• RADIOTHERAPY

INTRODUCTION

Radiotherapy is an integral component of treatment of cancer and other diseases. Surgery, RT

and chemotherapy are the 3 major cancer treatment entities which determine patient survival.

It is used in over 60%. It has become a significant therapy due to the growth in the

knowledge.

Each cancer is unique. To fully understand RT, it is essential to understand the various

principles of radiation therapy and radiobiology and also is essential to better educate, care

for, and manage the adverse effects of treatment.

DEFINITION

That 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 therapy is also defined as “a clinical modality dealing with the use of ionizing

radiations in the treatment of patients with malignant neoplasias ( and occasionally benign

diseases)”

It exists at the juncture of physics and biology. It addresses the therapeutic uses of ionizing

radiation alone or in combination with other treatment modalities such as biologic therapies,

surgery, drugs, oxygen & heat

Radiation oncology – that branch which deals with the investigation of fundamental

principles of cancer biology, the biologic interaction of radiation with normal & malignant

tissue, physical basis of therapeutic radiation

Aim : to deliver a precisely measured dose of irradiation to a defined tumor volume with as

minimal damage as possible to surrounding healthy tissue , resulting in eradication survival at

a reasonable cost.

In addition to curative efforts , RT plays a major role in cancer management in the effective

palliation or prevention of symptoms of the disease :

– Pain can be alleviated

– Luminal patency can be restored

– Skeletal integrity can be preserved

– Organ function can be re-established with minimal morbidity

In 1962, Buschke defined a radiotherapist as a physician whose practice is limited to

radiation therapy.

PHYSICAL BASIS

The raising of an electron in an atom or molecule to a higher level, without the actual ejection

of that electron from the atom or molecule is called excitation. If the radiation has sufficient

energy to eject one or more orbital electrons from the atom or molecule – ionization

Radiation – ionizing radiation. Important characteristic of IR – localized release of large

amount of energy

HISTORY OF RADIOTHERAPY

In november 1895, Wilhelm Roentgen discovered X-ray. In 1896 - Henri Becquerel –

discovered capability of different substances to produce x-rays. He observed the darkening of

photographic plates by uranium salts and concluded that the same x-rays were emitted
spontaneously and continuously from the uranium. Pierre and Marie Curie - coined the term

radioactivity. In 1898 - radioactivity 60 times higher than uranium and called it radium.

Antoine Becquerel noticed “burn” on his chest while carrying radium salt in his pocket. This

led to the discovery that these salts have the ability to produce profound biologic changes and

was considered as a magical cure for almost every known illness. The first documented

success – 1899 - 49-year-old woman's nasal basal cell carcinoma. Thereafter they had

conducted 100 treatments in the course of 9 months. In 1901 - lip cancer was first treated

using this. Very large single exposures resulted in extensive skin toxicities. Later they started

to insert radium directly into deep-seated tumors.

1922, Claude Regaud started using fractionated treatments in advanced laryngeal Cancer

Henri Courtard used this technique in Head & Neck Cancer. 1936 – Ralston Paterson –

standard field arrangements. They include primary tumor & potential tumor zone in one

block. 1960 – Fletcher put forward the concept of subclinical disease, which could be

destroyed effectively using small doses of Radiation. This was termed as “Shrinking field

technique”.

Development in machinery
As technology has progressed, RT has become increasingly sophisticated, with computer

controls to deliver exact and modulated doses to depths and specific areas within the

treatment field. Advances in energy technologies have led to the routine use of high-energy

and accurate deep-penetrating radiation produced by linear accelerators. Nuclear physics

innovations have produced many artificial radioisotopes, enabling the use of high-dose

brachytherapy, which shortens treatment time and simplifies the radioprotection procedures.

TERMINOLOGIES IN RADIOTHERAPY

Gross tumor volume:Visible or palpable or imaging detectable macroscopic tumor

Clinical target volume:Potential microscopic tumor spread

Planning target volume : Daily setup uncertainities such as organ motion

Fractionation : Repeated low doses of radiation within a course of treatment

Teletherapy :Projection of radiation through space. It is also referred to as “External beam

radiotherapy”

Brachytherapy: A sealed radiation source is placed directly inside or next to the tumor. It is

also referred to as “Internal radiation therapy”

PRINCIPLE OF RT

Dose of radiation sufficient to kill cancer cells is considerable, but not irreparable damage to

normal tissue, so that the latter recovers whereas malignant tissue does not. Excessive

radiation can result in destruction of the normal tissue while inadequate radiation fails to kill

the cancer cells. The cells may recover from such damage as they have sustained , regain

their vitality & start to multiply again (tumor recurrence)

General aim of RT

The general aim is to deliver as uniform a dose of radiation as possible to all parts of the

tumor-bearing zone. Outside this zone there must be as low a dose as possible is aimed at.

Indications for radiotherapy

It can either be radical or palliative

Curative RT

Reduce the number of tumour cells to a level that achieves permanent local control

Palliative RT

Designed to ameliorate a specific symptom such as pain, obstruction or bleeding

Modes of therapy
The planning & conduct of a course of RT

When a physician proposes administering RT to a patient , 6 fundamental questions must be

answered:

– What is the indication for RT?

– What is the goal of RT?

– What is the planned treatment outcome?

– What is the planned treatment technique?

– What is the planned treatment tumor dose and fractionation?

– What is the radiation tolerance of surrounding normal tissues (organs at risk) ?

Indication :

– That body of data that can be brought to bear showing that radiation therapy

wold be efficacious for patient’s condition

 – Phase I and phase II studies – safety & possible efficacy

– Gold standard – phase III trial

– RT can be justified either because it improves local tumr control , ameliorates

a specific symptom, improves the quality of life , or increases the probability

of cure.

Goals :

– Curative RT – purpose of curing where one is willing to endanger a small risk

of significant side effects in return for the possibilty of cure

– Palliative RT – designed to ameliorate a specific symptom such as pain,

obstruction or bleeding

Volume:

– What is the appropriate volume of tissue that needs to be irradiated for the

purpose of achieving the desired curative or palliative goalin the context of

justification?

– Does one need to treat strictly the visualized or palpable tumor mass?

– Is it also appropriate to treat the mass and surrounding lymphatic drainage?

• Does one need to worry about the routes of the spread of microscopic disease?

