Discussion
In this case report, an appendicular osteosarcoma affecting the left third and second metacarpal bones was diagnosed based on radiography and excisional bone biopsy. Initial treatment consisted of surgical resection of the tumour followed by chemotherapy. Three years later, the tumour recurred and was treated successfully with SBRT, as no further resection was possible due to the risk of pathological fractures. The clinical outcome of this approach included stabilization and flattening of the bone surface radiographically, as well as resolving lameness at walk and trot during the current two and a half years of follow-up. Until now, the horse appears in healthy condition without suspicion of pulmonary or skeletal metastasis based on telephone interviews and regular veterinary checks at home. This is the first case report describing radiation therapy as a treatment of appendicular osteosarcoma in horses.
To diagnose osteosarcoma in horses, preferably a histological examination or immunohistochemistry of excised tissues is performed. Differentiating between osteosarcoma, fibrosarcoma and chondrosarcoma histologically can be difficult, but the presence of malignant osteoblasts is typical for osteosarcoma. Additionally, multiple subclassifications of osteosarcoma are described, depending on the extracellular matrix and the histological characteristics of the cells (Thompson and Pool, 2002). In the present case, the tumour was diagnosed as a fibroblastic osteosarcoma because of the presence of spindle cells (similar to fibrosarcoma’s) along with osteoid matrix. It is difficult to assess any correlation between histologic subtype and prognosis because most horses are either euthanized at the time of diagnosis, or no further treatment is attempted resulting in a loss to follow-up. Main reasons for considering euthanasia upon diagnosis include concerns about the potential development of a pathological fracture, a lack of positive response to previous analgesics, or mechanical restrictions caused by the mass (Jenner, 2010; Kilcoyne, 2010 ; Leite, 2019). In the presented case, no clinical signs suggestive of metastases were observed. Since metastatic spread to other organs is assumed to be slower or even absent in horses compared to osteosarcoma in dogs and humans (Luu et al., 2005; Jenner, 2010; Bush et al., 2007; Koch et al., 2014; Leite, 2019), no further examinations were performed to check for metastatic disease. In dogs, common metastatic sites typically involve the lungs, distant bones, skin, cerebrum, eyes and lymph nodes. These can be diagnosed through methods such as radiography, CT scans or positron emission tomography (PET) /CT scans.
The osteosarcoma was initially treated with resection of the affected bone. Subsequently, chemotherapy involving carboplatin injections was administered at the level of the bone defect eleven weeks later, once full wound healing had been achieved. Various studies have been performed to assess if the survival of dogs with osteosarcoma can be prolonged by adjuvant therapies after tumour resection. In studies by Philips et al., dogs treated with adjunctive chemotherapy had a prolonged median survival time (307-322 days) in comparison to those after surgical resection of the tumour alone (approximately 138 days). Carboplatin was well tolerated and the results in different administration techniques (intravenously vs. subcutaneously) have been equivocal (Philips et al., 2009; Saam et al;, 2011). Additionally, carboplatin has been proven to cause less side effects like nephrotoxicity, nausea and gastrointestinal toxicity in comparison to cisplatin in dogs (Lokich et al., 1998; Guan et al., 2016). In horses, the use of cisplatin and carboplatin is well documented for treatment of neoplastic conditions of the skin. Other chemotherapeutics frequently described in equine tumours are bleomycin and mitomycin. The choice of using carboplatin for this case was made due to logistic reasons. In the context of osteosarcoma in the horse, only one case report describes a positive outcome after lining the remaining defect and margins of a resected osteosarcoma with cisplatin beads (Gutierrez-Nibeyro et al., 2010).
The tumour remained stable during three years after initial treatment but recurred eventually. As resection of the newly affected bone would have increased the risk of pathological fractures due to the interrupted cortex of the third metacarpal bone, SBRT was employed as a treatment. SBRT is able to deliver a high dose of radiation precisely and accurately to the tumour site. This approach is particularly profitable in bone tumours, which are usually not very sensitive to radiation, to maximize tumour control and pain reduction in the affected region. Due to the ability to spare normal tissues, the occurrence of adverse radiation effects are reduced (Farese et al., 2004; Martin et al., 2021).
In human and small animal oncology, radiation therapy is utilized to relieve pain and slow down tumour growth. Osteosarcomas are typically more resistant to radiation therapy and therefore, it is not considered a primary definitive treatment approach for surgically removable tumours. Instead, it is mostly used as an adjuvant therapy after an incomplete resection, or as a definitive treatment in cases of unresectable tumours (Withrow et al., 2013). In dogs, the primary approach involves amputation of the affected limb, as recurrence of osteosarcoma has been reported in 15-25% of the cases after surgical resection of the tumour alone (Henry and Higginbotham, 2010). In equine medicine, amputation of the affected limb is not a viable treatment (Crawley et al., 1989; Kelmer et al., 2010). Therefore, adjuvant therapies to surgical resection of the osteosarcoma, such as chemotherapy or radiation therapy, are advisable.
Only a few reports describe the use of radiation therapy in horses as an adjuvant treatment for non-cutaneous tumours (Mosunic et al., 2004; Pfeifle et al., 2021; Will et al., 2023), and only one report mentions SBRT in the successful treatment of sinonasal osteosarcoma (Gillen et al., 2020). This is thus the first case report describing radiation therapy as a successful treatment for appendicular osteosarcoma in horses. Presumably, this may be due to the technical requirements needed to perform highly qualitative radiation therapy in horses. The integration of CT in radiation therapy is a feasible strategy to apply in horses although its clinical implementation is highly demanding and requires strong technical, computational, and logistic efforts (Fonti et al., 2019). CT-based computer planning and isocentric modulating techniques should be used more often as this is the case in small animal radiation therapy. Another factor to take in account is the requirement of repeated episodes of general anaesthesia (and subsequent recovery) within few days. Although the duration of anaesthesia during radiation therapy is short (usually less than 30 minutes), general anaesthesia is less tolerated in horses in comparison to other species and age and general condition of the horse should be taken into account. For patients with a higher complication risk, assistance can be provided during the recovery phase. In this case, the disrupted cortex of the third metacarpal bone and the location of the tumour at the level of the diaphysis increased the risk of developing a pathological fracture during recovery from anaesthesia. Because of the good general condition and the calm and well-behaved character of the horse, the risk factor of the required anaesthesia deemed lower than the risk of not treating at all. In the early stages following treatment, possible side effects that may occur in the treated area include hair loss, swelling of the skin, dry desquamation and, in rare cases, moist desquamation (Withrow, 2013; Gillen et al., 2020). The potential side effects in late stages include hair greying or alopecia. In cases treated with SBRT, a higher risk of pathological fracture is described in comparison to conventional radiation protocols (Farese et al., 2004; Martin et al., 2021). This risk decreases if cases with a minimum of 50% intact cortex are selected for the treatment (Martin et al., 2021). None of these reported complications were observed in the present case.