Osteosarcoma following tibial plateau

SMALL ANIMALS/
leveling osteotomy in dogs:

EXOTIC
29 cases (1997–2011)
Laura E. Selmic, BVetMed, MPH; Stewart D. Ryan, BVSc, MS; Sarah E. Boston, DVM, DVSc; Julius M. Liptak, BVSc, MVetClinStud;
William T. N. Culp, VMD; Angela J. Sartor, DVM; Cassandra Y. Prpich, BVSc; Stephen J. Withrow, DVM

Objective—To determine the signalment, tibial plateau leveling osteotomy (TPLO) plate
type, clinical staging information, treatment, and oncological outcome in dogs that devel-
oped osteosarcoma at the proximal aspect of the tibia following TPLO and to calculate the
interval between TPLO and osteosarcoma diagnosis.
Design—Multi-institutional retrospective case series.
Animals—29 dogs.
Procedures—Medical records from 8 participating institutions were searched for dogs that
developed osteosarcoma (confirmed through cytologic or histologic evaluation) at previous
TPLO sites. Signalment, TPLO details, staging tests, treatment data, and outcome informa-
tion were recorded. Descriptive statistics were calculated, and disease-free intervals and
survival times were evaluated by means of Kaplan-Meier analysis.
Results—29 dogs met the inclusion criteria. The mean age was 9.2 years and mean weight
was 45.1 kg (99.2 lb) at the time of osteosarcoma diagnosis. Most dogs had swelling over
the proximal aspect of the tibia (17/21) and lameness of the affected limb (28/29). The mean
interval between TPLO and osteosarcoma diagnosis was 5.3 years. One type of cast stain-
less steel TPLO plate was used in most (18) dogs; the remaining dogs had received plates
of wrought stainless steel (n = 4) or unrecorded type (7). Twenty-three of 29 dogs under-
went treatment for osteosarcoma. Median survival time for 10 dogs that underwent am-
putation of the affected limb and received ≥ 1 chemotherapeutic treatment was 313 days.
Conclusions and Clinical Relevance—Results supported that osteosarcoma should be a
differential diagnosis for dogs with a history of TPLO that later develop lameness and swell-
ing at the previous surgical site. Oncological outcome following amputation and chemo-
therapy appeared to be similar to outcomes previously reported for dogs with appendicular
osteosarcoma. (J Am Vet Med Assoc 2014;244:1053–1059)

O steosarcoma commonly arises in metaphyseal bone

of large- or giant-breed dogs and is the most com-
mon primary bone tumor in dogs.1–5 In previous re- ALP
ABBREVIATIONS
Alkaline phosphatase
ports,1,6 spontaneously occurring osteosarcoma of the DFI Disease-free interval
tibia accounted for 19 of 128 (14.8%) to 31 of 153 MST Median survival time
(20.3%) of appendicular osteosarcoma cases in dogs, SRT Stereotactic radiation therapy
with the proximal aspect of the tibia affected in 11 of 153 TPLO Tibial plateau leveling osteotomy
(approx 7%) appendicular osteosarcoma cases and up to
10 of 19 (approx 53%) tibial osteosarcoma cases.
The TPLO procedure was developed in the early tion of the tibial plateau are performed to decrease the
1990s to alter the biomechanics of the stifle joint in tibial plateau angle with the purpose of eliminating cra-
dogs with cranial cruciate ligament disease.7 Biradial nial tibial thrust. The osteotomy site is then stabilized
osteotomy of the proximal tibial metaphysis and rota- with a specialized TPLO plate.

From the Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins,
CO 80523 (Selmic, Ryan, Withrow); the Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1H
3N2, Canada (Boston); Alta Vista Animal Hospital, 2616 Bank’s St, Ottawa, ON K1T 1M9, Canada (Liptak); the Department of Surgical and
Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (Culp); SAGE Centers for Veterinary
Specialty and Emergency Care, 1410 Monument Blvd, Concord, CA 94520 (Sartor); and Southpaws Specialty Surgery for Animals, 3 Roper
St, Moorabbin, VIC 3189, Australia (Prpich). Dr Selmic’s present address is Department of Veterinary Clinical Medicine, College of Veterinary
Medicine, University of Illinois, Urbana, IL 61802. Dr. Ryan’s present address is Small Animal Surgery Service, Faculty of Veterinary Science,
University of Melbourne, Werribee, VIC 3030, Australia. Dr. Boston’s present address is Department of Small Animal Clinical Sciences, College
of Veterinary Medicine, University of Florida, Gainesville, FL 32608.
