mesothelioma - Photon Therapy Radiation Oncologist

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					The Ultimate Healing Beam:
    The Future is Now
  -Radiation Oncologist-
                  Road Map
 Background
 History – When and Where
 Proton Mechanics – How to
 Applications/Prostate Cancer – What for
 Conclusion
High End Image Guided
Glorified Tanning Booths
Modality and Delivery Must Work
            Together


                                   Techniques to Improve
  Radiation Modality
                                     Radiation Delivery




                        OPTIMAL
                       RADIATION
                       THERAPY
Protons through the Ages
Bragg Peak
Named after the British physicist
William Henry Bragg (1862 - 1942)
Protons: “Ancient” History 101




                                              Hydrogen Atom




           R.R. Wilson, Radiology 1946; 47:487-491
    Scientists have been perfecting proton therapy as a
             treatment for cancer for 65 years

 Robert R. Wilson, PhD
   "Radiological Use of Fast
    Protons" (Radiology
    1946:47:487-91)
   Berkeley and Harvard
   Fermilab
Protons: History 101

    1946 – Robert Wilson proposes using protons clinically

    1955 – The first patient is treated at Berkley
    1961 – The Harvard Cyclotron Lab (HCL) begins therapy

    1991 – Loma Linda (LL) operates the first proton gantry

    2001 – HCL closes  NPTC opens
Protons: “Modern” History 101

  •   Loma Linda Univ Medical Center – Loma Linda, CA 1990
  •   MGH – NPTC Boston, Massachusetts 2002
  •   MPRI – Bloomington, Indiana 2004
  •   MDAH – Houston, Texas 2006
  •   FPTI – Jacksonville, Florida 2006
  •   PPC – Oklahoma City, Oklahoma 2009
  •   RPTC – Philadelphia, Pennsylvania 2010
  •   HUPTI – Hampton, VA 2010
  •   CDH – Chicago, IL 2010



                                 10
      Proton therapy found its first clinical home in California
 Loma Linda
    First patient 1990




                                      First facility designed as patient
                                       treatment center
The CDH Proton Center, A Procure Center, Warrenville, Ill.




                                          We are dedicated to
                                         providing exceptional
                                            care in a healing
                                        environment to patients
                                              with cancer
Mechanism of Action
                       Protons have Fewer Side Effects than Photons
                                           There is no reason to irradiate healthy tissue
              Photons deposit only 20% of their energy in the tumor                         Protons deposit more than 80% of their energy in the tumor
         Photons deposit only 20% of their energy in the tumor


  Higher                                                                     Higher

                                                                                                               20%                         80%           0%




                                                                           Radiation Dose
Radiation Dose




                                             Prescribed Dose                                                             Prescribed Dose
                                               to Kill Tumor                                                               to Kill Tumor




  Lower                                                                      Lower
                                     70%                       20%   10%

                   Depth in Tissue                                                          Depth in Tissue


                  In order for photons to reach a                                           Protons put 80% of their energy into the
                   prescribed dose at the tumor depth,                                        tumor and only 20% into healthy tissue
                   healthy tissue gets four times the
                   radiation as the tumor
                                        The Physics of Protons

                                   Depth Dose Curves for Different Treatment Types

                                                   High Energy X-Rays



                                                                                     Spread Out Bragg Peak (SOBP)
                100



                 80
Relative Dose




                 60



                 40
                                       200 MeV Protons


                 20

                                  Healthy Tissue                             Tumor                      Healthy Tissue
                      0
                          0   5            10            15             20            25           30
                                             Depth in Tissue (cm)
                                                           The Value of Protons

       Protons are physically superior to X-rays
       Protons behave differently than x-rays:
                  Protons
                  X-Rays do not
       Protons improve the “therapeutic ratio”
                  maximizing tumor control while minimizing side effects
       At a given radiation dose to a tumor protons deliver, on average, less than half the radiation dose
        to normal tissues than do x-rays 1




