Review Article

Radiotherapy : Basic Concepts and Recent Advances

Lt Gen SR Mehta, AVSM, VSM, PHS , Maj V Suhag+, M Semwal#, Maj N Sharma**
*

Abstract
Radiation therapy (RT) is a clinical modality dealing with the use of ionizing radiations to treat malignant neoplasias (and
occasionally benign diseases). Since its inception, the goal of RT has been to cure cancer locally without excessive side effects.
The most important factors affecting the results of RT are the tumor type, its location and regional extent, the anatomic area of
involvement and the geometric accuracy with which a calculated radiation dose is delivered. Although higher doses of radiation
can produce better tumor control, the dosage which can be given is limited by the possibility of normal tissue damage. Approximately
60-65% of all cancer patients require RT as the sole treatment modality and / or in combination with surgery or chemotherapeutic
drugs. There is a huge gap between demand and supply of radiotherapy facilities and infrastructure. Most of the oncocentres are
located in urban areas in private sector and are beyond the reach of the common man.
MJAFI 2010; 66 : 158-162
Key Words : Radiotherapy; Radiation biology; Radiation physics

Inroduction Molybdenum in the anode of a x-ray tube, while γ rays

C ancer prevalence in India is estimated to be around are produced by intra-nuclear disintegration. Particulate
2.5 million, with over 8,00,000 new cases and radiation refers to the energy propagated by travelling
5,50,000 deaths occurring each year due to this disease corpuscles, which have definite rest mass, definite
in the country [1,2]. Carcinoma breast and cervix are momentum and a defined position at any instant,
the most common malignancies noted in Indian females; examples include electron, proton, neutron etc. Despite
while in males the most common malignancies are those several decades of research, photon-beam still
of aerodigestive tract i.e. lung, stomach, esophagus and constitutes the main therapeutic modality in RT, because
head and neck [1,3]. About 2/3 of cancer patients need of several unresolved technical problems with the use
radiation therapy (RT) i.e. 500,000 patients per year. of particulate radiation [4,5].
Like surgery, RT is a locoregional treatment modality. When an x-ray or γ -ray beam passes through a
The main aim of RT is to maximize tumour control whilst medium, interactions occur between the photon and the
minimizing damage to normal tissues. Over the last 20 matter and energy is transferred to the medium. The
years major technological advances have helped greatly photon-beam may undergo attenuation, absorption,
to improve the accuracy of treatment with resulting scattering or transmission. The three major forms of
improvements in the outcome. interaction of radiation with matter, which are of clinical
importance in RT, are Compton effect, photoelectric
Basics of Radiation Physics
effect and pair production. Compton effect is the most
The term radiation applies to the emission and important in modern-day megavoltage RT. The
propagation of energy through space or a material photoelectric effect is of primary importance in diagnostic
medium. Broadly, it may be classified into radiology and has only historical importance in present
electromagnetic radiation and particulate radiation. day RT. In Compton effect (Fig. 1), photons interact
Electromagnetic radiation is characterized by oscillating with free electrons and hand over part of their energy
electrical and magnetic fields and has a dual nature. X- to it. The angle through which the photon is scattered,
rays and Gamma (γ ) rays are the two major forms of the energy handed on to the electron and energy lost by
electromagnetic radiation used in radiotherapy. X-rays the photon is interconnected. The wavelength change
are produced when high speed electrons collide with a depends neither on the material being irradiated nor on
material of high atomic number like Tungsten- the radiation energy, but only upon the angle through

*
DGMS (Army) & Col Comdt, O/o DGMS, IHQ of MoD, “L” Block, New Delhi-110001. +Graded Specialist (Radiotherapy), Command
Hospital (AF), Bangalore-7. #Scientist-E (Medical Physicist & RSO), Army Hospital (R&R), Delhi Cantt-10. **Graded Specialist
(Radiotherapy), Command Hospital (SC), Pune-40.
Receved : 11.03.08; Accepted : 08.02.10 E-mail : virendersuhag@gmail.com
Radiotherapy : Basic Concepts and Recent Advances 159

Fig. 1 : Compton effect : Interaction of photons with free electrons

and scattering by an angle θ .

