5

Radiotherapy
HISTORY further producing chain reaction. This chain reaction is
controlled by moderators in nuclear reactors, which cannot
„„ X-Ray was discovered by Röntgen in 1885 be done when used as nuclear bombs.
„„ First treatment for malignancy was done in 1896 by using „„ Nuclear fusion: When two low mass nuclei combined
X-rays together to produce one nucleus
„„ Radium was discovered by Marie Curie in 1898 „„ X-Rays are produced when fast moving electron is stopped
„„ First Cobalt-60 therapy Unit was installed in 1951 by a high atomic material anode
„„ First linear accelerator therapy unit was installed in 1970s „„ Electrons are produced by the cathode by thermionic
emission
Electrons have less penetrating property

e
„„
DEFINITION „„ As the energy increases for the photon the penetrating

„„ Radiation therapy is a clinical modality dealing with the

use of ionizing radiations in the treatment of patients with
2/ „„
property increases
The photons of energy more than 15 MV are not clinically
used in radiotherapy due to neutron contamination
malignant neoplasms and occasionally benign diseases.
„„ Protons are particulate rays and have a characteristic
P,
property called ‘Bragg Peak’
RADIATION PHYSICS „„ X-rays travel only very minute distance and mostly used as
injectables
R

„„ Nucleus contains Protons (postive charge) and Neutrons Table 1:  Units of radiation
(No Charge)
SA

„„ An atom is specified by the formula zXA . CGS Unit SI Unit

„„ Mass number (A) is the number of nucleons (neutron and Absorbed radiation Rad Gray, Gy (100 Rad
proton) in the nucleus dose = 1Gy)
„„ Atomic number (Z) is the number of protons in the nucleus Radiation exposure Röentgen, R
or number of electrons in the orbiting shells
„„ Isotope is defined as the element, which has same atomic Activity Curie, Ci Becquerel, Bq
number but different mass number. Dose equivalent Röentgen Sievert, Sv
„„ Radioactivity: Emission of radiation from a nucleus in the equivalent man,
form of particles, X-rays or both. rem
„„ Half-Life is the time required for either the activity or the Table 2:  Half-lives of different radioactive substances
number of radioactive atoms to decay to half the initial
value. Cobalt-60 5.26 years
„„ The elements in the periodic table with atomic number Cesium-137 30 years
(Z) up to 82 (Lead) are nonradioactive. The elements with
Radium-226 16,00 years
atomic number more than 82 are all radioactive, i.e. they are
unstable elements. Radon-222 3.83 days
„„ The other nonradioactive elements can be made radioactive Iridium-192 73.8 days
in nuclear reactors. (Cobalt for radiotherapy, fluoride for
Gold-198 2.7 days
PET CT Scan as 18FDG, Carbon, etc.)
„„ Nuclear fission: High atomic number nuclei splits into Iodine-125 59.4 days
lower atomic nuclei with the release of high energy and Palladium-103 17 days
 ENERGY OF RADIATION zz Medium dose rate (MDR) brachytherapy: Energy
between 1.2Gy and 12Gy/hr
The energy of the radiation emitted by the isotopes is fixed for „„ The half-life of the isotope determines whether it is
that specific isotope. permanent or temporary. Longer half–life—temporary,
shorter half–life—permanent (shorter half–life and it looses
Table 3:  Isotopes and the energy released from them
its effect after short time, hence no effect in longterm, longer
Isotope Energy half–life will have radiation hazard)
Cobalt-60 Average-1.25 MeV (Two energies: „„ Radiation from the isotopes (γ rays, α-rays and β-rays)
1.17 MeV and 1.33 MeV and the linear accelerators (X-rays) are indirectly ionizing
radiation and are in general called photons (Packets of
Iridium-192 0.3 MeV charged particles with zero mass)
Radium-226 0.83 MeV average
Cesium-137 0.66 MeV
RADIOPHARMACEUTICAL
The energies of radiation coming out of a linear accelerator can be
manually selected by adjusting the acceleration of the electrons. „„ Radiopharmaceuticals are radioactive substance injected
In General, 4 MV, 6 MV, 15 MV are clinically used. Photons with intravenously or instilled into the tumor to produce
energies more than 20MV are not recommended for clinical use. radiotherapy effects.
Proton beams (Particle beam) are generally in the energy „„ The bones seeking radiopharmaceuticals are widely used
range of 150–250 MeV. for bone tumors:
„„ Phosphorus – 32 (P-32), Strontium – 89 (Sr-89),
Samarium-153 (Sm-153), Rhenium-186 (Rh-186), Rhenium
TYPES OF RADIATIONS – 188 (Rh-188).

