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http://jfm.sagepub.com/content/15/5/366Theonline version of this article can be foundat:
DOI: 10.1177/1098612X13483235
2013 15: 366Journal of Feline Medicine and SurgeryLaura Blackwood
Cats with Cancer : Where to start
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366 JFMS CLINICAL PRACTICE DOI: 10.1177/1098612X13483235 ISFM and AAFP 2013
Journal of Feline Medicine and Surgery (2013) 15, 366377
CATS WITH CANCER
Where to start
Laura Blackwood
Cancer in cats
The most common tumours in cats are summarised with their pre-senting features and differentials in Table 1, and some are illustrated onpage 368. Often, there may be non-neoplastic differentials for masslesions as cats develop more granulomatous lesions than other species.They can also develop quite marked lymphadenopathy due to reactiveor infectious causes. Furthermore, extranodal lymphoma can arise atany site, and is much more common in feline patients than in theircanine counterparts, as are the alimentary/abdominal and cranialmediastinal forms of the disease.
Clinical signs
Patients with cancer may present with a mass lesion (eg, a palpablemammary lesion) or with signs secondary to a mass such as halitosis,poor grooming or a malodor-ous coat in those with oral
masses. The different behav-iour patterns of individual catsaffect how quickly masslesions are noted and, unfortu-nately, many cats present latein the disease course. Cats withcancer may present with non-specific signs, such as alter-ations in appetite, reducedactivity levels or weight loss(Figure 1). Nonetheless, a greatdeal of information can beobtained from clinical exami-nation in cats, as abdominalmasses are often readily palpa-ble, and changes in thoraciccompressibility may be apparent where there is a cranial mediastinalmass.
Some cats present with clinical signs of metastatic disease rather thansigns relating to the primary tumour. This is seen most often in cases of
Figure 1 Elderly male neutered (MN) domesticshorthair (DSH) cat, which presented with weight lossdue to alimentary and renal lymphoma
Practical relevance: Many cats
develop cancer and may or may not
present with an obvious mass lesion.
As our feline patients are living longer
and their owners are increasingly
seeking veterinary care, the apparent incidence
and prevalence of cancer is increasing.
Clinical challenges: Neoplasia is a differential
for many clinical presentations in cats. Often
tumours are relatively advanced at the point of
presentation, and this can make management
difficult. In addition, many cats find clinic visits
stressful and this can influence owners
decisions about treatment.
Audience: This review provides an overview
of the approach to the feline cancer patient, and
is aimed at all veterinary practitioners that see
cats. It is intended as a starting point for more
detailed discussions in accompanying articlesin this special issue on feline oncology.
Evidence base: There is limited data on most
feline tumours compared with tumours in canine
or human patients, so a robust evidence base is
often lacking.
Laura BlackwoodBVMS PhD MVM CertVR DipECVIM-CA (Onc) MRCVSRCVS & European Specialist in Veterinary Oncology
Small Animal Teaching Hospital,University of Liverpool, Chester High Road,
Neston, Wirral, CH64 7TE, UKEmail: L.Blackwood@liverpool.ac.uk
C L I N I C A L R E V I E W
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JFMS CLINICAL PRACTICE 367
REV IEW/Cancer in cats an introduction
Tumour type Site Signalment/clinical signs/comments Differentials
LYMPHOMA Alimentary Older catsInsidious weight loss
Anorexia/reduced appetiteDiarrhoeaOccasionally vomiting
Malabsorption/protein-losing enteropathyIf gastric involvement, secondary gastritis/ulceration
All other causes of weight loss and gastrointestinalsigns including:
Inflammatory bowel diseasePancreatitis/triaditisInfectious/antibiotic-responsive disease
Endocrine diseaseRenal disease
All other causes of mesenteric lymphadenopathyincluding:
Feline infectious peritonitis (FIP)Inflammatory bowel diseaseMetastatic neoplasiaPancreatitisMycobacterial infection
Multicentric Any ageNon-painful lymph node enlargement (may be regional)
AnorexiaDepressionNon-specific malaisePyrexia(Polyuria/polydipsia uncommon)
Retroviral/viral, bacterial, fungal, mycobacterial(and protozoal) infectionsImmune-mediated diseaseIdiopathic lymphadenopathyOther haematopoetic malignanciesMetastatic disease (regional)
Cranialmediastinal
Younger cats, OrientalsRespiratory distressRegurgitation/dysphagiaWeight lossLethargy, exercise intolerancePalpable reduction in cranial thoracic compressibilityCough (uncommon)
ThymomaOther cranial mediastinal lymphadenopathyOther causes of pleural effusion:
Congestive heart failurePyothoraxFIP(Trauma/haemothorax)
Extranodal:nasal
Nasal dischargeEpistaxisNasal obstructionFacial distortionExophthalmosReduced appetite
Other nasal tumoursChronic rhinitis/sinusitis
Extranodal:renal
MalaiseAnorexiaRenomegaly (often bilateral)
Azotaemia
Chronic renal failureOther renal tumours
Extranodal:central nervoussystem (CNS)
Signs depend on siteRarely solitary may find other sites on stagingCNS lymphoma can be difficult to confirm:
Extradural masses: no tumour cells incerebrospinal fluidBone marrow aspirate?
