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Radiotherapy : Past Present Future KMIO 2015

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Radiation Oncology, Past present and the future

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Radiotherapy : Past Present Future KMIO 2015

  1. 1. Radiation Therapy Rays of Hope The Past , The Present & The Future Lokesh Viswanath M.D Professor & Head of Unit II , Radiation Oncology, Kidwai Memorial Institute of Oncology 2015
  2. 2. Radiotherapy
  3. 3. Definition of Radiation Oncology • discipline of human medicine concerned with the generation, conservation, and dissemination of knowledge concerning the causes, prevention, and treatment of cancer and other diseases involving special expertise in the therapeutic applications of ionizing radiation. • radiation oncology is concerned with the investigation of the fundamental principles of cancer biology, the biologic interaction of radiation with normal and malignant tissue, and the physical basis of therapeutic radiation. • As a learned profession, radiation oncology is concerned with clinical care, scientific research, and the education of professionals within the discipline.
  4. 4. Radiation Oncology Principle & Practice of Oncology Radiation therapy & Technology Radiation Physics Radiation Safety & Protection Quality assurance Regulations Radiation Biology Clinical -Basic Science / Cellular / Genetic
  5. 5. The aim of radiation therapy • to deliver a precisely measured dose of radiation to a defined tumor volume with as minimal damage as possible to surrounding healthy tissue, resulting in eradication of the tumor, a high quality of life, and prolongation of survival at competitive cost.
  6. 6. • under our care we take full and exclusive responsibility, exactly as does the surgeon who takes care of a patient with cancer. • This means that we examine the patient personally, review the microscopic material, perform examinations and take a biopsy if necessary. • On the basis of this thorough clinical investigation we consider the plan of treatment and suggest it to the referring physician and to the patient. • We reserve for ourselves the right to an independent opinion regarding diagnosis and advisable therapy and if necessary, the right of disagreement with the referring physician. • During the course of treatment, we ourselves direct any additional medication that may be necessary and are ready to be called in an emergency at any time.
  7. 7. Radiation Oncology Team • Physician : Radiation Oncologist • Radiation Physicist • Dosimetrist • RT Technologist (RTTs) – Radiotherapist • RT Nurses
  8. 8. Radiation Therapy : Fundamentals
  9. 9. ELECTROMAGNETIC RADIATIONS Photon E = h(energy = Planck’s const x frequency) = hc/ (c = speed of light,  = wave length) 10-9 10-8 10-7 10-6 10-5 10-4 10-3 10-2 10-1 1 10 102 103 104  rays X-rays U.V. v i s i b l e Infra Red Radio Waves Microwaves Short Waves T.V. Radio Radar IONIZING RADIATION NON-IONIZING RADIATION  (cms) E (eV) 1.24x107 1.24x102 1.24x10-13
  10. 10. Incandescent Light Bulbs Diagnostic X Ray tube Voltage of a Lightning Bolt 110-240 Volts 80-140Kilo Volts 3 to 120 million volts Telecobalt Machine Linear Accelerator 1.1 Mv (Mega = Million Volts) Low Energy - 4-6 MV High Energy - 18 Mv 6 Million Volts 18 Million Volts
  11. 11. Introduction • Basics of Radiation Therapy – High energy Ionizing Radiation – X / γ Rays – Interaction of Radiation with matter Transmission Attenuation Scatter Absorption Rad / Gray / cGy
  12. 12. Cancer Cell & Ionizing Radiation • Cancer cell multiply faster than normal cell • DNA is primary target • Double Strand breaks >>> Reproductive Cell Death
  13. 13. • Injury to DNA is the primary mechanism by which ionizing radiation kills cells . – Most DNA damage is repaired – Lethal double-strand breaks -persist (locally multiply damaged sites (300) of about 15 to 20 nucleotides in size) – Micronuclei formation – Chromosome aberrations – Cell death through loss of the reproductive integrity of the cell's genome. • Many biologic factors affect the relationship between the amount of physical energy deposited, the extent of DNA damage that is caused, the number of cells that are killed, and the severity of the tissue response
