Optimising tracking accuracy and dose delivery in Stereotactic Body Radiotherapy

289 Pages·2017·5.52 MB·English

Individualising anti-cancer treatment:

Optimising tracking accuracy and dose delivery in
Stereotactic Body Radiotherapy (SBRT)

Dr Christy Saron Goldsmith,
MBBS, B.Sc., MRCP, FRCR

Submitted for MD (Res)

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Abstract

Introduction:
Stereotactic Body Radiotherapy (SBRT) is a form of highly focal radiation therapy. Treatment delivery
is largely guided (“tracked”) by gold-marker fiducials for non-spinal body sites. CyberKnife (CK) is
purpose-built todeliver SBRT.
Methods:
An experimental system, using a radiotherapy “phantom”, was designed to assess the accuracy of the
CK system in imaging static and migrating fiducials (Chapter 2). An assumption in fiducial-tracked
treatments is that the exact arrangement of fiducials at planning CT is maintained at treatment. It is
also crucial that relative Organ At Risk (OAR) and tumour position, is consistent between planning CT
scan and treatment. The validity of this assumption was assessed by comparing fiducial locations on
Planning and Treatment CTs (Chapter 3). The feasibility of achieving consistent bladder filling, and
the impact of consistent filling on the ability to track translations/rotations in prostate cancer
therapy was explored (Chapter 4). Uncertainties in treatment planning/delivery for CK prostate
patients was explored, and ideal planning margins were calculated (Chapter 5). Optimum SBRT dose
for localised pancreatic cancer, lymph node oligometastasis and oligometastatic breast cancer was
explored (Chapter 6).
Results:
Imaging of fiducial position was accurate and reproducible across a clinically appropriate tracking
range. However, findings highlighted the need for vigilance at treatment delivery. The reliability and
“trackability” of implanted fiducials, as well as consistency of OAR position, varied according to
tumour and implantation site. Guidelines were generated accordingly. Bladder filling/Margins
guidelines have been generated. Radiobiological analysis has indicated that there is scope for
cautious dose escalation in the SBRT treatment of pancreatic cancer. Analysis of SBRT-treated lymph
node oligometastases has demonstrated that Local Control is 100% when SBRT is prescribed to a
threshold 72Gy
10.
Conclusion:
Refinements in patient preparation, fiducial placement, and dose/fractionation selection can
optimise tracking accuracy and dose delivery in SBRT.
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Table of Contents

Content Page number
Title page 1
Abstract 2
Table of Contents 3
Chapter 1 4
Chapter 2 29
Chapter 3 70
Chapter 4 150
Chapter 5 205
Chapter 6 239
Acknowledgements 286
Abstracts and Publications arising 287

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CHAPTER 1

Background and Introduction

1.1 Conventionally fractionated Conformal Radiotherapy
1.1.1: Treatment planning
- Simulation
- ICRU Target Concepts
- Tumour localisation
- Planning
- Limitations of Conformal radiotherapy
1.1.2: Dose Fractionation issues

1.2 Intensity Modulated RadioTherapy
1.2.1 Treatment planning
1.2.2 Clinical evidence for gain over Conformal radiotherapy

1.3 Stereotactic Body Radiotherapy
1.3.1 Definition
1.3.2 Key Components
- Immobilisation
- Tumour motion
1.3.3 SBRT Treatment delivery systems
1.3.4 Conformality
1.3.5 Dose-fractionation issues

1.4 Summary
1.5 Aims of this Research

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CHAPTER 1
Background and Introduction

1.1 Conventionally fractionated Conformal Radiotherapy
Radiotherapy is the medical use of ionising radiation to kill malignant cells in order to control cancer.
Ionising radiation is able to kill cancer cells (but also normal body cells), by damaging cellular DNA, via
a number of different mechanisms. Radiotherapy is a local form of treatment, and as normal tissue is
radiosensitive, it is important that the deposition of radiation dose is accurately deposited on the
tumour and spares collateral damage to adjacent normal healthy tissues.
Once a patient is seen in clinic and consented for Radiotherapy, there a number of important steps in
the Radiotherapy Planning Process which must occur before a patient can receive their treatment.

