This document discusses the evolution of radiation therapy from its discovery in the late 19th century to modern techniques. It traces developments such as the discovery of x-rays and radioactivity, early radium and x-ray therapies, and the introduction of cobalt-60 and linear accelerators to improve targeting ability. Modern advances discussed include intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT), proton beam therapy, and radiosurgery techniques like Gamma Knife and Cyberknife which allow extremely precise high dose radiation treatments.

1. The Evolution of Radiation Therapy

4. Thomas Hodgkin in 1832
Boy with Hodgkin’s in 1920
Until the 1960s, among patients with an advanced stage of
Hodgkin's disease the median survival was 2 years, and only 5% of
patients lived beyond 4 years.
Currently it is curable in 85 to 95% of cases, depending on its stage

5. History of Radiotherapy
 1895 Roentgen discovers Xrays
 1896 Becquerel discovers radioactivity
 1898 Curie discovers radium
 late 1890’s therapeutic use
 1920’s reliable Xray tubes (150-300Kv)
 1950’s Cobalt (1Mv or million volt)
 1960’s Linear Accelerator (4 - 25 million)
 1970’s computers and CT scans
 1980’s 3-D radiotherapy
 1990’s 3D conformal therapy
 2002 IMRT (intensity modulated radiotherapy)
 2002+ IGRT (image guided and radiosurgery)

6. Wilhelm Conrad Röntgen
On the evening of November 8, 1895, he
found that, if the discharge tube is enclosed in
a sealed, thick black carton to exclude all light,
and if he worked in a dark room, a paper plate
covered on one side with barium
platinocyanide placed in the
path of the rays became
fluorescent even when it was
as far as two meters from the
discharge tube.
( 27 March 1845 – 10 February 1923) was a
German physicist, an achievement that earned
him the first Nobel Prize in Physics in 1901

7. Emil Grubbe
Medical Student in
Chicago
March 29, 1896 in an X-ray Tube factory in Chicago he began
to bombard Rose Lee an elderly woman with recurrent breast
cancer and had the first documented response to radiation

8. Antoine Henri Becquerel
In 1896, decided to investigate whether there was
any connection between X-rays and naturally
occurring phosphorescence. He had inherited from
his father a supply of uranium salts, which
phosphoresce on exposure to light. When the salts
were placed near to a photographic plate covered
with opaque paper, the plate was discovered to be
fogged.
(15 December 1852 – 25 August 1908) was a French physicist, Nobel
laureate, and the discoverer of radioactivity along with Marie Skłodowska-
Curie and Pierre Curie, for which all three won the 1903 Nobel Prize in
Physics.

9. Marie Curie
The discovery of radioactivity by Henri
Becquerel led to in 1898 the Curies to the
isolation of polonium, named after the
country of Marie's birth, and radium. Mme.
Curie developed methods for the separation
of radium from radioactive residues in
sufficient quantities to allow for its
characterization and the careful study of its
properties, therapeutic properties in
particular.
(7 November 1867 – 4 July 1934) was a French-Polish physicist and chemist, She
was the first person honored with two Nobel Prizes—in physics and chemistry. She
was the first female professor at the University of Paris, and in 1995 became the
first woman to be entombed on her own merits in the Pantheon in Paris.

10. What is polonium-210, how can it kill you?
Saturday, November 25, 2006
LONDON - Polonium-210 - the radioactive substance that
killed a former Russian spy in London - is one of the world's
rarest elements, first discovered in the 19th century by scientists
Marie and Pierre Curie.
Alexander Litvenko

11. internet Nov. 2006

12. Pre- 1904 X-ray Machine

13. Radium Pack

14. Early Radium Applicators

15. 1902 Cervix Contact X-ray Tube

16. 1930 Radium Tele-Curie Machine

17. Radiation in the early 20th Century
“Weak Discouraged Men!
Now Bubble Over with
Joyous Vitality
Through the Use of
Glands and Radium”
Vita Radium Suppositories (ca.1930)

18. Any Risks of Harm from Radiation?

19. Undark and the Radium Girls

20. Undark and the Radium Girls

21. Undark and the Radium Girls
In 1902, inventor William J. Hammer left Paris with a curious souvenir. The famous scientists
Pierre and Marie Curie had provided him with some samples of their radium salt crystals.
Radioactivity was somewhat new to science, so its properties and dangers were not well
understood; but the radium’s slight blue-green glow and natural warmth indicated that it was
clearly a fascinating material. Hammer went on to combine his radium salt with glue and a
compound called zinc sulfide which glowed in the presence of radiation. The result was glow-
in-the-dark paint.
US Radium employed hundreds of women at their factory in Orange, New Jersey, After a few
strokes a brush tended to lose its shape, so the women’s managers encouraged them to use
their lips and tongues to keep the tips of the camel hair brushes sharp and clean. The glowing
paint was completely flavorless, and the supervisors assured them that rosy cheeks would be
the only physical side effect