  14. 14. • Radiation therapy is the art of using high energy ionizing radiation to destroy malignant tumors while being able to minimize damage to normal tissue. • To be practiced like a Religion • SOPs
  15. 15. RT is a Double Edge Sword
  16. 16. ↑ RT Dose ↓ RT Dose ↑ T – Control ↓↓ T – Control ↑↑ Normal Tissue Toxicitites ↓ Normal Tissue Toxicitites
  17. 17. Radiation therapy BrachytherapyTeletherapy
  18. 18. Tele Radiation Equipments γ –Rays (Radioactive Source based) - Radium Bomb Tele Cesium Telecobalt Gamma Knife X - Rays Linear Accelerator 2D Electrons 3DCRT SRS/SRT IMRT IGRT Rapid Arc FFF SBRT 4DRT – Target tracking 6D Couch IORT Tomotherapy Cyber Knife Particle Beam Protons Carbon Neutrons
  19. 19. Brachytherapy : Radioactive source loading Temporary Pre Loaded After loading Remote LDR HDR Manual Permanent After Plan Pre Plan – Intracavitory / Luminal – Interstitial – Surface Mould
  20. 20. THE PAST 1895- 1920s : Seeding - X - Ray & Radium 1920 – 1930 : embryo Phase 1930 -1950 : Quisent phase : World War I & II •Artificial Radioactivity, •Development in Radar Technology 1950 – 1970 : Development Phase: Telecobalt & Linear Acclelrator – 1980 – 2000 : Infancy 2000-2005 : Growth Phase 2005 – 2010 : Maturation Phase 2010 – 2015 : Flower > 2015 : Fruits
  21. 21. Marie Curie (1867 – 1934) Born in Poland University of Paris age 24 Discovered Radium 1898 t1/2 = 1602 years
  22. 22. Irene Joliot-Curie and Frederic Joliot Curie • Artificial radioactivity
  23. 23. Emil Grubbe (1875-1960) : the World’s first Radiation Oncologist. • medical student in Chicago • convinced his professor to allow him to irradiate a cancer patient, a woman named Rose Lee • Ms. Lee benefited greatly from Grubbe’s intervention, demonstrating the potential value of x-ray treatments.
  24. 24. Claude Regaud (1870-1940) : Paris • recognized that treatment may be better tolerated and more effective if delivered more slowly with modest doses per day over several weeks.
  25. 25. Henri Coutard (1876-1950) Paris • pioneered the use of fractionated Radiotherapy in a wide variety of tumors. • Note, he reported impressive results using this approach in patients with locally advanced laryngeal cancers. His seminal 1934 report of the outcome of these patients is still quoted today.
  26. 26. Ralston Patterson (1897-1981) : England • Holt Radium Hospital - center for radiation treatment and research
  27. 27. Gilbert Fletcher • MD Anderson Cancer Center • established optimal treatment regimens in a wide variety of tumor sites including head and neck cancers and cervical cancer.
  28. 28. Brief History of Radiation Therapy Chronologic Milestones: • 1895 W.K.Rontgen discovered X-Rays. • The first patient was treated with radiation in 1896, two months after the discovery of the X-ray. • 1896 Becquerel reported natural radioactivity in Uranium compounds. • 1898 Marie and Pierre Curie isolated radium from pitchblende. • 1900 Villard reported that radium emitted alpha, beta and gamma radiations. • 1934 Frederic and Irene Joliot (Curie’s daughter) discovered artificial radioactivity.
  29. 29. FIRST CURE OF CANCER BY X-RAYS 1899 - BASAL CELL CARCINOMA X-rays were used to cure cancer very soon after their discovery
  30. 30. Natural radioactivity was discovered by Becquerel, who was awarded the Nobel Prize in Physics in 1903 along with Marie and Pierre Curie "in recognition of the extraordinary services they have rendered by their joint researches on the radiation phenomena" “One wraps a Lumiere photographic plate with a bromide emulsion in two sheets of very thick black paper, such that the plate does not become clouded upon being exposed to the sun for a day. One places on the sheet of paper, on the outside, a slab of the phosphorescent substance, and one exposes the whole to the sun for several hours. When one then develops the photographic plate, one recognizes that the silhouette of the phosphorescent substance appears in black on the negative. If one places between the phosphorescent substance and the paper a piece of money or a metal screen pierced with a cut-out design, one sees the image of these objects appear on the negative. One must conclude from these experiments that the phosphorescent substance in question emits rays which pass through the opaque paper and reduces silver salts.” Paris 1896 Maltese crossHenri Becquerel Marie Curie