e
„„ For thyroid cancers: Iodine-125 (I-125), Iodine-131 (I-131),
Electromagnetic radiation is a spectrum, which is divided into:
Iodine-123 (I-123)
„„ Nonionizing (visible light, radio waves, cellular signals, etc.)
2/
„„ Ionizing radiation How Photons Interact with Matter? (Tissue
Directly ionizing (Charged Particle—Electrons,
zz
protons)
in Clinical setting)
P,
zz Indirectly ionizing (Neutral Particles—Photons, „„ Coherent scattering, photoelectric effect, compton effect,
Neutrons) pair production)
„„ Photoelectric effect – Utilized in radiodiagnosis (Energy of
R

Photon less than 1:MV)

RADIOTHERAPY „„ Compton effect: Utilized in radiation therapy (Energy of
SA

Photon more than 1:MV)

„„ Teletherapy: When the source of radiation is away from the
patient
„„ Brachytherapy: When the source of radiation is near and or STEREOTACTIC RADIOSURGERY (SRS)
into the tumor. Brachytherapy may be:
zz Interstitial: Source is inside the tumor (Tongue, prostate „„ High dose of radiation is delivered than the conventional
and sarcoma) dose to achieve a rapid ablative effect, it is called stereotactic
zz Intracavitory: Source is in the cavity (Cervix and radiosurgery.
esophagus) „„ It can be given in a single fraction as in brain tumors or 3–5
zz Mold: Source is on the tumor (Skin). fractions as in lung and prostate.
„„ Gamma knife is a Cobalt isotope based SRS system. X-Knife,
R „„ Commonly Used Isotopes in Radiotherapy: Cobalt-60,
Cesium-137, Iridium-192, Radium – 226, Gold-198, Cyberknife, etc. are LINAC-based SRS system.
A Iodine-125, Palladium-103, etc.,
D „„ Depending on the duration of implant in brachytherapy, it
RADIATION TECHNIQUES
may be
I zz Temporary: Minutes, hours or days (Cervix, esophagus Two-dimensional radiotherapy: When planning and
O and tongue)
„„
delivery of radiation is done based on two-dimensional view
L zz Permanent – Once implanted/injected/ingested will of the tumor. Lots of normal tissue will be irradiated
O not be removed (Prostate-Gold, Thyroid-Iodine) „„ Three-dimensional conformal radiotherapy: When
„„ Depending on dose rate planning and delivery of radiation is done by utilizing the
G zz Low-dose rate (LDR) brachytherapy: Energy 0.5 to 1.2 3D view of the tumor and by using computerized program
Y Gy/hr in delivery. Lots of normal tissue can be saved by decreasing
zz High dose rate (HDR) brachytherapy: Energy more long-term side effects and increasing the dose to the tumor.
than 12Gy/hr
320
„„ Intensity Modulated Radiotherapy (IMRT): The intensity Fractionation in Radiotherapy
of the radiation is changed with in the tumor volume so as to
achieve a highly conformal dose delivery plan This is highly „„ Conventional fractionation: When radiation is delivered
recommended highly for brain, head and neck, lung, etc. single fraction a day, 1.8 to 2.25 Gy per day, five days a week
„„ Image-Guided radiotherapy (IGRT): It is a form of IMRT „„ Hyperfractionation: In this, the total dose is kept same as
utilizing the image guidance for the mobile organ irradiation in conventional fractionation, but giving two fractions in
a day with less dose per fraction than conventional. (Total
„„ Four-dimensional Gated IGRT: This technique utilizes the
treatment duration may same or extended)
software and hardware advantage to deliver the radiation in
accordance to the movement of tumor as in the lung tumor, „„ Hypofractionation: The total duration is decreased, total
liver tumor etc., dose is decreased but the dose per fraction is increased.
dose 2.25Gy to 4 Gy is Hypofractionation, 4-6Gy is Ultra-
hypofractionation and above 6 Gy is radiosurgery.
TOTAL BODY IRRADIATION
Mechanism of DNA damage
„„ Used in preparative cytoreductive regimens for „„ Direct actions: The radiation directly affects the DNA
hematopoietic cell transplantation (protons and neutrons)
„„ Leukemia and lymphomas are most common situation „„ Indirect action: The radiation interacts with oxygen in
where TBI is used tissues producing free radicals which in turn damages the
„„ Photons are used in TBI DNA. (X-Rays, γ-rays) (Blood which supplies oxygen is
„„ Total skin electron beam irradiation (TSEBT) is used to treat needed for radiation to work on the tumor)
only the skin sparing underlying tissue
„„ Mycosis fungoides is the common condition where TSEBT
is used. ACUTE RADIATION SYNDROME

