Radiological investigations and treatments
The principles of radiology are to use different types of scans to identify and diagnose problems inside the human body that cannot be seen or felt by external examination. Different scans give different information, some scans (CT) are very good for looking at anatomy and blood vessels to allow a surgeon to plan an operation. Others are good at picking up small lesions in specific organs (MRI) or tell us about disease activity and patterns of distant spread (octreoscan). It is common for us to do several types of scan when a patient is newly diagnosed to give us as much information as possible about all the sites of the disease. This process is called “staging” the tumour, it enables us to plan treatments and then monitor how the disease responds to the treatment.
Radiologists are the doctors who look at scans to make diagnoses and plan and carry out treatments.
Radiographers are the highly trained technicians who operate the scanners and ensure that the scan is carried out correctly. In some departments very experienced radiographers may also make some diagnoses of specific conditions on ultrasound themselves (e.g. gallstones, pregnancy checks)
This is an investigation in which the radiologist places some jelly on your tummy or on the skin over the part of you that is about to be scanned and then puts a hand held probe onto your skin. The probe gives out high frequency sound waves (a bit like sonar) which the human ear cannot hear. These bounce back off the tissues inside you and show a picture on the screen made up of the “echoes” of the reflected sound waves. This is a very safe test, it is commonly used in children and pregnant women as it has no real risks. However the information it gives is of variable quality and value, depending on which organ we are looking at, what size the patient is, the skill of the person who is doing the scan and a certain element of luck. So we do not always rely on an ultrasound diagnosis unless there is a specific question that we know the scan can answer.
Occasionally we give an injection of intravenous contrast (a liquid compound called micro-bubbles) to show up the blood vessels inside you better on the scan.
CT stands for computerised tomography, also known sometimes as a CAT scan (A is for Axial). This scan uses a rapid series of Xray pictures taken as you go through a donut shaped scanner on an automated table to build up a picture of your insides. It is quick and gives very accurate anatomical information about your insides. We usually give an iodine based injection of a dye (or contrast agent) to show up the blood vessels as you go through the scanner, this often gives you a warm sensation as it goes around your circulation. Some people also get a funny taste in their mouth. If you are allergic to Iodine you must tell the scanner technicians and doctors and you should not have this type of contrast as it can trigger the allergy again.
MRI – Magnetic Resonance Imaging
An MRI scanner uses a very strong magnetic field combined with radio waves to create the required images of almost all the tissue in the body, onto a computer.
With an MRI scan it is possible to take pictures from almost every angle, whereas a CT scan only shows images horizontally. X-Ray’s are not involved in producing an MRI scan and the difference between normal and abnormal tissue is often clearer on an MRI scan.
An MRI is usually an outpatient procedure and during the scan it is important to lie completely still. Since an MRI exposes the patient to a powerful magnetic field, it is important not to wear jewellery or any other metal objects. The scan itself is painless as you cannot feel it and as radiation is not used for this type of scan the procedure can be repeated.
Contract agents/dye may be injected intravenously to make help make the appearance of blood vessels, tumors or inflammation more visible.
The most daunting thing about an MRI is lying in the large tunnel (about 1.5m long) while the scans are being captured, as this makes some people feel claustrophobic. The machine itself also makes a loud banging noise while it is working, which might be unpleasant for some, but his can be easily resolved by using headphones playing music that are readily available.
The radiographer sits in the control room next to the scanner and observes through the window. However, you can talk to them, via an intercom, whilst they watch you on a monitor.
There are no side-effects from and MRI scan and you can return to normal activities as soon as it is complete. The images from the scan are then studied by a specialist doctor (a radiologist) who sends a report to the doctor or consultant who requested the scan.
Radio-isotope scans (see radio-isotope treatments below) Octreoscan and MIBG scan
These scans may be used to find where the cancer started (the primary tumour), or to check for any spread of the disease (secondaries or metastases).