• For eg :

– Head & neck cancer – physical examination & diagnostic imaging – localized

at the site of origin

– Disseminated to the lymph nodes of the neck –

 – Appropriate RT – both the primary + the neck

Appropriate technique –

Teletherapy – It is similar etymology to telephone, telegraph , telepathy. Projection of

radiation occurs through space. It is administered with external beam sources – Cobalt -60

machine or a linear accelerator

– Treatment plans:

• Considerations such as whether the patient should be treated with

photons , electrons , neutrons , carbon ions , protons; with parallel –

opposed fields , four fields , or multiple oblique fields ; with IMRT ;

with or without respiratory gating ; with or without compensators

Brachytherapy : It is similar to Brachycephaly & brachydactyly. It is short or slow therapy

– It is done using Radioactive implant

– Several broad categores of brachytherapy –

• Interstitial brachytherapy

• Intracavitary brachytherapy
 • Mold therapy

• Interstitial- placement of radioactive sources directly into the tissue

• Intracavitary – placement of a radioactive source in a body cavity such as sources

placed within the nasopharynx or against & through the os of the uterine cervix

• Mold – placement of radioactive sources within the skin surface – such as treatment

utilized for a superficial malignancy on the back of the hand.

• Must determine the appropriate isotope & whether that isotope is to be delivered by

an afterloading technique or by a direct radioactive application (a hot implant)

• Dose:

– Complex issue

– Correct number of fractions of radiation per day, the correct dose per fraction,

the proposed tottal dose of irradiation

– The dose rate(ie, the number of cGy per minute) matters , such as in total body

irradiationfor bone marrow transplantation & in brachytherapy

• Normal tissue tolerance:

– Probability of acute & late ill effects of radiation is a function of dose

– Ultimately the prescription of the dose requires the radiation oncologist to

engage in a balancing act between a sufficient dose of radiation to achieve the

desired treatment goal & not giving so much dose as to endanger an

unacceptable risk of side effects.

BASIC RADIATION PHYSICS

Electro magnetic radiation : x-rays, gamma rays

Particulate Radiation : electrons, protons & neutrons

Treatment delivery equipment

Kilovoltage beam generators

Megavoltage equipment : Linear accelerator

Wave guide

It is an evacuated tube in which electron can be accelerated onto the target using the energy

of RF wave
Electron gun :

It is the source of electrons. It is emitted from directly heated filament / indirectly heated

oxide – coated cathode by thermionic emission. Cathode is mounted in an electron gun at the

input end of corrugated waveguide. Focussing cup helps in targeting the electrons.

Radiofrequency generator: Electrons are accelerated in straight line by RF generator /

klystron.

X ray head:

The electron beam will emerge from the accelerating guide and pass through magnetic field

to steer the electrons through an angle of upto 270 deg.

X ray target:

It is thick enough to stop all the electrons bombarding it and thin enough to minimize self

absorption. It is usually at earth potential. It is made up of tungsten , gold or platinum and

cooled by flow of water.

Flattening filter

It is the apparatus through which beam uniformity is achieved. It is added close to the target.

Metal filter with low atomic number, conical in section are used. It is thick at the centre – to

reduce the intensity of the central beam and tapering to zero at the edges so as not to reduce

the intensity of peripheral beam.

Dual dosimeter

It is placed immediately beyond the flattening filter, ie , nearer the patient. It is used to

measure the integrated dose at the isocentre, beam symmetry. It is sealed so that its response

doesnot vary according to the ambient conditions.

Beam collimation

It helps in limiting of the spread of the radiation to a predetermined direction & solid angle.

In practical RT , it is necessary to be able to vary the size of the beam to suit the needs of the

patient. It is called “Field size or beam size”

It is of two types: Primary / secondary collimation

Primary collimation:

It is a conical hole in a thick metal block close to the source of radiation. The axis of the hole

defines the beam axis. It passes through the centre of X ray target and determines the

maximum divergence of the beam – maximum field size at the specified treatment distance.

Secondary collimation:

Secondary collimation is a means of adjusting the field size to suit the particular

requirements. The various types used are:

 Interchangeable applicators

 Adjustable diaphragms

 Multileaf collimators

 Light beam diaphragm

Beam shaping & local shielding blocks

It is carried out using a multileaf diaphragm and by addition of heavy metal blocks (lead,

tungsten). The thickness of the blocks is determined by the degree of protection required.
Tailor – made shielding blocks: Radiograph is taken using a simulator. Area to be

shielded is marked on X ray. Styrofoam used directly as a cast over the precise shadow to

protect the area.

Beam direction devices

These are used to define the beam direction. They centre the beam axis and set the source-

skin distance. The most widely used devices are the front & back pointers.

Front pointer – shows the distance between the tip & source of rad

Back pointer – distance of tip from isocentre

 Isocentric gantry

There are 3 principal axes of rotation:

 Beam axis / axis of rotation of the diaphragm system

 Horizontal axis of the rotation of the gantry

 Vertical axis of the rotation of the couch

These three intersect at a point called the isocentre. The value helps in setting up the patient a

rotation about any of these axes and can be treated for the lesion on skin / inside by the

isocentre.
Radiation Production by Radioactive Decay

Radioactive materials disintegrate by emitting radiation to achieve nuclear stability. It is

measured in units of curie (ci) = 3.7 × 10 10 disintegrations per second

millicurie (mci) is the unit that is routinely used. Becquerel is the SI unit

Unstable nuclei decay by emitting α- or β-particles or γ-rays.

Particulate radiation

Charged particles :

Protons

Electrons

Negative pi- mesons

Uncharged particles :
Neutrons

Charged particles

Uncharged particles

Interaction of X-Rays with Matter

There are 5 possible interactions of x-rays with matter :

1) Coherent scattering

2) Photoelectric effect
3) Compton effect

4) Pair production

5) Photodisintegration

Radiation Biology in RT

Radiobiology deals with the events that follows the absorption of energy from ionizing

radiation. It deals with the efforts of the organism to compensate for the effects of the

energy absorption and the damage of the organism that may be produced.

LINEAR ENERGY TRANSFER

Depending on the composition of the incident beam - secondary particles formed. It may

directly or indirectly ionize the critical target. It is the rate at which a particular type of

radiation deposits energy as it travels through matter.

It varies considerably between different particles or rays. Electrons - superficial particles

– travel a short distance within the treatment field

X-rays - sparsely ionizing - low LET – because the secondary electrons are small

particles that deposit their energy over greta distance in the tissue

High LET - neutrons or alpha particles – bulkier

Factors affecting biological effect of radiation –

 Radiation dose

 Time over which the treatment is spread

  Pattern of ionizing radiation

Spacing of ionization along the track of ionizing radiations differs with the type and

energy of the radiation

Relative biologic effectiveness

Ability of radiations with different LETs delivered under the same conditions to produce

the same biologic effect. Differences in RBE - do not necessarily indicate differences in

ability to cure cancer. Therapeutic ratio is important , ie , the ratio of the damage

sustained by the tumor compared with the damage to the normal tissue. Any increase in

this ratio – valuable – does not seem change of physical factors has any effect upon it.

