University of Texas at Arlington Institutional Animal Care and Use Committee Scoring Endpoints
University of Texas at Arlington
Institutional Animal Care and Use Committee
Scoring Endpoints in Tumor Studies in Rats and Mice
A.BACKGROUND INFORMATION
a.Tumor (cancer)researchin animals is an importantexperimental activitywhichalsorequiresconsideration of theeffect of thetumoron the animal.
b.This policyis designedto insurethat rodents withinducedtumorsareassessedfrequentlyandmanagedtominimize pain and distress while at thesametimeaccomplishingtheresearchobjectives. ThePrincipalInvestigatorwill beconsultedconcerningthetermination ofanyanimal forhumane reasons.Insituationswherethe welfareof theanimal is an issue and thereis no clearagreement, the decisionof theattendingveterinarian concerningthe treatment ofthe animal will be final, as designatedbythe federalAnimalWelfareAct.
c.Tumor studies aswellasall otherstudies should bedonewith minimal pain,distress, or sufferingto the animals. Most tumor studies relyupon the abilityofthe investigatorsandallparties involved beingable to judge the signs ofmorbidity(disease/illness) in which the animal could recoverfromsigns ofmoribund condition (stateof dying).
B.RESPONSIBILITIES
a.Protocol personneland the Animal Care Facility (ACF)staffshall follow the proceduresoutlinedbelow.
C.PROCEDURES
a.Protocol personnel are responsible for monitoring animals and assessing tumors atleastthree times perweekuntil thetumoris palpableas a part ofamonitoringplan.Oncepalpable, theanimal and tumorshould be observedatleast oncedaily. Measuringthe tumordimensions with calipers is a reliablemethod of monitoringtumorgrowth. Bodyweight should berecordedatleasttwice per week.
b.All induced tumor studiesare recommended to be atleast CategoryDdueto theulceration of tumors andthe undetectable presenceof metastatic cells.
c.Animals will be isolated if tumorsare found to beulcerated,abradedand/orbleedingand the veterinarianandinvestigatorcontacted.Since superficial tumorscanopen, drain and evenregress in size, there maybea significantindividualvariation in the responseananimal has to a tumorburden; it isnecessarytorelyon experience andclinicaljudgment in assessingthe need for euthanasia.Ifthe
tumoris excised, the animals must be able to ambulateandaccess food/waterfollowingthe surgicalprocedure.
d.For subcutaneous tumors, the maximum size allowed for amouseis 20 mm indiameterand 40 mm diameter in arat. Ifananimal has morethan one tumor,thesesizes are the maximum allowable sizes forall tumors combined.Ifatumoris required for studyreasonsto growlarger than theserecommendations,scientific justification must be includedin theanimal use protocol.
e.Ifdeath is to beusedas an endpoint,fullscientificjustificationanddocumentation must be providedbytheprincipalinvestigatorand must bereviewedandapprovedbyall votingmembers ofthe UTAIACUC.
f.To address biosafety guidelines, all tumor cell lines must be MAP (Mouse Antibody Production) or RAP (Rat Antibody Production) tested prior to injection into animals. All UTA safety and health guidelines will be followed in testing, handling, deriving and injecting all tumor cell lines.
i.If the tumor cell line is obtained from a commercial source, no additional documentation is required.
ii.If the line is obtained from a non-commercial source, additional documentation of MAP (or RAP) testing is required.
g.When extendedsurvival data are neededfromatumormodel it becomesnecessaryto tryto determine a specificpoint or parameterat which to record theanimal as ‘moribund’ or as‘dead’without causingtheanimalneedless distress orsuffering.Alternatives topainfulprocedures should be researched thoroughlybefore usingdeath as anendpoint.
h.Alternatives to death-as-endpointstudiescan be determinedseveral ways.
i.Determine aspecific tumorsizeto designateas ‘moribund’ or ‘dead’
ii.Determine ameasurableconcentration ofatumormarkerassociatedwiththe model.
iii.Usea scientificapproachinvolvingtermination afterafixed period oftime.
i.Investigators usinga tumormodel to gathersurvival datashould investigatearelevant parameter that willyield a statisticallysignificant efficacywithoutjeopardizingthe humanetreatment of the animals, and will not necessitate theuseof death asanendpoint.
