Radiation Therapy 2013 The Role of Protons. Bob Gaston, D.O.

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1 Radiation Therapy 2013 The Role of Protons Bob Gaston, D.O.

2 Disclosures Oklahoma ProCure Treatment Center Radiation Medicine Associates

3 Goal of Radiation Therapy Increase the Therapeutic Ratio Therapeutic ratio = Tumor control Normal tissue complications Goals of radiation oncology for 100 years: Get more radiation into the tumor Reduce amount of radiation in healthy surrounding tissue

4 Megavoltage Photons High energy packets of light D-max Skin sparing properties Energy loss with depth (per cm of tissue) 18 mv 2.0% Dmax 3.0 cm 6 mv 3.5% Dmax 1.5 cm 1.25 mv 4.5% Dmax 0.5 cm superficial 50% Dmax 0.0 cm PHOTONS EXIT

5 Photon Depth Dose Profiles

6 Linear Accelerators with Image Guidance Varian Trilogy Elekta Synergy

7 Linear Accelerator Integration with CT Tomotherapy A linear accelerator built in to CT scanner

8 Gamma Knife Gamma = Intranuclear Knife = Photon No linear accelerator Same type of radiation Slide Reference # or Date

9 CyberKnife Linear accelerator on a robotic arm Long treatment time = increased opportunity for intra-fraction motion

10 Brachytherapy

11 Cyclotron

12 Cyclotron

13 Beam Line and Bending Magnets

14 Inclined Beam Treatment Room

15 Field Design ACT Foundation,LLC.

16 Bragg Peak Treatment range <5 mm at 14.8 cm depth

17 Spread Out Bragg Peak

18 For the same target volume, X-rays deliver a greater dose outside the target than protons do Depth dose curve comparison for protons and photons 300 X-rays 250 Additional dose outside the target delivered with photons Relative dose (%) Proton spread out Bragg peak Protons Tumor Depth in water (mm)

19 Protons Deliver More Radiation to the Tumor and Less to Healthy Tissue There is no reason to irradiate healthy tissue. Photons Protons Higher Higher Radiation Dose Prescribed Dose to Kill Tumor Radiation Dose 20% 80% 0% Prescribed Dose to Kill Tumor Lower Lower 70% 20% 10% Depth in Tissue Depth in Tissue The total dose to healthy tissue typically will be 5 times higher with photons than with protons.

20 Improvements in Radiation Dose Distribution 6X parallel opposed fields 3D 5-fields IMRT 9 -fields 4-field plan tumor photons photons photons protons Tumor

21 Case Study: Paraspinal Ewing s Sarcoma Sameer Keole, M.D.

22 Paraspinal Ewing s Sarcoma IMRT Plan Multiple Conformal Fields Proton Sameer Keole, M.D.

23 Post Treatment Imaging IMRT Plan Proton Sameer Keole, M.D.

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25 Breast Cancer It is estimated that 226,870 women will be diagnosed with and 39,510 women will die of cancer of the breast in 2012 Stage at Diagnosis Stage Distribution (%) 5-year Relative Survival(%) Localized (organ confined) Regional (lymph nodes) Distant (distant spread) Unknown (unstaged) SEER incidence and NCHS mortality statistics

26 Breast Cancer Therapy LAD and left circumflex Artery Right coronary artery *Arrows point to subsections of the coronary arteries which are hotspots for stenosis after left breast radiation Nilsson G et al. J Clin Oncol. 30(4)2012:

27 Protons Versus Combined Photon/Electron Plans Protons Electron / X-ray match

28 BRE Phase II Study of Postoperative, Cardiac-Sparing Proton Radiotherapy for Women with Stage III, Loco-Regional, Non-Metastatic Breast Cancer Breast and regional nodes 50.4 Gy + Surgical bed boost of 10.8 Gy in 6 fractions; cumulative dose of 61.2 Gy or Chest wall and regional nodes 50.4 Gy + Optional chest wall scar boost of 10.8 Gy; cumulative dose of 61.2 Gy

29 Extra Dose

30 PCG BRE Proton Therapy for Partial Breast Irradiation in Early Stage Breast Cancer *Invasive Ductal Carcinoma or DCIS, negative surgical margins, Stage 0, I, II, < 3.0 cm, pn0, > 50 years of age, ER positive disease Lumpectomy Within 8 wks after completion of chemotherapy OR Within 12 weeks after surgery Radiotherapy 4.0 Gy (RBE) x10 fractions

31 Whole Breast Versus Partial Breast Treatment David Bush, MD Loma Linda University Medical Center Phoenix, AZ Breast Workshop-Feb 2013

32 Direct Radiation Complications Never Occur in Unirradiated Tissues 1 IMRT immerses more healthy tissue with radiation IMRT 7-field co-planer Radiation therapy plans for prostate cancer Proton therapy 2-field DS Blue 13% Green 51% Purple 63% Yellow 76% Red 95% Higher dose bath to healthy tissue with IMRT: Pelvis, rectum and bladder Tumor Less healthy tissue exposed to radiation 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):

33 Dosimetry Data Keole, Zheng, et al ASTRO 2012 Actual OKC patient data treated with both uniform scanning protons and IMRT. IMRT advances cannot overcome physics properties resulting in high volume low dose bath.

