Defining The Future of Radiation Oncology: Latest Updates on Proton - PowerPoint PPT Presentation

Defining The Future of Radiation Oncology: Latest Updates on Proton Arc Therapy Peyman Kabolizadeh, MD; PhD Director of Beaumont Proton Therapy Center

Disclosure • The SPArc research project was supported by: – Ion Beam Application S.A. – Beaumont Herb and Betty Fisher Research Seed Grant Award • A patent related to the Proton Arc Therapy 11/11/18 2

Overview • Properties, Dose Distribution • Proton Therapy Technology (Passive vs PBS) • Proton Arc Therapy

Technical Advances In Radiotherapy • Higher radiation doses to tumor increase rate of local control in animals and patients • Higher radiation doses to larger volumes of normal tissue increase the risk of normal tissue complications

Protons: Potential Clinical Advantages • Lower integral dose and absence of exit dose: – Lower normal tissue doses decrease toxicity – Improve Rx tolerance: Uninterrupted Rx • Allows integration with systemic chemotherapy – Reduce late effects ( i.e. growth arrest in child)

Over 93,000 patients treated to date Bill Chu LBL

Current Sites for Proton Delivery in the United States (2018) 29 in Op., 10 under Construction

Proton Technology • Passive double scatter – Modulation/Spread Out Bragg Peak (SOBP) – Brass aperture – Lucite Compensator – Patching planning technique very demanding

Pencil Beam Scanning- IMPT • No spinning modulator, brass aperture, or lucite compensator are needed.

RT in the Era of Precision Medicine

Proton Arc Therapy Concept • IMPT-PBS provides superior tumor coverage while delivering less body integral dose. • However, the robustness and dosimetric quality of a proton plan rely heavily on the number of fields as well as beam angle selections. • The total number of beam angles that IMPT-PBS can deliver to each patient per faction is limited by current available planning and beam delivery techniques as well as the limited proton machine efficiency. • To improve the quality of proton beam therapy, the concept of arc delivery remains of interest 11/11/18 11

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Proton Arc Therapy • The potential to provide superior treatment to cancer patients – Dosimetric quality – Treatment robustness – Delivery efficiency – Better Tumor Motion Management 11/11/18 13

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Beam delivery time New generation of energy selection system or Synchrotron multi-energy layers extraction technique from 5 years ago Limitations synchrotron 160 0 140 0 120 0 Total Delivery time(s) 100 0 I MPT 800 ps- SPA r c 600 400 200 0 6 5 4 3 2 1 0. 5 0. 2 Energy Layer Switching Time (s) 11/11/18 15

Proton Arc Therapy in CNS 11/11/18 16

Protons: less radiation to normal tissue

Whole Brain Radiotherapy with Hippocampal and cochlea sparing Hippocampus VMAT ro-IMPT SPArc Mean Dose 10.89Gy 9.38Gy 6.2 Gy D100% 9.16Gy 7.02Gy 4.5Gy Maximum 13.84Gy 14.55Gy 11.14Gy Cochlea VMAT ro-IMPT SPArc Dose Mean Dose 11.52Gy 10.52Gy 7.75Gy Ding et al. 2018, under review 11/11/18 18

Brain SRS PTCOG 2017 11/11/18 19

SPArc: A Tool That Allows for Dose Escalation IMPT Proton Arc VMAT IMRT clival chordoma

Proton Arc Therapy in Lung Cancer 11/11/18 21

Interplay effects for proton therapy • The motion of the beam could interfere with the motion of target • May result in distortion of the planned dose distribution, target over- and under- dosage • One of the major concerns for treating lung cancer with scanning beam proton 22

Single-fraction 4D dynamic dose IMPT SPArc Li et al. Rad Onc 2018, AAPM 2017 Patient 6, ITV volume of 402cc, S-I motion of 1.2 cm 24

Both SPArc and RO-IMPT plans achieved similar robust target volume coverage for all patients, while SPArc significantly reduced the doses to critical structures as well as decreasing the interplay effect. 11/11/18 25

Proton Arc Therapy in Head and Neck Cancer 11/11/18 26

HNC: Dosimetric comparison The spot-scanning proton arc therapy was able to provide equivalent or better robust target coverage while demonstrating significant dosimetric improvements over RO-IMPT in most of OARs sparing. AAPM 2017 11/11/18 27

Result: Plan robustness and delivery efficiency 1. Equal or better robust target coverage 2. Reducing 28.0%, 30.8% and 35.5% of mean dose to the ipsilateral parotid (p<0.001), contralateral parotid (p<0.001), and oral cavity (p<0.001) respectively. 3. The D1 of brain stem also reduced by a factor of 22.5% (p=0.004). 4. Comparable treatment delivery time when ELST is less than 0.5s 5. Better OARs sparing and robustness Ding et al. AAPM 2017 11/11/18 28

Proton Arc Therapy in GU 11/11/18 29

SPArc for prostate cancer -SPArc could complete the treatment delivery through only one arc, and therefore, it would potentially save the patient’s time on the treatment table for the beam waiting time for each fraction in a multi-room center when compared to ro-IMPT Ding et al. Acta Oncologica (2017) PTCOG 2017 11/11/18 30

Road to Clinical Testing

Prototype Proton Arc Delivery Deliver sequence optimization

World First Proton Arc Delivery Proton arc therapy proof of concept in collaboration with Beaumont Health Proton Therapy Center in Royal Oak, Michigan. Plan delivered in August 2018 Irradiation on a Gafchromic Simulation film Target volume: 123 cc Target dose: 6 Gy Delivery time: 4m27’ Target diameter: 9.5 cm Number of spots: 2624 Minimum energy: 100 MeV Target thickness: 3 cm Number of energy layers: 58 Maximum energy: 166 MeV 33 IBA CONFIDENTIAL

A robust, delivery efficient continuous Proton Arc delivery An advanced IMPT optimization algorithm § First technique paper (IJROBP 2016) § Advanced staged lung cancer (NA-PTCOG 2016) § Prostate (PTCOG 2017) § WBRT Hippocampus sparing (AAPM 2017) § Cranial SRS (ASTRO 2017) § Spine SRS (ASTRO 2017) § Bilateral Head & Neck (AAPM 2017) § Mobile tumor – interplay (AAPM 2017) § Re-define the role of range shifter (JACMP 2018) § Delivery sequence optimization algorithm (PTCOG 2018) § Lung SBRT (ESTRO 2018) § Comparison with collimator based IMPT (ASTRO 2018) § Many more to come... 34 IBA CONFIDENTIAL

Technical and clinical Challenges § Quality Assurance technique and device § Hardware and system control software improvement to further increase efficiency of delivery § Low dose bath 35 IBA CONFIDENTIAL

Potential sites with most benefits § Targets abut critical OARs such as in head and neck and base of skull malignancies § Targets that need dose escalation § Non-mobile and mobile targets § Targets that need high comfomality § arc reduces the range uncertainty and ultimately improves the target conformality § Better Delivery efficiency and simplified proton clinical work flow 36 IBA CONFIDENTIAL

Future of SPArc § All QA data is being processed and a manuscript is being written § Phase I/II clinical trial is being written undergoing IRB evaluation soon § Further improvement of hardware and software basis for SPArc § Further improvement of QA procedures and devices § Development of advisory committee by IBA to define the role of SPArc in clinical practice 37 IBA CONFIDENTIAL

Proton Therapy Center Physics: Leo Ding, Xiaoqiang Li; Di Yan Physicians: Peyman Kabolizadeh MD/PhD Craig Stevens MD/PhD IBA: Guilliaune Janssens; Anotoine Pouppez; Damien Prieels, Gregory and many more