General information about radiotherapy as a treatment option

Radiation therapy is a local treatment that is not reversible, like the surgical operation, and is different from the whole body effect (systemic) of chemotherapy.

In contrast to surgery, radiotherapy does not cut the acoustic neuroma out of the body, as the terms .... surgery or ... knife could lead you to believe, nor does it melt the tumour away.

Radiotherapy changes the DNA of the tumour cells and in doing so prevents them from dividing and further increasing. The objective of radioactive radiation is also to halt the growth of the acoustic neuroma tumour.

Due to the inevitable «joint radiation» of healthy tissue between the radiation source and the target tumour, and also due to the not fully avoidable joint radiation of the surrounding area, an acoustic neuroma with an average diameter larger than 2.5 up to max. 3.0 cm is not suitable for radiotherapy.

The active principle of radioactive radiation

Physicians have used radioactive radiation against malignant and benign growth for decades. They work above all with x-rays or gamma rays that consist of small light particles so-called photons. The effect of radioactive radiation is based on energy transmission to the radiated human tissue. With quicker speed and higher energy the photons act on the tumour. There the electrons knock against the atoms of the tumour cells. In doing so this leads both to direct hits on molecules, that are essential for cell growth, as well as to ionisation of water molecules which consist of free radicals with a highly toxic effect. Hits and damage to the genetic make-up of the cells, the so-called DNA (deoxyribonucleic acid) are responsible for the hostile effect on a tumour during radiation. At the same time, the blueprints for many vital proteins are lost. If the damages to the tumour cells are so great that they exceed the cells own ability to repair themselves, the increase in tumour cells through cell division is prevented and this halts its growth.

Dosages and radiotherapy planning
Dosages and radiotherapy planning
(Source: Wikipedia)
Principle of radiation focussing
Principle of radiation focussing
(Source: Accuray)
 

For the radiation to be effective, several hits must arise in close spatial and time proximity. The success requires exact knowledge of the respective tumour contours and also a targeted calculation of the radiation dosage. However, one problem is that there are restrictions on the concentrated energy output on the tumour lying within healthy tissue in the body. Nowadays, modern technology helps to overcome this problem: the radiation is directed on the tumour from different directions. They overlap at the calculated target point and concentrate their strongest effects on the central point (they are focussed). At the same time, the moving panels shield the sensitive healthy tissue from the radiation.

Furthermore, a «whim of nature» can be exploited here for the benefit of mankind: Normal tissues has another sensitivity to radioactive rays than tumour tissue. In other words: tumour cells generally have a worse reparability to DNA damages than normal cells. The oxygen rich tumour cells take in more radiation than the healthy cells. An optimal radiation dosage achieves an average of >90 % tumour destruction with <5 % more or less severe side effects on the healthy tissue.

This difference is exploited, if the total planned radiation dosage is divided (fractionation) into numerous small individual doses of 1,8 – 2,5 Gy (Gray). This way the share of healthy cells destroyed is lower with the same total dosage. In the time between two radiotherapy treatments, the healthy tissue cells that are unintentionally affected have a chance to regenerate, whilst the tumour cells don't. Normal tissue will tolerate a maximum total dose (approx. 10 Gy in small volumes), it can also increase many times (up to 80 Gy).

Different forms of acoustic neuroma radiation

Stereotactic radiotherapy is understood to be the treatment methods and technologies that allow precise control of a high radiation dosage in an exact target volume defined previously. Through a steep drop in the dosage outside of the target volume, the adjacent, radiation sensitive, healthy tissue and structures are optimally preserved.

The essential, geometric precision is achieved through three dimensional, stereotactic localisation and positioning systems. Through external, three dimensional coordinate systems, the target in the patient's body can be defined with a millimetre range precision (the equipment manufacturer specifies a position accuracy of 0.2 – 0.3 mm) and brought into the focus of a radiation device.

After three dimensional, computer-supported planning, the tumour is radiated from several external directions with pinpoint accuracy. The doses of individual rays are adapted to the geometry of the target volume and along the ray they have such a low energy that the radiated healthy tissue is only charged slightly. In the target volume all the rays meet at one firing point and here the desired higher dosage is added, which leads to damage up to annihilation of the tumour cells.

It is not only the radiated tissue lying between the source and target that needs to be spared as much as possible, but also the healthy tissue surrounding the target zone. For brain tumours and especially for acoustic neuroma this is a very sensitive area due to the proximity of very important cranial nerves. Therefore, radiotherapy planning must start by determining the most accurate and detailed three dimensional tumour volume. This is aided by CTs, MRTs and other imaging processes immediately before the treatment begins, in order to be extremely up-to-date.

TH-6 Linear accelerator
TH-6 Linear accelerator
(Source: website UK Heidelberg)
TH-7 Gamma knife device
TH-7 Gamma knife device
(Source: Wikipedia)
TH-7 Cyber knife device
TH-7 Cyber knife device
(Source: GKZ München)

Stereotactic radiotherapy with a single high dosage of approx. 11 to 13 Gy (in special cases 12 to 18 Gy) is termed one-time radiation or radiosurgery. This includes the GammaKnife and CyberKnife. The treatment takes between 30 minutes and 3 hours.

On the other hand, fractionated stereotactic radiation or radiotherapy (FSRT) splits the total dosage over several days up to six weeks into a number of small single doses. The actual radiation takes around 1 minute, with preparation of some 10 – 20 minutes.

