Effects of Interstitial Laser Photocoagulation and Photodynamic Therapy on lung parenchyma

Interstitial Laser Photocoagulation(ILP) and interstitial Photodynamic Therapy (PDT) are minimally invasive treatments for cancer. They use laser light passed directly into the tumour via thin optical fibres to cause tumour necrosis. Some patients with lung cancer have potentially curable tumours but cannot undergo surgery due to medical contraindications. ILP and PDT could potentially be used as an alternative treatment for these patients. Thin laser fibres could be passed into small parenchymal lung cancers (Stage T1) in the manner of a fine needle aspiration biopsy under CT control. To obtain the best chance of local cure of a lung tumour with ILP and PDT, some normal tissue around the tumour should be treated. Tumours are always at least as sensitive to ILP and PDT as the normal surrounding tissue. For these reasons it is essential to know the effects of the treatment on normal parenchyma before applying them to tumours in a new organ. The aims of this thesis were therefore to see if it was possible to perform these treatments in normal lung parenchyma, and whether after initial necrosis there was safe healing. Initial experiments were on rats. Reproducible well localised necrotic lesions of up to 12 mm diameter could be created with both ILP and PDT using single laser fibres. Differing patterns of histological necrosis were observed, however there was safe healing with both. 3 different PDT photosensitizers were used, with mTHPC giving the largest lesions. Assessments of lung physiology showed no adverse effect, and the pneumothorax rate was low. A possible self-sealing effect on the lung parenchyma was observed where the fibre was inserted. Subsequent experiments were performed in pigs using multiple laser fibres inserted simultaneously to cause larger lesions of a size which could incorporate a T1 tumour. Lesions of overlapping necrosis of between 3 and 4 cm diameter were made with both treatments and they were well tolerated. The unique features of PDT necrosis were observed in that the initial necrosis only affected epithelial structures and did not affect lung connective tissue. In contrast ILP caused non selective tissue necrosis. With time there was lesion shrinkage due to local fibrosis, however the lung adjacent to these well localised lesions remained normal. This study has shown the feasibility of performing these techniques on a small group of patients with lung cancer and pilot clinical studies are planned.