22. Undark and the Radium Girls
At their first appearance in court in January 1928, two were bedridden, and none could raise their
arms to take the oath. Grace Fryer, still described by reporters as “pretty,” was unable to walk,
required a back brace to sit up, and had lost all of her teeth. The “Radium Girls” began appearing in
headlines nationwide, and the grim descriptions of their hopeless condition reached Marie Curie in
Paris. “I would be only too happy to give any aid that I could,” she said, adding, “there is
absolutely no means of destroying the substance once it enters the human body.” The last of the
famous Radium Girls died in the 1930s,
the dial painters had ingested anywhere from a few hundred to a
few thousand microcuries of radium per year. One tenth of a
microcurie is now considered to be the maximum safe exposure.
Marie Curie herself died of radiation-related ailments in 1934.
Because radium has a half-life of 1,600 years, her lab notebooks
are said to be too highly contaminated to be safely handled even
today. Radium continued to be used to illuminate watches until
about 1968, but under much safer conditions.

23. At the recommendation of his doctor, Byers began
drinking Radithor, and he continued to do so long
averaged three bottles a day for two years.
Byers stopped consuming Radithor in 1930 when
his teeth started falling out and holes appeared in
his skull.
Perhaps more than anything else, his death in 1932
alerted the public, and much of the medical
Radithor (ca. 1928) profession, of the harmful effects of "mild" radium
therapy.

24. Shoe-Fitting X-Ray Machine
The shoe fitting fluoroscope x-ray machine was a common fixture in shoe stores
during the 1930s, 1940s and 1950s. A typical unit consisted of a vertical wooden
cabinet with an opening near the bottom into which the feet were placed.
When you looked through one of the three viewing ports on the top of the cabinet
(e.g., one for the child being fitted, one for the child's parent, and the third for the
shoe salesman or saleswoman), you would see a fluorescent image of the bones
of the feet and the outline of the shoes.

25. The Gra-Maze
Uranium Comforter
(ca. 1965)
"This is your personal
radioactive uranium
comforter. Actually your
own health mine in
miniature, If you
followed the suggestion
on the pad and checked it
with a Geiger counter,
you would find it to be
measurably radioactive.

26. Sluys-Kessler
Radium Apparatus
Paris. 1930

27. Radium Therapy
Device
1934 Villejuif,
France

28. Skull Film Roentgenogram circa 1923

29. Electron Charged Rays for Cancer, Vienna, 1938

30. Radium Bomb London 1934
4 Radium sources close to the patient’s skin. Each source focused on the cancer from
a different angle, maximizing the dose to the localized area. Protective devices for the
medical practitioner were non-existent at this time

31. COBALT
The use of 60Co sources for
teletherapy was begun in the
1950s as a replacement for
the 250 kVp x-ray treatment
machines that were then in
common use.
The skin-sparing effects of
60Co treatment were
immediately recognized and
such effects were no longer
limitations on treatment.

32. Henry Kaplan
"In the 1950s, I began to hear
cocktail party conversations about
an interesting new atom smasher
being developed on the campus,"
An atom smasher, otherwise
known as a particle accelerator,
uses electromagnetic fields to
propel charged particles to great
energies. By slamming
accelerated electrons into a target
made of heavy metal, high-energy
X-ray beams result.
Kaplan thought this machine
could be harnessed to deliver X-
ray therapy that was superior to
the unreliable, weak and
unfocused radiation therapy
approaches of his day.

33. First Medical Linear Accelerator at
Stanford in 1956

34. In January 1956 the machine was ready to be used on their first patient, a boy with retinoblastoma in his
one remaining eye after surgeons had removed the tumor in the other eye. Destroying the tumor while
sparing the eye would have been impossible with earlier, less-focused radiation sources.

