DISCUSSION ON RADIOTHERAPY

 by DR KASSIM A. J
 1. DISCUSS THE USE OF RADIOTHERAPY IN
THE TREATMENT OF HEAD AND NECK CANCERS

2. WHAT ORAL COMPLICATIONS MAY ARISE

AND HOW CAN THEY BE PREVENTED
 OUTLINE
 INTRODUCTION
- Definition of radiotherapy
- Objectives of radiotherapy
- Mechanism of radiotherapy
 USES OF RADIOTHERAPY IN TREATMENT
-curative
-combination therapy
-palliative
 ADVANTAGES AND DISADVANTAGES
 ORAL COMPLICATIONS THAT MAY ARISE
- Acute
- Chronic
 PREVENTION
 CONCLUSION
 INTRODUCTION
Radiotherapy is the only other treatment
modality like surgery which is potentially
curative in the treatment of oral cancer.
 can be used alone or in conjunction with

surgery.
 DEFINITION
Radiotherapy is defined as the medical
application of radiation for the clinical
treatment of human diseases such as cancer.
 OBJECTIVES
These include
 Cure primary tumors

 Reduce bulk of tumor

 Reduce fixation of tumors to surrounding structures

 Decrease incidence of local recurrence

 Eliminate positive tumor margins following

incomplete resection
 Reduce incidence of neck recurrence after surgery if

more than one lymph node involved, or if there is

extra capsular spread.
MECHANISM OF RADIOTHERAPY

RADIOPHYSICS:
Absorbed dose: this is the measure of energy
imparted by ionizing radiation to matter.
Traditional unit of measure is the ‘rad’ (radiation
absorbed dose)
Current standard of (SI unit) of measure is ‘Gray’
1Gy =100 rad =1joule/kg
RADIOBIOLOGY: effects of radiation on biological
tissues. This depends on
 Source of radiation

 Amount of radiation administered

 Time period over which radiation is administered

 Filtration removing extraneous radiation

 Area of tissue radiated

 Depth or penetration of tissue

Lethal dose for most tumors is 45-60 Gy. Most side

effects in human tissues occur with doses >45Gy.
 Amount of radiation absorbed by tissues
depends on
a. density of tissue – ‘Compton effect’
b. average atomic number of tissue –
‘Photoelectric effect’
c. depth of tissue penetration.
 MECHANISM OF TISSUE
DESTRUCTION BY IRRADIATION
 Cytotoxic effects: cell death is produced by 2 ways
a. direct damage to DNA RNA molecules
b. free radicals: radiation causing ionization of
water in cells. Hydrogen peroxide which forms
cause DNA and chromosome disruption
-proteins :denaturation and impairment of enzyme
function
-nucleic acids: loss of base, disruption of H-bonds
between DNA strands and cross-linking of DNA
either within the helix or to other DNA, or to
proteins.
 Effects on cellular kinetics:
Neoplastic cells are more sensitive than normal cells
especially during cell division. Radiation of these cells
will cause a reduction in size of the population by
mitotic delay which in turn inhibits progression of
cells through cell cycle and cell death during mitosis.
 The degree of tissue sensitivity to the effects of

irradiation is directly proportional to

-rate of turnover
-degree of oxygenation
-degree of differentiation
 FACTORS ENHANCING CELL
RESPONSE TO RADIATION
 Fractionating/High dose:
Increasing the dose over a short period of time
appears to cause more damage to neoplastic
cells compared to using low dose over a long
period of time.
 Oxygenation of tissues:

