The EQD2 Concept for Practical - AOIC - Home

1 6/27/20141 The eqd2 Concept for Practical Reporting of Cervix BrachytherapyChristian Kirisits, MSc, PhDMedical University of ViennaVienna, AustriaDisclosuresChristian Kirisits, MSc, PhD, was a consultant to NucletronanElektaCompanyNucletron, an Elekta University of Vienna receives financial and equipment support for training and research activities from Nucletron, an Elekta Company and Varian patterns of response guided adaptive CTVR adiobiology: Time Dose PatternChapter 7 from new ICRU/GEC ESTRO report 88 General Principles for Assessment and Reporting of Physical and Equieffective EBRT and BT Dose (All Reporting Levels) Physical dose and number of fractions is assessed for target, OARs, dose points: BT EBRTT otal equieffective dose ( eqd2 ) is calculated according to the linear quadratic model through the following steps: BT eqd2 for each fraction Total BT eqd2 Total EBRT eqd2 Accumulated total EBRT+BT eqd2 **Based on current assumptions outlined in chapter 9 Reporting of radiobiological parameters:a/b values for tumor and OARs*In addition T1/2and recovery model for LDR and PDR treatments**At present: a/b=3 Gy for late effects in OAR and 10 Gy for tumor, and T1/2= 7 from new ICRU/GEC ESTRO report 886/27/20143 Dose Response StudiesExamples From EMBRACE and RetroEMBRACEB ladderDose response curve80%90%100%G 2 Vagina0%10%20%30%40%50%60%70%80%02040608 0100 120140160 180200 Dose to the ICRU rectal point in Gy ( eqd2 )Probability fo r v ag.

2 Stenosis GLinear quadratic model for incomplete monoexponential sublethal (DNA) damage repairRadiobiological ConsiderationsThe Role of Dose Rate Biologically Effective Dose: BED = nd [ 1 + g d / ( ) ] BED .. virtual dose value that produces the same biological effect asthe physical dose with an infinite low dose ratein Brachytherapy(J. Dutreix)In: A Practical Manual of Brachytherapy(Pierquin / Marinello,Medical Physics Publishing)S = e ( D + gD )n .. number of equal fractionsd ..dose per fractiontissue dependent parameters: parameter describing lethal/sublethal lesionsg .. repair function depending on half time for cell repair T1/2 fractionation6/27/20144 Mathematical DescriptionExternal beam radiotherapy and HDR brachytherapy: No repair during irradiation (min)repairfunctiong1repair function g = 1 LDR, MDR brachytherapy: Repair during irradiation (hours days) is significant eMDRLDRgt 1122ln ttMDRLDRg 1,21T m.

3 Repair rateT1 half time for repairt .. irradiation time Mathematical DescriptionPDR brachytherapy: Repair between successive pulses (hours) andduring the wholefraction(hoursdays)issignificantwho le fraction (hours days) is significant tnsynytPDRg 212tey 1xek 2121tntntkeekenkknks T2ln 21T .. repair rateT1 half time for repairt .. irradiation time for each pulsex .. time between pulses without irradiationn .. number of equal pulses6/27/20145 Values of Biological Parameters Tumorand early reacting normal tissue: ~10Gy7 20 Gyformosttumors 10 Gy720 Gy for most tumors9 10 Gy for cervix carcinomaT1/2~ hours Late reacting normal tissue: ~ 3 6 Gy3 4 Gy for bladder, rectum, sigmoidT1/2~ hours1 2 hoursClinical and experimental experienceMathematical Description LQ model gives biological equivalence for 1. Classical LDR brachytherapy (50 cGy/h) and2.

4 Conventional external beam therapy (2 Gy/fraction) with T15h(lii liICRU38 ICRU88)T1/2 = hours(clinical experience, ICRU 38, ICRU 88) Calculated BED values are normalized toconventional EBT with 2 Gy/fraction(reference schedule):BED = DIsoE[ 1 + 2 / ( ) ]DIsoE= BED / [ 1 + 2 / ( ) ]= eqd2 isoeffective dose = equivalent dose in 2Gy fractions To calculate thetotal isoeffective dose DIsoE of a combined treatment, all isoeffective doses DIsoEare added up:DIsoE,TOTAL= DIsoE,EXTERNAL+ DIsoE,BRACHY6/27/20146 Application of Biological Model to Clinical SituationAssumptions: Time between fractions is long enough to enable full sublethal ggdamage repair (min. ~ 8 12 hours) All investigated points and volumes from BT receive full EBT dose In fractionated treatments the investigated points or volumes represent the same anatomical position throughout the whole treatment(staticsituationassumption)trea tment (static situation assumption) The same absorbed dose and time dose pattern of EBT and BT produces the same biological effect ATTENTION.

