Techniques of Radiotherapy in Oral Cancer / dental courses

Techniques of Radiotherapy
in Oral Cancer
INDIAN DENTAL ACADEMY
Leader in continuing Dental

Contents
 History
 Radiation Physics
 Radiation biology
 Altered fractionation therapy
 General concepts of Radiotherapeutic technique
 Techniques of Radiotherapy
 Advances in Radiotherapy
 Role of Radiation therapy for H & N tumors - BY SITE
 Dental care of the patients receiving radiation
 Complications & management
www.indiandentalacademy.com

 Radiation Oncology is a medical specialty that focuses predominantly on
treatment of Neoplastic diseases with the use of ionizing radiation given
either alone or in combination with surgery, chemotherapy or both.
 Radiotherapy ( Radiation therapy) is the treatment of diseases with
ionizing radiation.
 It is one of the principle mode of management of head & neck
carcinomas as these tumors are radiosensitive.

History
 Sir Wilhelm Conrad Roentgen discovered x-rays on 8th November
1895
 In 1898 Madam Curie discovered radium.
 In the beginning of 20th
century high single dose radiation was used by
Dermatologists and Surgeons as a form of cautery.
 In 1920- Fractionation of Radiotherapy was introduced by Thames and
Hendry and radiation was accepted as a modality of treating cancers

 Major & rapid advance in radiotherapy – Development of CO60
Teletherapy, Linear Accelerator, Mega Voltage therapy and
Super Voltage therapy following 2nd
World war .
 In 1960s Cesium, Iridium, Palladium, Iodine in Brachytherapy were
developed
 Over the past 20 years , much of advances is seen in treatment
planning such as 3 - dimensional treatment planning systems,
IMRT etc to localize the radiation dose.

Radiation Physics
 Radiation is transmission of energy through space and matter.
 There are two types of Therapeutic Radiation:-
(1)Electromagnetic radiation (photons) : X-rays, Gamma rays.
(2) Particulate radiation : Electrons, Positrons, Protons, Neutrons, α particles.

 High energy X- rays and Gamma rays are used most often in radiation
therapy
 These electromagnetic radiation subtypes do not differ in any physical
characteristic or in their biologic action.
 The only distinction is - how they are produced and tissue penetration
characteristics.
Electromagnetic Radiation

X-rays
 X-rays are created by linear accelerators (linacs).
- which involve an electrical input that causes a filament to become
heated and which serves as a source of electrons.
- These high energy electrons are directed to hit a metal target ( made of
tungsten),their by converting part of the kinetic energy of electrons to x-
rays
 The energy of x-rays is specified by MeV (megavolt, million volt).

Gamma - rays
 Gamma rays are produced by materials such as radium, uranium, cobalt60
 These materials undergo radioactive decay, resulting in the emission of
gamma ray photons.
 Because of high radiation dose and perceived radiation safety, most
modern radiotherapy centers use high energy x- rays produced by linacs.

Particle therapy
 This type of therapy differs from photon radiotherapy in that it involves the
use of fast-moving subatomic particles to treat localized cancers.
 Such as electrons , positrons, protons, neutrons, alpha particles, negative
π mesions beams.

Electron Therapy
 Small, negatively charged particles
 These are accelerated to high energy(upto 50 MeV) by means of linacs.
 A charged particle deposits uniform dose for a certain distance & then
virtually none
 Hence, the tissue beyond the tumor gets little irradiation
 Deliver maximum dose to superficial tissues
 Used in treatment of malignant lesions located at limited depths , such as
BCC or metastasis to cervical LN

Electron Beam Therapy Machines
 Kilovoltage Machines
 Linear Accelerators

Kilovoltage Machines
 Earliest X- ray machines used in treatment of cancer
 Generate low energy radiates from 50 kV-100 kV
 Poor penetrating quality
 Used in treatment of superficial tumours

Linear Accelerators (linacs)
 High energy X ray machines
 In electron mode of linac opertion, the electon beam is directed to strike
an electron scattering foil instead of tungsten target.
 High penetrating power of the radiation
 More effective in treatment of deep seated tumours with reduced dose of
radiation
 Skin sparing

Proton therapy
 Protons are positively charged particles, its mass is 1835 times greater
than electrons.
 Essentially it has same radiobiologic properties such as electron or
photon beam.
 Because of the heavier masses - more complex and expensive
equipment like cyclotron or synchrotron is needed to accelerate protons
to clinically useful energies.
 Because of greater flexibility of modulating protons beams to conform to
target volume.
 Proton therapy are used in irradiating tumors located close to critical
organs ( chorodial melanomas, skull base chondromas and sarcomas)

Neutron beam therapy
 Large, neutral particles with high linear energy transfer (LET) - thus
producing denser ionization in tissues
 2 major sources of neutrons:
Cyclotron for External beam therapy
Californium for interstitial therapy
 Chief advantage of Neutrons: effective against hypoxic cells because
neutrons produce much denser ionization in tissues
 Used mainly for unresectable or recurrent salivary gland cancers.
 Disadvantage: fast neutrons lack skin sparing and therefore can cause
more acute dermal reactions compared to photons

Absorbed dose
 Is a ratio between the average amount of energy (E) deposited in a small
volume with mass(M).
- Older unit of absorbed dose is Rad, which is 100 ergs of energy
deposited in 1 gram of material.
- Standard unit is changed to Gray(Gy), which represents 1 joule of energy
deposited in kilogram of material.
1 Gy = 100 rad.