  31. 31. Radioisotopes also were soon being used to treat and cure cancer. Radium applicators were used for many other conditions! Radioactive plaques and implants are still in common use, for example in prostate implant seeds. cure of cancer by radium plaque - 1922
  32. 32. • 1898 Becquerel’s vest-pocket skin erythema and reports of x-ray ‘burns’. • 1903 Bergonie and Tribondeau described radiosenstivity of proliferating cells. • 1930 Coutard proposed treatment fractionation. • 1950 Paterson’s definition of Therapeutic Ratio: Normal Tissue Tolerance/ Tumor Control Dose. Chronologic Milestones
  33. 33. THE EVOLUTION OF RADIOTHERAPEUTIC TECHNIQUES :EARLY CHALLENGES • Detection of Ionizing Radiation • Defining the Quality of Radiation • Defining the Quantity of Radiation • Understanding the Mechanism of Action of Radiation • Optimizing Radiation Delivery Equipments
  34. 34. THE EVOLUTION: Measuring Radiation Dose: • Skin Erythema Dose. • 1902 Holzknecht in Vienna developed the Chromoradiometer - An apparatus once used for estimating radiation exposure by means of the color changes produced in slides placed next to the skin. • 1904 Sabouraud and Noire in France modified Holzknecht’s method to Pastille-dose technique using pastilles of barium platinocyanide. • 1913 Ionization current measurement developed in Paris, and adopted in 1928 at the ICR as the standard unit “r”: x or gamma radiation producing 1 e.s.u in 1 cc of air. • 1953 at the ICR the ‘rad’ was introduced as the unit of absorbed dose: equal to 100 ergs per gram. • 1970 the rad was redefined in a metric system: the Gray: joules absorbed per kg. 1 Gray = 100 rads.
  35. 35. THE EVOLUTION : Quality of Radiation  1913 Coolidge in the USA engineered the first successful X-ray tube using hot-filament and Tungsten target.  1920 higher voltages X ray units with more powerful transformers and rectifiers:  Contact therapy @ 50 KV,  Superficial @ 100-150 KV  Deep X-rays @ 200-400 KV.  Effect of added filtration.  Quality measured by HVL.  1933-1950 the evolution Megavolt era:  Van de Graaff electrostatic,  the Betatron,  the Cobalt units and  the Linear accelerator.
  36. 36. History of Particle Beam Therapy 1938 Neutron therapy by John Lawrence and R.S. Stone (Berkeley) 1946 Robert Wilson suggests protons 1948 Extensive studies at Berkeley confirm Wilson 1954 Protons used on patients in Berkeley 1957 Uppsala duplicates Berkeley results on patients 1961 First treatment at Harvard (By the time the facility closed in 2002, 9,111patients had been treated.) 1968 Dubna proton facility opens 1969 Moscow proton facility opens 1972 Neutron therapy initiated at MD Anderson (Soon 6 places in USA.) 1974 Patient treated with pi meson beam at Los Alamos (Terminate in 1981) (Starts and stops also at PSI and TRIUMF)
  37. 37. (Cont) 1975 St. Petersburg proton therapy facility opens 1975 Harvard team pioneers eye cancer treatment with protons 1976 Neutron therapy initiated at Fermilab. (By the time the facility closed in 2003, 3,100 patients had been treated) 1977 Bevalac starts ion treatment of patients. (By the time the facility closed in 1992, 223 patients had been treated.) 1979 Chiba opens with proton therapy 1988 Proton therapy approved by FDA 1989 Proton therapy at Clatterbridge 1990 Medicare covers proton therapy and Particle Therapy Cooperative Group (PTCOG) is formed: 1990 First hospital-based facility at Loma Linda (California)
  38. 38. Hammersmith Hospital, London, 1905
  39. 39. KMIO: 100 Kv : Orthovoltage / Superficial X Ray Unit
  40. 40. Telecesium • At KMIO Decomissioned few years back
  41. 41. Selectron • Remote controlled after loading brachytherapy unit • Pneumatic driven
  42. 42. 1951 – First Cobalt machine • Saskatoon, Saskatchewan • London, Ontario • Co 60 – t ½ = 5.26 years – Gamma emitter – Energy 1.25 MV
  43. 43. 1956, Henry Kaplan, MD • The first patient to receive radiation therapy from the medical linear accelerator • Stanford • 2-year-old boy with retinoblastoma
  44. 44. History of Radiation Delivery • Linear Accelerators: 1950 to present – Traveling wave systems – Standing wave systems – Microtron – Reflexotron
  45. 45. THE EVOLUTION OF RADIOTHERAPEUTIC TECHNIQUES 1970 & 80s Treatment Planning:  Central Axis % Depth Dose.  Plotting Isodose Curves.  Multiple Fields Cross-Fire.  Manual Patient Contouring and Manual Isodose Curve Summation.  Computer Treatment Planning Central Axis and Off- Axis.  Image Based 3-D Dose Distribution.