Therapeutic ratio

It is defined as the relationship between the desired and unwanted effects of therapy. To

reduce the risk of normal tissue injury and increase the therapeutic ratio, it is advisable to

fractionate treatment. An alternative approach is to administer continuous low dose rate

radiation directly into or adjacent to the tumour – brachytherapy.

Fractionation

Fractionation is the process of administering repeated low doses of radiation within a

course of treatment. It increases the differential cytotoxic effects on tumour and normal

tissues. The more radiosensitive the tumour, the wider the therapeutic window; the less

radiosensitive the normal tissue, the greater the risk of permanent radiation damage.

Damage to organs such as the spinal cord - profound importance - lack of normal tissue

repair. Other late effects of radiotherapy include carcinogenicity, mutagenecity and

teratogenicity. All can be ascribed to the effect of ionizing radiation on nuclear DNA,

with consequent permanent damage to nuclear material.

A good example is the CHART regime (continuous hyperfractionated accelerated

radiotherapy) where 1.5Gy per fraction is given three times daily and continuously for 12

days to a total dose of 54Gy (i.e. Without a weekend break).

CELLULAR RESPONSE TO RADIATION THERAPY

The biological effects result from damage to the DNA of the cell - the target of radiation.

It can deposit its energy directly onto DNA or can cause an indirect damage – interaction

of the radiation with cellular water, forming ion radicals, which then attack the DNA.

OXYGEN EFFECT
Well-oxygenated tumors shows much greater response to radiation – more radiosensitive

than poorly oxygenated tumors. The mechanism of the oxygen effect is related to the

ability of oxygen to combine with free radicals formed during ionization, producing new

and toxic combinations. Presence of oxygen at the time of radiation prevents the reversal

of some of the chemical changes that occur as the result of the oxygen effect.

SENSITIVITY OF THE CELL

The sensitivity of the cell vary in sensitivity to radiation. This is reflected in the total dose

needed for the cure of refractory tumors. The various resistant tumors include head and

neck cancers, esophageal cancer, and anal cancer.

RELATIVE RADIOSENSITIVITY OF VARIOUS ORGANS:

TISSUE TOLERANCE

Normal tissues depend on the presence of a sufficient number of mature cells to allow

maintenance of normal organ function. Normal tissues limit with regard to the amount of

radiation they can receive and still remain functional. The amount of radiation used to
treat a specific tumor is limited by the tolerance of the surrounding normal tissue, not by

the tumor.

Tolerance can be defined as the total dose at which additional radiation will significantly

increase the probability for the occurrence of severe normal tissue reactions.

PRINCIPAL FACTORS THAT DETERMINE THE RESPONSE OF ANY TISSUE TO

FRACTIONATED RADIOTHERAPY

Repair of sub-lethal damage (or recovery):

Ability of a cell to repair sub-lethal damage depends on the tumour type- and normal

tissue-dependent. It may be reduced by tissue hypoxia. It may change with radiation dose-

rate.

Redistribution of cells within the cell cycle:

The most sensitive parts of the cell cycle- M and G2 phases. Cells in early G1 phase of

the cell cycle are more sensitive to radiation than those in the S phase. Delay of a few

hours may allow the cells to survive within the S phase to move through to G2, where

they will be more sensitive to a second treatment.

Re-population:

If the time between treatments is extended, a proportion of surviving cells may be able to

go through to mitosis, increasing the total number of tumour cells that need to be killed

throughout the treatment course.

Local control rates in head and neck cancer seem to be improved by shortening the

overall treatment time, and by the use of continuous hyper-fractionated accelerated

radiotherapy (CHART), where treatment is given three times a day over twelve days.
Tissue oxygenation:

Tissue oxygenation is the ability of ionizing radiation to kill a cell is critically dependent

on tumour oxygenation. Malignant cells irradiated under hypoxic conditions require 2–3

times the radiation dose for a particular level of cell killing. Focal areas of necrosis are a

common feature of tumours. Tumour cells ≥150 μm from patent blood vessels are likely

to be hypoxic. Direct evidence using direct needle oxygen measurements have indicated

that tumours with higher oxygen levels seem to be more responsive to radiotherapy than

those with lower tissue oxygenation levels.

BIOLOGICAL EFFECTS OF RADIATION: DNA DAMAGE AND REPAIR

Sublethal damage refers to DNA damage that can be repaired given the right cellular

conditions and sufficient time. Sublethal damage repair is less efficient in tumour cells

than in normal cells and in areas of hypoxia or low pH.

Changes in cell kinetics and oxygenation during a course of radiotherapy

Tumour cells do not die immediately after irradiation. As cells die, oxygen penetrates

progressively further into hypoxic areas stimulating hypoxic cells to proliferate. In normal

tissues, resting cells enter the cell cycle, the cell cycle time shortens and the rate of

proliferation increases.

This accelerated proliferation accounts for the rapid healing of acutely responding normal

tissues, such as mucosa and skin, after an initial latent period. Accelerated proliferation

within tumours probably starts within the third week of treatment

Pre-treatment work up

Multidisciplinary setting
Surgeons

Oncologists – dental & medical

Pathologists

Radiologists

Palliative care doctors

Dietitians

Speech and language therapists

Clinical nurse specialists.

Initial visit - full history and examination

Including Tumour biopsy, Imaging, Full blood count, urea and electrolytes, liver function

tests, Dietitian assessment and assessment by speech and language therapist.

Poor dietary intake and a low BMI – elective percutaneous gastrostomy or nasogastric

feeding

Dental assessment

Written informed consent- regarding the acute and late toxicities

Patients are advised regarding smoking & Alcohol cessation.

Role of Imaging in RT

CT, MRI, X – ray examinations of skull , sinuses & soft tissue are done.

Symptomatic patients – Barium swallow + chest films & bone scan to rule out Metastasis.
 PET can be done for locating occult tumor. FDG PET is done to assess treatment

response after IMRT. CT can be done to determine extent of the disease , esp deep

invasion , determine bone invasion , regional lymph node assessment. MRI – assess

muscle invasion retromolar trigone lesions

PET : Helpful in patients with locally advanced disease. The sensitivity & specificity of

90% in nodal staging. High sensitivity for restaging after radiation therapy. The

recommended time – 3 months after RT.

PLANNING TECHNIQUE

 Patient position and immobilization

 Volume definition

 Volume localization

 Dose prescription

 Field arrangement and beam modification

 Implementation of treatment

 Verification

 Toxicity of radiation and care during treatment

Patient position and immobilization

Critical structures are frequently in close proximity, such as the spinal cord, brainstem, optic

apparatus, mucosa and salivary glands. These structures are defined as organs at risk (OAR).
Most sites are immobilized in the head neutral position with the spinal cord straight. In IMRT

the patient is immobilized in the neck extended position. This is done to limit the volume of

oral cavity irradiated.

