Verifying Clinical AccuracyFrom Kim et al [3]:“Clinical Commissioning and Use of the Novalis Tx Linear Accelerator for SRS and SBRT”

Demonstrates agreement between CBCT, MV/kV and ExacTrac setup

A useful strategy for measuring clinical treatment accuracy, as distinct from accuracy in end-to-end phantom tests,is to:

1. Ask your IGRT equipment provider for their estimate of the system’s clinical accuracy

2. Take end-to-end phantom accuracy and multiply by 2

3. Use primary or secondary imaging system to make repeat measurements of isocenter shifts at points during treatment

4. Take published clinical margins and reverse engineer the van Herk margin formula to deduce standard deviations of clinical setup errors

5. Use fluoroscopic imaging to quantify intra-fraction motion

10

A useful strategy for measuring clinical treatment accuracy, as distinct from accuracy in end-to-end phantom tests,is to:

6%

1%

89%

1%

2% 1. Ask your IGRT equipment provider for their estimate of the system’s clinical accuracy





Correct answer: 3

Ref: An example is given in: Kim, Jinkoo, Ning Wen, Jian-Yue Jin, Nicole Walls, Sangroh Kim, Haisen Li, Lei Ren, et al. “Clinical Commissioning and Use of the Novalis Tx Linear Accelerator for SRS and SBRT.” Journal of Applied Clinical Medical Physics / American College of Medical Physics 13, no. 3 (2012): 3729

1. Ask your IGRT equipment provider for their estimate of the system’s clinical accuracy







• Ability to verify clinical setup / localization accuracy

• Ability to setup / localize at non-zero couch angles• Ability to monitor positional deviations during treatment



Single-Isocenter Treatment of Multiple Targets

• Single-isocenter treatments of multiple targets ─ e.g., use of VMAT to treat multiple targets simultaneously ─ is being explored [5,6]

• Traditional treatments of a single target at isocenter are in many cases insensitive to small angular setup errors; this may not hold when treating multiple targets lying at a distance from the isocenter

• FMEA can be applied to this scenario: how many checks exist in your treatment process to detect angular setup errors?

• For cranial treatments, where non-zero couch angles are routinely employed, imaging systems which can check setup accuracy at non-zero couch angles are desirable (e.g., OSMS, ExacTrac)

For setup of spine patients, your IGRT system exhibits residual rotationalerrors of up to 5 degrees around the patient’s long axis. Your plan is touse spine SRS (single fraction) to treat a vertebral body plus a small lunglesion that is 5 cm lateral to the vertebral body, using a VMAT single-isocenter multiple-target approach. Reasonable due-diligence to ensuretreatment accuracy in this case would be to:

1. consult the literature for margins to use around the lung lesion

2. assume standard translational residual uncertainties used for single target treatments, and rely on the IGRT system to eliminate rotational uncertainty

3. during IGRT localization, view alignment for both targets and ‘split the difference’ due to any relative motion between targets

4. determine margins based on translational and rotational residual uncertainties measured in your clinic, and the specific patient geometry

5. if the patient does not setup well on first attempt, repeat the setup until satisfactory

10

For setup of spine patients, your IGRT system exhibits residual rotationalerrors of up to 5 degrees around the patient’s long axis. Your plan is touse spine SRS (single fraction) to treat a vertebral body plus a small lunglesion that is 5 cm lateral to the vertebral body, using a VMAT single-isocenter multiple-target approach. Reasonable due-diligence to ensuretreatment accuracy in this case would be to:

13%72%8%7%0% 1. consult the literature for margins to use around the lung lesion





Correct answer: 4

Although protocols (e.g., RTOG 0631) offer guidance on planning for the vertebral body alone, published literature does not offer a lot of guidance at this time on treatment margins for single-isocenter, multiple-target treatments. In this example, if the isocenter is in the vertebral body, a 5 degree residual rotational uncertainty could result in a ~4mm offset of the lung lesion. It is necessary to perform measurements in your clinic to quantify the magnitudes of residual translational and rotational uncertainties, and incorporate those measurements into treatment margins. Repeat setup of the patient may help, but may not eliminate uncertainties due to relative motion between targets. Fractionated RT is generally more tolerant of residual uncertainties. If residual relative motion is large, the targets should be treated with separate isocenters. Ref: See e.g., Schreibmann, Fox, Crocker. Dosimetric effects of manual cone-beam CT (CBCT) matching for spinal radiosurgery: our experience. J Appl Clin Med Phys. 2011 Apr 13;12(3):3467.

1. consult the literature for margins to use around the lung lesion







• Ability to verify clinical setup / localization accuracy

• Ability to setup / localize at non-zero couch angles




IGRT Support for Margin Determination

• In [19] Purdy writes: “While advanced IGRT treatment machines are now installed in many facilities, few sites have taken the steps to use their IGRT data to determine PTV margins specific for their clinic’s work. These values are readily available from each clinic’s IGRT practice data using well-established methodologies.”