How Does Radiation Act ??
 Absorption of the energy (electromagnetic or particulate radiation) in the
body produces a minimal amount of heat, and ionizations that lead to a
variety of biological effects.
 The type of physical interaction depends on the energy and type of the
incident photon and on the characteristics of the absorbing material.
 X-ray or gamma Photons (upto 10 MV) interact with atoms through three
processes
(1)Compton effect,
(2)Photoelectric effect, and
(3)Pair production.

 In particle radiation
- electrons entering tissues undergo either elastic or inelastic collision
with electrons or atoms of the absorbing material.
 The elastic interaction between the electrons cause transfer of energy
and producing ionization by removing one outer electron from neutral
atom.
 Because the binding energy of an outer electron in most elements in
tissue is small, this scattering process continues, leaving a track of
ionization and biologic damage.
 The elastic interaction between the electron and nucleus of the atom, the
electron converts some of its energy to gamma ray photon.

Radiation biology
 Ionization radiation delivered to cells or tissues initiates a chain of events
based on energy and type of radiation.
 The energy deposited is converted into secondary
electrons that break chemical bonds directly
or indirectly.
 Direct Effect – Radiation causes a change in the
molecular structure of organic compounds.
 Indirect Effect - Photons interact with water
producing free radicals which cause
biological changeswww.indiandentalacademy.com

 Sparsely ionizing radiation , such as X- rays or gamma rays, induce
damage mainly through Indirect effects
 Densely ionizing radiation such as Neutrons & α- particles cause damage
primarily through Direct effects

Effects On Cell Kinetics
 Radiation affects the expression of cyclins and cyclin dependent kinases.
 These are group of proteins which progress the cell division cycle.
 This effect is most pronounced at early part of G1 phase & at the G1 to S
boundary resulting in a net delay in cellular progression through division
cycle.
 Low dose induces mild mitotic delay
 Moderate dose results in longer mitotic delay & some cell death
 Larger doses may cause profound mitotic delay with incomplete recovery

 Although ionization radiation can affect tissue through many mechanisms,
depending on the size of the dose.
 Cell killing is the major effect in the therapeutic dose range.
 Lethally injured cells die in 2 ways:
- Mitotic (Reproductive) death
- Cell death by Apoptosis

Mitotic (Reproductive) death
 Dominant mode of cell killing in radiotherapy
 Cells die when they attempt to divide.
 At molecular level
- Damage during late S & G2 phase- 1 arm of chr break seen- chromatid
aberration or single strand breaks (SSbs)
- Damage during G1 & early S phase- Both arms of chr break seen at
mitosis as 1 broken arm replicates into 2 broken arms- chromosomal
aberration or double strand breaks (DSBs).
 These molecular events are main cause for mitotic cell death.

Cell death by Apoptosis
 Usually occurs within hours of radiation exposure.
 Typically seen in after lower radiation doses.
 Apoptosis is an active mode of cell death characterized by distinct
biochemical and morphological features.
 Which includes endonuleases activation, chromatin condensation and
margination, along with cellular shrinkage and fragmentation

Factors affecting radiation sensitivity
 Many factors affect the sensitivity of normal and malignant cells and the
response of normal tissues and tumors to radiation.
- i) Oxygen status
- ii) Cell age in in the division cycle
- iii) Type of radiation

Oxygen status
 The ability of ionizing radiation to cause biologic change is very much
dependent on the amount of oxygen present in the tissue environment.
 Greater cell damage sustained in the presence of oxygen is related to
increased amount of hydrogen peroxide & hydroperoxyl free radicals
formed which causes DNA damage and prevents its repair,which
ultimately leads to cellular death.
 Oxygen is the most potent radiosensitizer .
 Cells in a 100 percent oxygen environment are 3times more
radiosensitive than cells in complete anoxia.

Cell age in in the division cycle

Type of radiation
 Different type of radiation induce different densities of ionization or energy
deposition per unit length of track, called linear energy transfer (LET).
 X-rays , gamma rays, electrons and protons are low LET radiation
because they produce sparse density of ionization.
 Neutrons and heavy nuclei produce dense ionization hence referred as
high LET radiation.

Dose
 The Radiation Therapy Oncology Group (RTOG) has conducted a dose-
searching study to determine the maximum dose that could safely be
given for patients with head and neck cancers.
67.2, 72, 76.8, or 81.6 Gy at 1.2-1.5 Gy given twice daily
They all incorporate at least a 6-hour interval between sequential
radiation treatments to allow for repair of sub lethal and potentially lethal
damage in the irradiated healthy tissues.

