Abstract
Aim
Local recurrence after surgery of soft tissue sarcomas is dependent on surgical margins. Wide margins require large resections which may lead to impaired function or loss of limb. In some cases it may be technical impossible or even ethical unacceptable to achieve ideal surgical margins. Standard adjuvant treatment in such cases is ionising radiation, which may cause severe toxic side effects.
PCI is a unique procedure for site-specific delivery of several types of membrane impermeable molecules. The technology is based on the photochemical induced cytosolic release of endocytosed macromolecules from endosomes and lysosomes into the cytosol. PCI has in this study been evaluated as an adjuvant to the surgical resection of sarcoma.
Method
Human fibrosarcom (HT1080) was transplanted to athymic mice. The photosensitizer aluminium phthalocyanine disulfonat (AlPcS2a), and bleomycin (BLM) was systemically administrated 48 hours and 30 minutes respectively prior to surgery and light exposure. After resection with intralesional margin the tumour bed was illuminated at 670 nm (15 J/cm2).
Results
PCI was found to induce longer delay in tumour growth than photodynamic therapy (PDT). In combination with surgery little was achieved with respect to tumour growth delay by adding the photosensitizer and light (photodynamic therapy, PDT) while PCI induced synergistic effect.
Conclusion
The results indicate that PCI targets the viable peripheral zone of the tumour where PDT is apparently less effective. PCI with BLM seems promising as an adjuvant treatment after inadequate resection of sarcomas. The PCI technology is currently explored in a Phase I/II trial in University Hospital (London, UK)
