The Promise of Protons The Economic Club of Florida, Tallahassee 2018 - PowerPoint PPT Presentation

The Economic Club of Florida Tallahassee August 13, 2018 Nancy P Mendenhall, MD The Promise of Protons

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons • Cancer and radiation therapy • The promise of protons • UFHPTI: missions and operation • The economic impact • The future…….

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons Cancer and Radiation

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Cancer & Radiation • Cancer affects 1 in every 3 Americans • Cancer is 2nd most common cause of death in the US

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Cancer & Radiation Standard Cancer Therapy Local Systemic Hormonal & Surgery Radiation Targeted Chemotherapy Immunotherapy therapy • Cryosurgery, laser, & HIFU are local therapies used in certain settings. • Radiation may be delivered with an external source (external beam therapy), an implanted or intracavitary source (brachytherapy), or an isotope (systemic)

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Cancer & Radiation • Radiation used in ~50% of cancer patients • Most is External Beam Radiation Therapy using a radiation source external to patient’s body • Most EBRT uses X rays ( Photons ) aka “conventional radiation therapy” Including cancers of the prostate, breast, lung, colorectum, brain, head & neck, female organs, male organs, urinary tract, lymphatic system, and children

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons The Promise of Protons

First Principles of Radiation Therapy Radiation Therapy is a non- specific treatment • Damages normal tissue as well as cancer • Damage is dose-related and volume-related • Dose distribution is key determinant of the patient’s outcome

Dose Distribution: Depth dose for X rays & Protons Depth dose comparison of 18 MV X-rays & Protons 100.0 18 MV Photon (X ray) 90.0 Proton 80.0 70.0 Percent Depth Dose 60.0 50.0 40.0 30.0 20.0 10.0 0.0 0 5 10 15 20 25 30 Water-Equivalent Depth (g/cm 2 ) 18 MV Photon (X ray)

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Photons (X rays) Protons are particles with mass; they only penetrate X rays leave a track of damage like a bullet   the body according to the energy they are given  The dose decreases with depth of penetration  They can be programmed to stop in the target (tumor)  There is a higher dose (red) along the entrance The entrance dose is much less and there is no exit path than in the target, and more dose along the  dose exit path

WHAT IS THE IMPACT OF RADIATION DOSE TO NORMAL TISSUE? Modeling Radiation Dosimetry to Predict Cognitive Outcomes in Pediatric Patients with CNS Embryonal Tumors Including Medulloblastoma Merchant et al, IJROBP - 2006 • Each Gy increased IQ decline • THERE WAS NO DOSE THRESHOLD Merchant. Cancer J 15:298-305. Merchant et al. J Neurosurg 104: 94-102. Merchant et al. Pediatr Blood Cancer 51: 110-117. Merchant et al. J Clin Oncol 27: 3691-3697.

Craniopharyngioma-Comparative Dose Distribution Craniopharyngioma: IMRT vs SRT vs PT IMRT: photons SBRT: photons Protons Mean Dose IMRT STR PT % dec cGyE with PT body 233 215 63 71% brain 888 810 358 65% CLINICAL DATA: ~850 pediatric brain tumors treated, including >100 LTL 951 1200 370 61% craniopharyngiomas, pc Dr. Daniel LH 2749 3299 815 61% Indelicato.. Collaboration with St. Jude Research Hospital, NHS, PPCR Target Dose of 54 GyE

Medulloblastoma: Photons & Protons Craniospinal Axis Irradiation: 3DCRT vs PT RATIONALE: Increased risk of 2 nd malignancy with dose ≥ 4 Gy (Travis et al, 2002, 2003, Tukenova, 2010) Increased risk of cardiac disease with doses ≥1Gy (Mulrooney 2009, Darby 2013). Dosimetry: courtesy of Z Li PhD, D Louis CMD. 36 Gy/CGE Mean Dose Cardiac IMRT Proton Mean Dose 20 1 CLINICAL DATA: Giantsoudi et al, IJROBP 95: 2016: 111 children, 5 y, similar disease control and acute toxicity to historical controls. …anticipating less late effects.