 Between 66 and 70 Gy are usually prescribed for primary tumors
measuring 2 cm or less.
 When radiotherapy alone is delivered to a patient with more advanced
disease, doses of 70 Gy or more are necessary to control the primary
tumor and involved nodes.
 The dose of radiation required for loco-regional control increases as
tumor size increases.
 Patients with lymphadenopathy of neck nodes that measure 2 cm or
less - EBRT alone can control more than 90%
 Nodes that measure 2 to 3 cm - doses of 70 Gy or more sterilizes only
approximately 80%

Radiobiological Basis of Fractionation
 Use of multiple fractions over many weeks of radiation therapy is based
on the principle of improving the therapeutic ratio between normal tissue
& tumor
 The goal is to maximize the cell death of tumors and to minimize
unacceptable damage to normal cells.
 This can be accomplished through the use of multiple fractions and is
explained by 4 radiobiologic process
Conventional regimen
Curative -1.8 – 2 Gy / day given amounting to 66 – 70 Gy in 33 fractions over 6
½ weeks.
Palliative - 3 Gy/day is given i.e., 30 Gy in 10 fractions over 2 weeks.www.indiandentalacademy.com

Radiobiological Basis of Fractionation
 Repair
 Re-oxygenation
 Repopulation
 Redistribution

Repair of sublethal cells
 Fractionation helps in recovery of sub lethally damaged cells.
 The repair capacity varies among different cells and tissues.
 Repair may occur to a greater degree in slowly dividing normal
tissue(late responding) compared to tumors (rapidly reacting tissues)
- thus contributing to beneficial therapeutic ratio

Repopulation (Regeneration)
 Depletion of cells (during therapy), in both normal & neoplastic tissues,
triggers a regenerative response
 This accelerates the - rate of cellular proliferation, results in net increase
in cell production
 Which is beneficial interms of reducing injury to normal tissue
 But tumor with rapid cell turnover exhibit early onset of regenerative
response, which reduce the likelyhood of cure.

Redistribution
 In initially asynchronous cell population , the 1st
radiation dose
preferentially kills cells in sensitive phases.
 Consequently cell surviving in the 1st
dose tend to be partially
synchronized in more resistant phases.
 And these cells will resume their progression to more radiosensitive
phases of cell division cycle, resulting in a net sensitization to next dose
fraction.
 It takes place mainly in tissues with moderate to rapid cell turn
over(actually reacting normal tissues & tumors) and is negligible in late
responding normal tissues.

Reoxygenation
 Bulky tumors may have centers that relatively hypoxic due to their
location away from a blood vessel
 Tumor cells located in this region would be more resistant to radiation due
to the low oxygen tension
 During course of fractioned radiation the oxygen status of originally
hypoxic cells gradually improves before subsequent doses.

 This process(reoxygenation) results from a number of mechanisms, such
as:
- the preferential elimination of more radiosensitive oxygenated cells
increases oxygen availability to surviving hypoxic cells.
-also lowers the interstitial pressure on micro vessels with in the tumor
resulting in improved microcirculation and oxygen supply.
- tumor shrinkage and active tumor cell migration bring previously hypoxic
micro regions closer to blood vessels.

Altered Fractionation Techniques For Radiation
Therapy

 Wilhers identified hazard of accelerated tumour clonogen repopulation
during conventional once-a-day radiation therapy as one likely cause of
treatment failure
 4 primary fractionation factors
- Dose per fraction
- Total dose
- Overall treatment
- Treatment interval

Altered fractionation stratergies
A) Hyperfractionation
- Decreased fraction size
- Increased fraction number
- Increased total dose
- Maintain overall treatment time
- Rationale : Allows safe delivery of high tumors dose without increase in
late normal tissue toxicity

 Strategy of Hyperfractionation is to use an increased no. of smaller
doses per fraction than conventional 1.8 - 2.0 Gy per day
1.2 to 1.5 Gy twice daily to a total dose of 80.5 Gy over 7 weeks.
 This is associated with increase in acute complications and reduction in
the late complication

B) Acceleration Fractionation
 Decrease in overall treatment time
- Maintain or slightly reduce
- Fraction size
- Fraction number
- Total dose
 Accelerated fractionations attempt to reduce tumor proliferation, which is
the major cause of RT failure.
 Rationale: Counteract adverse effects of tumor cells repopulation by
decreasing over all treatment time.

Newer Regime
Continous Hyper Fractionated Accelerated Radiation Therapy (CHART)
54 Gy in 36 fractions – 1.5 Gy T.I.D. over 12 consecutive days.

Indications for Radiotherapy
 T1-T2 lesions
 T3,T4 Locally advanced lesions
- Post surgical treatment
- Only therapy if surgery not possible
 Cervical lymph node
Pre-surgical & post surgical in combination with neck dissection for
clinically positive lymph nodes.

General Concept Of Radiotherapeutic Techniques

Treatment planning
 Radiation treatment plan is based on tumor site, tumor size, the total
volume to be radiated , the number of treatment fractions, total number of
days of treatment, and tolerance of patients.
 Also includes planning for sparing of uninvolved tissues or organs.

Patient positioning & Immobilization
 Radiotherapy can be delivered in supine, prone or even sitting position
 Immobilization, accuracy & reproducibility are better achieved in supine or
prone position
 Immobilization is essential as high dose must be given accurately to a small
volume avoiding adjacent vital radiosensitive structures.
 Head holders , bandages ,laser positioning, head and neck “landmarks” or
tattoos and custom acrylic shells are used for positioning and
immobilization.
 Thin transparent plastic shell is moulded to patient’s skin to mark the field
size, entry & exit points.