Other neoplastic CNS disease (especially meningioma)Inflammatory CNS diseaseInfectious CNS disease:
ToxoplasmosisFIPFeline leukaemia virus (FeLV)/felineimmunodeficiency virus (FIV) infection
SQUAMOUSCELLCARCINOMA
Oral cavity HalitosisUnkempt coatOral mass lesion (commonly sublingual)
Dental diseaseFibrosarcomaLymphomaGranulomaOther tumour (eg, osteosarcoma)
Rhinarium/pinna/eyelid/
other cutaneous
Plaque-like or papillated, scaly, crusty, crateriformor ulcerated mass
Papillary or fungiform massOften indurated (fixed and firm)
Eosinophilic granulomaActinic keratitis (precursor of squamous cell carcinoma)
Basal cell tumour
MAMMARYCARCINOMA
Mammaryglands
Mass associated with mammary glandSize has prognostic significance (3 cm worse prognosis)
SarcomaBenign mammary tumourMammary hypertrophy/fibroadenomatous hyperplasia
SOFT TISSUESARCOMA
Injection siteOthercutaneous/subcutaneous
Firm, poorly circumscribed massMay be multilobular
Alopecia/ulceration
Cutaneous:Basal cell tumourMast cell tumourSquamous cell carcinoma
Subcutaneous:Mast cell tumourOther sarcoma
Abscess(Lipoma relatively uncommon)
Table 1 Common tumours in cats clinical signs and differentials
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a
b
Intestinal lymphoma, with renal involvement, in the elderly MN DSH catpictured in Figure 1. This lateral abdominal radiograph showsgastric/intestinal gravel sign consistent with partial obstruction, a largemid-ventral abdominal soft tissue mass, and a rounded irregularenlarged renal shadow. The cat responded well to cyclophosphamide,vincristine and prednisolone, but on relapse did not respond to rescuetherapy. Survival time was 7 months
Oral mass, diagnosed as lymphoma, in an adult female neutered(FN) DSH cat (recently rescued). The cat responded well tocyclophosphamide, vincristine and prednisolone and had a survivaltime of more than 2 years
Lymphoma
Squamous cell carcinoma
Soft tissuesarcoma
Unresectable sublingual and lingual squamous cellcarcinoma in an 8-year-old MN DSH cat. There was noresponse to palliative medical therapy or chemotherapyand the cat was euthanased 3 weeks after diagnosis
Early cutaneous squamous cellcarcinoma in a 17-year-old FNDSH cat that presented forpostoperative radiation therapyof a labial squamous cellcarcinoma. Surgical excision ofthis mass was curative, but therewas relapse at the site of thelabial squamous cell carcinomaafter 5 months
Advanced rhinarialsquamous cellcarcinoma in an8-year-old MN DSH cat,presented for radiationtherapy. Short-termpalliation was achieved
Maxillary fibrosarcoma causing grossfacial distortion in an 11-year-old FNDSH cat. Suture is present from arecent biopsy
Large soft tissue sarcoma (suspected injection site-associated sarcoma) in an adult MN DSH cat
C o m m o n f e l i n e t u m o u r s
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JFMS CLINICAL PRACTICE 369
lungdigit syndrome (Figure 2), wherepatients present with metastatic lesions of thedigits (usually multiple) secondary to primarylung tumours.1,2 Cats may also infrequentlypresent with signs due to paraneoplastic dis-ease. Cutaneous manifestations of neoplasiaare uncommon butdramatic (eg, para-neoplastic alopeciain pancreatic, hepaticor bile duct carcino-ma; exfoliative der-matitis with thymo-ma), and neoplasiashould be a dif-ferential for cats pre-senting with thesedermatological com-
plaints (Figure 3).36
REV IEW/Cancer in cats an introduction
Getting a diagnosis
Key to appropriately managing cancer cases ishaving an accurate diagnosis, so that correcttumour staging can be performed and thebest treatment recommended. Clinical fea-tures typical of a malignant tumour includerapid growth, fixation, invasion into deep tis-sues or overlying skin, ulceration and poorlydefined margins. Clinical criteria can suggesta lesion is malignant, but apparently lessaggressive behaviour should not result in thelesion being assumed benign. For example,aggressive mesenchymal tumours may
appear well demarcated due to pseudocap-sule formation. Sampling of mass lesions bycytology or histology is required.