Mouth bites – can be used in tumours of the oral cavity, nasal cavity and maxillary sinus. The

basic action is to open the jaw and depress the tongue. It is thus possible to exclude either the

upper or lower half of the mouth from the treatment field, thereby reducing the acute toxicity

of the treatment.

Volume definition
Volume localization

Volume localization is done by using a radiotherapy simulator to define the fields. The field

borders are defined in relation to standard bony anatomical landmarks which represent the

extent of a given tumour subsite. It is modified in individual patients. It usually includes PTV

+ a physical margin for penumbra

CT planning (intravenous contrast ) are indicated in head and neck cancer patients. Thereby it

is used to define the GTV, CTV, PTV and OAR.

Outlining of these structures are done with the aid of diagnostic imaging(CT / MRI) and

confirmed by clinical examination, flexible nasoendoscopy.

Dose prescription

Specify:

 Total dose
  Number of fractions or treatments

 Schedule of treatment delivery (daily, twice daily, etc.)

 Prescription point

 Photon or electron beam energy

Plans are normalized to the ICRU reference point. Checked to ensure adequate PTV

coverage, dose homogeneity, and also that the doses to OAR are within tolerance.

Conventional radiotherapy -

Daily radiation, Monday to Friday, with a dose of 1.8–2Gy per fraction to a total dose of 66–

70Gy

Hypofractionated regime

Delivering 55Gy in 20 fractions daily, Monday to Friday over 4 weeks (2.75Gy per fraction)

Field arrangement and beam modification

This is done using wedges and shielding. Shieldingis the method of shaping the radiation

beam for conformal treatments. Use of multileaf collimators where 20–80 leaves arranged in

opposing pairs which can be positioned under computer control to create an irregular field

which conforms to the tumour shape

However, some still use customized alloy blocks which must manually be placed on a

template prior to irradiation.

Implementation of treatment

Radiographers are responsible for the day-to-day implementation of treatments. They must

check for shell loosening during the course of therapy(esp. significant weight loss).

Effect of shell loosening may result in inaccuracies of target volume, and OAR localization.

In such cases, it is advisable to make a new shell, and replan the volume.

Verification

Prior to treatment, verification is done by using

 Treatment isocentre

 Radiation fields

 Beam shaping

Achieved either using fluoroscopy in a simulator or immediately prior to treatment using

electronic portal imaging (EPI). Initial 3 days, EPI is used to verify RT field position and

confirm set-up reproducibility.

Toxicity of radiation and care during treatment

Prior written informed consent is obtained from the patient. They are informed regarding the

acute and late complications.

SITE-SPECIFIC TREATMENT PLANNING

Oral cavity:

Several subsites: oral tongue, floor of mouth, buccal mucosa, alveolus and hard palate

These tumors are mostly treated with surgery, followed by adjuvant radiation with or without

chemotherapy. It depends on the presence of intermediate or high risk pathological features.

Interstitial brachytherapy

It is indicated mostly in small (T1/T2), superficial (0.5mm thickness) lesions of the oral

tongue and floor of mouth. The procedure involves surgically implanting small radioactive

sources directly into the target tissues. The procedure is conducted with the assistance of the

surgical oncologist. Low dose rate (LDR) temporary iridium-192, with an activity of

approximately 50 cGy per hour, or 10Gy per day are commonly used.

Mostly used system is the Paris system. It is a simple system, founded on empirical clinical

practice and mathematical calculations. It is adaptable to many clinical situations, since it is

applicable to both single- and multi-plane implants. Implants should be parallel, uncrossed

and straight. Wire spacing - equidistant from 5 to 20 mm. Wire separation determined by

target volume thickness. Wire length - approximately 1.5 times the target volume length.

ORAL TONGUE

Small superficial lesions may be treated with interstitial brachytherapy. Usually two to three

iridium-192 hairpins are required to implant the target volume.

CTV

Primary lesion with a 1 cm margin.

Patients unsuitable for brachytherapy - but also not suitable for surgery, definitive external

beam radiation (EBRT) may be offered.

Immobilization

Patient is positioned in a supine position with the cervical spine straight. Mouth bite may be

considered.

CTV

Primary tumour with a 2 cm margin, which if well lateralized, may be achieved with a

wedged pair field arrangement

More deeply infiltrating or approaching the midline, lateral parallel opposed beams are

required

Dose prescription

For interstitial brachytherapy - 60Gy over 6 days with iridium-192 LDR

For EBRT, the total dose is 66–70Gy in 2Gy per fraction, treating daily, five fractions a week,

to macroscopic disease and 44–50Gy in 2Gy per fraction, treating daily, five fractions a

week, to microscopic disease.

FLOOR OF MOUTH

Small, superficial lesions - interstitial brachytherapy is used.

EBRT - the mouth should be held open during immobilization with a mouth bite, to limit the

dose to the upper oral cavity, in particular the hard palate.

Thumors can be seen frequently in the midline. EBRT requires the use of lateral parallel

opposed radiation portals to cover the target volume, which includes the primary tumour and

locoregional lymph nodes.

Dose prescription – same as tongue.

BUCCAL MUCOSA, ALVEOLUS AND SMALL HARD PALATE TUMOURS

These sites are almost invariably treated in the postoperative setting.

Oropharynx

Oropharynx is divided into four main subsites: the tonsil, tongue base, soft palate and

posterior pharyngeal wall.

All lesions - relatively high risk of nodal metastasis.

Lateralized - unilateral irradiation - sparing of the contralateral normal tissues, especially the

contralateral parotid gland.

Midline tumours, such as tongue base and soft palate - may metastasize to either side of the

neck - bilateral neck irradiation

IMRT should therefore be considered

TONSIL

Small (T1/T2, N0) well-lateralized tumours of the tonsil - irradiation alone

Immobilization

Supine position with the cervical spine straight

Target volume:

Macroscopic dose includes the tonsillar fossa

Microscopic dose : ipsilateral cervical lymph nodes, levels Ib–IV

Dose prescription

Total dose is 66–70Gy in 2Gy per fraction, treating daily, five fractions a week, to

macroscopic disease and 44–50Gy in 2Gy per fraction, treating daily, five fractions a week,

to microscopic disease

TONGUE BASE

Tongue base tumours (T1/T2) presenting early (N0), particularly exophytic tumours without

fixity - radical radiotherapy

Bilateral neck irradiation to levels Ib–V is mandatory.