                                                                          16

(1) Jay Loeffler, Massachusetts General Hospital, “Proton Therapy 2009”
      Evidence of Distal Range Stopping

Before treatment   Treatment plan   After treatment
Why would we chose Protons?
          Production of Clinically-Useful Proton Beams
                      Proton Accelerators



Cyclotron (spiral path)
Constant magnetic field
   Variable Radius
  Continuous Beam
Treatment Delivery
Production of Clinically-Useful Proton Beams
    Proton Accelerators - CYCLOTRON
Production of Clinically-Useful Proton Beams
                 Beam Line
 Energy Selection System (230 MeV  70 MeV)
 Beam Transport and Switching System
         Gantry 1 NPTC- Harvard


Nozzle                  Snout (with aperture &
                        compensator)




                  6-axis patient positioner
Robotic Table
Protons are delivered to patients in specialized treatment
rooms




                                                        Fixed Beam Room




Gantry Room
                   Clinical Indications
 Current                           Planned
    Pediatrics                        Lung
       Paraspinal Ewing’s                Organ motion
       Optic pathway glioma              Density changes
       Optic nerve meningioma                Tumor response
       Prostate/Pelvic RMS                   Inspiration: Expiration
       Exophytic BSG                  GI
       Craniospinal irradiation          Organ motion
       Suprasellar NGGCT                 Density changes
    Prostate                          Breast - API
    Head and Neck/Base of Skull       Lymphoma
    Intracranial                      Ocular
       Meningioma
    Paraspinal/Sacrum
       Chordoma
Prostate Cancer
      Radiation Treatment Options
 Radiation therapy options include
   Brachytherapy (BT) is vastly underutilized
     Effective
     Safe (in the appropriately selected patients)
     Convenient (1 to 2 day procedure)
   External Beam Radiation Therapy (EBRT): Proton beam
    is superior to IMRT
     Higher cure rates
     Lower complication rates
   Stereotactic Body Radiotherapy (SBRT)
     Effective
     Convenient (3 to 5 day non-invasive procedure)
     Safety seems to be similar to IMRT (it is still X-rays)
    Invasive                           Non-Invasive




But, don’t forget about active surveillance!
                   Misconceptions About
                      Proton Therapy
      “Just because someone keeps saying it doesn’t make it true.”

 The typical quote: “The DVH of IMRT is better than the DVH
  of protons in the high dose region, and that’s what really counts”
    FACT: Protons, regardless of delivery method, and with
     equivalent PTVs, should yield superior DVH curves without
     overlap
 The typical quote: “There is no data showing protons have
  better control rates”
    FACT: Protons do have better control
    By definition, protons will never have worse control rates
     than x-rays
                   Misconceptions About
                      Proton Therapy
      “Just because someone keeps saying it doesn’t make it true.”

 The typical quote: “There is no data showing that side effects
  and complications (“toxicity”) are lower with protons”
    FACT: At a similar treatment dose and volumes, the toxicity
     is lower with protons
 The typical quote: “Protons are 2x to 5x times more expensive
  than IMRT”
    FACT: Protons are at most 40% – 60% more than IMRT,
     based on Medicare, and offer a much better value
    The lifetime costs of protons are much less than IMRT
   Patient access must not be based on misconceptions.
  We must rely on science and data to drive these decisions.
                       Protons have Fewer Side Effects than Photons
                                           There is no reason to irradiate healthy tissue
              Photons deposit only 20% of their energy in the tumor                         Protons deposit more than 80% of their energy in the tumor
         Photons deposit only 20% of their energy in the tumor


  Higher                                                                     Higher

                                                                                                               20%                         80%           0%




                                                                           Radiation Dose
Radiation Dose




                                             Prescribed Dose                                                             Prescribed Dose
                                               to Kill Tumor                                                               to Kill Tumor




  Lower                                                                      Lower
                                     70%                       20%   10%

                   Depth in Tissue                                                          Depth in Tissue