Patient positioning and immobilization devices are used to
achieve true reproducibility and accuracy in set up.
Head Frame With Bite Block

Simulation & Beam verification
 Simulator is an isocentrically mounted diagnostic X-ray unit that mimics
geometrical arrangement of radiotherapy machine.
 The aim of simulation is to accurately target or localize the volume which is
to be treated
 A patient is placed on the couch in treatment position & field are aligned
 Alignment is done either clinically or with Flouroscopic screening facility
 Tumor volume is localized & verification X ray is taken
 Lead blocks and shields made to ensure that radiation reaches only the
target tissue.www.indiandentalacademy.com

Clinical Radiotherapy Techniques
Brachytherapy Teletherapy

Brachytherapy
 Brachio in greek means short range
 Brachytherapy is the sub specialty of radiation oncology
which uses selected Radioisotopes and specialized
instruments to directly administer radiation to tumor bed

 Two types of implants:
Removable Implants:
Radium, Tantalum, I 125
& Ir 192
& Co60
Permanent Implants: (left insitu to decay completely)
Gold grains & Radon seeds
 Brachytherapy radiation travels only a short distance to the desired target
region without effecting surrounding normal tissues
- Its dose intensity has a rapid fall off with distance according to the inverse
square law
[I~ 1/ D2]
This causes sharp ↓ in dosage in surrounding tissues
The dose rate can be low and continuous
LDR - 40 to 200 cGy / hr
HDR – 1200 cGy / hrwww.indiandentalacademy.com

Here radioactive sources are implanted into the tumor for definite period
(temporary implants) or indefinitely (permanent).
The source can be in the form of needles, wires, and seeds.
Used in management of squamous cell carcinoma of Head and Neck, skin,
breast tumor, soft tissue sarcoma and many others.

Intracavitary brachytherapy
 Treatment by placement of radioactive sources inside natural body
cavities.
 Mainly used in gynecological malignancies.

Advantages:
 Ideally suited for anatomical locations where tumor is well localised to
tissues (Anterior part of tongue)
 High doses of radiation delivered in & near the tumor
Disadvantages:
 GA is necessary for insertion of these sources
 Increased radiation exposure to radiation personnel
 Treated volume is small

Dose:
 Typically, about 3.0 to 3.5 Gy is given to a distance of about 1 cm ( from the
periphery of the catheters), and two daily treatments are given about 6
hours apart. Each treatment takes about 15 to 30 minutes
Precautions for Brachytherapy:
 Patient -nurse contact is kept to the minimum
 Patient remains in the ward for up to seven days
 Patient is sedated before plastic tubes are removed

Radioactive Isotopes
 Systemic radiation in which isotopes are injected IV
 Useful therapeutic effects can be obtained if the target organ concentrates the
isotopes & increases the specific dose
 Systemic radiation therapy is sometimes used to treat cancer of the
thyroid(I131
), polycythemia Vera(P32
)and adult non-Hodgkin's lymphoma.
 Ideal requisites of a radiopharmaceutical for RT
i. Effective half-life should be in hours to days.
ii. Medium/high energy (>1 MeV).
iii. Minimal radiation dose to patient and Nuclear Medicine personnel
iv. Patient Safety
v. Should be readily available

Teletherapy (External beam thearpy)
 “Tele” means far or distant
 Here beam comes from a source located at a distance from the patient
and directed towards the patient.
 External beam therapy can be broadly divide into two types based on
beam quality and their use.
 Kilovoltage therapy
- Megavoltage therapy
Kilovoltage is further divided into 3 types
i) Contact therapy
ii) Superficial therapy
iii) Orthovoltage or deep therapy

Contact therapy
 Contact therapy operates at potentials of 40-50 kV and tube current of
2mA.
 Facilitates irradiation of accessible lesions from very short source to
surface distance(SSD) i.e 2 cm or less
 Because of very short (SSD) and low voltage, the contact beam produces
a very rapidly decreasing depth dose in tissue hence skin surface is
maximally irradiated but the underlying tissues spared.
 Useful for tumors less than 1 -2 mm in thickness.

Superficial therapy
 Term superficial therapy applies to treatment with x-rays produced at a
energy ranging from 50 to 150 kV and tube current of 5-8mA .
 SSD ranges from 15 cm to 20 cms .
 Is useful for irradiating tumors confined to about 5mm.
 Beyond this, the dose fall off is too sharp to deliver adequate dose.

Orthovoltage or deep therapy
 Term orthovoltage therapy is used to describe treatment with x-rays
ranging from 150 – 500 kV. At a tube current of 10 to 20 mA.
 SSD is approximately 50cms.
 The maximum dose is delivered close to the skin surface, with 90%
isodose value occurring value occurring at a depth of about 2cms.
 Disadvantage – Higher skin dose
 Increased scatter
 Greater bone absorption – leading to beam energies unsuitable for
treatment for the treatment of tumors behind the bone.