which the radiation is scattered. It has several important

implications in designing radiation protection. The
reduced scattering suffered by high-energy radiation as
well as the almost homogeneous tissue dosage is
primarily due to the Compton effect. In photoelectric
effect (Fig. 2), the photon disappears altogether after
interacting with the bound electron, some of the energy Fig. 2 : Photoelectric effect : The photon disappears altogether
being used to remove the electrons from the shell, while after interacting with the bound electron and emit
the rest is imparted as kinetic energy to the photo- characteristic radiation.
electron. The energy of the characteristic radiation
(fluorescent radiation) varies from atom to atom and and permanent regression of tumor in vivo in zone
for low atomic number elements, which make up most irradiated. Therapeutic index (TI) is the ratio of NTT/
of the biological materials, it is of such low energy that TLD and it determines whether a particular disease can
it is probably absorbed by the same cell in which the be treated or not. Radiosensitivity expresses the response
initial event occurs. Pair production results from an of the tumour to irradiation and is greater for highly
interaction with the electromagnetic field of the nucleus mitotic, undifferentiated cells like malignant cells. For
and as such the probability of this process increases highly radiosensitive tumours, NTT is much greater than
rapidly with the atomic number (Z2). When the photon TLD and TI is high (e.g. lymphoma, seminoma,
with energy in excess of 1.02 MeV (million electron dysgerminoma, leukemia etc). For moderately
volt) passes close to the nucleus of an atom, the photon radiosensitive tumours, NTT exceeds TLD by a few
disappears and a positron and an electron appear [5]. fractions and TI is low (e.g. most squamous cell
carcinomas and adenocarcinomas). For radioresistant
Biologic Basis of Radiation Therapy tumours, TLD is much higher than NTT and TI is very
The exact mechanism of cell death due to radiation low e.g. soft tissue sarcomas, bone tumours, melanoma
is still an area of active investigation. A large body of etc.
evidence supports double-stranded breaks of nuclear Delivery of tumorocidal dose in small dose fractions
deoxyribose nucleic acid (DNA) as the most important in conventional multifraction regimen is based on 4R’s
cellular effect of radiation. This breakage leads to of radiobiology namely, repair of sub lethal damage,
irreversible loss of the reproductive integrity of the cell repopulation, redistribution and reoxygenation. Repair
and eventual cell death. Radiation damage can be is considered as the most important rationale for
directly ionizing. However, in clinical therapy, damage fractionation. Dose fractionation enables normal tissue
is most commonly indirect ionizing via free-radical to recover between two fractions reducing damage to
intermediaries formed from the radiolysis of cellular normal tissues. Redistribution of proliferating cell
water. Radiation can also affect the processes of the populations from radioresistant to radiosensitive phase
cell cycle necessary for cell growth, cell senescence throughout the cell cycle increases cell kill in fractionated
and apoptosis [6]. treatment relative to a single session treatment. If interval
In RT the success of eradicating tumor depends on is more than six hours then cells will repopulate and
radio sensitivity of tumour as well as surrounding normal results in increase of surviving fraction, referred to as
tissue tolerance (NTT) [7]. Tumour lethal dose (TLD) repopulation. Cells at the centre of tumor are hypoxic
is defined as the dose of radiation that produces complete and are resistant to radiation. Hypoxic cells get
MJAFI, Vol. 66, No. 2, 2010
160 Mehta et al