34 Protons Reduce Dose To The Rectum By 59% Rectal Volume Receiving Radiation (%) IJROBP 2008 Radiation dose to the rectum proton therapy and IMRT 1 90% 80% 70% 60% 50% 40% 30% 20% 10% Proton IMRT Dose to rectum is more than 2x with IMRT vs. protons at 32 Gy Dose to rectum is almost 2x with IMRT vs. protons at 70 Gy Background on study First prostate patients seen at University of Florida Proton Therapy Institute ( UFPTI ) Both proton and IMRT plans were planned prospectively for each patient The results Relative and absolute mean rectal dose savings of 59.2% and 20.1%, respectively, with proton therapy Why this is important Entire Dose Volume Histogram ( DVH ) does matter, not just high the dose region Rectal wall volume irradiated at 32.4 Gy is biggest predictor of rectal toxicity 2 Extremely high correlation between rectal volume irradiation to 70 Gy and 5-year toxicity rates 3 0% 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): (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): (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):

35 PROTONS ARE SAFER 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-S Naeem Bhojani et al., The rate of secondary malignancies after radical prostatectomy versus external beam radiation therapy for localized prostate cancer: a population-based study on 17,845 patients, International Journal Radiation Oncology Biology Physics 76 No. 2 (2010): 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): 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 A 2008 MGH study determined that protons decreases the risk of patients developing a secondary cancer by 50 percent (1) According to the study, 6.4 percent of patients who underwent proton therapy developed a secondary cancer while 12.8 percent of patients who had photon treatment [x-rays] developed another type of cancer. Protons significantly decrease the risk of secondary malignancies in prostate cancer treatment over five year period Modality Risk of induced tumor Baseline risk 2 4% Conventional 3,4 10% IMRT % Protons 6 6%

36 Proton Collaborative Group GU A Phase III Randomized Trial of Standard-fractionation vs. Hypofractionation with Proton Radiation Therapy for Low Risk Adenocarcinoma of the Prostate Conformal Proton Radiation Arm I: Dose: 79.2 CGE 1.8 CGE five days a week in 44 treatments over weeks Arm II: Dose: 38 CGE 7.6 CGE five days a week in 5 treatments over 1-2 weeks

37 Proton Collaborative Group GU Phase III Study of Mildly Hypo-fractionated Image Guided Proton Beam Radiation Therapy With or without Androgen Suppression for Intermediate Risk Adenocarcinoma of the Prostate Radiation Therapy Dose: 70 CGE 2.5 CGE five days a week in 28 treatments over weeks Androgen Deprivation Arm I: Proton therapy alone Arm II: Proton Therapy and androgen deprivation for 6 months

38 Proton Collaborative Group GU Phase III Study of Image Guided Proton Beam Radiation Therapy With or Without Chemotherapy for High Risk Adenocarcinoma of the Prostate Conformal Proton Radiation Radiation Therapy Dose: 79.2 CGE 1.8 CGE five days a week in 43 treatments over weeks Arm I Androgen Deprivation Proton Therapy and androgen deprivation for 24 months Arm II Chemotherapy Proton Therapy and concurrent chemotherapy (weekly Taxotere)

39 Proton Appropriate Sites? Head / Neck Eye Sinus/nasal Throat Ear Pediatric Brain Spinal Cord Bone Neurologic Brain Spinal Cord Other Solid Tumors Breast Cancer Lung Cancer Colorectal Cancer Prostate select

40 Radiation Medicine Associates Melissa Boersma M.D. Integris ICIO Nancy Cersonsky, M.D. Integris ICIO Michael Confer, M.D. Saint Anthony Shawnee Hospital, Deaconess Hospital Lucius Doh, M.D. Integris SW, Integris ICIO, Integris Clinton Bob Gaston, D.O. Norman Regional, Saint Anthony Shawnee Hospital Gary Larson, M.D. (Medical Director), Integris SW, Integris ICIO, Integris Clinton Elaine Nordhues, M.D. Deaconess Hospital, Saint Anthony Shawnee Hospital, Norman Regional Kiran Prabhu, M.D. Integris SW, Integris ICIO John Taylor, M.D. Deaconess Hospital, Saint Anthony Shawnee Hospital

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