Megavoltage therapy
 X-ray beams of energy 1 MV or greater can be classified as megavoltage
beams
 The term strictly applies to the X-ray beams, the gamma- ray beams of
energy 1 MeV or greater.
 Examples for clinical megavoltage machines are Van de Graaff generator,
linear accelerator, betatron, microtron and telecobalt units

The Radiotherapeutic Techniques
 Single field arrangement
 Parallel opposed fields
 Wedge lateral field
 Multiple fields
 Rotational & Arc therapy

Single Field Arrangement
 Tumor is treated with one field only
 Quick & easily reproducible therapy
Parallel opposed fields
 Two parallel fields are opposite to one another
 Produces fairly even distribution through out the irradiated area

Radiation fields
Lateral field Antero Posterior Field

Wedge lateral field
 Two right angled fields can be combined to irradiate a discrete tumor
volume rather than placing them parallel.
Multiple fields
 Most common form is with 4 fields
arranged 2 parallel & 2 opposed pairs
(4 Field Brick technique)
produces good tumor localization

 Moving field techniques which are modifications of multiple field therapy
 Radiation source rotates around the tumor isocentrically
 To provide an even dose through out the tumor volume
 To spare a selected normal tissue from the primary beam, only a part of
rotation ( Arc therapy) is made
Rotational & Arc therapy

Methods to Reduce Side Effects:
 Collimation/filtration
 Fractionation of dose
 Use of high LET radiation
 Chemical radio sensitizers
 Hyperbaric oxygen

Combined Therapy: Multimodality
Therapy

Preoperative Radiotherapy
Advantages:
 Eradicate subclinical disease beyond resection margins
 Prevention of marginal recurrences
 Prevention of implantation of tumor cells at surgery
 Control of subclinical disease at 1º site & in LN

 Dosage
 180 to 200 cGy/ fraction
1 fraction/day ;5 days/ wk, to a total dosage of 5,000 to 6,000 cGy
After completion of treatment - 4 to 6 wk gap prior to surgery
 To allow for patient recovery,
 To decrease acute inflammatory reaction
 To allow for a maximum clinical shrinkage of tumor

Disadvantages
 Diminished wound healing
 Delay of definitive surgery
 Can’t cure already developed occult distant metastasis
 Increased cost
 Combined therapy is unnecessary for early lesion

Post operative Radiotherapy
 Indications
- When estimated risk of loco regional recurrence is > 20 %
- Advanced T3 or T4 lesions
- Positive or close margins of resection
- Perineural/vascular invasion
- High-grade histology

Drawbacks of Post operative Radiotherapy
- Delay in initiation of radiation therapy due to wound complications from
surgery
- Scarring & vascular modifications from surgery may decrease tissue
oxygenation- adversely affects radiation tumor cell kill

Concomitant Chemoradiotherapy
 Unresectable disease to improve local & regional control
 Mechanism for interaction b/w cytotoxic drugs & radiation that results
in additive or synergistic phenomenon rests on several mechanisms
- Inhibition of DNA repair
- Redistribution of cells in sensitive phases of the cell cycle
- Promoting oxygenation of anoxic tissues
 The net effect is to improve cellular cytotoxicity
 Specific chemotherapeutic drugs such as fluorouracil, cisplatin, and
taxanes induce cell cycle arrest at the G2 checkpoint, where the cell is
most radiosensitive

Multiple Agents & Radiotherapy
 Improved survival time- primary goal
 Combining several drugs with radiation- Acute toxicity- trials designed
with split course radiation- allow healthy tissue recovery
 Infusional 5-FU + cisplatin or Hydroxyurea + concurrent split-course
single daily fraction radiation- promising survival and response data but
also severe toxicity

Modification Of Tumor Hypoxia
 Cellular Hypoxia is considered as an important factor in control of head &
neck cancer
 Methods to increase tumor oxygenation:
- Hyperbaric oxygen
- Oxygen mimetic hypoxic cell sensitizers
- Modified Radiation Fractionation

Hyperbaric oxygen therapy
 Oxygen under high pressure is given to the patient
 Usually given as 20-30 dives at 100% oxygen &
2-2.5 atm pressure
 Increases oxygenation of irradiated tissue
 Promotes Angiogenesis
 Enhances osteoblast repopulation

Hypoxic Cell Sensitizers
 Group of Bioreductive Nitroimidazole drugs which mimic oxygen
 Selectively Radiosensitised hypoxic cells
 Misonidazole & Etanidazole
 Side effect: Neurotoxicity
 Nimorazole- decreased toxicity & well tolerated

Tirapazamine
 New bioreductive agent
 Undergo selective electron reduction in hypoxic conditions, forming free
radicals, which result in cell death
 Potentiates the cytotoxicity of ionizing radiation & several
chemotherapeutic drugs
 Nicotinamide, which causes vasodilation – reduces transient or acute
hypoxia

Radio protectors
 Amifistone (Ethyol)- sulfhydryl compound that acts as potent scavenger of
free radicals generated in tissues exposed to radiation
 Approved by the US FDA for management of RT- induced salivary
dysfunction
 The sulfhydryl compound, WR- 2721 selectively protected the normal
tissues against effects of radiation.

Conventional external beam radiotherapy
 Conventional external beam radiotherapy (2DXRT) is delivered via two-
dimensional beams ( height and width) using linear accelerator machines.
 2DXRT mainly consists of a single beam of radiation delivered to the
patient from several directions: often front or back, and both sides.
 2DXRT are planned by using a specially calibrated diagnostic x-ray
machine known as a simulator because it recreates the linear accelerator
action.
 This technique is well established and is generally quick and reliable.

