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Cancer treatment typically involves systemic therapy such as chemotherapy, targeted therapy or immunotherapy, in combination with a local therapy. Local therapy such as surgery, radiation therapy or other energy ablation treatment options are used. For small tumours, stereotactic ablative body radiotherapy (SABR) is an emerging standard of care. SABR is a non-invasive local treatment for small tumours, delivered in an out-patient setting. SABR is also known as Stereotactic treatment or Stereotactic Body Radiotherapy (SBRT).
Dr Nicholas Hardcastle PhD
Medical Physicist
Educational Information for Patients and Professionals
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The foundations of safe and effective SABR has been built on rigorous clinical trials. SABR had initial success in the treatment of small lung tumours, leading to improved survival compared to standard radiation therapy for inoperable, early-stage lung cancer 1. SABR has also benefited cancer patients with limited metastatic deposits; a number of trials have shown local treatment including SABR, to a small number of metastases, may lead to increased survival 2,3 and can delay the need to progress onto systemic treatments 4. There are numerous ongoing clinical trials in SABR to further probe the clinical and technological aspects of the technique. If you are a cancer patient, you may find a clinical trial suitable for you at your treatment centre.
What does SABR mean?
Research and development work by medical physicists and biomedical engineers has resulted in advances in mathematical computation methods, treatment technology and imaging capabilities on conventional radiation therapy linear accelerators. Such advancement has enabled the stereotactic ablative technique to be applied to small primary tumours and metastases throughout the body. SABR is now a well-established method of treatment of lesions in the lung, liver, adrenal glands and bone.
Stereotactic is a term used to describe a geometric relationship between the tumour (what we want to hit), and the patient’s anatomy that we can see by imaging techniques. The radiation therapy linear accelerator can be used to accurately target the tumour by this geometric relationship (see ‘What is stereotactic radiosurgery?).
Ablative describes the very high doses we deliver to the tumour in each session, which governs the biology of how the tumour reacts to the radiation. It is different to standard radiation therapy.
‘Body’ refers to use of these treatments outside of the head, where Stereotactic RadioSurgery (SRS) has been used with great success for small brain tumours over many decades.
The conventional radiation therapy prescription is normally a 2-3 Gy X-ray dose given in each of 20-30 treatment sessions. SABR is delivered in 1 – 5 sessions, with a much higher X-ray dose given for each session. For example, a small lung tumour may receive 18 Gy in each of three SABR sessions. This high, ablative dose per treatment session provides a superior treatment response. But the treatment must be designed to safely protect adjacent critical organ structures from irreparable radiation damage.
There are two key aspects:
- SABR can only be applied to ‘small’, locally constrained tumours (typically less than 5 cm); and
- SABR tumour targeting must be very precise.
Imaging for SABR
The detection and treatment of very small tumours in any part of the body have been significantly improved in recent times. The use of modern imaging equipment is essential for SABR. These include (Figure 1.):
- Computed tomography (CT);
- Positron emission tomography (PET);
- Magnetic resonance imaging (MRI);
The patient is scanned from head to toe to obtain ‘high definition’ images. The images are stored in the computer as digital information which can be later used when the patient’s X-ray treatment is planned.
CT scans provide high quality information about the density of the patient’s internal anatomy. This is necessary for accurate radiation dose calculations that allow for different tissue densities (especially lung). Often we are interested in blood flow through, or adjacent to the tumour, so we use intravenous (IV) contrast during the scan. This shows up blood flow during the scan.
For thorax or upper abdominal tumours, affected by the patients breathing or heartbeat, we also collect the respiratory or cardiac cycles as data linked in time to the images. This is referred to as a 4D-CT. 4D-CT data provides us an understanding of how tumours and the adjacent critical organs move as the patient breathes or as the heart beats. Since the radiotherapy exposure takes minutes to deliver, the 4D-CT is really important information for SABR. It ensures we can precisely hit the tumour while the patient breathes or the heart beats during the treatment session.
PET scans provide metabolic information of the tumour. PET can also detect tumour specific cells before they are clearly visible on CT scans.
MRI scans provide exquisite anatomical detail about organs and tumours based on the molecular structure of the tissues. Organs or tissues that may appear to have the same density on a CT scan, can appear different on an MRI scan due to the tissue having variable magnetic resonant properties.
