Radiotherapy

Presented by: Dr. Nikil Jain

contents

Introduction

The Basis of Radiotherapy

Radiation Techniques

Side effects of radiotherapy

Future Development in Radiotherapy

What is Radiotherapy

Use of ionising radiation to treat cancers

Source of ionising radiation :

 Natural : Uranium, Plutonium,
Radium Cobalt, Iodine, Gold, Iridium
 Man made : LINAC, cyclotrons
Introduction
1898 - Roentgen discovers x-rays
1903 - Gruber treats Ca Breast with radiotherapy
1950 - Cobalt teletherapy
- Gamma knife
1970 - LINAC
1990 - “Conformal RT techniques”
- Stereotactic Radiotherapy
- 3D conformal RT
- Inverse treatment planning
- cyberknife,
- intra-operative RT
- chemo-RT
- altered fractionation
Role of RT

50% of all Ca will require RT

2/3 of these for curative intent

Curative Role :
Head and Neck Ca
Ca Cervix
Anal and skin Ca
Prostate Ca
Bladder Ca
Early Lung Ca
Early Ca Oesophagus
Seminoma
Hodgkin’s disease and NHL
Medulloblastomas and some brain
tumours
How are x-rays produced?

Natural : radioactive decay

Man-made : sudden deceleration of high

speed electrons when it hits a
tungsten target
Biological Effects of RT

1. RT causes “ionization” in tissue

2. This forms “free radicals”

3. Free radicals - interact and damage DNA

4. During mitosis, abnormal DNA unable to

replicate, causing cell death
Cellular Effects of Radiation
Inhibition of specific biochemical processes in
cells (eg respiration, protein synthesis)

require very high doses (10-100Gy)

Chromosomal aberrations (1Gy)

Inhibition of reproductive ability :

< 10Gy - divide a few times
> 20Gy - lyse without entering mitosis
Interaction of RT and Matter
Direct action
direct interaction with critical targets in
cells

Indirect action
reacts with H20 to form free radical
free radical highly reactive
free radicals diffuse to DNA
- produce damage to DNA
biological effects results
Biological Effects of RT
DNA strand breaks

Breaks in the chromosomes

results in - restitution (rejoin)
- aberration (fail to rejoin)
- rejoin other broken ends
(give rise to gross
distortion)
Outcome of Radiation Damage

Cell survives

Cell dies - mitotic cell death

- intermitotic death

(lymphocytes, ova, salivary

gland cells)

Cell repairs - given time, energy and nutrients

Itself
Chromosome aberrations in human
lymphocytes

Used as biomarkers of radiation exposure

Blood samples taken within days-weeks

Lymphocytes stimulated to divide and

incidence of dicentrics and rings is scored

Dose can be estimated by comparing with in-

vitro cultures exposed to known doses
repair
Radiation results in : lethal damage - ie
irreversible sublethal damage - ie can be
repaired unless 2nd dose of RT
repair - because of shoulder in cell survival
curve
repopulation
When RT administered, some cells die,
some cells repair or escape damage
with time these cells will replicate and
replace or repopulate the dead cells
if the rate of repopulation exceeds the rate of cell
death, then the tumour will grow despite treatment
thus repopulation
 good for normal tissue
 bad for tumour
fractionation
Allows repair of normal tissue
Allows repopulation of normal tissue

Allows re-oxygenation of tumour

Allows re-assortment

 But

Allows repair of tumour

Allows proliferation of tumour
Treatment plan is based on
 Staging of disease using TNM classification

 age of patient

co-morbid conditions-
Medical
Dental
Speech
Nutrition
Psychosocial
Socioeconomic
Treatment Options

Primary surgery OR Primary Radiotherapy

+/- +/-
Adjuvant Concurrent
Radiotherapy Chemotherapy
+/- +/-
Concurrent Surgery for Salvage
Chemotherapy
 No treatment

 Palliation
 Radiation therapy is indicated following
surgery if:
soft tissue margin positive
one or more lymph nodes exhibit
extracapsular invasion
bone invasion present
more than one lymph node positive in the
absence of extracapsular invasion
comorbid immunosuppressive disease
present, or
perineural invasion occurre
Aims of radiation
 Deliver a precise dose of radiation to a defined
tumor volume with as minimal damage as
possible to surrounding normal tissues

