背景:骨肉瘤(OS)是一种侵袭性恶性骨肿瘤,死亡率高。远端转移或多药耐药患者预后不良。作为一种新兴的抗肿瘤策略,由可见光和近红外光介导的光动力疗法(PDT)由于其靶标选择性而引起了广泛的关注,远程可控性,最小或非侵入性的特征。然而,PDT也有明显的局限性。具体来说,由于光线的穿透力有限,它主要用于浅表恶性肿瘤的临床治疗,比如肌肉骨骼肉瘤和黑色素瘤,但除了极少量的深犬OS模型实验外,它尚未应用于深部恶性骨肿瘤的临床治疗。
方法:我们在过去十年中基于体外实验和动物模型搜索了专注于PDT用于OS的有效性和安全性的研究。使用电子数据库进行了系统的搜索,包括PubMed,ClinicalTrials.gov,还有Cochrane图书馆.
方法:(1)有关PDTforOS的原始研究文章;(2)英文文章;(3)体外或动物模型研究;(4)详细信息,包括单元格名称,注量,辐照波长,与PS孵育的时间,PS治疗和照射之间的持续时间,以及辐照和活力测定之间的持续时间。
方法:(1)研究是一篇综述/系统综述文章,专利,信,或会议摘要/论文;(2)文章没有以英文发表;(3)包含重叠或不足数据的研究。
结果:我们确定了201种出版物,44篇文章符合纳入标准,被纳入综合。不幸的是,目前尚无使用PDT治疗人类OS的相关临床报道。在这些研究中,8项研究仅在体内实验中用于评估OS动物模型中PDT的效率,19项研究专门进行了在不同条件下用PDT处理的细胞的体外活力测定,17项研究包括体外细胞实验和体内动物OS模型,以评估体内和体外PDT对OS的影响。所有研究表明,PDT对OS细胞具有细胞毒性,或者可以在异源或同源动物OS模型中抑制OS的生长,但在一定剂量范围内表现出最小的细胞毒性。
结论:基于此系统评价,PDT可以根除细胞培养物中的OS细胞,并且在动物模型中有一些有效性的证据。然而,PDT控制人类操作系统的能力尚不清楚,动物和人类报告没有显示人类OS控制的证据,他们只是证明了可行性。关于用PDT治疗骨肉瘤的潜力的主要问题是,应将足够的光传输到肿瘤部位,并且如果在转移之前发现疾病并且对肿瘤部位进行照射是可行的,治疗潜力是存在的。否则,PDT可能主要是姑息性的。为了确定PDT是否可以安全有效地用于OS的临床治疗,必须进行许多临床前原位动物OS模型和多个系统性转移的OS模型,间质PDT或术中PDT可能是人类OS治疗的良好和潜在候选者.如果这些问题能够得到很好的解决,PDT可能是治疗OS患者的潜在有效策略。
BACKGROUND: Osteosarcoma (OS) is an aggressive malignant bone tumour with high mortality. A poor prognosis is noted in patients with distal metastases or multidrug resistance. As an emerging antitumor strategy, photodynamic therapy (PDT) mediated by visible and near infrared light has attracted intensive attention given its target selectivity, remote controllability, minimal or non-invasive features. However, PDT also has obvious limitations. Specifically, due to the limited penetration of light, it is mainly used in the clinical treatment of superficial malignant tumours, such as musculoskeletal sarcomas and melanoma, but it has not been applied to the clinical treatment of deep malignant bone tumours except for a very small number of experiments on deep canine OS models.
METHODS: We searched for studies that focused on the effectiveness and safety of PDT for OS based on in vitro experiments and animal models in the last decade. A systematic search was conducted using electronic databases, including PubMed, ClinicalTrials.gov, and the Cochrane Library.
METHODS: (1) original research articles about PDT for OS; (2) articles in English; (3) in vitro or animal model research; and (4) detailed information, including cell name, fluence, irradiation wavelength, time of incubation with PS, duration between PS treatment and irradiation, and duration between irradiation and viability assays.
METHODS: (1) study was a review/systemic review article, patent, letter, or conference abstract/paper; (2) articles were not published in English; (3) studies containing overlapping or insufficient data.
RESULTS: We identified 201 publications, and 44 articles met the inclusion criteria and were included in the synthesis. Unfortunately, there are no relevant clinical
reports of the use of PDT in the treatment of human OS. In these studies, 8 studies only employed in vivo experiments to evaluate the efficiency of PDT in an OS animal model, 19 studies exclusively performed in vitro viability assays of cells treated with PDT under different conditions, and 17 studies included in vitro cell experiments and in vivo animal OS models to evaluate the effect of PDT on OS in vivo and in vitro. All studies have shown that PDT is cytotoxic to OS cells or can inhibit the growth of OS in heterologous or homologous animal OS models but exhibits minimal cytotoxicity at a certain range of dosages.
CONCLUSIONS: Based on this systematic review, PDT can eradicate OS cells in cell culture and there is some evidence for efficacy in animal models. However, the ability for PDT to control human OS is unclear, the animal and human
reports do not show evidence of human OS control, they just do show feasibility. The major issues concerning the potential for treatment of osteosarcoma with PDT are that adequate light should be transmitted to tumor loci and if the disease is caught before metastasis and irradiation of tumor sites is feasible, curative potential is there. Otherwise, PDT may be mainly palliative. To determine whether PDT can safely and efficiently be used in the clinical treatment of OS, many preclinical orthotopic animal OS models and OS models of multiple systemic metastases must be performed and interstitial PDT or intraoperative PDT may be a good and potential candidate for human OS treatment. If these problems can be well solved, PDT may be a potentially effective strategy for the treatment of OS patients.