Presented in abstract form at the Veterinary Society of Surgical Oncology Symposium, Fort Collins, Colo, May 2012, and the Veterinary Ortho-
pedic Society Meeting, Park City, Utah, March 2013.
The authors thank Jeffrey Neu, Mary Lafferty, Irene Mok, Vicky Jamieson, and Drs. Maura O’Brien and Simon Kudnig for technical assistance.
Address correspondence to Dr. Selmic (lselmic@illinois.edu).

JAVMA, Vol 244, No. 9, May 1, 2014 Scientific Reports 1053

 There have been multiple descriptions of fracture- or
implant-associated osteosarcoma in companion animals.8–16
SMALL ANIMALS/
The diaphysis is reported as the most commonly affected
EXOTIC
location for both fracture- and implant-associated sarcoma.
Because they are typically diaphyseal, it is thought that frac-
ture-associated tumors do not represent spontaneously oc-
curring osteosarcoma.17 There are many hypotheses about
why fracture- or implant-associated sarcomas develop, in-
cluding tumor development as the result of biological ef-
fects of metals released from implants, corrosion of metallic
implants, altered cellular activity or excessive tissue damage
caused by the fracture or presence of the implant, or infec-
tion resulting in osteomyelitis.17 The mean interval between
fracture occurrence and osteosarcoma diagnosis has been
reported as 5.8 years (range, 1 to 12 years).15
A few clinical reports18–20 have described osteosarcoma
development at the site of triple pelvic osteotomy and total
hip arthroplasty in dogs. Reports of sarcoma development
at the proximal aspect of the tibia following TPLO in dogs
are also rare; 7 cases found in the literature included histo-
pathologic diagnoses of osteosarcoma (5 dogs), histiocytic
sarcoma (1), and poorly differentiated sarcoma (1).21–24 A
low incidence (23 of 30,636 [< 0.075%] cases) of neoplasia
at TPLO sites has been reported in an abstracta based on
results of a surgeon questionnaire.
Only a few cases of osteosarcoma at the site of a
TPLO have been reported; thus, information on these
types of cases remains scant. The purpose of the retro-
spective study reported here was to determine the sig-
nalment, TPLO plate type, clinical staging information,
treatment, and oncological outcome in a cohort of dogs
that developed osteosarcoma at the proximal aspect of
the tibia following TPLO and to calculate the interval
between TPLO and osteosarcoma diagnosis. The wider
aims were to summarize clinical data in a larger num-
ber of cases than previously reported, to increase clinical
awareness of osteosarcoma at TPLO sites, and to inform
the design of future studies to investigate the potential
relationship between TPLO and osteosarcoma in dogs.
Materials and Methods
Case selection—Hard copy and electronic medical
records at each of 8 participating institutions (Colorado
State University, Ontario Veterinary College, Alta Vista
Animal Hospital, University of California-Davis, SAGE
Centers for Veterinary Specialty and Emergency Care,
Southpaws Specialty Surgery for Animals, Melbourne
Veterinary Specialist Centre, and Orchard Road Veteri-
nary Surgery Inc) were searched to identify dogs with
osteosarcoma at the site of a prior TPLO that were evalu-
ated between January 1, 1997, and December 31, 2011.
Dogs were eligible for study inclusion if they had osteo-
sarcoma of the proximal aspect of the tibia confirmed by
histologic analysis of a biopsy sample or cytologic evalu-
ation of a fine-needle aspirate and had undergone TPLO
at the same site ≥ 1 year prior to osteosarcoma diagnosis.