• Potential exists to exploit IGRT data for process control purposes: to detect & correct systematic treatment errors, and quantify random uncertainties, in SRS / SBRT delivery.

• This depends on imaging & R&V systems providing motion data in mine-able format.

Additional Considerations• Documentation of treatment workflows• Margin formulas & action levels• Training material

Documentation of Treatment Workflows

From Kim et al [3]:“Clinical Commissioning and Use of the Novalis Tx Linear Accelerator for SRS and SBRT”

See also flow chart examples in references [20] & [21]

OBI = on-board kV imager

CBCT = cone beam CT

ETX = Brainlab ExacTrac

Snap Verification = ExacTrac kV snapshot during treatment to verify target alignment

Margin Formulas and Action Levels• The commonly-used version of the van Herk margin formula [22] was

derived for fractionated therapy where many random errors ‘blur’ the dose distribution

– that formula will not necessarily apply to hypofractionated treatments [23]

– Ecclestone et al [24] conclude that it is acceptable (conservative) for lung treatments, but suggest ways to improve

– the full version of the formula [22] can potentially be applied to these scenarios

• The IGRT workflow should include a correction strategy that avoids ‘chasing’ the target with daily shifts

– the IGRT correction strategy should correct systematic offsets without over-responding to random uncertainties

– reference [20] discusses No Action Level (NAL) and Shrinking Action Level (SAL) correction strategies

Training MaterialIGRT training can help ensure consistent treatment quality

These examples are from reference [20]: On Target: Ensuring Geometric Accuracy in Radiotherapy. Royal College of Radiologists, 2008.

References[1] Bujold, Alexis, Tim Craig, David Jaffray, and Laura A Dawson. “Image-Guided Radiotherapy: Has It Influenced Patient Outcomes?”

Seminars in Radiation Oncology 22, no. 1 (January 2012): 50–61. [2] De Los Santos, Jennifer, Richard Popple, Nzhde Agazaryan, John E. Bayouth, Jean-Pierre Bissonnette, Mary Kara Bucci, Sonja

Dieterich, et al. “Image Guided Radiation Therapy (IGRT) Technologies for Radiation Therapy Localization and Delivery.” International Journal of Radiation Oncology*Biology*Physics 87, no. 1 (September 1, 2013): 33–45.

[3] Kim, Jinkoo, Ning Wen, Jian-Yue Jin, Nicole Walls, Sangroh Kim, Haisen Li, Lei Ren, et al. “Clinical Commissioning and Use of the Novalis Tx Linear Accelerator for SRS and SBRT.” Journal of Applied Clinical Medical Physics / American College of Medical Physics13, no. 3 (2012): 3729.

[4] Boda-Heggemann, Judit, Frank Lohr, Frederik Wenz, Michael Flentje, and Matthias Guckenberger. “kV Cone-Beam CT-Based IGRT: A Clinical Review.” Strahlentherapie Und Onkologie 187, no. 5 (May 2011): 284–91.

[5] Sterzing, Florian, Thomas Welzel, Gabriele Sroka-Perez, Kai Schubert, Jürgen Debus, and Klaus K Herfarth. “Reirradiation of Multiple Brain Metastases with Helical Tomotherapy. A Multifocal Simultaneous Integrated Boost for Eight or More Lesions.” Strahlentherapie Und Onkologie 185, no. 2 (February 2009): 89–93.

[6] Clark, Grant M, Richard A Popple, Brendan M Prendergast, Sharon A Spencer, Evan M Thomas, John G Stewart, Barton L Guthrie, James M Markert, and John B Fiveash. “Plan Quality and Treatment Planning Technique for Single Isocenter Cranial Radiosurgery with Volumetric Modulated Arc Therapy.” Practical Radiation Oncology 2, no. 4 (December 2012): 306–13.

[7] Ramakrishna, Naren, Florin Rosca, Scott Friesen, Evrim Tezcanli, Piotr Zygmanszki, and Fred Hacker. “A Clinical Comparison of Patient Setup and Intra-Fraction Motion Using Frame-Based Radiosurgery versus a Frameless Image-Guided Radiosurgery System for Intracranial Lesions.” Radiotherapy and Oncology 95, no. 1 (April 2010): 109–15.

[8] AAPM Task Group 76 Report 91: The Management of Respiratory Motion in Radiation Oncology, AAPM 2006.[9] Sonke, Jan-Jakob, and José Belderbos. Adaptive Radiotherapy for Lung Cancer. Seminars in Radiation Oncology 20, no. 2 (April

2010): 94–106. [10] Zhao, Bo, Yong Yang, Tianfang Li, Xiang Li, Dwight E Heron, and M Saiful Huq. Statistical Analysis of Target Motion in Gated Lung

Stereotactic Body Radiation Therapy. Physics in Medicine and Biology 56, no. 5 (March 7, 2011): 1385–95.

