this presentation is about radiotherapy principles and the how it works

1. Radiotherapy
Presented by: Dr. Nikil Jain

2. contents
Introduction
The Basis of Radiotherapy
Radiation Techniques
Side effects of radiotherapy
Future Development in Radiotherapy

3. 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

4. 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

5. Role of RT
50% of all Ca will require RT
2/3 of these for curative intent

6. 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

7. How are x-rays produced?
Natural : radioactive decay
Man-made : sudden deceleration of high
speed electrons when it hits a
tungsten target

8. 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

9. 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

11. 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

14. 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)

15. 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

16. 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

18. 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

19. 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

20. 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

22. Treatment plan is based on

23.  Staging of disease using TNM classification
 age of patient
 co-morbid conditions-
Medical
Dental
Speech
Nutrition
Psychosocial
Socioeconomic

24. Treatment Options
Primary surgery
Adjuvant
Radiotherapy
Concurrent
Chemotherapy
OR Primary Radiotherapy
Concurrent
Chemotherapy
Surgery for Salvage
+/-
+/-
+/-
+/-

25.  No treatment
 Palliation

26.  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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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.

33.  Medical Linac
 Electrically Driven
 Investment more
 Sharper Beams.
 Higher tissue penetration
 Technically Superior
 Can produce Electron beams ,used to treat Neck
nodes.

35. Medical Linear Accelarator

36. Linac Treatment Options
 X- Rays : Simple
Complex
3D Conformal
IMRT
 Electrons : In Head & Neck for LN, any
Skin Cancers,Recurrence

37. IMRTIMRT
 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)

38. Clinical Processing for IMRT

39. Aquaplast Face Mask

40. 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

41. 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.

42. • How much?
• Where?
Radiation dosimetry

43.  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

44. 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

45. 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.

46.  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

47. 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


48. 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.

49. 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.

50. 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

51. 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

52. 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

53. 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

54. 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

55. 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

56. 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

57. 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

58. Hypoalimentation
 nutrition counselling
 enteral feeding
 appetite stimulants (Megace,
anabolic steroids)

59. 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

60. 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

61. Skin reactions
 Sense of Taste-
 Begins with in one week
 Recovers with in 1-3 months
 Alopecia
 Only in areas which are irradiated
 Begins during the 3rd
week of RT

62. 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

63. 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

64. 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

65. Management
Small exposures - conservative
- patience (mths)
HBO - 30-60 dives
of 2.4atm/90min/day/5day/week
Surgical resection

66. 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/#

67. 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

68. 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

69. RT Induced Thyroid Ca
Latent period : 10-30 yrs
Low doses of RT (<20Gy)

70. 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

71. Chemo-RT
“Spatial co-operation”
 eg ALL (CNS)
 ‘hypoxic’ drugs
Synergistic actions
 eg 5FU, DDP, Paclitaxel

72. 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

73. Improving oxygenation
HBO
Hypoxic cell sensitiser
Erythropoeitin
Carbogen (95%CO2, 5%O2)
Nicotinamide
Angiogenesis
Endothelial cell biology
Vascular targetting
Ratioprotectors (Ethyol)

74. 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

75. 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)

76. Conclusion
 Early detection 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.

77. 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

78. Thank you