Outcomes following surgical excision or surgical excision combined with adjunctive, hypofractionated radiotherapy in dogs with oral squamous cell carcinoma or fibrosarcoma

Julia Riggs Queen's Veterinary School Hospital, Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES England.

Search for other papers by Julia Riggs in
Current site
Google Scholar
PubMed
Close
 MA, VetMB
,
Vicki J. Adams Vet Epi, Abbey Farm Cottage, Heath Rd, Ixworth, Suffolk, IP31 2JP England.

Search for other papers by Vicki J. Adams in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Joanna V. Hermer Queen's Veterinary School Hospital, Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES England.

Search for other papers by Joanna V. Hermer in
Current site
Google Scholar
PubMed
Close
 BVM&S
,
Jane M. Dobson Queen's Veterinary School Hospital, Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES England.

Search for other papers by Jane M. Dobson in
Current site
Google Scholar
PubMed
Close
 MA, DVetMed
,
Suzanne Murphy Animal Health Trust, Lanwades Park, Newmarket, CB8 7UU England.

Search for other papers by Suzanne Murphy in
Current site
Google Scholar
PubMed
Close
 BVM&S, MSc
, and
Jane F. Ladlow Queen's Veterinary School Hospital, Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES England.

Search for other papers by Jane F. Ladlow in
Current site
Google Scholar
PubMed
Close
 MA, VetMB

Abstract

OBJECTIVE To compare outcomes of dogs treated surgically for oral, nontonsillar, squamous cell carcinomas (SCCs) and fibrosarcomas (FSAs) with outcomes of dogs treated with a combination of surgery and postoperative radiotherapy; to explore whether postoperative, hypofractionated radiotherapy improved outcomes of dogs with incomplete excisions; and to identify prognostic factors associated with outcome.

DESIGN Retrospective cohort study.

ANIMALS 87 client-owned dogs that had undergone maxillectomy or mandibulectomy for treatment of oral SCC or FSA between 2000 and 2009.

PROCEDURES Medical records were retrospectively reviewed. Survival analysis was performed with Kaplan-Meier and Cox regression analyses to evaluate potential prognostic factors associated with patient outcome.

RESULTS Median survival time (MST) for all 87 dogs was 2,049 days, but was not reached for dogs with SCC, and was only 557 days for dogs with FSA; tumor type was a significant predictor of survival time. Dogs undergoing postoperative radiotherapy after incomplete excision of oral SCCs had a significantly longer MST (2,051 days) than did dogs with incompletely excised tumors and no radiotherapy (MST, 181 days). Postoperative radiotherapy of dogs with incompletely excised FSAs did not appear to offer protective value (MST, 299 days with radiotherapy and 694 days without radiotherapy).

CONCLUSIONS AND CLINICAL RELEVANCE Wide-margin surgical excision should be considered the gold-standard treatment for dogs with oral SCC or FSA. For dogs with oral SCCs without clean surgical margins, survival times may be improved by providing postoperative, hypofractionated radiotherapy.

Abstract

OBJECTIVE To compare outcomes of dogs treated surgically for oral, nontonsillar, squamous cell carcinomas (SCCs) and fibrosarcomas (FSAs) with outcomes of dogs treated with a combination of surgery and postoperative radiotherapy; to explore whether postoperative, hypofractionated radiotherapy improved outcomes of dogs with incomplete excisions; and to identify prognostic factors associated with outcome.

DESIGN Retrospective cohort study.

ANIMALS 87 client-owned dogs that had undergone maxillectomy or mandibulectomy for treatment of oral SCC or FSA between 2000 and 2009.

PROCEDURES Medical records were retrospectively reviewed. Survival analysis was performed with Kaplan-Meier and Cox regression analyses to evaluate potential prognostic factors associated with patient outcome.

RESULTS Median survival time (MST) for all 87 dogs was 2,049 days, but was not reached for dogs with SCC, and was only 557 days for dogs with FSA; tumor type was a significant predictor of survival time. Dogs undergoing postoperative radiotherapy after incomplete excision of oral SCCs had a significantly longer MST (2,051 days) than did dogs with incompletely excised tumors and no radiotherapy (MST, 181 days). Postoperative radiotherapy of dogs with incompletely excised FSAs did not appear to offer protective value (MST, 299 days with radiotherapy and 694 days without radiotherapy).

CONCLUSIONS AND CLINICAL RELEVANCE Wide-margin surgical excision should be considered the gold-standard treatment for dogs with oral SCC or FSA. For dogs with oral SCCs without clean surgical margins, survival times may be improved by providing postoperative, hypofractionated radiotherapy.

The oral cavity is the fourth most common site for development of malignant tumors in dogs, accounting for 5% to 7% of all neoplasms.1–3 After melanomas, nontonsillar SCCs (prevalence range, 17% to 28%) and FSAs (prevalence range, 8% to 25%) are the second and third most common types of malignant oral neoplasms encountered.1–3 Although the rate of distant metastasis is relatively low for both tumors (unlike that of oral malignant melanomas), local invasion into the underlying bone is frequently documented regardless of tumor location in the oral cavity,1,4 and local tumor recurrence (up to 58%) is thought to be a major cause of treatment failure.4–10 Therefore, aggressive local treatment is important in successful management of patients with nonmelanotic oral malignancies. Radical surgical excision (ie, mandibulectomy or maxillectomy) constitutes the treatment of choice, with the aim of incorporating a minimum 1-cm margin of grossly normal tissue surrounding the mass.11 The rostral aspect of the oral cavity appears to be a predilection site for SCC in dogs, and wide-margin excision of smaller masses in this location may be achieved without compromising function or cosmesis.4,7 However, wide-margin excision of tumors that are larger or that are located more caudally in the oral cavity may be limited by anatomic constraints.11–15 Extirpation of the local LNs for which metastasis is evident has also been advocated.1

Historically, outcomes following mandibulectomy or maxillectomy for SCC have been reported4,5-9 to include MSTs of 3.5 to 19.2 months, a disease-free interval of 26 months, and 1-year survival rates of 57% to 91%. However, more recent results for SCC treatment outcomes have been reported16 and include more optimistic rates, such as a 1-year survival rate of 93.5% for 21 dogs that had undergone curative-intent surgery and an MST of 365 days for dogs > 10 years old. As for patients with oral FSA for which surgical excision was the sole treatment modality, investigators have reported5–10,13,17 MSTs of 7 to 33.7 months and 1-year survival rates of 21% to 50%.

For dogs with oral SCCs and FSAs in which surgery is not feasible because of tumor location or size or in which surgery has been declined, radiotherapy has been advocated as an alternative treatment option. The use of orthovoltage radiotherapy alone for treatment of oral SCC has been reported,18,19 with MSTs of 1.5 to 58 months and a median progression-free survival time of 36 months. The use of radiotherapy alone, but with various protocols, for oral FSAs has been associated with poorer outcomes (eg, MSTs of 6 to 16 months),17,20,21 compared with results for surgery alone.