Increasing the oxygen content of neoplastic tissue

results in increased formation of radicals and
hence increases therapeutic or tumor damaging
effects of irradiation.
 Chemical modifiers:
Chemical agents administered to enhance or
reduce the effect of radiation on certain tissues.
They are either ‘sensitizers’-increase the
destructive effects of radiation or ‘protectors’-
act as free radical scavengers e. g. cysteine
 USES OF RADIOTHERAPY
 CURATIVE
Radiotherapy is equally effective as surgery in the
management of lip cancers especially where
cosmesis is of great concern e.g. lower lip.
Also can be used for early lesions (T1 and T2) of
the tongue (anterior 2/3 rds)and floor of the
mouth with simultaneous treatment of local
nodes.
Early lesions of the retromolar area provided the
mandible is not involved.
 COMBINATION THERAPY
Radiotherapy can be used in combination with
surgery in advanced lesions of the tongue (ant 2/3
rds) and floor of the mouth i.e. stages iii and iv
including neck dissection and also the presence of
nodes larger than 2cm.
In the retromolar area where mandible is involved or
for stages iii and iv lesions post operatively.
In the buccal mucosa where small tumors are
amenable to surgery radiotherapy can be used post
operatively if indicated.
In the maxilla surgery alone gives good results and
because of the frequent involvement of bone in
this region radiotherapy is not usually indicated.
Radical neck dissection and radical tumor removal is
advocated and radiotherapy can be used post
operatively for stage iii and iv lesions.
Clinically positive lymph nodes in the neck should
be treated with surgery and radiotherapy is useful
in preventing neck recurrence in patients with
more than one positive lymph node or where there
is extracapsular spread.
 SURGERY
 Surgery and radiotherapy are complimentary to

each other and is the only proven effective

method in treatment of squamous cell carcinomas
of the oral cavity. Can be used in 2 ways
a. Before surgery: to help reduce bulk of tumor and
reduce fixation of tumor to surrounding
structures. This causes a lot of complications and
renders reconstructive surgery more complex
hence dose should be limited to 45-50 Gy.
b. After surgery: post operative radiation could be
used for the following reasons
-to eliminate tumor margins and remaining
neoplastic tissue left behind following resection
-to decrease likelihood of local recurrence
-to treat micrometastasis in cervical lymph
nodes
 CHEMOTHERAPY
 Administration of cytotoxic drugs either before during or
after irradiation has the potential for significant
exacerbation of normal tissue reactions, both acute and
late.
 Induction chemotherapy however, increases tumor
sensitivity to radiotherapy by
-decreasing tumor size
-increasing vascularization
-increasing oxygenation of tumor
radiosensitizer effect e.g methotrexate increases
radiosensitivity.
 PALLIATIVE
Radiotherapy is indicated in patients not fit for
surgery.
EFFECTS OF RADIOTHERAPY
STOCHASTIC EFFECTS (IRREVERSIBLE)
 Cumulative effects of radiation
 Not dose dependent
 Takes sometimes years to develop
 And often irreversible effects

NON STOCHASTIC EFFECTS (REVERSIBLE)

 Dose dependent effects
 That are non cummulative
 Mostly reversible changes

Almost all oral sequelae are non-stochastic effects

 Oral sequelae of radiation therapy in the head and
neck can be divided into , divided into ACUTE tissue
reactions and LATE tissue reactions
 Acute tissue reactions typically occur during treatment
or shortly thereafter, and they are really related to the
acute toxicity of the treatment from the radiation
therapy.
 They generally resolve shortly after termination of the
therapy, but they are significant in that they
significantly affect the patient’s quality of life during
the therapy, and they can become severe enough to
interfere with treatment
 Acute tissue reactions typically occur at sites
where there are rapidly proliferating cells such as
the mucosa or skin.
 The late tissue reactions are defined as reactions
occurring more than 90 days after treatment. These
are more often permanent and frequently
irreversible complications.
 They tend to be more severe, and affect slowly
dividing cells such as bone or cartilage as well as
neurons.
 Only about 5-15%of patients are affected
ORAL COMPLICATIONS THAT MAY
ARISE
Complications of radiotherapy are dependent on
the area of the body irradiated as well as the
dose received. They include
 Malaise, nausea and vomiting: commoner in

total body irradiation than that confined to

head and neck region.
 Skin: when affected may result in

-erythema -fades in 7-10 days

-oedema, desquamation and ulceration –
where heavy doses are applied
 -atrophy and dryness- sebaceous and sweat
glands affected
-occlusion of superficial blood vessels.
 Oral mucosa: lower doses needed to give the
same effect as skin.
-rapid loss of taste – reversible
-mucositis – ulceration and necrosis of oral
mucous membrane
-erythema and dryness due to loss of
salivary land function
 Salivary glands:
a. Acute post-irradiation sialadenitis
-congestion
-oedema
-inflammatory cell infiltrate
-depressed number of secretory granules in
acinar cells
-ducts unaffected
 Teeth:
. radiation caries
-demineralization around necks of teeth due to
decreased salivary flow and pH
 Others :
a. increased incidence of malignancy e.g. leukemia
b. eyes – conjuctivitis, cataracts
c. blood – pancytopenia
d. bone – osteoradionecrosis
e. jaw function – fibrosis of TMJ and muscles of
mastication i.e. trismus
 Acute tissue reactions
These include
 Mucositis

