Large-fraction radiation therapy can be used as a primary treatment option for oral melanoma or for palliation of any oral
tumor that is too large to surgically resect. Radiation can also be used in a definitive setting as an adjunct therapy after
surgery with incomplete margins.
Melanoma. Previously considered resistant to radiation therapy, melanomas were discovered to be sensitive to large doses, or coarse
fractions, of ionizing radiation when used as a primary treatment (Figure 6).9,14,42-44 Patients that underwent coarse fractionation not only had good responses but also had limited to no local radiation reactions.
This discovery in dogs was made when patients with large, nonresectable tumors were treated with large fractions of radiation
in a palliative attempt. In five studies reporting on 245 dogs with melanoma treated with various large-fraction radiation
protocols, the MST ranged from seven to 12 months.9,14,42-44 Overall response rate was reported for 53 dogs in two of the studies and was 77% to 94%, with 53% to 69% having complete
6. The same dog as in Figure 1 two months after coarse-fraction radiation therapy.
One of the five studies evaluated 140 dogs, 92 of which (66%) had macroscopic disease before starting radiation therapy.9 Several different radiation protocols were evaluated, including fractions of 10 Gy weekly for three weeks, 9 Gy weekly for
four weeks, or 2 to 4 Gy daily for 12 to 19 total days.9 No significant survival advantage or response was found between these three protocols.
This same study identified three risk factors that affected the prognosis in these dogs: rostral vs. caudal location, microscopic
vs. macroscopic disease volume, and the absence vs. presence of bone lysis.9 Dogs with no risk factors (rostral microscopic tumor with no bone lysis) had a MST of 21 months. Survival times decreased
with increasing numbers of risk factors with a MST of 11, five, and three months for one, two, and three risk factors present,
The longest reported MST without segregating for risk factors (12 months) was found in 39 dogs that had tumor debulking surgery
followed by large-fraction radiation in conjunction with low-dose cisplatin or carboplatin for radiation sensitization.44 Whether the surgical debulking or the chemotherapy extended these patients' survival times or whether this is a normal variation
with small sample sizes cannot be determined.
These studies reveal that coarse-fraction radiation therapy as a first- or second-line treatment is comparable to surgical
resection in terms of local tumor control and survival time in dogs with melanoma.
Squamous cell carcinoma. Radiation therapy is used most commonly as an adjunctive treatment after incomplete surgical removal for nontonsillar squamous
cell carcinoma, but it can also be a primary modality if surgery is not an option. A radiation protocol using 4 Gy per fraction
for a total of 48 Gy for macroscopic squamous cell carcinoma in 39 dogs provided reasonable local control, without complete
remission, with a median progression-free survival of 36 months.19 Another study evaluated 14 dogs treated with megavoltage radiation of 3 or 4 Gy fractions for a total dose between 48 and
57 Gy.45 Six of the 14 dogs had previous surgeries, but all had gross disease at the time of radiation treatment. The MST for all
dogs was 15 months. The MST of dogs > 9 years old was 10.5 months vs. 36 months for dogs < 9 years. Age-related complications
were suggested as a possible cause of this survival disparity. Because of small case numbers, no other prognostic factors
Radiation after surgery for tonsillar squamous cell carcinoma was reported in eight dogs, seven of which had lymph node metastases
that were not surgically excised.27 Dogs were treated on a Monday-Wednesday-Friday basis with a total dose ranging from 35 to 42.5 Gy. The MST for these eight
patients was 3.6 months.27 Widespread metastasis occurred in all of the cases, supporting the need for systemic therapy as well as local therapy in
Fibrosarcoma. Fibrosarcomas are, unfortunately, considered relatively radioresistant. A protocol of 4 Gy Monday, Wednesday, and Friday
for a total of 48 Gy was used to treat 28 dogs with macroscopic fibrosarcoma and provided a median progression-free survival,
without complete remission, of 26 months.19 The median progression-free survival decreased with increasing tumor stage, with T1, T2, and T3 tumors having a median progression-free
survival of 45, 31, and seven months, respectively. Thus, larger fibrosarcomas are not only harder to resect but are also
less likely to be treated successfully with radiation therapy.
A separate study evaluating the use of radiation at 3 to 4.2 Gy daily for a total of 42 to 57 Gy for microscopic residual
tumor after incomplete surgical resection of seven oral fibrosarcomas and one anaplastic oral sarcoma showed a MST of 18 months.30 It is odd that dogs treated for microscopic fibrosarcoma had shorter survival times than those treated for T1 or T2 bulky
tumors. The authors of the microscopic residual disease study commented that the behavior of those particular tumors was similar
to the aggressive histologically low-grade, biologically high-grade tumors; this variant of fibrosarcoma may be the reason
for the disparity in results. Additionally, dogs with fibrosarcoma involving full thickness of the associated bone were excluded
from the macroscopic disease study; thus, a selection bias may exist in this study, leading to longer survival times.