R E C U R R E N T O V A R I A N C A R C I N O M A

North Florida Regional CyberKnife® Team:

RadiationOncologists: MarkPerman,M.D. CherylleA.Hayes,M.D.

Gynecologist: KelliC.Ross,M.D.

ChiefMedicalPhysicist: DonaldDubois,Ph.D.

MedicalPhysicist: HowardSalmon,Ph.D.

MedicalDosimetrist: EricLarsen,CMD,RTT

CyberKnifeTherapists: JeanneWilson,RTT ScottMcGee,RTT

DirectorofNorthFloridaRadiationOncologyCenter: GailSuarez,MSHSA,RT(R)(T)

CyberKnifeCenter: NorthFloridaRegional MedicalCenter Gainesville,FL

CASE STUDY

R E C U R R E N T O V A R I A N C A N C E R

DEMOGRAPHICSSex: FemaleAge: 60 years Histology: Poorly differentiated serous papillary

ovarian carcinoma

CLINICAL HISTORYReferred by: GynecologistPast Medical History: Stage IV ovarian carcinoma

Case HistoryA60-year-oldfemalewithahistoryofStageIVovariancarcinomapresentedwithrisingCA-125levels(21.1U/mlto34.4Uml),signifyingaprobableovariancarcinomarecurrence.SubsequentMRIshoweda2.8x2.5cmnoduleintheregionoftheleftuppervaginalcuffwhichwasconfirmedbybimanualexamination.

InitialdiagnosisofStageIVovariancarcinomawasmadesixyearsearlierwhenthepatientpresentedwithright-sidedpleuraleffusionandCA-125of1482U/ml.Anexploratorylaparotomywasdoneandanomentalcake,peritonealstuddingandanoduleadjacenttotherectosigmoidwereresected.Pathologyshowedpoorlydifferentiatedserouspapillaryovariancarcinoma.Overthenextfouryearsthepatientunderwentmultipleroundsofchemotherapyaswellasstemcelltransplantandadditionalsurgicalresectionintheefforttocontrolherdisease.Thepatient’slatestchemotherapywasprematurelydiscontinuedwhensheexperiencedasevereanaphylactoidreaction.AtthattimethedecisionwasmadetofollowhercloselywithimagingandCA-125measurements.

CyberKnife® Treatment Rationale EpithelialovariancanceristheleadingcauseofdeathamongwomenwithgynecologicmalignanciesandisthefifthmostcommoncancerinwomenintheUS.Morethan70%ofwomenwithepithelialovariancancerhaveStageIIIorIVdiseaseatthetimeofdiagnosis.1Adjuvantchemotherapyisrecommendedforallpatientswithadvancedstageovariancancerafterappropriatesurgery.However,morethan70%ofpatientsrelapse,withamediantimetoprogressionoflessthan2years.2Secondarysurgeryforrecurrentpatientshasnotsignificantlyimprovedsurvival.Radiationtherapyhasimprovedsurvivalinasubsetofpatientswithchemotherapy-refractorydisease,particularlythosepatientswithminimalresidualorrelapseddiseasetothepelvis,andhasprovidedgoodpalliationinpatientswithlocalabdominopelvicsymptoms.3Thispatientpresentedwitharecurrentovariancancerintheleftvaginalcuff.Duetothepatient’smedicalhistory,shewasnotacandidateforfurtherchemotherapyorsurgery.Nevertheless,theleftvaginalcuffrecurrencewasandhadalwaysbeentheonlysiteofrecurrenceinthispatient,thereforeaggressivedefinitivecarewasindicated.Highdoseratebrachytherapywasconsidered,butwasdeclinedduetoitsinvasivenatureandassociatedrisks.Externalbeamradiationwasconsideredaninferioroptionduetotheinabilitytolimitthedosetoadjacentcriticalstructureswithincreasedrisksofbladder,vaginalandrectaltoxicities.Theuseofstereotacticbodyradiotherapyasanalternativetobrachytherapyforgynecologictumorshasbeenreportedtoachieveexcellentlocalcontrolrateswithminimaltoxicities.4TheCyberKnife®RadiosurgerySystemofferedaminimallyinvasivemethodfordeliveringhypofractionatedradiationtotheleftvaginalcuffofapatientwhohadfailedtwosurgicalresectionsandnumerouscyclesofchemotherapy.

Planning ProcessThepatientwaspreparedfortreatmentplanningbyimplantingfourfiducialsintotheperipheryofthetumorbythegynecologist.AplanningCTscanwasobtained7dayslater.Thefiducialswereidentifiedandthelesionwasoutlinedonthescans.TheGTVwasdefinedasthetumorandthePTVwasdefinedastheGTVplusa3-mmexpansionresultinginatreatmentvolumeof42.53cc.Thefinalplanwascreatedtodeliver30Gyin3fractionstothe69%isodoseline.Thepatientbegantreatment6daysaftertheplanningCTimagesweretaken.