The essential radioactive radiation can be obtained from natural sources (cobalt 60), used with the GammaKnife, or artificially generated through an accelerator, such as with the CyberKnife or LINAC or Siemens linear accelerators.

Side effects of acoustic neuroma radiation

Radiotherapy has a few preferences compared with a surgical operation:

  • It involves no operation, which means no incisions in the body (except for fixed points for attaching the frame with the GammaKnife), no opening in the body, no risk of infection and no anaesthesia.
  • The treatment is quick and pain free.
  • Outpatient treatment, no hospital stay.
  • Minimal physical effects, therefore no loss of working hours.
  • No considerable rehabilitation time.

According to the position and size of the tumour, there can be occasional, weak early reactions. These may include dizziness, nausea, vomiting, mucosa inflammation in the mouth and throat area, localised hair loss, headaches, numbness of the scalp and discomfort where the head mask was placed. These early reactions mostly only last a short time and they always disappear again completely.
Later reactions after several months can be vasoconstriction and fibrosis (scarring) of the connective tissue. These remain for life. These late reactions are also relative to the value of the radiotherapy on the acoustic neuroma overall.

Results of radiotherapy – tumour control

Radiation does not remove the acoustic neuroma, rather it inactivates it. This needs to be repeatedly emphasised. Malignant metastases in the brain begin to shrink approx. six weeks after the radiation. However, acoustic neuromas often swell for a time even after radiation. A withdrawal of the tumour, a healing of the inactive tumour, often only happens after two to four years.

Reports from several clinics and countries show over 90 percent tumour control, in other words in at least nine out of ten cases it leads to a halt in growth. It also leads to further growth of the tumour, immediately or after a long time. Possible reasons for this are the use of an insufficient dosage or because the tumour didn't receive the necessary dose, particularly at the margins. This is not surprising due to the efforts made not to radiate the healthy tissue beyond the edges of the tumour, and also due to the often multiformed, uneven shape of the tumour.

The real, noteworthy side effects or long-lasting late consequences of radiotherapy can often only be judged after years. The fear is circulation disorders of the cerebrospinal fluid with damming (hydrocephalus). An impairment of the facial nerves is very rare, occurring in under two percent. Deterioration of the auditory nerve occurs in some 20 percent. Often there is one-sided deafness that is delayed for years. Radiotherapy does not eliminate vertigo and tinnitus that existed before treatment! The reason is simple: the space occupied, that put pressure on the nerves and led to these symptoms, fundamentally still exists.

In the MRT image on the left an acoustic neuroma can be seen, which extends to the right cerebellopontine angle.
In the MRT image on the left an acoustic neuroma can be seen, which extends to the right cerebellopontine angle.
(Source: website Cyber-Knife-Zentrum München)
The monitoring image on the right was taken 2.5 years after the one-off cyberknife treatment. It shows a typical scar in the inner ear canal.
The monitoring image on the right was taken 2.5 years after the one-off cyberknife treatment. It shows a typical scar in the inner ear canal.
(Source: website Cyber-Knife-Zentrum München)

Pre-eradicated organs and tissue are very sensitive and tend to have severe side effects and even necrosis with further doses. If the acoustic neuroma grows again after radiotherapy, it can be radiated with a low dosage again after a few years, according to radiotherapeutic rules of the thumb. The essential reduction of the dosage is suggestive of an incomplete effect of a second radiotherapy. A second round of radiation results most certainly in deafness on one side.

If the patient requires an operation after radiotherapy, the conditions for the operation are worse, as regards both the complete removal of the acoustic neuroma and the prevention of facial paralysis and hearing preservation. The reasons are tissue changes in the tumour itself and in the immediate vicinity and an adhesion and fusion of the tumour with the surrounding structures, even including the nerves. The radiated tissue has changed in terms of colour and consistency, it is more difficult to distinguish from its surrounding and to remove.

Conclusions on recommendations for radiotherapy

Although acoustic neuroma have been radiated for many years, there is still no randomised studies over the success or late consequences. Randomised studies are those that are carried out for different criteria over a long enough time period with a sufficient number of people absolutely randomly. Therefore, there is an uncertainty with regards to all recommendations for acoustic neuroma radiotherapy, concerning the durability of results in the future. In the end the question is still open today as to how a radiated tumour will behave in the future. This is of great importance when it comes to deciding on treatment – above all for patients who still have a considerable life expectancy.

It is indisputable that radiotherapy and radiosurgery today present an alternative to an open operation for patients who are high risk for anaesthesia and an operation (internal problems that would make an operation dangerous). Similarly, radiotherapy is a useful therapy for patients who are against an operation for whatever reasons. Particularly older patients, who are suffering from slight symptoms, could choose the gentler path of radiotherapy and almost «play for time». In this case maybe a very probable zero growth for a few more years is enough, given that a subsequent operation will probably be unnecessary.

However, other parameters must not be disregarded, for example the position and size of the tumour and the impairments on the patient's health that already exist, but also personal factors such as the family and work situation and the individual's ability to withstand suffering (tolerance of some of the symptoms).

One thing that must be taken into consideration: after acoustic neuroma radiotherapy a yearly MRT monitoring examination is required for life. The anxiety that an acoustic neuroma could grow again is very stressful for some people. And if it does, then once again you have to make a decision.

However, above all there is the restriction that an acoustic neuroma with an average diameter greater than 2.5 to 3.0 cm cannot be treated with radiotherapy.

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