Development of photodynamic and radiodynamic therapy with acridine orange for new limb salvage surgery in musculoskeletal sarcomas

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Introduction : Recent our experimental study revealed that photodynamic or radiodynamic therapy with acridine orange (AO-PDT or AO-RDT) had a strong cytocidal effect in vitro as well as in vivo on mouse osteosarcoma cells. Also AO had a tumor visualization effect during surgery, because AO is tumorphilic and has a capability to emit fluorescence by excitation. In this study, we have attempted to apply reduction surgery of intralesional excision (curettage) by AO-PDT with/without AO-RDT to musculoskeletal sarcoma patients, to obtain good limb function.Materials & Methods : 47 patients with musculosketetal sarcomas were treated by curettage using AO-PDT with/without AO-RDT during July 1999 to February 2005. Clinical out come was analysed in 37 patients who are followed longer than 6 months after the treatment. Histologically, 6 were synovial sarcomas, 6 rhabdomyosarcomas, 5 Ewing'sarcomas/PNETs, 5 osteosarcomas, 3 MFHs, 2 MPNST, 2 chondrosarcomas, etc. Average age of these patients with … More 19 males and 13 females was 29 years (1 to 82 years). Follow-up period was ranged from 6 month to 68 months. For these patients, macroscopic curettage of tumor was first performed, and then microscopic curettage under tumor visualization was done after local administration of 1□g/ml AO solution for 5 minutes followed by excitation with blue light using fluorescence surgical microscope. Finally, AO-PDT was applied to tumor curettage area for 10 minutes using surgical microscope. After closure of surgical wound without washing of AO, 5 Gy of X-ray was immediately irradiated to resected area for AO-RTD.Results : Out of 21 patients primarily treated wit AO-PDT with/without AO-RDT, only one patient had a local recurrence. Local recurrence rate was 4.8%, which is quite better local control. However, 3(25%) of 12 lesions which recurred after primary surgery without AO-PDT recurred again even after AO-PDT. 5 patients with locally aggressive tumors such as bone GCT and desmoid tumor did not show local recurrence after AO-PDT. All of patients studied maintained an excellent limb or organ function. Any patients did not have systemic or local complications by AO administration or AO-PDT and AO-RDT.Conclusion : Based on these results, we concluded that AO-PDT with AO-RDT will become a novel limb salvage modality to inhibit local tumor recurrence and to preserve an excellent limb or organ function in musculoskeletal sarcomas. Less