Neuroendocrine tumours often absorb a substance called octreotide. A small amount of octreotide is ‘labelled’ with a mildly radioactive tracer to make it show up on scan pictures. The octreotide is then injected into the bloodstream and taken up by NETs, wherever they are.
This is a type of scan that takes place over 2 days in the nuclear medicine department. You are given iodine tablets to take on the morning before the scan (so the tracer isn’t taken up by the thyroid gland), followed by an injection containing the octreotide molecule (see below) with a very small amount of the radioactive tracer attached to it. One scan is taken that day and a second scan is taken the next day to see where the octreotide tracer (which acts like a dye) has been taken up showing up as “hot spots” on the scan.
Sometimes a substance called MIBG, which may be absorbed by NETs, is used for the scan. It’s also made mildly radioactive, and scans are done in a similar way to the scan using octreotide.
This is very similar to an octreoscan in that it uses a molecule (MIBG) to bind to the receptors on the neuro-endocrine cells. It is particularly good for looking at tumours from the adrenal glands (phaeochromocytomas) and similar tumours (e.g. paraganglioma). However many other NETs also show up on this scan, so in some centres it is used at least as much as octreoscanning.
The dose of radioactivity from these scans is very low (about the same amount you get from an x-ray), and almost all of it leaves your body within a week. If you are planning to travel abroad within three months of the scan, let the doctor in the scanning department know. They can give you a letter to show to customs officials. This is because ports and airports have very sensitive radiation detectors that may pick up tiny amounts of radioactivity.
Angiography is a test that uses an injection of a liquid dye to make the arteries easily visible on X-Rays. They are mainly used to check the condition of blood vessels and for many arteries, such as head, abdomen, or leg; these non-invasive tests are usually all that are required.
Angiography may be used if the doctor/consultant is considering surgery, because it can localise abnormalities and blockages and help to get a clear picture of blood vessels supplying a tumour, which can be particularly useful when planning surgery and deciding if an operation is necessary or indeed possible.
An Angiography is routinely performed under local anaesthetic. A thin wire is carefully inserted into the artery using a needle and guided to the area in question with the help of X-Ray images. The needle is then removed and a vascular sheath inserted around the wire and catheter inserted along the guide wire. When the catheter is in position the wire is pulled out and a liquid dye is injected into the blood vessels so that the results can be checked on screen /X- Ray taken
PET Scan- Positron Emission Tomography
PET scans produce 3D, colour images of your body using radio nuclides which highlight active cells and body tissues and is most commonly used in the diagnosis of Cancer.
By superimposing MRI and CT scan on top of each other, doctors/consultants can create very detailed pictures of the body.
CT Scans can pick up such things as fibrous tissue left over from cancer killed off by your treatment however, a PET scan will show if the tissue is actually cancer, or not. PET scanners are expensive and rare and not every hospital in theUKhas a PET scanner. This means that if you may need to travel to another hospital to have one. Your appointment letter will give you full details about what you need to do to prepare for your PET scan. You will normally be asked not to eat anything for several hours before your scan and when you arrive you will have an injection in your arm of a radioactive drug. The amount of radiation is very small and it only stays in the body for a few hours.
After an hour or so (to enable the drug to spread through the body) the scan can then be taken on the PET Machine, which has a round hole in the middle (very similar to a CT / MRI machine) It can take up to an hour to produce an image and when the scanning is completed, you may be asked to wait until the results are checked in case more images are needed. Occasionally, additional images are needed to clarify certain areas or structures. After your scan you should feel fine with no side affects and able to return to normal activities however, you should drink plenty of fluids afterwards to help flush the radioactive drug from your body
A radiologist will look at the images that a PET scan produces, and pass the results to your doctor/consultant ready for your next appointment.
Embolisation is a non surgical, minimally invasive procedure in which the blood vessels are plugged with a type of glue to stop the flow of blood to an area in the body/ a tumour so that it eventually becomes necrotic or shrinks the tumour. Under x-ray a catheter is guided from the main artery in the leg up into the area that is to be treated. This is repeated for each vessel that feeds the tumour. NET Patients can often require this procedure to be repeated and so this method is frequently combined with multi modality treatment for NETS.
