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Adverse radiation effects after Gamma Knife Surgery in relation to dose and volume

  • Clinical Article
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Abstract

Introduction

The relationship between target volume and adverse radiation effects (AREs) at low prescription doses requires elucidation. The development of AREs in three series of patients treated in the Gamma Knife is analysed in relation to prescription dose and target volume.

Materials and methods

There were three groups. In group 1, there were of 275 patients with meningiomas; in group 2, 132 patients with vestibular schwannomas; and in group 3, 107 patients with arteriovenous malformations (AVMs). The minimum follow-up for each group was more than 24 months. All patients were followed up at six monthly intervals. The patients with tumours received a prescription dose of 12 Gy, which was varied to protect normal structures but not in relation to tumour volume per se. The desired AVM prescription dose was 25 Gy, but this was also reduced to protect normal structures and to keep the total dose within certain pre-defined limits. All AREs refer to intra-parenchymal increased perilesional T2 signal on MR irrespective of clinical correlation.

Results

There was no relationship between tumour volume and the development of ARE in the tumour groups. There was a highly significant relationship between target volume and the development of ARE for the AVMs with their much higher dose. Radiation-induced clinical trigeminal and facial nerve deficits with both vestibular schwannomas and meningiomas were always associated with an increased T2 signal in the neighbouring brainstem parenchyma.

Conclusions

The relationship between target volume and the risk of adverse radiation effects may not apply with lower prescription doses. Individual radiosensitivity may explain why a minority suffer AREs unrelated to target volume. It is possible that radiation-induced brainstem parenchymal damage with concomitant cranial nerve deficits may be commoner after radiosurgery than is usually thought. If tumour control with lower doses is adequate, radiosurgery could be safely considered for larger targets associated with a high risk from microsurgery

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Authors and Affiliations

  1. Gamma Knife Center Cairo, Nasser Institute Shobra, Cairo, Egypt

    J. C. Ganz, W. A. Reda & K. Abdelkarim

  2. Department of Neurosurgery, Haukeland University Hospital, Jonas Liesvei 65, N-5021, Bergen, Norway

    J. C. Ganz

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  1. J. C. Ganz
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  2. W. A. Reda
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  3. K. Abdelkarim
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Correspondence to J. C. Ganz.

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The authors studied the incidence of imaging-confirmed new symptoms (adverse radiation effects) in a series of patients who had Gamma Knife radiosurgery for a benign pathology. This included meningiomas, vestibular schwannomas and arteriovenous malformations. Minimum follow-up for each group was in excess of 24 months, which is adequate in a study of potential complications. The authors state in the abstract that “radiation-induced clinical trigeminal and facial nerve deficits with both vestibular schwannomas and meningiomas were always associated with increased T2 signal in the neighbouring brainstem parenchyma.” Some may find this difficult to understand but likely reflects the fact that imaging does not show effects related to cranial nerves. Such imaging effects to the brainstem are rare after vestibular schwannoma or meningioma radiosurgery at a margin dose of 12 Gy. Cranial neuropathy can occur from effects on cranial nerves and does not necessarily require changes in the brainstem. Certainly, brainstem changes can occur and lead to neurologic deficits, but this is not necessary. Since arteriovenous malformations typically are surrounded by brain parenchyma and not by cranial nerves, it makes sense that the dose–volume relationship for AVMs would be different.

It is important to note that the morbidity rate was low for meningiomas (2.6%) and vestibular schwannomas (6%). This is in line with reports from other centres. In contrast, they found post-radiosurgery imaging changes (long relaxation time MRI) in 60% of patients with arteriovenous malformations. In some, these may have been haemodynamic related to AVM obliteration and not an adverse occurrence. In these 64 patients, only nine were symptomatic. In seven of the patients, the deficits were temporary.

I concur with the authors that there is a clear dose–response relationship for disorders of brain parenchyma. For extraaxial lesions more intimately associated with cranial nerves, these relationships are more complex. For example, hearing may be related to the cochlear dose rather than brainstem dose. Much work has been on AVM dose prescription, and a number of centres are conducting research into better understanding the effects on tumours near cranial nerves.

Douglas Kondziolka

Pittsburgh, Pennsylvania

The author compares three groups of patients. In the so-called low-dose group, 271 meningiomas and 107 vestibular schwannomas were treated with 12 Gy (over 90% cover, conformity index 1.25 or better). In these patients, the dose never was reduced because of tumour volume (volume range for meningiomas, 0.3 to 43.2 cm3; for schwannomas, 0.07 to 17.8 cm3). The “high-dose group” consisted of 132 patients with arteriovenous malformations (volume range 0.3 to 19 cm3). In this group, the prescription dose was aimed at 25 Gy but had to be reduced in 33 patients (range 14 to 25 Gy).

Evaluating the follow-up data, the author shows that target volume was not a determinant of adverse radiation effects in the meningioma and in the schwannoma group (low-dose group). On the other hand, in the group of patients with arteriovenous malformations, there was a significant relationship between volume of the lesion and the occurrence of adverse effects.

This paper is of importance because it forms a systematic basis for a multitude of case reports describing Gamma Knife treatment success in large tumours. It clearly shows that at low doses, even large lesions can be treated safely. Further evaluation should clarify the threshold dose and volume at which adverse effects start to rise in incidence significantly.

Michael Mokry

University of Graz

Ganz et al are providing us with an interesting contribution about the impact of volume on risk after radiosurgery depending on the reference dose used. This paper have the merrit to propose to support by data a concept quite communly accepted : the higher is the reference dose the more important is the impact of volume on risk prediction. Pionneers like Flickinger and Kjelberg have well demonstrated that in radiosurgery both marginal dose and treatment volume must be taken into account for risk prediction (1). Flickinger dose volume effect integrated formula demonstrates that the larger is the volume the lower is the dose threshold for risk and the higher the prescription dose is the lower is the threshold for acceptable volume.

However the role of other parameters must not be underestimated. The quality of the doseplanning in term of conformity and selectivity is also of major importance. Niranjan and Flickinger are demonstrating how radiosurgery with high selectivity reduces complications for the same treatment dose (2). Theoritical dose response curves for complication rate with different treatment volume are shown by these authors to be shifted « on the safe side » when more normal tissue surrounding the target is spared. Readers must keep in mind that the present series is coming from a neurosurgeon with one of the longer experience in this field of radiosurgery. Other potential risk factors are the nature of the lesion, the involvement of normal brain in the mass of the lesion, the location and the individual sensitivity to radiation...

In the neurosurgical community discussions related to the role of radiosurgery are frequently made difficult by the overall underestimation of basic knowledge and specially basic radiobiological principles of radiosurgery. Thus, any contribution participating to a better understanding of radiosurgery is of importance.

Jean Regis

La Timone University Hospital, Marseilles

Bibliographie

1. Flickinger JC, Lunsford LD, Kondziolka D: Dose prescription and dose-volume effects in radiosurgery. Neurosurgery Clinics of North America 3:51-59, 1992.

2. Niranjan A, Flickinger JC: Radiobiology, principle and technique of radiosurgery. Prog Neurol Surg 21:32-42, 2008.

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Ganz, J.C., Reda, W.A. & Abdelkarim, K. Adverse radiation effects after Gamma Knife Surgery in relation to dose and volume. Acta Neurochir (Wien) 151, 9–19 (2009). https://doi.org/10.1007/s00701-008-0174-4

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