Page 445 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 22 Soft Tissue Sarcomas 423

postoperatively. In another study investigating the effects of che- excision and treated with postoperative RT and chemotherapy
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motherapy in cats treated with surgery and postoperative RT, local with an MST of 29 months compared with 5 months for cats
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treated with surgery and postoperative RT.
tumor recurrence occurred in 28% of 25 cats with a median time to
VetBooks.ir first recurrence not reached in cats treated with surgery and RT alone cats treated with curative-intent surgery and RT. 214,226,232,233,243
Postoperative chemotherapy has minimal effect on survival in
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and 661 days in cats also treated with DOX. In a study of 46 cats
treated with surgery and curative-intent postoperative RT, the median Chemotherapy may, however, have beneficial effects on local
PFI was 37 months, with 1- and 2-year progression-free rates of 63% tumor control and time to local tumor recurrence. DOX and
and 60%, respectively. In comparison, 27 cats treated with post- liposome-encapsulated DOX significantly prolonged DFI after
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operative palliative hypofractioned protocols had a median PFI of 10 surgery, with a median DFI of 393 days for cats receiving che-
months and a MST of 24 months. Importantly, RT should start motherapy and 93 days for those in which chemotherapy was not
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10 to 14 days postoperatively as DFI and ST decreases as the interval administered. 243 The completeness of surgical margins may be a
between surgery and starting RT increases. Local tumor recurrence confounding factor in this analysis because the median DFI was
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does not influence ST and, regardless of the timing of RT relative to greater than 449 days in cats with complete surgical margins com-
surgery, survival data are encouraging with MSTs of 600 to 1307 days pared with 281 days after incomplete resection. 243 Chemotherapy
and 1-, 2-, and 3-year survival rates of 86%, 44% to 71%, and 28% has also been reported to affect MST but not DFI in cats treated
to 68%, respectively. 213,232–235 with hypofractionated RT for gross disease. 235 Carboplatin was
Local tumor control is still disappointing with 28% to 45% associated with an insignificant but numerically superior median
of tumors recurring after multimodality treatment with surgery DFI of greater than 986 days in cats treated with preoperative RT
using 2- to 3-cm lateral margins and RT. 213,232–236 The radia- and surgery. 234 Other studies have shown no effect of adjunctive
tion field used in these studies typically included a minimum of chemotherapy on either local tumor control or ST. 232,233
3-cm margins around the tumor or surgical scar. The majority of The tyrosine kinase inhibitors toceranib phosphate (Palla-
tumors recur within the radiation field, although tumors have dia), masitinib mesylate (Kinavet/Masivet), and imatinib mesyl-
been reported to recur outside the radiation field. 234 Similar to ate (Gleevec) have also been investigated for the therapy of
surgery alone, a more aggressive approach may be warranted to ISSs in cats based on dysregulation of PDGFR in feline ISS cell
improve local tumor control, such as higher radiation doses, larger lines. 245,246,247,248 Imatinib has been shown to result in inhibition
radiation fields, and more aggressive surgical resections. of the PDGF/PDGFR pathway and results in chemosensitiza-
tion of feline ISS cells. 245 Masitinib also resulted in inhibition of
Radiation Therapy for Gross Disease PDGFR and cellular proliferation in feline ISS cell lines, but at
Although RT alone is rarely effective for the management of cats doses that were higher than those readily achievable clinically. 246
and dogs with measurable STSs, RT may have a role in the pal- Masitinib was also investigated as a radiation sensitizer in feline ISS
liative setting for cats with large and unresectable ISSs. In a pilot cell lines, but was not found to result in sensitization in vitro. 247
study of 10 cats with ISSs, 7 cats achieved partial responses and 2 Finally, toceranib was administered to 18 cats with unresectable
cats had complete responses after treatment with liposomal DOX ISSs and, although well tolerated at doses commonly administered
as a radiation sensitizer and irradiation with a median of 5 fractions in dogs, responses were not documented. 248
of 4 Gy for a total dose of 20 Gy; however, PFIs were not durable Novel treatments such as electrochemotherapy and immuno-
(median of 117 days). 237 Similar findings were reported in 17 cats therapy are also being investigated with some encouraging results.
with gross disease treated with 4 fractions of 8 Gy for a total dose In one study, cats with high-grade STSs were treated either intraop-
of 32 Gy in which the median PFI was 4 months and MST was 7 eratively or postoperatively with intratumoral bleomycin followed
months. 235 Stereotactic RT (SRT) has also been reported in a series by eight biphasic pulses of up to 1300 V/cm. 249 The median time
of 11 cats. 238 These cats were treated with variable protocols (most to local tumor recurrence in the control (surgery only) group was 4
commonly 3 fractions of 10 Gy) with three complete and five par- months compared with 12 months for cats treated intraoperatively
tial responses documented. The median PFI was 242 days and the and 19 months for cats treated postoperatively. Of further interest,
MST was 301 days. 238 A margin for subclinical microscopic dis- the metastatic rate was only 1.7%. 249 In a second study, 64 cats with
ease was not utilized in these patients and thus the intent of SRT FSA were treated postoperatively with two rounds of electrochemo-
alone cannot be considered definitive; however, it may facilitate therapy utilizing cisplatin. 250 The local recurrence rate was 29%.
surgical resection or result in palliation of clinical signs. Minimal systemic toxicity, including pulmonary, renal, or cutaneous
toxicity, was documented in these cats. 250 It should be noted that cis-
Chemotherapy platin cannot be administered systemically in cats because cisplatin
The role of chemotherapy in the management of cats with ISS causes fatal pulmonary edema even at relatively low doses. 251
remains undefined. Metastasis has been reported in 0% to 26% Immunotherapy, using recombinant viruses expressing interleu-
of cats with ISSs, despite the aggressive histologic appearance and kin-2 (IL-2), has shown some promise in improving local tumor con-
prevalence of high-grade lesions in these tumors, with a median trol rates in cats with ISSs. After surgical resection and iridium-based
time to metastasis of 265 to 309 days. 209,210,220–222,228,230 ISS cell brachytherapy, the 1-year local tumor recurrence rate was 61% in cats
lines have shown in vitro sensitivity at clinically relevant doses to receiving no adjunctive treatment, 39% in cats administered human
DOX, mitoxantrone, vincristine, lomustine, and paclitaxel. 239–241 IL-2 using a vaccinia virus vector, and 28% with feline IL-2 using a
Clinically, partial and complete responses to DOX, either alone canary pox virus vector. In a randomized trial by the same group
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or in combination with cyclophosphamide, or lomustine have comparing surgery and brachytherapy with surgery and brachyther-
been reported in 25% to 50% of cats with gross tumors, but these apy combined with high- and low-dose IL-2 vaccine, the frequency
responses are often short-lived with a median duration of 83 to of relapse was significantly reduced in the groups receiving the IL-2
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125 days. 242–244 However, MSTs are significantly prolonged in vaccine at both 12 (52% vs 28%) and 24 months (59% vs 28%).
cats that respond to chemotherapy: 242 days for responders and This product is now commercially available in the United States and
83 days for nonresponders. 242 Furthermore, MSTs are signifi- European Union for the postoperative treatment of feline ISSs. In a
cantly increased for cats with gross residual disease after surgical phase I trial, two doses of intratumoral feline IL-2, interferon-gamma