Dogs that had a TPLO performed < 1 year before osteo-
sarcoma diagnosis were excluded to prevent inclusion of
dogs that had preexisting sarcomas at that site.17
Medical records review—Signalment information
collected from the medical records included date of birth,
sex, neuter status, breed, and body weight at time of osteo-
1054 Scientific Reports
sarcoma diagnosis. Additional information recorded in-
cluded date of osteosarcoma diagnosis, hind limb affected,
duration and severity of lameness (if applicable), whether
soft tissue swelling was present at the affected site, and
other clinically relevant physical examination findings
noted at the time of diagnosis. The severity of lameness
was characterized as weight bearing or non–weight bear-
ing on the basis of descriptions in the medical records.
For dogs that had hematologic analysis performed
at the time of osteosarcoma diagnosis, the serum total
ALP activity was recorded and any CBC or serum bio-
chemical abnormalities were recorded. Serum total ALP
activity was considered high if the value exceeded the
reference range at the participating institution where
the dog was evaluated. The method of osteosarcoma
diagnosis (histologic examination of a biopsy sample
or cytologic evaluation of a fine-needle aspirate) and
clinical stage (II [without metastases] or III [with me-
tastases])25 at the time of the diagnosis were recorded.
Details regarding the TPLO were recorded, including
the date of surgery, plate manufacturer, and size of plate.
Local infection at the TPLO site reported at any time
after surgery was recorded with information regarding
cultures performed and bacteria isolated, if applicable.
If the TPLO plate was removed, the date of removal was
recorded. The number of years from the date of TPLO to
the date of osteosarcoma diagnosis was calculated.
Any treatment for osteosarcoma, including am-
putation, radiation therapy, chemotherapy, and other
treatments (eg, bisphosphonate administration) and
the dates of treatment were recorded. Administration
of analgesics was also recorded if these were the only
treatment used. If radiation therapy was part of the
treatment protocol, the intent (curative vs palliative)
and type of radiation therapy (fractionated, stereotac-
tic [SRT], or coarse fractionated), the radiation therapy
protocol, and any complications of treatment were re-
corded. The chemotherapeutic protocol and number of
doses administered were noted if applicable.
Outcome information, which included whether
metastatic disease was detected during follow-up, the
date of detection, and location of any metastases, was
obtained by communication with the owner or refer-
ring veterinarian. Whether the dog was alive at the time
of last follow-up was recorded. For dogs that had died,
the date and cause of death were reported if known.
Statistical analysis—Descriptive statistics were
calculated for the following continuous variables: age
at TPLO and at osteosarcoma diagnosis, body weight,
and interval between TPLO and osteosarcoma diagno-
sis. The data for these variables were tested for normal-
ity by means of a Kolmogorov-Smirnov test. Normally
distributed data were described as mean ± SD, and
nonnormally distributed data were reported as median
(interquartile range). Frequencies (proportion and per-
centage of dogs) were calculated for categorical vari-
ables, including year of TPLO and surgical plate type.
A modified intent-to-treat analysis was used for assess-
ment of treatment outcomes. Dogs that were prescribed
curative-intent treatment with amputation or SRT and re-
ceived ≥ 1 IV dose of a chemotherapeutic agent were cat-
egorized as having received curative-intent treatment. This
approach was chosen to reduce bias associated with exclu-
JAVMA, Vol 244, No. 9, May 1, 2014
sion of dogs in which chemotherapy was terminated early and presence or absence of swelling was not recorded for
for any reason. Dogs that underwent repair of pathological 8 dogs. Additional physical examination abnormalities

SMALL ANIMALS/
fractures without chemotherapy, amputation without che- were reported for only 6 dogs. The following abnormali-
motherapy, or palliative-intent radiation therapy with or ties were described for 1 dog each: a cutaneous mass on

EXOTIC
without bisphosphonate treatment (eg, pamidronate diso- the neck (results of cytologic evaluation of a fine-needle
dium) or chemotherapy, and those that received analgesic aspirate were consistent with a mast cell tumor), drain-
medications alone were classified as receiving palliative- ing tract at the level of the proximal aspect of the af-
intent treatment. The DFI for dogs that underwent cura- fected tibia, firm and enlarged popliteal lymph node of
tive-intent treatment was calculated as the number of days the affected limb (no evidence of metastatic disease was
from date of amputation until the date that recurrence or seen on cytologic evaluation of a fine-needle aspirate),
metastasis of osteosarcoma was detected; patients that did instability at the proximal aspect of the tibia (owing to
not develop local recurrence or metastasis and were still a pathological fracture of the proximal diaphysis), signs
alive or had been lost to follow-up were censored on the of pain on manipulation of the contralateral hip joint,
day of last contact. Survival times were calculated as the and high rectal temperature (39.4°C [102.9°F]; reference
number of days from osteosarcoma diagnosis until death range, 37.7° to 39.2°C [99.9° to 102.6°F]).
