Malignant Pleural Mesothelioma - Photodynamic Therapy
Photodynamic therapy of malignant mesothelioma of pleura
T. Warloel, H. Heyerdahll, Q. Peng2, J. H0iel, E. Normannl, 0. Solheim3, J. Moan2, K.-E. Gierckskyl.
Departments of Surgical Oncologyl and Oncology3, The Norwegian Radium Hospital Departments of Biophysics2, Institute for Cancer Research Montebello, 0310 Oslo, Norway.
Abstract
Nine patients with malignant pleural mesothelioma underwent extensive surgery followed by intra-operative photodynamic therapy. 2 mg/kg Photofrin was given 48 hours prior to surgery. The thoracic cavity and eventual remaining lung were exposed to 15-30 Joules/cm2 of 630 nm laser light. Tumour tissue was analysed by microscopic photometrical techniques. Five patients with mixed or epitheloid tumours with fluorescence intensity >100 grey leveVpixel seemed to benefit from the given therapy.
One patient was free of disease 18 months after treatment. Two patients were treated for metastasis after 12 months with no sign of intrathoracic recurrency. Both are still alive, one without further sign of disease 32 months after initial treatment. Two patients presented generalized disease after 9 and 13 months and intrathoracic recurrency several months later.
Two patients with poorly differentiated tumours and 2 patients with moderate to highly differentiated tumours, but with fluorescence intensity <100 grey level/pixel, presented recurrencies after 4 months. PDT-efficiency seems to be predicted by the intensity and distribution of drug-induced fluorescence in tumour tissue. PDT may enhance the possibility to achieve complete local tumour control after excision. Multimodal therapeutic approach of local and systemic disease seems mandatory to further improve survival.
1. INTRODUCTION
Malignant mesothelioma is an almost invariably fatal cancer disease that occurs on serosal surfaces of the body. Induction of malignant pleural mesothelioma is most commonly caused by exposure to asbestos fibers, followed by a latency period of 20-40 years before appearance of symptomsl. There is no standard therapy for such disease. Radiotherapy and chemotherapy have little effect in the treatment of malignant pleural mesothelioma 2~4 and in some European countries surgery is considered to be even less effective.
Photodynamic therapy (PDT) is an investigative cancer treatment modality5-7 that has been under development during the last decades. The basis of this therapy involves the in situ activation of a photosensitiser accumulated in tumour and normal tissue by visible light, causing cell death8~10. The specificity of the PDT-effect correlates with the biodistribulion of the photosensitising substance8. Porfimer sodium, Photofrin, is the most widely used photosensitiser in current clinical trials.
PDT is mainly a local treatment and has the potential, as an adjuvant therapy, to enlarge the surgical margins and may thereby transform an incomplete surgical resection due to anatomic or structural limitations, to a complete local tumour eradication. PDT using Photofrin has been shown to be effective in human mesothelium grown as xenografts in rodentsll l2 and in a few humans cases using Photofrinl3 or a chlorin photosensitiserl4.