                  In order for photons to reach a                                           Protons put 80% of their energy into the
                   prescribed dose at the tumor depth,                                        tumor and only 20% into healthy tissue
                   healthy tissue gets four times the
                   radiation as the tumor
      “Direct Radiation Complications Never Occur
                In Unirradiated Tissues”
                                                                                      Dr. Herman Suit1

                                       IMRT immerses more healthy tissue with radiation
                               Radiation Therapy Plans for Prostate Cancer
      IMRT - 7-field co-planer                                                                                                    Proton Therapy - 2-field DS
                                                                                           Blue –         13%
                                                                                           Green – 51%
                                                                                           Purple – 63%
                                                                                           Yellow – 76%
                                                                                           Red –          95%




Higher dose bath to healthy tissue with IMRT:                                                      Tumor                              Less healthy tissue exposed to radiation
         Pelvis, rectum and bladder                                                                                                              compared to IMRT



(1)   Herman Suit, “The Grey Lecture 2001: Coming Technological Advances in Radiation Oncology,” International Journal of Radiation Oncology Biology Physics 53 No. 4 (2002): 798-809.


                                                                                                                                                                                         36
     Prostate Cancer Treatment Plans
                                                    IMRT- Protons:
  Protons                   IMRT                  Excess dose for IMRT




                                              Protons for
                                              rectum and
                                              bladder-dose
                                              is much
                                              lower
                                                             Dose -% of dose




IMRT immerses more healthy tissue with low to intermediate dose bath
The Data: Photons vs Protons
                                                   Prostate Cancer
                                     Proton Therapy vs. Conventional Radiation (by dose) in
                                              Locally Advanced Prostate Cancer
      Modality                                                    Dose    Recurrence      Complication
      Conventional Radiation                                    <60 GY       38%              22%

      Conventional Radiation                                 60 – 65 GY      36%              35%

      Conventional Radiation                                     70 GY       28%              45%

      Conventional Radiation                                    >75 GY       20%              60%

      Protons                                                    75 GY       15%              12%



Source: Presentation by Dr. N. Mendenhall, University of Florida, IBA
                                                                                    Rectum
                                                                 Rectum
         100
         90
         80
                                                             IMRT - MSK
                                                                                      The limit of the
                                                            3D CRT - MSK
                                                                                      photon modality
         70
         60                                                  IMRT - MGH
Volume




         50                                                  IMRT - UFPTI



         40                                                  Proton - MGH



         30
         20                                                 Proton - UFPTI



         10
           0
                                10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85
                                                                             Dose
Adapted from Zelefsky 2000, Trofimov 2007 and Vargas 2008
    Rectal dose comparison
                        IMRT plans
                              Rectum V70
            MSKCC                    14%
              MGH                14.5%
            MDACC                15.5%
               UF                    14%


           Protons UF                8%


Zelefsky et al Radiotherapy and Oncology 2000; 55:241-249
Trofimov et al IJROBP 2007; 69:pp. 444–453,
Zhang et al IJROBP 2007; 67: 620–629
Vargas et al IJROBP 2008; 70: pp. 744–751
                                          University of Florida Dosimetry Data Show Protons
                                                Reduce Dose To The Rectum By 59%
                                               IJROBP 2008
                                               Radiation dose to the rectum –
                                               proton therapy and IMRT1                                                                                                                        Background on study
                                         90%
                                                                                                                                                                                                     First prostate patients seen at University of Florida Proton
                                                                                                                                                                                                      Therapy Institute (“UFPTI”)
                                         80%
Rectal Volume Receiving Radiation (%)




                                                                                                                                                                                                     Both proton and IMRT plans were planned prospectively
                                                                                       IMRT                                                                                                           for each patient
                                         70%
                                                                                                                                                                                               The results
                                         60%                                                                                                                                                         Relative and absolute mean rectal dose savings of 59.2%
                                                                                                                                                                                                      and 20.1%, respectively, with proton therapy
                                         50%                                                                                                                                                   Why this is important
                                                                                                                                 Dose to rectum is more
                                                                                                                                 than 2x with IMRT vs.                                               Entire Dose Volume Histogram (“DVH”) does matter, not
                                         40%                                                                                        protons at 32 Gy
                                                                                                                                                                                                      just high the dose region