The advantages and disadvantages ofcytology and histopathology are summarisedin the box below. Neither technique is 100%sensitive or specific in the diagnosis oftumours, although histopathology remainsthe gold standard.
a b
Figure 2 Lungdigitsyndrome in an adult DSHcat. The patient presentedto the orthopaedic serviceat the authors hospital forinvestigation of lamenessand digital swellings (a). Apulmonary mass was foundon thoracic radiography, asdemonstrated by the rightlateral view shown in (b).Reproduced from Corr andBlackwood (2003)2
Figure 3 Severe exfoliativedermatitis, seborrhoea andalopecia in a 14-year-old MNDSH cat that was presentedas a dermatology referral (a).
A pulmonary mass was foundon thoracic radiography(dorsoventral view, b) andconfirmed cytologically as anadenocarcinoma. Courtesy ofDr Tim Nuttall
a
b
Cytology Relatively non-invasive
Minimal restraint often
sufficient
Minimal tissue disruption
Rapidly performed
Results obtained quickly
Cheaper
No architectural detail
Small numbers of cells
examined representative?
Limited assessment of tumour
type/grade
Histopathology More invasive
General anaesthesia (or
sedation) required
Moderate tissue disruption
More time-consuming
Delay in results
More expensive
Architecture apparent
Larger sample size
more representative?
More accurate assessment
of tumour type/grade
Comparison of cytology and histopathology
Key to appropriately managing cancer cases
is having an accurate diagnosis.
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Sampling by cytology
Cytology will usually differentiate betweenneoplastic and inflammatory lesions, anddetermine if tumours are malignant or benign.Cytology will also broadly ascertain tumourtype (epithelial, mesenchymal or round celltumour) but not the exact histogenesis; forexample, sarcoma may be diagnosed, but his-
tology will be required to determine the tissueof origin. There are other pitfalls to be wary oftoo: dysplastic epithelial or mesenchymal cellsmay mimic neoplastic change, and this isparticularly problematic where there is con-current inflammation.
Fine needle aspirates may be non-diagnos-tic due to low yield in some sarcomas. In cats,fine needle aspirates from lymph nodes areless likely to be diagnostic of lymphoma thanin dogs, and it may be impossible for theclinical pathologist to differentiate lymphomafrom a very reactive node; in many cases,biopsy is required. However, fine needle aspi-rates are very useful in extranodal lymphoma,and cytology of bone marrow may helpsupport a diagnosis of CNS lymphoma asmany affected cats are reported to have bonemarrow involvement.
Cytology is also very useful in making adiagnosis from fluid samples. In cases ofsuspected neoplastic effusion, the detection oftumour cells in samples with low cellularitycan be enhanced by preparing a sedimentsmear (see box).
