brief and condensed ppt for the radiotherapy in head and neck cancer

1. Moderator- Dr. Suja Sreedharan
Dr. Sourjya Banerjee
Presenter- Dr. Sreenivas Kamath

2. 1. Introduction
2. History of radiation
3. Basics of radiation biology
4. Role in H&N Ca
5. Methods of administration
6. Complications
7. Summary
8. Reference

3.  Radiation oncology is a medical specialty predominantly focused on the
treatment of neoplastic diseases with the use of ionization radiation
 Considerable inroads in radiation treatment planning and delivery
techniques have been made in the last decade toward improving the
practice and changing the philosophy of H&N radiation oncology

4. Wilhelm Conrad Röntgen
German physicist
08 NOV 1985- Xray
Nobel prize 1901
Professor Leopold Freund
Austrian
1897- X-ray in Hairy Mole
Father of Medical radiology
and radiotherapy
Marie Skłodowska Curie
Polish
1898- Radium discovery
Nobel prize 1903, 1911

5. 1905-1920- RT in single
High dose administration
1920- Fractionated
therapy
Studies from sterilisation of
animal testes.
1950- SRS
1990- CRT and IMRT

6.  Definition- “the emission of energy as electromagnetic waves or as
moving subatomic particles, especially high-energy particles which
cause ionization”.
 Radiation used in radiation therapy have the capacity to produce
excitation or ionisation
Excitation Ionization

7.  Ability to release large amounts of energy
locally, resulting in the breaking of chemical
bonds, consequentially producing a large
biologic effect for a relatively small total
amount of energy consumed

8.  Depending on the mechanism of action
 Directly ionizing radiation- Charged particle
 Indirectly ionizing radiation- Neutral particles
 Depending on the physical property
 Electromagnetic radiation – High energy X rays, γ rays
 Particle radiation- Electrons, Protons, Neutrons.

9.  Indirectly ionising
 X ray and γ rays
 X rays – Extranuclear origin- LINAC
 γ rays- Intranuclear origin- Radioactive particle
 Energy of rays expressed in Mega Volts (MeV)
 Spectrum of energy produced with max Value used for reference.

10.  Electron, Neutron, Proton, High energy heavy charged particle.
 More used- Favourable depth-dose distribution
 Electron and proton are more used in radiotherapy

11.  Electrons are light, negatively charged particles - linacs
 The higher the energy of the electron beam, the more deeply it
penetrates tissue
 Protons are 1835 times heavier- Cyclotron/ Synchrotron
 Due to mass have less scattering- focused radiation distribution
 Bragg Peak effect- Maximum dose at particular distance then steep fall.

13.  Fate of irradiated cells
 Effect of radiation on normal tissue
 Killing effect of radiation
 Radiation effect on cellular kinetics
 Cell survival and dose response curve
 Fractionation
 Factors effecting radio sensitivity

14.  Produce variety of biological and molecular effects- tumor killing or
normal cell toxicity
 The effect depends on various factor.
 Cells undego serveral process-
 Delay in division G2-M arrest
 Apoptosis
 Reproductive failure
 Genomic instability, mutation, transformation, bystander effects,
adaptive responses.

15. Primary target is DNA
 DNA damage can be due to direct effect or due to indirect effect by
reactive free radicals
 Can be single stranded or double stranded break
 Single stranded damage are more frequent and easier to repair
 Double stranded are rare- repair is complex and has molecular effects.

16.  Mostly tolerate the radiation exposure
 Tissue injury can occur if critical number of clonogenic cell are killed.
 Classified based on the time of onset
 Acute
 Subacute
 Chronic

17.  Described as following
 Lethal damage- Irreversible and irrerepairable
 Sublethal damage- can be repaired if given time
 Potentially lethal damage- lethal only in certain situations.
 Cell death- Reproductive failure or apoptosis

19.  Along with the lethal effect radiation may also effect certain processes
that are essential for normal cell functioning
 Still under investigation
 CDKs, P21, P27, Cyclins.