35. Linear Accelerator

36. Use of Cobalt in Cervix Cancer
Patterns of Care Data
100
80
60
Cobalt
40 LinAc
20
0
1978 1983 1988
Montana IJROBP 1995;32:14381

38. Penetration of Radiation by Energy Level

39. Skin Sparing and the Energy of the Beam

40. Selecting the Proper Dose of Radiation
“It may be a bit over-exposed”

41. Prostate Cancer Outcome based on Dose of Radiation
Biochemical relapse-free results by treatment modality.
The study population comprised 2991 consecutive patients treated at the Cleveland Clinic
Foundation or Memorial Sloan Kettering at Mercy Medical Center

42. How Much is Safe ?

43. Strategies to Improve the Effectiveness of
Radiation
 Use chemical or chemotherapy to make the cancer
cells more sensitive to radiation
 Design ways to focus the radiation more precisely
and allow the use of higher doses (conformal 3D,
IMRT or radiosurgery)
 Implant the radiation directly into the tumor
(brachytherapy, with wires or seeds) or isotopes or
monoclonal antibodies

44. Esophagus Cancer Survival - Radiation plus
Chemotherapy versus Radiation Alone
5 Year Survival
Radiation = 0%
Radiation plus
Chemotherapy = 26%

45. Erbitux + Radiation
ERBITUX binds specifically to epidermal growth factor
receptor on both normal and tumor cells, and
competitively inhibits the binding of (EGF)
Over-expression of EGFR is detected in many human
cancers.
Survival with Advanced Head and Neck Cancer
Radiation Alone: 19 months
Radiation + Erbitux: 36 months

46. Strategies to Improve the Effectiveness of
Radiation
 Use chemical or chemotherapy to make the cancer
cells more sensitive to radiation
 Design ways to focus the radiation more precisely
and allow the use of higher doses (conformal 3D,
IMRT or radiosurgery)
 Implant the radiation directly into the tumor
(brachytherapy, with wires or seeds, or isotopes or
monoclonal antibodies)

47. Accuracy in Targeting

48. Targets and Spread of Cancer Cells

49. Definition of Targets

50. MR Spectroscopy to Define Cancer Target
Determining the Tumor Target Volume for a Glioma
T1 images (break down of the blood brain barrier) tend to underestimate the size
of the cancer and T2 post contrast images (which includes the whole area of
edema) tend to over-estimate the size. MR spectroscopy may be more accurate

51. Using PET Scans to Define Cancer

52. Improving and Refining Radiation
Therapy
•First use improved imaging technology (CT/MRI/PET scans) to
define the proper target
•Then use increasingly sophisticated technology to bend the beam
so it will conform to the shape of the target (conformal therapy)
•Modulate the beam even more to get even better targeting (IMRT
or intensity modulated radiation therapy)
•Combine IMRT with technology that will more accurately
identify the target (IGRT or image guided radiotherapy)
•Once the techniques are extremely accurate then use extremely
high doses of radiation that will completely eliminate the cancer
(radiosurgery e.g. Gamma Knife or Cyberknife)

53. Conformal (3D) Radiation for
Prostate Cancer
A Randomized trial at MD Anderson comparing
conventional radiation with conformal therapy
PSA Cures
conventional 53%
conformal 72%
Pollack IRJOBP 1996;34:555

54. Treatment Results and Complications with
Prostate Cancer
Therapy Cure Potent Comps
Implant 87-96% 81-90% 2-12%
External 80-96% 33-70% 3-17%
Surgery 85-95% 22-90% 8-10%
Conformal 96% 70% 3-4%
D’Amico J Clin Onc 1996;14:304

55. Image Guided IMRT

58. In The Head
of the linear
accelerator is
the beam
shaping
MLC

61. Using image guided IMRT to
treat spinal cancer

62. Bone Metastases to the Spine
Involved vertebrae on the left and normal on the right

63. Kidney cancer in
the spinal vertebrae
surrounding the
cord, and
appearance after
radiation…is it
possible to safely
radiate further?

64. Combine a CT scan and linear accelerator to ultimate in
targeting (IGRT) and ultimate in delivery (dynamic, helical
IMRT) ability to daily adjust the beam (ART or adaptive
radiotherapy)

66. PROTON
BEAM

67. Improved Survival with Head and Neck
Cancer and IMRT

69. Conformal proton therapy
for prostate carcinoma.
Int J Radiat Oncol Biol Phys. 1998 Sep 1;42(2):299-
304
Department of Radiation Medicine, Loma Linda
Linac
University Medical Center
When post-treatment prostate-specific antigen (PSA)
was used as an endpoint for disease control, the 4.5- Proton beam
year disease-free survival rate 89%, 72%, and 53%
for patients with initial PSA levels of 4.1-10.0, 10.1-
20.0, and > 20.0, respectively.
External Beam using modern techniques and
a dose of at least 72Gy. Compared with most
recent data on Proton Beam from Loma Linda