reoxygenated which occurs during a fractionated course For treatment planning, a computer is used to help
of treatment, making them more radiosensitive to calculate the source position and the amount of time
subsequent doses of radiation [8]. needed to deliver the correct dose of radiation to the
tumor. Treatment may be delivered at a high dose-rate
Radiation Delivery Techniques
(HDR) or a low dose-rate (LDR). The dose rate in
External beam radiotherapy or teletherapy is the most LDR ranges from 0.4 to 2.0 Gy/hr, while that in HDR is
frequently used form of RT. The patient lies on a couch > 12 Gy/hr. HDR brachytherapy is usually an outpatient
and an external source of radiation is pointed at a procedure lasting only a few minutes. With LDR
particular part of the body. Cobalt units have been the brachytherapy, the in-patient is treated with radiation
traditional teletherapy equipments and are still in delivered at a continuous rate over several hours or days.
widespread use worldwide, since the machinery is Permanent brachytherapy, also called seed implantation,
relatively reliable and simple to maintain compared to involves placing radioactive seeds or pellets (about the
the modern linear accelerator. They produce stable, size of a grain of rice) in or near the tumour and leaving
dichromatic beams of 1.17 and 1.33 MeV, resulting in them there permanently. After several weeks or months,
average beam energy of 1.25 MeV. The role of the the radioactivity level of the implants eventually
cobalt unit has partly been replaced by the linear diminishes to nothing [11].
accelerator (linse, which can generate higher energy
X-rays as well as electrons; with energy range of 4, 6, Three-dimensional Conformal Radiotherapy
15 and 18 MeV. The shape and intensity of the beam (3-DCRT)
produced by a linac may be modified or collimated by a Here the radiation field conforms to the shape of the
variety of means. Thus, conventional, conformal, volume to be treated. 3-DCRT is most useful for tumours
intensity-modulated, tomographic and stereotactic RT that are close to important organs and structures,
are all produced by specially modified linear accelerators. examples include carcinomas of prostate, spine,
Electron beams are useful for treating superficial lesions esophagus, lung, bladder, pancreas, head and neck etc.
because the maximum of dose deposition occurs near Most 3-DCRT cases begin with a “virtual simulation”
the surface. The dose then decreases rapidly with depth, session that lasts between 30 and 90 minutes. CT scans
sparing underlying tissue. Although the X-ray target is are taken of the patient in the treatment position and the
removed in electron mode, the beam must be fanned images are transferred into the treatment-planning
out by sets of thin scattering foils in order to achieve computer. The clinician can then mark on each CT slice
flat and symmetric dose profiles in the treated tissue the required volume to be treated. The computer
[9]. generates a 3-D image of the volume to be treated and
Brachytherapy involves placing a radioactive material critical structures at risk can be highlighted [12]. This
directly inside or next to the tumor. It allows a physician helps define the best beam arrangement and the
to use a higher total dose of radiation to treat a smaller computer then calculates the optimum dose distribution.
area and in a shorter time than is possible with external A beam’s-eye view can be generated digitally to give
radiation treatment [10]. The delivery device may be an image of how the simulation film should look and this
inserted into a body cavity such as the vagina or uterus is also used in treatment verification. Critical structures
(intracavitary brachytherapy) or into a lumen like can be shielded by beam shaping, which can be achieved
esophagus (intraluminal brachytherapy) or applicators with customized lead blocks or the use of multileaf
may be inserted into body tissues as in prostate or breast collimators which are computer controlled motorized
(interstitial brachytherapy). “Conventional” movable lead leaves within the treatment machine which
brachytherapy may be more suitable in routine usage can block part of the radiation field. A typical treatment
than “temporary” brachytherapy. In temporary session lasts about 15-30 minutes.
brachytherapy, the radioactive material is placed inside Intensity Modulated Radiotherapy (IMRT) and
or near a tumour for a specific amount of time and then Image Guided Radiotherapy (IGRT)
withdrawn. It uses a delivery device, such as a catheter,
Intensity-modulated radiation therapy (IMRT) is an
needle, or applicator; placed into the tumour using
advanced form of 3-DCRT. It uses sophisticated
fluoroscopy, ultrasound, magnetic resonance imaging
software and hardware to vary the shape and intensity
(MRI) or computed tomography (CT) to help position
of radiation delivered to different parts of the treatment
the radiation sources. The radiation sources are then
area. Regular 3-DCRT and IMRT differ in how the
inserted by the radiation oncologist either manually
pattern and volume of radiation delivered to the tumor
causing high exposure risk or the source of radiation
is determined. In conventional 3-DCRT, clinicians input
may be inserted using a computer-controlled remote
delivery patterns into the computer. In IMRT, the
afterloading machine.
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Radiotherapy : Basic Concepts and Recent Advances 161