Sampling by biopsy
Biopsy is more invasive than harvesting sam-ples for cytology, and there are increased risksof haemorrhage, transplantation of tumourcells, compromise of future surgery anddamage to adjacent structures, although goodtechnique minimises these risks. If suspiciousof an infectious cause, it is advisable not to fix
all biopsy tissue so the procedure does nothave to be repeated to perform bacterial,fungal or mycobacterial culture. Tru-cut biopsies are useful for samplingparenchymatous organs non-invasively, butsamples are small. Tru-cut biopsies of lymphnodes are not recommended as they are ofteninsufficient to allow diagnosis of lymphoma,and may be no more sensitive than fineneedle aspiration for the detection ofmetastatic disease. Punch biopsies are most often used forskin lesions, but can be used for samplingoral masses (although the defect is harder toclose than an inverted wedge). They are oflittle value for lymph node biopsy. Grab biopsies tend to be used to sampletissue from the respiratory and alimentarytracts. Biopsy of suspected nasal tumours isbest achieved through the external nares witha small set of cup biopsy forceps. If these arenot available, a sharp bone curette can beused to try to scoop out tumour, or a cut-offurinary catheter can be inserted into themass, with gentle rotation and suction
The chances
of detecting
tumour cells
in effusion
samples with
low cellularity
can be
increased by
preparing a
sediment
smear.(a) Line smear from a thoracic effusion. The smear isprepared in the same way as a blood smear, but instead ofcreating a feathered edge, the aim is to create a line wherecells are concentrated together. This is achieved by abruptlystopping smearing mid-way and lifting the smearing slide off,creating a line. The technique is illustrated in (b) and (c) using abloody sample for easy visualisation
b
a
c
A sediment smear can be prepared in practice using the
urine setting on a StatSpin (or similar benchtop) centrifuge;
the aim is to use the slowest spin to minimise cell
damage/destruction. The majority of the supernatant is
decanted off and the sediment is gently resuspended
before making the smear or line smear (as illustrated here),
and these samples are submitted along with the fluid sam-
ple in EDTA. For very haemorrhagic samples, the laborato-
ry can prepare a buffy coat smear to maximise the
chances of finding tumour cells. Care is required in inter-
preting fluid samples from body cavities, as reactive
mesothelial cells can look similar to neoplastic epithelial
cells; submission to a clinical pathologist is recommended.
S e d i m e n t s m e a r t e c h n i q u e
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JFMS CLINICAL PRACTICE 371
REV IEW/Cancer in cats an introduction
applied to harvest a sample. Whichevermethod is employed, the biopsyforceps/catheter should first be measuredagainst the patient and the distance from theexternal nares to the medial canthus markedon the biopsy tool (or the catheter cut justshort of this length); it is vital that theinstrument is introduced no further than thispoint, to avoid the risk of biopsying braintissue (Figure 4). Endoscopic grab biopsies from thegastrointestinal tract produce small,superficial samples composed mainly of
mucosa. Multiple biopsies should be taken.In addition, biopsies from both duodenumand ileum (ie, using both upper and lowerendoscopy) are recommended in cases wherethe major differentials are inflammatorybowel disease or lymphoma, as biopsy froma single site is likely to fail to identifylymphoma in a significant proportion of
cases.7 Full thickness biopsies may berequired in feline intestinal disease. Incisional biopsies allow visualisationof tissue and harvesting of larger samplesthan Tru-cut, punch or grab biopsies. Wedgebiopsies are recommended to sampleaccessible masses, such as oral masses. Whenharvesting incisional biopsies, ulcerated andnecrotic areas should be avoided, as shouldthe junction between normal and neoplastictissue, which would otherwise increase thesurgical field. The biopsy site should beplanned so that the entire biopsy tract can
be removed at definitive surgery. Excisional biopsy is indicated for lymphnodes, some intestinal masses and formost mammary tumours in cats, but isotherwise seldom indicated. This is becauseinappropriate excisional biopsy canjeopardise future treatment, and the firstsurgery offers the best chance of cure. Thisis especially true for cats with soft tissuesarcomas. Reported recurrence rates for felinesarcoma are in excess of 70%, and every effortshould be made to avoid inappropriatemanagement.
Clinical staging
Clinical staging involves assessment of theprimary tumour (T), including involvement ofadjacent structures, and assessment for metas-tasis to local and regional lymph nodes (N)and distant sites (M). The aim of TMN stagingis to inform clinical decision making andensure the best treatment possible under theindividual circumstances of the case.
Assessment of the primary tumour shouldinclude evaluation of extent, by clinical exam-ination and appropriate diagnostic imaging
Figure 4 (a) Unilateral nasal discharge in a2-year-old MN Siamese cat. Biopsies in thiscase confirmed lymphoma. When takingbiopsies from nasal tumours, it is important firstto measure the grab biopsy forceps or cut-offurinary catheter either against the patient sothat the biopsy/catheter is not inserted anyfurther than the level of the medial canthus, oragainst a dorsoventral intraoral radiograph (b) toensure the biopsy/catheter ends within tumourand cranial to the cribriform plate
a
b
Sampling of feline skin lesionsBenign epithelial tumours and papillomas are uncom-
mon in cats, and 5060% of skin tumours are malignant.