 Dysgeusia (Taste loss)

 Infection

 Fistula formation

 Xerostomia
 Radiation mucositis:
 Typically begins about 1-2 weeks after the
onset of radiation therapy, and it occurs in at
least 80% of patients undergoing head and
neck radiation.
 It mucositis is a significant adverse reaction
that may interfere on the radiotherapy process
 It is occurs in 4 stages:
 Inflammatory/vascular stage which presents
with initial erythema,
 an epithelial stage in which pseudomembranes
are formed,
 a bacterial/ ulcerative stage in which there is
Gram-negative bacilli overgrowth,
 and a healing stage

 Some patients may actually require an

alteration or a halt in their radiotherapy
treatment due to their mucositis, it is therefore
a very significant complication
 The most used scale to measure oral mucositisis the one by
the WHO, which classifies mucositis into four degrees
based on the QOL of the patient undergoing the
radiotherapy
 In class 0 there are no signs or symptoms.
 Class1 the mucosa is erythematose and painful.
 Class 2 is characterized by ulcers, but the patient can eat
normally.
 Class 3 is when the patient has ulcers and can only drink
fluids.
 Class 4 is when the patient cannot eat or drink.
Mucositis is even worse when chemotherapy is used in
association with radiotherapy in cancer treatment
 Dysgeusia (Taste loss)
 Dysgeusia affects patients from the second or third
week of radiotherapy onwards, and it may last for
several weeks or even months.
 It occurs because the taste buds are radiosensitive.

 Radiation causes a degeneration of their normal

histological architecture.

 The increased salivary viscosity and biochemical

alteration also creates a mechanical barrier between the
tongue and foodstuff thus worsening the dysgeusia.
 approximately 70% of patients undergoing
head and neck radiotherapy have some level of
dysgeusia

 It results in in the loss of appetite and weight,

 recovery to normal levels takes place around 60

to 120 days after the end of treatment
Infection
 Radiated patients are more prone to
developing oral infections caused by fungi and
bacteria.
 patients receiving radiotherapy of the head
and neck have a higher number of microbial
species, such as Lactobacillus spp,
Streptococcus aureus and Candida albicans in
the oral cavity.
 Oral candidosis is the most common infection
in these patients.
 The occurrence of candida infection has been
attributed to the drop in salivary flow as a
consequence of radiotherapy
 Besides this, a possible explanation for a higher
predisposition of irradiated patients to
candidosis is a reduction phagocytic activity of
salivary granulocytes against these micro-
organisms
 Both pseudomembranous and erythematous
forms are present although the erythematous
form can be of difficult diagnosis, as it may be
confused with irradiation induced mucositis
 Late tissue reactions
 This include
 Xerostomia
 Radiation Caries
 Osteoradionecrosis
 Xerostomia
 This is a complication in both the acute and
chronic stages
 Among radiated patients in the head and neck
area, it is one of the most frequent complains
 During the first week of treatment, there may
be a thickening of the saliva which becomes
more mucoid and stickier, making it more
difficult to clean the mouth. This may be
particularly noticeable upon waking at night
and in the morning
 The saliva is more acidic and has reduced buffering
capacity
 it has less antimicrobial defenses than normal saliva
would have.
 It has also been shown that there is an alteration in the
form of the oral flora in these patients towards more
cariogenic bacteria species, such as Strep mutans, as
well as overgrowth of lactobacillus and Candida
 Xerostomia significantly alters the patient’s QOL. It
causes significant discomfort and pain and leads to a
more significant increase in the rate of caries formation
 There are more frequent oral infections and
difficulty with speaking, eating, chewing, and
tasting that result from the xerostomia.
 Pathologically, the parotid glands are most
frequently involved, though all salivary glands
can be involved.
 Osteoradionecrosis
 can be subdivided into a spontaneous type and a
traumatic type.
 The spontaneous typically occurs less than two years
from radiation therapy, and it is really thought to be
due to just overwhelming cell kill of osteocytes.

 whereas the traumatic type is typically much more

delayed, is a mixture of cell death, and cell injury
from trauma, and typically presents more than two
years out.
 Dental extraction is the most common source of
delayed trauma, which leads to traumatic
osteoradionecrosis.