Few reports describe surgery combined with adjuvant radiotherapy for dogs with oral SCC or FSA, and the benefit of such combination therapy has remained poorly defined. In a study22 of 14 dogs that had undergone radiotherapy of an oral SCC, 6 had undergone previous surgery for the condition; however, previous surgery did not affect overall survival time, compared with that for other dogs in the study.

Although combining surgery and adjuvant radiotherapy has been acknowledged10,17,23-25 to provide good outcomes in managing soft tissue sarcomas in locations other than the oral cavity, the authors found only 2 recent studies10,17 in which this combination approach for FSAs of the oral cavity has been explored. In these studies,10,17 MSTs of 505 days (n = 28 dogs) and 576 days (8) were reported; however, the surgical and radiotherapy treatment protocols were not standardized, and the influence of surgical margin status on therapeutic decision-making was not stated.

The objectives of the study reported here were to identify factors associated with outcome of dogs with oral SCCs or FSAs and to compare long-term outcome for dogs treated by means of curative-intent surgery alone with long-term outcome for dogs treated with a combination of curative-intent surgery and postoperative, hypofractionated radiotherapy.

Materials and Methods

Case selection

Medical records of dogs with oral SCC or FSA in which treatment included curative-intent surgery at either of 2 referral institutions (The Queen's Veterinary School Hospital, Cambridge, and The Animal Health Trust, Newmarket) between January 1, 2000, and October 31, 2009, were retrospectively reviewed. Dogs were included in the study if they had undergone LN palpation and aspiration as part of their preoperative physical examination, orthogonal radiographic views of the thorax had been obtained at the time of referral, and surgery had been performed by a board-certified surgeon of the European College of Veterinary Surgeons. Dogs with evidence of distant tumor metastasis during staging were excluded from the study. Curative-intent surgery was defined as planned surgical margins incorporating 1 to 2 cm of bone beyond the gross tumor margin or the margin of bone lysis visible on preoperative radiographic or MRI images. Dogs were excluded from analysis if they were lost to follow-up within a month after surgery.

Medical records review

Data abstracted from the medical records included patient signalment (eg, age at the time of surgery, breed, and sex [including neuter status]); dates of clinical onset, diagnosis, referral, surgery, and last follow-up; tumor type, location, size, and histopathologic grade and differentiation; completeness of resection as determined by margin assessment; local LN status before surgery; extent of bone lysis visible on radiographs or MRI images; and whether the patient underwent postoperative radiotherapy. Tumors of the mandible or maxilla located rostral to the first premolar tooth were defined as rostral; those located between the first premolar tooth and last molar tooth were defined as central; and those located caudal to the last molar tooth, along with central and rostral tumors with a caudal margin beyond the last molar tooth, were defined as caudal. Results of histopathologic examination of the excised tumor and bone (mandible or maxilla) from each dog performed by a board-certified pathologist were reviewed to determine the type of tumor and assess the margins. If the tumor extended to the margin of a specimen, the margin was defined as dirty. If a narrow (< 3 mm) rim of healthy tissue existed between the tumor and the margin of a specimen, the margin was defined as narrow. If there were no tumor cells present within 3 mm of the margin, the margin was defined as clean.

Adjunctive radiotherapy had been offered to all patients for which narrow or dirty margins were reported on histopathologic assessment and for which the tumor was deemed intermediately or poorly differentiated irrespective of margin status. The affected LNs were extirpated and submitted for histopathologic examination only for patients with cytologic evidence of metastasis to local LN. No patients received systemic chemotherapy, and owner consent had been obtained for all procedures conducted.

Radiotherapy

For dogs that underwent radiotherapy, megavoltage radiation was delivered with a 4-MV, external beam, linear accelerator.a Total radiotherapy doses of 32 to 36 Gy were delivered to the target volume in each dog as 4 fractions of 8 to 9 Gy/fraction administered at 7-day intervals (days 0, 7, 14, and 21). The treatment plan for each patient established the clinical target volume, delineated by 2- to 3-cm margins around the surgical scar laterally and at least 1 cm at the deep margin. Radiation was delivered from a single perpendicular port with manual, nongraphic planning to deliver at least 95% of the applied dose to the entire target volume. Tissue-equivalent boluses to a 0.5- or 1.0-cm depth were used for superficial sites.

Because the linear accelerator was not equipped with a multileaf collimator, all radiotherapy treatment fields were square or rectangular. Lead blocks were used to shield vital or sensitive structures (eg, eyes), but not at the cost of compromising radiation delivery to the target volume.

Follow-up

Long-term outcome was determined through repeated telephone interviews with referring veterinarians and owners. Each patient's status at the time of telephone interview was recorded along with, for dogs that were still alive, whether there was any evidence of tumor recurrence or metastasis after surgery. For dogs that were dead, the date and cause of death were recorded.

Dogs were considered to have died of tumor-related reasons if they were lost to follow-up but had evidence of recurrence or metastasis prior to this time or if they had died or been euthanized for reasons related to their tumor (eg, complications of treatment, documented tumor regrowth at the same location in the oral cavity, or metastasis in the absence of an identified, separate, neoplastic process). The censor date for survival analysis was October 22, 2014. Dogs that were still alive at this time without evidence of tumor recurrence or metastasis, that had been lost to follow-up with no evidence of tumor recurrence or metastasis, or that had died of other causes were censored.

Statistical methods

Survival analysis for all dogs that met the inclusion criteria and for each tumor type separately was performed with commercial software.b Initially, univariable Kaplan-Meier survival analysis was used to estimate survival times and to test for the effects of tumor type and 10 other potential explanatory variables on survival time. During the analysis, the authors created another variable that combined the original variables of margins and radiotherapy. Variables with P ≤ 0.1 in univariable analysis were considered for inclusion in multivariable Cox proportional hazards analysis with manual backward stepwise regression. Significance was set at P < 0.05 for the final model. Descriptive statistics were presented as median (range [minimum to maximum]) for continuous variables and as frequencies for categorical variables. Estimated MSTs and HRs were reported with 95% CIs, with the upper limit reported as not estimable when the statistical software could not estimate a confidence limit. When an MST was not reached, mean survival time from the Kaplan-Meier survival analysis was reported. Mean survival times and survival probabilities (eg, 1-year and 2-year survival probabilities) were reported with SEs.

Results

Records of 89 client-owned dogs that had undergone curative-intent maxillectomy or mandibulectomy for treatment of oral SCC or FSA during the study period at the 2 involved veterinary centers were reviewed. Some, but not all, dogs had undergone preoperative radiography or MRI of their skulls to facilitate surgical planning.