The embolisation procedure is carried out by a consultant radiologist who would have completed advanced post residency training in interventional radiology. It is most common for patients to have embolisation with little or no sedation, although this depends on the organ that is to be targeted.
A guide wire and catheter is carefully inserted into a suitable artery and guided to the area in question with the help of live images /digital subtraction angiography (DSA) so that the Radiologist can gain access to the correct vessel(s). Once the ‘glue’ is inserted another set of DSA images are taken.
TACE – transcatherter Arterial Chemoembolisation
Just like embolisation TACE is a minimally invasive procedure to restrict a tumor’s blood supply using a chemotherapeutic dose directed at the tumour rather than ‘glue’ as above. Again the radiologist would use the same process as above (embolisation) and when the most appropriate blood vessel supplying tumor has been chosen the chemotherapy dose /drug is injected through the catheter. This dose may be given in one vessel or alternatively it can be divided among several vessels that are supplying the tumor(s).
Patients are routinely kept in a hospital for one to two days following the procedure just in case inflammatory chemicals find their way into the blood stream.
RFA – Radio Frequency Ablation
RFA is a medical procedure whereby heat made by radio waves are used to kill cancer cells. This electrical current, heats the cancer cells to a point where the tumours are destroyed. Your doctor/consultant may recommend RFA because you may have several tumours or the position of the cancer in your body means that it would be very difficult for a surgeon to do e.g. if it is near a major blood vessel or if you are unable to have a general anesthetic.
First you are given a general anaesthetic (for a large area) or a sedative with a local anaesthetic to numb the area before a probe is inserted through your skin into the tumour itself. You can also have RFA during surgery/laparoscopy and timings can vary however, it usually takes about 30 minutes to treat one tumour.
Pain or discomfort in the treatment area and generally feeling unwell with high temperatures are a common side effect of RFA which you may have for a few days after treatment. Your doctor or specialist nurse will give you painkillers to take home with you and then you will usually be given a follow up appointment for a scan to show how well the procedure has worked.
MWA –Microwave Ablation
Microwave ablation is a procedure that uses heat from microwave energy to destroy cancer cells. MWA is used to treat cancer that has spread to the liver from other parts of the body. As with RFA this procedure can be performed during:
- Open Surgery
- Laparoscopic Surgery
- By needle through the skin.
Sirtex –SIR-Spheres microspheres
Oncology-focussed treatment company Sirtex Medical (ASX: SRX) recently announced the start of a new trial to see if chemotherapy used with SIR-Spheres® microspheres targeted radiation therapy, is more effective than just chemotherapy in patients with bowel cancer that has spread to the liver.
SIR-Spheres microspheres are an innovative means of treating liver cancer. In cases where it is not possible to surgically remove the liver tumours, SIR-Spheres microspheres can be used to deliver targeted, internal irradiation therapy directly to the tumour. This new therapy is called Selective Internal Radiation Therapy also know as SIRT. This technique uses millions of tiny resin microspheres which contain a radioactive element called yttrium-90. SIR-Spheres microspheres are very small, approximately 32 microns in size. A specially trained physician known as an interventional radiologist usually administers sIR-Spheres microspheres as an inpatient procedure. A small catheter is guided into the liver and the SIR-Spheres microspheres are infused through the catheter. The microspheres with the radioactive yttrium-90 are carried by the bloodstream directly to the tumours in the liver where they preferentially lodge in the small vssels feeding the tumour and deliver their dose of radiation. Unlike conventional external beam radiation, which can only be applied to limited areas of the body, SIR-Spheres microspheres selectively irradiate the tumours and therefore have the ability to deliver more potent doses of radiation directly to the cancer cells over a longer period of time.