Immobilization

Supine position with the cervical spine straight

CTV:

SOFT PALATE
Anteriorly - include the level Ib lymph nodes or 1 cm anterior to the tumour, whichever is the

more anterior

Posteriorly - posterior level II and level V lymph nodes

After 40–44Gy, the posterior border is reduced to come off the spinal cord and the primary

tumour continues to the radical dose

Lymph nodes below the level of the hyoid bone are treated

Dose prescription:

Total dose –

Macroscopic disease : 66–70Gy in 2Gy per fraction, treating daily, five fractions a week

Microscopic disease : 44–50Gy in 2Gy per fraction, treating daily, five fractions a week

MAXILLARY SINUS

Immobilization

Supine position with the cervical spine straight

Mouth bite in place to exclude the tongue and lower part of the oral cavity from the radiation

field

CTV

Maxillary sinus, the ethmoid sinus, the nasal cavity, pterygoid fossa and the lateral

pharyngeal node

Dose prescription

Total - 66–70Gy
2Gy per fraction, treating daily, five fractions a week.

Various methods of administration

 Elective RT

 Preoperative RT

 Adjuvant RT

 Concurrent chemoradiation

 Palliative

Elective Radiotherapy

Stand-alone therapy, with curative or radical intent, aimed at eradicating the disease.

Preoperative RT

Carried out before surgery, in order to reduce the tumor mass and foster its macroscopic

removal.
Indicated in :

Marginally resectable Ca or has a very rapid growth history

Small radiocurable primary tumors and large adenopathy

Bulky disease in the level IV nodal region, to eliminate the need to administer a total dose of

70 Gy to the Brachial plexus

Neck dissection performed approx. 6 weeks after RT

Dose – 50 Gy in 25 fractions over 5 weeks

Adjuvant post operative RT

Carried out after surgery to prevent local relapse

Indications:

Close or positive surgical margins

Perineural spread

Lymphovascular invasion

Contiguous tumor extension into bone or neck soft tissue

Multiple positive nodes

Extracapsular extension of nodal disease

The entire operative bed is included in the postoperative target volume

General rule : start RT as soon as the surgical wound has healed , usually 3-4 weeks after

surgery
Radiotherapy after chemotherapy

It is also referred to as Neoadjuvant / induction chemotherapy. Irradiation of the entire

anatomical region containing the entire anatomical region is done. Original tumor volume

with adequate margins to doses equivalent to those from primary RT alone.

Dose reduction – if tumor adjacent to critical organs , such as locally advanced

nasopharyngeal Ca, or when acute reactions are excessive

Concurrent radiation & chemotherapy

Combination of chemotherapy & radiotherapy to treat cancer

Factors influencing the effect of RT

Total dose:

accelerated and hyperfractionated regimes - increase in locoregional control of 1 per cent for

each 1Gy increase in effective total dose

Concurrent treatment with chemotherapy or biological agents:

Improvement in local control at five years with concurrent platinum-based chemotherapy.

Delays in starting treatment:

Radical radiotherapy should commence within 4 weeks of the decision to treat and palliative

radiotherapy within 2 weeks.

Treatment interruptions
Where a course of radiotherapy is prolonged beyond the prescribed duration, local control

falls by 1.4 per cent per extra day

Anaemia

Locoregional control and survival are reduced in patients who are anaemic at the time of

radiotherapy

Smoking:

Inhaled carbon monoxide displacing oxygen from haemoglobin

Encourage patients to stop smoking prior to radiotherapy

Use of a carbon monoxide monitor (of exhaled air) in clinic is a valuable adjunct to other

strategies aimed at patients stopping smoking.

Assessing response to radiotherapy

4–6 weeks after the end of a course of radiotherapy - for maximum tumour response to

become evident.

Minimum of 8 weeks - before reimaging with CT or carrying out further biopsies

Post-treatment magnetic resonance imaging (MRI) is best left until 12 weeks to allow the

general increase in signal in the irradiated area to subside.

Radiosensitizers

The objective of successful radiation therapy, therefore, is to maximize the radiation damage

in tumor cells and at the same time minimize the same in normal cells. This may be possible

either by better localization of radiation dose or by using differential radioprotectors for

normal cells and/ or radiosensitizers of tumor cells.

Radiosensitizers are agents that sensitize the tumor cells to radiation. These compounds

apparently promote fixation of the free radicals produced by radiation damage at the

molecular level. The mechanism of action is similar to the oxygen effect, in which

biochemical reactions in the damaged molecules prevent repair of the cellular radiation

damage. Free radicals such as OH+ are captured by the electron affinity of the

radiosensitizers, rendering the molecules incapable of repair.

Radioprotectors are compounds that are designed to reduce the damage in normal tissues

caused by radiation. These compounds are often antioxidants and must be present before or at

the time of radiation for effectiveness. Other agents, termed mitigators, may be used to

minimize toxicity even after radiation has been delivered.

HYPERBARIC OXYGEN
Oxygen is known to increase the radiosensitivity of cells. The reactions of oxygen with

aqueous as well as organic-free radicals induced by ionizing radiations may lead to the

production of very toxic and relatively stable peroxy radicals and hydrogen peroxide resulting

in the damage to biomolecules and structures. Therefore, the simplest approach to enhance

the radiosensitivity of hypoxic tumor cells would be to increase the oxygen tension in the

tumor. First clinical trials by keeping the patient in a high-pressure oxygen tank just before

tumor irradiation were carried out by Churchill–Davidson and Foster, et al. Hyperbaric

oxygen has been observed to be effective in relatively small tumors, whereas the advanced

tumors do not show an increased radiosensitization. The procedure of putting the patient in

high-pressure oxygen tank during every fraction is, however, cumbersome and increases

complications.

CARBOGEN

The notion of improving tumor oxygenation by breathing highly oxygenated air has been

revived recently by experiments in which subjects breathe carbogen, a mixture of 95%

oxygen and 5% carbon dioxide that does not produce vasoconstriction associated with

breathing 100% oxygen. Breathing carbogen at atmospheric pressure is an attempt to

overcome chronic (diffusion limited) hypoxia through much simpler means than the use of

hyperbaric chambers.

NICOTINAMIDE

Hypoxic cell radiosensitizers such as the nitro-imidazoles were designed primarily to

overcome chronic hypoxia that is diffusion-limited hypoxia resulting from the inability of

oxygen to diffuse further than 100 μm through respiring tissue. However, hypoxia also arises

through acute mechanisms (intermittent blockage of blood vessels).

METRONIDAZOLE AND ITS ANALOGS

The knowledge of oxygen effect led to the development of compounds that mimic the

radiosensitizing property of oxygen. Radiosensitizing abilities of the hypoxic cell sensitizers

have been observed to correlate with electron affinity. Metronidazole and its analogues such

as misonidazole, etanidazole, and nimorazole have been found to be effective in sensitizing

hypoxic tumor cells.