Two patients with FSA were excluded from the study because they were lost to follow-up 5 and 18 days after surgery, leaving a final total of 87 cases (SCC, n = 39; FSA, 48) for analyses. All 87 patients had been followed for at least 1 month after surgery, with follow-up time after surgery ranging from 37 to 2,815 days. The group of 87 dogs had a median disease-free interval of 594 days; an MST of 2,049 days (range, 591 days to not estimable); and survival probabilities for the first, second, third, and sixth years after surgery of 0.70 (SE, 0.05), 0.59 (SE, 0.06), 0.55 (SE, 0.06), and 0.45 (SE, 0.09), respectively. For all dogs, univariable survival analyses identified several variables of possible prognostic importance (Tables 1–3). Owing to the strong association between tumor type and survival time, multivariable Cox regression analyses were not performed for all tumors combined.

Table 1—

Results of univariable Kaplan-Meier analysis of survival times for 87 dogs with nonmelanotic, nontonsillar oral SCCs and FSAs that underwent curative-intent surgical excision with or without postoperative, hypofractionated radiotherapy.

    Survival time (d) 
VariableCategoryNo. of dogsNo. (%) of censored cases*MeanMedian (95% CI)Log-rank P value
Tumor type     0.01
 FSA4822 (46)1,259557 (327-NE) 
 SCC3928 (72)1,692NR 
Sex     0.4
 Female4222 (52)1,5431,069 (NE) 
 Male4528 (62)1,4692,051 (760–3,342) 
Neuter status     0.1
 No4119 (46)1,349963 (207–1,720) 
 Yes4631 (67)1,652NR 
Age at surgery (y)     0.5
 < 83820 (53)1,460NR 
 ≥ 84930 (61)1,541NR 
Affected bone     0.01
 Mandible3424 (71)1,998NR 
 Maxilla5326 (49)1,119594 (0–1,339) 
Oral cavity location     0.001
 Caudala248 (33)903327 (277–377) 
 Central2110 (48)1,1221,069 (0–2,160) 
 Rostrala4031 (78)2,200NR 
Tumor length (cm)     0.008
 < 2a,b2118 (86)1,936NR 
  4021 (53)1,4491,069 (471–1,667) 
 > 4b125 (42)1,046299 (0–1,272) 
LN affected     < 0.001
 No8450 (60)1,666NR 
 Yes30 (0)174197 (37–357) 
Surgical margin     0.002
 Cleana,b4333 (78)2,165NR 
 Narrowa81 (13)477333 (165–501) 
 Dirtyb2611 (42)1,069694 (0–1,702) 
 Unknown105 (50)1,208524 (NE) 
Radiotherapy     0.005
 No5839 (67)1,927NR 
 Yes2911 (38)927521 (153–889) 
Margin status X radiotherapy     0.001
 Cleana,b4333 (77)2,165NR 
 Narrow or dirty, RTa229 (41)1,024549 (126–1,062) 
 Narrow or dirty, no RTb123 (25)659268 (0–580) 
Bone lysis     0.006
 No99 (100)NENE 
 Yes3616 (44)NENE 

Dogs were censored if they were lost to follow-up with no evidence of tumor recurrence or metastasis, were still alive at the censor date without evidence of tumor recurrence or metastasis, or had died of causes that were not tumor related.

NR = Not reached. NE = Not estimable. RT = Radiotherapy.

Categories with the same superscript letters had significantly (P < 0.01) different survival times in pairwise comparisons.

Table 2—

Results of univariable Kaplan-Meier analysis of survival times for 39 dogs with nonmelanotic, nontonsillar oral SCCs that underwent curative-intent surgical excision with or without postoperative, hypofractionated radiotherapy.

    Survival time (d) 
VariableCategoryNo. of dogsNo. (%) of censored cases*MeanMedian (95% CI)Log-rank P value
Sex     0.8
 Female2216 (73)1,693NR 
 Male1712 (71)1,605NR 
Neuter status     0.1
 No158 (53)1,4352,051 (377–3,726) 
 Yes2420 (83)1,879NR 
Age at surgery (y)     0.6
 < 8129 (75)1,821NR 
 ≥ 82719 (70)1,628NR 
Affected bone     0.26
 Mandible1613 (81)1,870NR 
 Maxilla2313 (65)1,540NR 
Oral cavity location     0.14
 Caudal95 (56)1,220NR 
 Central63 (50)1,4672,051 (NE) 
 Rostral2420 (83)1,923NR 
Tumor length (cm)     0.07
 < 21111 (100)NENR 
 2-1149 (64)1,414NR 
 > 453 (60)1,595NR 
LN affected     0.001
 No3728 (76)1,776NR 
 Yes20 (0)16397 (NE) 
Surgical margin     0.005
 Clean2220 (91)1,982NR 
 Narrow or dirty135 (39)1,1371,140 (0–2,442) 
 Narrow10 (0)268268 (NE) 
 Dirty125 (42)1,2101,140 (0–3.008) 
 Unknown43 (75)1,730NR 
RT     0.3
 No2721 (78)1,787NR 
 Yes127 (58)1,4562,051 (0–5,080) 
Margin status X radiotherapy     < 0.001
 Cleana2220 (91)1,982NR 
 Dirty, RTb85 (63)1,6732,051 (NE) 
 Narrow or dirty50 (0)349181 (0.7–361) 
 no RTa,b     
Bone lysis     0.13
 No66 (100)NENE 
 Yes149 (64)NENE

See Table 1 for key.

Table 3—

Results of univariable Kaplan-Meier analysis of survival times for 48 dogs with oral FSAs that underwent curative-intent surgical excision with or without postoperative, hypofractionated radiotherapy.

    Survival time (d) 
VariableCategoryNo. of dogsNo. (%) of censored cases*MeanMedian (95% CI)Log-rank P value
Sex     0.05
 Female206 (30)782327 (243–411) 
 Male2816 (57)1,364963 (NE) 
Neuter status     0.9
 No2611 (42)1,149594 (363–825) 
 Yes2211 (50)1,188420 (104–736) 
Age at surgery (y)     0.6
 < 82611 (42)1,163521 (216–827) 
 ≥ 82211 (50)1,228694 (93–1296) 
Affected bone     0.01
 Mandible1811 (61)1,830NR 
 Maxilla3011 (37)602327 (277–377) 
Oral cavity location     0.045
 Caudala153 (20)744327 (284–370) 
 Central157 (47)797963 (0–370) 
 Rostrala1611 (67)1,889NR 
Tumor length (cm)     0.02
 < 2a107 (70)1,363NR 
 2–42612 (46)1,176591 (248–934) 
 > 4a72 (29)520235 (138–333) 
LN affected     0.02
 No4722 (47)1,283591 (386–796) 
 Yes10 (0)197NR 
Surgical margin     0.07
 Clean2113 (63)1,748NR 
 Narrow71 (14)507420 (197–643) 
 Dirty146 (43)743299 (0–679) 
 Unknown62 (33)409235 (0–540) 
Radiotherapy     0.01
 No3118 (58)1,632NR 
 Yes174 (24)497333 (259–407) 
Margin status X radiotherapy     0.02
 Cleana2113 (62)1,748NR 
 Narrow or dirty, RTa144 (29)467299 (234–364) 
 Narrow or dirty, no RT73 (43)887694 (132–1256) 
Bone lysis     0.04
 No33 (100)NENE 
 Yes227 (32)972420 (32–808) 

See Table 1 for key.

