Photodynamic Therapy Methods and Protocols
Biological interactions of visible light with photosensitizers have been studied for over a century while controlled clinical applications of light and photosensitizers to treat solid tumors, known as photodynamic therapy, have been evolving since the mid
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Introduction Malignant brain tumours such as anaplastic gliomas WHO grade III and glioblastoma multiforme WHO grade IV carry a lethal prognosis. Current treatment regimes, such as surgery, chemotherapy and radiotherapy, prolong the lifespan to a median survival of 15 months and recurrent glioblastoma demonstrate C.J. Gomer (ed.), Photodynamic Therapy, Methods in Molecular Biology 635, DOI 10.1007/978-1-60761-697-9_17, © Springer Science+Business Media, LLC 2010
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a median survival of 3 months (1, 2) (Table 17.1). The natural lifespan of patients after diagnosis suffering from glioblastoma multiforme WHO grade IV is around 3 months. The 5-year survival is under 1%. The incidence of malignant brain tumours varies from 4/100.000 in the United States to 14/100.000 in the Scandinavian countries with an increase of up to 70/100.000 in the elderly population above 65 years (3).
Table 17.1 Outcome of malignant gliomas WHO gradings and therapeutic strategies (1) Histology WHO
Therapy
Recurrence Median time survival
Glioblastoma multiforme WHO grade IV (GBM)
Surg, CHT, XRT
6 months
15 months
Anaplastic astrocytoma WHO grade III (AA)
Surg, CHT, XRT
18 months
3 years
Astrocytoma II
Surg, XRT
3 years
6 years
Astrocytoma I
Surg
8 years
10 years
Surg, surgery; XRT, radiotherapy; CHT, chemotherapy
Surgery is the first and most important step in the treatment of malignant gliomas and remains the mainstay of therapy. However, radical resection is hardly possible due to infiltrating growth into normal brain parenchyma. Recurrences occur 95% locally within 2 cm from the initial site and arise from tumour cells (guerrilla or satellite cells) embedded in the area of oedematous or normal brain adjacent to tumour brain adjacent to tumour (BAT) region) (4). Photodynamic therapy (PDT) is currently undergoing intensive clinical investigations as adjunctive treatment for malignant brain tumours (5–7). Photosensitizers are accumulated in pathological brain tissue to a higher extent than in normal brain parenchyma (8, 9). Subsequent light activation produces a variety of cytotoxic oxidative reactions which induce selective tumour destruction via vascular or direct cellular mechanisms (10, 11). Therefore PDT offers a more selective treatment of such malignancies as compared to other currently available treatment modalities and seems to be a logical concept for brain tumours infiltrating into normal brain (12). Clinical studies demonstrated a benefit for the patients treated with PS-mediated PDT in terms of prolongation of median survival time as well as quality of life (8). In the past, intraoperative fluorescence-guided delineation had been under investigation with fluorescine and tetracyclines
Photodynamic Diagnosis and Therapy and the Brain
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or autofluorescence (13, 14); however, the sensitivity and specificity were too low to be of clinical significance, especially for neurosurgery. Modern intraoperative imaging techniques now include techniques such as MRT and CT, neuronavigation and ultrasound,
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