  46. 46. IK/2007
  47. 47. IK/2007
  48. 48. IK/2007
  49. 49. IK/2007
  50. 50. IK/2007
  51. 51. THE EVOLUTION OF RADIOTHERAPEUTIC TECHNIQUES Understanding the biology of Cancer: The natural history of different tumors based on cell types. The importance of cancer staging. Retrospective outcome studies and prospective Clinical Trials. Identifying Dose Response expectations.
  52. 52. • 1970's Computed Tomography (CT) Ultrasound (US) • 1980's Magnetic Resonance Imaging (MRI) Digital Subtraction Angiography (DSA) Computed Radiography (CR) • 2000'sDigital Radiography (DR)
  53. 53. • >1985 – CT scan for RT Planning , Involved Manual Digitization of Contours only • > 1990 – CT Scan Data was used for Target localization & Contouring – 3 D Rendering of Body contours and Tumour and normal tissue Grids – Beams Eye view • > 1995 – 3D Planning – 3D Conformal Bocks • CD Scan data of Tissue Density used for RT calculation • > 1998 - 3 D Conformal RT • 2000 : Evolution of IMRT (Conceptualized in 1960s)
  54. 54. • Early 2000 IGRT – Cyber knife , non-isocentric mount , Celing mounted KV Imaging and advanced verification and repositioning • 2005 IMRT as a routine • With IGRT – Adaptive Radiotherpay need for advanced Imaging • CT on Rails or Onboard Mv/Kv Cones CT imaging, • Integration of ceiling mounted KV imaging
  55. 55. THE EVOLUTION OF RADIOTHERAPEUTIC TECHNIQUES Impact of Modern Technology: Impact of Computer technology. New Imaging technology. Advances in Molecular biology. The multidisciplinary approach to Cancer treatment.
  56. 56. MODERN RADIOTHERAPEUTIC TECHNIQUES Image based treatment planning. 3-d conformal treatment planning. Intensity Modulated Radiation Treatment (IMRT). Image Guided Radiation Treatment and Adaptive Radiation Treatment. Investigational: Proton and Particle Therapy.
  57. 57. Key Mile stone • Use of CT Scan DICOM image for RT Planning • 3 D rendering • BEV
  58. 58. MLC Multileaf collimator Advanced computerization and Hardware control and processing. Advanced radiation safety devices
  59. 59. Lateral Isocenter Verification Portal Imaging
  60. 60. Collimator Orientation
  61. 61. Multileaf Collimation MicroMLC • Maximum field size: 72 x 63 mm •Number of leaves: 40 per side •Leaf thickness: 1 mm •Material: tungsten • Maximum field size: 100 x 100 mm •Number of leaves: 26 per side •Leaf thickness: 5.5, 4.5, 3 mm •Material: tungsten
  62. 62. • Electronic portal imaging • Motion management Image Guidance Technology
  63. 63. Advanced Image Guidance Elekta Synergy Varian Trilogy
  64. 64. Solid state imaging panel Kilovoltage X-ray source 90cm Clearance Image Guidance - Components
  65. 65. Tele Radiation Equipments γ –Rays (Radioactive Source based) - Radium Bomb Tele Cesium Telecobalt Gamma Knife X - Rays Linear Accelerator 2D Electrons 3DCRT SRS/SRT IMRT IGRT Rapid Arc FFF SBRT 4DRT – Target tracking 6D Couch IORT Tomotherapy Cyber Knife Particle Beam Protons Carbon Neutrons
  66. 66. Tomotherapy - 2003
  67. 67. Synchrony™ camera Treatment couch Linear accelerator Manipulator Image detectors X-ray sources Targeting System Robotic Delivery System Cyber Knife – 2003+
  68. 68. IGRT - 2005
  69. 69. True beam - All in One FFF SBRT / 4DRT –
  70. 70. True Beam - 2010
  71. 71. Proton Beam therapy 2012
  72. 72. Brachytherapy : Radioactive source loading Temporary Pre Loaded After loading Remote LDR HDR Manual Permanent After Plan Pre Plan – Intracavitory / Luminal – Interstitial – Surface Mould
  73. 73. 125 I Seed Implant
  74. 74. Interstitial Brachytherapy
  75. 75. Prostate Brachytherapy
  76. 76. Prostate Brachytherapy Iodine 125 t ½ = 60 days Gamma emitter Energy 35 kV
  77. 77. Treatment Planning MLC Control Linac Control MLC User Interface Common Memory Linac MLC Console User Interface Linac Linac Control MLC Control MLC Control Linac Control MLCLinac Added GUI Record/Verify DB User Interface Electronics Hardware Control of Radiation Delivery
  78. 78. Present : KMIO RO Teletherapy • Orthovoltage – 1 (not working) • Telecobalt – 3 (1 due for decomissioning) • Linear Accelerator – Low energy : Simple – 1 – High – Dual energy : 3DCR /IMRT/Electorns - 1 Brachytherapy • HDR – 1 – ICBT - 2 – ISBT – due for decomissioning – ILBT - 1 • LDR – 2 sets
  79. 79. Telecobalt 1970s
  80. 80. Linear Accelerator • 3DCRT > 1998+ • IMRT > 2000+
  81. 81. Linear Accelerator : 3DCRT / IMRT
  82. 82. HDR - Brachytherapy
  83. 83. Future : KMIO RO • KMIO has been granted a status of State cancer Institute : Apex Institution in the State of Karnataka to forsee cancer related activities in the region.