due to any cause or until date of last follow-up. Dogs that Results of hematologic and biochemical analyses
were still alive or had been lost to follow-up were censored performed at the time of osteosarcoma diagnosis were
on the day of last contact. Kaplan-Meier survival curves available for 17 dogs. Serum total ALP activities were
were generated for dogs that received curative-intent and high in 11 of 17 dogs for which results were available.
palliative-intent treatments, MSTs were calculated with the Other clinicopathologic abnormalities were reported for
Kaplan-Meier method, and survival curves were compared 6 of the 17 dogs. One dog each had hyperglobulinemia
by means of the Mantel-Cox log rank test. (4.6 g/dL; reference range, 2.5 to 4.5 g/dL), high alanine
Univariable analysis was not performed to assess transaminase activity (140 U/L; reference range, 10 to 90
associations of variables with DFI or MST because of U/L), and hypercholesterolemia (438 mg/dL; reference
the low number of dogs in the study. Values of P ≤ 0.05 range, 130 to 300 mg/dL). One dog with diabetes had hy-
were considered significant. Statistical analysis was per- perglycemia (373 mg/dL; reference range, 70 to 115 mg/
formed with a commercially available statistical analy- dL). Another dog had high aspartate transaminase activ-
sis software program.b ity (47 U/L; reference range, 15 to 45 U/L), with mildly
high creatine kinase activity (340 U/L; reference range,
Results 50 to 275 U/L) and hypercholesterolemia (343 mg/dL;
reference range, 130 to 300 mg/dL). The remaining dog
Examination of dogs at osteosarcoma diagnosis— had high alanine transaminase (696 U/L; reference range,
Twenty-nine dogs met the study inclusion criteria. Six- 10 to 90 U/L) and aspartate transaminase (107 U/L; refer-
teen dogs were seen at Colorado State University, 4 at ence range, 15 to 45 U/L) activities.
SAGE Centers for Veterinary Specialty and Emergency Radiographs of the affected tibia were obtained for each
Care, 3 at Alta Vista Animal Hospital, 2 at University of dog and evaluated by board-certified radiologists at the par-
California-Davis, and 1 each at Melbourne Veterinary ticipating institutions, and all had recorded findings consis-
Specialist Centre, Ontario Veterinary College, Orchard tent with an aggressive bone lesion involving the proximal
Road Veterinary Surgery Inc, and Southpaws Specialty aspect of the tibia at the site of a previous TPLO (Figure 1).
Surgery for Animals. At the time of os-
teosarcoma diagnosis, the mean ± SD
body weight was 45.1 ± 13.5 kg (99.2
± 29.8 lb) and age was 9.2 ± 2.2 years.
There were 19 female dogs (all spayed)
and 10 male dogs (all castrated). Breeds
represented were Labrador Retriever (n
= 6), Rottweiler (4), mixed (4), Golden
Retriever (3), Bull Mastiff (2), Great
Dane (2), German Shepherd Dog (2),
Mastiff (2), and Great Pyrenees (2); 1
Newfoundland and 1 pit bull–type dog
were also included.
Lameness was reported in 28 dogs
and described as non–weight bearing in
9 dogs and weight bearing in 17; severity
was not recorded for 2 dogs. The median
duration of lameness prior to osteosar-
coma diagnosis was 4 weeks (interquar-
tile range, 1 to 7 weeks). The right limb
was affected in 16 dogs and the left in 13.