20.  Graphical representation of the cell survival after radiation exposure.
 Helped to show the benefit of fractionation
 Use of Linear- Quadrantic model
Two components
Alpha (α) Linear component
Beta (β)- Quadrantic component

21.  αD- cell death propotional to dose (D)
 βD2 – Propotional to the square of Dose (D)
 The survival fraction (S) to a given dose (D)
S(D) = e–αD– βD2,
 α/β – clinically important
 Early responder- high (9-12)
 Late responders- low (2-4)

22.  Since 20th centuary fractionation has replaced the single dose
radiotherapy
 1900- Study by Regaud- Ram sterilisation
 Single dose of radiation could not cause sterilisation- more skin
necrosis
 Series of smaller dose could sterilze and had lesser skin necrosis

23. Repair- of sublethal
damage
Reassortment
Repopulation Reoxygenation
Fractionation

24.  Repair of sub-lethal damage-
 Capacity to repair depends on the type of tissue- Mature cells with less
turn over
 Avoid injury to the late responding tissue.
 Reassortment
 Cell cycle are usually asynchronous. Cells in G2-M phase are killed
 Those that escaped will progress with cycle and reach more sensitive phase.
 More effective for tumors since they have high turn over
4R

25.  Repopulation
 When the tumor cells are depleted by either surgical or CTRT- There is a
regenerative response
 Accelerated population of the tumor cells
 Hence fractionation provides with better loco regional control
 Reoxygenation
 Due to tumor shrinkage with treatment the tumor cells which were far from the
feeding artery comes closer. (50-75Mm)
 Hypoxic tumor micro environment oxygenated
 More sensitive to subsequent radiation
4R

27. Fractionation Studies 5 year
survival
5 year
locoregional
Hyperfractionation EORTC 22791,
RTOG9003, RIO
36.7/28.5 57.9/48.5
Accelerated
Fractionation with dose
EORTC 22851,
RTOG 9003,
DAHANCA
44.4/42.4 47.4/40.2
The primary tumor sites were oropharynx and larynx, with the majority of patients having intermediate
to locally advanced H&N cancers

28. Reduce radiosensitivity Increase Radiosensitivity
Hypoxic state- Post operative scared tissue.
Tissue hypoxia.
Chemical radical scavengers
Low dose rate/ Hyperfractionation of RT High dose rate/ Single fraction
Physical factors- LET, relative biological
effectiveness (RBE), and fraction and
protraction
High LET radiation.
Cell cycle phase Late S phase Cell cycle phase- G2 M

29.  Indication of RT in Head and neck cancers
 Curative RT- Oral/ oropharyngeal SCC, Nasopharynx, early laryngeal,
superficial skin cancers.
 Adjuvant- PORT (post operative radiotherapy)
 Palliative RT

30.  A local control rate of 90% at 5 years

31.  Different methods of administration
 Newer high precision RT delivery system
 Approach to patient for RT

32.  The radiotherapy can be administered as
 Teletherapy
 Brachytherapy
 Stereotactic radiosurgery

33.  Teletherapy refers to radiation therapy given by an external radiation
source at a distance from the body
 Most commonly used
 Conventional fractionation used
 1.8-2Gy per day. 5 days a week. For 6-7 weeks (total dose of 66-
72Gy)

34.  Radioisotopes are placed to tumor bed using specialised devices
 Can be permanent or temporary placement
 Often used for recurrent tumors
 The depth of radiation is very less and only tumor bed gets radiated.

35.  Low dose rate- upto 2Gy per hour
 High dose rate- 12Gy per hour (temporary)
 Commonly used for
 Lip, floor of mouth, oral tongue, base of tongue, buccal mucosa,
tonsillar region, nasopharynx, skull base, and neck.
 T1, T2 lesion of tongue can be treated with only Brachy therapy.

37.  Developed during 1950-60 Takahashi Japan
 Conforming radiation doses to irregular tumor volumes
 Reduce radiation dose to critical normal structures nearby the tumor
without compromising dose delivery to the intended target

38.  highly sophisticated application of CRT
 Modifies the intensity of photon beams to provide greater flexibility and
precision in treating irregular tumor targets resulting in a sharper dose-fall off
gradient, concave dose distribution, and narrower treatment margins
 Requires proper planning and pre-treatment delineation of the tumor volume
and extent.
 CT, MRI, PET Scan

39.  Target volumes are dose painted and subclinical areas are painted with
lesser dose
 Results are almost at par with conventional RT
 Improve xerostomia, and swallowing function.
 Used advanced computer planning and Multileaf collimator
 Previously used the Dynamic rotational technique or Step and shoot
technique.
 Now Volumetric modulated arc therapy (VMAT)- radiation delivered 360
degrees

40.  Use of two-dimensional and three-dimensional imaging during the
course of treatment to account for setup uncertainties and patient
positioning on the treatment table and ensure accurate placement of
the radiation field according to the initial radiation treatment plan

41.  Changing of radiotherapy plans during treatment course to reoptimize
based on the changes in the tumor volume during treatment
 Patient factor- tumor shrinkage, weight loss, internal target motion, or
changes in tumor biology or function such as hypoxia.
 Technical factor- positioning accuracy or daily organ motion are the
center of attention
 Immobilization devices and daily onboard imaging to verify patient
positioning. Adding 3–5 mm planning target volume (PTV) margin

43.  Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT)
are techniques to administer precisely directed, high-dose irradiation
that tightly conforms to an intracranial target
 Gamma Knife, modified LINAC radiosurgery systems (including
CyberKnife and image-guided radiotherapy systems), TomoTherapy, or
proton beam systems.