SCC

Two of the 39 dogs with oral SCC had evidence of metastases to local LNs at the time of surgery and had caudally located primary tumors involving the maxilla. One of these 2 dogs underwent maxillectomy, unilateral mandibular lymphadenectomy, and postoperative radiotherapy, but subsequently developed pulmonary metastases and was euthanized 228 days after surgery. The other underwent surgery alone and developed an infection as a complication of treatment. No other complications related to surgery were recorded for this group.

Follow-up times for the 39 dogs with oral SCC ranged from 37 to 2,266 days, with a median disease-free interval of 1,047 days. Median follow-up time for the 11 dogs that died of tumor-related reasons was 181 days (range, 37 to 2,051 days) and was 1,191.5 days (range, 100 to 2,266 days) for the 28 dogs that were censored. The MST after surgery for dogs with oral SCC was not reached. The 1-year survival probability was 0.79 (SE, 0.07), and the survival probability was 0.76 (SE, 0.07) at 2 and 3 years after surgery, 0.53 (SE, 0.08) at 4 and 5 years after surgery, and 0.28 (SE, 0.14) at 6 years after surgery, with 4 dogs still alive at that time. The last dog alive at the censor date had survived 6 years and 7 months after surgery. Dogs with clean surgical margins had significantly (P = 0.005) longer survival times (MST not reached), compared with survival times for dogs with narrow or dirty surgical margins (MST, 1,140 days). The presence of LN metastases prior to surgery was also significantly (P = 0.001) associated with shorter survival times (Table 2).

Local recurrence of SCC occurred in 9 of the 39 (23%) dogs. Six of these 9 dogs subsequently died of tumor-related reasons, 2 were lost to follow-up, and 1 was euthanized for an unspecified reason not thought to be related to SCC. Two dogs developed metastases; one dog had metastasis to the lungs and local LNs, and another had metastasis to the lungs only. Both of these dogs died of tumor-related reasons.

Twelve of the 39 (31%) dogs with SCC underwent postoperative radiotherapy (rostral, n = 4; central, 4; and caudal, 4). Although 8 of these 12 dogs had dirty surgical margins, MST for all 12 dogs was 2,051 days (Table 2). Two of the 12 dogs had clean surgical margins, and margin status of the remaining 2 dogs was unknown. The 2 dogs with clean margins and 2 dogs with unknown margins had tumors described as intermediately or poorly differentiated SCC. No short- or long-term adverse effects of radiotherapy were documented in the patient records, and there was no indication that any of the dogs received chemotherapeutic agents, including NSAIDs.

Initially, postoperative radiotherapy was not identified as a significant (P = 0.3) prognostic indicator for oral SCC treatment outcome when it was considered as an isolated factor in univariable analysis. However, when a variable combining margin status and radiotherapy was created, a significant (P < 0.001) effect of postoperative radiotherapy on the outcomes of dogs with narrow or dirty surgical margins was identified (Table 2; Figure 1). Dogs that had narrow or dirty surgical margins but that did not receive radiotherapy were significantly (P = 0.025) more likely (HR, 6.3; 95% CI, 1.3 to 31) to die of tumor-related reasons than were dogs with dirty surgical margins that underwent radiotherapy (Table 4). Multivariable Cox regression analyses did not identify any variables that were associated with survival time while controlling for potential confounding effects of other variables, although the combination variable for margin status and radiotherapy had the strongest association with survival time.

Figure 1—
Figure 1—

Kaplan-Meier plot of survival time after surgery for 35 dogs with oral, nontonsillar SCCs that underwent curative-intent surgical excision and had clean surgical margins (dashed line; n = 22 [2 dogs with poorly differentiated tumors that underwent postoperative hypofractionated radiotherapy {RT} and 20 dogs that did not undergo postoperative RT]), had narrow or dirty surgical margins and underwent postoperative hypofractionated RT (dotted line; 8), or had narrow or dirty surgical margins but did not undergo postoperative RT (solid line; 5). Tick marks represent censored dogs.

Citation: Journal of the American Veterinary Medical Association 253, 1; 10.2460/javma.253.1.73

Table 4—

Results of Cox regression analysis of the combined effects of surgical margin and radiotherapy status for 35 dogs with nonmelanotic, nontonsillar oral SCCs that underwent curative-intent surgical excision with or without postoperative, hypofractionated radiotherapy.

Margin and RT statusNo. of dogsNo. that died*HR (95% CI)P value
Clean with or without RT222ReferentNA
Dirty, RTa853.0 (0.5–20)0.25
Narrow or dirty, no RTa5319.2 (3.6–102)0.001

Two of 22 dogs with clean surgical margins underwent radiotherapy, 1 dog with narrow surgical margins did not undergo radiotherapy, and 8 of 12 dogs with dirty surgical margins underwent radiotherapy. Four dogs for which information on surgical margins was not available were not included in the analysis.

Dogs were considered to have died of tumor-related reasons if they were lost to follow-up but had evidence of recurrence or metastasis prior to this time or if they had died or been euthanized for reasons related to their tumor.

NA = Not applicable. RT = Radiotherapy.

Dogs that had narrow or dirty surgical margins but did not undergo RT were significantly (P = 0.025) more likely (HR, 6.3; 95% CI, 1.3 to 31) to die of tumor-related reasons than were dogs with dirty surgical margins that underwent RT.

FSA

One of the 48 dogs with oral FSA had evidence of metastasis to a local LN at the time of surgery; the primary tumor in this dog was poorly differentiated and caudally located. Complications of surgery for dogs with oral FSA included major hemorrhage necessitating blood transfusion (n = 1), dehiscence requiring resuturing (1), and infection (1). Eight tumors had been graded by means of the Kuntz classification system for soft tissue sarcomas (grade 1 [low grade], n = 4; grade 2 [intermediate grade], 3; and grade 1 to 2 [low-intermediate grade], 1).26 Twenty tumors were classified on the basis of histopathologic differentiation alone (well-differentiated, n = 8; intermediately differentiated, 7; and poorly differentiated, 5).

Follow-up times after surgery for the 48 dogs with oral FSA ranged from 42 to 2,815 days, with a median disease-free interval of 389.5 days. Median follow-up time was 299 days (range, 42 to 1,069 days) for the 26 dogs with FSA that died of tumor-related reasons and was 868.5 days (range, 93 to 2,815 days) for the 22 dogs with FSA that were censored. The MST after surgery for dogs with oral FSA was 557 days (range, 327 days to not estimable), and this was significantly (P = 0.01) shorter than the MST for dogs with SCC. The 1-, 2-, and 3-year survival probabilities were 0.61 (SE, 0.07), 0.42 (SE, 0.08), and 0.35 (SE, 0.09), respectively, with survival probability remaining unchanged 5 years after surgery and 9 dogs still alive at that time. The last dog alive at the censor date had survived 7 years and 9 months after surgery. Patient sex, tumor location, radiotherapy, and LN metastasis prior to surgery were significantly (P ≤ 0.045) associated with shorter survival times in univariable analysis (Table 3).