Swelling at the proximal aspect of the tib-
ia was present at the time of osteosarcoma
Figure 1—Representative radiographic images of the proximal aspect of the tibia in
diagnosis in 17 dogs, lameness but no no- 2 of 29 dogs that developed osteosarcoma at previous TPLO sites. Notice the mixed
ticeable swelling was reported for 4 dogs, lytic-productive radiographic pattern consistent with primary bone neoplasia.

JAVMA, Vol 244, No. 9, May 1, 2014 Scientific Reports 1055

 Osteosarcoma of the proximal aspect of the tibia was diag-
nosed on the basis of histologic evaluation in 27 dogs and
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cytologic evaluation of a fine-needle aspirate in 2 dogs. Histo-
EXOTIC
pathologic or cytologic diagnosis of osteosarcoma was made
by board-certified pathologists or clinical pathologists, re-
spectively. Stage III disease was diagnosed in 5 of 24 dogs that
had staging tests performed at the time of osteosarcoma diag-
nosis; the remaining 19 dogs had stage II disease (Table 1).
TPLO information—All study dogs underwent
TPLO between 1998 and 2007, and 11 of the 29 surger-
ies had been performed at the participating institutions.
Mean ± SD age at the time of TPLO was 4.0 ± 2.6 years.
The TPLO plate type was known for 22 dogs; 3.5-mm
plates were used in all of these cases. In most dogs (n =
18), 1 type of cast stainless steel TPLO platec was used;
all of these surgeries were performed between 1998 and
2006. Four dogs had wrought stainless steel platesd,e
placed (2 dogs received plates [broad in one and nar-
row in the other] made by one manufacturer,d and 2
received plates made by another sourcee) in 2007. The
plate type was not reported for 7 dogs that underwent
TPLO. Four dogs had a history of infection at the TPLO
site, and a positive culture result was reported for 1 dog
(Staphylococcus pseudintermedius was isolated). The
TPLO plate was removed in 7 dogs; plate removal was
performed 527 and 1,403 days prior to osteosarcoma
diagnosis because of infection in 2 dogs and at the time
of osteosarcoma diagnosis (when biopsy samples were
obtained) in 5 dogs. The mean ± SD interval between
TPLO and osteosarcoma diagnosis was 5.3 ± 2.3 years
(range, 1.0 to 10.7 years).
Treatments for osteosarcoma—Twenty-three of 29
dogs underwent treatment for osteosarcoma at a previ-
ous TPLO site. Eleven dogs received curative-intent
treatment (amputation and adjuvant chemotherapy or
SRT and adjuvant chemotherapy). Twelve dogs received
palliative-intent treatment, consisting of palliative-
intent (coarse-fractionated) radiation therapy, palliative-
intent radiation therapy followed by amputation, amputa-
tion without chemotherapy, pathological fracture repair,
or treatment with analgesic medications alone.
CURATIVE-INTENT TREATMENTS
Ten dogs underwent amputation of the affected
limb and adjuvant chemotherapy. The only chemother-
apeutic agent administered was carboplatin (300 mg/
m2, IV, q 3 wk) for 6 of these dogs. The remaining 4
Table 1—Summary of clinical staging results at the time of diagnosis in 24 of 29 dogs that developed
osteosarcoma at a previous TPLO site.
No. of dogs
that had the
Clinical staging test test performed
Thoracic radiography 22
Abdominal ultrasonography 8 1
Full-body nuclear scintigraphy 4 1
Lymph node (cytologic or 16
histologic) evaluation
Five dogs had stage III (metastatic) disease.
1056 Scientific Reports
dogs received alternating carboplatin (300 mg/m2, IV,
q 6 wk) and doxorubicin hydrochloride (30 mg/m2, IV,
q 6 wk) treatment. Two of the 10 dogs had metastasis to
the popliteal lymph node diagnosed on the basis of his-
topathologic findings after limb amputation but did not
have evidence of metastatic disease at other sites prior
to or immediately following surgery. For dogs that had
amputation with carboplatin as the sole chemothera-
peutic agent, the number of doses administered was 4
(n = 4), 3 (1), or 1 (1). Three of the 4 dogs that received
alternating carboplatin and doxorubicin chemotherapy
had 3 doses of each drug administered, and 1 dog re-
ceived only 1 dose of each drug.
