Clinical and radiobiology applications of plasma-accelerated - - PowerPoint PPT Presentation

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Clinical and radiobiology applications of plasma-accelerated - - PowerPoint PPT Presentation

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Clinical and radiobiology applications of plasma-accelerated particles Ceferino Obcemea Radiation Research Program National Cancer Institute, Bethesda, MD, USA E-mail: obcemeach@nih.gov Capri 2017 No financial conflict of interest

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Clinical and radiobiology applications of plasma-accelerated particles

Ceferino Obcemea Radiation Research Program National Cancer Institute, Bethesda, MD, USA E-mail: obcemeach@nih.gov

Capri 2017

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  • No financial conflict of interest
  • Views expressed in this presentation are

those of the authors; no endorsement by NCI, NIH, HHS or any other US Government Agency agencies has been given, implied, or inferred

  • Images used in the presentation are obtained

from the public domain and are used for non- commercial educational use

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Some of Physicists’ contribution to Medicine:

  • 1. Curie therapy- radioactive isotope implants
  • 2. Computed Tomography CT
  • 3. Positron Emission Tomography PET
  • 4. Magnetic Resonance Imaging MRI
  • 5. Focused Ultrasound Imaging
  • 6. Artificial Intelligence (AI) in Image Fusions, Big Data
  • 7. Genome Sequencing
  • 8. Microfluidics for cell sorting
  • 9. X-ray, Linear accelerators, cyclotrons

10.New particle therapy machines (!?)

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Glioblastoma Multiforme (GBM)

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Guinness world record:303-lb tumor Patient:post-op:202 lbs

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Estimated New Cases in 2017 1,688,780 % Surviving after 5 Years 67.0% 2007-2013 Estimated Deaths in 2017 600,920

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Varian to equip New York proton consortium with ProBeam system Location: New York City Consortium: MSKCC , Mt Sinai, Montefiore , Opening date: 2018 Cost: $ 300 M Maintenance : $ 120 M/10 yrs

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Advantages of Laser-accelerated particle beams

  • 1. Low emittance, high fluence and micro-bunched

beam.

  • 2. Possible multiple ions source for p+, He, C, Li,

Be, B, …other ions.

  • 3. Compact beam delivery.
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Advantages of Laser-accelerated particle beams

  • 1. Low emittance  small penumbra, spares normal

tissue c/o PBS, high fluence and micro-bunched beam.

  • 2. Possible multiple ions source for p+, He, C, Li,

Be, B, …other ions.

  • 3. Compact beam delivery.
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The reason for using ion beam therapy vs photons

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Glioblastoma Multiforme (GBM) Low emittance, highly- peaked beam crucial to sparing normal tissues,& deliver effective tumor dose

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Advantages of Laser-accelerated particle beams

  • 1. Low emittance, high fluence == > protect normal

tissue+delivers lethal tumor dose and micro- bunched beam.

  • 2. Possible multiple ions source for p+, He, C, Li,

Be, B, …other ions.

  • 3. Compact beam delivery.
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Late (Cognitive injury) Intermediate (Pulmonary fibrosis) Acute (Ex: Mucositis)

Types of Normal Tissue Injuries

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Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s

, Vincent Favaudon b, et al a,⇑

,1 a Department of Radiation Oncology/DO/CHUV, Lausanne University

Hospital, Switzerland; b Institut Curie, INSERM U1021/CNRS UMR3347, Université Paris-Saclay, Orsay, France;

c

Radiotherapy and Oncology (2017)

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TLD measurements in the brain of a mouse cadaver, a: TLD chips positions at the center of the brain (sagittal) and at either side of the brain (Lateral left and right); b: measurement results for a 10 Gy WBI delivery with a single 1.8 μs electron pulse (filled markers) and at a 0.1 Gy/s dose rate (open markers). Error bars represent the (expanded, k = 2) uncertainty in the absorbed dose measurements with the TLD; c: Evaluation of the Recognition Ratio (RR) two months post irradiation for groups of mice that received sham irradiation (Control) and 10 Gy WBI with a dose rate of 0.1, 1.0, 3, 10, 20, 30, 60, 100, or 500 Gy/s, or with a single 1.8 μs electron pulse (1 Pulse). Bars represent mean values and whiskers the standard deviations.