e
Occurs when there is whole body exposure nonclinically. The
RADIOBIOLOGY 2/ clinical features depends on the dose of radiation
„„ Cerebrovascular syndrome: More than 100 Gy, death
„„ In this DNA is a target in killing cells occurs after 24-48 hours of exposure
„„ Cells which are actively proliferating and poorly „„ Gastrointestinal syndrome: 5 to 12 Gy, death occurs after
P,
differentiated are radiosensitive 10 days
„„ Cells are sensitive at or close to mitosis „„ Hematopoietic syndrome: 2.5 to 5 Gy, death occurs after
„„ Late S Phase: Radioresistant (Because repair occurs in this several weeks to 2 months of exposure.
R

phase) Chernobyl nuclear accident provided the biggest data on acute

„„ Early G1 Phase: Radioresistant radiation syndrome.
SA

„„ Late G1: Radiosensitive (The defective cell attempts to

multiply)
„„ G2M Phase: Highly radiosensitive RADIOPROTECTORS
The functioning of molecular checkpoint genes of the cell cycle
„„ Radioprotectors are chemicals that reduce the biologic
determines the radiosensitivity of the cell. In general normal,
effects of radiation.
cells, have good check point gene function which is lacking in
„„ Amifostine (WR-1065), which primarily developed during
tumor cells. Hence when given sufficient time for the repair,
world war to protect the soldiers against possible nuclear
the cells repopulate. This is the reason, radiation treatment is
attacks, is the only FDA approved radioprotector for clinical
fractionated and given over the period (for normal cell repair
use.
process). But when abnormally interrupted, tumor cells also gain
the repair capability. „„ Used in head and neck cancer to protect parotid glands and
in prostate cancer to protect rectum. Chapter 5  •  Radiotherapy
4Rs of Radiobiology
„„ Reoxygenation (of tumor cells), Reassortment (of tumor RADIATION SENSITIZERS
cells into radiosensitive phase of cell cycle), Repair (of
normal cells), Repopulation (of normal cells) „„ Given along with radiation to increase the effect of radiation
„„ Radiosensitivity (of tumor cells) is considered to be 5th R of by sensitizing the cells for radiation kill
the radiobiology. „„ The common radiosensitizers are 5-Flurouracil, Cisplatin,
„„ Fractionation in radiotherapy is based on the principle of Carboplatin, Gemcitabine, Paclitaxel, Docetaxel, Targeted
4 Rs of Radiobiology. agents like cetuximab, etc.,
„„ Hyperthermia is a method to sensitize the tumor for
radiation kill.

321
 RADIATION CARCINOGENESIS Normal tissue reaction to radiation depends on the type of the
structurally defined functional subunit of the organ. Depending
„„ Stochastic Effect: Random, no threshold dose, severity is on this, organs are divided into,
not dose related, damage occurs in germ cell, mutation may „„ Serial organ: Spinal cord
occur „„ Parallel organ: Intestinal Mucosa
„„ Deterministic Effect: Threshold dose present, severity is
dose related. For example 2Gy is the threshold dose for the
lens of eye to develop cataract and for spinal cord 45 Gy is HYPERTHERMIA
the threshold dose for developing injury.
The is a modality used in radiotherapy by utilizing the “heat
„„ Leukemia, thyroid cancer, breast cancer, lung cancer and
shock” range of temperature varies of 41 to 45° is an additive in
bone cancer, skin cancers have radiation-induced etiology.
radiosensitizing as well as synergistic effect for tumor killing.
„„ Cesium-137, Americium – 241, polonium – 210 are used in
Hyperthermic intraperitoneal chemotherapy (HIPEC)
making dirty bombs or for poisoning with radiation.
surgery utilizes this property of thermal killing.