One dog received SRT, with 3 radiation fractions
administered (a total dose of 34.3 Gy was administered
to 95% of the planned target volume). One dose of
pamidronate (1.0 mg/kg [0.45 mg/lb], IV, given over 2
hours) was administered prior to SRT, and carboplatin
(300 mg/m2, IV) was administered every 3 weeks start-
ing at the time of SRT. Six doses of carboplatin were
planned, but only 5 doses were given because the treat-
ment was discontinued when pulmonary metastatic
disease was detected.
PALLIATIVE-INTENT TREATMENTS
Of 4 dogs that received palliative-intent radiation
therapy, 3 had no adjunctive chemotherapy. Two of
these 3 dogs each received two 8-Gy radiation fractions
administered on consecutive days; one of the 2 had sus-
pected metastases to the proximal aspect of the right
humerus and left fourth rib and was also treated with
pamidronate (1.0 mg/kg, IV). This dog later underwent
hind limb amputation because of extensive soft tissue
swelling in the proximal aspect of the tibia. The radia-
tion dose per fraction was not recorded for the third
dog. One dog had four 8-Gy radiation fractions admin-
istered weekly and received adjunctive chemotherapy
via a continuous SC infusion that delivered 300 mg/m2
of carboplatin over 3 days.26
One dog had pathological fracture of the proximal
tibial diaphysis, which was stabilized with a plate (type
not recorded) placed on the medial aspect of the tibia.
No adjuvant chemotherapy was administered following
surgery. Five dogs underwent amputation to treat pri-
mary tumor pain with no adjuvant chemotherapy. Two
dogs received oral analgesic medications alone, includ-
ing tramadol hydrochloride (3.0 to 5.0 mg/kg [1.36 to
2.27 mg/lb], PO, q 8 h) and gabapentin (5.0 mg/kg, PO,
No. of dogs
with
metastases Site of metastases
1 Lungs
Liver and kidney
Proximal aspect of the right humerus and
left fourth rib
2 Popliteal lymph node
JAVMA, Vol 244, No. 9, May 1, 2014
q 8 h). One of the 2 dogs that received analgesic treat-
ment alone had documented evidence of metastatic dis-
ease in the liver and spleen.
Outcomes—The date of death was known for 22
dogs: 17 were euthanized because of poor quality of life
or progressive disease, 3 were euthanized for other rea-
sons (including fecal incontinence, development of an
atrial tumor, and progressive myelopathy), and 2 died
of unknown causes (no necropsies were performed).
Two dogs were still alive at the time of last follow-up
(14 and 1,388 days). Five dogs were lost to follow-up
(4 immediately after the diagnosis of osteosarcoma and
1 at 241 days after the diagnosis).
The median DFI for the 11 dogs that received curative-
intent treatment was 195 days (range, 13 to 587 days). The
median DFI for the 10 dogs treated with amputation and
chemotherapy was also 195 days (range, 13 to 587 days;
Figure 2). The 1 dog that underwent SRT and chemother-
apy had a DFI of 116 days before pulmonary metastases
were detected.
The MST for all dogs was 222 days (range, 5 to
1,388 days). The MST for dogs that received curative-
intent treatment was 222 days (range, 96 to 1,388
Figure 2—Kaplan-Meier curve of DFI for dogs that received cu-
rative-intent treatment for osteosarcoma at a previous TPLO site
(n = 11).
Figure 3—Kaplan-Meier curve of survival times for dogs that re-
ceived curative-intent (n = 11) versus palliative-intent (12) treat-
ments for osteosarcoma at a previous TPLO site. Survival time
did not differ significantly (P = 0.68) between groups.