Local recurrence of FSA occurred in 18 of the 48 (38%) dogs. Fifteen of these dogs died of tumor-related reasons, and the other 3 were lost to follow-up after recurrence. Seven of the 48 dogs developed metastases to the lungs or local LNs after surgery, and all 7 were euthanized when their metastases were diagnosed.

Seventeen of the 48 (35%) dogs with FSA underwent postoperative radiotherapy (dirty margins, n = 9; narrow margins, 5; clean margins, 2; and unknown margins, 1). The 2 dogs with clean surgical margins had tumors described as intermediately or poorly differentiated. All dogs that underwent radiotherapy had maxillary tumors (caudal, n = 8; central, 6; and rostral, 3). Two dogs that underwent radiotherapy after maxillectomy developed oronasal fistulae during treatment. This complication was well tolerated by one dog, but the other dog was euthanized because of this complication 9 months after surgery. No other long-term adverse effects of radiotherapy were documented.

For dogs with FSA, postoperative radiotherapy was identified as a significant (P = 0.01) negative prognostic indicator. To further investigate this negative effect, a variable combining the margin status and radiotherapy was created. Analyses that incorporated this new variable revealed that the combination of narrow or dirty margins with radiotherapy was associated with notably poorer survival times, compared with survival times for dogs with clean surgical margins (Tables 3 and 5; Figure 2).

Figure 2—
Figure 2—

Kaplan-Meier plot of survival time after surgery for 42 dogs with oral FSAs that underwent curative-intent surgical excision and had clean surgical margins (dashed line; n = 21), had narrow or dirty surgical margins and underwent postoperative hypofractionated RT (dotted line; 14), or had narrow or dirty surgical margins but did not undergo postoperative RT (solid line; 7). Tick marks represent censored dogs. See Figure 1 for key.

Citation: Journal of the American Veterinary Medical Association 253, 1; 10.2460/javma.253.1.73

Table 5—

Results of Cox regression analysis of the combined effects of surgical margin and radiotherapy status for 42 dogs with oral FSAs that underwent curative-intent surgical excision with or without postoperative, hypofractionated radiotherapy.

Margin and RT statusNo. of dogsNo. that died*HR (95% CI)P value
Clean with or without RT218ReferentNA
Narrow or dirty, RTa1483.7 (1.4–9.8)0.009
Narrow or dirty, no RTa731.7 (0.5–5.6)0.4

Two of 21 dogs with clean surgical margins underwent radiotherapy, 5 of 7 dogs with narrow surgical margins underwent radiotherapy, and 9 of 14 dogs with dirty surgical margins underwent radiotherapy. Six dogs for which information on surgical margins was not available were not included in the analysis.

Dogs that had narrow or dirty surgical margins but did not undergo RT were not significantly (P = 0.2) more likely (HR, 2.2; 95% CI, 0.7 to 7.2) to die of tumor-related reasons than were dogs with narrow or dirty surgical margins that underwent RT.

See Table 4 for remainder of key.

Multivariable Cox regression analyses identified 2 potential models. The first model included 2 variables that were independently associated with outcome: affected bone (mandible or maxilla) and whether local LNs were affected at the time of surgery (model not shown). However, only 1 dog with FSA had affected local LNs at the time of surgery. The second model included 2 variables that were independently associated with outcome: sex of the dog and location of the tumor in the oral cavity (rostral, central, or caudal; Table 6). After adjusting for location of the tumor, female dogs were 2.5 times (P = 0.03) as likely to die of tumor-related reasons as were male dogs; however, after adjusting for sex, dogs with caudally located tumors were 4.1 times (P = 0.01) as likely to die of tumor-related reasons as were dogs with rostrally located tumors.

Table 6—

Final multivariable Cox proportional hazards regression model of the likelihood of dying of tumor-related reasons for 46 dogs with oral FSA.

    UnadjustedAdjusted 
VariableCategoryNo. of dogsNo. of dogs that diedHR (95% CI)P valueHR (95% CI)P value
Sex       
 Male2711Referent Referent 
 Female19132.2 (1.0–4.7)0.052.5 (1.1–5.7)0.03
Oral cavity location       
 Rostral165Referent Referent 
 Central1562.3 (0.7–7.0)0.152.3 (0.8–7.1)0.14
 Caudal15113.5 (1.2–9.9)0.024.1 (1.4–12.0)0.01

Two dogs for which information on oral cavity location of the tumor was not available were not included in the analysis.

Discussion

The first aim of this study was to describe the long-term outcomes of dogs undergoing curative-intent surgical treatment, with or without postoperative, hypofractionated, radiotherapy, for oral SCC and FSA. Considering both tumor types together, their combined MST was 2,049 days, and 61 of the 87 (70%) dogs were alive 1 year after surgery. When each tumor type was investigated independently, a notably longer MST and higher 1-, 2- and 3-year survival probabilities were apparent for dogs with oral, nontonsillar SCC than for dogs with oral FSA, suggesting that prognosis was dependent on tumor type. Regardless, corroborating the recent veterinary literature on oral malignancies in dogs, findings of the present study suggested that favorable outcomes could be achieved with aggressive local treatment if the tumor was amenable and metastases were not present. For both SCC and FSA, local recurrence was the predominant manifestation of treatment failure, with 9 of the 39 (23%) dogs with SCC having a local recurrence (of which 8 had dirty surgical margins) and 18 of the 48 (37.5%) dogs with FSA having recurrence (of which 10 had dirty or narrow surgical margins), and metastases were less frequently observed (2/39 [5%] dogs with SCC; 7/48 [15%] dogs with FSA). Nineteen of the 39 (49%) dogs with SCC in the present study ultimately died of causes unrelated to their tumor; however, this was the case for only 14 of the 48 (29%) dogs with FSA.

The second aim of the present study was to identify prognostic factors associated with outcome. Previous studies10,16–18,22,27 of dogs with oral SCCs and FSAs have suggested that patient age and breed; tumor location, stage, and grade; surgery type; and margin status may affect outcome. In the present study, tumor location, tumor size, local LN metastasis, incomplete excision, underlying bone involvement, and radiotherapy use were identified as prognostic factors in univariable analyses of the combined data set for nonmelanotic malignant oral tumors. Considering the SCC data in isolation, LN metastasis and incomplete excision were negative prognostic factors in univariable analyses. Although local LN involvement (ie, higher tumor stage) was anticipated to be a negative prognostic factor, it should be emphasized that LN involvement was noted in only 2 of the 39 dogs with SCC at the time of surgery and that benefits of local lymphadenectomy or LN irradiation in the treatment of locally metastasized SCC remain uncertain and warrant further investigation. Considering the FSA data of the present study in isolation, multivariable analysis revealed that female sex and caudally located tumors were negative prognostic factors. The correlation between sex and outcome was an unexpected result, which, to the authors' knowledge, has not been reported previously and may be attributed to sample size rather than a true confounding effect.