j.In order to maximizestudydata acquisitionandminimize animal pain anddistress, the generalhealth andwelfareof test subjects willneed to be continuallyand comprehensivelyassessed anddocumented astumors and associated diseaseprogresses. With thesehealth assessments,including the use of the Tumor Scoring Sheet, the ACF veterinarystaff inconjunction with researchpersonnelcan determine wheneuthanasia is appropriateforthe animal. Intheabsence ofresponsiblelabpersonnel, euthanasia will beperformedat thediscretion ofthe facilityveterinarian or theirdesignees.
k.Theanimals should be euthanized if: (1)Themassseverelyrestricts theanimal’sabilityto eat, drink, eliminatewastes,breathe or move, (2) Themass becomesnecrotic orruptures, (3)Bodyfluid is excessive, (4)Thetumorweight vs.body
weightexceeds 15%, (5)Animal is becomingemaciated and/or loses morethan20%oftheirpre-studyweight, or(6)Thereis a largemass around thehead.
l.When assessingthe health of animals utilized forcancer studies, the followingclinicalpresentationswarrantspecialattentionas theyindicate diminished healthstatus that mayresult from increasingtumorburden andmetastasis:
i.Weight loss and decreasingbodycondition
ii.Severediarrhea
iii.Progressive dermatitis
iv.Roughhaircoat, hunched posture,lethargicand/orrecumbent
v.Respiratory-associatedsymptoms such as laboredbreathing, coughingandnasaldischarge
vi.Icterus/Jaundice
vii.Hemorrhage from anyorifice
viii.Neurological signs suchas circlingor ataxia
ix.Self-inflicted Trauma
x.Impairment of ambulation likelyto interferewithaccess to foodand water
xi.Ulcerationand necrosis of visible tumors
m.When assessingtumorsinrodents,see thecharts,attached below, and followrecommendations on vetcareand/oreuthanasia.
D.REFERENCES
a.Wallace,J.Humane Endpoints andCancerResearch.ILAR41(2), 2000
E.ATTACHMENTS
a.Mouse TumorScoring
b. Rat Tumor Scoring
1.AppearanceandBodyCondition (BC) Score:
a.BCS of 3: Normal;Score=0.
Mouse Tumor Scoring
b.BCS of 3: poor haircoat,decreasedactivity, normal posture andmobility;Score=2.
c.BCS of 2: poor haircoat,decreasedactivityor hunchedposture;Score=3.
d.BCS of 1: poor haircoat,severelethargy; Score=6.
e.Moribund and/or severe cachexia; Score=19.
2.Tumor °ree of necrosis or ulceration(degreeof ulceration to bedeterminedbyACFstaff):
a.Tumor≤ 7mm in anydimension; Score=0.
b.Tumor≤ 7mm in anydimension with minor ulceration;Score=4.
c.Tumor 7-17mm in anydimension; Score=9.
d.Tumor ≥ 18mm in anydimension, or abdominaldistention;Score=12.
e.Tumor ≥ 20mm in anydimension; Score=14.
3.BodyweightChange(for growing animalssubtractpercent deviation fromnormalgrowth pattern).
a.No changefrompre-tumor weight;Score=0.
b.Weight loss of 5-10%, orgain of 5%; Score=9.
c.Weight loss of 10-15%,or gain of 6-9%; Score=12.
d.Weight loss of >15%, orgain of 10%; Score=15.
e.Weight loss of >25%;Score=18.
1.AppearanceandBodyCondition (BC) Score:
a.BCS of 3: Normal;Score=0.
RatTumor Scoring
b.BCS of 3: poor haircoat,decreasedactivity, normal posture andmobility;Score=2.
c.BCS of 2: poor haircoat,decreasedactivityor hunchedposture;Score=3.
d.BCS of 1: poor haircoat,severelethargy; Score=6.
e.Moribund and/or severe cachexia; Score=19.
2.Tumor °ree of necrosis or ulceration(degreeof ulceration to bedeterminedbyACFstaff):
a.Tumor≤ 20mm in anydimension; Score=0.
b.Tumor≤ 20mm in anydimension with minor ulceration;Score=4.
c.Tumor 20-34mm in anydimension;Score=9.
d.Tumor ≥ 35mm in anydimension, or abdominaldistention;Score=12.
e.Tumor ≥40mm in anydimension; Score=14.
3.BodyweightChange(for growing animalssubtractpercent deviation fromnormalgrowth pattern).
a.No changefrompre-tumor weight;Score=0.
b.Weight loss of 5-10%, orgain of 5%; Score=9.
c.Weight loss of 10-15%,or gain of 6-9%; Score=12.
d.Weight loss of >15%, orgain of 10%; Score=15.
e.Weight loss of >25%;Score=18.