Radio-isotope Scans and Treatments for NET
One of the main stays of treatment for NET is by administration of targeted radio isotope treatments. The mechanism of how this works is quite complicated and is explained in the “mechanism of action” section after this.
What are the risks of radio-isotope scans and treatments?
In general the amount of radioactivity given during an octreoscan or MIBG scan is so tiny that it is of no more risk to you than an ordinary CT body scan. Larger doses of radio-isotope are needed to achieve therapeutic levels which kill the cancer cells. The nuclear medicine doctors and physicists calculate very carefully the exact amount that is safe for the stronger treatment doses. In general these treatments have very few side effects, but occasionally the kidneys or bone marrow can be affected, this is more likely if several treatments are required.
When should therapeutic radio-isotopes be used?
There are many differing opinions on the best timing for use of radio-isotope therapy. Our preference in Southampton is to use it for patients with disease that is not easy to treat with other modalities such as surgery, embolisation, ablation or chemotherapy.
Radio-isotope therapy is limited by the laws of physics and human biology
- Firstly the human body can only cope with a certain amount of radiation at one time, otherwise the short term effects of radiation sickness take effect. The human bodies tolerance for radiation dosage have been very well documented in the 20th century and clearly safe levels established so in practice toxic dosages are never reached.
- Radiation has a cumulative effect with repeated doses, so treatments cannot be repeated too close together and there is a small long term risk of developing other tumours from these treatments.
- The radio-isotopes are concentrated and excreted by the kidneys so it is important to watch renal function in patients with any kidney problems as they can be damaged by the radiation.
- Tumours must have high concentrations of the receptors on them to make the treatment effective, if they do not have many receptors then not many radiolabelled molecules attach to the tumour cells and consequently only a small dose of radiation is given.
- If there is a very large quantity of tumour then the treatment may not work very well as only a fixed dose of radioactivity can be given, which must be spread around all the tumour sites, again giving a weak or dilute effect.
- Radiation particles emitted by these drugs travel in a straight line and have only a short penetration into adjacent tissue. If a tumour is very small then the radioactive molecules that are released from it mainly pass out of the tumour into the surrounding tissue, so again the dose received by the tumour cells is very small.
Putting all of these points together it becomes apparent that the treatment works best for smaller numbers (<10) of small or medium sized tumours (1-6cm diameter) with high concentrations of receptors and is less effective for very bulky or very diffuse patterns of disease.
Due to these limitations and limited availability of the treatment we tend to hold it back in reserve to treat tumours that are inaccessible or unsuitable for other treatments. Ideally we would use it more frequently than we do, however we are effectively rationed by the limited availability of the products at a national level due to the costs of providing and administering the treatment.
In many centres treatment is limited to patients with severe symptoms and progressive disease.
Mechanism of Action
Neuro endocrine tumour cells often have protein molecules on their surface or cell membrane which act as receptors for specific hormones. Hormones are chemical messengers that the body produces that are released into the blood stream from one organ and then travel in the blood stream to another organ to pass the message on. A receptor acts to give the inside of the cell the message in response to the hormone on the outside; in NETs this message is often the trigger to release other hormones such as Serotonin (5-HT), Gastrin, VIP, Insulin or Glucagon.
The most commonly identified receptor in NETs is the somatostatin hormone receptor. Somatostatin is a hormone that circulates inside all of us in varying levels and it is an important part of our normal make up and function. The somatostatin receptor can be blocked by an inactive molecule called Octreotide, this looks very similar to somatostatin and binds to the somatostatin receptors on the surface of the cell, but it does so in such a way that no message is transmitted to the cell. In this way the receptor can be blocked.
If a radio-active particle (commonly radio-active Iodine) is attached to the octreotide molecule then you effectively have a “magic bullet” that binds preferentially to the receptors on tumour cells, blocking them from acting and delivering radiation to the cell to either make it show up on a scan or damage or kill it. This is the basis of radio isotope scans and treatments.