Page 464 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

442 PART IV Specific Malignancies in the Small Animal Patient

of dogs with oral MM owing to the high metastatic risk. Unfor- with an overall MST of 34 months. This improved prognosis
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tunately, these tumors, in dogs and people, are generally poorly may reflect the location of these lesions (lip compared with oral
cavity) or the degree of differentiation. Nuclear atypia and mitotic
responsive to cytotoxic chemotherapy and effective immuno-
VetBooks.ir therapies that result in meaningful immunologic responses in the index have also been shown to be prognostic in dogs with oral
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majority of patients are currently lacking.
MM.
In a small study of 17 dogs treated with surgery and adjuvant
carboplatin, the median PFS was 259 days (with 41% of dogs Canine Oral Squamous Cell Carcinoma
developing local tumor recurrence and 41% of dogs developing
metastasis) and the MST was 440 days. However, two recent The prognosis for dogs with oral SCC is good, particularly for
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studies have shown no benefit in STs with the use of adjunctive rostral tumor locations. Local tumor control is usually the most
chemotherapy, 40,41 with overall MSTs of 335 days and 352 days important challenge, although metastasis to the regional LNs is
in dogs that were and were not treated with systemic adjuvant reported in up to 10% of dogs and to the lungs in 3% to 36% of
therapy. 41 dogs. 24,43,76–85,179 In contrast, SCC of the tonsils and base of the
Immunotherapy holds the most promise for effective manage- tongue are highly metastatic, with metastasis reported in up to
ment in dogs with MM and this is an area of very active research 73% of dogs, and locoregional recurrence is common. 138–141,180,181
in both veterinary and physician-based oncology. The use of DNA Surgery and RT can both be used for locoregional control of oral
vaccinations with either murine or human tyrosinase in dogs with SCC in dogs. Photodynamic therapy has also been reported with
advanced stages of oral MM (clinical stage II–IV) results in MSTs of fair-to-good results in 11 dogs with smaller oral SCC. 182
224 to 389 days. 61–66 In one study of nine dogs treated with DNA Surgery is the most common treatment for nontonsillar
vaccine encoded for human tyrosinase, complete response was SCC. 13–24,74,78,79,179 Overall local recurrence rates vary from 18%
observed in one dog with lung metastasis, two dogs with stage IV to 23% 24,179 and, in one study, local recurrence was significantly
disease and bulky metastasis lived for greater than 400 days, and two associated with incomplete histologic excision. After mandibu-
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dogs with stage II or III disease died of other causes approximately lectomy, the local recurrence rate is 0% to 10% and the MST var-
500 days after treatment with no evidence of tumor at necropsy. ies from 19 to 43 months with 88% to 100%, 79%, and 58% 1-,
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The MST is significantly improved to 589 days when the primary 2-, and 3-year STs, respectively. 20,74,78,79 In comparison, the local
oral site and regional LNs are controlled with surgery or RT. In a recurrence rate is 14% to 29% after maxillectomy, with an MST
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prospective study of dogs with surgically excised stage II or III oral of 10 to 39 months and a 1-, 2- and 3-year survival rates of 57%
MM that compared 58 dogs treated with DNA vaccine encoded for to 94%, 69%, and 38%, respectively. 21,78,79 The reason for the
human tyrosinase with a historical control of 53 unvaccinated dogs, higher local control and survival rates with mandibular resections
the MST was significantly longer for dogs in the vaccinated group is probably that the rostral mandible is the most common loca-
(not reached compared with 324 days) with tumor-related deaths tion for oral SCC in dogs and complete surgical resection is more
in only 26% of vaccinated dogs compared with 64% of unvac- likely for these rostral tumors. However, tumor location (both
cinated dogs. In two prospective studies investigating human mandibular vs. maxillary and location within the oral cavity) was
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recombinant chondroitin sulfate proteoglycan-4 DNA–based elec- not prognostic after surgical excision in three recent studies. 77–79
trovaccination after surgical resection in dogs with stage II or III In one study, the MST for untreated dogs was 54 days, with a 0%
oral MMs, the survival outcomes were significantly longer in vacci- 1-year survival rate. In comparison, the 1-year survival rate for
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nated dogs. 67,68 For vaccinated and unvaccinated dogs, respectively, dogs with surgically excised oral SCC was 94%, with MSTs not
the local recurrence rates were 21% to 35% and 39% to 42%; the reached for dogs with stage I oral SCC and 420, 365, and 50 days
metastatic rates were less than 36% and 79% to 90%; the 6-month for dogs with stage II, III, and IV oral SCC, respectively. The
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survival rates were 96% to 100% and 63% to 69%; the 12-month presence of tumor-associated inflammation and risk score of 2 or
survival rates were 64% to 74% and 15% to 26%; the 24-month ≥3 (combination of tumor-associated inflammation, lymphatic or
survival rates were 30% and 5%; the median disease-free intervals vascular invasion, and peripheral nerve invasion) were associated
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(DFIs) were 477 days and 180 days; and the MSTs were 653 to 684 with a significantly worse prognosis. In two studies of dogs with
days and 200 to 220 days. 67,68 For vaccinated dogs, outcomes were surgically resected mandibular and maxillary SCC, overall median
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significantly better for dogs weighing less than 20 kg. A thorough disease-free STs were not reached with 1- and 2-year disease-free
discussion of MM and its prognosis after definitive treatment with survival rates of 75% to 79% and 61% to 76%, respectively. 76,179
surgery, RT, chemotherapy, and/or immunomodulatory agents is The median disease-free survival was significantly shorter for dogs
provided in Chapter 20. with grade III SCCs (138 days) and SCCs with a proliferating cell
The location of MM may also have some prognostic signifi- nuclear antigen expression greater than 65% (155 days) compared
cance. Melanomas of the lip and tongue may have a lower meta- with dogs with grade II SCCs and SCCs with a proliferating cell
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static rate, with survival more dependent on local control of the nuclear antigen expression ≤65% (not reached). In one study,
tumor. In one series of 60 dogs with oral MMs at various sites incomplete histologic margins were associated with a significantly
treated with combinations of surgery, RT, chemotherapy, and worse outcome (MST 1140 days compared with not reached for
immunotherapy, the MST for dogs with lip and tongue MMs was dogs with complete histologic excision), but dogs with incomplete
580 days and was greater than 551 days, respectively. In compari- histologic margins treated with adjuvant hypofractionated RT
9
son, the MST was 319 days for maxillary MMs and 330 days for were significantly less likely to die of tumor-related reasons than
9
MMs of the hard palate. In another study, the MST was signifi- dogs not treated with adjuvant RT. 179
cantly longer for dogs with labial mucosal MMs (310 days) than Full-course RT, either alone or as an adjunct after incomplete
mandibular and maxillary MMs (123 days). 38 surgical resection, is also a successful treatment modality for the
In another study, only 5% of 64 dogs with well-differentiated management of oral SCC in dogs. 43,80,81,179 The local tumor recur-
melanomas of the mucous membranes of the lips and oral cavities rence rate is 31%. 80,81 The MST for RT alone is 15 to 16 months
treated with surgery alone had died from tumor-related causes, and increases to 34 months when combined with surgery. 80,81