- Eradication of the tumor

- Improvement of quality of life
- Prolongation of survival
Terms used in Radiotherapy
 Gray is Radiation Absorption Dose in the
medium= RAD
 1 Gy = 100 rads

 1 cGy = 1 rad

 Field or portal = The name of the radiation beam

entering thro’ the anatomical site of body. Eg) Rt
lateral, Lt lateral face portals
DIFFERENT TYPES OF RADIOTHERAPY
 External beam therapy
 Brachytherapy

 Combined external beam and interstitial

brachytherapy
 Modification of tumor hypoxia

 Modified radiation fractionation

 Combined chemotherapy/radiotherapy

 Combined modified radiation fractionation and

simultaneous chemotherapy
 Intensity modulated radiotherapy or IMRT
Process of radiation oncology
 Clinical evaluation
- Pathology

- Staging work up

- Patterns of spread and failure

 Therapeutic decision:goal of therapy

- Curative:definitive,neoadjuvant or adjuvant

- Palliative
 Selection of therapeutic modalities

- Integration with surgery(pre op or post op)

- Integration with chemotherapy

 Periodic evaluation (during treatment) and follow- up

- Careful assessment of acute and late toxicity

Pt-Radiation Processing
 Decision made for Treatment
 Consent

 CT Simulation with markers

 From CT Scan CT cuts are exported to TPS

 In TPS ,target volume/ critical structures are contoured

by Oncologists
 Medical physicist plans for RT with TPS

 Once plan is ready- for approval by Oncologist

 Plan exported to workstation

 Treatment setup done

 Setup verification done thro Portal Vision

 Treatment delivered

 Documentation
Treatment Machines
 Tele Cobalt-60
 Cobalt 60- Gamma rays

 Capital Investment less

 Useful in most Practical Situations.

 Easy Installation

 Few Staff required

 Maintenance/Repair Easy
 Medical Linac
 Electrically Driven
 Investment more
 Sharper Beams.
 Higher tissue penetration
 Technically Superior
 Can produce Electron beams ,used to treat Neck
nodes.
 Medical Linac
 Electrically Driven
 Investment more
 Sharper Beams.
 Higher tissue penetration
 Technically Superior
 Can produce Electron beams ,used to treat Neck
nodes.
Medical Linear Accelarator
Linac Treatment Options
 X- Rays : Simple
Complex
3D Conformal
IMRT
 Electrons : In Head & Neck for LN, any
Skin Cancers,Recurrence
IMRT
 Intensity modulated radiotherapy

 Advanced form of 3D - conformal radiotherapy

 based on the use of optimised non uniform beam

intensities

 determined by computer-based optimisation

techniques (Inverse planning)
Clinical Processing for IMRT
Aquaplast Face Mask
Intra Oral Cone therapy
 Localized radiation technique
 More suitable for anteriorly located lesions

 RT by Intra oral cones uses 250 KeV x rays or

Electron beams
 Indications same like Brachytherapy

 Used after Ext Beam RT

Interstitial Brachytherapy
 Depends upon volume of growth.
 May be single plane,double plane, volume
implants.
 0.5 – 1.0 cm margin around the growth.
 Stainless steel needles or after loading catheters
used for this.
 LDR (Caesium ) or HDR (Iridium) isotope used
thro after loading catheter.
Radiation dosimetry
• How much?

• Where?
 1 “rad” = 1 centiGray (cGy)

 200 cGy per day

 5 days per week

 1000 cGy per week

 Total dose ranges from
 6000 cGy – 7000 cGy

 6 – 7 WEEKS of treatment
Dental Care and Radiation
 Dental care should be a comprehensive part
 Evaluation before RT

 For dental carries Teeth Extn before RT

 RT will be delayed for 2 weeks after Extn.

