PDT uses nonthermal coherent light delivered via fiber optic cable to locally activate a photosensitive chemotherapeutic agent that ablates tumor tissue. It is unknown whether PDT can treat large osseous tumors owing to the limitations of light penetration. In this pilot study, we determined if PDT can induce necrosis in large osseous tumors and quantified the volume of treated tissue in seven dogs with spontaneous osteosarcomas of the distal radius.
Osteosarcomas are common in dogs and commonly affect the radius. The characteristics of canine osteosarcomas are histologically similar to those of human osteosarcomas and we therefore presumed this was a good model to test our hypothesis. Limits to this study include the limited number of dogs that were treated and the limited number of control animals. However, this was a pilot study, and owing to ethical reasons, a limited number of animals were used with limited followup (48 hours) before amputation. The long-term clinical followup of the dogs was not reported because the dogs were lost to followup (<1 year), making it difficult to determine whether the treatment had either a positive or negative effect on the dog’s survival. Likewise, a potential downside of the technique used is potential seeding of tumor tissue into adjacent tissue during placement and withdrawal of the fiber optic cable and hemorrhage secondary to fiber placement. Our assessments were not blinded, although we did not believe this essential for this pilot study. Finally, our study was limited in that there was variability in lesion sizes produced in animals with the same type of tumor. This can be explained in part by the following: the osteosarcomas in this study were all Stage IIb and some dogs had areas of spontaneous necrosis noted preoperatively. Placement of fibers in an area of preexisting necrosis served to limit the measurable effect attributed to PDT and skewed the results negatively. For example, the cylindrical diffusing tip was placed in an area of preexisting necrosis in the tumor of one animal (Dog JR, Table ). The measurable lesion in this animal’s osteosarcoma was limited on the post-PDT MRI because the preexisting necrosis was indiscernible in the mediolateral plane from the lesion created from the PDT, rather than because there was a poor response to treatment in that tumor. In contrast, in animals in which there was no or limited spontaneous necrosis preoperatively, large areas of necrosis from PDT treatment were determined easily.
We observed necrosis histologically and on MRI. Although necrosis was seen in all tumors except one before PDT, the extent of necrosis after PDT was substantial in all of the PDT-treated radii except for the control. The hypointense tissue on MRI matched the area of necrosis seen on histologic specimen, and we were able to obtain a volumetric measurement from the MRI to determine the volume of necrosis after PDT was substantially increased.
The effect of PDT is mediated through direct ablation and immune-mediated vascular stasis [11
]. We found a mean treatment effect size of approximately 16 cm3
, with a consistent effect seen in the anteroposterior (2.5 cm) and mediolateral (2.6 cm) dimensions. The effect measured along the rostrocaudal (5.2 cm) plane correlated well with the length of the diffusing tip used for treatment in this study (5 cm).
Our results are consistent with those of several trials in rodents largely consisting of experiments in orthotopic osteosarcoma, chondrosarcoma, and fibrosarcoma models [8
]. In these studies, PDT was able to ablate primary bone tumors, although the size of the tumors was small. Several other animal studies showed PDT can induce necrosis in metastatic adenocarcinomas in bone as well [4
]. Burch et al. [4
] showed, with a bioluminescent metastatic rat model, PDT ablated human breast cancer in the axial and appendicular skeleton. Several other early-phase clinical trials have shown PDT is capable of ablating various primary human cancers, including breast, prostate, bladder, and lung cancer [2
]. However, the extent of ablation was limited in most of these studies because the light source had to be placed on the surface of the diseased tissue and not directly in the tumor. In contrast, the fiber can be placed in the center of the tumor in osseous tumors. It may be the skeleton is the ideal place for PDT since the fiber optic cable can be placed directly in the bone without compromising the native tissue.
Our data show PDT can induce tumor necrosis in relatively large bone tumors and the light penetration does not appear to be a limiting factor in the animals treated. The treatment protocol in our study used one 0.94-mm fiber. However, the treatment effect could be increased by using multiple fibers placed accordingly. Arguably, complete ablation of the osteosarcoma in a dog may have been obtained if several fibers were appropriately arranged in the tumor in the medullary canal. The technique also is applicable to the axial skeleton, and Burch et al. [5
] also examined safe application of low-dose PDT in porcine vertebrae and canine vertebrae. The average volume of necrosis in dogs in the current study is approximately the size of large metastatic lesions seen in the thoracic and lumbar spine [1
]. PDT may have potential as an adjunctive therapy for treatment of spinal metastases along with radiation and bisphosphonates [22
Our pilot data suggest PDT can ablate a considerable volume of large bone tumors and the light penetration in osseous tumors is not a limiting factor. The other benefits of PDT are that it is minimally invasive (the treatment fiber is less than 1 mm in diameter); because it is targeted, it has limited systemic and local side effects and repeat treatments can be made; the treatment time is, on average, extremely short (33 minutes); and it could easily be used as an adjunct with other strategies to treat osseous tumors.