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.