 Sound teeth or teeth in good repair need not be

sacrificed.
 Post RT dental Extn possible with antibiotic
coverage,but better avoided within short period
Treatment Recommendations
Lip Cancers
 T1 N0 :Surgery or RT if commissural
involvement or poorly different. Cancers
 T2 N0 :Surgery or RT
Post op RT if margin +ve ; node +ve
 T 3-4 N0: Surgery ? Cosmetic/Functional
Outcome
Post op RT +/- Chemo if +ve margin; node +ve
 Alternatively Concomitant Chemo+RT first and
Surgery for Salvage.
 T 1-4 Any N :Surgery +/- Contra lateral ND
 Post Op Chemo RT as indicated

Margin + ve ; Margin close

Node(s) + ve ;
Poorly Different.Cancers
Lympho Vascular Space invasion
Treatment Recommendations
Floor of mouth Cancers
 T1 N0 : Surgery or RT +/- Brachytherapy Post op
RT as indicated .
 T2 N0 ,T3N0(Resectable):Surgery
 Post op Chemo RT as indicated.
 T1-4 N+ :Surgery
 Post op Chemo RT as indicated
 Locally advanced –unresectable
 Chemoradiation first
 Surgery for salvage

Treatment Recommendations
Oral Tongue Cancers
 T1 & Early T2 N0:Surgery or RT
 In both Neck Treatment is required

 Post op RT as indicated

 Large T2 N0: Surgery

Post Op Chemo RT
 If inoperable -Definitive RT

 T3-4 N0 or T1-4 N+ :Surgery

Post op Chemo RT
 Alternatively Chemo RT first

 Surgery for Salvage if any nodes or residual

primary disease.
Treatment recommendation
buccal mucosa
 External beam therapy most commonly used for
T1 and T2 tumors

 Larger T3 and operable T4 tumors are more

approptietly treated with surgery and post
operative RT.
Treatment modalities
lower alveolar mucosa
Close proximity to underlying mandible ,bone
invation occurs

T1 and T2 tumors most frequently treated with

external beam therapy

Extensively advanced tumor with more extensive

require surgery and postoperative radiotherapy
to include prophylactic lymphnode iiradiation
Treatment modalities
retromolar trigone
 T1 and T2 Tumors can be effectively treated
with external beam therapy

 Important to include ant. border of ramus and

ptrygoid fossa superiorly to skull base with
elective irradiation to ipsilateral lymphnode
drainage

 More advanced tumor require surgery followed

by radiotherapy
Post op rt

 Advantages-

 Benefit of pathology,surgical findings

 Better staging,no need to over treat

 Disadvantages

 Larger RT fields to cover surgical bed

 Poorer blood suply – RT less effective

 More late morbidity

Pre-op RT

Advantages
-Downstage tumour, less multilating surgery
-Sterilise surgical margins
-Remove RT damaged parts during surgery

Disadvantages - Clinical staging, therefore

treat some unnecessary
-What if tumour not sensitive to RT?
-May increase surgical morbidity
What Happens To A Patient Undergoing
RT
Acute sequale
 General

- Weight loss

- Nausea

- Fatigue

- Depression

 Extra-Oral Intra-Oral
- Cutaneous burns mucositis
- Alopecia erythema
- Xeroderma ulceration
Side Effects of RT

Epidermal layers of skin, GIT - fast turnover

Thus RT kills the epidermal layers as they go into

mitosis

Lower layers insufficient time to repopulate

Thus de-sloughing occurs :-

-skin : erythema, dry then moist desquamation “sun
burn”
-mucosa : mucositis, oesophagitis, gastritis,
colitis proctitis, cystitis
- marrow : pan-cytopaenia
Side effects of RT to head & neck
Xerostomia

 From day 1
 - Pilocarpine 5-10mg tid
 - Saliva substitutes (oral balance)
 - Ethyol (amifostine)

 Serous component of saliva affected most

often
 - Bicarbonate mouth rinses
Mucositis

 direct mucosal (basal layer) damage

 secondary infection
Treatment
- good oral hygiene
- anti-fungals
- salt water rinses
- pain killers, steroids
- lidocaine
- soft diet
- avoid spices, smokes, spirits
Hypoalimentation

 nutrition counselling
 enteral feeding
 appetite stimulants (Megace,
anabolic steroids)
Skin Reactions

Erythema

Dry desquamation (peeling)

 hydrocortisone 1%

Moist desquamation (dermis exposed and

oozes serum)
 gentian violet
 paraminol cream
 healing within 2-4 weeks after RT
Sialadenitis

5% develop it within 12 hrs of 1st

RT
transient painless enlargement of
salivary gland
usually disappears within a week
despite continuation of treatment
Skin reactions
 Sense of Taste-