Conformal Radiotherapy
 Conformal radiotherapy is also called 3D conformal radiotherapy (3DCRT).
 It uses a special way of planning and giving radiotherapy.
 In conformal RT the image of the tumours obtained in three dimensions
(3D);width, height and depth, using CT scan or MRI Scan,PET.
 The information from these scans feeds directly into the radiotherapy
planning computer.
 Then the computer programme the designs radiation beams that ‘conform’
more closely to the shape of the tumour and avoid healthy tissue as far as
possible.

Intensity Modulated Radiotherapy
 Like conformal radiotherapy, IMRT shapes the radiation beams to closely
fit the area where the cancer is.
 And also alters the radiotherapy dose depending on the shape of the
tumour - Using radiation beams of varying intensity (beamlets),
- i.e the central part of the cancer receives the highest dose of
radiotherapy and a surrounding area of tissue gets lower doses.
 IMRT is ideally suited for H & N malignancies, if there is proximity of the
tumor to the critical structures.

 IMRT is done with Linear accelerator (LINAC) with multi-leaf collimator
that moves around the patient and shapes the beams of radiotherapy to fit
the tumour.

Image-guided radiation therapy (IGRT)
 Traditionally, imaging technology has been used to produce three-
dimensional scans of the patient’s anatomy to identify the exact location
of the cancer tumor prior to treatment.
 However, difficulty arises when trying to administer the radiation, since
cancer tumors are constantly moving within the body (for example, from
movement caused by breathing or tumor shrinkage).
 Hence, the exact location of the tumor may have changed between the
time of scan and actual treatment and fractionation.

 IGRT combines scanning and radiation equipment,
- i.e IGRT uses a linear accelerator (IMRT), equipped with a kilovoltage
imaging source and solid state X-ray detector (X-ray Volume Imaging).
 This enables physicians to adjust the radiation beam based on the
position of the target tumor and critical organs, while the patient is in the
treatment position.
 Thus IGRT reduce the exposure of healthy tissue during radiation
treatments.

Hyperthermia & Radiation Therapy
 Supra normal temperature in the range of 41-430
C sensitizes cells to
radiation.
 It selectively injures 2 kinds of cells that are most resistant to irradiation:
Hypoxic cells & cells in late S phase of cell cycle
Greater Hyperthermia occurs in cancer cells because:
 Sluggish heat dissipation by tumor blood flow
 Heat makes micro environment in tumor more acidic & nutritionally deprived
 Radiofrequency, Microwaves, Ultrasound
 Giving heat 1-5hrs after irradiation can attain max. therapeutic gain

Radioimmunotherapy
 Use of radio labeled antibodies to deliver doses of radiation directly to the
cancer site
 Antibodies are highly specific proteins that are made by the body in
response to the presence of antigens (substances recognized as foreign by
the immune system).
 Some tumor cells contain specific antigens that trigger the body's immune
system to produce tumor-specific antibodies.
 Large quantities of these antibodies can be made in the laboratory and
attached to radioactive substances (a process known as radiolabeling).

 Once injected into the body, the antibodies actively seek out the cancer
cells, which are destroyed by the cell-killing (cytotoxic) action of the
radiation.
 The benefit to this approach is that it can minimize the risk of radiation
damage to the body's healthy cells.
 The success of this technique will depend upon both the identification of
appropriate radioactive substances and determination of the safe and
effective dose of radiation that can be delivered in this way.

TREATMENT OF RECCURENCE
 90% of the recurrence occurs within 2 years.
 8% of recurrence occurs after 5 years. In such cases debulking or
radical surgery should be attempted.
 Reirradiation will be helpful only after one year.
 50-65 Gy Hyper fractionation / Brachytherapy are used to improve the
tolerance of tissues to radiotherapy.

THE ROLE OF RADIATION THERAPY ALONE FOR
HEAD AND NECK TUMOR - BY SITE

Lip
 T1 to T2 lip cancers - Surgery / radiation therapy can be considered for
primary treatment of based on specific anatomic location and size of the
lesion.
 Radiation therapy is indicated for:
- Commissure involvement,
- Patients who refuse surgery, and superficial lip cancers involving less
than one-third of the entire lip.
- Small lesions are treated with interstitial implant alone.
- Larger lesions may require external beam radiation therapy with an
interstitial boost.

Oral cavity
 For early T1 & T2 lesions - radiation therapy & surgery are equally
effective in achieving local control.
 Superficial lesions that are ≤ 2 cm (T1), away from the bone – can be
treated with interstitial implant alone.
 Lesions > 2 cm and ≤ 4 cm (T2)
- without clinical lymphadenopathy can be treated with external radiation
therapy (5,000 cGy)
- with adjacent regional lymph nodes involvement - external radiation
therapy (5,000 cGy) + temporary interstitiary implant (2,000 to 2,500 cGy).

 For moderately advanced T2 to T3 lesions, full course external beam
radiation therapy is used.
 For lesions in the floor of mouth and tongue, extension of disease deep
into the musculature and into adjacent mandibular bone would best be
treated with surgery and postoperative radiation therapy.