Non-neoplastic conditions may also present as
proliferative or ulcerative lesions, including eosinophilic
granuloma complex, flea allergic dermatitis, mycoses,
poxvirus, dermatophytoses and immune-mediated disease.
The commonest skin tumours are basal cell tumours
(probably these were over-diagnosed historically),
squamous cell carcinomas, mast cell tumours and
fibrosarcomas.8 Excisional biopsy is generally not
recommended for feline skin tumours. Fine
needle aspiration or biopsy is recommended
to identify those lesions where local
excision is inappropriate.
Inappropriate
excisional
biopsy can
jeopardise
future
treatment.
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or endoscopic techniques, and a diagnosis oftumour type based on cytology or histology(see earlier). The sensitivity of tests should beborne in mind. For example, clinical examina-tion of a maxillary squamous cell carcinomamay suggest a less extensive tumour thanwould radiography, which in turn is lesssensitive than computed tomography (CT).
Exploratory laparotomy in a suspected orconfirmed cancer patient should always con-tribute to tumour staging (see box).
Lymph node evaluation
Carcinomas most commonly metastasise bythe lymphatic route, and local and regionallymph nodes should be evaluated in cats with
carcinoma by palpation (eg, of axillary andinguinal nodes in cats with mammarytumours), diagnostic imaging, and aspirationand cytology. Mast cell tumours also metasta-sise by the lymphatic route, but reportedmetastatic rates for cutaneous mast celltumours in cats vary, ranging from 022%,and most histologically well-differentiatedtumours have a low metastatic potential.Poorly differentiated tumours are moremalignant. (Visceral mast cell tumours aregenerally malignant and metastases may bewidespread at presentation.)
Thoracic radiographs
Primary lung tumours are relatively readilydiagnosed radiographically (Figures 2 and 3).Compared with dogs, cats less frequentlydevelop classical well-defined cannon ballmetastases, and metastatic disease can appearas ill-defined mass lesions or diffuse alveolar,interstitial or mixed patterns (Figure 5).9 Abronchial component is relatively commonin metastatic patterns in bronchoalveolarcarcinoma.10 Cytology of lung aspirates orbronchoalveolar lavage fluid may be requiredto confirm a diagnosis.
Abdominal ultrasoundMass lesions and markedly enlarged lymphnodes may be detectable on abdominal pal-pation, but abdominal ultrasound allowsdetection of lesions not apparent on clinicalexamination, including lesions within hepatic,splenic and renal parenchyma, as well aschanges in layering of the gastrointestinaltract and more subtle lymph node enlarge-ment.
Advanced imaging
Advanced imaging is increasingly availablefor veterinary patients, and is very valuable.However, it is expensive, and, as with anydiagnostic test, should be utilised with full
consideration of the value of the study andthe cost implications for future managementof the case. When mass lesions are found,samples should be harvested to allow adiagnosis.
Have a plan: do not perform a peek and shriek!
Achieve adequate access
Biopsy (or fine needle aspirate) any suspicious
lesions
Examine/fine needle aspirate/biopsy local and
regional nodes
Examine/fine needle aspirate/biopsy
parenchymatous organs
If you resect a mass
Think about your margins
Resect adhesions with the mass
Discard contaminated instruments (tumour
or gastrointestinal contents)
Decide if you should place a feeding tube
(Keep a fresh piece of tissue for culture if
suspicious of a granulomatous lesion)
Figure 5 Lateral thoracic radiograph (inflated) of an elderly FN DSH cat. Multiple poorlydefined soft tissue opacities are seen, which represent metastases from an unknown primary.There are also increased interstitial and bronchial markings
Compared
with dogs, cats
less frequently
develop
classical
well-definedcannon ball
metastases.
E x p l o r a t o r y l a p a r o t o m y a n d t u m o u r s t a g i n g
The importance of clinical staging is sometimes forgotten during abdominal surgery, particularly
when exploratory surgery is performed and a mass is discovered. At the time of surgery, there is the
opportunity to assess the primary tumour/mass and also to evaluate other organs. Some pointers
for getting the best outcome from exploratory laparotomy are given below.
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Computed tomography is most useful forevaluation of tumours where there is likely
to be skeletal involvement, and is generallyrequired for radiation planning (Figure 6).CT is also useful for the identificationand staging of pulmonary neoplasia(including evaluation of bronchial nodes)and pulmonary metastatic disease. Magnetic resonance imaging is usefulfor the evaluation of soft tissue lesions andlesions in the CNS. It is particularly valuablein planning surgery in cases of soft tissuesarcoma.
