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M. Zeverino, S. Agostinelli, G. Taccini, F. Cavagnetto, S. Garelli, M. Gusinu,

Total Marrow Irradiation with Helical Tomotherapy along the entire Patient ’s Axis : a Planning Technique to Merge Helical Dose Distributions producing Uniform Dose in the Junction Region. M. Zeverino, S. Agostinelli, G. Taccini, F. Cavagnetto, S. Garelli, M. Gusinu,

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M. Zeverino, S. Agostinelli, G. Taccini, F. Cavagnetto, S. Garelli, M. Gusinu,

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  1. Total MarrowIrradiationwithHelicalTomotherapyalong the entirePatient’s Axis: a Planning TechniquetoMergeHelical Dose DistributionsproducingUniform Dose in the JunctionRegion M. Zeverino, S. Agostinelli, G. Taccini, F. Cavagnetto, S. Garelli, M. Gusinu, S. Vagge, S. Barra , R. Corvò National InstituteforCancerResearch Genova- ITALY

  2. Outlines • TMI rationale and its potential over TBI treatments • TMI treatment technical issues • Patient selection and treatment approach • The strategy to overcome limits and delivery a “Full TOMO” treatment • Dose junction manipulation • Treatment delivery QA M. Zeverino ASTRO 2010, San Diego

  3. Outlines • TMI rationale and itspotentialover TBI treatments • TMI treatment technicalissues • Patientselection and treatment approach • The strategytoovercomelimits and delivery a “Full TOMO” treatment • Dose junctionmanipulation • Treatment delivery QA M. Zeverino ASTRO 2010, San Diego

  4. TMI rationale • Leukemia relapse (LR) cause of failure after allogeneic stem cell trasplantation • LR first cause of death for patient with advanced hematologic diseases • Total Body Irradiation (TBI) dose escalation may reduce LR ratio but is associated with higher toxicity • TMI has the potential to fulfill a dose escalation protocol and reduce the dose delivered to the organs at risks M. Zeverino ASTRO 2010, San Diego

  5. Dose Volume HistogramsTBI vs TMI TBI TMI Entire target STILL receives full dose Critical Organ receives LESS dose TMI – H&N vs. M. Zeverino ASTRO 2010, San Diego TMI – Trunk Typical TBI Dose Volume Histogram • 9 entries in PubMed for TMI with HT: • Hui SK et al. Feasibility study of helical tomotherapy for total body or total marrow irradiation. Med Phys. 2005 • Wong JY et al. Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation. IJROBP 2009

  6. Outlines • TMI rationale and itspotentialover TBI treatments • TMI treatment technicalissues • Patientselection and treatment approach • The strategytoovercomelimits and delivery a “Full TOMO” treatment • Dose junctionmanipulation • Treatment delivery QA M. Zeverino ASTRO 2010, San Diego

  7. Howto deal with the couch Y limit? • Maximumcouchtravelabilityofabout 160 cm • Treatment hastobesplit in twosegments: • Upper body TMI (UTMI) • Lower body TMI (LTMI) • Twodifferent treatment approaches: • Totreatlowerlimbswith LINAC • Extended SSD AP/PA technique • 4 fixedfields (minimum) with at least 2 junctions in addition • Totreatlowerlimbswith TOMO • FFS oriented • Single junction • A methodformatchingfieldsshouldbeused M. Zeverino ASTRO 2010, San Diego

  8. Outlines • TMI rationale and itspotentialover TBI treatments • TMI treatment technicalissues • Patientselection and treatment approach • The strategytoovercomelimits and delivery a “Full TOMO” treatment • Dose junctionmanipulation • Treatment delivery QA M. Zeverino ASTRO 2010, San Diego

  9. Patientselection • 15 patients (10 M, 5 F) from 07/2009 to 06/2010 • Median age 35 y (range 18 y – 55 y) • 10 patients with acute myeloid leukemia (AML) • 5 in relapse status • 5 in second remission • 5 patients with acute lymphoid leukemia (ALL) • 3 in relapse status • 1 in second remission • 1 in third remission M. Zeverino ASTRO 2010, San Diego