The ‘oxygen fixation’ hypothesis has been proposed to explain the mechanism of action of

this class of sensitizers. They fix the radiation damage by preventing the chemical restitutions

of free radicals. Misonidazole has been observed to deplete sulfhydral groups in cells, inhibit

glycolysis and the repair of radiation-induced cellular potentially lethal damage.

Clinical trials with misonidazole have shown side effects in the form of peripheral

neuropathy, convulsions, and encephalopathy.

HYPOXIC CELL CYTOTOXIC AGENTS

Hypoxic cell cytotoxic agents include Mitomycin-C and Tirapazamine. Mitomycin-c is a

bioreductive alkylating agent that has been studied in pancreatic and head and neck cancer.

Tirapazamine is another bioreductive agent that is preferentially cytotoxic to hypoxic cells in

vitro. It differs from oxygen mimetic sensitizers in which it requires metabolic activation and

enhancement is seen when this agent is given prior to or after radiotherapy.

Side effects include nausea, muscle cramps, and hematologic toxicities. While under hypoxic

conditions tirapazamine is reduced to a highly reactive radical that produces strand breaks in

the DNA, under aerobic conditions, the radical is back-oxidized to the nontoxic parent

compound with a concomitant production of the superoxide radical, which is much less toxic

than the tirapazamine radical.

MEMBRANE ACTIVE DRUGS

Cell membranes, besides DNA, could also be critical targets for cell killing. Membrane-

specific drugs, such as local anesthetic (procaine and lidocaine hydrochloride) and

tranquilizers, for example chlorpromazine etc., interact with cell membranes and alter their

structural and functional organization. These drugs were observed to increase the

radiosensitivity of bacterial cells (Escherichia coli) under hypoxic conditions. Membrane-

specific drugs have been observed to enhance radiosensitivity of hypoxic mouse lymphoma

cells and radioprotect these cells under euoxic conditions. Inhibition of the rejoining of

radiation induced DNA strands breaks by chlorpromazine has been observed in mammalian

and human cancer cells.

RADIOSENSITIZING NUCLEOSIDES

Fluoropyrimidines

5-Fluorouracil (FUra) and Fluorodeoxyuridine (FdUrd) are analogues of uracil and

deoxyuridine, respectively. Randomized trials have demonstrated local control and survival

advantages with systemic FUra and radiation compared with radiation alone in patients with

rectal cancer, esophageal cancer, and pancreatic cancer.

FUra and FdUrd, through their metabolites lead to cell cycle redistribution, DNA

fragmentation, and cell death. Whereas clinically achievable concentrations of FdUrd

produce only DNA-mediated cytotoxic effects, FUra can also kill cells by RNA-dependent

mechanisms.

Hydroxyurea

Not a nucleoside analog, its primary mechanism of cytotoxicity is related to its inhibition of

ribonucleotide reductase, a key enzyme for the transformation of ribonucleotides to

deoxyribonucleotides. Its role in the treatment of hematologic malignancies and

myeloproliferative disorders is well established.

Gemcitabine

Gemcitabine is an analog of deoxycytidine that has demonstrated effectiveness as a single

agent against solid tumors, including pancreatic cancer, non-small-cell lung cancer, head and

neck cancer, and breast cancer. The mechanism by which gemcitabine radiosensitizer tumor

cells is not yet clear. Our preliminary studies indicate that the observed radiosensitization is

not associated with either an increase in the radiation-induced DNA double-strand breaks or

with a slowing of DNA double-strand break repair. This suggests that radiosensitization by

gemcitabine is unlike that produced by the fluoropyrimidines and the thymidine analogs. The

relationships between gemcitabine radiosensitization and DNA incorporation, alterations in

DNA synthesis, or alteration in cell cycle kinetics remain to be investigated.

In addition, it would be logical to investigate the role of apoptosis in gemcitabine-mediated

radiosensitization, since this mechanism of cell death has been shown to be the pathway by

which the drug exerts its cytotoxic action, at least in lymphoid cell lines.

Fludarabine

Fludarabine is a well-studied DNA damage repair inhibitor. The incorporation of the

corresponding nucleotides into DNA results in potent inhibition of DNA synthesis.

Fludarabine has clinical activity against hematologic cancers such as chronic lymphocytic

leukemia and follicular non-Hodgkin’s lymphoma. The mechanism of cytotoxicity has been

attributed to inhibition of enzymes critical for DNA synthesis and repair, including DNA

polymerases, ribonucleotide reductase, DNA primase, and DNA ligase. Incorporation of fl

udarabine at the DNA chain terminus results in gene deletions and increased mutational

frequency. Fludarabine also inhibits RNA synthesis and induces apoptosis.

MOTEXAFIN GADOLINIUM

Motexafin gadolinium, which is currently being studied in clinical trials, is the first in a class

of pharmaceuticals known as texaphyrins to reach human testing. Texaphyrins accumulate

inside cancer cells due to their high rate of metabolism and induce programmed cell death. A

phase-1 study of patients who are receiving hyperfractionated irradiation and concurrent 5-fl

ourouracil/cisplatin for head and neck cancer reported interim results recently. Nine of the ten

evaluable patients demonstrated a complete tumor response and eight of these remained in

complete remission with a median follow-up of 1 year. Side effects reported include

mucositis and radiation dermatitis. A randomized phase III trial is currently investigating the

use of motexafin in patients with brain metastases who receive whole body radiation therapy.

SUPPRESSORS OF SULFHYDRAL GROUPS

Intracellular compounds containing sulfhydral (thiol) groups are known to protect

biomolecules against radiation damage. The depletion of intracellular thiol groups may

therefore increase the radiosensitivity of cells. N-Ethylmalemide, diamide, and

diethylmaleate have been observed to lower the intracellular glutathione content, which is the

major intracellular sulfhydral compound. The depletion of intracellular glutathione content

may increase the radiation sensitivity of cells due to a reduction in the radioprotective

reaction. Decrease in the glutathione content has also been observed to correlate with

inhibition of repair of DNA single strand breaks, induced under aerobic conditions.

HYPERTHERMIA
Hyperthermia alone or in combination with ionizing radiation has been used in the treatment

of radioresistant tumors. It has been observed to enhance cell killing. Cells with higher

radioresistance such as chronically hypoxic cells with a low intracellular Ph, and those in S-

phase of cell cycle are more susceptible to thermal killing and radiosensitization.

Hyperthermia could lead to radiosensitization of cells by the following mechanisms:

• Elevated temperatures increase the fl uidity of membranes and this critically determines

survival after thermal insult

• Inhibition of energy metabolism

• Inhibition of macromolecular (DNA, RNA, and protein) synthesis

• Inhibition of DNA repair as well as the repair of sublethal, and potentially lethal cellular

damage.