Impact of Radiation on Ischemic Heart Disease in Breast Cancer Patients DESPITE A SURVIVAL ADVANTAGE WITH with RADIATION in breast cancer…. The rate of major cardiac events increased by 7.4% for each increase of 1 Gy in the mean RT dose to the heart Darby S et al. Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer. New England Journal of Medicine 2013; 368(11):987-98

Breast Cancer: IMRT and PT IMRT 3DPT Mean heart dose 5 Gy 1Gy Xu et al Can proton therapy improve the therapeutic ratio in breast cancer patients at risk for nodal disease? Am J Clin Oncol 2013. Bradley et al. Early Clinical Results. 2017.

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons UFHPTI: The University of Florida Proton Therapy Institute Mission and Operation

University of Florida Proton Therapy Institute Mission With the compelling rationale for protons, UF decided to create a proton facility Missions • Provide best patient care possible • Conduct research into best indications and techniques for proton therapy • Fiscal stewardship* • Education *Funded by state grants, city loans, bonds, philanthropy

University of Florida Proton Therapy Institute: Operations • 1st proton facility in Southeast US, opened in 2006 • 501c3, Affiliated with University of Florida • Mission of Patient Care and Proton Therapy Research • >255K treatments to >7500 patients, >1500 children • ~40 Prospective Clinical Trials and Studies • ~98% of patients involved in outcome studies • 150 staff including 11 subspecialty MDs, 11 PhD Physicists, and 12 engineers

 Gainesville: University of Florida and College of Medicine (COM)  Jacksonville: second UF COM campus and site of the UF Proton Therapy Institute  Population ~ 1.3 m  International air and sea ports  Excellent interstate highways

UFHPTI Treatment Floor Proton Area Eye Treatment Room PET-CT Simulation Large Bore CT 230 MeV Cyclotron MR Photon Area

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Facility 440,000 lbs Cyclotron

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Facility

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Facility 3 Story - 200,000 lbs Gantry

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Facility Proton Treatment Room and Nozzle

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Clinical Operation Clinical Mission Daily >90 patients 14-16 operating hours • Prostate • Breast • Pediatrics • Lung • Lymphoma • Pancreas • Head & Neck • Sarcoma • Bone • Eye

Current Expansion Project Current Expansion Project

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Expansion Expansion Fun Facts:  ~ 11,000 Sq. Ft. project  172 tons (344K pounds) of steel rebar  210 trucks of high density concrete  8.8 million pounds of concrete

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Research Operation UFHPTI Research Mission  98% patient participation in in-house IRB approved Outcomes Tracking Protocol  ~40% also in bench mark, optimization, comparative IRB approved studies  ~40 clinical research trials/studies conducted  Currently 18 open  >130 publications to date in peer reviewed medical journals dealing with technical issues and clinical outcomes treatment

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Research Operation UFHPTI Research Mission  Collaborations with  St. Jude  Pediatric Proton Cooperative Registry  Proton Cooperative Group  Mayo Clinic  University of Pennsylvania  PROSTQA Prostate Study Group  Radiation Therapy Oncology Group/NRG  Aarhus University Netherlands  University of Groningen  COMPPARE consortium  First UFHPTI/UF federal funded research grant 2018

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons UFHPTI: The Economic Impact of UFHPTI

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Economic Impact  Covered by Medicare and most major insurers  The actual proton treatment takes 1-10 minutes  Each treatment visit takes 15-60 minutes  Patients receive proton therapy daily for 6-8 weeks after a 1-2 week planning interval  ~900 patients are evaluated for protons each year  ~3000 physical followup visits annually

The Economic Club of Florida, Tallahassee 2018 0813 The Promise of Protons: Economic Impact • Initial capital investment = $125 million* • Current expansion / equipment upgrade project = $44 million • Total employees = 193 FTEs [152 (UFHPTI) + 26(UF) +15(IBA)] • Total annual operating budget = ~$46.1 million *State grants, city loans, bonds, philanthropy