Diagnostic and treatment image procedures
Initial treatment imaging defines the reference geometry to be used for planning and treatment. This provides information to the treatment team on the relationship between the tumour and nearby critical organs, and how these are positioned within the body. We then aim to replicate this geometry at every treatment session. Various medical imaging modalities are employed to achieve this. The important points are:
- The patient is immobilised as much as possible while lying on the diagnostic and therapy couches. How the patient lies on the couch for imaging and treatment, must be comfortable and reproducible
- The way the patient lies is optimised for best delivery of radiation therapy. For example, this may involve the patient raising their arms above their head to remove them out of the way of the X-ray treatment beam.
- An evacuated bean bag is typically used as a mould. It is placed around the patient to maintain the same position for each session.
- The bean bag is ‘fixed’ between the patient and couch for all imaging and treatment sessions to ensure the patient is always lying in the same position.
- The patient’s tumour site must be visible so that we can accurately target to within millimetres
- The patient is imaged in the treatment position for the CT, PET and MRI scans, or a combination of these.
All the images are combined as one. This is called image registration; spatially registered images are used to provide different information about the treatment area from each image mode. We are able to view from image registration the tumour position, its metabolic character and how much it might be moving during treatment.
Dose Calculations
The computer treatment planning system (TPS) uses the image registration data in the mathematical algorithms which ‘optimises’ the ‘best’ X-ray radiation arrangement to give the prescribed dose to the tumour target. A radiation oncologist creates a 3D model of the tumour and its nearby critical organs based on this imaging (Figure 2-4).
Based on this 3D model, the TPS calculates the different geometries and X-ray exposures that the treatment machine will use to target the tumour. It involves optimising the prescribed tumour dose and limiting dose to the surrounding critical organs or tissues.
Figure 2: Animation of the radiation therapy treatment – the treatment machine rotates around the patient, treating the tumour from many directions and (right) the radiation beam is shaped by mathematical algorithms to cover the tumour with the prescription dose while minimising the dose to adjacent organs
Treatment
Although consistent patient positioning is established and detailed information of the tumour position and movement (relative to surrounding organs) can be acquired during the imaging session (Figure 5.), the actual treatment session does not occur until a number of days later.
The tumour position may have shifted, adjacent organs may have deformed or breathing may be different to how it was during the planning image scans.
This is all expected! Fortunately, there are now a number of different technologies that can be employed to account for any day-to-day variations in tumour and organ position/shape.
Improved treatment imaging facilities
Conventional linear accelerators used for cancer treatment have computed tomography 3D imaging accessories attached to them. Introduction of such imaging was a fundamental game changer to enable SABR. 3D imaging facilities ensures accurate measurements and alignment of the patient’s tumour for x-ray treatment. In more recent specialised machines, a 3D MRI scanner is incorporated into the treatment linear accelerator. This provides improved tumour and organ imaging capabilities over computed tomography for some anatomy.
The 3D image at treatment set-up is compared with the previous planning image and the patient’s set up is re-aligned as needed (Figure 6.). This procedure is very similar to the SRS procedure. An equivalent ‘stereotactic’ frame 3D co-ordinate system is established.
However, unlike SRS, the patient’s tumour in SABR is typically moving within a deforming organ system. It’s possible to view a 3D image with adjacent critical organs, compare them with the planning images and ensure the radiation hitting critical organs is minimised.
Using imaging to account for tumour movement and distortion
The tumour is often moving during an X-ray treatment due to respiration or cardiac motion, or through peristalsis (movement of the bowel linked with digestion) or similar body functions. Periodic tumour movement during the X-ray exposure, or movement and distortion of the tumour and adjacent critical organs can be accounted for in a few different ways.
A very common approach in treatment of lung tumours is to treat a slightly larger volume than the tumour, to encompass everywhere it may be during (for example) the respiratory cycle. But this needs to be safe to do without exceeding dose limits to adjacent critical organs.
If the tumour motion is too large, or there are nearby critical organs that must be completely avoided, then we need to develop an alternative means of reducing the volume of tissue more tightly about the moving tumour only.
The volume of tissue receiving the high ablative dose can be reduced by turning the beam ‘on’ when it is favourable , and ‘off’ when it isn’t – called ‘beam gating’.