  10. Treatment approach @ IST TBI + TMI Day 1 Day 2 Day 3 Day 4 time TBI + TMI 14 Gy TBI 2 Gy (x2) TBI 2 Gy (x2) TBI 2 Gy (x2) TMI 2 Gy (x1) + + + =

  11. Outlines • TMI rationale and itspotentialover TBI treatments • TMI treatment technicalissues • Patientselection and treatment approach • The strategytoovercomelimits and delivery a “Full TOMO” treatment • Dose junctionmanipulation • Treatment delivery QA M. Zeverino ESTRO 2010, Barcelona

  12. Matching UTMI and LTMI CT data sets Two CT scans • Upper body HFS oriented (from vertex to knees) • Lower body FFS oriented (lower limbs including knees) M. Zeverino ESTRO 2010, Barcelona Two CT data sets • Whole body CT = lower body images are mirrored and properlymatchedwith upper body images • Lowerlimbs CT = originalimagesoflower body

  13. Matching UTMI and LTMITreatment planning • UTMI planned on the whole body CT data set with PTV goingfromvertextoknees 1 • LTMI planned on the lower limbs CT data set M. Zeverino ASTRO 2010, San Diego 2 Trunk • Generation of a “twin” LTMI plan on the whole body CT data set H&N 3

  14. Twin LTMI plan Generation Method Evaluation • LTMI easy toplan (rounded PTV, no OARs) • LTMI planfeatures: • Fixednumber (50) ofiterationsallowed • No changesof dose constraintduringoptimization • Plansavedasprotocol • LTMI protocolwasloaded on the whole body CT data set providingidentitybetweenstructures • tLTMI dose distributionwasthencalculatedwith the samefixednumberofiterations • DVH comparisontoassess dose identity M. Zeverino ASTRO 2010, San Diego • “Modified” γindex (1 % dose/ 1% volume) • Plans are definedtwinsonlyiffor >99% ofpointsγ<1

  15. Full Helical TMI Dose Distribution Finally UTMI and tLTMI plans can be summed on the same CT data set M. Zeverino ASTRO 2010, San Diego

  16. Outlines • TMI rationale and itspotentialover TBI treatments • TMI treatment technicalissues • Patientselection and treatment approach • The strategytoovercomelimits and delivery a “Full TOMO” treatment • Dose junctionmanipulation • Treatment delivery QA M. Zeverino ASTRO 2010, San Diego

  17. Producinguniform dose in the junctionregion • A couple of transition volumes were used to improve dose uniformity in the abutment region for UTMI, LTMI and tLTMI plans by replacing the PTV segments • PTV Stop replaced the last two segments for UTMI and the first two segments for LTMI • PTV Trans replaced the two PTV segments preceding and following PTV Stop for UTMI and LTMI, respectively M. Zeverino ASTRO 2010, San Diego • Optimizationtips: • PTVStopis a RAR (zero dose requested) • PTVTransis a PTV (actingas a dose modulator) LTMI UTMI

  18. Junction dose evaluation Overall 3D dose distribution allows to evaluate calculated dose in the abutment region by means of: DVH Dose profile M. Zeverino ASTRO 2010, San Diego Our policy allowsmaximum dose inhomogeneity of ± 10% ofprescribed dose. Otherwise LTMI isreplannedacting on the dose constraintsofbothPTVStop and PTVTrans

  19. Junction Dose Evaluation:Tomo vs Linac TMI dose junctionregion Regionsof < 50 % ofprescribed dose M. Zeverino ASTRO 2010, San Diego Staticfields dose junctionregion LINAC TOMO • “Full TOMO” TMI features: • Easy todeliver (quicksetup, no patientshifts) • More conformal (sparingoflowerlimbsvessels)