RADIATION PROTECTION RADIATION RECALL REACTION

„„ Half value layer: The thickness of any material required
„„ It is an acute inflammatory reaction confined to an
to decrease the intensity of the given radiation to half its
area of previous radiation exposure that is triggered by
incident intensity. In simple word, it is to decrease the value
chemotherapeutic agents or other drugs.
to half.
„„ Common agents: Doxorubicin, Docetaxel, Paclitaxel,
„„ The commonly used materials to block radiation are lead,
Gemcitabine, Capecitabine and EGFR Inhibitors.
aluminium, concrete, and brick.
„„ Common manifestations: Mild rash, dry desquamation,

e
„„ ALARA – As low as reasonably achievable.
pruritis, swelling, maculopapular rash, ulceration.
„„ To achieve the radiation protection with reasonable cost Sometimes may involve lung, oral mucosa or GIT.
and sufficient quality, the thickness of material is important:
Concrete wall for the room, lead for the apron and cerrobend
2/ Radiation (Radiotherapy)-Induced Second
alloy for the patient blocking.
Cancers
P,
Objectives of Radiation Protection To name a second malignancy as radiotherapy-induced,
As stated by National Council on Radiation Protection (NCRP) following criteria should be satisfied (Cahan’s Criteria)
Time lag of at least 3 years (sometimes 4 years) after initial
R

„„
„„ To prevent clinically significant radiation-induced
deterministic effects by adhering to dose limits that are treatment
below the apparent or practical threshold „„ The lesion should be within the initial radiation field or in
SA

„„ To limit the risk of stochastic effects to a reasonable level in the vicinity

relation to societal needs, values and benefits „„ The histology should be different from the initial diagnosis
In india, radiation related regulation and laws are governed by „„ The site of second malignancy should have been free of
Atomic Energy Regulatory Board (AERB) disease prior to initial treatment
This criterion is originally described for defining the
Table 4:  Recommended dose limits by various organisations radiotherapy-induced sarcomas, but now used for defining all
NCRP ICRP AERB radiation-induced second malignancy.

Occupational
Exposure MALIGNANCIES WHERE
R Cumulative 10 mSv x age 20 mSv/yr 20 mSv/yr RADIOTHERAPY IS USED AS RADICAL
A averaged averaged over
TREATMENT WITH OR WITHOUT
over 5 yrs 5 consecutive
D years CHEMOTHERAPY
I Annual 50 mSv/Yr 50 mSv/yr 30 mSv/yr
„„ Cancer cervix
O for Embryo/ 0.5 mSv/ Total 1 mSv 1 mSv total to „„ Oropharyngeal cancers
L Fetus month to abdominal the fetus „„ Laryngeal cancers
(Effective surface
O dose after
„„ Nasopharyngeal cancers
G pregnancy
„„ Cancer anal canal
„„ Cancer esophagus
Y declared
„„ Oral cavity cancers.
Public- 5 mSv/yr 1 mSv/yr 1 mSv/yr
Effective Dose
322
 MALIGNANCIES WHERE PALLIATIVE RADIOTHERAPY
RADIOTHERAPY IS USED AS It is indicated in the following conditions:
ADJUVANT TREATMENT (AFTER „„ Bleeding
SURGERY) „„ Bone pain due to metastasis
„„ To relieve obstruction in esophageal cancer
„„ Breast cancer
„„ Respiratory obstruction due to external malignancy.
„„ Brain tumors
„„ Oral cavity cancers
„„ Gastric cancers CRANIOSPINAL IRRADIATION
„„ Endometrial cancers
„„ Medulloblastoma
„„ Ependymoma
NONMALIGNANT CONDITIONS „„ Intracranial Germinoma
TREATED WITH RADIATION „„ Astrocytoma with subarachnoid seeding.

„„ Meningioma
„„ Craniopharyngioma PROPHYLACTIC CRANIAL
„„ Acoustic schwannoma IRRADIATION
„„ AV malformations
„„ Trigeminal neuralgia „„ Acute lymphoblastic leukemia
„„ Pituitary adenoma. „„ Small cell carcinoma of lung after chemotherapy.

e
STANDARD THERAPEUTIC DOSES 2/ HIGHLY RADIOSENSITIVE TUMORS
„„ Cancer cervix – 85 Gy to point A (Point where ureter crosses „„ Ewings Sarcoma
uterine artery) „„ Seminoma
P,
„„ Head and neck cancers: 66 Gy to 72 Gy „„ Dysgerminoma
„„ Brain tumors – 54 Gy to 60 Gy „„ Nasopharyngeal carcinoma.
„„ Prostate cancer – 80 Gy
R

Breast cancer (Adjuvant) – 45 Gy to 50 Gy

RADIORESISTANT TUMORS
„„
„„ Esophageal cancer: 54 Gy to 60 Gy
SA

„„ Melanoma
Osteosarcoma
EMERGENCY RADIOTHERAPY „„
The radioresistance can be overcome by hypofractionation of
It is indicated in the following conditions: radiation (High dose per fraction as in stereotactic radiosurgery).
„„ Spinal cord compression due to metastasis
„„ Malignant bleeding
„„ Superior venacava syndrome
„„ Brain metastases.

Chapter 5  •  Radiotherapy

323