Monitor patient breathing
Beam gating is typically used for treatments involving patient breathing. The patient’s respiration is electronically monitored and ‘beam on’ is activated when the patient has exhaled. As the patient starts to breathe in, the tumour starts to move, and ‘beam off’ is activated.
Patient breath hold
An alternative method is to arrange the patient to take a breath in and hold, or breathe out and hold. This may ‘freeze’ the tumour in position for treatment, and/or it may help to move critical organs away from the treatment beams – as the patient inhales, the lungs expand and organs such as the heart displace. The treatment beam is then only turned on when the patient is in the preferred breath hold.
Tumour tracking
The most recent method developed is called tumour tracking. It’s an advanced technique that involves tracking the tumour, or a surrogate for the tumour such as implanted metal seeds. These are continually imaged during treatment. Any change in the tumour/surrogate position is detected so that the radiation beam position can be automatically adjusted to follow the moving tumour during respiration (Figure 7). Tumour tracking is a highly complex development of the linear accelerator imaging and control system and is limited to specialised treatment delivery systems.
The 3D imaging acquired prior to treatment for alignment of the patient enables ready detection of any movement or deformation of the tumour or adjacent critical organs compared to what was originally planned. In some cancer locations, such as pancreas, adjacent organs can distort the tumour volume and result in variations between the planned target and organ dose, and that which is delivered. High quality 3D anatomical imaging at the time of treatment provides potential of ‘adaptive radiation therapy’, in which, prior to treatment, the patient’s treatment beam geometry can be modified to account for organ deformation and treat with a new plan more suited to the anatomy for that day.
Ensuring High Quality SABR
To ensure maximum benefit from SABR, there must be very close collaboration between all involved – the radiation oncologists, medical physicists and radiation therapists – from the initial patient consultation to imaging to planning to treatment. A number of quality checks are performed at each point in the patient journey:
- Suitability of the patient and technical feasibility for a SABR treatment approach is reviewed – is this a target that we can safely and effectively treat?
- All images used for treatment planning are reviewed to ensure accurate interpretation and geometric location in the face of image acquisition uncertainties that arise from patient and machine factors – are we seeing everything about the tumour and surrounding environment that we need?
- The spatial relationship between images used for treatment – image registration – is reviewed to ensure the correct information from each image is at the right location in our stereotactic frame of reference – is all of our targeting aiming at the correct location?
- The treatment plan is assessed to ensure the input to the beam optimisation algorithms is appropriate, and to quantify and limit any uncertainties in the algorithms that may result in the delivered dose varying from the planned dose – is this treatment plan optimal for this patient, to ensure the target is treated as planned, and dose to adjacent critical structures minimised?
- The treatment session typically has radiation therapists, medical physicists and radiation oncologists present to review different aspects of the treatment, from patient positioning, image acquisition and targeting accuracy prior to beam delivery – is the patient in the correct position, and tumour located accurately to achieve the planned treatment?
- The SABR team reviews treatment outcomes to enable continuous refinement of all aspects of the SABR process – are there improvements to improve effectiveness, safety, or experience for the patient?
Conclusion
SABR is a non-invasive local cancer therapy treated in an out-patient setting on conventional radiation therapy equipment. SABR provides highly effective local tumour control. Safe delivery of SABR relies on highly precise targeting of the tumour, and as such is a technically demanding treatment modality. Specialised treatment equipment designed specifically for the challenges of SABR have potential to further improve the effectiveness and applicability of this treatment technique.
References
1. Ball D, Mai GT, Vinod S, et al. Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial. Lancet Oncol. 2019;20(4):494-503. doi:10.1016/S1470-2045(18)30896-9
2. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051-2058. doi:10.1016/S0140-6736(18)32487-5
3. Gomez DR, Tang C, Zhang J, et al. Local consolidative therapy vs. Maintenance therapy or observation for patients with oligometastatic non–small-cell lung cancer: Long-term results of a multi-institutional, phase II, randomized study. J Clin Oncol. 2019;37(18):1558-1565. doi:10.1200/JCO.19.00201
4. Siva S, Bressel M, Murphy DG, et al. Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial. Eur Urol. 2018;0(0). doi:10.1016/j.eururo.2018.06.004
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Nicholas Hardcastle PhD, 7 May 2020
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