References[11] Kestin, Larry, Inga Grills, Matthias Guckenberger, Jose Belderbos, Andrew J Hope, Maria Werner-Wasik, Jan-Jakob Sonke, et al.

“Dose-Response Relationship with Clinical Outcome for Lung Stereotactic Body Radiotherapy (SBRT) Delivered via Online Image Guidance.” Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology, March 11, 2014.

[12] Galerani, Ana Paula, Inga Grills, Geoffrey Hugo, Larry Kestin, Nasiruddin Mohammed, K Kenneth Chao, Andrew Suen, Alvaro Martinez, and Di Yan. Dosimetric Impact of Online Correction via Cone-Beam CT-Based Image Guidance for Stereotactic Lung Radiotherapy. International Journal of Radiation Oncology, Biology, Physics 78, no. 5 (December 1, 2010): 1571–78.

[13] Schmidt, Mai Lykkegaard, Lone Hoffmann, Maria Kandi, Ditte S Møller, and Per Rugaard Poulsen. “Dosimetric Impact of Respiratory Motion, Interfraction Baseline Shifts, and Anatomical Changes in Radiotherapy of Non-Small Cell Lung Cancer.” Acta Oncologica(Stockholm, Sweden) 52, no. 7 (October 2013): 1490–96. doi:10.3109/0284186X.2013.815798.

[14] Mohammed, Nasiruddin, Larry Kestin, Inga Grills, Chirag Shah, Carri Glide-Hurst, Di Yan, and Dan Ionascu. “Comparison of IGRT Registration Strategies for Optimal Coverage of Primary Lung Tumors and Involved Nodes Based on Multiple Four-Dimensional CT Scans Obtained Throughout the Radiotherapy Course.” International Journal of Radiation Oncology*Biology*Physics 82, no. 4 (March 2012): 1541–48.

[15] Ong, Chin Loon, Max Dahele, Ben J Slotman, and Wilko F A R Verbakel. “Dosimetric Impact of the Interplay Effect during Stereotactic Lung Radiation Therapy Delivery Using Flattening Filter-Free Beams and Volumetric Modulated Arc Therapy.” International Journal of Radiation Oncology, Biology, Physics 86, no. 4 (July 15, 2013): 743–48.

[16] Li, Xiang, Yong Yang, Tianfang Li, Kevin Fallon, Dwight E Heron, and M Saiful Huq. “Dosimetric Effect of Respiratory Motion on Volumetric-Modulated Arc Therapy-Based Lung SBRT Treatment Delivered by TrueBeam Machine with Flattening Filter-Free Beam.” Journal of Applied Clinical Medical Physics / American College of Medical Physics 14, no. 6 (2013): 4370.

[17] L. Dawson, PMH, Imagining Image Guidance in Liver SBRT, https://www.youtube.com/watch?v=BjEN8zFYsJ0. [18] Dawson, Laura A, Cynthia Eccles, Jean-Pierre Bissonnette, and Kristy K Brock. “Accuracy of Daily Image Guidance for

Hypofractionated Liver Radiotherapy with Active Breathing Control.” International Journal of Radiation Oncology, Biology, Physics 62, no. 4 (July 15, 2005): 1247–52.

[19] Meyer, J. L. IMRT, IGRT, SBRT. Karger Medical and Scientific Publishers, 2011.

References[20] On Target: Ensuring Geometric Accuracy in Radiotherapy. Royal College of Radiologists, 2008. (At time of writing available at:

http://www.rcr.ac.uk/docs/oncology/pdf/BFCO(08)5_On_target.pdf )[21] Image Guided Radiotherapy (IGRT): Guidance for implementation and use. National Radiotherapy Implementation Group Report, 2012.

(At time of writing available at: http://www.hpa.org.uk/ProductsServices/Radiation/Radiotherapy/RadiotherapyGuidanceDocuments/ ) [22] Van Herk, M., P. Remeijer, C. Rasch, and J. V. Lebesque. “The Probability of Correct Target Dosage: Dose-Population Histograms for

Deriving Treatment Margins in Radiotherapy.” Int.J.Radiat.Oncol.Biol.Phys. 47, no. 4 (July 1, 2000): 1121–35.[23] Zhang, Qinghui, Maria F Chan, Chandra Burman, Yulin Song, and Mutian Zhang. “Three Independent One-Dimensional Margins for

Single-Fraction Frameless Stereotactic Radiosurgery Brain Cases Using CBCT.” Medical Physics 40, no. 12 (December 2013): 121715.

[24] Ecclestone, Gillian, Jean-Pierre Bissonnette, and Emily Heath. “Experimental Validation of the van Herk Margin Formula for Lung Radiation Therapy.” Medical Physics 40, no. 11 (November 2013): 111721.