NOVEL RADIOSENSITIZERS

Taxanes

This group of anticancer agents have a novel mechanism of action, broad clinical activity, and

potential as clinical radiosensitizers. Paclitaxel is the prototype of taxanes. Docetaxel is

another agent in this group. Paclitaxel may be the most efficacious single chemotherapy agent

for head and neck cancer with a 40% response rate for patients with recurrent disease. As it is

possible to achieve durable control with radiotherapy of locally advanced head and neck

cancer in only a minority of cases, chemotherapy drugs, such as paclitaxel, are being used

with radiotherapy in an attempt to improve tumor control. Paclitaxel stabilizes microtubules

and leads to accumulation of cells at the G2/mitosis phase of the cell cycle, which is a

necessary condition for its antitumor effect, and also the phase with the greatest relative

radiosensitivity. Paclitaxel has been shown to be a radiosensitizer in vitro for some but not all
cell lines studied.

Irinotecan

It is a camptothecin derivative that is thought to exert its cytotoxic effects by targeting

topoisomerase I. It is believed that irinotecan stabilizes a DNA-topoisomerase I cleavable

complex, and that interactions between this complex and the replication machinery may lead

to cell death. There is a significant volume of in-vitro and in-vivo data demonstrating that

irinotecan acts as a radiosensitizer.

The exact mechanism of this radiosensitization is currently unknown. The increasing amount

of data demonstrating improved outcomes with concurrent chemoradiation treatment of

malignancies like lung cancer and head and neck cancer provides impetus for pursuing the

addition of other drugs as radiosensitizers to improve local control further.

RADIATION PROTECTORS

Radioprotectors are chemical compounds that protect the nontumor (normal) cells from

radiation during radiotherapy.

Amifostine

Amifostine (WR-2721) is one of today’s most widely studied protectors. Amifostine

selectively protects a broad range of normal tissues, including the oral mucosa, salivary

glands, lungs, bone marrow, heart, intestines, and kidneys. It is actually a pro-drug, which
cannot readily permeate cell membranes. Amifostine on administration undergoes

metabolism and gets converted into WR-1065, which can readily permeate the cell

membrane. A phase III study of patients who received radiotherapy for head and neck cancer

demonstrated that those who received 200 mg/m[2] of amifostine, IVP 15-30 min prior to

radiation daily, had a statistically significant decrease in acute (P < 0.001) and late (P <

0.0001) grade 2 xerostomia.

Patients also experienced a statistically significant improvement in the time of onset of grade

2 xerostomia (30 days vs 45 days). Amifostine may be administered intravenously or

subcutaneously and should be dosed daily before radiation therapy. Side effects of this agent

include nausea, vomiting and hypotension. Amifostine was the first FDA approved

radioprotector. Clinical trials with patients receiving head and neck, thoracic, and pelvic

radiation therapy are ongoing.

A major mechanism underlying the radioprotective effect of WR2721 is the scavenging

highly reactive free radicals induced by ionizing radiation. Since damage inflicted by free

radicals is a major event responsible not only for killing mammalian cells by radiation, but

also for malignant transformation of these cells.

Amifostine also protects against the cytotoxic effects of chemotherapeutic agents. It offers

signifi cant protection against the nephrotoxicity, ototoxicity, and neuropathy associated with

cisplatin and hematologic toxicity associated with cyclophosphamide.

Nitroxides

Amifostine is the only radioprotector currently in clinical use. A number of other compounds

are in various stages along the pathway of clinical development as radiation protectors.

Nitroxides are among the most promising agents for future use as radiation protectors.
Laboratory studies have shown that stable nitroxide-free radicals and their one-electron

reduction products, hydroxylamines, are recycling antioxidants that protect cells when

exposed to oxidative stress, including superoxide and hydrogen peroxide. Likewise,

preclinical studies have shown that the oxidized form of a nitroxide is a radioprotector in both

in vitro (cell survival) and in vivo (lethal total body radiation) models. Although the

hydroxylamine exhibits antioxidant activity, it is incapable of protecting against radiation

damage. The lead compound from this class for radioprotection is Tempol.

Tempol protects against radiation-induced damage to salivary glands and does not alter tumor

growth after irradiation suggesting that delivery of the agent prior to irradiation would not

alter tumor control. In the oxidized form, tempol is paramagnetic and provides T1 contrast on

magnetic resonance imaging (MRI). Because of this unique property, the active,

radioprotective form of tempol can therefore be followed temporally using MRI. Tumors

were grown on the neck region of a mouse that would allow a single MRI slice to include the

tumor, salivary gland area, and normal leg muscle. These preclinical findings provide

feasibility to evaluate tempol as a radioprotector in clinical trials for cancer patients treated

with radiation. Coupling MRI with such a trial would permit a novel dimension that could

provide extremely important information with respect to the timing of tempol administration

and radiation treatment.

Other antioxidants

With the understanding that free radicals perpetuate a significant amount of the damage

caused by ionizing radiation, multiple vitamin antioxidants have been tested as a method to

reduce the toxicity of radiotherapy. Antioxidant compounds such as glutathione, lipoic acid,

and the antioxidant vitamins A, C, and E have been evaluated in this context. A great deal of

preclinical and clinical information has been accumulated that describes the effects of
combining radiotherapy with antioxidants. In general, the efficacy of these naturally

occurring agents as radioprotectors is less than that for the synthetic agents previously

described. One of the major concerns with the use of supplemental nutritive antioxidants or

other antioxidants during the course of radiotherapy is the possibility of tumor protection

through nonselective free radical scavenging. As described earlier for agents such as

amifostine, selective uptake, or activity in tumor tissue is essential to realize a gain in the

therapeutic ratio.

A number of trials have been performed with antioxidants delivered during the course of

radiotherapy, with the goal of reducing normal tissue toxicity, in many instances with

promising results. For example, antioxidants have been delivered concurrently during the

course of radiotherapy to reduce xerostomia, mucositis, pulmonary fibrosis, cystitis, and

alopecia.

Unfortunately, the use of antioxidant vitamins, such as alpha-tocopherol and beta carotene,

during the course of radiotherapy was associated with evidence of poorer tumor control in

randomized trials. The lower toxicity associated with the use of these agents is appealing, but

not at the cost of poorer tumor control. These findings reinforce the importance of preclinical

testing of radioprotectors to verify a lack of tumor protection. Topical application has been

used to minimize the possibility of systemic absorption and interference with tumor response

to radiation; however, caution is advised because even topical applications for the prevention

of mucositis in head and neck cancers have been associated with evidence of poorer tumor

control.

Ionizing radiation results in the formation of superoxide radicals that are highly reactive and

potentially damaging to cells. SOD is an enzyme that is naturally present in human cells. It
catalyzes the conversion of superoxide to oxygen and hydrogen peroxide and functions as an

antioxidant during normal conditions and after radiation.