1.1.1 Treatment Planning Process:
Simulation
The Radiotherapy planning process starts with the process of “simulation”. The process of
“simulation”, for many years, involved a patient being immobilised in their treatment position on a
couch. A “conventional” radiotherapy simulator would then capture two-dimensional (2D)
information. A conventional simulator comprised a diagnostic X-ray tube mounted to reproduce the
geometric movements of a radiotherapy treatment machine, which was capable of imaging with
fluoroscopy and diagnostic film. Three-Dimensional (3D) information was inferred by taking
orthogonal X-Ray films. As conventional planning can only infer 3D information, this is a limitation of
the technique, as accurate dosimetry requires full 3D information in order to fully evaluate
attenuation of the photon beam within tissue.
In order to overcome this limitation, conventional simulators have now largely been replaced by
Computed Tomography (CT), or “virtual” CT simulators. These simulators comprise a CT scanner,
laser marking system, and 3D work-station to allow the visualisation and manipulation of the CT data
for treatment localisation. The information derived through CT is inherently 3D, and contains both
contour and tissue density information which is required for the planning process (1). A 3D based
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environment for imaging, planning and radiotherapy delivery is the current baseline standard
according to the most recent National Radiotherapy Advisory Group (NRAG) report (2).

Scanned images taken at virtual simulation are linked into treatment planning software that allows
Clinical Oncologists to visualise and localise the tumour target in 3D.

The International Commission on Radiation Units and Measurements Guidelines (ICRU):
Target Concepts

The ICRU 50 report (1993) defines standards for describing Radiotherapy prescription volumes.
Gross Tumour Volume (GTV) represents the gross palpable or visible extent of disease.
Clinical Target Volume (CTV) incorporates a margin of normal tissue for unknown subclinical or
microscopic disease.
Planning Target Volume (PTV) includes all other errors and uncertainties e.g. tumour motion and set-
up errors (3).

The ICRU 62 report (1999) acknowledges the effect of organ/tumour movement, the resulting
uncertainties are accommodated by expanding the CTV to an Internal Target Volume (ITV) by an
Internal Margin (IM). The report also accounts for uncertainties in treatment delivery due to errors
in beam-patient positioning, called the Set Up margin (SM), to develop a Planning Target Volume
(PTV) (4). See Figure 1.

Figure 1: Diagram to illustrate the concepts of GTV, CTV, ITV, and PTV

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Tumour localisation

There have been a number of advances in recent years that have made it possible to more accurately
delineate a target.

It is now possible to fuse the 3D CT data set with Magnetic Resonance Imaging (MRI) scans. This aids
the outlining process, as some tumours, e.g. brain and prostate are more easily seen on MRI than CT
(5). In a study by Sannazzari et al, the CTV for localised prostate cancer (prostate plus seminal
vesicles) was delineated on both CT and MRI studies. Image fusion was achieved by fusing to
anatomical fiducial markers. There was a mean over-estimation of CTV of 34% with CT compared
with MRI (6).

The outlining of other tumours that are glucose-avid, e.g. Non-Small Cell Lung Cancer (NSCLC),
Squamous cell cancers of the Head and Neck is helped by the ability to fuse Positron Emission
Tomography (PET) scans to the Primary CT scan (7, 8).

PET scans are performed following the administration of 18F-Fluoro-DeoxyGlucose (FDG), a glucose
analogue. As the FDG is labeled with 18F at the 2-prime hydroxyl position, the normal degradation
that occurs during glycolysis is prevented, and the radio-labelled FDG accumulates within the tissue
(9). In this way, PET scans provide functional information (metabolic rate), and are good for
identifying nodal disease Head &Neck cancers (see Figure 2, page 8), as well as areas of atelectasis in
Thoracic cancer.