A further aim of the present study was to explore whether inclusion of postoperative, hypofractionated radiotherapy afforded any benefit for patient outcome in the eventuality of incomplete tumor excision. The results of the present study differed between oral tumor type. For SCC, adjunctive, hypofractionated radiotherapy appeared beneficial. The MST of dogs with narrow or dirty surgical margins that underwent radiotherapy was 2,051 days, whereas the MST of dogs with such margins that did not undergo radiotherapy was 181 days. Of particular note, the dog with the longest survival time at the censor date (2,266 days) had a dirty surgical margin following excision of a rostral maxillary SCC and underwent radiotherapy; no apparent recurrence or metastasis was reported before the dog was lost to follow-up. Conversely for FSA, the same radiotherapy protocol was identified as a negative prognostic indicator. This could have been attributed to the fact that, in the present study, all dogs with FSA that underwent radiotherapy had predominantly caudally or centrally located maxillary tumors for which clean surgical margins were less easily achieved. However, because a subset of clients whose dogs were found to have dirty or narrow surgical margins following FSA excision declined radiotherapy, the effect of adjunctive radiotherapy on outcome for dogs with such margins should be investigated further. There was no significant difference in survival times between dogs with FSA that had dirty surgical margins and underwent radiotherapy and those that did not. Thus, it appeared that the benefit of adjunctive, hypofractionated radiotherapy in the control of FSA in the present study was minimal if surgery was not successful. The authors found that medical literature suggests this is also true for the treatment of oral FSA in humans.28–32

There were no documented long-term complications of hypofractionated radiotherapy in the present study. However, considering the long survival times for dogs with SCC and the relatively low number of dogs (n = 12) that underwent radiotherapy, the authors suggest that the potential risk of late radiation toxicoses should be considered carefully and communicated to the clients in each case and that patients should be monitored closely.

The authors acknowledge that by offering only adjunctive, postoperative radiotherapy to dogs with dirty or narrow surgical margins or with intermediately or poorly differentiated tumors, an inherent selection bias was introduced. However, this selection bias was applicable to both SCC and FSA patients and therefore did not account for the differential sensitivity to postoperative radiotherapy that was found.

In the present study, dogs that underwent radiotherapy received a standardized, hypofractionated radiation protocol. Such an approach has been advocated in the veterinary and human medicine literature for the treatment of carcinomas and sarcomas arising in various anatomic locations, although the exact fractionation protocols used across these studies24,25,33,34 vary substantially from the protocol used for the dogs in the present study. For instance, it has been suggested that definitive protocols (eg, delivery of total doses > 50 Gy in daily fractions) may lead to better outcomes than palliative hypofractionated protocols in the treatment of oral FSA in dogs.17,23,35,36 This may partially explain the lack of appreciable postoperative benefit for adjunctive radiotherapy in dogs with FSA in the present study. However, such a radiotherapy protocol has limitations that may preclude its use. For example, the requirement for daily anesthesia, higher risk of radiation toxicoses (eg, skin burns, mucositis, and wound dehiscence), and higher cost may result in some clients' unwillingness to proceed with such a regimen.

The present study had a number of inherent limitations because of its retrospective design. The total number of patients was small, and a moderate proportion was lost to follow-up (21/87 [24%]) or had incomplete medical records. Outcomes were frequently extrapolated from assessments of owners or referring veterinarians in the absence of rigorous diagnostic testing or necropsy. Conclusions drawn from univariable analysis should be considered exploratory and could be corrected for multiple comparisons. We acknowledge that the power of the multivariate analysis for FSA was limited by the low number of patients in relation to the number of variables being investigated; however, the number of patients reported in the present study was favorable in comparison to much of the existing literature on oral SCC and FSA in dogs. Histopathologic grading and definition of margin status for both tumors were inconsistent across the study population because different pathologists interpreted the samples from the 2 participating veterinary centers. Furthermore, there were insufficient tissue blocks available for independent review for the present study. Although cellular differentiation and biological behavior of oral SCC in dogs have been associated with outcome,16,37 there was no apparent correlation of tumor grade (Kuntz system) with progression-free survival time in a recent study17 that investigated outcomes following treatment for FSA.

None of the dogs in the present study underwent preoperative CT imaging to better define the margins of the tumor and facilitate surgical planning. The authors acknowledge that such imaging would have likely improved the chances of achieving clean surgical margins, but suggest that with the local anatomic constraints involved and the inability to detect microscopic tumor seeding adjacent to the bulk of the masses, incomplete tumor excision still could have occurred despite advanced imaging.

In conclusion, results of the present study suggested that favorable outcomes can be expected for dogs undergoing curative-intent surgical excision of oral SCC and FSA if clean surgical margins can be obtained. Furthermore, our findings supported the use of postoperative, hypofractionated radiotherapy for dogs with incompletely excised oral SCC; however, benefits remained unproven for the use of such radiotherapy for dogs with incompletely excised oral FSAs.

Acknowledgments

No third-party funding or support was received in connection with this study or the writing or publication of the manuscript.

The authors did not have any financial interests with companies that manufactured products used in the present research or with companies that manufactured competing products.

Results of this research were presented in abstract form at the 54th Annual Congress of the British Small Animal Veterinary Association, Birmingham, England, March–April 2011.

ABBREVIATIONS

CI

Confidence interval

FSA

Fibrosarcoma

HR

Hazard ratio

LN

Lymph node

MST

Median survival time

SCC

Squamous cell carcinoma

Footnotes

a.

Dynaray, Radiation Technology Ltd, Wantage, England.

b.

SPSS Statistics, version 22.0, IBM Corp, Chicago, Ill.

References

  • 1. Hoyt RF, Withrow SJ. Oral malignancy in the dog. J Am Anim Hosp Assoc 1984;20:8392.

  • 2. Bronden LB, Eriksen T, Kristensen AT. Oral malignant melanomas and other head and neck neoplasms in Danish dogs—data from the Danish Veterinary Cancer Registry. Acta Vet Scand 2009;51:5459.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Liptak JM, Withrow SJ. Oral tumours. In: Vail DM, ed. Withrow and MacEwen's small animal clinical oncology. 5th ed. St Louis: Elsevier Saunders, 2013;381398.

    • Search Google Scholar
    • Export Citation
  • 4. Todoroff RJ, Brodey RS. Oral and pharyngeal neoplasia in the dog: a retrospective survey of 361 cases. J Am Vet Med Assoc 1979;175:567571.

    • Search Google Scholar
    • Export Citation
  • 5. Salisbury SK, Lantz GC. Long-term results of partial mandibulectomy for treatment of oral tumours in 30 dogs. J Am Anim Hosp Assoc 1988;24:285294.

    • Search Google Scholar
    • Export Citation
  • 6. Kosovsky JK, Matthiesen DT, Marretta SM, et al. Results of partial mandibulectomy for the treatment of oral tumours in 142 dogs. Vet Surg 1991;20:397401.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Schwarz PD, Withrow SJ, Curtis CR, et al. Partial maxillary resection as a treatment for oral cancer in 61 dogs. J Am Anim Hosp Assoc 1991;27:617624.