  84. 84. Radiation Oncology Expansion Plans
  85. 85. >2015 Radiation Oncology Block Fully Automated , Paperless environment Sanctione d Equipments Number State of the Art High energy Linear Accelerators 4 IMRT – Advanced rotational IGRT 4D / 6D Advanced tumor tracking FFF SRS/SRT Whole body SBRT HDR Brachytherapy 2 IR / Cobalt Virtual Widebore CT Simulators 2 Permanent Implant Brachytherapy suit with advanced planning system 1 Capable of handling Iodine seed – BARC / Imported Intra operative Electronic Brachytherapy / Electorns suit 1 Advanced Doismetry equipments Set
  86. 86. Future - Research • Cell biology - understand effects of ionizing radiation on cells, tumors, and normal tissues. • molecular cancer biology - clinical decision-making in oncology • development of novel biology-driven strategies in the multidisciplinary clinical environment. – Molecular pathology of tumors - basis for improved treatment stratification in oncology . – Molecular pathophysiology - manifestation of radiation sequelae in normal tissues . – Molecular imaging - staging , biologic characterization of tumors, and for determination of target volumes in radiation oncology, including new approaches such as dose painting. – Molecular targeting in radiotherapy - enhancing the therapeutic gain of the treatment.
  87. 87. Proton Therapy vs. IMRTProton Beam
  88. 88. Thank you
  89. 89. Cobalt- 60
  90. 90. Co 60 Radiosurgery – “Gamma Knife”
  91. 91. Linear Accelerator
  92. 92. Linac Radiosurgery – “X Knife” • High energy beam • 1 moving source • 5mm – 4cm target
  93. 93. Linac Radiosurgery – “X Knife” Advantages • Allows multiple fractions • More widely available • Linac has other uses
  94. 94. Couch CT Simulator
  95. 95. Treatment Planning Beam Placement
  96. 96. Multileaf Collimator (MLC) No more lead blocks!
  97. 97. Synchrony™ camera Linear accelerator Manipulator Image detectors X-ray sources Targeting System Robotic Delivery System
  98. 98. Proton Therapy Center Czech
  99. 99. rapid dose fall-off unecessary radiation in normal tissues beam exit beam exit
  100. 100. Physical and technical principles Leksell gamma knife
  101. 101. Exposure to the gel dosimeters by Leksell Gamma Knife of varying diameter collimator 4 mm 18 mm14 mm8 mm
  102. 102. Name: B. H. DOB: 1941 SCLC extensive disease
  103. 103. Name: B. H. DOB: 1941 SCLC extensive disease
  104. 104. Grenz Rays Megavoltage Orthovoltage Superficial Therapy Contact Therapy 20 KeV 50 KeV 150 KeV 500 KeV 1-25 MeV Major improvements in RT during the mid-1900s came from improved penumbra and decreased skin dose associated with higher energy x-rays, cobalt, and high energy photons. More recently conformal RT, IMRT, IGRT, Gammaknife, Cyberknife, tomotherapy, SRS, SRT, protons, heavy ions, etc. have added considerable variety to the choices for physical radiation delivery and present radiobiological challenges.

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