JAVMA, Vol 244, No. 9, May 1, 2014
days), and that for dogs in this group that underwent
both amputation and IV chemotherapy was 313 days
SMALL ANIMALS/
(range, 96 to 1,388 days). Survival time of the dog that
EXOTIC
underwent SRT and chemotherapy was 141 days. The
MST for the 12 dogs that had palliative-intent treatment
was 316 days (range, 21 to 574 days). The 4 dogs that
received palliative-intent radiation therapy had survival
times of 67, 165, 316, and 387 days. There was no sig-
nificant (P = 0.68) difference between the MSTs of dogs
that received palliative- and curative-intent treatments
(Figure 3). The 6 dogs that did not receive treatment
were all euthanized ≤ 14 days after the diagnosis of
osteosarcoma.
Discussion
Results of the present study supported that os-
teosarcoma should be a differential diagnosis for dogs
with a history of TPLO that later develop lameness and
swelling at the previous surgical site. Diagnostic tests
such as radiography, with cytologic or histologic evalu-
ation of samples, can be used to confirm the diagnosis.2
The MST for dogs treated with amputation and adju-
vant chemotherapy was 313 days in the present study,
which is comparable to MSTs of 235 to 540 days previ-
ously reported for dogs with osteosarcoma treated by
means of amputation and adjuvant chemotherapy.27–41
The ages of dogs at the time of osteosarcoma di-
agnosis and TPLO in the present study were similar to
those of dogs at the time of treatment for appendicular
osteosarcoma and cranial cruciate ligament rupture, re-
spectively, in other reports.1,42–49 The study population
predominantly comprised large-breed dogs, which is a
consistent finding in other studies1,42–49 of treatment of
appendicular osteosarcoma and cranial cruciate liga-
ment rupture. In the present study, all dogs were neu-
tered and most dogs were females, which may reflect
the higher prevalence of cranial cruciate ligament rup-
ture that has been reported for these groups, compared
with the prevalence for other dogs.50
Most TPLO plates used for the surgery in this
case series were cast stainless steel plates from a single
sourcec; this reflects the exclusive availability of this
specialized surgical plate through part of the study pe-
riod and is attributable to a patent for this plate in the
late 1990s and early 2000s together with the long in-
terval commonly observed between fracture or implant
placement and the development of fracture- or implant-
associated osteosarcoma.15 These TPLO plates differ
from other stainless steel TPLO plates in that they are
made of cast rather than wrought stainless steel. One
case report23 raised concerns about the metallurgy of
this specific type of TPLO platec and formation of sarco-
ma at the site of a TPLO. In that case report,22 intra- and
extracellular debris was found within the tumor that
was assumed (on the basis of appearance) to have origi-
nated from the plate; additionally, osteolysis was pres-
ent immediately beneath the plate. Analysis of the plate
following amputation of the affected limb revealed a de-
gree of pitting and loss of metal on the side of the plate
that had been in contact with the tibia, indicating the
presence of corrosion.22
Two studies51,52 have assessed the material com-
position of the same type of cast stainless steel TPLO
Scientific Reports 1057
 platec used in the present study, with different findings;
SMALL ANIMALS/
Boudrieau et al51 reported that not all plates examined
met specifications for chemical composition of cast sur-
EXOTIC
gical implants (American Society for Testing Materials
standard 745) and that tissues surrounding the plate
had evidence of adverse reactions consistent with cor-
rosion. In contrast, Lackowski et al52 found consistent
composition of all cast TPLO platesc evaluated. Charles
and Ness53 examined TPLO plates of this typec follow-
ing explantation and found evidence of crevice corro-
sion that may have been initiated in surface irregulari-
ties and pores of the plates resulting from their casting
manufacture.
One case report21 has documented osteosarcoma
following TPLO in which a wrought stainless steel
TPLO plate was placed. Results of the present case se-
ries further confirm that osteosarcoma can develop at
the site of previous TPLO when wrought stainless steel
TPLO plates are used for fixation. Further study is mer-
ited to determine the incidence of osteosarcoma at the
proximal aspect of the tibia following TPLO with plates
of various types.
