Brain tumors: What benefit does a PET scan have in recurrence of high-grade gliomas?

Whether positron emission tomography (PET) for detecting recurrence improves the treatment of people who have high-grade glioma, has not been studied in suitable trials. It also remains unclear how accurately recurrence can be determined using PET.

Once the initial treatment  of a brain tumor is completed, possible recurrence – also called relapse – should be detected as early as possible. To do this it is crucial that the examination used is able to tell the difference between the harmless remains of already treated brain tumor tissue and newly created tumor tissue. It is also important to determine the exact location of the tumor tissue in the brain to more precisely plan the treatment of the recurrent tumor using, for instance, radiation therapy. In theory, more exact planning could lead to better treatment outcomes.

PET is one type of examination that is assumed to be able to provide a more exact diagnosis of a recurrent tumor than other techniques like CT or MRT scans. Whether this assumption is valid, and if more exact diagnosis and planning of therapy does lead to better treatment outcomes benefitting the patient, was tested and the results were published by IQWiG.

The term glioma refers to a group of tumors of the brain and the spinal cord that form in the tissue supporting the nerve cells. How well these tumors respond to treatment depends on the type of tumor. Some gliomas grow slowly; they remain limited, and they are called low-grade gliomas. Other gliomas grow more rapidly and penetrate neighboring tissue. This makes it difficult to treat them and they do not have a very good prognosis. These gliomas are called high-grade gliomas. This research summary is only about these high-grade gliomas.

Gliomas are brain tumors that arise from what are called glial cells. The glial cells form a protective layer that covers the nerve fibers in the brain. There are different types of glial cells that tumors can develop from. The type of cell most like the tumor cells also determines the name of the tumor – for instance there are within the group of gliomas so-called ependymomas, astrocytomas or oligodendrogliomas. The World Health Organization (WHO) categorizes the gliomas in four different grades of severity. The WHO grade describes how quickly the tumors grow and whether they are growing into neighboring tissue. The higher the grade, the more dangerous the tumor is and the more difficult treatment is. High-grade gliomas – tumors that are growing very fast and that usually push into neighboring tissue – are categorized as WHO grade III and WHO grade IV.

Gliomas can cause serious symptoms: for example, headaches, seizures, disorientation, memory disorders and changes in personality. But a glioma may also not cause any trouble and have no symptoms for a long time, and remain undetected. Which symptoms are experienced, depends on, among other things, in which part of the brain the tumor is located. Overall, gliomas are relatively rare: about 5 to 6 out of 100,000 people develop a glioma in Germany every year.

Causes and treatment options for gliomas

It is not completely clear why gliomas occur. Yet there are strong indications that they occur more frequently if someone has received radiation because of another tumor disease. Inheritance also seems to play a part. A relation between the use of mobile phones and the development of gliomas was studied, but this connection could not be established. Neither is there scientific evidence of the effects of electromagnetic fields, food preservatives, or head injuries.

If a glioma is detected, an attempt is made to surgically remove the tumor. But in most cases high-grade gliomas cannot be eliminated completely. Then the goal of the operation is to reduce the size of the tumor as much as possible and to relieve the associated symptoms. This operation is supplemented by radiation therapy and/or chemotherapy. Only few people with high-grade gliomas will survive for several years. For this reason, the primary goal of treatment is usually to relieve the symptoms of the tumor.

Diagnostics using positron emission tomography

Upon suspicion of a brain tumor, the doctor first performs a physical examination and then asks about the symptoms and the medical history. After that, the doctor will try to find out whether the patient actually has a brain tumor. Usually magnetic resonance tomography (MRT) is used to find this out. With this method – also called magnetic resonance imaging (MRI) – very exact spatial cross-section images of the brain can be made. In addition, x-ray computed tomography (CT) is sometimes performed, which also makes cross-section images. Using these images the tumor’s size and location can be determined.

What is called positron emission tomography (PET) is another type of imaging. The hope is to use PET to better detect recurrences, in particular. There is a recurrence (relapse) when the tumor starts growing again much faster after initial treatment and a phase without growth, or with only very slow growth. If a patient with a brain tumor received radiation, a CT or MRT image frequently cannot make a distinction between new tumor tissue or the remains of tumor tissue already killed by radiation. It is hoped that the PET images are able to better tell the difference. While a CT or MRT image only provides information about the location of the tumor tissue, metabolic activity can be measured and visualized using PET: because tumors grow faster and have a more active metabolism than healthy brain tissue, they appear more vividly on the PET image and can be recognized more clearly.

