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

吖啶橙光动力和放射动力疗法在肌肉骨骼肉瘤保肢手术中的应用进展

基本信息

批准号：
14207058
负责人：
KUSUZAKI Katsuyuki
金额：
$ 16.06万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

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

简介：我们最近的实验研究表明，吖啶橙光动力或放射动力疗法（AO-PDT 或 AO-RDT）对小鼠骨肉瘤细胞在体外和体内均具有很强的杀细胞作用，并且 AO 在手术过程中也具有肿瘤可视化效果。，因为 AO 是亲瘤性的，并且具有通过激发发出荧光的能力。在本研究中，我们尝试应用 AO-PDT 联合/不联合的病灶内切除（刮除）手术。对肌肉骨骼肉瘤患者进行AO-RDT，以获得良好的肢体功能。材料与方法：1999年7月至2005年2月期间，采用AO-PDT联合/不联合AO-RDT进行刮宫治疗47例肌肉骨骼肉瘤患者。 37 名患者在治疗后进行了超过 6 个月的组织学随访，其中 6 名患者接受了治疗。滑膜肉瘤、横纹肌肉瘤 6 例、尤文氏肉瘤/PNET 5 例、骨肉瘤 5 例、MFH 3 例、MPNST 2 例、软骨肉瘤 2 例等。这些患者中有 19 名男性和 13 名女性，平均年龄为 29 岁（1 至 82 岁）对于这些患者，宏观随访期为 6 个月至 68 个月。首先对肿瘤进行刮除，然后局部给予1μg/ml AO溶液5分钟，然后用荧光手术显微镜进行蓝光激发，在肿瘤可视化下进行显微刮除，最后对肿瘤进行AO-PDT。使用手术显微镜刮除区域 10 分钟，在不冲洗 AO 的情况下闭合手术伤口后，立即将 5 Gy 的 X 射线照射到切除区域进行 AO-RTD。在 21 名主要接受 AO-PDT 并/不接受 AO-RDT 的患者中，只有 1 名患者出现局部复发，局部复发率为 4.8%，这是相当好的局部控制，然而，12 个病灶中有 3 个（25%）复发。未进行 AO-PDT 的初次手术后，即使在 AO-PDT 后再次复发，5 例骨 GCT 和硬纤维瘤等局部侵袭性肿瘤患者在 AO-PDT 后均未出现局部复发。研究的患者通过 AO 给药或 AO-PDT 和 AO-RDT 均保持了良好的肢体或器官功能。结论：基于这些结果，我们得出结论，AO-PDT 与 AO-RDT 将成为一体。一种新颖的保肢方式，可抑制肌肉骨骼肉瘤的局部肿瘤复发并保留良好的肢体或器官功能。