Blood testsMost blood tests do not help to make a diag-nosis of cancer in cats, but they can help toidentify common co-morbidities, and this canbe very important in decision making.
On haematology, there may be a mildnon-regenerative anaemia and a stress haem -ogram. These are the commonest findingsin lymphoma patients.11 Abnormal circulatingcells and/or lymphocytosis is relatively
uncommon. Even in cats with leukaemia, theremay be no abnormal circulating cells on
haematology.On biochemistry, changes are often non-
specific and may reflect stress (eg, hyper-glycaemia), co-morbidity or organ involve-ment (eg, hypoalbuminaemia in diffusealimentary lymphoma). Urine specific gravityshould be measured in azotaemic patients toconfirm renal or pre-renal origin. (Urinespecific gravity will be low in azotaemichypercalcaemic patients even if the renal con-centrating ability is normal because of antago-nism of antidiuretic hormone.) Paraneoplastichypercalcaemia is uncommon in cases offeline lymphoma, and is more commonly seenin patients with myeloma. Hypercalcaemiacan also be seen with other tumours, particu-larly carcinomas.
In the UK, most cats with lymphoma noware FeLV antigen negative on ELISA.However, testing is valid where there is aninfection risk to others, and where concurrentdisease may affect treatment decision making.
Figure 6 (a) Transverse CTscan of an 8-year-old MNDSH cat with poorlycontrolled diabetes mellitusdue to acromegaly, showing
a mass in the pituitary fossa.The positioning device seenis a thermoplastic mould,which is shaped round thepatient, whose head issupported on a mouldablepillow (not visible on thiswindow). The mould issecured to a baseplate.(b) CT scan of a 7-year-oldFN cat with a nasal tumour(extending into the orbit)after positioning in the samemould system (c)
a
cb
The aim of staging is to inform clinical decision making and ensure
the best treatment possible under the individual circumstances of the case.
PItuitary tumour
Thermoplasticmould
Baseplate
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Treatment options andconsiderations
In broad terms, surgery and radiotherapy canbe considered as local treatments for primarydisease or primary disease with local lymphnode involvment, and chemotherapy as sys-temic treatment for disseminated disease.
Surgery
In cats, treatment of primary mass lesionsmay be limited by small patient size and dif-ficulties in achieving wide local excision.However, surgery remains the mainstay oftreatment for solid tumours.
Mammary tumours are most often resectedby radical mastectomy, as most feline mamma-ry tumours are malignant. Both axillary andinguinal lymph nodes on the affected sideshould be resected en bloc with the mammary
tissue, but often the axillary nodes are notremoved if deemed normal as they are lessreadily identifiable than the inguinal nodes.Local excision of malignant mammary tumoursis associated with a high rate of recurrence.
Oral tumours are often unresectable by thetime of presentation: the overall cure rate fororal squamous cell carcinoma is less than 5%.Where excision is possible, considerationshould be given to placing a feeding tube at thetime of surgery to facilitate postoperative careand recovery, as cats may cope less well with,for example, mandibulectomy than dogs do,particularly in the immediate postoperativeperiod. Cosmetic and functional results may bevery good in the longer term (Figure 7).
Excision of soft tissue sarcomas, which mayhave extensive fronds of invading tumourcells, is particularly challenging in smallpatients, and compartmental excision is onlyachievable for tumours on (distal) limbs.
Radiotherapy
Radiation therapy is most often used either as apostoperative adjunctive therapy, ideally in aminimal residual disease setting, or palliativelyin the face of unresectable gross disease. When
radiation is used postoperatively, it is veryimportant to ensure that the radiation therapistis aware of the original tumour site, extent anddimensions, or the planned radiation field maynot include all of the affected tissue. This canresult in a geographical miss, where microscop-ic residual disease is not included in the treatedarea. The risk of geographical miss increases asrepeat surgeries are performed and normalanatomy becomes increasingly distorted.
The best results are likely to be achieved ifradiotherapy is considered prior to surgery,and presurgical measurements and images areavailable (ie, photographs with measurements,drawings, radiographic or other images) tohelp plan the treatment. Placement of metalsurgical clips at the margins of the surgical bedalso helps to avoid geographical miss duringradiotherapy, as there may be migration ofsubcutaneous tissues that may contain residual
tumour (Figure 8).