The interval from TPLO to diagnosis of osteosarcoma
at the previous TPLO site in dogs of the present study was
5.3 years, with a range of 1.0 to 10.7 years. This is similar
to previously reported postsurgical intervals for the di-
agnosis of sarcomas at TPLO sites (3.0 to 6.5 years).21–24
Reported mean time to diagnosis of fracture-associated
sarcoma (5.8 years [range, 1 to 12 years]),15,17 for osteo-
sarcoma at site of a triple pelvic osteotomy (11 years), and
for osteosarcoma at the site of total hip replacement (8
years) following surgery are similar.18–20 This similarity in
time to the development of sarcomas may imply similar
causal factors. Several inciting or causal factors have been
proposed for development of fracture- or implant-associ-
ated sarcoma, including chronic infection and inflamma-
tion, local tissue reaction to the implant, corrosion of the
implant and resultant corrosion products effects on local
tissue, delayed bone healing, and decreased vascularity of
the fractured bone.15,17
Prevalence of fracture-associated osteosarcoma has
been reported as 4.5% (12/264 dogs).12 Although the in-
cidence of osteosarcoma at previous TPLO sites in dogs
has yet to be investigated in a peer-reviewed study, it is
thought to be low (< 1%).a The present case series was
designed to elucidate the clinical characteristics and out-
come in a group of dogs with this condition; we did not
estimate incidence, which would be outside of the scope
of the case series design. Because the study focused on
dogs with a diagnosis of osteosarcoma following TPLO
at different institutions, this case series did not include
evaluation of dogs that underwent TPLO and did not de-
velop osteosarcoma, which would allow an estimate of
incidence to be calculated. The findings from the present
study, particularly the interval between TPLO and diag-
nosis of osteosarcoma, will be important for design of a
cohort study to assess the incidence and any potential
causal relationship between TPLO and osteosarcoma at
the proximal aspect of the tibia.
Five dogs in the present study received radiation
treatment, and 2 of these dogs had the TPLO plate re-
moved prior to treatment as part of a biopsy procedure.
However, in the authors’ experience, both SRT and
1058 Scientific Reports
palliative-intent radiation therapy can be performed
adequately without plate removal with the guidance
of a medical radiation physicist. Interestingly, 2 of 10
dogs that received curative-intent treatment had metas-
tasis to a regional lymph node, which is uncommon-
ly reported in dogs with appendicular osteosarcoma
(10/228 [4.4%] in 1 study54) and has been associated
with a poorer prognosis (MST, 59 days and 318 days
for dogs with and without metastases to lymph nodes,
respectively). The 2 dogs with metastases to popliteal
lymph nodes in the present study had survival times
(405 and 1,388 days) that were longer than the MST. A
wider-scale, multi-institutional study would be useful
to determine whether the prevalence of metastases to
lymph nodes is higher in dogs with TPLO-site osteo-
sarcoma than in other dogs with appendicular osteo-
sarcoma and whether survival time differs significantly
between these groups.
The limitations of the present study should be con-
sidered when interpreting the results. These data were col-
lected from multiple institutions to maximize the number
of cases that could be described for a rare problem; how-
ever, the authors acknowledge that treatment advice and
treatment protocols used likely varied. The retrospective
nature of the study could also have contributed to diffi-
culty in obtaining complete data for each dog. Another
limitation of the study was that the radiographic, cyto-
logic, and pathological examinations were performed by
different radiologists, clinical pathologists, and anatomic
pathologists, which introduces variability in reporting
and interpretation. The specific relationship between
TPLO and osteosarcoma was not investigated, and further
research is needed to evaluate the incidence of osteosar-
coma in dogs treated with this procedure. The results of
this study suggest osteosarcoma should be a differential
diagnosis for dogs with a history of TPLO that later de-
velop lameness and swelling at the previous surgical site.
a. Slocum TD. Incidence of neoplasia with TPLO surgery and Slo-
cum implant (abstr), in Proceedings. 32nd Annu Conf Vet Or-
thop Soc 2005;16.
b. Prism, version 5.0, GraphPad Software Inc, La Jolla, Calif.
c. Slocum 3.5-mm TPLO plate, Slocum Enterprises, Eugene, Ore.
d. Synthes 3.5-mm TPLO plate, Synthes Veterinary, West Chester, Pa.
e. Veterinary Instrumentation 3.5-mm TPLO plates, Veterinary In-
strumentation Ltd, Sheffield, South Yorkshire, England.
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