Photodynamic therapy of brain tumours — post-operative “field fractionation”

Abstract

Malignant primary cerebral tumours account for 3% of the cancer burden and constitute the most common solid tumour in the paediatric age group. In spite of the advances in the surgical treatment, radiation therapy and chemotherapy of these tumours, the prognosis remains very poor. Patients with glioblastoma multiforme, the most common primary cerebral glioma, have a median survival of less than 1 year and a 2 year survival rate of less than 20%. Malignant primary cerebral gliomas cause disability and death as the consequence of local effects. Their invasion and destruction of brain tissue results in neurological disability and the associated increase in intracranial pressure eventually leads to coma and death. Most malignant primary cerebral tumours do not metastasize. Therefore, these tumours represent an excellent example of a highly malignant solid tumour where local tumour control should be of survival value. However, patients with malignant glial brain tumours tend to present clinically with sizable tumours. In a series of 100 consecutive patients with malignant cerebral astrocytic tumours, computed tomography (CT) scan assessment showed the median tumour mass to be 35 g (not including tumour-associated cerebral oedema) [l]. This mass is within two or three doublings of the lethal mass of 100 g. The penetration depth of 630 nm light in brain tumour tissue in vivo is limited to approximately 3 mm [2, 31; the killing distance might thus be estimated to be 8-12 mm. By assuming a spherical geometry, the mass of tissue destroyed with a 1 cm killing radius is estimated to be only 4 g when a point source is used for interstitial photoillumination. A diffusion fibre with a 2 cm cylindrical tip might destroy 6-10 g of tumour tissue if the killing radius is 1 cm. By creating a spherical cavity with a radius of 2 cm within the solid tumour by surgical means and then using intracavitary photoillumination with a 1 cm killing radius, a much larger tumour mass of 80 g of tissue could be destroyed. Thus a combination of intraoperative intracavitsry photoillumination and multiple interstitially placed diffusion fibres may result in a substantial volume of tissue photoillumination and destruction.