R E C U R R E N T O V A R I A N C A N C E R

Treatment Volume: 42.53 ccImaging Technique(s): CTRx Dose & Isodose: 30 Gy to 69%Dose and Fractions: 10 Gy x 3 fractionsNumber of Beams: 114Number of Fiducials: 4

Number of Nodes: 140Conformality Index: 1.25Tracking Method: FiducialCollimator(s): 35 mmTumor Coverage: 94.9%

TREATMENT DETAILS

Axial treatment plan showing isodose curves to the tumor while sparing the rectum and bladder (outlined in yellow). The orange line indicates the prescription dose to the 69% isodose line providing 94.9% coverage of the PTV.

Treatment DeliveryThepatientreceived30Gydeliveredinthreefractionsoverfourdays.Thetreatmentwasdeliveredtoavolumeof42.53ccusing114beamsanda35-mmcollimator.The69%isodoselineprovided94.9%coverageofthePTV,withaconformalityindexof1.25.Themaximumrectaldosewas30.33Gy.Lessthan0.22ccoftherectumreceivedgreaterthan28.8Gy,meetingtherectalconstraintoflessthan1ccoftherectumreceivingthatdose.Themaximumbladderdosewas31.8Gywithlessthan0.47ccofthebladderreceivinggreaterthan30Gy.Thebladderconstraintoflessthan10ccofthebladderreceivinggreaterthan30Gywaseasilymet.

3D image of the bony anatomy and CyberKnife beam positions delivered to the left vaginal cuff.

Sagittal view of the treatment plan showing isodose curves to the tumor while sparing the rectum and bladder (outlined in yellow). The orange line indicates the prescription dose to the 69% isodose line.

R E C U R R E N T O V A R I A N C A N C E R

NORTH FLORIDA REGIONAL MEDICAL CENTERThe CyberKnife Center at North Florida Radiation Oncology opened its doors on August 1, 2006 and treated more than 170 patients in its first year. The cases consist of 71% extracranial, 23% intracranial and 6% spinal treatments. HCA and North Florida Regional Medical Center, a 325-bed community hospital, are working together to develop a comprehensive cancer community oncology program to provide patients with quality care supported by state of the art technologies such as the CyberKnife.

Contact the CyberKnife Center at North Florida Radiation Oncology at 1-800-621-0575 or 352-333-5643.

Outcome and Follow-Up• OnemonthfollowingtheCyberKnife®treatmentaCTscandemonstratedadecreaseinsizeoftheleftvaginalcufflesion,whichmeasured1.86cmx2.14cm

• EightmonthsaftertheCyberKnifetreatmentthemasscouldnotbeseenandonlyminimalfullnessintheleftvaginalwallcouldbedetectedonCTimaging

• ThepatientexperiencedminimaltoxicitiesfollowingCyberKnifetreatment,whichincludedoccasionalloosestoolsandmildvaginaldischargethatresolvedsixweekspost-treatmentwithoutmedications,aswellasmildurinary urgencyandfatiguewhichcompletelyresolvedbyfivemonthspost-treatmentwithoutmedications

• EightmonthsafterCyberKnifetreatment,CA-125levelsdecreasedto7.9U/ml

References1. Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2006. CA Cancer J Clin 56: 106-130, 2006.2. McGuire WP, Hoskins WJ, Brady MF et al. N Engl J Med 334: 1-6, 1996.3. Fein DA, Morgan LS, Marcus RB et al. Int J Rad Oncol Biol Phys 29: 169-176, 1994.4. Molla M, Escude L, Nouet P, et al. Int J Rad Oncol Biol Phys 62: 118-124, 2005.

T1 and T2 MRI of 28 mm x 25 mm recurrent ovarian mass located at the left vaginal cuff prior to CyberKnife treatment.

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CT image demonstrating no evidence of the left vaginal cuff mass or recurrence 8 months after CyberKnife treatment.

2 monthspre-treatment

�rst CyberKnife treatment day

2 monthspost-treatment

5 monthspost-treatment

8 monthspost-treatment

Conclusion and CyberKnife Advantages ThispatienthadanexcellentinitialoutcomewiththeCyberKnifeSystemforthetreatmentofarecurrentovariancarcinomalocatedatthevaginalcuff TheCyberKnifeSystemprovidedaconvenientandminimallyinvasivetreatmentoptionforthispatientwithrecurrentovariancarcinomawhohadfailedprevioussurgeryandchemotherapy AbenefitoftheCyberKnifeSystem’scapacitytotargetlesionsaccuratelyisthepotentialforlowtoxicitytonearbycriticalorganssuchasthebladder,rectum,urethraandvagina