                                         30%                                                                                                                                                          – Rectal wall volume irradiated at 32.4 Gy is biggest
                                                                                                                                                              Dose to rectum is
                                                                                                                                                            almost 2x with IMRT
                                                                                                                                                                                                        predictor of rectal toxicity2
                                                                                                                                                            vs. protons at 70 Gy                     Extremely high correlation between rectal volume
                                         20%
                                                                Proton                                                                                                                                irradiation to 70 Gy and 5-year toxicity rates3
                                         10%

                                              0%
                                                    0            10            20             30     40     50    60   70                                            80            90
                                                                                               Radiation Dose (CGE/Gy)
(1)                                     Carlos Vargas et al., “Dose-Volume Comparison of Proton Therapy and Intensity-Modulated Radiotherapy for Prostate Cancer,” International Journal of Radiation Oncology Biology Physics 70 No.3 (2008): 744-751.
(2)                                     Susan Tucker, Lei Dong, Rex Cheung, et al., “Comparison of Rectal Dose-Wall Histogram Versus Dose-Volume Histogram for Modeling the Incidence of Late Rectal Bleeding After Radiotherapy,” International Journal of Radiation Oncology Biology Physics 60 (2004):
                                        1589-1601.
(3)                                     Mark Storey, Alan Pollack, Gunar Zagars et al., “Complications from Radiotherapy Dose Escalation in Prostate Cancer: Preliminary Results of a Randomized Trial,” International Journal of Radiation Oncology Biology Physics 48 (2000): 635-642.
     GI (Rectal) Side Effects and Complications
           The probability of damage to the GI tract is much higher
                           with x-rays than protons
                Chronic Radiation Proctitis in the
                            GI tract




Inflammation caused
     by radiation




43
                            Necrosis and ulcer
       Dose Escalation Trials Support the Use of Protons for
                         Prostate Cancer
                      Protons offer better control and lower toxicity than X-Rays
Randomized                                       Boost                         Planning                             High                          5-year                                 GI toxicity
trial1-4                                     Modality                         Technique                         dose arm                          control                        ≥G2                          ≥G3

MD Anderson                                     X-rays                          2-D/3-D                           78.0 Gy                          78%                          28%                          10%


CKVO96-10                                       X-rays                               3-D                          78.0 Gy                          64%                          32%                             5%


MRC RT01                                        X-rays                               3-D                          74.0 Gy                          71%                          33%                          10%


PROG 95-09                              X-rays/Protons                               3-D                          79.2 Gy                          92%                          17%                             1%



            The best outcome for control AND toxicity was achieved
                                using protons
(1)   DA Kuban, SL Tucker, L Dong et al., “Long-term results of the M.D. Anderson randomized dose-escalation trial for prostate cancer,” International Journal of Radiation Oncology Biology Physics 70 (2008):
      67-74. (Note: toxicity updated from Viani et al, ref 6)
(2)   ST Peters, WD Heemsbergen, PC Koper et al., “Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy
      with 78 Gy,” 24 (2006): 1990-1196.
(3)   DP Dearnaley, MR Sydes, JD Graham et al, “Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT101 randomized controlled trial,” Lancet
      Oncology 8 (2007): 475-487.
(4)   Anthony L. Zietman, “Correction: Inaccurate analysis and results in a Study of Radiation Therapy in Adenocarcinoma of the Prostate,” JAMA 299 No. 8 (2008): 898-900. Anthony L. Zietman et al., “Comparison of
      Conventional-Dose vs. High-Dose Conformal Radiation Therapy in Clinically Localized Adenocarcinoma of the Prostate. A Randomized Controlled Trial,” JAMA 294 No. 10 (2005): 1233-1239.
(5)   Beckendorf V, Guerif S, Le Prise E, et al. The GETUG 70 Gy vs. 80 Gy randomized trial for localized prostate cancer: Feasibility and acute toxicity. Int J Radiat Oncol Biol Phys 2004;60: 1056–1065. (Note: no 5-year
      control rates given)
(6)   Viani GA et al. Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys. 2009 Aug 1;74(5):1405-18.
                     Reviewing the Data
Parameter                   PROG 9509                     MSK
Collection                  Prospective                   Retrospective
Institutions                Multi-instituion              Single-instituion
Follow-up                   >10 year                      8 years
Photon RT                   3D CRT                        IMRT
Image Guidance?             No                            Yes