Floor of Mouth
 T1 & T2 lesions can be treated - surgery / radiation therapy.
 T1 & T2 lesions + clinically positive nodes - surgical resection of the
primary lesion and a neck dissection .
 Postoperative external beam radiation therapy is indicated for close or
positive margins in the primary site and/or nodal disease.
 Post operative radiation is to be given, within 6 weeks after surgery to a
dosage of 6,300 cGy to the primary site and high-risk node.
 An early lesion extends to the ventral aspect of the tongue - radiation
therapy is preferred to avoid functional morbidity.

Tongue
 T1 and T2 lesions can be treated with surgery / radiation therapy.
 Primary radiation therapy - dosage of 4,000 cGy of external beam
irradiation to tongue and regional nodes
- with a subsequent brachytherapy boost of 3,000 cGy. 5,000 to 5,400 cGy
is administered for elective nodal irradiation.
 Advanced T3 & T4 lesions are generally approached with surgery and
postoperative radiation therapy within 6 weeks of the procedure.

Base of Tongue
 T1 and T2 lesions can be successfully treated by either surgery or
radiation therapy.
 Majority of patients are usually treated with radiation therapy, as it
provides a better functional outcome and quality of life with equivalent
control rates.
 Patients with T1 and T2 lesions - conventional fractionation of primary
lesion upto 5,400 cGy, the involved neck nodes to 6,000 cGy and elective
nodal irradiation to 5,000 to 5,400cGy .

• Following a 3-week break - iridium 192 temporary
interstitiary implant ionto the base of the tongue
delivering 2,400 to 3,000 cGy.
• Advanced T3 and T4 lesions often would require
surgery with a partial or total glossectomy, and neck
dissection to be followed by postoperative radiation
therapy.

Salivary glands
 Surgery is the treatment of choice for both primary and locally recurrent
salivary gland tumors.
 For unresectable primary or recurrent lesions, the use of neutrons is
indicated.
 Postoperative radiation therapy is an important part of treatment and is
indicated:
(1) resectable primary T4 and recurrent tumors,
(2) high grade lesions,
(3) positive or close margins,
(4) perineural/vascular invasion
(5) locoregional lymph node metastasis.

 Dosage: 6 MV x-rays are administered,
 If the treatment is postoperative, 180 cGy per fraction is given to a total
dosage at 6,300 cGy to the primary area and high risk lymph node levels.
 5,000 to 5,400 cGy is administered for elective nodal irradiation when
indicated

Pre Irradiation Dental Care
 Extraction of unrestorable teeth & those with advanced periodontal
disease
 Extractions done14-21 days prior to radiation therapy
 Antibiotic use
 Fluoride (neutral sodium fluoride 1%) application
 Oral prophylaxis
 Restore large caries
 Remove partially erupted third molars, may leave full bony impacted
teeth if surgical difficulty.

Post-treatment Protocol
 Regular application of fluorides & regular check up
 Salivary substitutes for salivary dysfunction
 Proper nutrition - especially proteinaceous food
 Post treatment follows up at regular intervals
 Counseling and group therapy and other methods for proper emotional
adaptation of the patient.
 Avoidance of all surgical procedures involving bone for a minimum of
six months

 Under 3,000 cGy — Mucositis, candidiasis, xerostomia & dysgeusia begin
 Over 3,000 cGy - xerostomia (permanent) and taste dysgeusia , altered
saliva (thick, more acid, changed flora)
 Over 5,000 cGy - Trismus - concerns for osteoradionecrosis
 Over 6,000-6,500 cGy significant concern for osteoradionecrosis
 Stimulated Whole Salivary Flow Rates - 57% decrease in a week after
beginning of RT & after 5 weeks (end of treatment) 76% decrease..
 Endocrine abnormalities: Hypothyroidism, Parathyroid adenoma and
hyperthyroidism.
 Atherosclerosis occurs in doses more than 50 Gy

 Progressive muscle fibrosis may limit the neck and shoulder function.
Some times trismus may also seen.
 Visual impairment may occur due to radiation keratitis, cataract and optic
neuritis.
 Radiation neuritis.
 Secondary infection.
 Development of maxillofacial deformity and defective tooth development
in children.

Sequelae of radiation therapy
ORN
Oral candidiasis
Xerostomia
Soft tissue fibrosis
Trismus
Obliterative endartritis
Slow/ non healing ulcerswww.indiandentalacademy.com

Mucositis
 The oral mucous membrane consists of
Basal layer composed of radiosensitive vegetative & differentiating
intermitotic cells
 Near the end of 2nd
week of therapy, as some cells die, mucous membrane
begins to show some areas of redness & inflammation – Mucositis
 The irradiated mucous membrane begins to break down, with the formation
of white to yellow pseudo membrane

 After irradiation is completed, mucosa begins to heal rapidly
 Healing is complete by about 2 months
 After months to yrs, mucous membrane tends to become atrophic, thin &
avascular
 This long term atrophy results from
progressive obliteration of fine vasculature
Fibrosis of underlying connective tissue