Figure 7 An 8-year-old MNDSH cat, which presentedwith an early mandibularfibrosarcoma. A partialmandibulectomy wasperformed, and a feedingtube placed, visible in (a),which shows the patient2 days postsurgery.(b) The cat 6 months later.In this case, surgery wascurative, but complete
excision of feline oraltumours is frequentlyimpossible
ba
Surgery
remains the
mainstay of
treatment for
solid tumours
Figure 8 Dorsoventral radiograph obtained to check the radiation field in an adult MN DSH catreceiving postoperative adjunctive radiation therapy for an incompletely resected soft tissuesarcoma. The solid line is the scar, and dots represent a margin round this of 5 cm. Two of the dotsalong the caudal margin are joined by a dotted line to show where the caudal edge of the treatmentfield lies. Two clips are positioned beyond (caudal to) this margin, indicating that a larger marginmust be used. This illustrates the limitations of basing radiation treatment fields on surgical scars
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In the clinic, radiation therapy is used to treatfeline patients in a variety of ways (see box). Pituitary tumours in acromegalic cats(Figure 6) are one of the most commonindications for teletherapy. Soft tissue sarcomas (Figures 8 and 9)are also commonly treated using teletherapy,mostly following surgical resection. The
majority of the published work in this areahas focused on injection site-associatedsarcomas. Good presurgical tumourrecording is essential for these patients, andthe risk of recurrence is greater if radiation iscarried out after multiple surgeries. Nasal and paranasal tumours (Figure 6b,c)may be treated with radiotherapy, and this isthe treatment of choice for nasal carcinomas. Itsuse in nasal lymphoma is controversial as thesecats may relapse with lymphoma in other sites.In the authors hospital, patients with nasallymphoma are most often treated withchemotherapy, with radiation used as a rescuetherapy if there is relapse of the nasal disease.A study comparing survival in patients treatedwith radiotherapy alone, chemotherapy alone,or both modalities, showed no difference inoutcome between groups.12
Abdominal cavity lymphoma has morerecently been treated with radiation therapyused in conjunction with chemotherapy or asa rescue therapy.13,14
Oral squamous cell carcinoma (Figure 10)has been treated with a variety of radiationtherapy protocols, but results have been fairlydisappointing, with short median survival
times (2 or 3 months in most studies).1517
Oncologists continue to try to find aneffective protocol for this disease, withlimited success, though a recent pilot studyof multimodality therapy reported survivalof greater than a year in 3/6 cats.18
Superficial cutaneous or rhinarialsquamous cell carcinoma may be treatedusing electrons of different energies, withtheir variable penetrations, though treatmentwith strontium is preferred as this can bedelivered as a single treatment rather thanmultiple fractions. Photodynamic therapy(PDT) may also be appropriate for superficiallesions, but recurrence is common. Eitherradiotherapy or PDT may achieve long-termcontrol after a single treatment in very
superficial lesions,19but relapse is morecommon after PDT.20,21 Topical imiquimodhas also been reported to produce clinicalremission. For invasive tumours, surgicalexcision is the treatment of choice.
Figure 9 A 9-year-old MN Birman being prepared forpostoperative adjunctive radiation therapy using electrons,for treatment of an incompletely excised, high grade injectionsite-associated sarcoma. The electron applicator has acut out made to shape the field for the individual patient.The treatment field is illuminated on the patient.Unfortunately, this cat, which also received chemotherapywith epirubicin, developed widespread metastatic disease(but no local recurrence) 18 months after radiotherapy
Figure 10 A 14-year-old MNDSH cat with a maxillarysquamous cell carcinomaat the beginning (a) andend (b) of a course ofhypofractionated radiationtherapy for a gingivalsquamous cell carcinoma.
After an initial favourableresponse, the tumourrecurred and the patientwas euthanased just over3 months after radiotherapy
b
Radiationtherapy is most
often used as a
postoperative
adjunctive
therapy, or
palliatively
in the face of
unresectablegross disease.
R a d i o t h e r a p y m e t h o d s u s e d i n c a t s
Systemic administration of iodine 131 (gamma and beta emitter) is used,
for example, to treat hyperthyroidism.
Brachytherapy (internal radiation therapy) using a strontium 90 wand,
which produces beta particles with a maximum penetration of 34 mm, is
used to treat superficial (non-oral) squamous cell carcinoma.
Teletherapy (external beam radiation) is delivered using linear
accelerators producing x-rays (photons) at 420 MV. These high energy x-rays are deeply penetrating, and high energy beams allow a more uniform
distribution of dose, particularly for deep tumours and those involving bone.