How a PET examination works

In positron emission tomography, a solution of sugar or protein is first injected into a vein. The sugar or protein building blocks (amino acids) in this solution are also bound to a weakly radioactive substance that is not harmful to humans. The PET scanner can precisely trace this substance’s path through the blood as it makes its way around the body and creates images that allow different types of tissue to be seen. Because the tumorous cells use more sugar and amino acids than healthy tissue does, they are especially noticeable in the PET image, because much of the carrier substance and therefore also a lot of the weakly radioactive substance builds up here. But it is not only cancer cells that have increased activity; the metabolism of other cells may also be increased – for example, if there is an inflammation.

It is now also possible to combine CT and PET technology in one device – in what is called a PET/CT scanner. This allows the anatomic information from the computer tomography to be combined with the metabolic information from the PET. Doctors hope that using this scanning technology will help them to be able to determine the exact location of even very small tumors, in order to, for example, plan following radiation therapy more precisely.

Even if PET provides more information, it does not automatically mean that patients will also have a benefit. The deciding factor is whether this improves treatment and for instance helps to find the best therapy.

The German Institute for Quality and Efficiency in Health Care (IQWiG) – who publish this website – together with researchers from Germany, England and the Netherlands has evaluated trials on the benefit PET and PET/CT have in detecting recurrence of high-grade gliomas.

Assessment of PET scans in detecting recurrent tumors

To be able to estimate how exact any examination method is, so-called diagnostic trials are needed. In these types of trials different diagnostic techniques are compared with one another: for example, to test whether the results of PET determining brain tumor size, location and how far the tumor has spread are more reliable than the results of magnetic resonance imaging.

Better still are trials that also test what influence the result of a particular examination method has on the success of treatment. This is the actual crucial issue for patients. Because an additional examination only makes sense from a medical point of view, if it also leads to better treatment or can help to avoid unnecessary treatments.

This can be determined using so-called randomized controlled trials. In these types of trials participants are randomly divided into two or more groups. In one group, for example, magnetic resonance tomography is conducted, while in the other group PET or a combination of both techniques is used. Afterwards the patients from both groups are treated according to their individual examination results. At the end of the trial, the treatment results of both groups are compared. Then it is possible to find out whether one of the two examinations is better suited for finding a beneficial treatment. You can read more about this here (URL: http://www.informedhealthonline.org/index.61.en.html) .

In scientific research, these types of trials are regarded as the best way to test the benefits of medical diagnostics and therapies. But good trials also take up a lot of time and resources, which means there are only few that meet these requirements.

The influence of PET on the success of treatment is not clear

The IQWiG researchers did not find any suitable trials that studied, how the use of PET influences the results of treatment – although PET has already been used since the 1980s. So it remains an open question as to whether people with a high-grade glioma survive for a longer time or have fewer complications from the disease or treatment or profit from a higher quality of life, when PET or PET/CT techniques for detecting recurrence are used.

On the topic of how certain and exact the detection of recurrence is, the researchers found 12 trials – but the results of these trials were not very conclusive and the PET method had very mixed results. What is more, some of the examinations were performed over 20 years ago, and others recently. This makes it difficult to compare the results, because both the quality of the scanners and experience in treating gliomas have changed over the years.

There was not a single trial on combined PET/CT. There were only few suitable trials comparing PET with other diagnostic tests such as MRT. For this reason it cannot be said how well recurrence can be detected in a high-grade glioma using PET or PET/CT techniques in comparison with other methods, and therefore it is also hard to say how well the further course of the disease can be predicted.

Author: German Institute for Quality and Efficiency in Health Care (IQWiG)

Note

This health information is a summary of a scientific report published by IQWiG. It is not an assessment of the right to have health care services reimbursed by statutory health insurance funds in Germany. By law, decisions about the reimbursement of diagnostic and therapeutic procedures can only be made by the German Federal Joint Committee (G-BA). The Federal Joint Committee takes IQWiG reports into consideration in its decision-making process. You can find information about the decisions of the German Federal Joint Committee on its English-language website, www.english.g-ba.de (URL: http://www.english.g-ba.de/) .

Next planned update: April, 2014. You can find out more about how our health information is updated here (URL: http://www.gesundheitsinformation.de/our-methods.643.en.html?bab[subpage_id]=0-8) .