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Most 28-Gy FLASH–treated animals were cured, and the lungs had a microscopic normal appearance with thin alveoli and normal vessels and bronchi, without inflammatory infiltration or extracellular matrix deposition. High fluence, high dose rate protects normal tissue or expedite recovery, w/o sacrificing tumor control

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Advantages of Laser-accelerated particle beams

  • 1. Low emittance, high fluence and micro-bunched

beam == > higher LET == > higher RBE

  • 2. Possible multiple ions source for p+, He, C, Li,

Be, B, …other ions.

  • 3. Compact beam delivery.
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PHYSICAL REVIEW B VOLUME 20, NUMBER 7 1 OCTOBER 1979

Spatial excitation patterns induced by swift ions in condensed matter

  • P. M. Echenique• and R. H. Ritchie

It is shown that a charged particle moving with velocity V in a medium of resonance frequency n0 may set up two types of electron-density fluctuations. Collective fluctuations trail the particle, composing a conical pattern in a relatively extended periodic wake.. They constitute a mode of energy transport from the particle track leading eventually to particle-hole excitations. Single-particle interactions give rise to bow waves ahead of the particles of wavelength The gradient along V, at the site of the ion, of the wake potential set up by density fluctuations, multiplied by the ionic charge, yields an expression for the retarding force

  • f the medium on the projectile in exact agreement with the Bethe stopping-power

formula appropriate to the medium.

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The energy loss of large hydrogen clusters incident on Al and amorphous C targets is analyzed as a function of the cluster size and velocity. With Al targets: for each cluster velocity there is a ‘‘resonant’’ cluster size for which the intermolecular contribution to the energy loss is maximum. For C targets, the intermolecular contribution to the energy loss clusters saturates with the cluster size. The origin of this behavior lies in the low-energy plasmon present in the energy loss function of amorphous C.

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particle ionization track

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Cell Killing Mechanisms: Back to Basics DNA Damage and Damage Response

IR D I R E C T A C T I O N IR I N D I R E C T A C T I O N Free Radicals

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Advantages of Laser-accelerated particle beams

  • 1. Low emittance, high fluence and micro-bunched

beam == > higher LET == > higher RBE

  • 2. Possible multiple ions source for p+, He, C, Li,

Be, B, …other ions.

  • 3. Compact beam delivery.
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Advantages of Laser-accelerated particle beams

  • 1. Low emittance, high fluence and micro-bunched

beam.

  • 2. Possible multiple ions source for p+, He, C, Li,

Be, B, …other ions == > increased differential response,

More adaptive to tumor stage, type, genomic status.

  • 3. Compact beam delivery.
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Fluency and Number of Hits per Nucleus will Depend on Radiation Type

Prasanna et al. 1997

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ICTR 2003 Translational Research in Clinics

RECENT ADVANCES IN LIGHT ION RADIATION THERAPY

ANDERS BRAHME, Department of Medical Radiation Physics, Karolinska Institute

and Hospital, Stockholm, Sweden Besides the “classical” approaches using low ionization density H ions (protons, but also deuterium and tritium nuclei) and high ionization density C ions, two new approaches 1 Li or Be or B ions, which induce the least detrimental biologic effect to normal tissues for a given biologic effect in a small volume of the tumor, will be key particles.

  • 2. Patients will be given a high-dose, high-precision “boost” treatment with C or O

ions during 1 week preceding the first treatment with conventional radiation in the referring hospital. The rationale behind these approaches is to minimize the high ionization density dose to the normal-tissue stroma outside but sometimes also inside the tumor bed and to ensure a more uniform and optimal biologic effectiveness in the tumor,

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New Ions for Therapy

Francesco Tommasino, PhD

1,2; Emanuele Scifoni, PhD 1; Marco Durante, PhD 1,2

1 Biophysics Department, GSI Helmholtzzentrum fu

¨ r Schwerionenforschung, Darmstadt, Germany

2Trento Institute for Fundamental Physics and Applications (TIFPA), National Institute for Nuclear Physics