70. Best Radiation Treatment for Localized Prostate Cancer
SEER Data 2000-2009. J Clin Onc 2012:30 (s5a3)
Treatment GI Toxicity Hip Fxt RxFailure
Conformal 9.7% + 25% + 24% +
IMRT - - -
Proton Beam 45% + - -
Conformal therapy had higher GI toxicity and hip fractures than IMRT and a
higher relapse rate. Proton had more GI toxicity and no improvement in
outcome compared to IMRT

71. Radiosurgery – using extremely well targeted
radiation to totally eliminate the tumor
Gamma Knife or Cyberknife

72. RadioSurgery the Old Way
Man Survives 18-Inch Drill Bit in Head
Ron Hunt lost an eye but suffered no brain damage after a freak accident with a large
drill bit.
Sept. 2— 2003

73. Lars Leksell. (1907-
1986). ... introduced his
stereotactic
instrument for human
functional neurosurgery
in 1949. ...
Professor Lars Leksell, Swedish physician and Professor of Neurosurgery at
the Karolinska Institute in Stockholm, introduced his stereotactic instrument
for human functional neurosurgery in 1949.
In 1951, using the Uppsala University cyclotron, Leksell developed the
concept of radiosurgery, employed proton beams coming from several
directions into a small area into the brain, in experiments in animals and in the
first treatments of human patients. Therefore, he achieved a new non-invasive
method of destroying discrete anatomical regions within the brain while
preserving the surrounding normal tissues. In 1967, the first Gamma Knife
unit was put into clinical use in Karolinska and this was a 179 cobalt 60
source.

75. The Mayo Clinic gamma knife experience:
indications and initial results.

76. On average, about 92% of acoustic neuromas treated with Gamma
Knife radiosurgery demonstrate tumor shrinkage or growth
cessation over two to five years. Hearing is preserved at pre-
Gamma Knife levels in as many as 51% of patients

77. Brain Metastases
Treatment Median Survival Local Failure
Whole brain external 8 – 15 w 52%
surgical resection 33 – 38 w 20%
rasdiosurgery 44 w 14%

78. Brain Metastasis and External Beam
Irradiation

79. Brain Metastasis
and Radiosurgery

80. Cyberknife Radiosurgery

81. Cyberknife Radiosurgery of the Spine

82. Strategies to Improve the Effectiveness of
Radiation
 Use chemical or chemotherapy to make the cancer
cells more sensitive to radiation
 Design ways to focus the radiation more precisely
and allow the use of higher doses (conformal 3D,
IMRT or radiosurgery)
 Implant the radiation directly into the tumor
(brachytherapy, with wires or seeds, or isotopes or
monoclonal antibodies)

84. HDR Treatments

85. GYN Intracavitary Cesium

86. Interstitial Implant

87. Prostate Seed Implantation

88. Prostate Cancer Cure Rates
External Beam versus Seeds versus Surgery

89. Mammosite for Breast Cancer

90. HDR = high dose rate machine that can run
radiation through a tube that reaches the patient
through skin applicators

91. Radiation for Skin Cancer
HDR skin applicators – three times a week
for 6 treatments over a two week period

92. The HDR Skin applicator is taped in
place over the cancer

93. The applicator is attached by cable to the machine that
makes it radioactive for a few minutes

94. Small squamous
cancer of the chin,
appearance 3.5
weeks after
radiation (HDR)

95. Radiation Isotope
Therapy for Bone
Metastases
Samarium 153 (SM 153) or Quadramet Samarium is now
being used along with Strontium. Samarium has a short half-
life (46 hours) with 75% of the dose absorbed within 4 days.
The beta particle energy (233keV) penetrates 1.7mm in bone
and 3.1 mm in soft tissue. In trials, 48-54% get pain relief.
Metastron or Strontium-89 (Sr-89) Sr-89 is a beta-emitting
radionuclide with a long physical half-life (50.5 days)

96. Radio-active Monoclonal Antibodies
monoclonal antibody targets the CD20 antigen, which is found on the surface of B-cell tumors

97. Radio-active Monoclonal Antibodies
In February 2002, Zevalin was the first radioimmunotherapy to
receive FDA approval. Zevalin consists of a monoclonal antibody
linked to the radioactive isotope yttrium-90. After infusion into a
patient, the monoclonal antibody targets the CD20 antigen, which
is found on the surface of B-cell tumors. In this manner, cytotoxic
radiation is delivered directly to malignant cells.
On June 30, 2003 announced FDA approval of BEXXAR
(Tositumomab and Iodine I 131 Tositumomab)

98. www.aboutcancer.com
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Cancer News, Stages, Old Stages
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