Some linear accelerators also produce electrons in a range of energies,
which are variably penetrating, allowing treatment of superficial lesions and
avoidance of toxicity to deep structures, which is useful in small patients
like cats. Radiation therapy using these sources requires multiple treatments
(usually between three and 20) delivered under general anaesthesia.
a
Applicator
Cut out
Treatment field
(illuminated)
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Chemotherapy
Chemotherapy is used where systemic deliv-ery of treatment is required to treat widelydisseminated but chemoresponsive disease(eg, lymphoma) or where there is a high riskof development of metastatic disease andmicrometastases are likely to be present (eg,some high grade sarcomas). It is generally not
a suitable option as the primary treatment fora large solid non-lymphoid tumour, which islikely to be poorly chemosensitive. Lymphoma The optimum protocolfor feline lymphoma remains to bedetermined.2224 This, at least in part, reflectsthe larger variation in clinical forms oflymphoma seen in cats compared with dogs.The role of doxorubicin/epirubicin remainscontroversial.22,24,25 Lymphoma is reviewedelsewhere2630 and extranodal disease withinthe current special issue. Some cats withlymphoma will respond very well tochemotherapy, and the best prognosticindicator is achieving complete remission.Individual cats may need more adjustmentof their protocol than dogs, but this is notinsurmountable. The major challenge intreating feline lymphoma remains the poorresponse of cats to rescue therapy comparedwith dogs, though some cats will do wellwith lomustine as a rescue agent.31
Soft tissue sarcoma The impact ofchemotherapy on survival of cats with highgrade (grade 3) soft tissue sarcomas isunproven, with most work concentratingon injection site/vaccine-associated
sarcomas.32,33 However, there may be apositive impact on disease-free interval andpossibly local tumour control in patientsreceiving radiotherapy and chemotherapywith doxorubicin,33,34 and multimodalitytreatment is recommended.35
Mast cell tumour Chemotherapy is lesscommonly used for the other tumours that
readers may be familiar with in dogs(eg, metastatic mast cell tumours,osteosarcoma), because of differing biologicalbehaviour of the tumours, and differingresponses and drug toxicities across species.The role of chemotherapy for palliative oradjuvant treatment of feline mast celltumours has not been clearly established,36
and chemotherapy is generally reserved forcats with histologically poorly differentiated,locally invasive and/or metastatic tumours.Vinblastine, chlorambucil and lomustine havebeen used. One study reports an overallresponse rate of 50% in cats with measurabledisease treated with lomustine, and a medianduration of response of 168 days.37 There isno proven role for corticosteroids in thetreatment of feline mast cell tumours.
Further discussion on the use of chemother-apy and targeted therapies in cats, with aparticular focus on the idiosyncracies of felinepatients, is provided in an accompanyingarticle in this special issue.
Funding
The author received no specific grant from anyfunding agency in the public, commercial or not-for-profit sectors for the preparation of this article.
Conflict of interest
The author does not have any potential conflicts ofinterest to declare.
Cancer is a differential for cats with
mass lesions and many non-specific
clinical signs.
For many cancers in cats, early
treatment holds the only chance of cure:
raising awareness is important,
particularly for squamous cell
carcinomas and soft tissue sarcomas.
Diagnosis and staging inform clinical
decision making; tests should be chosen
sensibly (and cost effectively when
funds are limited), based on the
information required.
Inappropriate excisional biopsy can
jeopardise future treatment, particularly
for soft tissue sarcomas.
Radiotherapy and chemotherapy are
evolving fields in feline medicine and
there is still much to learn.
KEYPOINTS
Chemotherapy
is used to treat
widely
disseminated but
chemoresponsive
disease
(eg, lymphoma)
or where there is
a high risk of
development of
metastatic
disease.
Targeted therapiesTyrosine kinase inhibitors (TKIs) have been used to
treat cats with cancer, though neither masitinib nor
toceranib is licensed in this species. There is limited data
on toxicity and efficacy. The main target tumours are
mast cell tumours, injection site/vaccine-associated
sarcomas and possibly squamous cell carcinoma.
Combination TKI and radiation therapy is being
investigated in the treatment of sarcomas and oral
squamous cell carcinomas. The main potential
toxicities of the TKIs are gastrointestinal
toxicity and myelosuppression, and
nephrotoxicity should also be
monitored for.
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