(INFN), Department of Physics, University of Trento, Povo, Italy

Abstract

Purpose: Charged particle therapy (CPT) is currently based on the use of protons or carbon ions for the treatment of deep-seated and/or radioresistant tumors, which are known to return poor prognosis in photon treatments. A renovated interest has recently been observed in the possibility of extending the spectrum of ions used in CPT. The potential and limitations of different particle species will be discussed in this work, with special regard to 1H, 4He, 12C, and 16O, that is, those presently available in the most advanced particle therapy clinical centers.

Int.J.Particle Therapy Aug 2015

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Results The in-house developed script generated similar or superior plans to the clinically used plans. In the comparisons between the modalities, the integral dose was lowest for the PPBS-generated plans in all

  • cases. For the prostate case, the 200 MeV VHEE plan showed reduced

integral dose and reduced organ at risk (OAR) dose compared to the VMAT plan. For all other cases, both the 100 and the 200 MeV VHEE plans were superior to the VMAT plans, and the VHEE plans showed better conformity and lower spinal cord dose in the pediatric brain case and lower brain stem dose in the HNC case when compared to the PPBS plan

Very high-energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS

  • E. Schueler et. al. May 2017
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Very high‐energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS

Medical Physics 44,2544-2555 (2017)

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Very high‐energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS

Medical Physics Volume 44, Issue 6, pages 2544-2555, 4 MAY 2017 DOI: 10.1002/mp.12233 http://onlinelibrary.wiley.com/doi/10.1002/mp.12233/full#mp12233-fig-0005

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Very high‐energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS

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Advantages of Laser-accelerated particle beams

  • 1. Low emittance, high fluence and micro-bunched

beam.

  • 2. Possible multiple ions source for p+, He, C, Li,

Be, B, …other ions == > increased differential response,

More adaptive to tumor stage, type, genomic status.

  • 3. Compact beam delivery.
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Advantages of Laser-accelerated particle beams

  • 1. Low emittance, high fluence and micro-bunched

beam.

  • 2. Possible multiple ions source for p+, He, C, Li, Be,

B, …other ions

  • 3. Compact beam delivery == >

a) Smaller footprint, lowe facility/ maintenance cost: $$$$$ --- > $ b) versatile tx delivery c)

  • ffers much needed platform for fund amenta micro-dosimetry, modern-day

radiobiology.

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There is need to compactify beam delivery

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Ionization tracks using FNTD

(courtesy of S. Greilich, DKFZ Heidelberg)

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Lindhard Stopping Power formula

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*Approximate number for photons

  • K. Held (2011), modified from Ward JF 1988,

and Goodhead D., 1994;

Number of DNA lesions (Estimates) Friedland et al. 2003

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DNA lesions Sensors

PARP MRN Ku

RPA

Outcomes

Altered transcription Cell cycle delay Cell death DNA repair Transducers

ATM ATR DNA PKcs ChK1 ChK2

Effectors

Cdc25B CDK

  • Base Excision Repair
  • Nucleotide Excision Repair
  • DNA DSB Repair
  • NHEJ
  • Homologous Recombination
  • Single strand annealing
  • Cross-link Repair
  • Mismatch Repair
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Radiation and the Immune System

Abscopal Effect of local radiation

Gameiro et al IJROBP 2016.

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  • Fig. 1. 85-year-old patient received 50.4 GyE in 12 fractions for an ascending colon ca.

At the time of treatment the patient had mediastinal lymph node metastasis, at CT and

  • PET. 6 months later both the irradiated lesion (A) and the metastasis occurred (B)

resolved.

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Advantages of Laser-accelerated particle beams

  • 1. Low emittance, high fluence and micro-bunched

beam.

  • 2. Possible multiple ions source for p+, He, C, Li,

Be, B, …other ions.

  • 3. Compact beam delivery.
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Acknowledgement:

Thanks for the slides from P . Prasanna, S. Greilich, H. Paganetti.