44.  Veteran Affair (VA) larynx préservation trial in 1991
 Meta-Analysis of Chemotherapy on Head and Neck Cancer (MACHNC)
1. Induction chemotherapy
2. Adjuvant radiotherapy and chemotherapy
3. Altered fractionation with concurrent chemotherapy

45.  Cetuximab – antiEGFR monoclonal antibody
 Geftinib and erlotinib are currently being studied

46.  Biomarkers
 EBV DNA titres in NPC
 HPV and orophanryngeal cancer
 EGFR expression in the HNSCC

47.  Used for symptomatic relief of tumor burdern in patient with incurable
disease
 Conventional regimen- 30 Gy given in 10 fractions over 2 weeks
 Provides around 65% of symptomatic relief in ¾ of cases
 Hypofractionation has been used to reduce the treatment duration

48.  Pre-treatment assessment
 Treatment delivery
 Post treatment care

50.  Comprehensive evaluation
 Carious teeth that are not salvageable should be extracted
 Significant number of dental fillings- Personalised mouth guard
 Fluoride prophylaxis
 Hypothyroidism- evaluation and appropriate management
 Hematocrit level- more than 30%
 Ophthalmologic evaluation
 Nutritonal assessment, SLT counselling

51.  Patient Education
 Rationale for treatment
 Expected toxicities of treatment
 Process of treatment planning
 Rough time frame for starting treatment

52. Patient treatment position, immobilization, and planning imaging
Delineation of tumor/target volumes and organs at risk
Dose prescription
Plan evaluation and improvement
Plan implementation and treatment verification

53.  First step in setting up the radiation fields.
 CT / X ray imaging
 Conventional
 3D CRT/ IMRT- Volume delineation

54.  Get patient in optimal / acceptable treatment position
 Allows reproducible and verifiable treatment of tumour
 Possible additional benefit: allows / increases sparing of normal tissues
 Patient comfort is critical
 Pain control
 Use support devices and immobilization devices liberally
 Can patient maintain desired position for 15 – 30 minutes without
difficulty?
 For a given site, avoid treating same patient in different positions

55.  Gross tumour volume (GTV) is outlined
 A margin is included around the GTV to include areas at risk for
microscopic involvement, this is the clinical target volume (CTV)
 A margin is added onto the CTV to allow for differences in internal
organ motion or day-today set up variations, this is the planning target
volume (PTV)
 There is a margin added to the PTV to allow for physical characteristics
of the beam (penumbra), this is the actual treatment volume

59.  Weekly status check of patients undergoing radiation therapy
 sore mouth or throat, dysphagia, hoarseness, altered taste, xerostomia, skin reactions, and
ear symptoms
 Complete examination- Tumor and complications
 The general condition, body weight, and complete blood cell count should be
monitored

60.  Organs At Risk
 Class I organs : radiation lesions are fatal or result in severe
morbidity (spinal cord)
 Class II organs : radiation lesions result in mild to moderate morbidity
(bowel)
 Class III organs : radiation lesions are mild, transient and reversible,
or result in no significant morbidity (muscle)

61.  Acute-during or shortly after radiation
 Late- 3 months after the completion of treatment to lifetime
 Acute injury is related to toxic effects of radiation treatment on rapidly dividing
cells, whereas late injury manifests itself in slowly dividing tissues such as
connective and neural tissues
 Concurrent use of chemotherapy- increases the frequency and severity of
radiation related sequelae

62.  RTOG -toxicity scoring system
 0 to 4, with 0 having no change over baseline and 4 being severe. For
example, in the case of skin, grade 4 is ulceration, hemorrhage, and
necrosis

64. Acute Sequelae
 Affects mucous membranes, skin, and salivary tissues.
 Basal proliferating layer in the epidermis
 Lower levels of exposure to the basal layer- erythema and hyperpigmentation of
the skin
Erythema and
hyperpigmentation
Dry squamation,
peeling and
scaling
Wet desquamation
Slough off and
expose dermis
Skin moisturizers and antiseptic creams