Clinical features
 The early clinical sign of mucositis is Erythema presenting about
4–5 days following cumulative doses of head and neck radiation of about10
Gy.
 Patients also often complain of burning and intolerance of spicy foods
 Seven to 10 days after chemotherapy or at cumulative radiation doses of 30
Gy, ulcers develop, resulting in marked discomfort

Management Of Mucositis
Oral care & Topical therapy:
 Bland oral rinses & topical anesthetics
 Saline, Bicarbonate
 Lubricating jelly
 Milk of magnesia
 Benzydamine HCl
 Sucralfate suspension
 Povidone-iodine rinses

Management Of Mucositis
Methods to reduce exposure of the mucosa to damaging agents
 Ice chips
 Propantheline
Antimicrobials
 Aciclovir
 Antibiotics
 Amphotericin B
 Chlorhexidine
 Fluconazole

Anti-inflammatory medications
Biologic response modifiers
 Interleukin-1,11
 GM-CSF
 G-CSF
 Keratinocyte growth factors

Cytoprotective agents
 Amifostine
 Benzydamine
 Glutamine
 N-acetyl cysteine
 Prostaglandins
 Vitamin E
Low-energy lasers

Oral candidiasis
• A fair number of patients will develop an oral Candida
infection .
• May be asymptomatic / may complain of an acute
development or exacerbation of their sore mouth or throat.
•Initiation of antifungal medication will usually resolve the
problem.

Taste buds
 Extensive degeneration of normal histological architecture of taste buds
 Hypoguesia, Aguesia & Dysguesia
 Taste loss may begin with radiation dose of 20 Gy
 Returns to normal in about 1 yr after RT
 Zn sulfate 220 mg, twice daily – recovery of taste disturbances

Salivary glands
 Parenchymal component is radiosensitive
 Extent of reduced salivary flow is dose dependent
 Reaches zero at 60 Gy
 Mouth becomes dry (Xerostomia), tender, dysphagia
 Swallowing becomes painful & difficult
 Small volume of viscous saliva has Ph
of 5.5
 Buffering capacity decreases by 44%
 Alteration of micro flora ( Acidogenic)
 Increased Streptococcus mutans, Lactobacillus & candida

Management of Xerostomia
 Preventive therapy
( Topical Fluorides , Regular dental visits )
 Symptomatic treatment
(sipping water frequently , room humidifiers, oral rinses & gels,
Artificial saliva)
 Salivary stimulation
Topical
Systemic

SIALOGOGUES
Mechanical stimulants
 Eating foods which require Mastication
 Artificial Sweeteners
Chemical stimulants
 Mucopolysaccharide solutions containing Citric Acid
Electrical stimulants (TENS)

Proposed Systemic Sialogogues
 Pilocarpine
 Cevimeline
 Bethanechol
 Anetholetrithione
 Guaifensin
 Bromhexine
 Neostigmine
 Yohimbine
 Potassium iodide
 Nicotinic acid
 Malic acid
 Vit A

Radiation caries
 Rampant from of dental caries
 Due to exposure of salivary glands to therapeutic irradiation
 Reduced salivary flow, Ph
& buffering capacity
 Increased viscosity of saliva

Clinically 3 types are present:
 Widespread superficial lesions attacking all surfaces
 Involving primarily cementum & dentin in cervical region
 Dark pigmentation of entire crown
Management:
 Daily application of 1% neutral NaF gel for 5 min in custom made
applicator trays

Osteoradionecrosis
 Primary damage to mature bone results from radiation induced damage to
vasculature of periosteum & cortical bone, which are normally already
sparse
 Normal marrow replaced with fatty marrow & fibrous C.T
 Chronic non healing wound caused by Hypoxia, Hypocellularity &
Hypovascularity of irradiated tissue
 Destruction of osteoblasts & osteocytes
 Mandible is more commonly affected

Pathogenesis
Therapeutic irradiation
Endothelial death, thrombosis, hyalinization of BV
Progressive obliterative endarteritis
Decreased microcirculation
Ischemia & decrease in viable osteocytes
 Higher incidence of ORN when teeth are removed after radiotherapy

Clinical features
 Severe, deep, boring pain for weeks to months
 Soft tissue abscesses
 Persistently draining sinus
 Exposed bone with intra or extra oral fistulae
 Trismus
 Fetid odour
 Pathological fracture

Therapeutic Modalities To Decrease Incidence Of
ORN
 Dose fractionation
 Use of megavoltage
 Meticulous collimation
 shielding of normal tissues
 Maintenance of pre irradiation & post irradiation dental health

Management
 Debridement
 Antibiotics to control secondary infection
 Hydration, fluid therapy
 Narcotics
 Sequestrectomy & repeated irrigation
 HBO therapy
 Antioxidant supplements
 Reconstruction of pathological fracture

Reference
 Text book of Radiation Oncology – Principles and Practice
Goura K Rath, Bindhu K Mohanti
 Text of Oral Medicine
Burkits
 Cancer – Principle and Practice
Unicent T. Devita, Samuel Hellman
 Head And Neck – Surgery and Oncology
Jatin Shah
 Cancer of Head And Neck –
Eugene N .Myer’s, James Y. Suen
 Oxford hand book of Oncology
Jim Cassidy, Donald Bisselt
 Internetwww.indiandentalacademy.com

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