 Beginswith in one week

 Recovers with in 1-3 months

 Alopecia

 Only in areas which are irradiated

 Begins during the 3rd week of RT
 Late Effects Of RT
Xerostomia
dependent on dose (>35Gy) to parotids

Teeth
pathologic changes secondary to diminished salivary
flow
radiation caries

Trismus
fibrosis of muscles of mastication
expecially if treated with Sx+RT
Late effects of RT
 Brain Necrosis –
 Demyellination with loss of focal areas of white
matter necrosis
 Time interval : 8 months to 2 years
 Symptoms : dizziness
- Impaired memory, headache,
- Confusion, fits, personality change
- 16% - no sign or symptoms

 Treatment - steroids
Soft tissue and bone necrosis
Due to avascular effect of RT

Bone itself tolerates high dose of RT well, so long as

tissues overlying the bone remain intact and the bone
is not subjected to excessive stress or trauma

After RT, extraction of nonrestorable teeth within

high dose areas is to be avoided unless all other
measures fail. Try root-canal therapy

RT caries in teeth outside the field of RT does not

predispose to osteonecrosis since the bone at this
point has not received high-dose RT
Management
Small exposures - conservative
- patience (mths)

HBO - 30-60 dives

of 2.4atm/90min/day/5day/week

Surgical resection
Cranial nerve
Optic Nerve Neuropathy
 8% at doses of 60-73Gy
 No effective treatment
 Steroids, HBO

Hypoglossal Nerve
 esp if large subdiagastric LN
 RT -> fibrosis, nerve entrapment
 RT+RND - less risk

Brachial Plexus
 occur 6-24 mths later
 rare at 2Gy/#
 associated with large dose/#
RT induced 2nd Malignancies
1st case in1902 - hand of RT technician

RT induced Mucosal CA
 MDAH - 1163 patients (Radiology 1975)
- no excess new SCC

 UCLA - 2125 patients (IJROBP 1988)

- no diff in risk of 2nd Ca

 RTOG - NPC database (Cancer 1922)

- cf age-matched grp
- less 2nd Ca after RT
Rt induced sarcoma
Incidence (Hatfield; Philips; Seydel; Bataini)
 1-2 cases per 1000, 5yr survivor

Assuming 1 per 500, 5yr survivor

And overall 5 yr surv for RT is 40%

Most are :
 high grade sarcomas,
 advanced stage
 difficult to operate
 respond poorly to chemo
 and consequently poor prognosis
RT Induced Thyroid Ca

Latent period : 10-30 yrs

Low doses of RT (<20Gy)

Advances in rt techniques
 Altered Fractionation Regiments
 Balance between tumour & normal tissue :
 repair, re-oxygenation,
 re-assortment, re-population

Accelerated Fractionation
 overcome tumour repopulation

Hyperfractionation
 reduce dose/fraction to reduce late side effects and
permit higher total doses to be given to tumour
Chemo-RT
“Spatial co-operation”
 eg ALL (CNS)
 ‘hypoxic’ drugs

Synergistic actions
 eg 5FU, DDP, Paclitaxel
Sequencing chemo and RT

Neo-adjuvant

Concomitant

Adjuvant

 Most evidence suggest concomitant

chemo-RT is sequence which will result
in improved results
 H&N, lung, esophagus, cervix
Improving oxygenation
HBO
Hypoxic cell sensitiser
Erythropoeitin
Carbogen (95%CO2, 5%O2)
Nicotinamide

Angiogenesis
Endothelial cell biology
Vascular targetting

Ratioprotectors (Ethyol)
Improved technology

Fusion of CT/MRI/PET images

3D conformal RT

Inverse treatment planning

Real time target localisation

 Cyberknife
 BAT u/s system

“Tomotherapy” - like CT Scan

Charged particles
Precise dose localisation possible
eg protons

high LET (less dependence on O2)

eg neutrons

“stars” - causes disintegration of nucleus

eg pions (-ve pi mesons)
Conclusion
 Earlydetection of lesions is critical to
allow conservative treatment and protect
the patient’s quality of life.

 Many avenues constantly under

investigation, are available to treat oral
cancers, with improved methods

A multidisciplinary team can help oral

cancer patients deal with the aftermath of
treatment.
references
 Text book for oral cancer by Jatin P. Shah

 Text book of oral &maxillofacial surgery by Peter

Ward Booth.

 Text book of radiology white & ferrow

Thank you