 Other risk factors include increasing dosage of

radiation, increasing age, history of trauma,
alcohol and tobacco status, and nutritional
status of patients

 In addition, the primary site of the tumor and

its proximity to bone are risk factors for
development of osteoradionecrosis
 Mandibles are more affected than maxillas and
patients with their natural teeth have greater chances
of developing ORN.

 patients complain of pain, ranging from mild pain,

controlled with drugs, to extremely painful conditions
 Was thought to be as a result of infection. Current
thinking however, believe that it is a cycle of radiation
therapy causing chronic tissue hypoxia,
hypovascularity of the tissue microvasculature, and
hypocellularity of the tissue regions.
Others
Radiation caries
 Even patients who had not experienced tooth decay
for some time, may develop radiation caries when
submitted to radiotherapy.
 The main factor for the development of such
injuries is the decrease of saliva amount and its
qualitative alterations
 Besides this, radiation has a direct effect on teeth,
resulting in defective re-mineralisation making
them more susceptible to decalcification.
 Soft tissue necrosis
 Another possible consequence of radiotherapy is soft
tissue necrosis, which may be defined as an ulcer
located in the radiated tissue, without the presence of
residual malignancy..

 Since ulcerations are often seen on the tumour primary

site, regular evaluations are necessary until the necrosis
retreats, therefore excluding the possibility of
recurrence.

 In the most serious cases it causes trismus may interfere

with eating and dental care.
 PREVENTION
 The following general measures should be carried out
on all patients undergoing or about to undergo
radiotherapy.
a. Extract all teeth with dubious prognosis which will be
within the radiation field
-at least within 7-10days before commencement of
therapy
-within 7-10days after commencement of therapy with
appropriate antibiotic cover before vascularity of the
jaws becomes fully compromised
-avoid surgical extractions (raising flaps) wherever
possible
b. Application of topical fluoride to remaining
teeth in addition to meticulous oral hygiene
before, during and after radiotherapy.
c. Administration of replacement solutions for
tears and saliva.
d. Soft diet and avoid wearing dental prostheses
to minimize trauma to fragile mucosa during
acute phase of therapy
e. Treatment of mucositis e.g. benzydamine
hydrochloride mouthwashes.
Oral complications can be prevented or modified
generally by
 altered fractionation
 reducing the irradiated volume and avoiding
irradiating sensitive structures
 pharmacologic intervention

Altered fractionalisation
 This is the administration of small bursts of radiation
over a long period of time
 This is based on the principles of the four Rs: repair,
repopulation reoxygenation and redistribution.
Reducing the irradiated volume
 Reducing the high-dose volume, and especially
avoiding irradiating sensitive structures e.g the
parotid gland, is the basis for the increasing use of
conformal and intensity-modulated radiotherapy.

 Such techniques may eventually allow dose

escalation in tumour areas leading to increased
local tumour control while keeping morbidity at
an acceptable level
pharmacologic intervention
 The only agent with documented
radioprotective activity is amifostine, which can
reduce late xerostomia and radiation mucositis.
 However, it is still unclear whether amifostine

also protects tumor cells.

 Pilocarpine may relieve late xerostomia in some

patients with remaining functional salivary

gland reserve.
 Antimicrobials were necessary during cause of

treatment e.g. chlorhexidine mouthwashes

 CONCLUSION
 Radiotherapy is one of many procedures used
in the management of cancer but is not
without its own complications and should be
used with utmost care especially were the
benefits out way the complications and with a
knowledge of its complications care can be
taken to avoid some if not most.
 THANK YOU