Page 438 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

416 PART IV Specific Malignancies in the Small Animal Patient

surgery, the entire surgical site must be included in the field plus a six treatments. 165–168 Local recurrence was reported in 17% to
margin of normal tissue and this may contribute to local toxicity; 31%, and this was significantly more likely for dogs with grade III
STSs.
162–164
Wound complications are common after treatment
(2) a large number of peripheral tumor cells are inactivated (with
VetBooks.ir reduced contamination of the surgical site); and (3) tumor volume with intralesional chemotherapy and are reported in 47% to 84%
163–167
In a
15,151–153
reduction may make surgical resection less difficult.
of dogs.

randomized phase III human trial of preoperative compared with
postoperative RT, wound complications were found to be higher
in people treated with preoperative RT (35% vs 17%); however, Prognosis
OST was found to be marginally improved in patients treated Local Tumor Recurrence
with preoperative RT. 154 Other studies, including a meta-analysis
of 1098 patients, have confirmed these findings and further sug- Local tumor control is often the most challenging aspect of man-
gested that both local recurrence rates and ST may be improved in aging STSs, but this is dependent on a number of factors including
patients treated with preoperative RT. 155 Lower doses of preopera- tumor size, local tumor characteristics such as well-circumscribed
tive RT (<50 Gy) are generally used to reduce the risk of surgical or infiltrative, tumor location, histologic grade, completeness
complications. of histologic excision, and treatment methods. The overall local
recurrence rates are 0% to 5% after wide resection, 25,113 11% to
Chemotherapy 29% after marginal resection, 25,34,46,111,117,118 17% to 37% after
incomplete histologic excision and fractionated RT, 135–137 and
The role of chemotherapy in the management of dogs with STS 18% to 21% after incomplete histologic excision and hypofrac-
is controversial. The metastatic rates for dogs with grade I, II, tionated RT (see Table 22.2). 140,141 The DFIs and local tumor
and III cutaneous STSs are 0% to 13%, 7% to 27%, and 22% control rates are also similar between the different treatment
to 44%, respectively. 31,35,156 Metastasis often occurs late in the options, with a median DFI of 368 to 637 days to not reached and
course of disease, with a median time to metastasis of up to 365 disease-free rates of 89% to 93%, 78% to 82%, and 66% to 76%
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days, and this may minimize the beneficial effects of postopera- at 1, 2, and 3 years, respectively, after surgery alone 32,34,35,46,113 ; a
tive chemotherapy on the development of metastatic disease. In median DFI of 412 to more than 798 days and disease-free rates
one retrospective study of 39 dogs with grade III STSs arising of 71% to 84%, 60% to 81%, 57% to 81%, and up to 81%
from various locations, including noncutaneous and subcutane- at 1, 2, 3, and 4 years, respectively, for incomplete excision and
ous sites, treated with either surgery alone (n = 18) or surgery and fractionated RT 135,136,138 ; and a median DFI of 698 days to not
doxorubicin (DOX) (n = 21), there was no significant difference reached and disease-free rates of 81%, 73%, and 73% at 1, 2,
in survival outcomes with the addition of DOX to the treatment and 3 years, respectively, after incomplete excision and hypofrac-
protocol. 156 An alternating protocol of DOX and ifosfamide was tionated RT. 140,141 Poor prognostic factors for local tumor control
reported in 12 dogs with various STSs after surgical excision, but include large tumor size (>5 cm), infiltrative tumors, tumors in
survival outcomes were not investigated because of low case num- locations other than the limbs at or below the elbow or stifle, his-
bers. 157 DOX and ifosfamide are the most effective single agents in tologic subtypes, grade III STSs, and incomplete surgical margins.
the management of STS in humans, but meta-analyses show that In one study of 75 dogs, the local tumor recurrence rate after
single- and multiple-agent chemotherapy protocols do not signifi- incomplete histologic excision was 28% and 11 times more likely
cantly increase OST compared with surgery alone in people. 158,159 compared with STSs resected with complete histologic margins
Although adjuvant chemotherapy has not shown the same (Fig. 22.12). Complete histologic excision is significantly more
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effect on local tumor control in dogs with STSs as it does in likely when STSs are treated with wide resection rather than more
people, 158 metronomic and local chemotherapy protocols may conservative approaches, 31,32 and complete histologic excision
be effective in decreasing the rate of local tumor recurrence and is associated with long-term survival in up to 98% of dogs with
improving DFIs in dogs with STSs. Metronomic chemotherapy STSs. 31,32,35,113 Despite the importance of complete histologic
improves local tumor control in experimental and human stud- excision in the management of dogs with STSs, incomplete exci-
ies by inhibiting tumor angiogenesis and suppressing regulatory sion has infrequently been identified as a prognostic factor for local
T cells, and a similar effect was demonstrated in dogs with STSs tumor recurrence after marginal resection, 25,118 with the majority
treated with low-dose cyclophosphamide at a dose of 15.0 mg/ of studies showing no significant association between incomplete
2
2
m /day, but not 12.5 mg/m /day. 160 Clinically, metronomic che- histologic excision and local tumor recurrence. 34,46,111,117
motherapy improved ST in dogs with macroscopic STSs treated Histologic grade has an effect on local tumor recurrence both
with hypofractionated RT. 148 Although not investigated clinically, overall and after incomplete histologic excision. Grade III STSs
there may be a role for tyrosine kinase inhibitors in the manage- have a six-fold greater risk for local recurrence compared with low-
34
ment of STS because increased vascular endothelial growth factor grade tumors. In one study of 236 dogs with subcutaneous STSs
(VEGF) and VEGF receptor expression has been demonstrated treated with excisional biopsy, the local recurrence rate was 0% for
in the peri- and intratumoral regions of canine STSs. 161–163 Fur- STSs excised with complete histologic margins and 19% overall
thermore, VEGF has been postulated to have a role in the angio- for incompletely excised STSs. 118 The recurrence rate for incom-
genesis of canine STSs because serum VEGF levels decrease after pletely excised grade I, II, and III STSs was 7%, 34%, and 75%
STS excision. 164 (three of four) respectively. 118
The effect of the local release of chemotherapy on local tumor Histologic subtype may also be associated with local tumor
recurrence rates after marginal excision of STSs has been inves- recurrence; however, it is important to recognize that differenti-
tigated in dogs. Intralesional chemotherapy agents include cis- ating histologic subtypes of STSs can be problematic, even with
platin, released locally from either a biodegradable polymer or IHC. 12,114 PWTs are often associated with a low risk of local
calcium sulfate and dextran sulfate beads implanted into the sur- tumor recurrence, 12,34 whereas FSAs have been associated with a
gical bed, and 5-fluorouracil, injected weekly for a minimum of higher local recurrence rate. 32–34