physician designates specific doses of radiation then precisely attached to the gamma knife unit so that
(constraints) that the tumor and normal surrounding when the unit is activated, the target is placed exactly in
tissues should receive [13]. The physics team then uses the centre of 201 precision-aimed, converging Co-60
a sophisticated computer program to develop an beams. Treatment takes anywhere from several minutes
individualized plan to meet the constraints. This process to a few hours to complete depending on the shape of
is termed “inverse treatment planning”. Typically, the target and the dose required.
combinations of several intensity-modulated fields Gamma knife is operated by a multidisciplinary team
coming from different beam directions produce a custom consisting of neurosurgeons, radiation oncologists,
tailored radiation dose that maximizes tumour dose while medical physicists, neuroradiologists and anaesthetist.
also protecting adjacent normal tissues. The area’s most The gamma knife is limited in use by its high cost, limited
commonly treated with IMRT are prostate, spine, lung, access, and inability to treat extracranial lesions or
breast, kidney, pancreas, liver, tongue and larynx. multiple lesions and unsuitability to treat targets larger
Patients who have previously received the maximum than 2.5 centimetres in size. In India, the cost of gamma
amount of radiation delivered by conventional radiation knife treatment package is around 2.5 lacs as the cost
therapy can also be treated with IMRT. The of equipment, set-up costs and operating costs are very
disadvantages include stringent patient set-up and high. It will be cost competitive only if demand for SRS
immobilization, cost escalation and increased treatment services is high enough to fully use equipment working
time for the patients. Some Linacs have an on-board time.
Imager, an automated system that uses high-resolution
X-knife is another form of stereotactic radiosurgery
X-rays to produce contrasting images of cancerous
where linear accelerator is used to deliver treatment. In
tumours and surrounding soft tissue, allowing physicians
addition to certain brain lesions, X-knife can be used to
to target the cancerous tumor more precisely during
treat selected extra-cranial lesions like spine, lung and
treatment and decreasing radiation exposure of healthy
liver; though precision is less as compared to Gamma
tissues. Before the on-board imager, physicians would
knife [16].
have to treat a larger area of the body near the cancerous
tumour to compensate for any tumor movement, exposing Cyber Knife or Robotic Radiosurgery is a frameless
healthy tissue to the radiation. This technique is called robotic radiosurgery system which uses real time image
image guided radiotherapy (IGRT) [14]. The imaging guidance technology and computer-controlled robotics
equipment can also be kept inside the treatment room to deliver a very high dosage of precisely targeted
separately (CT on rail) to acquire the scans in the radiation to kill cancer cells in 1-5 fractions [17]. The
treatment position. Thus IMRT improves the radiation biggest advantage is that this painless treatment can be
delivery precision and IGRT improves the radiation completed in a week’s time but the treatment cost ranges
delivery accuracy; thereby decreasing the volume of from 3-5 lacs.
normal tissue being irradiated. Acute and Late Normal Tissue Reactions
Stereotactic Radiosurgery (Gamma Knife) The acute effects occur within 90 days and late normal
The gamma knife works by a process called tissue complications of RT can occur even months and
stereotactic radiosurgery, which uses multiple beams of years after RT. The tissues that divide rapidly (e.g,
radiation converging in three dimensions to focus mucous membranes) respond acutely to radiation and
precisely on a small volume, such as a tumor, permitting are responsible for much of the acute morbidity of the
intense doses of radiation to be delivered to that volume treatment. Late side effects are attributed to the damage
safely while largely sparing the surrounding tissues. It of the microvasculature or to stem cell depletion. The
can be used for a wide variety of problems including acute and chronic effects are related to site, dose,
selected malignant tumours that arise in or spread to volume and time of treatment. Other therapies, such as
the brain (primary brain tumours or metastatic tumours), surgery and chemotherapy, can increase the probability
benign brain tumours (meningiomas, pituitary adenomas, and severity of radiation-related morbidity. The tolerance
acoustic neuromas), blood vessel defects (arterio-venous dose of various critical organs is given in Table 1 [18].
malformations) and functional problems (trigeminal Indian Scenario
neuralgia) [15]. A special headframe that has three- In our country, there is a big divide in the facilities
dimensional coordinates built into it is attached to the available in rural and urban areas. Presently only 337
patient’s skull with four screws, CT/MRI is done and teletherapy units are functional in the entire country.
the images are sent to the gamma knife’s planning Based on a rate of nearly one machine per every 800 -
computer system to determine the exact relationship 1000 new cases of cancer, the number of treatment
between the target lesions and the frame. The frame is
MJAFI, Vol. 66, No. 2, 2010
162 Mehta et al

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None identified

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