SOD as a radioprotector has used gene therapy to increase the levels of SOD in tissues to be

irradiated to prevent or decrease radiation-induced mucositis, esophagitis, pneumonitis, and

fibrosis in animal models.

Melatonin

Melatonin is thought to act as an antioxidant itself, but also acts to increase the expression of

antioxidant enzymes such as SOD and glutathione peroxidase. Radioprotection with

melatonin and melatonin analogs has been documented in a number of animal models.

Importantly, melatonin has also been shown to have direct antitumor effects and has been

described as a radiation sensitizer for tumors in animal models. The use of melatonin as a

radiation sensitizer for tumor cells and as a radioprotector for normal cells was tested

clinically in a phase II Radiation Therapy Oncology Group trial. In that study, patients were

randomized to either morning- or night-time high-dose melatonin during radiotherapy.

Melatonin was continued after radiotherapy until progression or until 6 months.

Novel radioprotectors

Tetracyclines and fluoroquinolones, which share a common planar ring moiety, were found to

be radioprotective by Kwanghee Kim et al. 2009. Tetracycline protected murine

hematopoietic stem and progenitor cell populations from radiation damage and allowed

87.5% of mice to survive when given before and 35% when given 24 h after lethal TBI.

Interestingly, tetracycline did not alter the radiosensitivity of Lewis lung cancer cells.

Tetracycline and ciprofloxacin also protected human lymphoblastoid cells, reducing

radiation-induced DNA double-strand breaks by 33% and 21%, respectively. The effects of
these agents on radiation lethality are not due to the classic mechanism of free radical

scavenging but potentially through activation of the Tip60 histone acetyltransferase and

altered chromatin structure.

RADIATION MITIGATORS

Radiation-induced late normal tissue toxicity is increasingly being appreciated as a

phenomenon of ongoing changes in tissue after radiation but prior to the manifestation of

toxicity. These events include ongoing mitotic cell death and perpetually active cytokine

cascades that can lead to vascular damage, tissue hypoxia, and excessive extracellular matrix

deposition. Radiation mitigators aim to interrupt these cascades or intervene to prevent the

perpetuation of damage and thus reduce the expression of toxicity.

Alternatively, radiation mitigators can be agents delivered during or shortly after exposure to

repopulate a critical cell compartment such as the mucosa or bone marrow. In this instance,

the mitigator is used to prevent acute toxicity. For radiologic terrorism and space research,

much of the focus of mitigators has been in the field of developing chemopreventatives to

reduce carcinogenesis of total body exposures.

In conclusion, radiosensitizers and radioprotectors have a special role in the treatment of

malignancies by radiotherapy. Every agent has its own application, mode of action, and

adverse effects. The novel agents are exhibiting promising results. In majority of instances,
the success rate of radiotherapy is related to radiosensitizers and the patient’s quality of life is

dependent on the radioprotectors and radiation mitigators.

Radiation protection & quality assurance

Gas filled detectors

Thermoluminescent dosimeters

Film

Gas filled detectors

These consist of a chamber filled with a gas that is ionized in part or whole when radiation is

present. The total quantity of electrical charge is measured or the rate at which the charge is

produced is measured. These are of 2 types : ionization chamber & Geiger – Muller detector.

New developments in RT

Intensity modulated RT
It is basically used to treat carcinomas of the nasopharynx and oropharynx. Effectively

reduces parotid dose resulting in reduced long-term dryness of the mouth. Submandibular

gland dose and subsequent symptoms may be reduced. Tumour control - improved by

providing more even coverage of the target volume, and therefore avoiding underdosing areas

adjacent to critical normal tissues

Intensity-Modulated Radiotherapy and Arc Therapy

The advanced planning techniques use hundreds to thousands of beamlets to deliver highly

conformal radiation. It is useful when the tumor target volume is near critical structures such

as the brainstem, optic chiasm, or optic nerves. It uses multileaf collimators or customized

beam compensators to modulate the intensity of the beamlets. Rotational IMRT is called

intensity-modulated arc therapy or volumetric modulated arc therapy.

Gamma Knife plan

To achieve high dose conformality, multiple beams consisting of multiple beamlets and field

segments are used

There are 3 major drawbacks:

More radiation is administered from the treatment head of the machine, increasing scatter

radiation

Low-dose radiation volume is greater with IMRT compared to 3D conformal radiation.

Together, this may contribute to an increased risk of radiation-induced secondary malignancy

Multiple segments effectively increases the total treatment time from approximately 10

minutes for a 3D conformal plan to approximately 25 to 30 minutes for an IMRT plan.

Image-guided radiotherapy

Fitting the linear accelerator with CT capability

Patient position may be confirmed prior to treatment and programming the linear accelerator

to carry out any necessary shifts in treatment position

Useful in Head and neck cancer

Drawback of this extra imaging is greater radiation exposure to the patient because

approximately 2 cGy per scan is required

PET-based radiotherapy planning

Tumours are poorly defined on CT or MRI or where there are sites of active disease in areas

which appear anatomically normal

Fused PET/CT images - improve accuracy of target definition

PET images + hypoxia marker, - delivering a greater dose to hypoxic areas in order to

overcome their relative radioresistance

Heavy particles

Neutron beams are more densely ionizing than photons and there is less to be gained by

fractionation. Hypoxic cells are relatively less resistant. Early neutron beams had poor

penetrating power. Although higher energy neutrons may penetrate deeper tissues better, the

problem with greater normal tissue morbidity remains.

Protons –

Similar radiobiological properties to photons with greater penetration the very tight edge to

the beam. Chordomas within the clivus are a good indication for proton beam irradiation

whereby a high dose can be delivered to the tumour with relative sparing of the brainstem

Stereotactic Radiosurgery and Stereotactic Radiotherapy

Highly conformal radiation typically to smaller targets, and at greater doses than achievable

with IMRT or arc therapy.

Normal tissues are typically exposed to very low doses of radiation

Very low risk of radiation-induced malignancies associated with SRS

CONCLUSION

With advances in radiation technology - highly conformal, fast, image-guided methods and

orders of magnitude increased complexity as compared to radiation therapy as recently as 15

years ago. Knowledge of the type of radiation and its effect on jaws will be helpful in

management of acute & chronic side complications of RT.

References

Stell & Marans Textbook of Head & Neck Surgery

Textbook of Radiotherapy : Walter & Millers ; 6th ed

Principles & practice of radiotherapy : Charles M Washington ; 3rd ed

White & Pharoah Textbook of Oral radiology

Jayam, et al. Radiosensitizers, radioprotectors and radiation mitigators. Indian Journal of

Dental Research, 25(1), 2014