    • Search Google Scholar
    • Export Citation
  • 8. White RAS. Mandibulectomy and maxillectomy in the dog: long term survival in 100 cases. J Small Anim Pract 1991;32:6974.

  • 9. Wallace J, Matthiesen DT, Patnaik AK. Hemimaxillectomy for the treatment of oral tumours in 69 dogs. Vet Surg 1992;21:337341.

  • 10. Frazier SA, Johns SM, Ortega J, et al. Outcome in dogs with surgically resected oral fibrosarcoma (1997–2008). Vet Comp Oncol 2012;10:3343.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Withrow SJ, Holmberg DL. Mandibulectomy in the treatment of oral cancer. J Am Anim Hosp Assoc 1983;19:273286.

  • 12. Vernon FT, Helphrey M. Rostral mandibulectomy—three case reports in dogs. Vet Surg 1983;12:2629.

  • 13. White RAS, Gorman NT, Watkins SB, et al. The surgical management of bone-involved oral tumours in the dog. J Small Anim Pract 1985;26:693708.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Withrow SJ, Nelson AW, Manley PA, et al. Premaxillectomy in the dog. J Am Anim Hosp Assoc 1985;21:4955.

  • 15. Salisbury SK, Richardson DC, Lantz GC. Partial maxillectomy and premaxillectomy in the treatment of oral neoplasia in the dog and cat. Vet Surg 1986;15:1626.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Fulton AJ, Nemec A, Murphy BG, et al. Risk factors associated with survival in dogs with nontonsillar oral squamous cell carcinoma: 31 cases (1990–2010). J Am Vet Med Assoc 2013;243:696702.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Gardner H, Fidel J, Haldorson G, et al. Canine oral fibrosarcomas: a retrospective analysis of 65 cases (1998–2010). Vet Comp Oncol 2015;13:4047.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Evans SM, Shofer F. Canine oral nontonsillar squamous cell carcinoma—prognostic factors for recurrence and survival following orthovoltage radiation therapy. Vet Radiol Ultrasound 1988;29:133137.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Théon AP, Rodriguez C, Madewell BR. Analysis of prognostic factors and patterns of failure in dogs with malignant oral tumors treated with megavoltage irradiation. J Am Vet Med Assoc 1997;210:778784.

    • Search Google Scholar
    • Export Citation
  • 20. Thrall DE. Orthovoltage radiotherapy of oral fibrosarcomas in dogs. J Am Vet Med Assoc 1981;179:159162.

  • 21. Brewer WG Jr, Turrel JM. Radiotherapy and hyperthermia in the treatment of fibrosarcomas in the dog. J Am Vet Med Assoc 1982;181:146150.

    • Search Google Scholar
    • Export Citation
  • 22. LaDue-Miller T, Price GS, Page RL, et al. Radiotherapy of canine non-tonsillar squamous cell carcinoma. Vet Radiol Ultrasound 1996;37:7477.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Forrest LJ, Chun R, Adams WM, et al. Postoperative radiotherapy for canine soft tissue sarcoma. J Vet Intern Med 2000;14:578582.

  • 24. Demetriou JL, Brearley MJ, Constantino-Casas F, et al. Intentional marginal excision of canine limb soft tissue sarcomas followed by radiotherapy. J Small Anim Pract 2012;53:174181.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Kung MBJ, Poirer VJ, Dennis MM, et al. Hypofractionated radiation therapy for the treatment of microscopic canine soft tissue sarcoma. Vet Comp Oncol 2016;14:e135e145.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Kuntz CA, Dernell WS, Powers BE, et al. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc 1997;211:11471151.

    • Search Google Scholar
    • Export Citation
  • 27. Kühnel S, Kessler M. Prognosis of canine oral (gingival) squamous cell carcinoma after surgical therapy. A retrospective analysis in 40 patients [in German]. Tierarztl Prax Ausg K Klientiere Heimtiere 2014;42:359366.

    • Search Google Scholar
    • Export Citation
  • 28. Greager JA, Reichard K, Campana JP, et al. Fibrosarcoma of the head and neck. Am J Surg 1994;167:437439.

  • 29. Kraus DH, Dubner S, Harrison LB, et al. Prognostic factors for recurrence and survival in head and neck soft tissue sarcomas. Cancer 1994;74:697702.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Barker JL, Paulino AC, Feeney S, et al. Locoregional treatment for adult soft tissue sarcomas of the head and neck: an institutional review. Cancer J 2003;9:4957.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol 2003;15:239252.

  • 32. Gamoh S, Nakashima Y, Akiyama H, et al. Fibrosarcoma of the temporomandibular joint area: benefits of magnetic resonance imaging and computed tomography. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;118:262266.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Holloway CL, Panet-Raymond V, Olivotto I. Hypofractionation should be the new ‘standard’ for radiation therapy after breast conserving surgery. Breast 2010;19:163167.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. McQuown B, Keyerleber MA, Rosen K, et al. Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999–2013). Vet Comp Oncol 2017;15:840851.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Mauldin GN. Soft tissue sarcomas. Vet Clin North Am Small Anim Pract 1997;27:139148.

  • 36. McKnight JA, Mauldin GN, McEntee MC, et al. Radiation treatment for incompletely resected soft-tissue sarcomas in dogs. J Am Vet Med Assoc 2000;217:205210.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Nemec A, Murphy BG, Jordan RC, et al. Oral papillary squamous cell carcinoma in twelve dogs. J Comp Pathol 2014;150:155161.

Contributor Notes

Dr. Riggs' present address is Willows Veterinary Centre & Referral Service, Highlands Rd, Shirley, B90 4NH England. Dr. Hermer's present address is Taverham Veterinary Practice, Fir Covert Rd, Norwich, NR8 6HT England. Dr. Murphy's present address is The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG Scotland.

Address correspondence to Ms. Riggs (julia.riggs@cantab.net).
  • Figure 1—

    Kaplan-Meier plot of survival time after surgery for 35 dogs with oral, nontonsillar SCCs that underwent curative-intent surgical excision and had clean surgical margins (dashed line; n = 22 [2 dogs with poorly differentiated tumors that underwent postoperative hypofractionated radiotherapy {RT} and 20 dogs that did not undergo postoperative RT]), had narrow or dirty surgical margins and underwent postoperative hypofractionated RT (dotted line; 8), or had narrow or dirty surgical margins but did not undergo postoperative RT (solid line; 5). Tick marks represent censored dogs.

  • Figure 2—

    Kaplan-Meier plot of survival time after surgery for 42 dogs with oral FSAs that underwent curative-intent surgical excision and had clean surgical margins (dashed line; n = 21), had narrow or dirty surgical margins and underwent postoperative hypofractionated RT (dotted line; 14), or had narrow or dirty surgical margins but did not undergo postoperative RT (solid line; 7). Tick marks represent censored dogs. See Figure 1 for key.