       The Only Difference – Proton Boost
   i.e., this wasn’t even all protons – this was protons tacked onto what would be
              considered, by today’s standards, inferior radiation therapy
                                                    Protons are Safer and More Effective
              A 2008 MGH study determined that protons                                                                       Protons significantly decrease the risk of secondary
              decreases the risk of patients developing a                                                                     malignancies in prostate cancer treatment over 5
                     secondary cancer by 50%(1)                                                                                                  year period



          “According to the study, 6.4 percent of patients who                                                                                       Modality                                    Risk of Induced Tumor
          underwent proton therapy developed a secondary
                                                                                                                              Baseline risk2                                                                     4%
          cancer while 12.8 percent of patients who had photon
          treatment [x-rays] developed another type of cancer.”                                                               Conventional3                                                                     10%

                                                                                                                              IMRT4                                                                           11-15%

                                                                                                                              Protons5                                                                           6%




(1)   “Comparative Analysis of Second Malignancy Risk in Patients Treated with Proton Therapy versus Conventional Photon Therapy,” presented by Nancy Tarbell, M.D. at ASTRO 2008 (Chung et al. study)
(2)   SEER data
(3)   McGee et al., “Comparison of Second Cancer Risk in Prostate Cancer Patients Treated with Neutron/Photon Irradiation, Photon Irradiation, or Prostatectomy,” International Journal Radiation Oncology Biology Physics 66 (2006): S318-S319
(4)   Fontenot et al., “Risk of secondary malignant neoplasms from proton therapy and intensity-modulated x-ray therapy for early-stage prostate cancer,” International Journal Radiation Oncology Biology Physics 74 (2009): 616-622
(5)   Chung et al., “Comparative Analysis of Second Malignancy Risk in Patients Treated with Proton Therapy versus Conventional Photon Therapy,” International Journal Radiation Oncology Biology Physics 72 (2008) :S8
        Prostate Cancer Summary
 Protons are AN option for prostate cancer
  treatment
 Protons are superior to IMRT
 Protons are different from surgery and
  brachytherapy
 Active surveillance is perfectly acceptable for
  many men with prostate cancer
 Discussions should be had with patients about
  ALL the options
                   Parting Shots
 Take home points:
   All cancers should be approached in a multi-specialty
    or multi-disciplinary fashion
   Patient care should be performed in team approach:
    Concierge/Receptionists, Nurses, Therapists,
     Physicists/Dosimetrists, Physicians
   State of the Art Radiation Therapy @ CDH/Procure
    FULL Spectrum of Radiation Treatment options
       HDR Brachytherapy
       SBRT/SRS
       IMRT/3D CRT/IGRT
       Proton Beam Therapy
                Parting Shots
 Photons/Electrons will still be needed
 Brachytherapy will still be utilized
 Image guidance will remain critical for all
  modalities of radiation therapy
 Proton beam therapy can improve the side effects
  profile in many of the disease we currently treat
  with photon radiation.
 We are seeing just the tip of the iceberg
Tumors we are and will be able to treat:

                   Head / Neck
                                           Pediatric
                   •   Eye
                                           •   Brain
                   •   Sinus/nasal
                                           •   Spinal Cord
                   •   Throat
                                           •   Bone
                   •   Ear




               Neurologic                  Other Solid Tumors
               •       Brain               •   Breast Cancer (2011)
               •       Spinal Cord         •   Lung Cancer (2011)
                                           •   Colorectal Cancer
                                           •   Prostate

				
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