Studies have demonstrated a change in the PTV in approximately 30% of cases of NSCLC, which may
have important consequences for both toxicity and tumour control. PET-fusion may allow smaller
volumes to be outlined (especially likely in cases of atelectasis), this would allow smaller volumes of
normal lung to be irradiated, which should improve the toxicity profile of the treatment (10).
Alternatively, PET may increase the outlined tumour volumes (due to positive lymph nodes), which is
likely to have a positive impact on tumour control (11).

A disadvantage to PET (compared to CT), however, is that PET has poorer spatial resolution (12).

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Figure 2: Image A shows a CT image taken at the level of the thoracic inlet. The arrow shows a
pathological lymph node which is relatively difficult to identify. Image B shows a co-registered PET-
CT image. The arrowed node avidly takes up radio-labelled FDG and is now easy to identify.

The localisation of tumours can also be improved by the use of intravenous (or oral) contrast agents.
If CT is being used as the imaging modality, contrast agents are iodinated. These agents improve the
delineation of anatomic structures, especially vascular structures, and improve the accuracy of lesion
characterisation (13).

Planning

Once a tumour has been outlined on the primary CT (possibly with reference to other imaging e.g.
MRI, PET), the planning process can begin. As well as localising the target, it is important to also
localise “Organs at Risk” (OAR), these are the adjacent critical normal body structures that limit the
dose that can be safely delivered to target. If safe doses to OARs are not respected the consequence
will be increased toxicity of treatment (14). Conformal planning techniques modify the shape of the
beam, to match the shape of the tumour, hence decreasing the volume of normal tissue that is
irradiated. The beam shape is modified by the use of computer-controlled Multi-Leaf Collimators
(MLCs) which are 0.5cm thick and are mounted in the treatment head of the Linear Accelerators (the
machines used to deliver MegaVoltage (MV) Radiotherapy). The movement of the MLCs at the time
of treatment is pre-specified in the generated radiotherapy plan. The use of MLCs for Conformal
radiotherapy delivery represents an advance over previous shaping techniques both in terms of
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conformality of treatment, and resources. Previous techniques either employed the straight edges of
the jaws in the treatment head (e.g. for a “4-field brick” prostate plan following 2D conventional
simulation). Alternatively, custom-made lead alloy blocks were used for beam shaping. This
technique had many resource implications as the blocks were time-consuming to make, and there
were manual-handling issues as the blocks were heavy (15). In Conformal radiotherapy, the fluence
is uniform across the radiation field.

Limitations of conformal radiotherapy

Despite the improvements described above with respect to conformality of treatment with
conformal over conventional radiotherapy technique, there are limitations. It is not possible for
conformal radiotherapy to cover concave clinical targets such as prostate and seminal vesicles, or
thyroid, without irradiating normal tissue contained within the concavity as shown in Figure 3 (page
10).

Conformal radiotherapy has limitations also, in that it does not include any inherent motion
management strategies. This means that for tumours such as lung cancer, which are subject to a
considerable degree of movement during a treatment fraction, generous CTV to PTV margins are
required in order to ensure no geographic miss of target at any stage of the respiratory cycle. The
unfortunate consequence of this, however, is that a large volume of normal lung is irradiated.

These limitations have been addressed in more recent advances in radiotherapy, which are discussed
subsequently in this chapter.

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Figure 3:
Three-dimensional conformal radiotherapy (3D-CRT) plan-showing the isodose distribution for the
prostate gland (royal blue outline) and surrounding structures (bladder=pink outline, rectum=yellow
outline, femoral heads = red and sky blue outline). The 3D analysis shows the extent of the high-dose
area (red shaded area) with regards to covering the prostate and allows an appreciation for the
volume of the rectum and bowel within the high-dose area.

Image taken from “Technological advances in radiotherapy for the treatment of localised prostate
cancer”, Mangar SA et al, European Journal of Cancer 41 (2005) 908–921.

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