Savita Dandapani, MD, PhD City of Hope Duarte, CA

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1 Savita Dandapani, MD, PhD City of Hope Duarte, CA

2 Financial Disclosures Accuray Funding

3 Outline TomoTherapy at City of Hope: TBI TMI Recent experience at City of Hope with TomoDirect : TomoDirect for Lower Extremity as part of TMI TomoDirect for early stage right sided breast cancer

4 Hematologic Malignancies Myeloablative conditioning regimen TBI Standard TBI: lung blocks, dose inhomogeneity

5 TBI Dose Escalation

6 TBI Dose Escalation Improves Outcomes

7 Hematologic Malignancies TBI vs. TMI Decrease acute and late toxicities Dose escalation Reduced intensity conditioning regimen for stem cell transplants Dose painting/boost minimal residual disease City of Hope Experience Dr Jeffrey Wong, MD, Chair, City of Hope

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9 TMI Dose constraints Target: Bone+BoneMarrow (Example 85% IDL 9Gy) Bladder Brain Breasts Esophagus Eyes Heart (40-50% of dose) Kidneys (50-60% dose) Lens Liver (50-60% dose) Lungs (40% of dose) -- > 10% of organ receiving 6Gy Optic Nerve Oral Cavity Ovary Parotids Rectum Small Intestine Stomach Testis Thyroid

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12 1 st TMI Trial at COH Phase I TMI dose escalation and tandem autologous HCT in Multiple Myeloma Melphalan TMI TMI alone 200cGy BID 10Gy 18Gy Primary endpoint: MTD and baseline TMI toxicities Somlo et al Clin Ca Res 2011 Wong IJROBP 2009

13 Phase I TMI trial Results Multiple Myeloma: melphalan + TMI / HCT 54 patients Median follow-up: 73 mos 50% CR 5yr PFS: 43% OS 66% Wong, Somlo et al ASCO 2015

14 Hematologic Malignancies TMI experience at City of Hope transplants/year st tomotherapy machine at COH 235 TMI patients treated thus far 5 clinical trials completed Normal organs receive 16-60% of target dose (Normal tissue spared with TMI vs. TBI) 16Gy feasible and well tolerated MM, AML, ALL, NHL

15 TBI vs. TMI relapses

16 TMI TMLI TMI + TLI + liver + spleen + brain/testes Pilot Trial Fludarabine + Melphalan 150cGy BID 12Gy Rosenthal et al Blood 2011 Chemo+TMLI Chemo alone

17 Current TMI/TMLI Trials 07173: Correlating Organ Dose and Dose-Volume with Toxicities After Total Marrow Irradiation (TMI) Using Helical Tomotherapy in Patients Undergoing Hematopoietic Cell Transplantation (HCT) 09171: Phase I Study of Bortezomib +- TMI in Combination with Fludarabine (FLU) and Melphalan (MEL) for Allogeneic HCT (MM) 14106: Phase I Study of Escalating Doses of TMLI During Conditioning for HLA-Haploidentical HCT with Post-Transplant Cyclophosphamide (MDS, ALL) 14102: Phase II Study of TMLI with Cyclophosphamide and Etoposide as Conditioning for AlloHCT (ALL, AML)

18 TomoTherapy and TMI Limit of TomoTherapy machine to 1.3meters (51in, 4 3 ) S/I Need to treat bone/bone marrow in lower extremity bones: femur/tibia/fibula/feet 3DCRT Gap at mid thigh 3DCRT plan for legs bone/bone marrow xrt AP/PA with field match at bone

19 TomoDirect Lower Extremity Bone/Bone Marrow Used AP/PA fields for legs Gap calc at skin: match fields at bone Used Port Xrays for matching tomotherapy plan with AP/PA Risk of hot/cold spots and gap in bone (& bone marrow) Now with TomoDirect can match lower extremity bone treatment with upper TMI plan

20 TomoDirect Legs Steps: 2 plans: TMI and TomoDirect Legs Merge both plans to Eclipse to assess hot spots/cold spots ~85-90% IDL coverage of lower extremity bones IGRT with MVCT for each fraction for matching fields Benefits of TomoDirect for Lower Extremity bone treatment: Better coverage of bone/bone marrow MVCT more accurate than Port Xrays No need to move patient from TomoTherapy machine to Linac to finish TMI treatment

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23 Advantages of TomoDirect legs Dose homogeneous, better coverage No potential gaps between matching fields to treat all of extremities.

24 From head to toe to specific targets TBI TMI TomoDirect Legs TomoDirect Early stage breast cancer

25 Early stage breast cancer Right sided breast cancer Traditional fields: tangents TomoDirect Plan similar to tangents? Move volume of breast ca patients from Linac to TomoDirect

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28 Right breast contour: more conformal dose with TomoDirect Lung optimized to be ~equivalent (V5, V20)

29 Same patient showing heart DVH CTV = tumor bed boost: more conformal with TomoDirect

30 This patient initial plan using the breast contour PTV breast PTV better coverage on TomoDirect but lung worse (standard 3DCRT breast plan generated respecting treating less than 1.5cm-2cm lung)

31 Same patient now optimized (medial 239degree to 242 degree) Equivalent right ipsilateral lung dose Still better breast coverage with TomoDirect over Tangents

32 Early breast, right sided Size of breast Dose homogeneity on breast TomoDirect more homogeneous b/c similar to IMRT plan Normal tissue dose constraints Equivalency low and high xrt dose to lung

33 TomoDirect Plans TomoDirect requires PTV, OAR for optimization even of tangent angles to cover breast For now we compare 3DCRT breast to TomoDirect If equivalent treat with TomoDirect Minimize contralateral structures: heart, left lung by delineating as OAR

34 TomoDirect vs. 3DCRT Anatomy more important than in 3DCRT plans Similar to the shift from 3DCRT to IMRT PTV contouring essential Contouring Target and Normal Organs Critical to prevent Marginal Misses

35 Acknowledgments City of Hope Radiation Oncology Department Jeffrey Wong, MD Nayana Vora, MD Eric Radany, MD, PhD Yi-Jen Chen, MD, PhD Sagus Sampath, MD Physics: Timothy Schultheiss, PhD An Liu, PhD Dosimetrists: Dan Azizi Robert Martin Thomas Joseph Peter Tsai