  • 1. Hoyt RF, Withrow SJ. Oral malignancy in the dog. J Am Anim Hosp Assoc 1984;20:8392.

  • 2. Bronden LB, Eriksen T, Kristensen AT. Oral malignant melanomas and other head and neck neoplasms in Danish dogs—data from the Danish Veterinary Cancer Registry. Acta Vet Scand 2009;51:5459.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Liptak JM, Withrow SJ. Oral tumours. In: Vail DM, ed. Withrow and MacEwen's small animal clinical oncology. 5th ed. St Louis: Elsevier Saunders, 2013;381398.

    • Search Google Scholar
    • Export Citation
  • 4. Todoroff RJ, Brodey RS. Oral and pharyngeal neoplasia in the dog: a retrospective survey of 361 cases. J Am Vet Med Assoc 1979;175:567571.

    • Search Google Scholar
    • Export Citation
  • 5. Salisbury SK, Lantz GC. Long-term results of partial mandibulectomy for treatment of oral tumours in 30 dogs. J Am Anim Hosp Assoc 1988;24:285294.

    • Search Google Scholar
    • Export Citation
  • 6. Kosovsky JK, Matthiesen DT, Marretta SM, et al. Results of partial mandibulectomy for the treatment of oral tumours in 142 dogs. Vet Surg 1991;20:397401.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Schwarz PD, Withrow SJ, Curtis CR, et al. Partial maxillary resection as a treatment for oral cancer in 61 dogs. J Am Anim Hosp Assoc 1991;27:617624.

    • Search Google Scholar
    • Export Citation
  • 8. White RAS. Mandibulectomy and maxillectomy in the dog: long term survival in 100 cases. J Small Anim Pract 1991;32:6974.

  • 9. Wallace J, Matthiesen DT, Patnaik AK. Hemimaxillectomy for the treatment of oral tumours in 69 dogs. Vet Surg 1992;21:337341.

  • 10. Frazier SA, Johns SM, Ortega J, et al. Outcome in dogs with surgically resected oral fibrosarcoma (1997–2008). Vet Comp Oncol 2012;10:3343.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Withrow SJ, Holmberg DL. Mandibulectomy in the treatment of oral cancer. J Am Anim Hosp Assoc 1983;19:273286.

  • 12. Vernon FT, Helphrey M. Rostral mandibulectomy—three case reports in dogs. Vet Surg 1983;12:2629.

  • 13. White RAS, Gorman NT, Watkins SB, et al. The surgical management of bone-involved oral tumours in the dog. J Small Anim Pract 1985;26:693708.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Withrow SJ, Nelson AW, Manley PA, et al. Premaxillectomy in the dog. J Am Anim Hosp Assoc 1985;21:4955.

  • 15. Salisbury SK, Richardson DC, Lantz GC. Partial maxillectomy and premaxillectomy in the treatment of oral neoplasia in the dog and cat. Vet Surg 1986;15:1626.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Fulton AJ, Nemec A, Murphy BG, et al. Risk factors associated with survival in dogs with nontonsillar oral squamous cell carcinoma: 31 cases (1990–2010). J Am Vet Med Assoc 2013;243:696702.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Gardner H, Fidel J, Haldorson G, et al. Canine oral fibrosarcomas: a retrospective analysis of 65 cases (1998–2010). Vet Comp Oncol 2015;13:4047.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Evans SM, Shofer F. Canine oral nontonsillar squamous cell carcinoma—prognostic factors for recurrence and survival following orthovoltage radiation therapy. Vet Radiol Ultrasound 1988;29:133137.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Théon AP, Rodriguez C, Madewell BR. Analysis of prognostic factors and patterns of failure in dogs with malignant oral tumors treated with megavoltage irradiation. J Am Vet Med Assoc 1997;210:778784.

    • Search Google Scholar
    • Export Citation
  • 20. Thrall DE. Orthovoltage radiotherapy of oral fibrosarcomas in dogs. J Am Vet Med Assoc 1981;179:159162.

  • 21. Brewer WG Jr, Turrel JM. Radiotherapy and hyperthermia in the treatment of fibrosarcomas in the dog. J Am Vet Med Assoc 1982;181:146150.

    • Search Google Scholar
    • Export Citation
  • 22. LaDue-Miller T, Price GS, Page RL, et al. Radiotherapy of canine non-tonsillar squamous cell carcinoma. Vet Radiol Ultrasound 1996;37:7477.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Forrest LJ, Chun R, Adams WM, et al. Postoperative radiotherapy for canine soft tissue sarcoma. J Vet Intern Med 2000;14:578582.

  • 24. Demetriou JL, Brearley MJ, Constantino-Casas F, et al. Intentional marginal excision of canine limb soft tissue sarcomas followed by radiotherapy. J Small Anim Pract 2012;53:174181.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Kung MBJ, Poirer VJ, Dennis MM, et al. Hypofractionated radiation therapy for the treatment of microscopic canine soft tissue sarcoma. Vet Comp Oncol 2016;14:e135e145.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Kuntz CA, Dernell WS, Powers BE, et al. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc 1997;211:11471151.

    • Search Google Scholar
    • Export Citation
  • 27. Kühnel S, Kessler M. Prognosis of canine oral (gingival) squamous cell carcinoma after surgical therapy. A retrospective analysis in 40 patients [in German]. Tierarztl Prax Ausg K Klientiere Heimtiere 2014;42:359366.

    • Search Google Scholar
    • Export Citation
  • 28. Greager JA, Reichard K, Campana JP, et al. Fibrosarcoma of the head and neck. Am J Surg 1994;167:437439.

  • 29. Kraus DH, Dubner S, Harrison LB, et al. Prognostic factors for recurrence and survival in head and neck soft tissue sarcomas. Cancer 1994;74:697702.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Barker JL, Paulino AC, Feeney S, et al. Locoregional treatment for adult soft tissue sarcomas of the head and neck: an institutional review. Cancer J 2003;9:4957.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol 2003;15:239252.

  • 32. Gamoh S, Nakashima Y, Akiyama H, et al. Fibrosarcoma of the temporomandibular joint area: benefits of magnetic resonance imaging and computed tomography. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;118:262266.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Holloway CL, Panet-Raymond V, Olivotto I. Hypofractionation should be the new ‘standard’ for radiation therapy after breast conserving surgery. Breast 2010;19:163167.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. McQuown B, Keyerleber MA, Rosen K, et al. Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999–2013). Vet Comp Oncol 2017;15:840851.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Mauldin GN. Soft tissue sarcomas. Vet Clin North Am Small Anim Pract 1997;27:139148.

  • 36. McKnight JA, Mauldin GN, McEntee MC, et al. Radiation treatment for incompletely resected soft-tissue sarcomas in dogs. J Am Vet Med Assoc 2000;217:205210.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Nemec A, Murphy BG, Jordan RC, et al. Oral papillary squamous cell carcinoma in twelve dogs. J Comp Pathol 2014;150:155161.

Advertisement