65.  Mucus membranes -dose-dependent acute toxicity
 At lower doses, mucosal erythema develops, which progresses to
pseudomembranous-like mucositis
Erythema,
Pseudomembrane
Confluent and
ulcerate
Soft tissue
necrosis,
laryngeal edema,
serous otits media

66.  Salivary tissues are exquisitely sensitive -change in the volume and
composition of saliva
 The viscosity of saliva is increased - dryness of the mucous
membranes and the formation of crusts.
 These areas can be a nidus for infection and should be addressed with
oral irrigation with use of a solution that contains baking soda and salt
 Alteration in taste occurs as a result of the direct effect on taste buds,
as do changes in the biochemical composition of saliva.
 Bland and metallic taste
 Sense of taste spontaneously recovers over time.

67.  Acute radiation sequelae can severely impair oral intake of regular food
 Dietary modification and nutritional supplements must be provided
 Nasogastric or gastrostomy tube feeding should be considered as a last
resort
 Analgesic drugs, steroids, and antifungal medications also may be
required to alleviate acute manifestations of radiation mucositis

68. Late Sequelae
 A combination of vascular endothelial damage, fibrosis from scarring,
and muscle atrophy along with death of the parenchymal cellular
network
 Skin-atrophy and the development of telangiectasias
 Subdermal fibrosis and contracture
 Skin carcinomas

69.  Surgical procedures in previously irradiated fields have an inherent risk
of delayed healing and/or skin and soft tissue necrosis
 Surgical planning should include excision of heavily irradiated skin and
reconstruction of the surgical defect with non irradiated vascularized
tissue.

70.  Xerostomia -difficulty in swallowing and increased risk of dental caries.
Affects the patient's quality of life
 At present, no therapeutic agents are available to effectively treat
xerostomia
 Prevention of xerostomia
 Amifostine
 Regular, frequent oral irrigation with a weak solution of salt and
sodium bicarbonate
 High humidity in inhaled air, particularly during the winter when the
heating of rooms

71.  Continued dental care- to minimize the development of caries and the
risk of osteoradionecrosis
 Hyperbaric oxygen-prevention of radionecrosis. No benefit once the
bone has already become necrotic.

72.  Thyroid function tests including TSH-all patients who have been treated
with radiation in the central compartment of the neck
 Biochemical hypothyroidism is observed in a significant number of
patients
 Thyroid hormone replacement therapy is started if the TSH level rises
above the normal range, irrespective of the T3 and T4 values, which
may be within normal limits
 If the hypothalamic–pituitary axis has been exposed to radiation, a
complete endocrine screening should be obtained.

73.  Fibrosis and muscle atrophy can lead to development of motor
dysfunction, contracture, and strictures
 Pharyngo-esophageal stricture - repeated dilatations , surgical
reconstruction
 Fibrosis of the muscles of mastication - trismus
 No effective treatment
 Prevention with jaw-stretching active and passive exercises instituted
soon after the completion of therapy and continued until satisfactory
jaw opening is achieved
 Post radiation fibrosis and scarring also may hamper shoulder
movement- daily range of motion exercises for the neck and shoulders to
prevent

74.  Cartilage and bone-impairment of growth in children, atrophy, and
occasionally radiation chondritis or osteonecrosis
 Radiation necrosis of the larynx
 0.1% to 0.5% risk of a radiation-induced second cancer in the irradiated
field
 These second tumors typically are squamous cell carcinomas of the
skin and high-grade sarcomas that may be difficult to treat
 The risk for development of radiation-induced cancers increases with
time

75.  L’hermitte syndrome may develop in some patients whose cervical spinal cord
is exposed to radiation
 Symmetrical shooting pain like an electrical shock radiating down the spine
and extremities with flexion of the neck
 Benign, self-limiting myelopathy
 Due to demyelination1
 1 to 3 months after radiation therapy and can last for up to 9 months or more
 If these symptoms develop for the first time 9 to 12 months after radiation
therapy, the more likely diagnosis is radiation myelitis, which is a more serious
problem.

76.  The field of H&N radiation oncology has been exciting and rewarding in the
past few decades
Recent advances in radiation oncology have generated a great deal of
optimism as novel strategies for improving quality of life and survival rates are
being developed for clinical testing
 Better radiobiologic insight to help identify new molecular targets for
selectively sensitizing tumor to radiation and thus improve upon the
therapeutic ratio