  20. Junction Dose Evaluation:Tomo vs Linac TMI dose junctionregion Regionsof < 50 % ofprescribed dose M. Zeverino ASTRO 2010, San Diego Staticfields dose junctionregion LINAC TOMO • “Full TOMO” TMI features: • Easy todeliver (quicksetup, no patientshifts) • More conformal (sparingoflowerlimbsvessels)

  21. Junction Dose Homogeneity:Tomo vs Linac M. Zeverino ASTRO 2010, San Diego “Full TOMO” junction - 2% Dmin +8% Dmax

  22. Junction Dose Homogeneity:Tomo vs Linac M. Zeverino ASTRO 2010, San Diego TOMO – Linacjunction (NO GAP) - 14% Dmin +10% Dmax

  23. Junction Dose Homogeneity:Tomo vs Linac M. Zeverino ASTRO 2010, San Diego TOMO – Linacjunction (5 mm GAP) - 28% Dmin +3% Dmax

  24. Junction Dose Homogeneity:Tomo vs Linac M. Zeverino ASTRO 2010, San Diego TOMO – Linacjunction (5 mm OVERLAP) - 10% Dmin +34% Dmax

  25. Junction Dose Homogeneity:Tomo vs Linac M. Zeverino ASTRO 2010, San Diego Inverse planning allowstoobtain a more uniform dose distribution in the overlapping area Target over- or under-dosage can beeasilyavoided These are calculatedvalues! MV/kVCTregistrationprocesswillaffect dose uniformity in the overlapping area

  26. Junction Dose Homogeneityresults M. Zeverino ASTRO 2010, San Diego

  27. Outlines • TMI rationale and itspotentialover TBI treatments • TMI treatment technicalissues • Patientselection and treatment approach • The strategytoovercomelimits and delivery a “Full TOMO” treatment • Dose junctionmanipulation • Treatment delivery QA M. Zeverino ASTRO 2010, San Diego

  28. PlanVerification • Dose point verification • A1SL ion chamber & Cheese Phantom • Target sites (i.e. bone marrow) • 3% ∆D • 2D dose verification • GafChromic EBT/EBT2 • Anthropomorphic phantom (head and chest) • Lung equivalent tissue slabs • γ (3%/3mm) M. Zeverino ASTRO 2010, San Diego

  29. MV-kV REGISTRATION • Results from the first 8 treated patients: • Treatment setup (TS) = Observed Shift – Averaged Shift < 4 mm • If 4 mm < TS < 6 mm, physician review and evaluation • If TS > 6 mm, patient repositioning M. Zeverino ASTRO 2010, San Diego

  30. In vivo dosimetry In vivo dosimetry = assessing the accuracy of dose delivered in the field junction • Gafchromic EBT2 • Two stripes of approximately 10 cm long and 2 cm wide • Placed on the skin according to the tattoo individuating the junction MOSFET 5 detectors placed on the skin 1 cm apart in the long direction according to the tattoo individuating the junction M. Zeverino ASTRO 2010, San Diego

  31. Some numbers… • Legenda: • D95 = dose receivedby 95 % of PTV volume • D90 = dose receivedby 90 % of PTV volume • D5 = dose receivedby 5 % of PTV volume M. Zeverino ASTRO 2010, San Diego • Considerations: • Organ sparing is achievable in terms of median dose reduction (i.e. dose delivered to 50% of organ volume) • Small organs are penalized because of technical parameters of treatment • Optimal PTV coverage and homogeneity • Mean overall beam-on time < 30 min

  32. Remarks and conclusions • Full helical dose distribution is true as long as dose identity between LTMI and tLTMI exists • Different solutions can be adopted for producing uniform dose in the junction through inverse planning • In vivo dosimetry is mandatory to assess the dosimetric impact of the patient shifts on the junction • Patient alignment process may cause over- or under-dosage to PTV. Split the treatment at the knees (= lack of bone marrow) • On a total of 17 patients underwent TMI with HT (first patient July 2009), 11 were treated using the presented technique • Treatments well tolerated (1 severe nausea episode) • Short median FU (7 months) . 12/17 patients are currently alive in CR M. Zeverino ASTRO 2010, San Diego

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