5 Dose and dose rate inhomogeneity within BT volumeDVH for Target VolumesChapter 8 from new ICRU/GEC ESTRO report 886/27/20147 Different Fractionation Schedules (examples HDR) Point A 45 Gy EBT + 4 x 7 Gy 45 Gy EBT + 4 x 6 Gy 50 Gy EBT + 2 x GyOrgans at Risk (ICRU point) 45 Gy EBT + 4 x5 Gy Rectum6 GBl dd6 GyBladder 45 Gy EBT + 4 Gy Rectum5 Gy Bladder 50 Gy EBT + 2 x6 Gy Rectum7 Gy BladderDifferent Fractionation Schedules (examples HDR) Point A 45 Gy EBT + 4 x 7 Gy~ 84 Gy EQD210 45 Gy EBT + 4 x 6 Gy~ 76 Gy EQD210 50 Gy EBT + 2 x Gy~ 76 Gy EQD210 Organs at Risk (ICRU point) 45 Gy EBT + 4 x5 Gy Rectum~ 75 Gy EQD236 GBl dd~86 GEQD26 GyBladder~ 86 GyEQD23 45 Gy EBT + 4 Gy Rectum~ 70 Gy EQD235 Gy Bladder~ 75 Gy EQD23 50 Gy EBT + 2 x6 Gy Rectum~ 72 Gy EQD237 Gy Bladder~ 78 Gy EQD236/27/20148 = 10 Gy for cervical tumor = 3 Gy for OAR (bladder, rectum, sigmoid)Example: HDR Brachytherapy for Cervical CarcinomaPoint APhysical doseTotal doseExternal beam 25 x Gy =45 Gy44 Gy EQD210 Brachytherapy4 x Gy=28 Gy40 Gy EQD210 Total dose73 Gy84 Gy EQD210 OARbrachy dose to OAR 70% of dose to point AExternal beam 25 x Gy =45 Gy43 Gy EQD23 Brachytherapy4 x Gy=20 Gy31 Gy EQD23 Total dose65 Gy74 Gy EQD23 = 10 Gy for cervical tumor = 3 Gy for OAR (bladder, rectum, sigmoid)T/=15hforcervicaltumorandOARE xample.

6 LDR/PDR Brachytherapy for Cervical CarcinomaT1/2= h for cervical tumor and OARB rachytherapy treatment time: 80h (PDR: pulse time = 15 min, interval = 1h)Point APhysical doseTotal doseExternal beam 25 x Gy =45 Gy44 Gy EQD210 Brachy Gy/h 40 Gy=40 Gy40 Gy EQD210 Total dose85 Gy84 Gy EQD210 OARbrachy dose to OAR 70% of dose to point AExternal beam 25 x Gy =45 Gy43 Gy EQD23 Brachy Gy/h 28 Gy=28 Gy25 Gy EQD23 Total dose73 Gy68 Gy EQD236/27/20149 EBRT25 x Gy 25 x GyBT4x7Gy5x55 GyTotal Dose Values ( eqd2 ) for 2 HDR Fractions BT 4 x 7 Gy 5 x Gy D90 HR CTV 84 Gy80 Gy ( = 10 Gy)D2ccrectum 74 Gy70 Gy( , ~ 70% of D90 = 3 Gy) (g, y)D2ccbladder ( , ~ 90% of D90 = 3 Gy)90 Gy83 Gy Treatment Planning Documentation of Fractionated Gynecological BT (HDR)BRACHYTHERAPYF 1F 2F 3F 4F 5F 6datedose values in Gyphysic ist MR / CT TOTALTOTAL applicator(s): typeBTBT + EBTapplicator(s): type BTBT + EBTapplicator(s).

7 Dimensionseval plan, remarksmeanstddevTRAK [cGy at 1m]0,00 Planning aim for D90 CTVH7777planning aim EQD2109,99,99,99,90,00,039,783,9volume of 7 G y [c m3]#DIV/0!#DIV/0!volume of 14 G y [c m3]#DIV/0!#DIV/0!dose to + A left6,66,66,46,4 Alef t EQ D2109,19,18,78,70,00,035,880,0dose to - A rightAright EQ D2100,00,00,00,00,00,00,044,3gdose to A mean3,33,23,20,00,0 Amean EQ D2100,03,73,53,50,00,010,754,96/27/20141 0 Calculation of DVH for Several FractionsDVH rectumDVH rectum01234565101520 Volume (%)1. BT2. BT0123456 Volume (%)1. BT2. BT1. + 2. BT+=5101520 Dose (Gy)5 101520 Dose (Gy)ApproximationWorst case assumptionProvided by K TanderupRectum Wall DVH in eqd2 cm Longitudinal Shift of Whole Organ< Gy EQD26/27/201411 Combination of EBRT and BT2xF1 optimized PDREB + Node Boost2xF1optimized PDRP rovided by Astrid de Leeuw /van de Kamer et al. Radiother Oncol 2010 Differences Between 2 Methods Adding 3D Distributions vs.

8 Adding Parameters HR-CTVB ladderRectumwithoutwith paraBoostwithoutwith paraBoostwithoutwith adding parameters a valid approximation?Yes, provided no EB boost!Provided by Astrid de Leeuw/van de Kamer et al. Radiother Oncol 20106/27/201412200250Gy3 cm Shielding After 30 Gy AP/PA10015020080 Gy10203040506070809050mm eqd2 Concept is reproducible and able to compare different dose rate and dose fractionation schedulesConclusion Has to be used within comparable settings (similar EBRT Concept , ) Final parameters will be determined in dose response analysisperformedwithinlargemulticentert rialsThanks for your attention!analysis performed within large multicenter trials